Transition Metals Characteristics Properties and Uses PDF

CHEMICAL ENGINEERING METHODS AND TECHNOLOGY
TRANSITION METALS
CHARACTERISTICS, PROPERTIES AND USES
No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or
by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no
expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No
liability is assumed for incidental or consequential damages in connection with or arising out of information
contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in
rendering legal, medical or any other professional services.
CHEMICAL ENGINEERING METHODS
AND TECHNOLOGY
Additional books in this series can be found on Nova’s website

under the Series tab.
Additional E-books in this series can be found on Nova’s website

under the E-book tab.
MATERIALS SCIENCE AND TECHNOLOGIES
Additional books in this series can be found on Nova’s website

under the Series tab.
Additional E-books in this series can be found on Nova’s website

under the E-book tab.
CHEMICAL ENGINEERING METHODS AND TECHNOLOGY
TRANSITION METALS
CHARACTERISTICS, PROPERTIES AND USES
AJAY KUMAR MISHRA

EDITOR
Nova Science Publishers, Inc.

New York
Copyright © 2012 by Nova Science Publishers, Inc.
All rights reserved. No part of this book may be reproduced, stored in a retrieval system or
transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical
photocopying, recording or otherwise without the written permission of the Publisher.
For permission to use material from this book please contact us:
Telephone 631-231-7269; Fax 631-231-8175
Web Site: http://www.novapublishers.com
NOTICE TO THE READER
The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or
implied warranty of any kind and assumes no responsibility for any errors or omissions. No
liability is assumed for incidental or consequential damages in connection with or arising out of
information contained in this book. The Publisher shall not be liable for any special,
consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or
reliance upon, this material. Any parts of this book based on government reports are so indicated
and copyright is claimed for those parts to the extent applicable to compilations of such works.
Independent verification should be sought for any data, advice or recommendations contained in
this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage
to persons or property arising from any methods, products, instructions, ideas or otherwise
contained in this publication.
This publication is designed to provide accurate and authoritative information with regard to the
subject matter covered herein. It is sold with the clear understanding that the Publisher is not
engaged in rendering legal or any other professional services. If legal or any other expert
assistance is required, the services of a competent person should be sought. FROM A
DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE
AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS.
Additional color graphics may be available in the e-book version of this book.
Library of Congress Cataloging-in-Publication Data
Transition metals : characteristics, properties and uses / editor, Ajay Kumar Mishra.
p. cm.
Includes index.
ISBN: (eBook)
1. Transition metal alloys. I. Mishra, Ajay Kumar, 1965-
TN693.T7T73 2011
661'.06--dc23
Published by Nova Science Publishers, Inc. † New York

CONTENTS
Preface vii
Chapter 1 Role of Reactivity of Transition Elements in Life 1
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam
and Afaf Ezzat
Chapter 2 Nonlinear Optical Properties of Transition Metal Nanoparticles
Synthesized by Ion Implantation 63
Andrey L. Stepanov
Chapter 3 Self-Organization of the Nanocrystalline Structure
and Radiation Resistance of Structural Materials 119
V. P. Kolotushkin and A. A. Parfenov
Chapter 4 Transition Metal Complexes of Schiff Base Ligands
of 3-Formylsalicylic Acid: Synthetic Pathways
and Useful Properties 165
Saikat Sarkar and Kamalendu Dey
Chapter 5 Structural and Magnetic Characterization of Cu-Picolinate
and Cu-Quinaldinate Molecular Systems 221
Bogumiła Żurowska
Chapter 6 Review: Transition Metals in Medicine 263
Hanan F. Abdel-Halim
Chapter 7 Application of Transition Metals as Active Compounds
in Separation Techniques 299
Iwona Rykowska and Wiesław Wasiak
Chapter 8 Chromium Pigment 327
Mohammad Fikry Ragai Fouda , Hanan. F.Abdel-Halim
and Samia Abdul Raouf Mostafa
Chapter 9 Transition Metals: Bioinorganic and Redox Reactions
in Biological Systems 349
Marisa G. Repetto and Alberto Boveris
vi Contents
Chapter 10 Hydrodesulfurization of Dibenzothiophene over Various

CoMoP/Al2O3 Sulfide Catalysts Prepared from Co and Mo
Phosphoric Acids 371
Masatoshi Nagai, Yuki Nakamura and Shoji Kurata
Chapter 11 Mixed Transition Metal Acetylides with Different Metals
Connected by Carbon-Rich Bridging Units: On the Way
to Hetero-Multimetallic Organometallics 383
Heinrich Lang and Alexander Jakob
Chapter 12 Reactivity of Unstable Chemicals in the Presence
of Transition Metals 453
Mieko Kumasaki
Index 483
PREFACE
In this book, the authors present topical research in the study of the characteristics,
properties and uses of transition metals. Topics discussed include the nonlinear optical
properties of transition metal nanoparticles synthesized by ion implantation; the structural and
magnetic characterization of Cu-Picolinate and Cu-Quinaldinate molecular systems;
application of transition metals as active compounds in separation techniques; the reactivity
of unstable chemicals in the presence of transition metals and the bioinorganic and redox
reactions in biological systems of transition metals. (Imprint: Nova)
Transition metals are commonly known as d-block elements that forms the bridge
between the main group elements of the periodic table. These elements are lustrous / shiny
solids or liquids and possess metallic properties which include hardness, toughness and strong
metallic atom-atom bonding. Some of the characteristic properties of these metals include its
ability to form colour compounds, exhibiting many oxidations states and their magnetic
behaviour. Besides these properties, these metals are good conductors of heat and electricity
and have many free electrons per atom to carry thermal and electrical energy. These metals
can be easily hammered and bent into different shapes. Due to the strong metallic bonding,
the transition elements show high melting point, boiling point and high density. Transition
metals are used as alloy and useful as structural materials due to their strength and hardness
properties. They are also used as pigments for artwork and give bright colours to stained glass
and ceramic glazes.
Due to metallic properties, the transition metals have been exploited for many industrial,
commercial, strategic, environmental, ornamental, medial, biomedical applications. Among
these, the common use at technological scale is their use as catalysts in industrial chemical
processes and also in the anti-pollution catalytic converters in car exhausts. Due to the
catalysis behaviour of the transition metals, a variety of new synthetic methodologies has
been developed and applied to industrial processes. It is very difficult to find a multi-step
synthesis of complex organic molecules where transition metal catalyzed processes are not
employed. Significant progress in homogeneous catalysis and the depth understanding of the
mechanisms and also from developments based on the new information derived in studying
the behaviour of organotransition metal complexes. The organotransition metal chemistry and
homogeneous catalysis area has been extensively studied with the ferrocene, Ziegler catalyst,
and the Hoechst-Wacker process. This prompted the organotransition metal chemistry in a
significant increase in the number and novel chemical features that are applicable to catalysis.
The advantage of homogeneous catalysis over conventional heterogeneous catalysis allows
viii Ajay Kumar Mishra
the clarification of the reaction mechanisms at the molecular level by catalytic cycles
consisting of elementary processes.
Transition metals have a key role in the development of medicine, coordination
chemistry, plant biology, materials science, polymer science and also by biochemists and
biologists as well. The transition metals ions and complexes play a central role in controlling
the reactivity and mechanism of the chemical reaction of interest. This can be due to the
actual reaction occurring at the metal centre and/or the catalytic activity of the metal complex
in an overall chemical process. The unique ability of transition metal ions and complexes to
control the chemistry of environmental, industrial, and biological processes has increased the
importance of clarifying their mechanistic behaviour in simple and complex chemical
processes. The role of the central metal atom or ion has received considerable attention not
only in fundamental inorganic and organometallic chemistry but also in more applied areas
such as in environmental, bioinorganic, and bioorganic chemistry.
Transition metal catalyzed polymerization, synthesis of compounds of interest for
material research, the use of non-conventional solvents such as water, supercritical fluids, and
ionic liquids, and reactions employing polymer supported reactants have gained enormous
attentions. The polymer synthesis has also been widely studied by the olefin polymerization
and copolymerization by late transition metal catalysts. Polymer synthesis has been
influenced by the development of single-site polymerization of olefins by complexes of the
transition metals where the coordination and insertion modes of monomers are controlled by
the ligand. Ring opening metathesis polymerization developed the studies of metal carbene
type transition metal complexes. This methodology can be involved through studies on the
elementary processes which can be applied to prepare new materials of unique properties for
various applications.
This book covers the a wider domain of research and development where the use of
transition metals have been investigated for various applications such as drug delivery,
organometallics, bio-organometallic chemistry, chemotherapy, clinical and pharmaceutical
aspects. This will enlighten the beginners by providing an excellent source of high quality
information for experts in the field. This book will also allow the bioinorganic chemists, the
pharmaceutical industry, chemists and biochemists to innovate their ideas using
multidisciplinary approach and applications of transition metals.
The book covers broad literatures in the area of transition metals in organic synthesis
including novel reactions, new catalysts, ligands, and reaction conditions and applications in
synthesis of complex organic molecules. The book is especially beneficial to the scholars who
are planning or are working towards their graduate and postgraduate degrees in this field of
bioinorganic chemistry. The advance aspects of the bioinorganic chemistry is a platform for
all levels of academics and research as it provides background for the recent research
literature, abbreviation summaries of the inorganic chemistry, biochemistry and spectroscopy.
The book is thus an interesting read for those who wish to obtain a general overview of the
most important transition metals, fundamentals concept and also will provide a useful
steppingstone for further exploration of the literature. The book also covers a wide research
area that integrates biology, chemistry, materials science, engineering and nanotechnology to
present an interdisciplinary approach for solving multitude problems. The unique approach to
cover the fundamental knowledge along with the recent advancements for the research and
development in the field of transition metals is sure to make a niche for extensive knowledge
dissipation to all ages.
In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0
Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc.
Chapter 1
ROLE OF REACTIVITY OF TRANSITION

ELEMENTS IN LIFE
Mohamed Fikry Ragai Fouda1, Omar Mohamed Abdel-Salam2

and Afaf Ezzat3
1
Professor of Inorganic Chemistry, Department of Inorganic Chemistry,
National Research Centre, Cairo, Egypt
2
Professor of Pharmacology, Department of Toxicology and Narcotics,
3
Professor of Biochemistry, Department of Nutrition and Food Sciences,
INTRODUCTION
In the last two decades, the field of biological inorganic chemistry has shown a rapid
explosion with a tremendous increase in our understanding of the roles of transition metals in
both higher plants and human life. The 25 elements that have been shown to be essential to
life in microorganisms are belonging to "s", 'b' and 'd' block elements. The "s" block
elements are namely H, Na, B, K, Mg and Ca, whereas the "b" block elements are; C, N, O, F,
Si, P, S, Cl, Se, I and As. The "d" block elements namely are V, Cr, Mn, Fe, Co, Ni, Cu and
Mo, whereas the "d" closed shell elements are Zn and Cd. Amongst all the following four 'b"
block elements, H, C, N and O are the most abundant elements in living organisms, where
they make up 99.3% of all the atoms in the body, but the remaining 21 elements only account
for 0.7 %.
Apart form the last four elements, which constitute the outermost percentage of elements
essential for life, the remaining twenty one elements can be divided into two groups: (i) the
macronutrients: these consist of seven elements; calcium, phosphorous, potassium, sulphur,
chlorine, sodium and magnesium, which are found in greater concentrations in the body than
are the remainder of the 21 elements; (ii) the trace elements: these consist of fourteen
elements; iron, manganese, copper, zinc, molybdenum, cobalt, vanadium, chromium, nickel,
fluorine, silicon, selenium, arsenic and iodine. All the 21 elements of the macronutrients and
2 Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al.
the trace elements are found in living systems, either as ions, or covalently bonded to organic
residues.
This monograph is confined to throw the light on the importance of V, Cr, Mn, Fe, Co,
Ni, Cu, which are belonging to first transition series, as well as closed shell zinc element, in
addition to molybdenum which is a member in the second transition series. This monograph
is also oriented to clarify the importance of the elements mentioned before as micronutrients
for higher plants and their participation in various enzyme systems in the plant. In that context
the sources of these inorganic micronutrients in the soil is taken into consideration. In
addition, it is aimed to explain the important role of these elements in body life, where they
are able to create oxidative stress inside the body on one hand and the ability of them to act as
antioxidants in case of attachment to some proteins, on the other hand.
Some of these metals are contained in several enzymes such as iron (transferrin),
molybdenum (xanthine oxidase), vanadium (hemovanadin), zinc (carbonic anhydrase), and
copper (hepatocuprein). There is also an evidence linking some diseases and the deficiency of
a number of transition elements. At the same time, an increase in some of transition elements
has been suggested to lead to neurodegenerative disorders e.g., iron in case of Parkinson's
disease and copper in Alzheimer's disease. In addition, the so called metallo- therapeutics
have been used in the last few decades in the treatment of some human aliments. The
application of metallo-therapy includes the use of some organometallics or metal-organic
complexes, such as using some gold and platinum complexes as antiarthritis and antitumour
drugs, respectively. The metal-based photodynamically active compounds are in use
nowadays in treatment of some types of human malignancies. Deficiency in the first raw
transition elements as well as Zn and Mo leads to deficiency in enzymes containing them in
the body. The excess amounts of these soft and borderline metals prefer to react with the soft
bases e.g., glutathione and sulfur proteins which are considered antioxidants. The different
phenomena showed by the aforementioned elements will be discussed in the light of affinity
of their cations towards several anions.
TRANSITION METALS AND PLANTS

The higher plants which are usually contain chlorophyll as a photosensitizer synthesize
their nutrients and tissues from simple substances from air and different constituents in the
soil (e.g.CO2,O2, H2O, NO-3, SO-24, Cl-, Ca2+, Mg2+, Fe+2, Mn2+, CO2-3, etc.). These elements
can be classified to three categories based on demands of them by plant. These categories are
macro-micro- and benefitial nutrients [1, 2].
The macronutrients are those elements which are required for plant with a quantities
ranged between few- and many hundreds of kilograms / hectare. These elements namely are,
hydrogen, oxygen, nitrogen, carbon, phosphorous, calcium, magnesium and sulphur. Based
on the electronic configuration of these elements one can be classified as "s" and "b" block
elements [3].
On the other hand both micro- and beneficial elements (Mn, Fe, Co, Ni, Cu, Zn, Mo, B)
are belonging to "d" block elements except B which belongs to "s" block elements.
The last two categories of elements are required for healthy plants, with a quantity ranged
between few and several hundreds of grams/hectare. These elements have important roles in
Role of Reactivity of Transition Elements in Life 3
plants and microbial vital processes [4]. The most common ones of these roles especially their
participation in the enzyme systems [see table (1)][2].
Table 1. Functions of several micronutrients in higher plants
Micronutrients Functions in higher plants

Manganese Activates decarboxylase, dehydrogenase, and oxidase enzymes;
important in photosynthesis, nitrogen metabolism, and nitrogen
assimilation.
Iron Present in several peroxidase, catalase, and cytochrome oxidase
enzymes; found in ferredoxine which participates in oxidation
reduction reactions (e.g. NO-3 and SO42- reduction, nitrogen
fixation; important in chlorophyll.
Cobalt Essential for nitrogen fixation; found in vitamin B12.
Nickel Required as a component of the urease enzyme.
Zinc Present in several dehydrogenase, proteinase and peptidase
enzymes; promostes growth hormones and starch formation;
promotes seed maturation and production.
Molybdenum Present in nitrogenase (nitrogen fixation) and nitrate reductase
enzymes; essential for nitrogen fixation and high oxidizing.
Boron Activates certain dehydrogenase enymes; facilitates sugar
translocation and synthesis of nucleic acids and plant hormones;
essential for cell division and development.
Copper Present in laccase and several other oxidase enzymes; important in
photosynthesis, protein and carbohydrate metabolism, and probably
nitrogen fixation.
Based on these foregoing findings one can notices that macronutrient elements all among
the highly abundant elements in nature, where as micro- and beneficial elements are
considered as ones from less common elements [3], except iron.
The requirements of higher plants for hard acidic ions such as Ca2+, K+, [PO2]1 can be
gained from constituents of soil as well as from artificial fertilizers such as Ca(NO3)2,
(NH4)2SO4, Ca (H2PO4)2, K2SO4, KNO3 etc. These fertilizers do not suffer from
inconsistency in case if they applied in an alkaline soil.
The microand beneficial nutrients are considered as soft and borderline elements except
Fe3+ and B3+.
The positive ions of these elements are being soft or borderline ones except Fe3+ and B3+
which are hard acidic species. Based on the foregoing discussions one can say that their
bearing compounds are found as of insoluble compounds. The last ones are found in nature
[3] according to the following:
Mn (Mn-oxides, silicates and carbonates); Fe (Fe-oxides, sulphides and silicates); Co(Co-
sulphides and silicates); Ni (Ni-sulphides and silicates); Cu (Cu- sulphides, hydroxy
carbonates and oxides); Zn (Zn-sulphides, carbonates, and silicates). The molybdenum may
be found as sulphides, oxides and molybdates [3].
The previous forms are mostly insoluble so that they are converted to soluble salts (e.g.
sulphates, nitrates) before application as fertilizers). In case of application of these salts as
fertilizers in an alkaline soil, their ions suffer from inconsistancy and transformed to
insoluble hydroxides. In such case these nutrients given to the plant in the form of metal-
organic complexes stable at alkaline medium [4]. Here in the following one can find the
nomenclature as well as chemical formulae and abbreviations of the most chelating agents
used in preparation of the corresponding micro and beneficial metal – organic complexes
which derived from ethylencdiaminetelra acetic acid and its derivates as well as citric and
oxalic acids: Ethylendiaminetetroacetic acid, (C10 H16 O8 N2, EDTA); Diethylemetriamepenta
acetic acid (C14 H22 O12 N3); cyclohexanediaminetetroacetic (C14 H22 O8 N2, CDTA);
Nitriloacetic acid (C6 H9 O6 N, HEDTA); Hydroxyethylemediaminetetroacetic acid (C10 H18
O7 N2); Ethylenediaminedichydroxyphenyl-acetic acid (C18 H20 O6 , EDDHA); Citric acid (C6
H8 O7 , CIT); Oxalic acid (C2 H2 O4,OX) [5].
CHEMICAL ELEMENTS IN LIFE

Chemical elements essential to life forms can be divided into: (1) bulk elements (H, C, N,
O, P, S) which are present in large quantities; (2) macrominerals and ions; are those needed
by the body in relatively large amounts; being composed of the "s" block elements Na, K, Ca,
Mg and "p" block elements Cl and PO3- 4); (3) micro/trace minerals; are those needed in
small amounts and consist of the d-block elements vanadium, chromium, molybdenum,
manganese, iron, cobalt, nickel, copper and zinc, and are also known as the trace metals as
well as fluorine, silicon, selenium, arsenic and iodine. The bulk metals form 1–2% of the
human body-weight whereas the trace elements represent less than 0.01% [6]. Within cells,
distribution of metal ions is more complex in that the cells must themselves control any
competition between the metal ions in the same internal compartment; moreover, the metal
ions must also have a functional value. Those elements that are found prominently in most
cells, together with their free concentrations in the central cell compartment [6-8]. The
concentration of these elements varied from an element to another.
Table 2. The concentration of selected elements in the human body [6,7]
Element Concentration in body Concentration in

(Wt) cytoplasm (mol/L)
Na+ 0.1 10-3
K+ 0.1 10-1
Mg2+ 0.04 10-3
Ca2+ 10-7
Mn2+ 2 x 10-5 10-7
Fe2+ 0.005 10-7
Co2+ 9 x 10-6 < 10-9
Ni2+ 2 x 10-5 < 10-9
Cu2+ (Cu+) 2 x 10-4 < 10-14
Zn2+ 0.003 10-11
MoO4-2 10-8
NUTRITIONALLY ESSENTIAL AND NON-ESSENTIAL METALS

Metals can also be classified as being nutritionally essential for humans such as cobalt,
chromium (III), copper, iron (II) and iron (III), manganese and molybdenum, in addition to
non-metal namely selenium and "d" closed zinc element. On the other hand metals one such
as arsenic, cadmium, lead, and mercury, and their inorganic compounds can even be toxic to
human health [9]. One can satte that these elements are considered as soft ones and can
perform stable compounds with soft sulfur compounds such as glutathione reductase and
thioproteins, preventing the last ones from preventing oxidative stress. Still there are some
metals which are not essential to human health but may have some beneficial effects at low
levels of exposure e.g., silicon, nickel, boron, and vanadium. These elements have the
capability of forming oxygen compounds. Meanwhile, boron, nickel, silicon, and vanadium
have been shown to have biological functions in plants and some animals but essentiality for
humans has not been demonstrated [9].
Soft elements are characterized by high polarizability, low electronegativity, small
negative charge, large size, covanent π type of bond usually associated with the base (electron
donor), available empty orbitals on donor atom are low lying and associative. Hard elements
are characterized by low polarizability, high electronegativity, large negative charge, small
size, ionic electrostatic type of bond usually associated with the base, high energy and
associative available empty orbitals on donor atom.
Table 3. Nutritionally essential and non-essential elements
Nutritionally essential Elements with possible Elements with no known

elements (soft and beneficial effects (hard and beneficial effects (soft and
borderline elements) borderline elements) hard elements)
Cobalt : d block element Boron : s block element Aluminum s: block element
Chromium III : d block Vanadium : d block element Barium s : block element
element Nickel : d block element Beryllium s : block element
Copper : d block element Silicon : p block element Strontium s: block element
Iron: d block element Thallium s: block element
Manganese : d block element Silver : d block element
Molybdenum : d block Antimony : p block element
element Arsenic : p block element
Zinc : d block element Cadmium : p block element
Selenium : b block element Lead : p block element
Mercury (p)
THE BIOLOGICAL VALUES OF IRON, COPPER, MANGANESE,

NIKEL, CHROMIUM, ZINC, MOLYBDENUM, COBALT AND
VANADIUM IN HUMAN
Trace elements are those elements occurring in the human body but constituting 0.01% of
body weight [10]. The trace elements include iron, manganese, copper, zinc, molybdenum,
cobalt, vanadium, chromium, nickel, fluorine, silicon, selenium, arsenic and iodine. Their
concentrations, however, vary in different tissues. In particular iron, copper, selenium,
manganese, chromium, molybdenum and iodine are essential to human health that
metalloproteins represent about one third of all structurally characterized proteins with a
biological activity and over 40% of all enzymes contain metals [6, 11]. These metals are also
required to maintain the brain's biochemistry. Their interchangeable prevalent ionic forms and
affinity for functional groups occurring in proteins are unique properties of transition metals
that make them useful in biochemical redox reactions [12, 13]. Metals determine the
geometry of enzymatic active sites, act as centers for enzyme reactivity, and act as biological
oxidation–reduction facilitators [8]. Transition metals that exist in multiple oxidation states
serve as electron carriers e.g., iron ions in cytochromes; as facilitators of oxygen transport
e.g., iron ions in hemoglobin and as sites at which enzyme catalysis occurs e.g., copper ions
in superoxide dismutase. Transition metal ions that exist in single oxidation states, such as
zinc(II), function as structural elements in superoxide dismutase and zinc-finger motifs [8].
Proteins with which transition metals and zinc are most commonly associated catalyze the
intramolecular or intermolecular rearrangement of electrons. Although the redox properties of
the metals are important in many of the reactions, in others the metal appears to contribute to
the structure of the active state, e.g., zinc in the Cu-Zn dismutases and some of the iron in the
photosynthetic reaction center. Sometimes equivalent reactions are catalyzed by proteins with
different metal centers; the metal binding sites and proteins have evolved separately for each
type of metal center [7].Copper- and zinc-containing superoxide dismutase, manganese-
containing superoxide dismutase, catalase, and glutathione peroxidase form the primary
enzymic defense against toxic oxygen reduction metabolites. But, metal-induced uncontrolled
redox reactions or displacement of endogenous metal cofactors from their cellular binding
sites can also lead to cellular perturbations [12, 13]. Moreover, any of the trace elements has
the potential to be toxic if given in sufficiently large quantities, but that for most trace
elements normal physiological or dietary conditions are extremely unlikely to achieve such
levels [14]. Whilst Fe, Cu, Cr, V and Co undergo redox-cycling reactions, for a second group
of metals, Hg, Cd and Ni, the primary route for their toxicity is depletion of glutathione and
bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical
thiols, however, other mechanisms, involving formation of hydrogen peroxide under
physiological conditions, have been proposed [15]. [As5+ + H2O2 → •OH + As3+]. Iron and
copper are redox-active metals (i.e. can switch between oxidized and reduced forms:
Cu2+/Cu1+ and Fe3+/ Fe2+) and often participate in electron transfer [16] (see below). Iron and
copper are also involved in dioxygen (O2) storage and carriage via metalloproteins [e.g.
hemoglobin, myoglobin and hemocyanin] [6]. Copper is found in essential proteins such as
cytochrome c oxidase, catechol oxidase, and ascorbate oxidase, a Cu/Zn superoxide
dismutase, and many other oxidoreductases, and monooxygenases. It is responsible for
oxidation-reduction processes that involve electron transfer, dioxygen chemistry, and
reduction of nitrogen oxides. Its position in the middle of the elements of the first transition
series (so designated because their ions have incompletely filled d orbitals) implies that iron
has the possibility of various oxidation states (from −II to +VI), the principal ones being II
(d6) and III (d5), although a number of iron-dependent monooxygenases generate high valent
Fe(IV) or Fe(V) reactive intermediates during their catalytic cycle [17](Crichton, 2001).
Copper exists mainly in two oxidation states, Cu(I) and Cu(II), and often changes between
these two states while catalyzing reactions. Transition metals such as iron and copper are
involved in both metal-catalyzed (“auto”) oxidations and reactions leading to hydroxy1

radical production from superoxide, a species frequently proposed to initiate lipid
peroxidation. Similar mechanisms involving the Fenton-like production of superoxide anion
and hydroxyl radical appear to be involved for iron, copper, chromium, and vanadium.
However, with some metal ions, such as mercury, nickel, lead, and cadmium, depletion of
glutathione and protein-bound sulfhydryls may play a primary role in the overall toxic
manifestations [12].
2O2-+2H+ →H2O2+O2
Fe2++H2O2 → Fe3+ +•OH+OH-
Traces of Fe3+ can react further with H2O2:
Fe3++H2O2→Fe2++O2-+H+
Possible more reactions:
OH+H2O2→H2O+H++O2-
O2-+Fe3+ →Fe2++O2
OH+Fe2+→Fe3++OH-
2H2O2 + Fe salt catalyst→2H2O+O2
Cu++ H2O2→ Cu2+ +•OH +OH-
• •
CH3OH+ OH →H2O+ CH2OH
Cl+•OH→Cl•+OH-
H2O2+O2-→O2+OH-+•OH
Fe3++O2-→Fe2++ O2
(O2- reducing the iron salt)
Fe2++ H2O2 →Fe3+ +•OH +OH-

(Fenton reaction)
Net : O2-+H2O2 + Fe salt catalyst →O2+•OH+OH-
The levels of essential metals are strictly regulated by specific metal transporters at
gastrointestinal tract and blood-brain barrier. When dietary levels of essential metals are low,
levels of the corresponding transporters increase in the intestine, after which there is a greater
potential for increased transport of toxic metals. The divalent metal transporter 1 (DMT1),
actively transport Fe, Zn, Mn, Co, Cd, Cu, Ni, and Pb, via a proton-coupled mechanism [18].
Involvement of intracellular transporters for copper and zinc has been shown in animal
models of Alzheimer's disease, raising the possibility that higher levels of iron, zinc and
copper might be due to a disruption in the activity of transporters. Accordingly, exposure to
toxicants that affect the activity of transporters potentially could contribute to the
aetiology/progression of neurodegenerative diseases [19] as we will see later. Two non-
enzymatic proteins, ferritin and ceruloplasmin, also appear to play important roles in
transition-metal storage and antioxidant defense in vivo. Ferritin, which binds iron in the
cytoplasm of mammalian cells, and ceruloplasmin, which binds copper in plasma, are thought
by many to contribute a significant antioxidant capacity to bodily fluids. Other proteins that
bind metals include transferrin, haptoglobin, albumin and metallothioneins are in the same
sense protective. The latter belong to a family of low molecular weight, cysteine rich
intracellular proteins that bind transition metals, including zinc and cadmium [20].
Iron
Iron is the most abundant transition metal and the second most prevalent metal of the
earth’s crust [17]. Iron is essential for microbial, plant, animal, and human life [21]. The
amount of total body iron is around 3 to 4 grams which is contained mainly in the
haemoglobin of the erythrocytes. The major site of iron storage in the body is the liver. Red
cell turnover constitutes the major pool of iron turnover in the body [22, 23]. Most iron is in
the form of heme iron that is found in hemoglobin, myoglobin, and iron-containing enzymes
(such as catalase and the cytochromes). More than two thirds of the body’s iron content is
incorporated into hemoglobin in developing erythroid precursors and mature red cells. The
rest of the total body iron exists as a nonheme iron, which consists of plasma iron, iron bound
to transferrin, and stored iron in ferritin and hemosiderin [22, 24]. Iron is a key player in some
of the most central processes of biological systems, including oxygen transport and
utilization, electron transfer, metabolism of nucleic acids and many other key biological
molecules, degradation of biological pollutants, and many other reactions [25]. The
duodenum and proximal jejunum are the main sites of absorption of dietary iron. Haem iron is
absorbed more efficiently than non-haem iron, apparently by endocytosis of the intact iron–
protoporphyrin complex at the enterocyte brush border. Iron is then liberated from the haem
moiety by the action of haem oxygenase and enters the intracellular iron pool from which it
can be transferred across the basolateral membrane, bind to transferrin and enter the
circulation. Meanwhile, absorption of non-haem iron requires reduction of ferric iron at the
brush border membrane, followed by internalization by a proton coupled transporter [2]. In
normal human plasma, serum iron (~ 20 µM) exists primarily in the Fe3+ form and is
complexed with the high affinity iron binding protein transferrin, an 80-kd glycoprotein that
is synthesized in the liver (Tf; ~ 40 µM) in a 2:1 ratio. At blood pH (7.4), each molecule of
transferrin can bind two atoms of ferric iron [27]. Only one third of the transferrin is saturated
with iron which implies that all the iron in the circulation is bound to transferring. In
circumstances in which the binding capacity of transferring becomes saturated, as for
example in iron loading disorders, iron forms low-molecular-weight complexes, the most
abundant of which is iron citrate [26]. Most cellular uptake of ferric iron (Fe3+) occurs via
receptor-mediated endocytosis of transferrin (vesicular import pathway IN2) which binds to
specific membrane-bound transferrin receptor (TfR). Inside the cell, members of the Steap
family of ferric reductases localize to the endosome and reduce Fe3+ (ferric) to its Fe2+
(ferrous) form before Fe2+ is released into the cytosol by the divalent metal transporter-1
(DMT1) in an H+-dependent manner [28]. DMT1 is not specific to iron; it can transport a
wide variety of divalent metal ions, including manganese, cobalt, copper, zinc, cadmium, and
lead [22]. Free Fe2+ in the cytosol constitutes a “labile iron” pool (~ 2-3 µM) for cellular
utilization, supplying Fe2+ molecules as co-factors for many Fe2+-dependent enzymes in the
cytosol, mitochondria, and nucleus. If cytosolic iron is not immediately used, it can also be
rapidly sequestered by cytosolic Ft into a non-reactive Fe3+- Ft complexes. Iron can be
released from cells by the iron exporter ferroportin [29]. Fe3+ can be bound in the
extracellular space by Tf, citrate, ascorbate, or ATP. Cytosolic or intralysosomal iron
overload may catalyze the production of free radical oxides via the Fenton reaction. Radical
oxides may cause cellular damage by oxidizing macromoleucles such as lipids, DNA, and
proteins. Iron transport across the blood brain barrier is the result of receptor-mediated
endocytosis of iron-containing transferrin by capillary endothelial cells, followed by recycling
of transferrin to the blood and transport of non-transferrin-bound iron into the brain. The
principle sources of extracellular transferrin in the brain are hepatocytes, oligodendrocytes,
and the choroid plexus [30].
Copper
Copper is the third most abundant metallic element in the human body, following iron
and zinc, and it is important in all other life forms. The daily intake of Cu ranges from 0.6 to
1.6 mg / day with the main sources of Cu being seeds, grains, nuts, beans, shellfish, and liver.
It is estimated that the adult human body contains between 50-150 mg [31, 32]. Free Cu2+
content of human plasma is approximately 2x10-16 M [33-36] and total copper
concentrations in most tissues are approximately 5x10-5 M total copper [37]. Clinically
apparent copper deficiency is extremely rare and difficult to achieve by dietary means, but
loss-of-function mutations in the ATP7A gene encoding a copper-transporting P1B-type
Atpase, involved in the delivery of copper to the secreted copper enzymes and required for
copper absorption and homeostasis is associated with Menkes disease, resulting severe tissue
copper deficiency, seizures, neurodegeneration, psychomotor deterioration, failure to thrive,
and death in early infancy [38, 39]. On the other hand, the toxicity associated with excess
copper manifest in Wilson disease, a rare, autosomal recessive disorder of copper metabolism
where tissue copper accumulation results in hepatic, neurologic, or psychiatric
disturbances. Mutations in the ATP7B gene which is located on the long arm (q) of
chromosome 13 (13q14.3) cause failure of copper excretion into the bile and a defective
incorporation of copper into ceruloplasmin [40]. Copper homeostasis is maintained by
adjusting intestinal copper absorption and copper excretion in bile. Copper is absorbed in the
proximal intestinal tract, facilitated by the simultaneous absorption of amino acids and
decreased by zinc and vitamin C. Excretion which occurs primarily through the bile is
increased by molybdenum, as well as by diets high in calcium and phosphorus. The excretion
of copper into the gastrointestinal tract increases when dietary copper is high and more is
absorbed, thereby, protecting against excess accumulation of copper in the body. Vice versa,
low copper intake is associated with little endogenous copper is excreted, protecting against
copper depletion [41]. This is controlled by specific transporters that take up metals at the
apical surface and export them at the basolateral surface of intestinal cells, and are involved in
their intracellular distribution. The level of these transporters increases or decreases in the
intestine according to the dietary levels of essential metals [19]. The uptake of Cu into the
cells is mediated by two transporter proteins; Cu transporter 1 (Ctr1) and divalent metal
transporter 1 (DMT1) that transports Cu across the plasma membrane (located on the plasma
membrane). ATP7A and ATP7B are membrane-bound copper-transporting P-type ATPases
that catalyze an ATP-dependent transfer of Cu to intracellular compartments or participate in
Cu efflux from the cell [42]. Cellular copper excretion also involves COMMD1 [copper
metabolism (Murr1) domain containing 1] [43]. Most of Cu ions absorbed from the small
intestine are distributed to liver and kidneys; they are transported in blood mostly (65-90%)
by tightly binding to protein "ceruloplasmin", synthesized in the liver where it binds Cu and
the rest of Cu loosely binds with albumin, transcuprein and amino acids (e.g., histidine) [33].
Only reduced Cu can be transported [43]. Cu is transported into the brain through the blood
brain barrier as a free Cu ion [44]. Redox cycling between Cu2+ and Cu1+ can catalyse the
production of highly toxic hydroxyl radicals, with subsequent damage to lipids, proteins,
DNA and other biomolecules. Free intracellular copper is detoxified primarily by
metallothionein (MT) proteins. Metallothioneins are ubiquitous low molecular weight
proteins rich in cysteine residues that have high metal-binding capacities. They bind heavy
metal ions (mainly Cd, Zn and Cu) via metal-thiolate clusters, thus they are essential in metal
homeostasis and protect against metal toxicity [45, 46]. The incorporation of intracellular
copper into the structure of different cuproenzymes is carried out by copper chaperones;
Atox1 (delivers copper to copper transporting ATPases in the late Golgi), CCS (copper
chaperone for SOD, required for copper incorporation into Cu/Zn superoxide dismutase), and
Cox17, Sco1 and Sco2 (delivers copper to subunits of mitochondrial cytochrome c oxidase)
[43, 47]. Copper chaperones through transporting copper in the cytoplasm to the site of
utilization by copper-dependent proteins, ensure that copper can reach its specific target
protein and also prevent inappropriate copper interactions with other cellular, protecting the
cell from the deleterious effects of free copper e.g., protection against oxidative stress [48].
An increase in the endogenous level of Atox1 expression have been demonstrated protect
neurons against oxidative stress. Furthermore, overexpression of an Atox1 metal binding
mutant is detrimental to cell viability. Furthermore, mutations in the copper binding motif of
Atox1 result in a dominant negative phenotype where the cell viability is diminished [49].
The copper chaperone for the superoxide dismutase gene is necessary for expression of an
active, copper-bound form of superoxide dismutase in vivo in spite of the high affinity of
superoxide dismutase for copper. This metallochaperone protein activates the target enzyme
through direct insertion of the copper cofactor and apparently functions to protect the metal
ion from binding to intracellular copper scavengers. Thus intracellular [Cu]free is limited to
less than one free copper ion per cell and a pool of free copper ions is not used in
physiological activation of metalloenzymes [50]. The highest concentration of CCS is found
in the kidney and liver. There is also a significant amount of this copper chaperone protein in
the CNS being found throughout the neuropil, with expression largely confined to neurons
and some astrocytes [51]. Cu is required as a catalytic cofactor in various cuproenzymes,
including the mitochondrial cytochrome c oxidase, a component of the electron transport
chain, caeruloplasmin, monoamine oxidase, dopamine B-hydroxylase, tyrosinase, involved in
the production of melanin histaminase, lysyl oxidase, involved in the cross-linking of elastin
and collagen, and Cu/Zn-superoxide dismutase. The enzyme superoxide dismutase (SOD)
occurs in three forms in mammalian systems: (1) CuZnSOD (SOD1) found in the cytosol, (2)
MnSOD (SOD2) found in mitochondria, and (3) CuZnSOD found in extracellular space
(SOD3). The active site in Cn/Zn superoxide dismutase consists of one Cu atom and one Zn
atom, coordinated to a common histidine ligand; His63 in human SOD1 and His61 in human
SOD2. The copper atom is coordinated by three other histidine residues and zinc is
coordinated by two other histidine residues and one asparagines [52]. Additionally, many
bacterial SOD enzymes contain iron. Copper is also an essential component of chromatin and
is involved in chromatin scaffold proteins. Food copper (organic copper) is processed by the
liver and is transported and sequestered in a safe manner. Inorganic copper, such as that in
drinking water and copper supplements, largely bypasses the liver and enters the free copper
pool of the blood directly. This copper is potentially toxic because it may penetrate the
blood/brain barrier [53]. Cu toxicity comes about from its ability to produce reactive oxygen
species, displace other metal ions, peroxidize lipids, and directly cleave DNA and RNA.
Copper exists physiologically in two redox states, as cuprous Cu1+ (reduced) or cupric Cu2+
(oxidized) and can interchange between these forms by accepting or donating an electron.
This allows the cation to participate in biochemical reactions as a reducing or oxidizing agent
[54]. This same properties which make copper being essential for various enzymatic
reactions, is also responsible for copper toxicity via its ability to generate free radicals, in
particular, the highly reactive hydroxyl radical through Fenton chemistry, which subsequently
can damage lipids, proteins, DNA and other biomolecules [55]. Most extracellular copper is
Cu(II) and most, if not all, intracellular copper is Cu(I). Typical intracellular copper-binding
proteins, such as the Cu-transporting P-type ATPases ATP7B and ATP7A bind copper as
Cu(I)[54]. It has been suggested that, the toxic and carcinogenic potential of mineral dusts
inhaled into the lungs is related, in part, to biochemical reaction mechanisms involving iron
and reactive oxygen species that occur at the mineral surface [56, 57]. Many cancer tissues
contain highly elevated levels of Cu [58, 59]. The reasons for this elevation are unclear but
one possible result is increased angiogenesis [60, 61]. The copper-chelating agent, trientine,
suppressed tumor development and angiogenesis in the murine hepatocellular carcinoma cells
[62]. A copper transporter, Ctr1p, was discovered to mediate cisplatin uptake in yeast and
mammals. Increased cisplatin resistance caused by deletion of the Ctr1 gene suggests its
important role in cellular resistance. This finding presents a potential target for modulating
cisplatin antitumor efficacy [63].The combined treatment with a copper chelator and cisplatin
increased cisplatin-DNA adduct levels in cancerous but not in normal tissues, impaired
angiogenesis, and improved therapeutic efficacy. Others reported increased accumulation of
iron, nickel, chromium, zinc, cadmium, mercury, and lead in breast cancer samples [64].
Cancerous cells have more transferrin receptors than normal cells [65] because of their need
for oxygen. In our opinion, the high levels of singlet oxygen attacks the species of sulphur
(glutathione) which acts as an antioxidant. The complexation of metals with SH bearing
compounds leads to a decrease in antioxidant capacity.
Manganese
Manganese (Mn) is the 12th most abundant element in the earth’s crust comprising about
0.1% of the earth’s crust [66, 67]. Manganese is an essential mineral for humans, animals, and
plants. It is present in virtually all diets at low concentrations. Mn is present in most tissues of
all living organisms and is present naturally in rocks, soil, water, and food. Humans maintain
stable tissue levels of Mn via tight homeostatic control of both absorption and excretion of
ingested Mn and limit tissue uptake at low to moderate levels of inhalation exposure [68-70].
The most significant source of manganese exposure for the general population is food. The
highest manganese concentrations are found in nuts (up to 47 µg/g) and grains (up to 41
µg/g). Lower levels are found in milk products (0.02–0.49 µg/g), meat, poultry, fish, and eggs
(0.10–3.99 µg/g), and fruits (0.20–10.38µg/g). Tea and leafy green vegetables have also been
found to be dietary sources of manganese [71]. Mn is absorbed from the gastrointestinal tract,
within the plasma, Mn is largely bound to gamma-globulin and albumin, and a small fraction
of trivalent (3+)Mn is bound to the iron-carrying protein, transferring [70]. The Mn adequate
intake for adult men and women is 2.3 and 1.8 mg/day, respectively [71]. Serum
concentration of Mn in healthy subjects is about 0.05–0.12 µg/dl [72].
The total amount of manganese in the adult human (70 kg) has been determined to be
about 10-20 mg, most of which is found in skeleton, liver, kidney, pancreas and the heart. The
rest is distributed widely throughout all the tissues and fluids. A daily requirement for
manganese has not been established; however, it appears that a minimum intake of 2.5 to 7
milligrams per day meets human needs. In humans, manganese is an essential nutrient that
plays a role in bone mineralization, protein and energy metabolism, metabolic regulation,
cellular protection from damaging free radical species, and the formation of
glycosaminoglycans. An adequate amount of this trace mineral would be absolutely vital
during gestation for normal foetal growth and development [73,74]. Mn dependent enzyme
families include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.
Manganese metalloenzymes include arginase (liver urea), glutamine synthetase (brain
ammonia metabolism), phosphoenolpyruvate decarboxylase (gluconeogenesis). Mn is also the
key component of superoxide dismutase (Mn-SOD) found in mitochondria of the cells. The
manganese-containing superoxide dismutase (MnSOD) is a major component of the cellular
defence mechanisms against the toxic effects of the superoxide radical [75].
While Mn deficiency is extremely rare in humans, toxicity due to overexposure of Mn is
more prevalent. Mn toxicity has been reported in individuals exposed to high environmental
levels of Mn e.g. miners, welders and those living near ferroalloy processing plants. Toxicity
can also result from dietary overexposure and is evidenced primarily in the central nervous
system, although lung, cardiac, liver, reproductive and fetal toxicity have been noted [72].
The brain appears to be especially vulnerable to Mn accumulation resulting in is an
established clinical entity, referred to as manganism which is a progressive disorder of the
extrapyramidal system similar to Parkinson's disease in its clinical features, both in laboratory
animals and humans [69, 70]. Neurotoxicity due to excessive brain manganese (Mn)
accumulation can occur via occupational exposure to aerosols or dusts that contain extremely
high levels (>1-5 mg Mn/m(3)) of Mn, consumption of contaminated well water, or parenteral
nutrition therapy in patients with liver disease or immature hepatic functioning such as the
neonate(decreased biliary excretion). Although Mn exposure via parenteral nutrition is
uncommon in adults, in premature infants, it is more prevalent [76].
Transport of manganese across the blood-brain barrier occurs by means of a series of
transporters. Movement can take place by facilitated diffusion, active transport [77] via
divalent metal transport and transferring (Tf)-dependent transport. Biliary excretion
represents the main mechanism by which manganese is eliminated from the body [78]. Mn
disposition in vivo is influenced by dietary iron intake and stores within the body since the
two metals compete for the same binding protein in serum (transferrin) and subsequent
transport systems (divalent metal transporter, DMT1). There appear to be two distinct carrier-
mediated transport systems for Mn and ferrous ion: a transferrin-dependent and a transferrin-
independent pathway, both of which utilize DMT1 as the transport protein [79]. In primary
astrocyte cultures derived from neonatal rats.. Both iron deprivation (ID) and iron overload
(+Fe) caused significant increases (p<0.05) in (54)Mn uptake in astrocytes. The decreased
TfR associated with +Fe treatment and the increased DMT-1 levels suggest that DMT-1 is a
likely putative transporter of Mn in astrocytes [80]. Fe deficiency can enhance brain Mn
accumulation even in the absence of excess Mn in the environment or the diet, suggesting that
there is homeostatic relationship among several essential metals in the brain and not simply
between Fe and Mn [81]. Mn transport appears to be temperature, energy, and pH dependent,
but not Fe or Na(+) dependent. These data suggest that Mn transport across the BBB is an
active process [82]. After intravenous contrast injection, normal (enteral) regulation
mechanisms for manganese homeostasis are bypassed, and there is a danger of individual
overdosing. Excess manganese, for example in patients with chronic liver disease or with
chronic parenteral nutrition, has already been detected by magnetic resonance imaging in the
basal ganglia and was found to coincide with neurologic symptoms [83].
Zinc
Zn is the trace element which is essential for cell growth and maintenance of cellular
integrity. It is an integral structural component of nearly 300 enzymes and other proteins
involved in the expression of genetic information and cellular signal transduction. Zinc is
present in all body tissues and fluids. The total body zinc content has been estimated to be
30mmol (2g). Skeletal muscle accounts for approximately 60% of the total body content and
bone mass, with a zinc concentration of 1.5–3µmol/g (100–200µg/g), for approximately 30%.
Lean red meat, whole-grain cereals, pulses, and legumes provide the highest concentrations of
zinc: concentrations in such foods are generally in the range of 25–50mg/kg (380–
760µmol/kg) raw weight. Fish, roots and tubers, green leafy vegetables, and fruits are only
modest sources of zinc, having concentrations <10mg/kg (<150µmol/kg) [84].
Zinc deficiency can result from low-zinc-containing diets (e.g., vegetarians), prolonged
intravenous alimentation, gastrointestinal disease associated with diarrhea [85]. In humans,
inherited zinc deficiency is rare and associated with defects in membrane-bound putative
zinc transporters leading to impairment of zinc absorption in the gut and the syndrome of
acrodermatitis enteropathica, characertized by skin lesions, alopecia, diarrhoea,
neuropsychological disturbances and reduce immune function and led to death of the patient
in the absence of treatment. A zinc deficiency disorder also occurs in premature breast fed
infants [86].
Zinc is relatively abundant in biological materials being an essential component of
hundreds of proteins and metalloenzymes including alkaline phosphatase, lactate
dehyrogenase, carbonic anhydrase, angiotensin-converting enzyme, collagenase, δ-
aminolevulinic acid anhydrase, protein kinase C, phospholipase C, aspartate
transcarbamylase, nucleotide phosphorylase (5’-nucleotidase) carboxypeptides, and DNA and
RNA polymerases found in most body tissues [85, 87]. The major location of zinc in the body
is metallothionein, which also binds copper, chromium, mercury, and other metals. Among
the well-characterized zinc proteins are the Cu-Zn superoxide dismutases (other forms have
Fe or Mn), carbonic anhydrase (an abundant protein in red blood cells responsible for
maintaining the pH of the blood), alcohol dehydrogenase, and a variety of hydrolases
involved in the metabolism of sugars, proteins, and nucleic acids. Zinc is a common element
in nucleic-acid polymerases and transcription factors, where its role is considered to be
structural rather than catalytic [88].
Zinc plays specific and important catalytic, co-catalytic and structural roles in enzyme
molecules and in many other proteins and biomembranes. A well-known example of the
structural role of zinc in cellular and subcellular metabolism is the zinc finger motif,
ubiquitous in transcription proteins. The configuration of zinc fingers, critical to DNA
binding, is determined by the single zinc atom at their base. The linking of zinc fingers to
corresponding sites on the DNA initiates the transcription process and gene expression.
Motifs similar to zinc fingers have been identified in nuclear hormonal receptors including
those for vitamin D, estrogen and testosterone. Zinc plays an important role as ionic signaling
in large number of cells and tissues. Zinc-binding proteins account for nearly half of the
transcription regulatory proteins in the human genome, and during the past two decades, well
over 2000 zinc-dependent transcription factors involved in gene expressions of various
proteins have been reported [87, 88].
Among the transition metals playing key roles in biological systems, zinc is second only
to iron in biological prevalence. Unlike iron and copper, zinc has only one oxidation state
accessible under physiological conditions, and therefore does not participate in catalysis of
redox chemistry or electron transfer reactions. Unlike other first-row transition metals (e.g.,
Sc2+, Ti2+, V2+, Cr2+, Mn2+, Fe2+, Co2+, Ni2+ and Cu2+), the zinc ion (Zn2+) contains a filled d
orbital (d10) and therefore does not participate in redox reactions but rather functions as a
Lewis acid to accept a pair of electrons [89]. The types of enzymatic reactions in which zinc
is found to play a role include peptidases and amidases, phosphatases, phospholipase,
phosphotriesterase, deaminases and alcohol dehydrogenase, among others. One mechanism
by which zinc is believed to facilitate some of these reactions is through binding and thereby
lowering the pKa of water, generating a localized high concentration of metal-bound
hydroxide in the active site, which can act as a nucleophile in the hydrolytic reactions [25].
Zinc is very different from magnesium, manganese and calcium. It binds nitrogen and
sulfur much more readily and also shows lower coordination numbers in spite of its size
(which is intermediate between that of magnesium and divalent manganese. It was found that
the predominant ligand to zinc depends on the coordination number of the metal ion, whereas
the other metal ions just listed each prefer oxygen at all coordination numbers. Zinc tends to
form 4-, 5-, and 6- coordinate complexes with about equal ease. When the coordination
number is four, sulfur is as likely a ligand as oxygen, when it is 5 nitrogen is the most
common ligand, and for coordination numbers 6 and 7 oxygen predominates as a ligand.
Thus, zinc can possibly replace magnesium or divalent manganese (since they both bind
oxygen when their coordination number is 6), but it has other options for coordination, in
keeping with its reactivity in the active sites of enzymes (often involving a change in
coordination number). [90].
Molybdenum
Molybdenum is a very rare element with a crustal abundance of about 1.2 mg/kg [91].
Molybdenum is the only second-row transition metal that is required by most living
organisms [92]. The tolerable upper intake level for the United States and Canada was set at 2
mg/d in 2002 [93], and the European Commission suggested an upper limit of 0.6 mg/d
[94].The availability of molybdenum to biological systems is due to the high water solubility
of oxidized forms of the metal. In man, absorption of molybdenum after oral intake is in the
range of 28-77% and urinary excretion is 17-80% of the total dose [95]. Stable-isotope studies
of molybdenum metabolism have been conducted in which molybdenum was added to the
diet and was assumed to be absorbed and utilized similarly to the molybdenum in foods.
These studies showed that molybdenum is well absorbed over a range of intakes, that it is
rapidly excreted via the urine, and that total body molybdenum retention is regulated
primarily via urinary excretion. With high molybdenum intake, molybdenum absorption
increases and excretion is more rapid [96]. In healthy young men, absorption of molybdenum
from the intestine increased at higher molybdenum intakes.Urinary output appears to be the
key pathway for regulating the body's exposure to molybdenum. Higher molybdenum intake
resulted in higher rates of urinary excretion [97]. Because molybdenum toxicity is associated
with copper intake or depleted copper stores in the body, humans who have an inadequate
intake of dietary copper or some dysfunction in their copper metabolism that makes them
copper-deficient could be at greater risk of molybdenum toxicity [95].
Deficiency is rare in humans and is limited primarily to genetic defects leading to serious
abnormalities. Molybdenum cofactor deficiency in humans results in the loss of the activity of
molybdoenzymes sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. The
resultant severe phenotype, which includes progressive neurological damage leading in most
cases to early childhood death, results primarily from the deficiency of sulfite oxidase.
Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are autosomal
recessive inborn errors of metabolism with severe neurological symptoms resulting from a
lack of sulfite oxidase activity [98, 99].
The metal itself is biologically inactive unless it is complexed by a special cofactor. With
the exception of bacterial nitrogenase, where Mo is a constituent of the FeMo-cofactor, Mo is
bound to a pterin, thus forming the molybdenum cofactor (Moco) which is the active
compound at the catalytic site of all other Mo-enzymes. Several enzymes in humans contain
molybdenum catalysing diverse redox reactions. In man, these enzymes, sulfite oxidase,
xanthine oxidase, and aldehyde oxidase, contain the same molybdenum complex,
molybdopterine. The molybdenum enzymes xanthine oxidase, sulfite oxidase and aldehyde
oxidase are involved in the human diseases of gout, combined oxidase deficiency and radical
damage following cardiac failure. Sulfite oxidase catalyzes the final step in the degradation of
sulfur-containing amino acids and is involved in detoxifying excess sulfite. Xanthine oxidase
is the final enzyme in the conversion of hypoxanthine to xanthine, and subsequently, to uric
acid. Aldehyde oxidase catalyzes the oxidation of aldehydes, pynmidines, purines, pteridines,
and related compounds [100, 101].
The metal is found in three different oxidation states (IV, V and VI) and has the desirable
ability to couple biological compounds that are obligatory two-electron carriers (e.g. NADH)
with obligatory one-electron carriers (e.g. iron-sulphur centres and cytochromes) [102].
Cobalt
Cobalt is the least abundant 3dr transition metal (in sea water and earth crust). Cobalt is
found in vitamin B12 , its only apparent biological site. Vitamin B12 occurs in the body
mainly as methylcobalamin, adenosylcobalamin and hydroxycobalamine(a precursor to
methyl and adenosylcobalamine). Hydroxycobalamine is most stable form of all cobalamine
and is water soluble. B 12 is found in animal protein and not in vegetables. Cobalt is an
essential metal for humans and has to be ingested in the form of cobalamines (vitamin B12).
Only microorganisms can biosynthesize cobalamine. Cobalt in cobalamines can be reduced
and oxidized (2-one electron steps), thus cobalamine containing enzymes participate in redox
reactions. Vitamin-B 12 deficiency causes the severe disease of pernicious anemia in humans,
which indicates the critical role of cobalt [103, 104].
The vitamin B12 cofactors coenzyme B12 or 5’-deoxy-5’-adenosylcobalamin (AdoCbl),
and methylcobalamin (MeCbl) consist of cobalt(III) bound to a substituted corrin ring and an
alkyl group (either adenosyl or methyl). Adenosylcobalamin (AdoCbl) or coenzyme B12 is an
organometallic cofactor that functions as a radical reservoir and is used by enzymes to
catalyze rearrangement reactions in which a hydrogen atom and a variable group on adjacent
carbons are interchanged (mutases and eliminases). Methylcobalamin (MeCbl) is the cofactor
of several methyltransferases, such as methionine synthase (MetH), which catalyzes
methionine biosynthesis both in mammals and bacteria [104, 105].
Chromium
Chromium is an essential nutrient required for sugar and fat metabolism. The estimated
safe and adequate daily dietary intake for Cr is 50 to 200 microg. However, most diets contain
less than 60% of the minimum suggested intake of 50 microg, suggesting that the normal
dietary intake of Cr for humans is suboptimal. Trivalent Cr has a very large safety range and
there have been no documented signs of Cr toxicity in any of the nutritional studies at levels
up to 1 mg per day [106]. Trivalent chromium is an essential nutrient required for sugar and
fat metabolism. Most recent evidence strongly supports the conclusion that there is little fear
of toxic reactions from chromium consumption. In addition to type 2 diabetes mellitus,
chromium supplementation may be useful to direct overall weight decrements specifically
towards fat loss with the retention of lean body mass and to ameliorate many manifestations
of aging [107]. There is growing evidence that chromium may facilitate insulin signaling and
chromium supplementation therefore may improve systemic insulin sensitivity. However,
supplementation with chromium picolinate, a stable and highly bioavailable form of
chromium, has been shown to reduce insulin resistance and to help reduce the risk of
cardiovascular disease and type 2 diabetes [108]. However, controversy exists as to whether
dietary supplementation with chromium should be routinely recommended in subjects
without documented deficiencies [109]. Whether chromium is an essential element has been
examined for the first time in carefully controlled metal-free conditions using a series of
purified diets containing various chromium contents. Animal studies reveal that a diet with as
little chromium as reasonably possible had no effect on body composition, glucose
metabolism, or insulin sensitivity compared with a chromium-"sufficient" diet [110].
Vanadium
Vanadium, a dietary micronutrient, is yet to be established as an essential part of the

human diet. Vanadium is abundant in rocks and soil [110]. Constituting 0.015% of earth's
crust, vanadium is about as abundant as zinc [111]. In water the presence of vanadium derives
almost exclusively from the solubilization of the metal present in soil and in rocks [110].
Exposure to the vanadium in water is enough to affects its presence in the daily diet and
determines greater values of the element in the principal biological liquids in people [112].
The metal is present in comparatively high concentration of vanadium in sea water, being
second most abundant transition metal (30 nM Na+2VO-4), only surpassed by molybdenum
(100 nM molybdate), and clearly more abundant than iron (0.02–1 nM). Vent-derived iron
oxides have been shown to scavenge vanadium from sea water and thus to contribute in
controlling the concentration and cycling of vanadium in the oceans [111]. Concentrations in
soil vary in the range 3-310 μg/g and may reach high values (up to 400 μg/g) in areas polluted
by fly ash. The concentration of vanadium in water is largely dependent on geographical
location and ranges from 0.2 to more than 100 μg/litre in freshwater, and from 0.2 to 29
μg/litre in seawater [113]. Vanadium is introduced into man through the intake of food,
especially whole meal cereals, but also beef, chicken, milk, spinach, mushrooms, parsley
[114]. The mean vanadium concentration in the diet was reported to be 32 μg/kg (range 19-50
μg) and the mean daily intake was estimated to be 20 μg/day [113]. Absorbed vanadium is
transported mainly in the plasma, bound to transferrin. Pentavalent vanadium is reduced in
erythrocytes to the tetravalent form. This reduction is a glutathione-dependent process [113].
It appears that values, around 1 nmol/l for blood and serum and around 10 nmol/l or slightly
lower for urine may be considered tentative normal values [115].
This transition element is known to influence a battery of enzymatic systems, namely
phosphatases, ATPases, peroxidases, ribonucleases, protein kinases and oxidoreductases.
In biological conditions, vanadium fulfils two conditions for a potential biometal: (i)
redox activity in an electrochemical potential (and free energy) frame relevant for
biochemical processes, and (ii) susceptibility for nucleophilic substrates.Vanadium easily
switches between the oxidation states V and IV (which, along with III, are the oxidation states
of naturally occurring vanadium compounds). The redox potential at pH 7 for the couple
H2VO4-+4H+ +e- VO2+ + 3H2O amounts to -0.341 V and thus is in the range where
2+
vanadyl (VO ) is oxidised to vanadate under aerobic conditions, and vanadate reduced to
vanadyl by cellular components such as cysteine containing peptides (glutathione) and
proteins, ascorbate, NADH, and phenolic compounds. The main species present under
physiological aerobic conditions is the acid-base pair H2VO4- → HVO42-+ H+ (pka = 8.1)
[111].
Nickel
Nickel is widely distributed in the environment. Natural sources of atmospheric nickel

include dusts from volcanic emissions and the weathering of rocks and soils. Thus, humans
are constantly exposed to this ubiquitous element although in variable amounts. The daily
dietary intake of nickel is 25–35 g, and it is more than triple the daily requirement [116].
Generally, greater than 250 µg nickel of Ni/g of diet are required to produce signs of Ni
toxicity such as depressed growth and anaemia in animals [117]. Ni-dependent enzymes are
urease, [NiFe] hydrogenase, [Ni] superoxide dismutase, CO dehydrogenase, and S-methyl-
CoM reductase, which catalyzes the terminal step in methane production by methanogenic
bacteria. All the Ni-proteins known to date are from plants or bacteria [116].
TRANSITION METALS AND HUMAN DISEASE

Role of Transition Elements in Cancer
Cancer is undoubtly one of the most grave human disease known so far. Several
transition metals, including chromium(vi), nickel, and cadmium have been suggested as
human carcinogens [118]. All these elements are soft and borderline elements i.e., they are
able to associate with thiols or compounds containing SH group. Metals are widely
distributed elements, usually occurring at low levels in the earth’s crust, although some
geographic areas have naturally high levels in soil. Metals are released into the environment
during mining operations, industrial and manufacturing processes, and as by-products of
combustion. Metals are generally present at low concentrations in ambient air, although much
higher concentrations have been measured near metal processing facilities. Metals typically
do not require bioactivation, at least not in the sense that an organic molecule undergoes
enzymatic modification that produces a reactive chemical species [119]. Cadmium, lead, and
nickel compounds have been shown to be mutagenic and carcinogenic in rodent studies [120]
because of their ability to inhibit the repair of damaged DNA. In addition, they can enhance
the mutagenicity and carcinogenecity of directly-acting genotoxic agents [121].
A case-control study of breast cancer and metal exposure found an increased risk for
women exposed to a group of metals (chromium, arsenic, beryllium, and nickel), as well as
exposure to lead and cadmium individually [122]. A highly significant accumulation of iron,
nickel, chromium, zinc, cadmium, mercury, and lead was found in the cancer samples when
compared to the control group [63]. Increased Cu concentrations were also found in human
lung cancer biopsies [123] and in other tumors [124]. Excessive lipid peroxidation induced
malondialdehyde-DNA adducts was detected in the breast tissue of women with breast cancer
leading to endogenous DNA modifications [125].
The most common airborne exposures to nickel compounds are to insoluble nickel
compounds such as elemental nickel, nickel sulfide, and the nickel oxides from dusts and
fumes. Contributions to nickel in the ambient air are made by combustion of fossil fuels,
nickel plating, and other metallurgical processes. The most common oxidation state of nickel
is the divalent (Ni2+) form [126]. Nickel is also used in electroplating baths, batteries, textile
dyes, and catalysts. Ni (II) in the presence of H2O2 produced greater base damage to the
DNA in chromatin than to isolated DNA, unlike Co (II) [127]. Nickel compounds are
carcinogenic to humans and metallic nickel is possibly carcinogenic to humans. A 2-year
inhalation study of nickel oxide in rats and mice conducted by the National Toxicology
Program [128] indicated a carcinogenic effect of nickel oxide in the lungs. Occupational
exposure to nickel producing anelevated risk of nasal cancer and a 30% excess of lung cancer
in the workforce nasal cancer and a 30% excess of lung cancer [129]. It has been shown that
histone demethylase JMJD1A and DNA repair enzyme ABH2 family of dioxygenases is
highly sensitive to inhibition by nickel ions through by replacing the ferrous iron in the
catalytic centers. Inhibition of these dioxygenases by nickel is likely to have widespread
impacts on cells (e.g. impaired epigenetic programs and DNA repair) and may eventually
lead to cancer development [130].
The U.S. National Toxicology Program (NTP, 2002)[131] carcinogenicity study of
inhaled V(2)O(5) in rats and mice, concluded that clear evidence of lung tumors was seen in
mice of both genders and that there was some evidence of carcinogenicity in male rats. In
response to this study, vanadium pentoxide (V(2)O(5)) and other inorganic vanadium
compounds have recently been evaluated by several occupational exposure limit setting
committees and expert groups. It has been argued that, because of inherent weaknesses in
design and procedure, the U.S. National Toxicology Program study of the carcinogenicity of
inhaled vanadium pentoxide does not provide adequate evidence to support the classification
by regulatory authorities of vanadium pentoxide as a Group 2B (possible) human carcinogen
[132, 133]. The lungs are a significant site of entry of vanadium in the case of community
exposure [113]. Vanadate enters cells where it is reduced by glutathione and other agents to
vanadyl species (VO2+) and stabilized as such by various ligands. Vanadyl binds readily to
proteins, amino acids, nucleic acids, phosphates, phospholipids, glutathione, citrate, oxalate,
lactate, ascorbate, edetate, etc. [134]. Welding fumes contain many different metals including
vanadium typically present as particulates containing vanadium pentoxide (V2O5). Recently,
inhalative exposure to vanadium pentoxide in workers from a V(2)O(5) factory has been
reported to cause oxidation of DNA bases, affect DNA repair, and induce formation of
nucleoplasmic bridges and nuclear buds in leukocytes, suggesting that the workers are at
increased risk for cancer and other diseases that are related to DNA instability [135]. In vitro,
human peripheral lymphocyte cultures were exposed to 1, 2, 4, or 8 microg/mL of
vanadium(III) trioxide, vanadium(IV) tetraoxide, or vanadium(V) pentoxide (V(2)O(3),

V(2)O(4), or V(2)O(5), respectively. These cultures were then screened for structural
chromosomal aberrations, and mitotic index (MI) measurements were made. Cytogenetic
evaluations showed that only V(2)O(4) increased the percentage of aberrant cells (without
gaps) and chromosome damage (including and excluding gaps), while all compounds led to a
decrease in the MI. These results demonstrate that vanadium(III), vanadium(IV), and
vanadium(V) are all capable of inducing cytotoxicity, but only oxidation state IV induces
clastogenic effects [136]. Furthermore, vanadium pentoxide induced pulmonary inflammation
and tumor promotion in some strains of mice [137]. Vanadate generates the hydroxyl radical
via a Fenton-like reaction rather than a Haber-Weiss reaction [138].
V(V)+O2•-→ V(ΙV)+ O2
V(ΙV)+ H2O2→ V(V) +•OH+OH-
Some essential metals e.g., chromium VI and iron can also be carcinogenic. Chromium is
naturally occurring in rocks, animals, plants, soil and in volcanic dust and gases. Trivalent
chromium (III) is an essential nutrient for the body. Hexavalent chromium (VI), is generally
produced by industrial processes. Non-occupational exposure to Cr(VI)compounds occurs
from cigarette smoke, automobile emissions, areas of landfills and hazardous waste disposal
sites [139, 140]. Cr(VI) compounds have been classified as group I human carcinogens by the
International Agency of Research in Cancer in 1990 [141]. When inhaled, chromate particles
dissolve to form soluble Cr(VI) oxyanions that enter cells through non-specific anionic
transporters and are metabolically reduced within the cell by ascorbic acid and low molecular
weight thiols glutathione and cysteine to their lower oxidation states such as Cr(V), Cr(IV)
and Cr(III) ), the most stable form of Cr in cells. During the one-electron reduction of Cr(VI),
superoxide anion (O2·–) and hydroxyl radicals are produced causing DNA damage [142,-146].
Reactive oxygen species were produced by the decomposition of Cr(V)(O2)4 -3 ion, resulting
in DNA damage. The generation of hydroxyl radical was detected by ESR [147]. Cr(III)
forms coordinate covalent and ionic interactions with DNA bases and the phosphodiester
backbone, respectively [148, 149].
Cr(ΙΙΙ)+O2•-→ Cr(ΙΙ)+ O2
Cr(ΙΙ)+ H2O2→ Cr(ΙΙΙ) +•OH+OH-
Cr(VΙ)+O2•-→ Cr(V)+ O2
Cr(V)+ H2O2→ Cr(VΙ) +•OH+OH-
Hypervalent Cr species (Cr(V), Cr(IV)), and carbon based and oxygen radicals may also
react with DNA following Cr(VI) reduction [147, 150]. During Cr(VI) reduction, a diverse
range of genetic lesions are generated including Cr-DNA binary (mono) adducts, Cr-DNA
ternary adducts, DNA-strand breaks, DNA-protein crosslinks, oxidized bases, abasic sites,
and DNA inter- and intrastrand crosslinks. The damage induced by Cr(VI) can lead to
dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints,

dysregulated DNA repair mechanisms, microsatelite instability, inflammatory responses, and
the disruption of key regulatory gene networks responsible for the balance of cell survival and
cell death, which may all play an important role in Cr(VI) carcinogenesis [151, 152]. Electron
spin resonance (ESR) and fluorescence analysis revealed that Cr(VI) increased intracellular
levels of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anion
radical in dose-dependent manner [153]. Mitochondrial ROS, specifically superoxide anion
(O2·–), mediates Cr(VI)-induced apoptosis of human lung epithelial H460 cells [154]. Cr(VI)
induced a mitochondrial-mediated and caspase-dependent apoptosis in skin epidermal cells
through reactive oxygen species-mediated activation of p53 [153]. Evidence indicates that
trivalent chromium compounds do not cause cancer, although high concentrations in some in
vitro systems have shown genetic toxicity. Hexavalent chromium compounds cause cancer in
humans, in experimental animals and exert genetic toxicity in bacteria and in mammalian
cells in vitro. Epidemiological evidence and animal studies indicate that the slightly soluble
hexavalent salts are the most potent carcinogens [155]. In their study, Gibb et al.[156]
demonstrated a strong dose-response relationship of cumulative hexavalent chromium
exposure and the risk for lung cancer in exposed human workers; cumulative trivalent
chromium exposure was not. The excess risk of lung cancer associated with cumulative
hexavalent chromium exposure was not confounded by smoking status.
Several epidemiological studies have reported a possible correlation between measures of
iron status and cancer among people in the general population and it is possible that iron
accumulation in the liver is a risk factor for hepatocellular carcinoma in patients with
haemochromatosis who also had increased incidence of extrahepatic cancer as well [157-
159]. In this disease status in which Fe++ accumulates in tissues as a result of an autosomal
recessive genetic disease leading to enhanced gastrointestinal absorption of iron that leads to
a progressive increase of iron stores, the concentration of this redoxactive transition metal
capable of catalyzing and/or generating free radicals like superoxide, hydrogen peroxide, and
hydroxyl radical is markedly increased inducing cellular lipid peroxidation and DNA-attack
[160, 161]. Studies have shown a greater ability than normal cells for tumor cells to grow and
survive in the presence of high concentrations of iron [162]. In contrast, tumor growth in iron-
deficient mice [163]. Iron may also act as a promoter of already initiated hepatocytes in the
development of liver cancer in the rat [164]. A study of a national cohort of United States
adults suggested an increased risk of dying from cancer with higher levels of serum iron,
transferrin, and serum copper at baseline in males and females. The association of cancer with
serum iron and transferrin tended to be stronger among women, whereas the association with
serum copper tended to be stronger among men [165]. One study found higher serum iron
concentrations in individuals with colorectal cancer than control subjects [9]. However, the
evidence for a relationship between dietary iron intake and cancer, particularly colorectal
cancer in the general population, is inconclusive, with reports linking high dietary Fe and Cu
to colorectal cancer [166, 167] and a more recent study founding a non-significant inverse
association for dietary iron and colorectal cancer risk, and a significant inverse association for
serum ferritin and colorectal cancer risk. In this study, serum ferritin, serum iron and
transferrin saturation were all inversely associated with colon cancer risk specifically, but not
rectal cancer risk, whereas serum serum unsaturated iron binding capacity was associated
with a greater risk for colon cancer [168].
There is a clear evidence linking over production of free radical species and the risk of
cancer development. Oxidative damage to DNA can cause single point mutations which,
when undetected and unrepaired by enzyme repair systems, can lead to transversion
mutations, and errors in the DNA sequence. Indeed the chemical properties of some transition
metals suggests a role for them in carcinogenesis. Fe or Cu can generate the reactive
oxygen species including hydroxyl radicals via Fenton- and Haber-Weiss-reactions,
ascorbate autoxidation, lipid peroxidation processes, and formation of DNA
strand breaks [169, 170]. Several mechanisms have been proposed to explain the
carcinogenic potential of iron. First, ferric ions are reduced by superoxide and the ferric
product is reoxydized by peroxide to yield hydroxyl radicals which can attack DNA causing
point mutations, DNA cross linking and DNA strand breaks. Second, iron can bolster the
growth of cancer cells by suppressing host defenses. Finally, being an essential micronutrient,
iron is important tumour cell multiplication [161].
It has been suggested that three predominant mechanisms generally account for
carcinogenicity: (1) interference with cellular redox regulation and induction of oxidative
stress, which may cause oxidative DNA damage or trigger signaling cascades leading to
stimulation of cell growth; (2) inhibition of major DNA repair systems resulting in genomic
instability and accumulation of critical mutations; (3) deregulation of cell proliferation by
induction of signaling pathways or inactivation of growth controls such as tumor suppressor
genes. In addition, specific metal compounds exhibit unique mechanisms such as interruption
of cell-cell adhesion by cadmium, direct DNA binding of trivalent chromium, and interaction
of vanadate with phosphate binding sites of protein phosphatase [171].
In our opinion it is thus possible to categorize transition metals that has been suspected
in the process of carcinogenesis into two categories depending on their reactivity. The first of
them are the oxidizing ones i.e., metals that have high oxidation number which can liberate
free radicals via the Fenton reaction eg., [VO3]1-, [CrO4]2-,[FeO2]1-,[CuO2]2- or V5+, Cr6+,
Fe3+ and Cu2+. The second group of them includes the soft and borderline (between soft and
hard) metals that can react with the antioxidant compounds containing SH or OH reactive
groups such as glutathione and picolines. These metals are namely Cu2+, Fe2+, Co2+, Ni2+
and Zn2+. Thus Fe3+complexes can react with H2O2 to produce free radicals while Fe2+an
react with the antioxidant glutathione thus impairing antioxidant defense mechanisms
increasing the vunerability of the cell to carcinogenic stimuli. It should also be noted that
As5+ reacts with H2O2 leading to the formation of As3+ + H2O + O-•2. (the latter species is a
highly reactive one which can lead to DNA alterations).
Role of Transition Elements in Some Neurodegenerative Diseases
The brain contains a relatively high concentration of a number of metals such as Fe, Zn,
and Cu (in the order of 0.1–0.5 µM) [172]. Metal ions, particularly redox-active metal ions
like copper and iron are the transition metals of marked significance in human disease and
have been reported to accumulate in particular brain regions with aging [173]. An increase in
their tissue concentration has been associated with the development of two important human
diseases; haemochromatosis and Wilson's disease. The former is characterized by a genetic
predisposition to an increased absorption of enteral iron with a consequent increased iron
level in the blood and tissues [174]. Wilson's disease, is a disorder of copper metabolism in
which copper accumulation in tissues causes liver inflammation, fibrosis and neurologic
complications including movement and psychiatric disorders [175]. Under these pathological
conditions, transition metals and their transport proteins may accumulate in different target
organs inducing cellular lipid peroxidation and DNA-attack. Redox active metals such as Cu,
Fe and Mn can result in metal-catalyzed protein oxidation, while metal-protein associations
can result in protein aggregation [176]. Recently, there has been much interest in the
contribution to transition metals and in particular iron and copper to neurodegenerative
diseases which will be highlighted in the following sections. We will focus on two well
known and indeed the most common brain diseases namely Alzheimer's disease and
Parkinson's disease.
Fe(ΙΙΙ)+O2•-→ Fe(ΙΙ)+ O2
Fe(ΙΙ)+ H2O2→ Fe(ΙΙΙ) +•OH +OH-
Cu(ΙΙ)+O2•-→ Cu(Ι)+ O2
Cu(Ι)+ H2O2→ Cu(ΙΙ) +•OH+OH-
2O2•-+2H+→ H2O2 +O2
Cu2++ H2O2 → •OH + Cu1+
TRANSITION METALS AND ALZHEIMER'S DISEASE

This progressive neurodegenerative disorder is characterized by a profound memory
impairment and cognitive decline [177, 178] which is associated with loss of central
cholinergic neurons in the neocortex. The disease is estimated to affect 15 million people
worldwide. The most common risk factor is age with an incidence of 0.5% per year at the age
of 65 years to nearly 8% per year after the age of 85 years [179]. Most cases (95%) are
sporadic, with only 5% of genetic origin. Neuropathologically, there is gliosis and tissue
atrophy, most pronounced in the frontal and temporal cortices [180]. The disease is also
characterized by the presence of amyloid beta (Aβ) senile plaques and neurofibrillary tangles
as well as dystrophic neuritis and degenerating neurons [181]. Senile or neuritic plaques
consist principally of extracellular deposites of an ~ 4.3 kDa polypeptide, amyloid β (Aβ)
peptide, derived from the proteolytic cleavage of the amyloid precursor protein (APP), a
membrane bound normal protein molecule with 771 amino acids produced by neuronal and
non-neuronal cells [182-184]. (forms when an alternative (beta-secretase and then gamma-
secretase) enzymatic pathway is utilized for processing.). The Aβ peptide can be between 39
and 43 residues in length. Neuritic plaques are composed of an extracellular core of filaments
that measure 5-10 nm in diameter and are surrounded by dystrophic neurites and other debris,
as well as microglial cytoplasmic processes and astrocytic processes containing glial
filaments. Dense bodies, autophagic vacuoles and other membranous debris are common
[185]. Neurofibrillary tangles are intracellular aggregates of a hyperphosphorylated form of
the microtubule associated protein "tau", whose function is to regulate microtubule assembly
and helps stabilize stabilize the neuronal microtubule skeleton [186].
Strong evidence implicates transition metals such copper, iron, and zinc in the
pathophysiology of Alzheimer’s disease. In this respect, copper appears to have an important
role, though zinc as well as iron have also been implicated. Increased iron was found within
the glial cells surrounding the neuritic plaques [187](Cu2+ is soft acid whereas Zn2+ and Fe2+
are borderline ones). High concentrations of copper (0.4 mM), zinc (1 mM) and iron (1mM)
have been found within amyloid plaques [188]. In red blood cells patients affected by
Alzheimer's disease, levels of Cu, Zn SOD activity increased early in the disease [189].
Studies suggested increased Zn in hippocampus, amygdala, and multiple neocortical areas of
patients with Alzheimer’s disease [190-192]. More recent studies suggest a significant
decrease of serum Zn in men with mild cognitive impairment (which accompany normal
aging) (MCI) compared to women with MCI and with normal men [193]. There were
significant elevations of the Zn transporter proteins ZnT-1 and ZnT-6, responsible for export
of Zn to the extracellular space in brain of Alzheimer's disease patients [194,195]. Copper
serum was increased in patients with Alzheimer’s disease patients when compared with
healthy controls [196] while a high concentration of copper was found within senile plaques
and neurofibrillary tangles of Alzheimer’s disease brains [188, 197, 198]. Free serum copper
(not bound to ceruloplasmin) was significantly elevated in patients with Alzheimer’s
compared to controls [53]. Free copper in serum predicted the annual change in Mini-Mental
State Examination. Hyperlipidemic patients with higher levels of free copper seemed more
prone to worse cognitive impairment [199]. In those with normal mental state, there was a
significant inverse correlation of the serum levels of free copper (though not ceruloplasmin-
bound copper) with both Mini-Mental State Examination and attention-related
neuropsychological tests scores [200]. Studies suggested that an increase of 1 micro mol/L in
serum copper account for 80% of the risk of having Alzheimer’s disease and correlate with
poor neuropsychological performance and medial temporal lobe atrophy. The latter correlated
also with decreased antioxidant capacity [196]. Oral Cu supplementation itself [Cu-(II)-
orotate-dihydrate; 8 mg Cu daily] in patients with mild Alzheimer’s disease for 12 months,
however, had neither a detrimental nor a promoting effect on the progression of the disease
[201]. Ceruloplasmin fragmentation occurs in the serum of Alzheimer’s disease patients,
possibly related to ‘free’ copper deregulation in this disease [202]. The loss of the copper
chaperone for superoxide dismutase (CCS) which binds to the β-site AβPP cleaving enzyme,
increases Aβ production [203, 204]. Strozyk et al. [204] suggested that excessive interaction
with copper and zinc may induce neocortical Aβ precipitation in Alzheimer’s disease, but
soluble Aβ degradation is normally promoted by physiological copper and zinc
concentrations. The authors observed a significant inverse correlation of cerebrospinal fluid
Aβ42 with copper, zinc, iron, manganese and chromium, but there was no association with
selenium or aluminum. In vitro data suggested that low concentrations (2 μM) of exogenous
Zn and Cu promoted the degradation of synthetic Aβ added to CSF samples.
Our opinion is that soft acid ion such as Cu2+ and borderline (laid between soft and hard
ions) ions such as Fe2+, Mn2+, Cr3+ could have a role in Alzheimer’s disease. On the
contrary, Alzheimer’s disease is not associated with hard acid ions e.g., Al3+. Based on the
results of numerous investigations, we can conclude that the first step in the pathogenesis of
Alzheimer’s disease (and possibly other neurodegenerative diseases)is the interaction
between reactive oxygen species e.g., O2·–, 1O2 with the cell membrane which in turn suffers
from alteration of its chemical structure; the highly polymerized membrane being changed to
a less polymerized one with the above mentioned species forming tetrahydral coordination
compounds. Change in membrane structure may lead to changes in its electricity, which
enhances the transportation of different metals such as Zn, Cu and Fe.
Amyloid Beta Protein (Aβ) Deposition in the Brain is a Hallmark of

Alzheimer's Disease
The analysis of the assembly pathway of Aβ in vitro and biochemical characterization of

Aβ deposits isolated from Alzheimer’s disease brains indicate that Aβ oligomerization occurs
via distinct intermediates, including oligomers of 3–50 Aβ monomers, annular oligomers,
protofibrils, fibrils and plaques. Of these, the most toxic species appear to be small Aβ
oligomers. Aggregation is believed to be transition metal-dependent [205].
Monomeric Aβ + metal ions → Dimers → Oligomers→Protofibrills→Amyloid
Peptides containing the 40- or 42-residue forms of Aβ, and shorter derivatives, form
amyloid-like fibrils in vitro, which are morphologically, tinctorially, immunologically,
spectroscopically and ultrastructurally similar to fibrillar aggregates extracted from
Alzheimer’s disease amyloid plaques. Structural model of amyloid-like fibrils have been
proposed that is composed of several protofilaments, which consist of hydrogen-bonding β-
sheet structures with the β-strands running perpendicular to the long fibre axis, a structure
known as a cross-βconformation [206]. There exist two conformational states for Aβ
aggregates: (i) the nonβ-sheet, an amorphous, non-fibrillar, state and (ii) the β-sheet, a highly
ordered, fibrillar, state which is neurotoxic [26]. It is largely thought that Aβ peptide
aggregation into insoluble fibrils is an important early event in a cascade of events leading to
neuronal cell death in the brains of Alzheimer’s disease patients [184, 207]. There is however
more convincing evidence that soluble oligomers may in fact be the most toxic species [208].
Oligomeric Abeta can disturb the structure and function of cell membranes and alter
membrane mechanical properties, such as membrane fluidity and molecular order. Much of
these effects are attributed to their capability to trigger oxidative stress and inflammation
[209].These oligomeric assemblies of Aβ, which surround plaques, induce calcium mediated
secondary cascades that lead to dystrophic neurites, dendritic simplification, and dendritic
spine loss in both neurons in culture and in the adult mouse brain [210]. The observation of
the co-deposition of metals and amyloid-β42 (Aβ42) in brain tissue in Alzheimer’s disease
indicated the need to understand the role of metals in Aβ aggregation. The aggregation of
Abeta can be induced by Zn(2+) or Cu(2+) [211]. Huang et al. (1999) [212] suggested an
obligatory role for metal ions in initiating Abeta amyloidosis and oligomerization. In vitro
precipitation and amyloidosis of Abeta1-40 initiated by Abeta1-42 were abolished by
chelation of trace metal contaminants. Iron(III) ion produced both the oligomerization of the
peptide and iron-rich high molecular mass complexes [213]. In our opinion, the oxidation of
thiol compounds to sulphoxides decreases the ability of soft and borderline ions such as Cu2+,
Hg2+, Co2+, Ni2+ and Zn2+ so that these ions preferentially form coordination complexes with
monomer and oligomer Aβ peptide species.
Human Aβ can bind metal ions [214, 215] due to the presence of a low and high affinity
binding site for both Cu and Zn via three N-terminal histidine imidazole rings with the
stoichiometry for Cu:Aβ being 1:1 and for Zn:Aβ ranging from 1:1 to 3:1[216, 217]. It has
been suggested that interaction of both Zn2+ and Cu2+ ions with Abeta peptides may occur in
brain areas affected by Alzheimer's disease and Zn2+-induced transition in the peptide
structure might contribute to amyloid plaque formation [218]. Elucidation of the chemistry
through which transition-metal ions participate in the assembly and toxicity of Abeta
oligomers is important to drug design efforts if inhibition of Abeta containing bound metal
ions becomes a treatment for Alzheimer's disease.
Figure 1. Illustration of CU2+ coordination by Aβ, where the metal is believed to be coordinated by His-
6, His-13 and His-14 and Tyr-10. The imidazole side chain of a His residue bridges between two CU2+
atoms to form dimeric Aβ.
The N-terminal region of Aβ can access different metal-ion-coordination environments

and different complexes can lead to profound changes in Aβ self-assembly kinetics,
morphology, and toxicity [219]. Metals can bind Aβ-peptides in an intra- as well as in an
inter-peptide coordination mode [220, 221]. Raman microscopy showed that Zn2+ ions are
bound to Aβ via the histidine imidazole rings within senile plaque cores [222]. One form of
metal coordination that can drive peptide aggregation is the formation of histidine bridges,
where the imidazole side chain of a His residue in a Cu-bound Aβ can also coordinate to the
copper of a second Aβ peptide [223]. The novel distorted six-coordinated (3N3O) geometry
around copper in the Aβ-Cu2+ complexes include three histidines: glutamic, or/and aspartic
acid, and axial water [217]. Aβ1-40 bound easily one copper ion to form the [M+Cu+ 4H]6+
complex [213]. Stellato et al [221]suggested differences in the structural conformation of the
complex that depend on the nature of the coordinated metal. In (Cu-Aβ)1 complex, the metal
is tightly bound to three histidines in a fairly closed structure, which “protects” the metal
against any further interaction. This contrasts with the open structure of the (Zn-Aβ)1
complex, making available the metal for further interaction [221]. Zn2+ coordination is
dominated by inter-molecular coordination and the formation of polymeric species. His6,
His13 and His14 residues are implicated in Zn-Ah binding [224]. Miller et al. [225] observed
that Zn2+ coordination promotes Aβ42 aggregation leading to less uniform structures. In
oligomeric Zn2+-Aβ42, Zn2+ can simultaneously coordinate intra- and intermolecularly,
bridging two peptides. Zinc coordination significantly decreases the solvation energy for large
Zn2+-Aβ42 oligomers and thus enhances their aggregation tendency. Increasing Zn2+
concentration could slow down the aggregation rate, even though the aggregation rates are
still much higher than in Zn2+-free solution.
Investigation of the temperature dependence of the EPR signal for Cu2+ bound to
soluble Aβ or Cu2+ in fibrillar Abeta showed that the Cu2+ center displays normal Curie
behavior, indicating that the site is a mononuclear Cu2+ site. Fibrils assembled in the presence
of Cu2+ contained one Cu2+ ion per peptide. Thus the ligand donor atom set to Cu2+ does not
change during organization of Abeta monomers into fibrils and neither soluble nor fibrillar
forms of Abeta(1-40) with Cu2+ contain antiferromagnetically exchange-coupled binuclear
Cu2+ sites in which two Cu2+ ions are bridged by an intervening ligand [214]. Jun et al. [226]
proposed that Aβ (1-40) has a second copper-binding site in a proton-rich environment and
that the second binding Cu(II) ion interferes with a conformational transition into amyloid
fibrils, inducing the formation of granular amorphous aggregates. Sarell et al. [227] suggested
that Aβ fibers are able to bind a full stoichiometric complement of Cu2+ ions with little
change in their secondary structure and have coordination geometry identical to that of
monomeric Aβ. A Cu2+ affinity for Aβ of 1011 M−1 supports a modified amyloid cascade
hypothesis in which Cu2+ is central to Aβ neurotoxicity.
Zn2+ causes rapid aggregation of Aβ [228]. It has also been reported that Zn2+ may play a
neuroprotective role since Aβ may capture redox inactive Zn2+ ion thereby preventing Aβ
from participating in redox cycling with other metals, in particular, Cu2+ ions [229]. Zn(II)
induces the Abeta aggregation at acidic-to-neutral pH, while Cu(II) is an effective inducer
only at mildly acidic pH. Zn(II) binds to the N(tau) atom of the histidine imidazole ring and
the peptide aggregates through intermolecular His(N(tau))-Zn(II)-His(N(tau)) bridges. The
N(tau)-metal ligation also occurs in Cu(II)-induced Abeta aggregation at mildly acidic pH. At
neutral pH, however, Cu(II) binds to N(pi), the other nitrogen of the histidine imidazole ring,
and to deprotonated amide nitrogens of the peptide main chain. The chelation of Cu(II) by
histidine and main-chain amide groups results in soluble Cu(II)-Abeta complexes. Under
normal physiological conditions, Cu(II) is thus expected to protect Abeta against Zn(II)-
induced aggregation by competing with Zn(II) for histidine residues of Abeta [220]. pH-
dependent metal binding to Aβ1-40 may induce conformational changes, which affect the
affinity toward other metals. A significant copper and zinc binding to Aβ1-40 peptide at pH
5.5 (and a 1:1 Cu:Aβ molar ratio ) was found, whereas nickel ions commonly bind to each
molecule of β-amyloid peptide. On increasing pH, up to 12 ions of zinc may bind to a single
Aβ molecule. Aβ1-40 peptide displayed a high affinity toward nickel ions even at low pH and
nickel ions proved to enhance Aβ oligomerization [213].
In that respect we can say that Zn 2+ ions are not involved in the creation of oxidation
stress like Cu2+, Cr3+, CrIV-V, Fe3+ and [MoO2] 2+, but only involved in formation of
tetrahedral complexes with monomeric and oligomeric Aβ species.
Suzuki et al. [230]found that Cu(II) effectively inhibits the Abeta aggregation by
competing with Zn(II) for histidine residues. The cross-linking of Abeta through binding of
Zn(II) to the N(tau) atom of histidine is prevented by chelation of Cu(II) by the N(pi) atom of
histidine and nearby amide nitrogens. The inhibitory effect is strongest at a Cu/Abeta molar
ratio of around 4. Above this ratio, Cu(II) itself promotes the Abeta aggregation by binding to
the phenolate oxygen of Tyr10. The authors emphasized the importance of regulation of
Cu(II) levels to inhibit Abeta aggregation. Other researchers provided data suggesting that
both Zn(II) and Cu(II) may in fact prevent Aβ from participating in fibrillogenesis by forming
metal-induced aggregates, whose structural characteristics are distinct from fibrous self β-
aggregates. Moreover, this inhibitory effect of metals on Aβ-aggregation via conformational
enforcement was directly correlated with their protective effects against cell toxicity. Soluble
Aβ also promoted cytotoxicity in the presence of Cu(II), indicating that Cu(II) is capable of
promoting potentially toxic, pro-oxidative reactions [231].
Karr et al. [232]suggested that peptides that contain the proposed binding site for
Cu(2+)-three histidines (H6, H13, and H14) and a tyrosine (Y10)-but lack one to three N-
terminal amino acids, do not bind Cu(2+) in the same coordination environment as the native
peptide. Cu(2+) binds to Abeta fibrils in a manner that permits exchange of Cu(2+) into and
out of the fibrillar architecture.
More recently, Smith et al. (2006) [223] have reported the formation of a toxic Aβ-Cu2+
complex formed via a histidine-bridged dimer, as observed at Cu2+/peptide ratios of >0.6:1 by
EPR spectroscopy. The toxicity of the Aβ-Cu2+ complex to cultured primary cortical neurons
was attenuated when either the π -or τ-nitrogen of the imidazole side chains of His were
methylated, thereby inhibiting formation of the His bridge. Aβ and Aβ-Cu2+ complexes
interacted at the surface of a lipid membrane.
The binding of metals to Aβ was found to be dependent on the Abeta conformation. The
latter was found to depend on pH and trifluoroethanol (TFE). The aggregation induced by
Abeta itself or its associated metals is completely diminished for Abeta in 40% TFE. Only in
5% and 25% TFE can Aβ undergo an alpha-helix to beta-sheet aggregation, which involve a
three-state mechanism for the metal-free state, and a two-state transition for the metal-bound
state, respectively. The aggregation-inducing activity of metals is in the order, Cu2+ > Fe3+ >
or = Al3+ > Zn2+.[233].
Copper facilitated the Aβ aggregation and precipitation of both wild-type and a mutant
Aβ in which a histidine residue was replaced by arginine [234]. Ha et al. [235]found that Cu2+
and Zn2+ ions accelerated both Abeta40 and Abeta42 deposition but resulted only in the
formation of "amorphous" aggregates. In contrast, Fe3+ induced the deposition of "fibrillar"
amyloid plaques at neutral pH. Under mildly acidic environments, the formation of fibrillar
amyloid plaques was not induced by the metal ions. Studies with mixed metal ions suggested
that Zn2+ was required at much lower concentrations than Cu2+ to yield nonfibrillar
amorphous Abeta deposits. Sequential addition of Zn2+ or Cu2+ on fibrillar aggregates formed
by Fe3+ demonstrated that Zn2+ and Cu2+ could possibly change the conformation of the
aggregates induced by Fe3+ [236].
Yang et al. [237]found that Cu(II) could disrupt the already formed beta-sheet structure,
convert beta-sheeted aggregates into non-beta-sheeted aggregates and promote oligomeric Aβ
to precipitate in a non-beta-sheeted aggregation way. Other researchers have shown that
copper abolished the β-sheet secondary structure of pre-formed, aged amyloid fibrils of Aβ42.
Copper may thus protect against the presence of β-sheets of Aβ42 in vivo, and its binding by
fibrillar Aβ42 could have implications for Alzheimer’s disease therapy [238].
In our opinion, one can say that reactive oxygen species (ROS) have two drawbacks. The
first arises from the formation of oxidized cellular molecules resulting from the interaction
with different chemical compounds (e.g., DNA , RNA ). The second arises from the oxidation
of thiols and mercaptans and the corresponding sulphoxides which leads to variation in their
function. The increase in ROS may lead to abstraction of borderline elements such as Zinc
which is found for example in the insulin molecule. The soft acidic ions such as Cu2+ and
Fe2+ play a role in the formation of reactive oxygen species in case of their interaction with
sulphur Aβ species as we can see later.
TRANSITION METALS, Aβ AND OXIDATIVE STRESS

Oxidative stress is increased in Alzheimer’s disease. Medial temporal lobe atrophy
appears to correlate with decreased antioxidant capacity [196] (Squitti et al., 2002b). Abeta
(1-42) causes oxidative stress and neurotoxicity to neurons in mechanisms that are inhibited
by Vitamin E and involve the single methionine residue of this peptide [239-241]. The ability
of Aβ to bind metals and the presence of redox-active iron in plaque cores could explain the
development of oxidative stress in the brain of Alzheimer’s disease patients. Oxidative stress,
probably mediated by the hydroxyl radical and generated by the Fenton reaction, is essential
for Aβ1–42 toxicity in vivo. Rival et al. [242] have shown that the expression of the 42-amino-
acid isoform of Aβ (Aβ1–42) changes the expression of genes involved in oxidative stress in a
Drosophila model of Alzheimer’s disease. the iron-binding protein ferritin and the H2O2
scavenger catalase were the most potent suppressors of the toxicity of wild-type and Arctic
(E22G) Aβ1–42. Copper may participate in oxidative stress through redox-cycling between its
+2 and +1 oxidation states to generate reactive oxygen species (ROS).Aβ peptide can reduce
Cu(II) and Fe(III) ions leading to Fenton and Haber-Weiss chemistry, the formation of
hydroxyl radicals, and oxidative damage in brain tissue. Solutions of A(beta) 1-40, A(beta) 1-
42, A(beta) 25-35 all liberate hydroxyl radicals upon incubation in vitro followed by the
addition of small amounts of Fe(II). These hydroxyl radicals were readily detected by means
of electron spin resonance spectroscopy, employing 5,5-dimethyl-1-pyrroline N-oxide
(DMPO) as a spin trapping agent. Hydroxyl radical formation was inhibited by the inclusion
of catalase or metal-chelators during A(beta) incubation. The direct production of hydrogen
peroxide during formation of the abnormal protein aggregates might thus be one fundamental
molecular mechanism underlying the pathogenesis of cell death in Alzheimer’s disease [243].
Ascorbate radical and hydroxyl radical (either via fluorescent detection or spin-trapped
adducts) have been detected upon redox-cycling of the AβCu system [244].
Metal-binding to Aβ is thought to induce its aggregation and redox chemistry that is toxic
to neurons through the generation of reactive oxygen species which induces membrane lipid
peroxidation and oxidative modification of various membrane and associated proteins (e.g.,
receptors, ion transporters and channels, and signal transduction and cytoskeletal proteins)
[245]. Neuronal cell death induced by GSH depletion was dependent on trace levels of
extracellular copper in the culture medium (1.6 microM). Neurons were protected against
GSH depletion-mediated toxicity when cultured in Chelex 100-treated medium containing
tenfold less copper (0.16 microM) than normal medium. The addition of copper, but not iron
or zinc, to Chelex 100-treated medium restored the neurotoxicity induced by GSH depletion.
The neurotoxic effects of copper in GSH-depleted neurons involved generation of copper(I)
and subsequent free radical-mediated oxidative stress [246]. The abnormal combination of Aβ
with Cu or Fe induces the production of hydrogen peroxide, which may mediate the oxidative
damage to the brain in Alzheimer’s disease [247]. An inevitable, age-dependent rise in brain
Cu and Fe might hypermetallate the Aβ peptide, causing the catalysis of H(2)O(2) production
that mediates the toxicity and auto-oxidation of Abeta [172] (Bush, 2003). In cellular
environments, the reduction potential of the Abeta-Cu(II) complex is sufficiently high to react
with antioxidants (e.g., ascorbic acid) and cellular redox buffers (e.g., glutathione), and the
Abeta-Cu(I) complex produced could subsequently reduce oxygen to form hydrogen peroxide
via a catalytic cycle. Hydrogen peroxide produced, in addition to its role in damaging DNA,
protein, and lipid molecules, can also be involved in the further consumption of antioxidants,
causing their depletion in neurons and eventually damaging the neuronal defense system.
Another possibility is that Abeta-Cu(II) could react with species involved in the cascade of
electron transfer events of mitochondria and might potentially sidetrack the electron transfer
processes in the respiratory chain, leading to mitochondrial dysfunction [248]. In human
cerebrospinal fluid, copper but not iron supplementation provoked a significant increase in
hydroxyl free radical generation in cerebrospinal fluid (CSF) treated with H2O2. However, in
a binary copper/iron containing Fenton system, iron catalytically activated copper. EDTA
completely prevented copper's redox activity in CSF, while iron chelation led to a significant
increase in hydroxyl radical generation, indicating that copper and iron do not only have
diverse catalytic properties in the CSF but also that their redox activities are differently
modulated by ligands [249]. Jiang et al. [250]found that in the presence of ascorbic acid,
Abeta-Cu(II) complexes facilitate the reduction of oxygen by producing H2O2 as a major
product. Cu(II) bound to oligomeric and fibrous Abeta aggregates was less effective than free
Cu(II) and the monomeric Abeta-Cu(II) complex in producing ROS. Other studies suggested
that monomeric and fibrillar forms of Abeta does not generate any more reactive oxygen
species (ROS) than controls of Cu(2+) and ascorbate. Rather hydroxyl radicals produced as a
result of Fenton-Haber Weiss reactions of ascorbate and Cu(2+) rapidly react with Abeta;
thus the potentially harmful radicals are quenched. Specific oxidation sites within the peptide
were identified at the histidine and methionine residues [251]. EPR spectroscopy of ascorbate
reduction of AβCuII under inert atmosphere and subsequent air oxidation of AβCuI to
regenerate AβCuII suggested that O2 oxidation of the AβCuI complex is kinetically sluggish,
and Aβ damage is occurring following reoxidation of AβCuI by O2. it was hypothesized that
CuI is ligated by His13 and His14 in a linear coordination environment in Aβ, that Aβ may be
playing a neuroprotective role, and that metal-mediated oxidative damage of Aβ occurs over
multiple redox-cycles [252]. Tabner et al., 2005 [253] have shown that Aβ(1–40), Aβ(1–42)
and Aβ(25–35) generate hydrogen peroxide which can be converted into hydroxyl radicals,
via the Fenton reaction, upon addition of Fe(II). Hydrogen peroxide was not generated
continuously throughout the aggregation process, but was formed as a short ‘burst’
comparatively early on during the peptide incubation period i.e., during the very early stages
of protein aggregation, when protofibrils or soluble oligomers were present as revealed by
atomic force microscopy. Mature Aβ fibrils lacked the ability to generate hydrogen peroxide.
Aβ1-42 is a potent inhibitor of the terminal complex cytochrome c oxidase in a dose-
dependent manner that was dependent on the presence of Cu2+ and specific "aging" of the
Aβ1-42 solution. Thus, Cu2+-dependent Aβ-mediated inhibition of cytochrome c oxidase may
be an important contributor to the neurodegeneration process in Alzheimer's disease [254].
It appears that when the sensitive metal balance in the brain is sufficiently disrupted, it
can lead to the self-perpetuating pathogenesis of Alzheimer’s disease. Maynard et al.,
2005)[215]. Aβ is derived from intracellular proteolytic cleavage of amyloid precursor
protein (APP). APP undergoes intramolecular cleavage by α-, β- and γ-secretases Aβ is a 39-
43-residue heterogeneous peptide derived from proteolytic processing of the β-amyloid
precursor protein (APP) by β-secretase, the protease that cleaves at the amino-terminus, and
γ-secretase, the protease that cleaves at the carboxy-terminus. Aβ1-40 is the major species
found in cerebrospinal fuid [182-184]. Amyloid precursor protein (APP) is a major regulator
of neuronal copper homeostasis via its copper binding domain, being acting as a neuronal
metallotransporter [256]. APP is able to bind Cu2+ and reduce it to Cu+ through its copper-
binding domain. APP knockout mice have elevated cellular copper levels [257], whereas
transgenic mice overexpressing the Swedish mutant of APP have reduced brain copper [258].
The interaction between Cu2+ and APP leads to a decrease in Aβ production. On the other
hand, lowering Cu concentrations can down regulate the transcription of APP, showing that
APP and Aβ form part of the Cu homeostatic machinery in the brain [215]. APP possesses
ferroxidase activity mediated by a conserved H-ferritin-like active site, which is inhibited
specifically by Zn2+. Like ceruloplasmin, APP catalytically oxidizes Fe2+, loads Fe3+ into
transferring. Duce et al. [259] proposed that endogenous Zn2+ originating from Zn2+-laden
amyloid aggregates and correlating with Aβ burden can inhibit APP ferroxidase activity,
inducing marked brain iron accumulation in Alzheimer’s disease. Metallothioneins (MTs) are
the major endogenous zinc- and copper- binding protein within the brain. MT-1/2 can bind 7
divalent (Zn2+) and up to 12 monovalent (Cu+) metal ions in vivo through two distinct metal-
thiolate clusters, termed the α- and β- domains [45, 260]. Metallothionein-3 (MT-3) binds
with a high affinity essential monovalent and divalent d10 metal ions Cu(I) and Zn(II). In cell
cultures Zn7MT-3, protects neurons from the toxicity of Aβ. Zn7MT-3 scavenges free Cu2+
ions through their reduction to Cu+ and binding to the protein. In this reaction thiolate ligands
are oxidized to disulfides concomitant with Zn2+ release. Zn7MT-3 in the presence of
ascorbate completely quenches the copper-catalyzed hydroxyl radical (OH·) production
[261]. MT-2A prevented the in vitro copper-mediated aggregation of Aβ1–40 and Aβ1–42. This
action of MT-2A appears to involve a metal-swap between Zn7MT-2A and Cu(II)-Aβ.
Zn7MT-2A blocked Cu(II)-Aβ induced changes in ionic homeostasis and subsequent
neurotoxicity of cultured cortical neurons [262].
Metals can also induce neurodegeneration via pathways independent of Aβ aggregation.
Neurotrophins are an important family of neurotrophic factors e.g., nerve growth factor, brain
derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5. They exert their effects by
binding to and activating specific cell surface receptors of the Trk gene family. Activated
receptors initiate a cascade of intracellular events, which ultimately induce gene expression
and modify neuronal morphology and function [263]. The amyloid protein precursor of
Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth
[264]. The transition metal cations Zn2+ and Cu2+ bind to histidine residues of nerve growth
factor (NGF) and other neurotrophins (a family of proteins important for neuronal survival)
leading to their inactivation. Cu2+ has greater binding affnity to NGF than Zn2+ at acidic
conditions, consistent with the higher affnity of Cu2+ for histidine residues [265].
METAL BRAIN LOWERING IN ALZHEIMER'S DISEASE

Metal ligands such as clioquinol , DP-109 or pyrrolidine dithiocarbamate (PDTC) have
shown promising results in animal models of AD and could have therapeutic benefits for
Alzheimer’s disease. The 8HQ (8-hydroxyquinoline) derivative 5-chloro-7-iodo-8-
hydroxyquinoline or clioquinol was shown to ‘dissolve’ plaques in vitro by removal of metals
[266].
Figure 2. Clioquinol.
A recent placebo-controlled trial in 36 patients with Alzheimer’s disease showed that

clioquinol (250-750 mg daily) reduced plasma concentrations of Aβ1–42, raised plasma
concentrations of zinc, and-in a subset with moderate dementia-slowed cognitive decline over
24 weeks [267]. In culture, cells over expressing APP when incubated with the metal ligand
clioquinol and Cu2+or Zn2+~ 85-90% reduction of secreted Abeta-(1-40) and Abeta-(1-42)
was observed compared with untreated controls. The secreted Abeta were rapidly degraded
through up-regulation of matrix metalloprotease (MMP)-2 and MMP-3 after addition of
clioquinol and Cu2+. Metal ligands that inhibited Aβ induced metal-dependent activation of
PI3K and JNK, resulted in JNK-mediated up-regulation of metalloprotease activity and
subsequent loss of secreted Aβ [268]. Dithiocarbamates are metal chelating compounds.
Pyrrolidine dithiocarbamate (PDTC) is a metal chelator and an inhibitor of nuclear factor-κB
which increases the intracellular level of copper [269]. Oral therapy with PDTC prevented the
decline in cognition in Alzheimer’s disease mice without altering β-amyloid burden or gliosis,
increased the copper concentration in the brain, rescued cultured hippocampal neurons from
the toxicity of oligomeric Aβ and reduced tau phosphorylation in the hippocampus of
Alzheimer’s disease mice [270]. In Drosophila model of Alzheimer’s disease, treatment with
clioquinol increased the lifespan of flies expressing Arctic Aβ1–42.[242]. Moreover, nicotine
treatment of APPV717I (London mutant form of APP) transgenic mice led to significant
reduction in the metal contents of copper and zinc in senile plaques and neuropil; effect that
appears to be independent of the activation of nicotinic acetylcholine-receptor [271].
Lowering of copper concentrations in brain of patients with Alzheimer’s disease is thus an
interesting therapeutic strategy. D-penicillamine, a copper chelating agent reduced extent of
oxidative stress (though not the rate of cognitive decline) in these patients [272]. There are
also data suggesting that copper deficiency markedly alters APP metabolism and can elevate
Aβ secretion [273] making the situation more complex. In their study, Crouch et al.
[274]found that in the brains of APP/PS1 transgenic AD model mice, the use of copper-
bis(thiosemicarbazonoto) complexes to increase intracellular copper bioavailability, can
restore cognitive function by inhibiting the accumulation of neurotoxic Aβ trimers and
phosphorylated tau. Hung et al. [275]found that total cellular copper is associated inversely
with lipid raft copper levels, so that under intracellular copper deficiency conditions,
Aβ·copper complexes are more likely to form. This explains the paradoxical hypermetallation
of Aβ with copper under tissue copper deficiency conditions in AD.
TRANSITION METALS AND PARKINSONS'S DISEASE

Parkinson's disease is the second most common neurodegenerative disorder after
Alzheimer’s disease and is also a disease of the aging population in which the prevalence
increases exponentially with age between 65 and 90 years. The mean age of onset is about 65
years and the overall age-adjusted prevalence is 1% worldwide. The clinical features of
Parkinson's disease result from a progressive degeneration of dopamine-producing neurons in
the substantia pars compacta (SNc) of the midbrain that project to the striatum. The SNC is
one of five distinct subcortical interconnected nuclei whose primary function is the control of
motor function. In Parkinson's disease there is slowness and difficulty with movement
initiation "bradykinesia", muscular rigidity as well as tremor of the hands. Parkinsonian
symptoms start to appear when 50–60% of SNc dopaminergic neuons and 70–80% of striatal
nerve terminals are lost [276]. Apart from an idiopathic form, the disorder can be the result of
vascular factors, brain trauma, manganese poisoning or drugs. Only ~5% of all cases are of
genetic origin. The exact cause that leads to the the selective destruction of the nigrostriatal
dopaminergic pathway has remained unknown but accumulating evidence suggests that it
might represent the final outcome of interactions among multiple factors, including a signifi-
cant genetic component for susceptibility to idiopathic Parkinson's disease, exposure to
environmental toxin (s) and the occurrence of inflammation in the brain [277].
Several factors underlie the unduly high susceptibility of the brain tissue to oxidative
stress. Owing to its high metabolic activity the brain has high oxygen consumption rate being
~ 20% of total oxygen consumption in adult human despite that it accounts for only a few
percent of body weight. Hence it processes a lot of O2 per unit tissue mass. The brain is also
rich in highly oxidizable polyunsaturated fatty acids. Other factors causing increased
oxidative burden are the metabolism of monoamine neurotramsmitters noradrenaline,
serotonin and dopamine, yielding free radicals and brain iron content [176].
Dopamine
Dopamine [2-(3,4-dihydroxyphenyl)-ethylamine] is a neurotransmitter that plays an

important role in PD. When a solution of dopamine is exposed to air, after a while it turns
pink due to oxidation to dopaminochrome even in the absence of metal ions. Finally the pink
colour disappears to be replaced by a precipitate of the polymeric material melanine. The rate
determining step is assumed to be hydrogen atom abstraction from the monodeprotonated
species by O2.Addition of a small amount of acid inhibits this oxidation, unless metal ions
such as Fe3+, Cu2+ or VO2+ are present. Although in acid solution added metal ions initially
start an oxidation process, this soon comes to an end as the metal ions are efficiently removed
from the solution by the melanine. The in vitro chemistry of dopamine reactions under the
presence of Fe (III) and dioxygen showed that the reaction pathway essentially involved an
FeL intermediate, which decomposes releasing Fe(II) and dopaminochrome which reacts
further under involvement of both Fe (III) and dioxygen [279].
Figure 3. Dopamine and Dopaminochrome.
The metabolism of dopamine can be a source of free radicals production via multiple
pathways. Dopamine can auto-oxidize to produce free radicals particularly in the presence of
iron and other heavy metals [280]. Dopamine forms quinones and semiquinones,which are
themselves toxic and may lead to generation of reactive oxygen species [281]. In addition, the
reduction of Cu2+to Cu1+and the formation of a peroxide lead to the oxidation of dopamine
with formation of DNA adducts and oxidative base damage [282]E:\Documents and
Settings\Lisa\Local Settings\Temporary Internet Files\Content.Outlook\9DAVGS4D\New
Folder33\science.htm - en976560fn1. It has been suggested that increased turnover of
dopamine in the early stages of PD should be associated with an oxidative stress derived
from increased production of hydrogen peroxide with the subsequent formation of hydroxyl
radical leading to dopaminergic cell death. The peroxide is formed during the oxidative
deamination of dopamine by monoamine oxidase [283]. It has been shown that increased
presynaptic metabolism of neurotransmitter alters the redox state of dopamine nerve terminals
in the striatum. The H202 that is generated by MAO is scavenged by glutathione (GSH)
peroxidase, leading to the formation of glutathione disulfide (GSSG).
(1)
(2)
(3)
Normally, GSSG is efficiently reduced by glutathione reductase. The ratio of oxidized to

reduced glutathione reflects, in part, the redox state of the tissue [283].
We can conclude that the formation of singlet oxygen and the derives ractive oxygen
species lead to the oxidation of thiol compounds to dimeric (GSSG). The alkaline medium
prohibits the formation of GSH as can be seen from equation [3] which clarified that the
transformation step usually takes place in an acidic medium. The liberation of ammonia
inside the cells raises the pH value intracellularly to the alkaline region. This situation may
lead to the precipitation of iron, copper and zinc which may alter the homeostasis of these
transition elements in the brain. In addition, the high pH value enhances the reaction between
hydrogen peroxide and sodium hypochlorite leading to formation of singlet oxygen which
possesses a very stron damaging effect on different molecules forming the different cellular
components (e.g., cell membrane, DNA) according to the following equation:
Role of
o Reactivity of
o Transition Elements
E in Liife 35
NaOCl + H2O2 → 1O2 + NaCl + H2O
The above is likely to haave an importaant implicationns also in somme pathologicall states like
heepatic precom ma where channges in conscioousness and neurobehaviou
n ural alterationss are highly
linnked to increaased brain amm monia level.
In additionn, brain MAO O-B (involved in the cataboolism of dopam mine) (but noot MAO-A)
acctivity increasses with age, thereby,
t expossing cells to oxidative
o stresss-mediated innjury [284].
The increased MAO-B activvity in aging is due to an increased conncentration off otherwise
unnchanged extrrasynaptosom mal MAO-B.. There are also data show wing that the activity of
M
MAO-B is siggnificantly inccreased by AlA 3+ [285], thuus implicatingg this metal ion in the
paathogenesis off PD.
radical
Fiigure 4. Formattion of free radicals from dopam mine (DA) by monoamine
m oxidase (MAO) orr auto-
oxxidation. In the presence of traansition metals, H2O2 is conveerted to hydroxyyl radical [286,2287].
Fiigure 5. Metaboolism of DA leaads to the formaation of several cytotoxic moleecules, includingg

suuperoxide anion
ns (O2·–), dopammine–quinone species
s (SQ·) annd hydroxyl raddicals (OH·)[286,287].
Brain metaabolism generaates excess H2O2, not only via

v superoxidee dismutases, but also by
otther enzymes e.g., monoammine oxidases A and B, flavvoprotein enzyymes located in
i the outer
m
mitochondrial membranes
m off neurons and glia. They catalyze the reacction
and generate substantial H2O2 in the brain [288].

DA quinone readily participates in nucleophilic addition reactions with sulfhydryl groups
on free cysteine, glutathione, or and sulfhydryl groups in proteins [289-292]. The reaction
between DA quinone and cysteine results in the formation of 5-cysteinyl-DA (Figure 1).
Because cysteinyl residues are often found at the active site of proteins, the covalent addition
of the catechol moiety to cysteine may inhibit protein function and possibly lead to cellular
damage and/or cell death. In addition, DA quinone is able to react with the sulfhydryl group
of cysteine in glutathione, which may decrease levels of this important antioxidant. The
reactive quinones and free radicals produced by the oxidation of DA may contribute to the
oxidative stress associated with PD.
Figure 6. The oxidation of DA to DA quinine and the resultant conjugation with cysteine (5-Cys-DA).
Oxidation of dopamine to an o-quinone and its subsequent product, aminochrome (2,3-

dihydroindole-5,6-dione) may also result in redox cycling. Key reactions promoting the
formation of reactive oxygen species, with a consequent prooxidant effect, include one-
electron reduction of quinines catalysed by favoproteins, such as NADPH:cytochrome P-450
reductase, and the subsequent reaction between the formed semiquinone radical and
dioxygen. One-electron reduction accompanied by autoxidation and redox cycling in the
presence of dioxygen contributes greatly to the toxicity characterizing many quinines [293].
The human glutathione transferases (GSTs), in particular GST M2-2 (also in the substantia
nigra of human brain), catalyse the formation of glutathione conjugates of o-quinones derived
from physiologically important catecholamines. Glutathione conjugation of these quinones is
a detoxication reaction that prevents redox cycling, thus indicating that GSTs have a
cytoprotective role involving elimination of reactive chemical species originating from the
oxidative metabolism of catecholamines [294].
Oxidized catecholamines can also induce modification of Cu,Zn-SOD that migkht induce
the perturbation of cellular antioxidant systems and led to a deleterious cell condition. When
Cu,Zn-SOD was incubated with the oxidized 3,4-dihydroxyphenylalanine (DOPA) or
dopamine, the protein was induced to be aggregated. The deoxyribose assay showed that
hydroxyl radicals were generated during the oxidation of catecholamines in the presence of
copper ion [295].
Neuromelanin
Neuromelanin (NM) is a dark pigment polymer belonging to the family of melanins.

which occupies a large proportion of the cytosol within certain catecholaminergic neurons in
the human brain [296]. Melanised neurons are most abundant in the human SN and The dark
appearance of the SN results from the presence of NM and for which it was named (lat.
substantia nigra, black body) [297, 298]. Less neuromelanin is found in Parkinson's disease
and depletion of this pigment results in pallor of the SN which is one of the most striking
pathological features. Neuromelanin is synthesized from quinones and semiquinones
produced by enzymatic or non-enzymatic oxidation of dopamine and noradrenaline in the SN
and LC, respectively. In substantia nigra, dopamine is the major source. In the locus
coeruleus, noradrenalin, and in the diffuse brain stem raphe system, serotonin is the chief
precursor. The complex polymers contain also other oxidation metabolites of dopamine and
L-DOPA, cysteinyl-DOPA [299], 5-S-cysteinyl-dopamine [300], proteinacious components
and lipids [301,302. Neuromelanin also accumulates α-synuclein [303] as well as transition
metals e.g., iron, copper and zinc [304].
The role of neuromelanin is a matter of debate. Neuromelanin has been proposed to play
a protective role via trapping free radicals [302] as well as its ability to chelate transition
metals, such as Fe Zn, Cu, Mn, Cr, Co, Hg, Pb, and Cd [301, 305, 306]. But the presence of
neuromelanin in dopaminergic neurons of the SNc was also be taken as an indication that NM
might in fact account for their vulnerability in Parkinson’s disease [307, 308]. Other
researchers reported that neuromelanin, in contrast to synthetic dopamine melanin without
iron, increased the oxidative stress and induces onset of oxidative stress in mitochondria.
Superoxide dismutase and deferoxamine completely suppressed the increase, indicating that
superoxide produced by an iron-mediated reaction plays a central role [309].Neuromelanin
binds iron in the ferric form. Neuromelanin contains both high- and low-affinity iron binding
sites and additional iron is added to existing iron clusters in NM, analogous to the formation
and growth of the ferritin iron core [310]. neuromelanin is thought to be only partially
saturated with iron in vivo, thus maintaining a residual chelating capacity to protect the
substantia nigra against iron toxicity [311]. It was suggested that the increased brain iron
content encountered in the SN of Parkinson's disease patients might saturate iron-chelating
sites on NM, and a looser association between iron and neuromelanin may result in an
increased, rather than decreased, production of free radical species (metal-ion binding
capacity will be exceeded). This redox-active iron could be released and involved in a
Fenton-like reaction leading to an increased production of oxidative radicals. The resultant
radical-mediated cytotoxicity may contribute to cellular damage observed in PD [312]. It is
likely that at low iron concentrations native neuromelanin does not induce cell damage but
rather protects cells in culture from oxidative stress. This protective function appears to be
lost at high iron concentrations where neuromelanin saturated with iron functions as a source
of oxidative load, rather than an iron chelator. Changes to the structure of neuromelanin and
tissue iron load in Parkinson’s disease may decrease the ability of the pigment to chelate iron,
thus increasing the potential for cell damage [313].
In our opinion, the protective role of neuromelanin may arise from its ability to form
metal-organic complexes with iron, Cu2+, which will prevent or reduce their involvement in
formation of free radicals via the Fenton reaction. In addition, neuromelanin might form a
stable free radicals which interact with potently oxidizing species (O2·–, 1O2 ) thereby
minimizing their effects on cellular molecules.this hypothesis is supported by the presence of
neuromelanin in healthy persons and its decrease or even absence in individuals with
Parkinson's disease.
THE ROLE OF IRON

Parkinson's disease is another neurodegenerative disorder in which transition metals and
in particular Fe appear to have an important role. Owing to iron’s ability to donate electrons
to oxygen, increased iron levels can lead to the formation of hydroxyl radicals and hydroxyl
anions via the Fenton Reaction (Fe2+ + H2O2 → Fe3+ + OH· + OH−). Iron is found throughout
the brain and important iron-containing proteins include cytochromes, ferritin, aconitases,
non-heme iron proteins in the mitochondrial electron transport chain, cytochromes P450, and
tyrosine and tryptophan hydroxylases [176]. The combination of high concentration of iron
and the neurotransmitter, dopamine, may contribute to the selective vulnerability of the SNPc.
Fe concentrations in SN values around 100–200 µg/g in normal subjects [301]. Increased Fe
content in the SNc of patients with Parkinson's disease has been reported. There was a
significant increase in total iron and iron (III) in substantia nigra of severely affected patients
and a shift in the iron (II)/iron (III) ratio in favor of iron (III) with a significant increase in the
iron (III)-binding protein, ferritin as well as a significantly lower glutathione content [314].
The increased iron content is mainly due to increased loading of ferritin [315]. High field
strength MRI demonstrated SNC abnormalities consistent with increased iron content early in
the disease [316]. It has been shown that the properties of the main iron-binding structure in
human brain, the ferritin differ from those of ferritin in liver or spleen with the iron-cores of
brain ferritin being significantly smaller than the iron-cores of liver ferritin. Also the ratio
between the heavy and light subunits of the protein shell of ferritin (H/L) is different in liver
and in brain structures, being the highest for hippocampus. Such differences in properties of
brain ferritin may speak in favor of more rapid iron turn-over in brain compared to liver
which might increase the possibility of oxidative stress [317].
Total iron intake was not associated with an increased risk of Parkinson's disease, but
dietary nonheme iron intake from food was associated with a 30% increased risk of
Parkinson's disease. This increase in risk was present in those who had low vitamin C intake
[318]. Epidemiological studies suggest that exposure to pesticides, such as rotenone, paraquat
or maneb, may contribute to the higher incidence of sporadic Parkinsonism among the
population of rural areas [319, 320]. The combined environmental exposure to paraquat and
Fe was shown to result in accelerated age-related degeneration of nigrostriatal dopaminergic
neurons [321]. The divalent metal transporter 1 (a widely expressed mammalian ferrous ion
(Fe2+) transporter [18] appears to be a key regulator of brain iron accumulation in PD. A
subtype containing iron response element (IRE) (DMT1+IRE) which is under control by iron
regulatory proteins is increased in 6-hydroxydopamine-induced PD model along with
elevation in iron uptake and oxidative stress [250, 322].
Fe accumulation in the SNc of patients with Parkinson's disease is particularly important

because iron is a redox-active metal, that can interact with molecular oxygen to generate
superoxide anion (O2·–), which in turn, generates hydroxyl radical (_OH), a highly reactive
oxygen specie (ROS). As a consequence of Fe2+ reaction with O2, Fe3+ is generated, that can
trigger lipid oxidation through its reaction with lipid hydroperoxides normally present in
biological systems. Finally, many neurotransmitters are auto-oxidizable molecules [323].
ROLE OF OTHER TRANSITION METALS

Parkinson's disease is also characterized by the presence of proteinaceous deposits in the
residual dopaminergic neurons of the SNc (Lewy bodies and Lewy neuritis). These consist
mainly of aggregated forms of α-synuclein [324] which is a normally placed presynaptic
protein involved in synaptic function and plasticity [325] (Clayton and George, 1998). The
mechanisms underlying the gradual transition of soluble α-synuclein into virtually insoluble
Lewy bodies or Lewy neurites are still unknown [326, 327]. Studies suggest that some metals
can directly induce α-synuclein fibril formation. Uversky et al. [328] noted that several di-
and trivalent metal ions caused significant accelerations in the rate of α-synuclein fibril
formation. Aluminum was the most effective, along with copper(II), iron(III), cobalt(III), and
manganese(II). The effectiveness correlated with increasing ion charge density. A correlation
was noted between efficiency in stimulating fibrillation and inducing a conformational
change, ascribed to formation of a partially folded intermediate. The potential for ligand
bridging by polyvalent metal ions is proposed to be an important factor in the metal-induced
conformational changes of α-synuclein.
It seems that Al3+ and Fe3+ which are considered as hard acids posses a large probability
to react with α-synuclein which can be considered in this case as hard or borderline base.
Copper(II) also interacts with α-synuclein ands binds tightly near the N-terminus at pH 7
[329]. Cu(II) ions are effective in accelerating α-synuclein aggregation at physiologically
relevant concentrations without altering the resultant fibrillar structures. By using numerous
spectroscopic techniques (absorption, CD, EPR, and NMR), the primary binding for Cu(II)
was delineated to a specific site in the N terminus, involving His-50 as the anchoring residue
and other nitrogen/oxygen donor atoms in a square planar or distorted tetragonal geometry.
The carboxylate-rich C terminus, originally thought to drive copper binding, is able to
coordinate a second Cu(II) equivalent, albeit with a 300-fold reduced affinity. The NMR
analysis of AS–Cu(II) complexes reveals the existence of conformational restrictions in the
native state of the protein [330].
Cu2+ binding of recombinant human α-synuclein was examined using Electron
Paramagnetic Resonance (EPR) spectroscopy [331]. Wild type α-synuclein was shown to
bind stoichiometric Cu2+ via two N-terminal binding modes at pH 7.4. Electron spin−echo
envelope modulation (ESEEM) studies of wild type α-synuclein confirmed the second
binding mode at pH 7.4 involved coordination of His50 and its g and A

parameters correlated with either {NH2, N−, β-COO−, NIm} or {NIm, 2N−} coordination
observed in α-synuclein fragments. At pH 5.0, His50-anchored Cu2+ binding was greatly
diminished, while {NH2, N−, β-COO−, H2O} binding persisted in conjunction with another
two binding modes.
Mn is another transition metal which has been linked to the development of a clinical
entity simulating Parkinson's disease in humans. Mn2 may be oxidized to Mn3, which is
rather reactive and more toxic than Mn3 rapidly associates with Tf to form a stable complex.
In tissues, Mn may exist primarily in the form of Mn2. Mn-induced neurotoxicity from excess
respiratory or dietary exposures has been well described. Oxidative stress is one of many
factors implicated in Mn induced neurotoxicity [68]. The divalent manganese ions can
interact with glutathione formaing a metal-organic complex which reduces the concentration
of free GSH in the cell.
Figure 7. Oxidative DNA damage induced by dopamine oxidation [332].
Dopamine oxidation by Mn is a potential mechanism for Mn-induced oxidative stress,

especially since Mn preferentially accumulates in dopamine-rich brain regions (e.g., basal
ganglia) [333]. Manganese toxicity has been suggested to relate to the formation of the
trivalent cation, which contains four unpaired d-orbital electrons which are
thermodynamically unstable compared to the three more favourably paired electrons present
in the divalent cationic state. Production of ROS can result from impairment of mitochondrial
function but may also be generated from the oxidation of dopamine in the presence of copper
(Cu (II))[78].
Figure 8. Manganese induced dopamine oxidation [334].
Vanadium compounds in high oxidation states can induce oxidative transformations. A

recent study found that vanadium can exert neurotoxic effects in dopaminergic neuronal cells
via caspase-3-dependent PKCdelta cleavage, suggesting that metal exposure may promote
nigral dopaminergic degeneration [335]. Studies on rat liver mitochondria revealed that
(VO(2+), VO(3)(-), VO(acac)(2) and VOcit (1-100microM) could induce mitochondrial
swelling in a concentration dependent manner and disrupt mitochondrial membrane potential
in a time dependent manner. Vanadium compounds thus induced oxidative stress on
mitochondrial [336]. The oxidation stress of [VO]1+ and [VO]2+ may be ascribed to the
ability of these cations to produce •OH radicals due to interaction with H2O2 in faintly or
acidic medium.
REFERENCES
[1] Jeffcry G H, Basset J, Mendham J, and Dcnney RC. (1989). Text Book of Quantitative
Chemical Analysis. Longman Group Limited, London, 5th ed.
[2] Nyle CB (1990). The Nature and the Properties of Soil", Macmillan Publishing
Company, U.S.A., 10th ed.
[3] Wild A (1988). Soil Condition and plant growth. Longman group UK, Ltd, 11.
[4] Coke GW (1975). Fertilizer for Maximun Yield. Granada publishing limited, Britain,
2nd ed.
[5] Sievers RE and Bailar JC (1962). Some metal chelates of ethylendiaminetetraacetic
acid, diethylenetriaminepentaacetic acid and tri ethylentetraminethexaacetic acid. Inorg.
Chem, 1, 174.
[6] Wilson CJ, Apiyo D and Wittung-Stafshede P (2004). Role of cofactors
inmetalloproteinfolding. Quarterly Reviews of Biophysics 37 (3/4): 285–314.
[7] Robert J & Williams RJP (2006). The Biodistribution of Metal Ions. In Kraatz HB and
Metzler-Nolte N (Eds), Concepts and Models in Bioinorganic Chemistry. Wiley-Vch
Verlag GmbH & Co.
[8] Roat-Malone RM (2002). Bioinorganic Chemistry: A Short Course. John Wiley &
Sons, Inc.
[9] Goyer R, Golub M, Choudhury H, Hughes M, Kenyon E, Stifelman M (2004). Issue
paper on the human health effects of metals.
[10] Solomons NW & Ruz M (1998). Trace element requirements in humans. An update. J.
Trace Elem. Exp. Med. 11, 177-195.
[11] Finney LA & O'Halloran TV (2003). Transition metal speciation in the cell: insights
from the chemistry of metal ion receptors. Science 300, 931–936.
[12] Stohs SJ & Bagchi D ( 1995 ). Oxidative mechanisms in the toxicity of metal ions .
Free Radic. Biol. Med. 18, 321 – 336 .
[13] Goyer RA ( 1997). Toxic and essential metal interactions . Annu. Rev. Nutr. 17, 37-50 .
[14] O’Connor JM (2001). Trace elements and DNA damage. Biochemical Society
Transactions, 29, 354–358.
[15] Valko M, Morris H & Cronin MT (2005). Metals, toxicity, and oxidative stress.
Curr.Med.Chem. 12, 1161–1208.
[16] Halliwell B and Gutteridget JMC (1984). Oxygen toxicity, oxygen radicals, transition
metals and disease. Biochem. J. 219, 1-14.
[17] Crichton R (2001). Inorganic Biochemistry of Iron Metabolism: From Molecular
Mechanisms to Clinical Consequences. 2nd ed.  John Wiley & Sons, Ltd Baffins Lane,
Chichester, West Sussex, England
[18] Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger
S, Gollan JL, Hediger MA (1997). Cloning and characterization of a mammalian
proton-coupled metal-ion transporter. Nature, 388 (6641), 482-488.
[19] Bressler JP, Olivi L, Cheong JH, Kim Y, Maerten A & Bannon D (2007). Metal
transporters in intestine and brain: their involvement in metal-associated
neurotoxicities. Hum Exp Toxicol. 26(3), 221-9.
[20] Kagi JH & Valee BL (1960). Metallothionein: a cadmium- and zinc-containing protein
from equine renal cortex. J Biol Chem. 235, 3460-5.
[21] Lieu PT, Heiskala M, Peterson PA, Yang Y. The roles of iron in health and disease
(2001). The roles of iron in health and disease. Mol Aspects Med. 22(1-2), 1-87.
[22] Andrews NC (1999). Disorders of iron metabolism. N Eng J Med. 341 (26), 1986-
1995.(1999)
[23] Andrews NC (2000). Iron Metabolism: Iron Deficiency and Iron Overload. Ann Rev
Genom and Hum Genet. 1, 75– 98.
[24] Conrad ME & Umbreit JN (2000). Iron absorption and transport: an update. Am J
Hematol. 64, 287-298.
[25] Broderick JB (2001). Coenzymes and Cofactors. In: Encyclopedia of Life Sciences.
Nature Publishing Group / www.els.net pp.1-11
[26] Brown KE (2007). Normal iron metabolism. In: The Textbook of Hepatology: From
Basic Science to Clinical Practice, 3rd Edition. By Joan Rodés, Jean-Pierre Benhamou,
Mario Rizzetto. Wiley-Blackwell. pp.221-226.
[27] Baker HM, Anderson BF & Baker EN (2003). Dealing with iron: common structural
principles in proteins that transport iron and heme. Proc. Natl. Acad. Sci. USA, 100,
3579-3583.
[28] Texel SJ, Xu X and Harris ZL (2008). Metal Metabolism: Transport, Development and
Neurodegeneration. Biochem. Soc. Trans. 36, 1277–1281.
[29] Wessling-Resnick M (2000). Iron transport. Annu Rev Nutr. 20, 129-151.
[30] Moos T (2002). Brain iron homeostasis. Dan Med Bull. 49(4), 279-301.
[31] Turnlund JR (1994). Copper. In: Shils ME, Olson JA, Shike M; Eds. Modern Nutrition
in Health and Disease 8th Ed. Philadelphia: Lea and Febiger.
[32] Turnlund JR, Keyes WR, Kim SK, Domek JM (2005). Long-term high copper intake:
effects on copper absorption, retention, and homeostasis in men. Am J Clin Nutr. 81(4),
822-8.
[33] Linder M (1991). Biochemistry of Copper. Plenum Press, New York.
[34] Linder MC, Lomeli NA, Donley S, Mehrbod F, Cerveza P, Cotton S & Wooten L
(1999). Copper Transport and Its Disorders in Advances in Experimental Medicine and
Biology, ed. By A. Leone, J. F. B. Mercer, Kluwer Academic/Plenum Pub., New York,
N.Y., pp. 1–16.
[35] Linder MC (2001). Copper and genomic stability in mammals. Mut Res 475, 141-152.
[36] Shike M (2009). Copper in parenteral nutrition. Gastroenterology137(5 Suppl), S13-7.
Review.
[37] Prohaska JR (1990). Biochemical changes in copper deficiency. J Nutr Biochem. 1,
452-461.
[38] Culotta VC & Gitlin JD (2001). In: The Molecular and Metabolic Basis of Inherited
Disease, eds Scriver CR, Beaudet AL, Sly WS, Valle D (McGraw–Hill, New York), pp
3105–3136.
[39] Tümer Z & Møller LB (2010). Menkes disease. Eur J Hum Genet. 18(5), 511-8.
[40] Hoogenraad TU. Monography: Wilson’s disease. In: Major Problems in Neurology.
Vol 30, London: W.B. Saunders 1996.
[41] Turnlund JR. (1988). Human whole-body copper metabolism A J Clin Nutri. 67, 960S-
964S.
[42] Lutsenko S, Barnes NL, Bartee MY & Dmitriev OY (2007). Function and regulation of
human copper-transporting ATPases. Physiol Rev. 87, 1011–1046.
[43] Formigari A, Alberton P, Cantale V, De Nadal V, Feltrin M, Ferronato S, Santon A,
Schiavon L & Irato P (2008). Relationship between metal transcription factor-1 and
zinc in resistance to metals producing free radicals. Current Chemical Biology. 2, 256-
266.
[44] Choi BS & Zheng W (2009). Copper transport to the brain by the blood-brain barrier
and bBlood-CSF barrier. Brain Res. 1248, 14–21.
[45] Coyle P, Philcox JC, Carey LC & Rofe AM (2002). Metallothionein: the multipurpose
protein. Cell Mol Life Sci. 59, 627–647.
[46] Vašák M (2005). Advances in metallothionein structure and functions. J Trace
Elements Med and Biol. 19 (1), 13-17.
[47] O'Halloran TV & Culotta VC (2000). Metallochaperones, an intracellular shuttle
service for metal ions. J Biol Chem. 275(33), 25057-60.
[48] Harrison MD, Jones CE, Solioz M & Dameron CT (2000). Intracellular copper routing:
the role of copper chaperones. TIBS 25.
[49] Gregory S. Kelner GS, Lee MH, Clark ME, Maciejewski D, McGrath D, Rabizadehi S,
Lyonsi T, Bredesen D, Jenner P & Maki RA (2000). The copper transport protein
Atox1 promotes neuronal survival. J Biol Chem. 275 (1), pp. 580–584.
[50] Rae TD, Schmidt PJ, Pufahl RA, Culotta VC & O'Halloran TV (1999). Undetectable
Intracellular Free Copper: The requirement of a copper chaperone for superoxide
dismutase. Science 284 (5415), 805 – 808.
[51] Rothstein JD, Dykes-Hoberg M, Corson LB, Becker M, Cleveland DW, Price DL,
Culotta VC & Wong PC (1999). The copper chaperone CCS is abundant in neurons
and astrocytes in human and rodent brain. Journal of neurochemistry 72(1), 422-9.
[52] Doucette, Peter A., Potter, Soshanna Z., & Valentine, Joan S (2005). Copper-zinc
superoxide dismutase and amyotrophic lateral sclerosis; Annu. Rev. Biochem. 2005.
74:563–93
[53] Brewer GJ (2010). Risks of copper and iron toxicity during aging in humans. Chem.
Res. Toxicol. 23 (2), 319–326.
[54] Sarkar B and Roberts EA (2011) . The puzzle posed by COMMD1, a newly discovered
protein binding Cu(II). Metallomics, 3, 20-27
[55] Cole MP, Chaiswing L, Oberley TD, Kiningham KK and St. Clair DK (2002).
Mechanisms of cardiovascular aging. Advances in Cell Aging and Gerontology, 11,
233-281.
[56] Schoonen MAA, Cohn CA, Roemer E, Laffers R, Simon SR & O’Riordan T (2006)
Mineral-induced formation of reactive oxygen species. In: Sahai N, Schoonen MAA
(eds) Medical Mineralogy and Geochemistry, Reviews in Mineralogy & Geochemistry,
64, 179-221
[57] Fubini B & Fenoglio I (2007). Toxic potential of mineral dusts. Elements, 3, 407-414
[58] Rizk SL & Sky-Peck HH (1984). Comparison between concentrations of trace elements
in normal and neoplastic human breast tissue. Cancer Res, 44, 5390-4.
[59] Kuo HW, Chen SF, Wu CC, Chen DR, & Lee JH (2002). Serum and tissue trace
elements in patients with breast cancer in Taiwan. Biol Trace Elem Res. 89, 1-11.
[60] Brewer GJ (2001). Copper control as an antiangiogenic anticancer therapy: lessons
from treating Wilson's disease. Exp Biol Med (Maywood), 226, 665-73.
[61] Theophanides T & Anastassopoulou J (2002). Copper and carcinogenesis. Crit Rev
Oncol Hematol. 42, 57-64.
[62] Yoshii J, H. Yoshiji, S. Kuriyama, Y. Ikenaka, R. Noguchi, H. Okuda, H. Tsujinoue, T.
Nakatani, H. Kishida, D. Nakae, D. E. Gomez, M. S. De Lorenzo, A. M. Tejera & H.
Fukui (2001). The copper-chelating agent, trientine, suppresses tumor development and
angiogenesis in the murine hepatocellular carcinoma cells. Int J Cancer. 94, 768-73.
[63] Ishida S, Lee J, Thiele DJ & Herskowitz I (2002). Uptake of the anticancer drug
cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Proc Natl
Acad Sci USA, 99, 14298-14302.
[64] Ionescu JG, Novotny J, Stejskal V, Latsch A, Blaurock-Busch E, & Eisenmann-Klein
M (2006). Increased levels of transition metals in breast cancer tissue. Neuroendocrinol
Lett. 27(Suppl 1):36–39
[65] Qian ZM, Li H, Sun H & Ho K (2002). Targeted drug delivery via the transferrin
receptor-mediated endocytosis pathway. Pharmacol. Rev. 54 (4), 561–87.
[66] National Research Council Committee on Medical and Biological Effects of
Environmental Pollutants: Manganese. Washington: National Academy of Sciences,
(1973). pp. 1-191.
[67] Graedel TE (1978). Inorganic elements, hydrides, oxides, and carbonates. In: Chemical
compounds in the atmosphere. New York, NY, Academic Press, pp. 35–41, 44–49.
[68] Aschner M (1997). Manganese neurotoxicity and oxidative damage. In: Connor, J.R.
(Ed.), Metals and Oxidative Damage in Neurological Disorders. Plenum Press, New
York, pp. 77–93.
[69] Aschner JL & Aschner M (2005). Nutritional aspects of manganese homeostasis. Mol
Aspects Med. 26(4-5), 353-62.
[70] Santamaria AB & Sulsky SI (2010). Risk assessment of an essential element:
manganese. J Toxicol Environ Health A. 73(2), 128-55.
[71] National Academy of Sciences (NAS) (2001). Dietary Reference Intakes for Vitamin A,
Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese,
Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Panel on Micronutrients,
Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use
of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation
of Dietary Reference Intakes. Available from: www.nap.edu/books/0309072794/html/.
[72] Crossgrove J & Zheng W (2004). Manganese toxicity upon overexposure. NMR
Biomed. 17, 544–553
[73] Hegsted BM (1976). Food fortification. In: Nutrition in the Community. McLaren,
D.S., ED. John Wiley, N.Y.
[74] Tuormaa TE (1996). The Adverse Effects of Manganese Deficiency on Reproduction
and Health: A Literature Review. Journal of Orthomolecular Medicine, 11 (2), 69-79.
[75] Hwang CS, Baek YU, Yim HS, Kang SO (2003). Protective roles of mitochondrial
manganese-containing superoxide dismutase against various stresses in Candida
albicans. Yeast. 20(11), 929-41.
[76] Erikson KM, Thompson K, Aschner J & Aschner M (2007). Manganese neurotoxicity:
a focus on the neonate. Pharmacol Ther. 113(2), 369-77.
[77] Aschner M &, Aschner JL (1991) Manganese neurotoxicity: cellular effects and blood-
brain barrier transport. Neurosci Biobehav Rev 15, 333–340.
[78] Bagga S &Levy L (2007). Manganese Health Research Program: Overview of Research
into the Health Effects of Manganese (2002-2007). The Institute of Environment and
Health (IEH), Cranfield Health, Cranfield University, Silsoe, Bedfordshire, UK.
http://www.silsoe.cranfield.ac.uk/ieh/
[79] Roth JA & Garrick MD (2003). Iron interactions and other biological reactions
mediating the physiological and toxic actions of manganese. Biochem Pharmacol.
66(1), 1-13.
[80] Erikson KM & Aschner M (2006). Increased manganese uptake by primary astrocyte
cultures with altered iron status is mediated primarily by divalent metal transporter..
Neurotoxicology. 27(1), :125-30.
[81] Garcia SJ, Gellein K, Syversen T & Aschner M (2007). Iron deficient and manganese
supplemented diets alter metals and transporters in the developing rat brain. Toxicol Sci.
95(1), 205-14..
[82] Fitsanakis VA, Zhang N, Garcia S, Aschner M (2010). Manganese (Mn) and iron (Fe):
interdependency of transport and regulation. Neurotox Res. 18(2), 124-31.
[83] Misselwitz B, Mühler A & Weinmann HJ (1995). A toxicologic risk for using
manganese complexes? A literature survey of existing data through several medical
specialties. Invest Radiol. 30(10), 611-20.
[84] Joint FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements.
Vitamin and Mineral Requirements In Human Nutrition (1998). Second edition.
Chapter 12. Zinc.pp.230-245). Bangkok, Thailand.
[85] Yanagisawa H (2002). Clinical aspects of zinc deficiency. The Journal of the Japan
Medical Association, 127(2), 261–268.
[86] Ackland ML & Michalczyk A (2006). Zinc deficiency and its inherited disorders – A
review. Genes & Nutrition 1 (1), 41-50.
[87] Nriagu J (2007). Zinc Toxicity in Humans. Web-based Resources . 2007 Elsevier B.V.
pp.1-7.
[88] Bertini I, Luchinat C (1994). The reaction pathways of zinc enzymes and related
biological catalysts. In Bioinorganic Chemistry. Edited by Bertini I, Gray HB.
University Science Books Mill Valley, California.
[89] Williams RJP (1987). The biochemistry of zinc. Polyhedron 6, 61–69.
[90] Glusker JP, Katz AK & Bock CW (1999). Metal ions in biological systems. The Rigaku
Journal. 16 (2), 8-16.
[91] Fortescue JAC (1992). Landscape geochemistry: retrospect and prospect. Applied
Geochemistry, 7, 1–53.
[92] Hille R (1999). Molybdenum enzymes. Essays Biochem. 34, 125-37.
[93] Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper,
iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc.
Washington, DC: National Academy Press; 2002. p. 420–41.
[94] Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of
Molybdenum. SCF/SC/NUT/UPPERLEV/22. Brussels: Scientific Committee on Food,
European Commission; 2000. p. 1–15.
[95] Vyskocil A & Viau C (1999). Assessment of molybdenum toxicity in humans. J Appl
Toxicol. 19(3), 185-92.
[96] Turnlund JR, Weaver CM, Kim SK, Keyes WR, Gizaw Y, Thompson KH, & Peiffer
GL (1999). Molybdenum absorption and utilization in humans from soy and kale
intrinsically labeled with stable isotopes of molybdenum. Am J Clin Nutr. 69, 1217–23.
[97] Novotny JA & Turnlund JR 92007). Molybdenum intake influences molybdenum
kinetics in men. Nutr. 137, 37-42.
[98] Johnson JL (2003). Prenatal diagnosis of molybdenum cofactor deficiency and isolated
sulfite oxidase deficiency. Prenat Diagn. 23(1), 6-8.
[99] Reiss J & Johnson JL (2003).Mutations in the molybdenum cofactor biosynthetic genes
MOCS1, MOCS2, and GEPH. Hum Mutat. 21(6), 569-76.
[100] Mendel RR & Hänsch R (2002). Molybdoenzymes and molybdenum cofactor in

plants. J. Exp. Bot. 53 (375), 1689-1698.
[101] Bogden JD, Klevay LM, eds. Clinical nutrition of the essential trace elements and
minerals: the guide for health professionals. Totowa, NJ: Humana Press Inc.
[102] Hille R (2002). Molybdenum and tungsten in biology. Trends in Biochemical Sciences,
27 (7), 360-367.
[103] Buckel W & Golding BT (2008). Cobalamin Coenzymes and Vitamin B12. In:
Encyclopaedia of Life Sciences, John Wiley & Sons, Ltd, online.
[104] Scott JW (1998) Vitamin B12. In: Kroschwitz JI, Howe-Grant M (eds) Kirk-Othman
encyclopedia of chemical technology, vol 25, 4th edn. Wiley, New York, pp 193–217.
[105] Randaccio L, Geremia S, Demitri N & Wuerges J (2010). Vitamin B12: unique
metalorganic compounds and the most complex vitamins. Molecules 15, 3228-3259;
[106] Anderson RA (1997). Chromium as an essential nutrient for humans. Regul Toxicol
Pharmacol. 26(1 Pt 2), S35-41.
[107] Preuss HG & Anderson RA (1998). Chromium update: examining recent literature
1997-1998. Curr Opin Clin Nutr Metab Care. 1(6), 509-12.
[108] Hummel M, Standl E & Schnell O (2007). Chromium in metabolic and cardiovascular
disease. Horm Metab Res. 39(10), 743-51.
[109] Wang ZQ & Cefalu WT. Current concepts about chromium supplementation in type 2
diabetes and insulin resistance. Curr Diab Rep. 10(2), 145-51.
[110] Di Bona KR, Love S, Rhodes NR, McAdory D, Sinha SH, Kern N, Kent J, Strickland J,
Wilson A, Beaird J, Ramage J, Rasco JF, Vincent JB (2011). Chromium is not an
essential trace element for mammals: effects of a "low-chromium" diet. J Biol Inorg
Chem. 16(3):381-90.
[111] WHO (1987). Air quality guidelines for Europe. Copenhagen, World Health
Organization Regional Office for Europe, 1987 (WHO Regional Publications, European
Series, No. 23).
[112] Rehder D (2003). Biological and medicinal aspects of vanadium. Inorganic Chemistry
Communications, 6, 604–617.
[113] Fallico R, Ferrante M, Fiore M, Madeddu A & Sciacca S (1998). Epidemiological
research into the consequences of vanadium assimilated through diet and of its effects
on human health following research carried out on people from the Etna massif. J Prev
Med Hyg. 39, 74-79.
[114] Air Quality Guidelines (2000). Second Edition Chapter 6.12 Vanadium WHO Regional
Office for Europe, Copenhagen, Denmark.
[115] INC (1986). Toxicology and Biological monitoring of metals in humans, including
feasibility and need. Lewis publischers.
[116] Sabbioni E, Kueera J, Pietra R, Vesterberg O (1996). A critical review on normal
concentrations of vanadium in human blood, serum, and urine. The Science of The Total
Environment, 188, 49-58.
[117] IlicV, Bojanic V & Jovic B (2007). Epidemiological and pathogenetic aspects of nickel
poisoning. Acta Medaca Medianae 46(2), 37-44.
[118] Nielsen FH (1993). Is nickel nutritionally important? Nutrition today. 28 (1), 14-19.
[119] Sabo-Attwood T, Ramos-Nino M & Mossman BT (2006). Environmental
carcinogenesis. In: Oncology: An Evidence-Based Approach. Edited by Alfred E.
Chang, Patricia A. Ganz, Daniel F. Hayes, and others. New York, Springer-Verlag.
[120] Waalkes M( 1995). Metal carcinogenesis. In: Goyer RA & Klaassen CD, eds. Metal
toxicology. New York: Academic Press, pp. 47-67.
[121] Gold LS, Zeiger E, editors (1997). Handbook of Carcinogenic Potency and
Genotoxicity Databases. New York, NY, USA: CRC Press.
[122] Beyersmann D (2002). Effects of carcinogenic metals on gene expression. Toxicol Lett.
127(1–3), 63–68.
[123] Cantor KP, Stewart PA, Brinton LA & Dosemeci M (1995). Occupational exposures
and female breast cancer mortality in the United States. J Occup Environ Med. 37(3),
336-48.
[124] Adachi S, Takemoto K, Ohshima S, Shimizu Y & Takahama M (1991). Metal
concentrations in lung tissue of subjects suffering from lung cancer. Int Arch Occup
Environ Health, 63, 193–197.
[125] Ebadi M & Swanson S (1988). The status of zinc, copper and methallothionein in
cancer patients. Prog Clin Biol Res. 259, 161–175.
[126] Wang M, Dhingra K, Hittelman WN, Liehr JG, de Andrade M & Li D (1996). Lipid
peroxidation-induced putative malondialdehye-DNA adducts in human breast tissue.
Cancer Epidemiol Biomarkers Prev. 5, 705–710.
[127] U.S. EPA (1985). United States Environmental Protection Agency. Health Assessment
Document for Nickel. EPA/600/8-83/012F, pp. 3-3.
[128] Nackerdien Z, Kasprzak KS, Rao G, Halliwell B & Dizdaroglu M (1991). Nickel(II)-
and cobalt(II)-dependent damage by hydrogen peroxide to the DNA bases in isolated
human chromatin. Cancer Res. 51, 5837-5842.
[129] NTP (1994). National Toxicology Program. Technical Report on the Toxicology and
Carcinogenesis Studies of Nickel Oxide in F344/N Rats and B6C3F1 Mice. NTP TR
451, NIH Publication No. 94-3363. U.S. Department of Health and Human Services.
[130] Grimsrud TK & Peto J (2006). Persisting risk of nickel related lung cancer and nasal
cancer among Clydach refiners. Occup Environ Med. 63, 365-366
[131] Chen H, Giri NC, Zhang R, Yamane K, Zhang Y, Maroney M & Costa M (2010).
Nickel ions inhibit histone demethylase JMJD1A and DNA repair enzyme ABH2 by
replacing the ferrous iron in the catalytic centers. J Biol Chem. 285, 7374-7383.
[132] National Toxicology Program. NTP toxicology and carcinogensis studies of vanadium
pentoxide (CAS No. 1314-62-1) in F344/N rats and B6C3F1 mice (inhalation). Natl
Toxicol Program Tech Rep Ser. (507), 1-343.
[133] Duffus JH (2007). Carcinogenicity classification of vanadium pentoxide and inorganic
vanadium compounds, the NTP study of carcinogenicity of inhaled vanadium
pentoxide, and vanadium chemistry. Regul Toxicol Pharmacol. 47(1), 110-4.
[134] Assem FL & Levy LS (2009). A review of current toxicological concerns on vanadium
pentoxide and other vanadium compounds: gaps in knowledge and directions for future
research. J Toxicol Environ Health B Crit Rev. 12(4), 289-306.
[135] Vanadyl binds readily to proteins, amino acids, nucleic acids, phosphates,
phospholipids, glutathione, citrate, oxalate, lactate, ascorbate, edetate, etc. [134]
(Nechay et al., 1986).
[136] Ehrlich VA, Nersesyan AK, Atefie K, Hoelzl C, Ferk F, Bichler J, Valic E, Schaffer A,
Schulte-Hermann R, Fenech M, Wagner KH, Knasmüller S (2008). Inhalative exposure
to vanadium pentoxide causes DNA damage in workers: results of a multiple end point
study. Environ Health Perspect. 116(12), 1689-93.
[137] Rodríguez-Mercado JJ, Alvarez-Barrera L & Altamirano-Lozano MA (2010).

Chromosomal damage induced by vanadium oxides in human peripheral lymphocytes.
Drug Chem Toxicol. 33(1), 97-102.
[138] Rondini EA, Walters DM, Bauer AK (2010). Vanadium pentoxide induces pulmonary
inflammation and tumor promotion in a strain-dependent manner. Part Fibre Toxicol.
12, 7:9.
[139] Shi X & Dalai NS (1993). Vanadate-mediated hydroxyl radical generation from
superoxide radical in the presence of NADH: Haber-Weiss vs. Fenton mechanism.
Arch. Biochem. Biophys. 3M, 336-341.
[140] Langard S (1990). One hundred years of chromium and cancer: a review of
epidemiological evidence and selected case reports. Am. J. Ind. Med., 17, 189–215.
[141] Langard S (1993). Role of chemical species and exposure characteristics in cancer
among persons occupationally exposed to chromium compounds. Scand. J. Work
Environ. Health, 19 (suppl. 1), 81–89.
[142] IARC (1990). Chromium, nickel, and welding. IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans. Vol. 49, IARC, Lyon, 49–445.
[143] Arslan P, Beltrame M & Tomasi A (1987). Intracellular chromium reduction. Biochim
Biophys Acta, 931, 10–15.
[144] Shi X, Chiu A, Chen CT, Halliwell B, Castranova V, Vallyathan V (1999). Reduction
of chromium(VI) and its relationship to carcinogenesis. J. Toxicol. Environ. Health B
Crit. Rev. 2, 87–104.
[145] Shi XL, Dalal NS. (1989) Chromium (V) and hydroxyl radical formation during the
glutathione reductase-catalyzed reduction of chromium (VI). Biochem. Biophys. Res.
Commun., 163, 627–634.
[146] Shi X, Mao Y, Knapton AD, Ding M, Rojanasakul Y, Gannett PM, Dalal N, Liu K.
(1994) Reaction of Cr(VI) with ascorbate and hydrogen peroxide generates hydroxyl
radicals and causes DNA damage: role of a Cr(IV)-mediated Fenton-like reaction.
Carcinogenesis, 15, 2475–2478.
[147] Luo H, Lu Y, Shi X, Mao Y, Dalal NS. (1996) Chromium (IV)-mediated fenton-like
reaction causes DNA damage: implication to genotoxicity of chromate. Ann. Clin. Lab
Sci., 26, 185–191.
[148] Kawanishi S Inoue S & Sano S (1986). Mechanism of DNA cleavage induced by
sodium chromate (VI) in the presence of hydrogen peroxide. J. Biol. Chem. 261, 5952-
5958.
[149] Tamino G, Peretta L & Levis AG (1981). Effects of the trivalent and hexavalent
chromium on the physicochemical properties of mammalian cell nucleic acids and
synthetic polynucleotides. Chem Biol Interact 37, 309–319.
[150] Arakawa H, Ahmad R, Naoui M & Tajmir-Riahi HA (2000). Acomparative study of
calf thymus DNA binding to Cr(III) and Cr(VI) ions. Evidence for the guanine N-7-
chromium-phosphate chelate formation. J Biol Chem. 275, 10150–10153.
[151] Stearns DM, Courtney KD, Giangrande PH, Phieffer LS & Wetterhahn KE (1994).
Chromium(VI) reduction by ascorbate: Role of reactive intermediates in DNA damage
in vitro. Environ Health Perspect 102(Suppl 3), 21–25.
[152] O'Brien TJ, Ceryak S, Patierno SR. (2003) Complexities of chromium carcinogenesis:
role of cellular response, repair and recovery mechanisms. Mutat. Res., 533, 3–36
[153] Nickens KP, Patierno SR, Ceryak S (2010). Chromium genotoxicity: A double-edged
sword. Chem Biol Interact. 188(2), 276-88.
[154] Son YO, Hitron JA, Wang X, Chang Q, Pan J, Zhang Z, Liu J, Wang S, Lee JC, Shi X
(2010).Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis
through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells. Toxicol
Appl Pharmacol. 245(2), 226-35.
[155] Mitochondrial ROS, specifically superoxide anion (O2·–), mediates Cr(VI)-induced
apoptosis of human lung epithelial H460 cells [154](Azad et al., 2008).
[156] Norseth T (1981). The carcinogenicity of chromium. Enviro Health Perspective, 40,
121-130.
[157] Gibb HJ, Lees PS, Pinsky PF , Rooney BC (2000). Lung cancer among workers in
chromium chemical production. Am J Ind Med. 38(2), 115-26.
[158] Ammann RW, Müller E, Bansky J, Schüler G, Häcki WH (1980). High incidence of
extrahepatic carcinomas in idiopathic hemochromatosis. Scand J Gastroenterol. 15(6),
733-6.
[159] Stevens RG, Jones DY, Micozzi MS, Taylor PR (1988). Body iron stores and the risk of
cancer. N Engl J Med. 319, 1047–1052.
[160] Elmberg M, Hultcrantz R, Ekbom A, Brandt L, Olsson S, Olsson R (2003). Cancer risk
in patients with hereditary hemochromatosis and in their first-degree relatives.
Gastroenterology, 125, 1733–1741.
[161] Okada S (1996). Iron-induced tissue damage and cancer: the role of reactive oxygen
species and free radicals. Pathol Int. 46, 311–332.
[162] Weinberg ED (1996). The role of iron in cancer. Eur J Cancer Prev. 5, 19–36.
[163] Taetle R, Rhyner K, Castagnola J, To D, Mendelsohn J (1985). Role of transferrin, Fe,
and transferrin receptors in myeloid leukemia cell growth. Studies with an
antitransferrin receptor monoclonal antibody. J Clin Invest 75, 1061–7.
[164] Hann HW, Stahlhut MW, Blumberg BS (1988). Iron nutrition and tumor growth:
decreased tumor growth in iron-deficient mice. Cancer Res 48, 4168–70.
[165] Carthew P, Nolan BM, Smith AG, Edwards RE (1997). Iron promotes DEN initiated
GST-P foci in rat liver. Carcinogenesis. 18(3), 599-603.
[166] Wu T, Sempos CT, Freudenheim JL, Muti, Smit E (2004 ). Serum iron, copper and zinc
concentrations and risk of cancer mortality in US adults. Ann Epidemiol. 14(3), 195-
201.
[167] Hughes R, Cross AJ, Pollock JR, Bingham S (2001). Dose-dependent effect of dietary
meat on endogenous colonic N-nitrosation. Carcinogenesis, 22, 199–202.
[168] Senesse P, Meance S, Cottet V, Faivre J, Boutron-Ruault MC (2004). High dietary iron
and copper and risk of colorectal cancer: a case-control study in Burgundy, France.
Nutr Cancer, 49, 66–71.
[169] Cross AJ, Gunter MJ, Wood RJ, Pietinen P, Taylor PR, Virtamo J, Albanes D, Sinha R
(2006). Iron and colorectal cancer risk in the alpha-tocopherol, beta-carotene cancer
prevention study. Int J Cancer. 118(12), 3147-52.
[170] Mello FA, Meneghini R (1984). In vivo formation of single-strand breaks in DNA by
hydrogen peroxide is mediated by the Haber-Weiss-reaction. Biochem Biophys Acta.
781, 56 63.
[171] Aust SD, Morehouse LA, Thomas CE (1985). Role of metals in oxygen radical
reactions. J Free Radic Biol Med. 1, 3-25.
[172] Beyersmann D, Hartwig A (2008). Carcinogenic metal compounds: recent insight into
molecular and cellular mechanisms. Arch Toxicol. 82(8), 493-512.
[173] Bush AI (2003). The metallobiology of Alzheimer's disease. Trends Neurosci. 26(4),
207-14.
[174] Crichton RR, Ward RJ (2006). Metal-based Neurodegeneration From Molecular
mechanisms to Therapeutic Strategies, John Wiley and Sons, Chichester, pp. 227.
[175] Alexander J, Kowdley KV (2009) HFE-associated hereditary hemochromatosis. Genet
Med. 11, 307–313.
[176] Hoogenraad TU (1996). Monography: Wilson’s disease. In: Major Problems in
Neurology. Vol 30, London: W.B. Saunders.
[177] Halliwell B (2006). Oxidative stress and neurodegeneration: where are we now?.
Journal of Neurochemistry, 97, 1634–1658.
[178] Khachaturian ZS (1985). Diagnosis of Alzheimer’s disease. Arch Neurol. 42, 1097–
105.
[179] Filley CM (1995). Alzheimer’s disease: it’s irreversible but not untreatable. Geriatrics,
50, 18–23.
[180] Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE,
Hennekens CH, Taylor JO (1989). Prevalence of Alzheimer’s disease in a community
population of older persons: higher than previously reported. JAMA, 262 (18), 2551-6.
[181] Probst A, Langui D, Ulrich J (1991). Alzheimer’s disease: a description of the structural
lesions. Brain. Pathol. 1, 229-239
[182] Price DL, Sisodia SS (1998) Mutant genes in familial Alzheimer's disease and
transgenic models. Annu Rev Neurosci 21, 479–505
[183] Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, et al. (1992) Isolation and
Quantification of Soluble Alzheimers Beta-Peptide from Biological-Fluids. Nature,
359, 325–327.
[184] Busciglio J, Gabuzda DH, Matsudaira P, Yankner BA (1993) Generation of Beta-
Amyloid in the Secretory Pathway in Neuronal and Nonneuronal Cells. Proceedings of
the National Academy of Sciences of the United States of America, 90, 2092–2096.
[185] Selkoe DJ (2001). Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 81,
741–766.
[186] Castellani RJ, Alexiev BA, Phillips D, Perry G and Smith MA (2007). Microscopic
Investigations in Neurodegenerative Diseases. Modern Research and Educational
Topics in Microscopy. Méndez-Vilas A and J. Díaz (eds) pp 171-182.
[187] Iqbal K, Alonso Adel C, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li,
B, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I (2005). Tau pathology in
Alzheimer’s disease and other tauopathies. Biochim. Biophys. Acta, 1739 (2-3), 198-
210.
[188] Quintana C, Bellefqih S, Laval JY, Guerquin-Kern JL, Wu TD, Avila J, Ferrer I, Arranz
R, Patino C (2006). Study of the localization of iron, ferritin, and hemosiderin in
Alzheimer’s disease hippocampus by analytical microscopy at the subcellular level. J
Struct Biol. 153, 42–54.
[189] Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998).
Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci. 158, 47-52.
[190] Rossi L, Squitti R, Pasqualetti P, Marchese E, Cassetta E, Forastiere E, Rotilio G,
Rossini PM, Finazzi-Agró A (2002). Red blood cell copper, zinc superoxide dismutase
activity is higher in Alzheimer's disease and is decreased by D-penicillamine. Neurosci

Lett. 329(2), 137-40.
[191] Danscher G, Jensen KB, Frederickson CJ, Kemp K, Andreasen A, Juhl S, Stoltenberg
M, Ravid R (1997). Increased amount of zinc in the hippocampus and amygdala of
Alzheimer's diseased brains: a proton-induced X-ray emission spectroscopic analysis of
cryostat sections from autopsy material. J Neurosci Methods. 76(1), 53-9.
[192] Cornett CR, Markesbery WR, Ehmann WD (1998). Imbalances of trace elements
related to oxidative damage in Alzheimer's disease brain. Neurotoxicology, 19(3), 339-
45.
[193] Cornett CR, Ehmann WD, Wekstein DR, Markesbery WR (1998). Trace elements in
Alzheimer's disease pituitary glands. Biol Trace Elem Res. 62(1-2), 107-14.
[194] Dong J, Robertson JD, Markesbery WR, Lovell MA (2008). Serum zinc in the
progression of Alzheimer's disease. J Alzheimers Dis. 15(3), 443-50.
[195] Lovell MA, Smith JL, Xiong S, Markesbery WR (2005). Alterations in zinc transporter
protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and
late-stage Alzheimer's disease. Neurotox Res. 7(4), 265-71.
[196] Lovell MA, Smith JL, Markesbery WR (2006). Elevated zinc transporter-6 in mild
cognitive impairment, Alzheimer disease, and pick disease. J Neuropathol Exp Neurol.
65(5), 489-98.
[197] Squitti R, Lupoi D, Pasqualetti P, Dal Forno G, Vernieri F, Chiovenda P (2002).
Elevation of serum copper levels in Alzheimer’s disease. Neurol 59, 1153-61.
[198] Sayre LM, Perry G, Harris PL, Liu Y, Schubert KA, Smith MA (2000). In situ catalysis
by neurofibrillary tangles and senile plaques in Alzheimer’s disease: a central role for
bound transition metals. J Neurochem. 74, 270-9.
[199] Miller LM, Wang Q, Telivala TP, Smith RJ, Lanzirotti A, Miklossy J (2006).
Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and
Zn co-localized with β-amyloid deposits in Alzheimer’s disease. J Struct Biol. 155, 30–
37.
[200] Squitti R, Bressi F, Pasqualetti P, Bonomini C, Ghidoni R, Binetti G, Cassetta E, Moffa
F, Ventriglia M, Vernieri F, Rossini PM (2009). Longitudinal prognostic value of
serum "free" copper in patients with Alzheimer disease. Neurology. 72(1), 50-5.
[201] Salustri C, Barbati G, Ghidoni R, Quintiliani L, Ciappina S, Binetti G, Squitti R (2010).
Is cognitive function linked to serum free copper levels? A cohort study in a normal
population. Clin Neurophysiol. 121(4), 502-7.
[202] Kessler H, Pajonk FG, Meisser P, Schneider-Axmann T, Hoffmann KH, Supprian T
(2006). Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and
ceruloplasmin in patients with Alzheimer’s disease. Neural Transm. 113, 1763-9.
[203] Squitti R, Quattrocchi CC, Salustri C and Rossini PM (2008). Ceruloplasmin
fragmentation is implicated in ‘free’ copper deregulation of Alzheimer’s disease. Prion
2:1, 23-27.
[204] Gray EH, De Vos KJ, Dingwall C, Perkinton MS, Miller CC (2010). Deficiency of the
Copper Chaperone for Superoxide Dismutase Increases Amyloid-β Production. J
Alzheimers Dis. 21(4), 1101-5.
[205] Strozyk D, Launer LJ, Adlard PA, Cherny RA, Tsatsanis A, Volitakis I, Blennow K,
Petrovitch H, White LR, Bush AI 92009). Zinc and copper modulate Alzheimer Abeta
levels in human cerebrospinal fluid. Neurobiol Aging. 30(7), 1069-77.
[206] Finder VH, Glockshuber R (2007). Amyloid-beta aggregation. Neurodegener Dis. 4(1),
13-27.
[207] Soto C (2003). Unfolding the role of protein misfolding in neurodegenerative diseases.
Nat Rev Neurosci. 4(1), 49-60.
[208] Shirwany NA, Payette D, Xie J, Guo Q (2007). The amyloid beta ion channel
hypothesis of Alzheimer's disease. Neuropsychiatr Dis Treat. 3(5), 597-612.
[209] McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, and
Masters CL (1999). Soluble pool of Aβ amyloid as a determinant of severity of
neurodegeneration in Alzheimer's disease. Ann. Neurol. 46, 860–866.
[210] Yang X, Askarova S, Lee JC (2010). Membrane biophysics and mechanics in
Alzheimer's disease. Mol Neurobiol. 41(2-3), 138-48.
[211] Wu HY, Hudry E, Hashimoto T, Kuchibhotla K, Rozkalne A, Fan Z, Spires-Jones T,
Xie H, Arbel-Ornath M, Grosskreutz CL, Bacskai BJ, Hyman BT (2010). Amyloid beta
induces the morphological neurodegenerative triad of spine loss, dendritic
simplification, and neuritic dystrophies through calcineurin activation. J Neurosci.
30(7), 2636-49.
[212] Chen T, Wang X, He Y, Zhang C, Wu Z, Liao K, Wang J, Guo Z (2009). Inorg Chem.
Effects of cyclen and cyclam on zinc(II)- and copper(II)-induced amyloid beta-peptide
aggregation and neurotoxicity. 48(13), 5801-9.
[213] Huang XD, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD (1999). Cu(II)
potentiation of Alzheimer A beta neurotoxicity. Correlation with cell-free hydrogen
peroxide production and metal reduction. Journal of Biological Chemistry, 274, 37111–
37116.
[214] Drochioiu G, Manea M, Dragusanu M, Murariu M, Dragan ES, Petre BA, Mezo G,
Przybylski M (2009). Interaction of β-amyloid(1-40) peptide with pairs of metal ions:
An electrospray ion trap mass spectrometric model study. Biophysical Chemistry, 144,
9–20.
[215] Karr JW, Kaupp LJ, Szalai VA (2004). Amyloid-beta binds Cu2+ in a mononuclear
metal ion binding site. J Am Chem Soc. 126(41), 13534-8.
[216] Maynard CJ, Bush AI, Masters CL, Cappai R, Li QX (2005). Metals and amyloid-β in
Alzheimer’s disease. Int J Exp Pathol. 86, 147–159.
[217] Streltsov V (2008). X-ray absorption and diffraction studies of the metal binding sites
in amyloid β-peptide. Eur Biophys J. 7, 257–263.
[218] Streltsov VA, Titmuss SJ, Epa VC, Barnham KJ, Masters CL and Varghese JN
(2008).The Structure of the Amyloid-β Peptide High-Affinity Copper II Binding Site in
Alzheimer Disease. Biophys J. 95(7), 3447–3456.
[219] Tõugu V, Karafin A, Palumaa P (2008). Binding of zinc(II) and copper(II) to the full-
length Alzheimer's amyloid-beta peptide. J Neurochem. 104(5), 1249-59.
[220] Dong J, Canfield JM, Mehta AK, Shokes JE, Tian B, Childers WS, Simmons JA, Mao
Z, Scott RA, Warncke K, and Lyn DG (2007). Engineering metal ion coordination to
regulate amyloid fibril assembly and toxicity. Proc Natl Acad Sci U S A. 104(33),
13313–13318.
[221] Miura T, Suzuki K, Kohata N, Takeuchi H (2000). Metal binding modes of Alzheimer's
amyloid beta-peptide in insoluble aggregates and soluble complexes. Biochemistry.
39(23), 7024-31.
[222] Stellato F, Menestrina G, Serra MD, Potrich C, Tomazzolli R, Meyer-Klaucke W,

Morante S (2006). Metal binding in amyloid beta-peptides shows intra- and inter-
peptide coordination modes. Eur Biophys J. 35(4), 340-51.
[223] Dong J, Atwood CS, Anderson VE, Siedlak SL, Smith MA, Perry G, Carey PR (2003).
Metal binding and oxidation of amyloid-beta within isolated senile plaque cores:
Raman microscopic evidence. Biochemistry, 42(10), 2768–73.
[224] Smith DP, Smith DG, Curtain CC, Boas JF, Pilbrow JR, Ciccotosto GD, Lau TL, Tew
DJ, Perez K, Wade JD, Bush AI, Drew SC, Separovic F, Masters CL, Cappai R,
Barnham KJ (2006). Copper-mediated amyloid-beta toxicity is associated with an
intermolecular histidine bridge. J Biolr Chem. 281(22), 15145-54.
[225] Syme CD, Viles JH (2006). Solution 1H NMR investigation of Zn2+ and Cd2+ binding
to amyloid-beta peptide (Abeta) of Alzheimer's disease. Biochim Biophys Acta.
1764(2), 246-56.
[226] Miller Y, Ma B and Nussinov R (2010). Zinc ions promote Alzheimer Aβ aggregation
via population shift of polymorphic states. Proc Natl Acad Sci U S A. 107(21), 9490–
9495.
[227] Jun S, Gillespie JR, Shin BK, Saxena S (2009). The second Cu(II)-binding site in a
proton-rich environment interferes with the aggregation of amyloid-beta(1-40) into
amyloid fibrils. Biochemistry. 48(45), 10724-32.
[228] Sarell CJ, Syme CD, Rigby SE, Viles JH (2009). Copper(II) binding to amyloid-beta
fibrils of Alzheimer's disease reveals a picomolar affinity: stoichiometry and
coordination geometry are independent of Abeta oligomeric form. Biochemistry.
48(20), 4388-402.
[229] Curtain CC, Barnham KJ and Bush AI. Aβ metallobiology and the development of
novel metal-protein attenuating compounds (MPACs) for Alzheimer's disease . Curr.
Med. Chem. – Immun., Endoc. & Metab. Agents, 2003, 3, 309-315
[230] Cuajungco MP, Goldstein LE, Nunomura A, Smith MA, Lim JT (2000). Evidence that
the beta-amyloid plaques of Alzheimer's disease represent the redox-silencing and
entombment of A beta by zinc. J Biol Chem. 275, 19439–19442.
[231] Suzuki K, Miura T, Takeuchi H (2001). Inhibitory effect of copper(II) on zinc(II)-
induced aggregation of amyloid beta-peptide. Biochem Biophys Res Commun. 285(4),
991-6.
[232] Yoshiike Y, Tanemura K, Murayama O, Akagi T, Murayama M, Sato S, Sun X, Tanaka
N, Takashima A (2001). New insights on how metals disrupt amyloid beta-aggregation
and their effects on amyloid-beta cytotoxicity. J Biol Chem. 276(34), 32293-9.
[233] Karr JW, Akintoye H, Kaupp LJ, Szalai VA (2005). N-Terminal deletions modify the
Cu2+ binding site in amyloid-beta. Biochemistry. 44(14), 5478-87.
[234] Chen YR, Huang HB, Chyan CL, Shiao MS, Lin TH, Chen YC (2006). The effect of
Abeta conformation on the metal affinity and aggregation mechanism studied by
circular dichroism spectroscopy. J Biochem. 139(4), 733-40.
[235] Dai X, Sun Y, Gao Z, Jiang Z (2010). Copper enhances amyloid-beta peptide
neurotoxicity and non beta-aggregation: a series of experiments conducted upon
copper-bound and copper-free amyloid-beta peptide. J Mol Neurosci. 41(1), 66-73.
[236] Ha C, Ryu J, Park CB (2007). Metal ions differentially influence the aggregation and
deposition of Alzheimer's beta-amyloid on a solid template. Biochemistry. 46(20),
6118-25.
[237] Ryu J, Girigoswami K, Ha C, Ku SH, Park CB (2008). Influence of multiple metal ions
on beta-amyloid aggregation and dissociation on a solid surface. Biochemistry. 47(19),
5328-35.
[238] Yang XH, Huang HC, Chen L, Xu W, Jiang ZF (2009). Coordinating to three histidine
residues: Cu(II) promotes oligomeric and fibrillar amyloid-beta peptide to precipitate in
a non-beta aggregation manner. J Alzheimers Dis. 18(4), 799-810.
[239] House E, Mold M, Collingwood J, Baldwin A, Goodwin S and Exley C (2009). Copper
Abolishes the β-Sheet Secondary Structure of Preformed Amyloid Fibrils of Amyloid-
β42. J Alzheimers Dis. 18(4), 811–817.
[240] Butterfield DA, Castegna A, Lauderback CM, Drake J (2002). Evidence that amyloid
beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain
contribute to neuronal death. Neurobiol Aging. 23(5), 655-64.
[241] Abramov AY, Canevari L, Duchen MR (2004).Beta-amyloid peptides induce
mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons
through activation of NADPH oxidase. J Neurosci. 24(2), 565-75.
[242] De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, Klein WL
(2007). Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-
aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug
memantine. J Biol Chem. 282(15), 11590-601.
[243] Rival T, Page RM, Chandraratna DS, Sendall TJ, Ryder E, Liu B, Lewis H, Rosahl T,
Hider R, Camargo LM, Shearman MS (2009), Fenton chemistry and oxidative stress
mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer's
disease. Eur J Neurosci. 29(7), 1335-47.
[244] Tabner BJ, Turnbull S, El-Agnaf OM, Allsop D (2002). Formation of hydrogen
peroxide and hydroxyl radicals from A(beta) and alpha-synuclein as a possible
mechanism of cell death in Alzheimer's disease and Parkinson's disease. Free Radic
Biol Med. 32(11), 1076-83.
[245] Guilloreau L, Combalbert S, Sournia-Saquet A, Mazarguil H, Faller P (2007). Redox
chemistry of copper-amyloid-beta: the generation of hydroxyl radical in the presence of
ascorbate is linked to redox-potentials and aggregation state. Chembiochem. 8(11),
1317-25.
[246] Mattson MP (2004). Metal-catalyzed disruption of membrane protein and lipid
signaling in the pathogenesis of neurodegenerative disorders. Ann N Y Acad Sci. 1012,
37-50.
[247] White AR, Cappai R (2003).Neurotoxicity from glutathione depletion is dependent on
extracellular trace copper. J Neurosci Res. 71(6), 889-97.
[248] Bush AI (2002). Metal complexing agents as therapies for Alzheimer's disease.
Neurobiol Aging. 23(6), 1031-8.
[249] Jiang D, Men L, Wang J, Zhang Y, Chickenyen S, Wang Y, Zhou F (2007). Redox
reactions of copper complexes formed with different beta-amyloid peptides and their
neuropathological [correction of neuropathalogical] relevance. Biochemistry. 46(32),
9270-82.
[250] Spasojević I, Mojović M, Stević Z, Spasić SD, Jones DR, Morina A, Spasić MB (2010).
Bioavailability and catalytic properties of copper and iron for Fenton chemistry in
human cerebrospinal fluid. Redox Rep. 15(1), 29-35.
[251] iang H, Song N, Xu H, Zhang S, Wang J, Xie J (2010). Up-regulation of divalent metal
transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent. Cell Res 20,
345–356.
[252] Nadal RC, Rigby SE, Viles JH (2008). Amyloid beta-Cu2+ complexes in both
monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl
radicals. Biochemistry. 47(44), 11653-64.
[253] Shearer J and Szalai VA (2008). The amyloid-β peptide of Alzheimer's disease binds
CuI in a linear bis-His coordination environment: Insight into a possible neuroprotective
mechanism for the amyloid-β peptide. J Am Chem Soc. 130(52), 17826–17835.
[254] Tabner BJ, El-Agnaf OM, Turnbull S, German MJ, Paleologou KE, Hayashi Y, Cooper
LJ, Fullwood NJ, Allsop D (2005). Hydrogen peroxide is generated during the very
early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and
familial British dementia. J Biol Chem. 280(43), 35789-92.
[255] [254] Crouch PJ, Blake R, Duce JA, Ciccotosto GD, Li QX, Barnham KJ, Curtain CC,
Cherny RA, Cappai R, Dyrks T, Masters CL, Trounce IA (2005). Copper-dependent
inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42.
J Neurosci. 25(3), 672-9.
[256] Barnham KJ, McKinstry WJ, Multhaup G, Galatis D, Morton CJ, Curtain CC,
Williamson NA, White AR, Hinds MG, Norton RS, Beyreuther K, Masters CL, Parker
MW, Cappai R (2003). Structure of the Alzheimer's disease amyloid precursor protein
copper binding domain. A regulator of neuronal copper homeostasis. J Biol Chem.
278(19), 17401-7.
[257] Bellingham S, Ciccotosto G, Needham B, Fodero A, White A, Masters C, Cappai R.
and Camakaris J (2004). Gene knockout of amyloid precursor protein and amyloid
precursor-like protein-2 increases cellular copper levels in primary mouse cortical
neuron and embryonic fibroblasts. J. Neurosci. 91, 423–428.
[258] Maynard C, Cappai, R, Volitakis I, Cherny R, White A, Beyreuther K, Masters C, Bush
A and Li QX (2002). Overexpression of Alzheimer's disease amyloid-β opposes the
age-dependent elevations of brain copper and iron. J. Biol. Chem. 277, 44670–44676
[259] Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K,
Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C,
Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI (2010). Iron-
export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in
Alzheimer's disease. Cell. 142(6), 857-67.
[260] Kägi JH, Kojima Y (1987). Chemistry and biochemistry of metallothionein. Experientia
Suppl. 52, 25–61.
[261] Meloni G, Faller P, Vasák M (2007). Redox silencing of copper in metal-linked
neurodegenerative disorders: reaction of Zn7metallothionein-3 with Cu2+ ions. J Biol
Chem. 282(22), 16068-78.
[262] Chung RS, Howells C, Eaton ED, Shabala L, Zovo K, et al. (2010) The native copper-
and zinc- binding protein metallothionein blocks copper-mediated Aβ aggregation and
toxicity in rat cortical neurons. PLoS ONE 5(8), e12030.
[263] Bothwell M (1995). Functional interactions of neurotrophins and neurotrophin
receptors. Annu Rev Neurosci. 18, 223–253.
[264] Milward EA, Papadopoulos R, Fuller SJ, Moir RD, Small D, Beyreuther K, Masters CL
(1992). The amyloid protein precursor of Alzheimer's disease is a mediator of the
effects of nerve growth factor on neurite outgrowth. Neuron. 9(1), 129-37.
[265] Ross GM, Shamovsky IL, Woo SB, Post JI, Vrkljan PN, Lawrance G, Solc M, Dostaler
SM, Neet KE, Riopelle RJ (2001). The binding of zinc and copper ions to nerve growth
factor is differentially affected by pH: implications for cerebral acidosis. J Neurochem.
78(3), 515-23.
[266] Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, Barnham KJ,
Volitakis I, Fraser FW, Kim Y (2001). Treatment with a copper-zinc chelator markedly
and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice.
Neuron. 30, 665–676.
[267] Doraiswamy PM, Finefrock AE (2004). Metals in our minds: therapeutic implications
for neurodegenerative disorders. Lancet Neurol. 3(7), 431-4.
[268] Caragounis A, Du T, Filiz G, Laughton KM, Volitakis I, Sharples RA, Cherny RA,
Masters CL, Drew SC, Hill AF, Li QX, Crouch PJ, Barnham KJ, White AR (2007).
Differential modulation of Alzheimer's disease amyloid beta-peptide accumulation by
diverse classes of metal ligands. Biochem J. 407(3), 435-50.
[269] Verhaegh GW, Richard MJ, Hainaut P (1997). Regulation of p53 by metal ions and by
antioxidants: dithiocarbamate down-regulates p53 DNA-binding activity by increasing
the intracellular level of copper. Mol Cell Biol. 17(10), 5699-706.
[270] Malm TM, Iivonen H, Goldsteins G, Keksa-Goldsteine V, Ahtoniemi T, Kanninen K,
Salminen A, Auriola S, Van Groen T, Tanila H, Koistinaho J (2007). Pyrrolidine
dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without
affecting beta-amyloid burden. J Neurosci. 27(14), 3712-21.
[271] Zhang J, Liu Q, Chen Q, Liu NQ, Li FL, Lu ZB, Qin C, Zhu H, Huang YY, He W,
Zhao BL (2006).Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating
metal homeostasis. FASEB J. 20(8), 1212-4.
[272] Squitti R, Rossini PM, Cassetta E, Moffa F, Pasqualetti P, Cortesi M, Colloca A, Rossi
L, Finazzi-Agró A(2002). d-penicillamine reduces serum oxidative stress in
Alzheimer's disease patients. Eur J Clin Invest. 32(1), 51-9.
[273] Cater MA, McInnes KT, Li QX, Volitakis I, La Fontaine S, Mercer JF, Bush AI (2008).
Intracellular copper deficiency increases amyloid-beta secretion by diverse
mechanisms. Biochem J. 412(1), 141-52.
[274] Crouch PJ, Hung LW, Adlard PA, Cortes M, Lal V, Filiz G, Perez KA, Nurjono M,
Caragounis A, Du T, Laughton K, Volitakis I, Bush AI, Li QX, Masters CL, Cappai R,
Cherny RA, Donnelly PS, White AR, Barnham KJ (2009).Increasing Cu bioavailability
inhibits Abeta oligomers and tau phosphorylation. Proc Natl Acad Sci U S A. 106(2),
381-6.
[275] Hung YH, Robb EL, Volitakis I, Ho M, Evin G, Li QX, Culvenor JG, Masters CL,
Cherny RA, Bush AI (2009). Paradoxical condensation of copper with elevated beta-
amyloid in lipid rafts under cellular copper deficiency conditions: implications for
Alzheimer disease. J Biol Chem. 284(33), 21899-907.
[276] Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973).
Brain dopamine and the syndromes of Parkinson and Huntington. Clinical,
morphological and neurochemical correlations. J Neurol Sci. 20(4), 415-55.
[277] Jenner P, Olanow CW (1996) Oxidative stress and the pathogenesis of Parkinson’s
disease. Neurology 47, S161–170.
[278] Lev N, Melamed E (2001). Heredity in Parkinson's disease: new findings. Isr Med
Assoc J. 3(6), 435-8.
[279] Montgomery EB Jr (1995).Heavy metals and the etiology of Parkinson's disease and
other movement disorders. Toxicology, 97(1-3), 3-9.
[280] Olanow CW (1990). Oxidation reactions in Parkinson's disease. Neurology. 40(10
Suppl 3), suppl 32-7
[281] Lévay G., Ye Q and Bodell WJ (1997). Formation of DNA adducts and oxidative base
damage by copper mediated oxidation of dopamine and 6-hydroxydopamine . Exp.
Neurol. 146 (2), 570-574.
[282] Spina MB, Cohen G (1989). Dopamine turnover and glutathione oxidation:
implications for Parkinson disease. Proc Natl Acad Sci U S A. 86(4), 1398-400.
[283] Oreland L, Gottfries CG (1986). Brain and brain monoamine oxidase in aging and in
dementia of Alzheimer's type. Prog Neuropsychopharmacol Biol Psychiatry. 10(3-5),
533-40.
[284] Zatta P, Zambenedetti P, Milanese M (1999). Activation of monoamine oxidase type-B
by aluminum in rat brain homogenate. Neuroreport. 10(17), 3645-8.
[285] Lotharius J, Brundin P (2002). Pathogenesis of Parkinson's disease: dopamine, vesicles
and alpha-synuclein. Nat Rev Neurosci. 3(12), 932-42.
[286] Yuan H, Zheng JC, Liu P, Zhang SF, Xu JY, Bai LM (2007). Pathogenesis of
Parkinson's disease: oxidative stress, environmental impact factors and inflammatory
processes. Neurosci Bull. 23(2), 125-30.
[287] Gal S, Zheng H, Fridkin M, Youdim MB (2005). Novel multifunctional neuroprotective
iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases. In
vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced
striatal dopamine depletion. J Neurochem. 95(1), 79-8
[288] Graham DG (1978) Oxidative pathways for catecholamines in the genesis of
neuromelanin and cytotoxic quinones. Mol Pharmacol 14, 633– 643.
[289] Graham DG, Tiffany SM, Bell Jr WR, Gutknecht WF (1978) Autoxidation versus
covalent binding of quinones as a mechanism of toxicity of dopamine, 6-
hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro.
Mol Pharmacol 14, 644–653.
[290] Fornstedt B, Rosengren E, Carlsson A (1986) Occurrence and distribution of 5-S-
cysteinyl derivatives of dopamine, dopa and dopac in the brains of eight mammalian
species. Neuropharmacology 25, 451-454
[291] Hastings TG, Zigmond MJ (1994). Identification of catechol-protein conjugates in
neostriatal slices incubated with [3H]-dopamine: impact of ascorbic acid and
glutathione. J Neurochem 63, 1126-1132.
[292] Baez S, Linderson Y and Segura-Aguilar J (1995). Superoxide dismutase and catalase
enhance autoxidation during one-electron reduction of aminochrome by NADPH-
cytochrome P-450 reductase. Biochem. Mol. Med. 54 (1), 12-18.
[293] Baez S, Segura-Aguilar J, Widersten M, Johansson AS, Mannervik B (1997).
Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones)
of catecholamines and may serve as an antioxidant system preventing degenerative
cellular processes. Biochem J. 324 ( Pt 1), 25-8.
[294] Kang, JH (2004). Modification of Cu,Zn-superoxide dismutase by oxidized

catecholamines. J Biochem Mol Biol. 37(3), 325-9.
[295] Dedov VN, Griffiths FM, Garner B, Halliday GM, Double KL (2007). Lipid content
determines aggregation of neuromelanin granules in vitro. J Neural Transm Suppl. (72),
35-8.
[296] Gerlach M, Deckert J, Double K, and Koutsilieri E, eds (2007). Neuropsychiatric
Disorders An Integrative Approach. New York: SpringerWien.
[297] Gerlach M, Double KL, Ben-Shachar D, Zecca L, Youdim MB, Riederer P (2003).
Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic
neurodegeneration underlying Parkinson's disease. Neurotox Res. 5(1-2), 35-44.
[298] Odh G, Carstam R, Paulson J, Wittbjer A, Rosengren E, Rorsman H. Neuromelanin of
the human substantia nigra: a mixed-type melanin (1994). J Neurochem. 62(5), 2030-6.
[299] Zhang F, Dryhurst G (1994). Effects of L-cysteine on the oxidation chemistry of
dopamine: new reaction pathways of potential relevance to idiopathic Parkinson's
disease. J Med Chem. 37(8), 1084-98.
[300] Zecca L, Tampellini D, Gerlach M, Riederer P, Fariello RG, Sulzer D (2001).
Substantia nigra neuromelanin: structure, synthesis, and molecular behaviour. J Clin
Pathol: Mol Pathol. 54, 414–418
[301] Zecca L, Zucca FA, Costi P, Tampellini D, Gatti A, Gerlach M, Riederer P, Fariello
RG, Ito S, Gallorini M, Sulzer D (2003). The neuromelanin of human substantia nigra:
structure, synthesis and molecular behaviour. J Neural Transm Suppl. (65), 145-55.
[302] [303] Fasano M, Giraudo S, Coha S, Bergamasco B, Lopiano L (2003) Residual
substantia nigra neuromelanin in Parkinson’s disease is cross-linked to alpha-synuclein.
Neurochem Int. 42: 603–606
[303] Bridelli MG, Tampellini D, Zecca L (1999). The structure of neuromelanin and its iron
binding site studied by infrared spectroscopy. FEBS Lett. 20, 457(1):18-22.
[304] Zecca L, Pietra R, Goj C. Mecacci C, Radice D, and Sabbioni E. (1994). Iron and other
metals in neuromelanin, substantia nigra and putamen of human brain. J. Neurochem.
62, 1097–1101.
[305] Bolzoni F, Giraudo S, Bergamasco B, Lopiano L, Fasano M, Crippa PR (2002).
Magnetic investigations of human mesencephalic neuromelanin. Biochim. Biophys.
Acta, 1586, 210-218.
[306] Hirsch E, Graybiel A, Agid Y (1988) Melanized dopamine neurons are differentially
susceptible to degeneration in Parkinson’s disease. Nature, 28, 345–348.
[307] Kastner A, Hirsch EC, Lejeune O, Javoy-Agid F, Rascol O, Agid Y (1992) Is the
vulnerability of neurons in the substantia nigra of patients with Parkinson’s disease
related to their neuromelanin contents? J Neurochem 59: 1080–1089.
[308] Shamoto-Nagai M, Maruyama W, Yi H, Akao Y, Tribl F, Gerlach M, Osawa T,
Riederer P, Naoi M (2006). Neuromelanin induces oxidative stress in mitochondria
through release of iron: mechanism behind the inhibition of 26S proteasome. J Neural
Transm. 113(5), 633-44.
[309] Double KL, Gerlach M, Sch€unemann V, Trautwein AX, Zecca L, Gallorini M,
Youdim MBH, Riederer P, Ben-Shachar D (2003) Iron binding characteristics of
neuromelanin of the human substantia nigra. Biochem Pharmacol. 66: 489–494.
[310] Shima T, Sarna T, Swartz H, Stroppolo A, Gerbasi R, Zecca L (1997) Binding of iron
to neuromelanin of human substantia nigra and synthetic melanin: an electron
paramagnetic resonance spectroscopy study. Free Radic Biol Med. 23: 110–119.
[311] Gerlach M, Double KL, Ben-Shachar D, Zecca L, Youdim MB, Riederer P (2003).
Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic
neurodegeneration underlying Parkinson's disease Neurotox Res.;5(1-2):35-44.
[312] Double KL (2006). Functional effects of neuromelanin and synthetic melanin in model
systems. J Neural Transm 113, 751–756.
[313] Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K, Youdim MB
(1989). Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains.
J Neurochem. 52, 515–520
[314] Griffiths PD, Dobson BR, Jones GR and Clarke DT (1999).Iron in the basal ganglia
in Parkinson's disease.An in vitro study using extended X-ray absorption fine structure
and cryo-electron microscopy. Brain, 122(4), 667-673.
[315] Martin WR, Wieler M, Gee M (2008).Midbrain iron content in early Parkinson
disease.A potential biomarker of disease status. Neurology70 (16 Part 2), 1411-1417.
[316] Galazka-Friedman J (2008). Iron as a risk factor in neurological diseases. J Hyperfine
Interactions, 182 (1–3),31–44.
[317] Logroscino G, Gao X, Chen H, Wing A, Ascherio A (2008). Dietary iron intake and
risk of Parkinson's disease. Am J Epidemiol. 168(12), 1381-8.
[318] Vanacore N, Nappo A, Gentile M, Brustolin A, Palange S, Liberati A, Di Rezzel S,
Caldoral G, Gasparinil M, Benedetti F, Bonifatil V, Forastiere F, Quercia A, Mecol G
(2002). Neurol. Sci. 23 (Suppl. 2), S119–S120.
[319] Kamel F, Tanner C, Umbach D, Hoppin J, Alavanja M, Blair A, Comyns K, Goldman
S, Korell M, Langston J, Ross G, Sandler D (2007). Am J Epidemiol. 165(4), 364-74.
[320] Peng J, Peng L, Stevenson FF, Doctrow SR and Andersen JK (2007). Iron and paraquat
as synergistic environmental risk factors in sporadic Parkinson's disease accelerate age-
related neurodegeneration. J Neurosci. 27(26), 6914-6922.
[321] Lee HP, Zhu X, Liu G, Chen SG, Perry G, Smith MA and Lee HG (2010). Divalent
metal transporter, iron, and Parkinson's disease: A pathological relationship. Cell Res.
20, 397–399.
[322] Verstraeten SV, Aimo L, Oteiza PI (2008). Aluminium and lead: molecular
mechanisms of brain toxicity. Arch Toxicol. 82(11), 789-802.
[323] Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha-
Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and
dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA. 95, 6469–6473.
[324] Clayton DF and George JM (1998). The synucleins: a family of proteins involved in
synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci., 21, 249–
254.
[325] Fornai F, Lenzi P, Gesi M, Ferrucci M, Lazzeri G, Natale G, Ruggieri S, Paparelli A
(2003). Recent knowledge on molecular components of Lewy bodies discloses future
therapeutic strategies in Parkinson’s disease. Curr. Drug. Target. CNS. Neurol. Disord.
2, 149–152.
[326] Savitt JM, Dawson VL, Dawson TM (2006). Diagnosis and treatment of Parkinson
disease: molecules to medicine. J. Clin. Invest. 116, 1744–1754.
[327] Uversky VN, Li J, Fink AL (2001). Metal-triggered structural transformations,

aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK
between Parkinson's disease and heavy metal exposure. J Biol Chem. 276(47), 44284-
96.
[328] Lee JC, Gray HB and Winkler JR (2008). Copper(II) Binding to α-Synuclein, the
Parkinson’s Protein. J. Am. Chem. Soc. 130 (22), 6898–6899.
[329] Rasia RM, Bertoncini CW, Marsh D, Hoyer W, Cherny D, Zweckstetter M, Griesinger
C, Jovin TM, Fernández CO (2005). Structural characterization of copper(II) binding to
alpha-synuclein: Insights into the bioinorganic chemistry of Parkinson's disease. Proc
Natl Acad Sci U S A. 102(12), 4294-9.
[330] Drew SC, Leong SL, Pham CL, Tew DJ, Masters CL, Miles LA, Cappai R, Barnham
KJ (2008). Cu2+ binding modes of recombinant alpha-synuclein--insights from EPR
spectroscopy. J Am Chem Soc. 130(24), 7766-73.
[331] [332] Oikawa, S., Hirosawa, I., Tada-Oikawa, S., et al. (2006) Mechanism for
manganese enhancement of dopamine-induced oxidative DNA damage and neuronal
cell death. Free Radical Biology & Medicine, 41(5), 748-756.
[332] Sloot WN, Korf J, Koster JF, DeWit LEA, Gramsbergen JBP (1996). Manganese-
induced hydroxyl radical formation in rat striatum is not attenuated by dopamine
depletion or iron chelation in vivo. Exp. Neurol. 138, 236–245.
[333] Lloyd RV (1995). Mechanism of the manganese-catalyzed autoxidation of dopamine.
Chem. Res. Toxicol. 8, 111–116.
[334] Afeseh Ngwa H, Kanthasamy A, Anantharam V, Song C, Witte T, Houk R,
Kanthasamy AG (2009). Vanadium induces dopaminergic neurotoxicity via protein
kinase Cdelta dependent oxidative signaling mechanisms: relevance to etiopathogenesis
of Parkinson's disease. Toxicol Appl Pharmacol. 240(2), 273-85.
[335] Zhao Y, Ye L, Liu H, Xia Q, Zhang Y, Yang X, Wang K (2010). Vanadium compounds
induced mitochondria permeability transition pore (PTP) opening related to oxidative
stress. J Inorg Biochem. 104(4), 371-8.
Chapter 2
NONLINEAR OPTICAL PROPERTIES OF TRANSITION

METAL NANOPARTICLES SYNTHESIZED BY
ION IMPLANTATION
Andrey L. Stepanov*
Laser Zentrum Hannover, Hannover, Germany
Kazan Federal University, Kazan, Russian Federation
Kazan Physical-Technical Institute, Russian Academy of Sciences,
Kazan, Russian Federation
ABSTRACT
Composite materials containing metal nanoparticles (MNPs) are now considered as a
basis for designing new photonic media for optoelectronics and nonlinear optics.
Simultaneously with the search for and development of modern technologies intended for
nanoparticle synthesis, substantial practical attention has been devoted to designing
techniques for controlling the MNP size. One of the promising methods for fabrication of
MNPs is ion implantation. Review of recent results on ion-synthesis and nonlinear optical
properties of cupper, silver and gold nanoparticles in surface area of various dielectrics as
glasses and crystals are presented. Composites prepared by the low energy ion
implantation are characterized with the growth of MNPs in thin layer of irradiated
substrate surface. Fabricated structures lead to specific optical nonlinear properties for
picosecond laser pulses in wide spectral area from UV to IR such as nonlinear refraction,
saturable and two-photon absorption, optical limiting. The practical recommendations for
fabrication of composites with implanted MNPs for optical components are presented.
1. INTRODUCTION
The search for new nanostructured materials is one of the defining characteristics of
modern science and technology [1-6]. Novel mechanical, electrical, magnetic, chemical,
*E-mail: aanstep@gmail.com
64 Andrey L. Stepanov
biological, and optical devices are often the result of the fabrication of new nanostructured
materials. The specific interest of this review is recent advantages in optical science and
technology, such as development of nonlinear optical random metal-dielectric and metal-
semiconductor composites based on metal nanoparticles (MNP) synthesized by ion
implantation. Simultaneously with the search for and development of novel technologies
intended for nanoparticle synthesis, substantial practical attention has been devoted to
designing techniques for controlling the MNP size. This is caused by the fact that the optical
properties of MNPs, which are required for various applications, take place up to a certain
MNP dimension. In this content, ion implantation nanotechnology allows one to fabricate
materials with almost any MNP structures, types of metals and their alloys [7-9]; this opens
new avenues in engineering nanomaterials with desired properties. Such composites possess
fascinating electromagnetic properties, which differ greatly from those of ordinary bulk
materials, and they are likely to become ever more important with a miniaturization of
electronic and optoelectronic components.
Nonlinear optics plays a key role in the implementation and development of many
photonics techniques for the optical signal processing of information at enhanced speed. The
fabrication of novel useful nonlinear optical materials with ultrafast time response, high
resistance to bulk and surface laser damage, low two-photon absorption and, of course, large
optical nonlinearities is a critical for implementation of those applications. In additional,
nonlinear materials for optical switching should be manufactured by processes compatible
with microelectronics technology. Nonlinear materials with such characteristics are
interesting for waveguide applications. The earliest studies of optical analogs to
electronicintegrated circuits – or integrated optics – were based on the recognition that
waveguide geometries allowed the most efficient interaction of light with materials.
Optoelectronic devices could be converted to all-optical configurations, with a number of
technological advantages, by developing waveguide media with intensity-dependent
refractive indices. Nonlinear optical switches must provide conversion of laser signal for
pulse duration as short as from nano- to femtoseconds. The nonlinear properties of MNP-
containing materials stem from the dependence of their refractive index and nonlinear
absorption on incident light intensity. Giant enhancement of nonlinear optical response in a
random media with MNPs is often associated with optical excitation of surface plasmon
resonances (SPR) that are collective electromagnetic modes and they are strongly dependent
on the geometry structure of the composite medium [4]. Therefore, MNP-containing
transparent dielectric and semiconductor materials can be effectively applied in novel
integrated optoelectronic devices.
Although both classic and quantum-mechanical effects in the linear optical response of
MNP composites have been studied for decades [4], the first experimental results on the
nonlinear optical effects of MNPs in ruby-glass was obtained quite recently in 1985 by
Ricard et al. [10]. Driven by the interest in creating nonlinear optical elements with MNPs for
applications in all-optical switching and computing devices, variety of experimental and
theoretical efforts have been directed at the preparation of composite materials. In practice, to
reach the strong linear absorption of a composite in the SPR spectra region, attempts are made
to increase the concentration (filling factor) of MNPs. Systems with a higher filling factor
offer a higher nonlinear susceptibility, when all other parameters of composites being the
same.
Nonlinear Optical Properties of Transition Metal Nanoparticles … 65
MNPs hold great technological promise because of the possibility of engineering their
electronic and optical properties through material design. The transition metals of choice are
usually gold, silver, or copper, as these metals show SPR modes in the visible or near-infrared
spectral range [4]. The advantages of devices based on MNP materials can be understood
from the spectacular successes of quantum well materials [11, 12]. The capability of band gap
engineering in these structures permits wavelength tuning, while their small size alters the
electronic structure of these particles. This provides greater pumping efficiency for
applications in optical limiting and switching. The potential advantages of MNP composites
as photonic materials are substantial improvement in the signal switching speed. Up to 100
GHz repetition frequencies are expected in communication and computingsystems of the 21th
century [11]. Figure 1 compares in graphical form the switching speed and switching energies
of various electronic, optical materials and devices (adapted from [11, 13]). Within the broad
range of parameters covered by “conventional semiconductor microelectronics”, current
metal-oxide-semiconductor field-effect transistor devices made in silicon have low switching
energies, but switching time in the nanosecond range. Photonic devices based on multiple
quantum well (MQW) structures – SEED and GaAs MQW devices and Fabry-Perot (FP)
cavities based on ferroelectric such as lithium niobate – have extremely low switching speed
in comparison to MNPs [11, 12].
Figure 1. Plot of various photonic materials showing their switching energies and switching speed.
Adapted from [11, 13].
Davenas et al.pioneered synthesis of MNPs in dielectrics by ion implantation in 1973

[14, 15], when nanoparticles of various metals (sodium, calcium, etc.) in ionic crystals of LiF
and MgO were created. Late in 1975, noble metal nanoparticles such as Au and Ag were
fabricated in silicate glasses by Arnold and Borders [16, 17]. As shown in reviews [7-9, 18-
23], now developments expanded from the metal implants to the use of compounds, including
metal alloys and totally different composition precipitate inclusions. Implanted MNP were
fabricated in various materials, as polymers, glass, artificial crystals, and minerals.
Number of publications on nonlinear optical properties of MNPs fabricated in transparent
dielectric and semiconductor matrix is increasing every year. There arereview articles
observed partly this progress [11, 18, 19, 24, 25]. Unfortunately, some of this reviews are
already quite old and do not reflect a modern knowledge of the field or restricted to numbers
of selected publications only. However, as followed from a comprehensive list of publications
presented in Table 1 by 2011 [26-118], the geography of interest to nonlinear properties of
ion-synthesized MNPs covers all world continents. The data in Table 1 includes information
on all known types of metal ions and transparent matrices, ion implantation conditions for
fabrication of MNPs and for measurements of their optical properties. Nonlinear optical
characteristics of composites such as nonlinear refraction (n2) and absorption (β) coefficients,
real (Re[χ(3)]) and imaging (Im[χ(3)])parts of third order nonlinear susceptibilities (χ(3)) and
saturation intensities (Isat) are presented as well. As shown in Table 1, near one hundred
articles were already published. It should be mention, that ion implantation technique was
first used for ion-synthesis of MNPs in dielectrics to create nonlinear optical materials in
1991 to form copper and gold nanoparticles in silica glass [42, 100]. The present review
focuses on advantages in nonlinear optical properties of MNPs fabricated generally by low-
energy ion implantation and measured in wide spectral area from ultraviolet to infrared.
2. OPTICS OF METAL NANOPARTICLE COMPOSITES

The nonlinear optical response of medium with MNPs can be described by expanding the
i-th component of the polarization P induced by an applied optical field to third order in a
power series in this electric field E = E0elex [11, 12]
Pi = ∑ χ y(1) E j +∑ χ yk(2) E j Ek +∑ χ yki

(3)
E j Ek Ei +W, (1)
j jk jki
where the summation indices refer to Cartesian conditions in the material-dependent χ(q) and
to the polarization of the applied optical field.
The first-order susceptibility χ(1) is related to the linear refractive index n0 and the linear
(Lambert-Beer’s law) absorption coefficient α0 through the following equation [13]
ω
n0 = Re ⎡⎣1+ χ (1) ⎤⎦ and α 0 = Im ⎡⎣ χ (1) ⎤⎦, (2)
n0 c
where c – speed of the light, ω - the optical frequency. The value χ(3) of a centrosymmetric
composite has an analogous relationship to the nonlinear coefficients n2 and β[45]
12π ⎡ (1) ⎤ 96π 2ω ⎡ (1) ⎤

n2 = Re⎣1+ χ ⎦ and β = 2 2 Im ⎣ χ ⎦ . (3)
n0 n0 c
Table 1. Types optically transparent dielectric and semiconductor matrixes with metal nanoparticles synthesized by ion implantation.
Abbreviations: soda-lime silicate glass (SLSG), indium-tin oxide (ITO), degenerate four wave mixing (DFWM), pump-probe transient
nonlinear spectroscopy (PPTNS), Z-scan and RZ-scan by reflection and vectorial self-diffraction (VSD)
Synthesis conditions: Study Laser parameters: Nonlinear parameters: Authors

Metal Matrix Energy (E), keV nonlinear Wavelength (λ), nm Refract. coef. (n2), cm2/W
(Ion) Dose (D), ion/cm2, optical Pulse duration (τ), ps Absorption coef. (β),
Current density (J), method Repetition rate (ν), cm/W
μA/cm2 Hz Satur. intensity (Isat),
Annealing temper. Intensity (I0), W/cm2 W/cm2
(T), °C and time Pulse energy (P), mJ Re[χ(3)], Im[χ(3)], |χ(3)|, esu
E = 50 λ = 770 n2 = 1.8⋅10-9 Cattaruzza et al. 1998
Co SiO2 D = 4⋅1016 Z-scan τ = 0.13 [26]
J=2 ν = 76⋅109
I0 = 11.4⋅109
E = 100 λ = 770 n2 = 1.7⋅10-10 Falconieri et al. 1998
Ni SiO2 D = 6⋅1016 Z-scan τ = 0.13 [27]
ν = 76⋅109 Cattaruzza et al. 2002
I0 = 9.8⋅109 [28]
E = 40 λ = 1064 n2 = -(1.3 – 1.7)⋅10-11 Ganeev et al. 2005 [29]
Cu Al2O3 D = (0.5 – 1.0)⋅1017 RZ-scan τ = 55 Re[χ(3)] = -(1.0 – 1.4)⋅10-9 2006 [30]
J = 2.5 – 12.5 ν=2 Ryasnyanskiy et al. 2005
I0 = 7.7⋅109 [31]
Table 1. (Continued)

(Ion) Dose (D), ion/cm2, optical Pulse duration (τ), ps Absorption coef. (β), cm/W
Current density (J), method Repetition rate (ν), Satur. intensity (Isat),
μA/cm2 Hz W/cm2
Annealing temper. Intensity (I0), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|,
(T), °C and time Pulse energy (P), mJ esu
E = 60 λ = 500 - 700 β500-580 < 0 Plaksin et al. 2008
Cu Al2O3 Z-scan τ = 0.2 β580-700 > 0 [32]
ν = 103
I0 = 1.1⋅107
E = 40 λ = 532 n2 = (5.2 – 8.3)⋅10-8 Ryasnyanskiy et al.
Cu ITO D = (0.5 – 7.5)⋅1016 Z-scan τ = 7.0⋅103 Re[χ(3)] = (5.4 – 7.4)⋅10-6 2006 [33]
J=4 ν = 10 β = -(3.5 – 3.6)⋅10-3
I0 = (6.2 - 15.5)⋅109 Im[χ(3)] = -(1.2 – 1.3)⋅10-6
|χ(3)| = (5.5 – 7.5)⋅10-6
E = 60 λ = 574 Bleaching absorption in 590 - Takeda et al. 2002
Cu LiNbO3 D = (0.3 – 2.0)⋅1017 PPTNS τ = 0.2 620 nm [34-36]
J = 10 ν = 103 Kishimoto et al.
P = 16 2003 [37]
Plaksin et al. 2005
[38]
2006 [39]
E = 60 λ = 532 |χ(3)| = (1.0 – 3.0)⋅10-8 Kishimoto et al.
Cu MgAl2O4 D = 3.0⋅1016 DFWM 2000 [40]
J = 10
μA/cm2 Hz W/cm2
Cu MgO2⋅Al2O4 D = 3.0⋅1016 PPTNS τ = 0.2 620 nm [34-36]
J = 1-100 ν = 103 2001 [41]
P = 16
E = 160 λ = 532 n2 = 2.0⋅10-15 Becker et al. 1991
Cu SiO2 D = 6.0⋅1016 Z-scan τ = 100 [42]
J = 2 – 7.5 ν = 76⋅109 Haglund et al. 1992
I0 = 5.0⋅106 [43]
E = 160 λ = 570 - 600 n2 = (2.0 – 4.2)⋅10-10 Haglund et al. 1993

Cu SiO2 D = 1.2⋅1017 Z-scan τ=6 Re[χ(3)] = 2.4⋅10-8 [44]
J = 2.5 I0 = 5.0⋅108 β = -(0.1 – 1.0)⋅10-6 1994 [45]
1998 [46]
Magruder et al. 1994
[47]
Yang et al. 1994 [48]

μA/cm2 Hz W/cm2
E = 160 λ = 532 n2 = 2.0⋅10-7 Haglund et al. 1994
Cu SiO2 D = 1.2⋅1017 DFWM τ = 10 and 35 |χ(3)| = (2.4 – 7.3)⋅10-8 [45]
J = 0.7 – 7.5 1998 [46]
1995 [42]
Yang et al. 1994 [48]
1996 [49]
[ E = 160 λ = 532 n2 = (2.0 – 4.2)⋅10-14 Magruder et al.
Cu SiO2 D = 1.2⋅1017 Z-scan τ = 100 Re[χ(3)] = 2.4⋅10-8 1994 [47]
J = 2.5 ν = 76⋅109 β = -(3.0 – - 8.0)⋅10-3
I0 = 1.0⋅107
E = 90 λ = 770 n2 = 5.0⋅10-11 Falconieri et al.
Cu SiO2 D = 6⋅1016 Z-scan τ = 0.13 1998 [27]
ν = 76⋅109 Cattaruzza et al.
I0 = 9.8⋅109 2002 [28]
E = 2.0⋅103 λ = 532 and 555 - 600 n2 = (4.0 – 6.8)⋅10-19 Ila et al. 1998 [50]
Cu SiO2 D = (1.0 – 4.0)⋅1017 Z-scan τ = 4.5 |χ(3)| = (0.3 – 4.7)⋅10-7 Sarkisov et al.
J = 2.0 ν = 76⋅109 1998 [51]
T = 1000, 1 h I0 = 8.8⋅109
μA/cm2 Hz W/cm2
E = 60 λ = 532 and 561 |χ(3)| = (0.2 – 2.2)⋅10-8 Takeda et al. 1999
Cu SiO2 D = 3.0⋅1016 DFWM τ = 7.0⋅103 [52]
J = 1-100 I0 = (0.1 – 1.0)⋅106 2000 [53]
E = 50 λ = 585 |χ(3)| = 1.0⋅10-7 Olivares et al. 2001

Cu SiO2 D = 8.0⋅1016 DFWM τ = 13 [54]
J = 10 ν = 400
I0 = 1.0⋅108

Cu SiO2 D = 3.0⋅1016 PPTNS τ = 0.2 620 nm [34-36, 55]
J = 1-30 ν = 103 2001 [41]
T = 800, 1 h I0 = 8.0⋅1011 2004 [56, 57]
E = 50 λ = 354.7 n2 = -0.6⋅10-7 Ganeev et al. 2003

Cu SiO2 D = 8.0⋅1016 Z-scan τ = 55 Re[χ(3)] = -1.3⋅10-8 [58]
J = 10 ν=2 β = -6.7⋅10-6 2004 [59]
I0 = 4.1⋅109 Im[χ(3)] = -2.9⋅10-9
|χ(3)| = 1.4⋅10-8

μA/cm2 Hz W/cm2
E = 50 λ = 532 β = -6.0⋅10-6 Ganeev et al. 2003
Cu SiO2 D = 8.0⋅1016 Z-scan τ = 55 Isat = 4.3⋅108 [60]
J = 10 ν=2 2004 [61]
I0 = 5.4⋅109
E = 50 λ = 1064 n2 = -1.4⋅10-7 Ganeev et al. 2003

Cu SiO2 D = 8.0⋅1016 Z-scan τ = 35 Re[χ(3)] = -3.2⋅10-8 [62, 63]
J = 10 ν=2 β = -9.0⋅10-6 2004 [64]
I0 = 1.0⋅1010 Im[χ(3)] = 6.5⋅10-9 Stepanov et al.
|χ(3)| = 3.3⋅10-8 2003 [65]
E = 60 λ = 540 - 610 Re[χ(3)] = -3.1⋅10-9 Takeda et al. 2005

Cu SiO2 D = 1.0⋅1017 Z-scan τ = 0.2 Im[χ(3)] = 1.7⋅10-9 [66]
J = 10 ν=1 |χ(3)| = -(-1.6 - 3.1)⋅10-8 Plaksin et al. 2008
T = 800, 1 h I0 = 8.0⋅1011 [32]
μA/cm2 Hz W/cm2
E = 180 λ = 790 - 800 n2 = -1.6⋅10-10 Ren et al. 2006
Cu SiO2 D = (0.5 - 2.0)⋅1017 Z-scan τ = 0.15 Re[χ(3)] = (0.9 – 1.4)⋅10-7 [67]
J = 1.5 ν = 76⋅109 β = -(1.6 - 9.0)⋅10-6 Wang et al. 2006
T = 500 - 900, 1 h I0 = (8.0 – 14.5)⋅109 Im[χ(3)] = (0.8 – 1.7)⋅10-7 [68, 69]
|χ(3)| = (1.2 - 2.3)⋅10-7
E = 100 -200 λ = 533 n2 = -3.7⋅10-15 Ghosh et al. 2007

Cu SiO2 D = 3.0⋅1016 Z-scan τ = 7⋅103 Re[χ(3)] = 3.7⋅10-12 [70]
T = 300 - 400, 1 h ν = 0.1 β = (2.8 - 6.4)⋅10-9 2009 [71]
I0 = 0.9⋅109 Im[χ(3)] = 3.7⋅10-14
|χ(3)| = 3.7⋅10-12
Isat = (2.9 – 5.0)⋅107
E = 2.0⋅103 λ = 533 n2 = -1.1⋅10-12 Torres-Torres et al.
Cu SiO2 D = 4.0⋅1016 VSD τ = 26 β = -2.0⋅10-11 2008 [72]
T = 900, 1 h P = 16 |χ(3)| = 8.4⋅10-11
E = 2.0⋅103 λ = 533 n2 = -1.2⋅10-11 Torres-Torres et al.

Cu SiO2 D = 4.0⋅1016 VSD τ = 7⋅103 β = -2.0⋅10-12 2008 [72]
T = 900, 1 h P = 16 |χ(3)| = 8.8⋅10-10

μA/cm2 Hz W/cm2
E = 180 λ = 532 n2 = -(1.3 – 0.6)⋅10-10 Wang et al. 2009
Cu SiO2 D = (0.5 – 1.0)⋅1017 Z-scan τ = 38 β = -(458- 151)⋅10-9 [73]
J = 1.5 ν = 10 |χ(3)| = (2.1 - 0.8)⋅10-7 Wang et al. 2010
I0 = 0.9⋅109 [74]
E = 180 λ = 1064 n2 = -(1.1 – 0.6)⋅10-10 Wang et al. 2009

Cu SiO2 D = (0.5 – 1.0)⋅1017 Z-scan τ = 38 |χ(3)| = (1.2 - 0.8)⋅10-7 [73]
J = 1.5 ν = 10 Wang et al. 2010
I0 = 0.38⋅109 [74, 75]
E = 50 λ = 1064 n2 = 3.6⋅10-8 Ganeev et al. 2003

Cu SLSG D = 8.0⋅1016 Z-scan τ = 35 Re[χ(3)] = 0.8⋅10-8 [62, 63]
J = 10 ν=2 β = -3.4⋅10-6 2004 [64]
I0 = 3.0⋅1010 Im[χ(3)] = 2.5⋅10-9 Stepanov et al.
|χ(3)| = 0.9⋅10-8 2003 [65]
μA/cm2 Hz W/cm2
Cu SrTiO3 D = 3.0⋅1016 PPTNS τ = 0.2 690 nm and positive [35, 55]
J = 10 ν = 103 absorption in 516 - 506 nm 2004 [76]
E = 60 λ = 540 - 610 Re[χ(3)] = -(0.1 – 2.0)⋅10-9 Takeda et al. 2006

Cu SrTiO3 D = 3.0⋅1016 Z-scan τ = 0.2 Im[χ(3)] = -(0.2 – 1.2)⋅10-9 [77]
J = 10 ν=1 |χ(3)| = (1.0 - 2.0)⋅10-9
T = 300, 1 h I0 = 6.0⋅1011
D = (0.1 - 1.0)⋅10 17
λ = 775 n2 = (1.8 – 6.2)⋅10-12 Cetin et al. 2010
Cu SrTiO3 DFWM τ = 0.25 |χ(3)| = (1.6 - 5.33)⋅10-10 [77]
Z-scan ν=1
Cu TiO2 D = 3.0⋅1016 PPTNS τ = 0.2 760 nm [35]
J = 10 ν = 103
E = 160 λ = 532 β = -(0.4 – 2.1)⋅10-3 Stepanov et al.
Cu ZnO D = (0.1 - 1.0)⋅1017 Z-scan τ = 55 2004 [79]
J = 20 ν=2 Ryasnyansky et al.
I0 = 5.0⋅108 2005 [80]

μA/cm2 Hz W/cm2
E = 160 λ = 532 β = -(0.7 – 5.5)⋅10-3 Ryasnyansky et al.
Cu ZnO D = (0.1 - 1.0)⋅1017 Z-scan τ = 7.5⋅103 2005 [80]
J = 20 ν = 10
I0 = 3.2⋅107
E = 30 λ = 1064 n2 = (1.1 – 1.8)⋅10-11 Ganeev et al. 2005
Ag Al2O3 D = 3.8⋅1017 RZ-scan τ = 55 Re[χ(3)] = (0.9 – 1.5)⋅10-9 [29]
J = 3 – 10 ν=2 2006 [30]
I0 = 4.3⋅109 Ryasnyanskiy et al.
2005 [81]
E = 1.5⋅103 λ = 555 - 600 n2 = (0.8 – 1.3)⋅10-8 Sarkisov et al.

Ag LiNbO3 D = 2.0⋅1016 Z-scan τ = 4.5 1998 [51]
T = 500, 1 h ν = 76⋅106
I0 = 8.8⋅107
E = 1.5⋅103 λ = 532 n2 = 5.0⋅10-10 Williams et al.
Ag LiNbO3 D = 2.0⋅1016 Z-scan τ = 40 - 70 1999 [82]
T = 500, 1 h ν = 10 Sarkisov et al.
I0 = 1.0⋅1010 2000 [83]
μA/cm2 Hz W/cm2
E = 1.5⋅103 λ = 532 |χ(3)| = 5.0⋅10-7 Ila et al. 1998 [50]
Ag SiO2 D = 4.0⋅1016 Z-scan τ = 4.5
J=2 ν = 76⋅106
T = 500, 1 h
E = 60 λ = 354.7 n2 = -2.7⋅10-7 Ganeev et al. 2003
Ag SiO2 D = 4.0⋅1016 Z-scan τ = 55 Re[χ(3)] = -6.0⋅10-8 [58]
J = 10 ν=2 β = -1.4⋅10-5 2004 [63]
I0 = 1.3⋅109 Im[χ(3)] = -6.1⋅10-9
|χ(3)| = 6.1⋅10-8
E = 60 λ = 532 n2 = -(6.2 - -0.7)⋅10-10 Ganeev et al. 2004

Ag SiO2 D = 4.0⋅1016 Z-scan τ = 55 Re[χ(3)] = -(3.5 - -0.4)⋅10-8 [84]
J = 10 ν=2 β = -(3.6 - -0.5)⋅10-5 Stepanov et al.
I0 = (2.5 – 14)⋅109 Im[χ(3)] = -(1.3 - -0.2)⋅10-8 2010 [85]
E = 60 λ = 1064 n2 = 1.5⋅10-8 Ganeev et al. 2003
Ag SiO2 D = 4.0⋅1016 Z-scan τ = 35 Re[χ(3)] = 2.5⋅10-9 [62]
J = 10 ν=2 2004 [63]
I0 = 1.0⋅1010
E = (1.7 – 2.4)⋅103 λ = 532 Three-photon absorption Joseph et al. 2007
Ag SiO2 D = (4.0 – 7.0)⋅1016 Z-scan τ = 7.0⋅103 [86]
J = 0.3 P = 0.14
T = 500, 1 h

μA/cm2 Hz W/cm2
E = 2.0⋅103 λ = 527 β = -(2.6 - 1.8)⋅10-6 Rangel-Rojo et al.
Ag SiO2 D = 7.0⋅1016 Z-scan τ = 0.233 Im[χ(3)] = 4.7⋅10-10 2009 [87]
T = 600, 1 h ν = ⋅103 Isat = (1.2 – 3.5)⋅107 2010 [88]
E = 200 λ = 532 n2 = -3.0⋅10-11 Wang et al. 2009
J = 2.5 ν = 10 β = -7.0⋅10-8
Im[χ(3)] = 2.6⋅10-8
|χ(3)| = 4.0⋅10-8
E = 200 λ = 1064 n2 = -1.7⋅10-10 Wang et al. 2009
J = 2.5 ν = 10 |χ(3)| = 1.8⋅10-7
E = 60 λ = 532 n2 = -(4.1 - -1.7)⋅10-10 Ganeev et al. 2004

Ag SLSG D = 4.0⋅1016 Z-scan τ = 55 Re[χ(3)] = -(2.4 - -1.4)⋅10-8 [84]
J = 10 ν=2 β = -(6.7 - -1.7)⋅10-5
I0 = (2.5 – 14)⋅109 Im[χ(3)] = -(0.6 - 2.4)⋅10-8
E = 60 λ = 1064 n2 = 3.5⋅10-8 Ganeev et al. 2003
J = 10 ν=2 2004 [64]
I0 = 3.0⋅1010
Current density (J), method Repetition rate (ν), Hz Satur. intensity (Isat),
μA/cm2 Intensity (I0), W/cm2 W/cm2
Annealing temper. Pulse energy (P), mJ Re[χ(3)], Im[χ(3)], |χ(3)|,
(T), °C and time esu
E = 400 λ = 460-540 |χ(3)| = 3.0⋅10-6 Takeda et al. 1993
Sn SiO2 D = 2.0⋅1017 DFWM τ = 5⋅103 [90]
J=1 I0 = 3.0⋅1010 1994 [91]
E = 350 λ = 460-540 |χ(3)| = 1.5⋅10-6 Ila et al. 1998 [50]
Sn SiO2 D = 8.0⋅1017 Z-scan τ = 4.5
J=2 ν = 76⋅106
T = 200, 0.5 - 1 h
Ta SiO2 D = 3.0⋅1016 PPTNS τ = 0.2 605 nm [92]
J = 0.3 ν = 103
T = 900, 1 h
E = (2.75 – 3.0)⋅103 λ = 532 |χ(3)| = 7.0⋅10-9 White et al. 1993
Au Al2O3 D = 2.2⋅1016 DFWM τ = 35 – 40 [93]
T = 1100, 1 h ν = 10
I0 = 1.0⋅109
E = 160 λ = 1064 n2 = -(0.1 – 1.5)⋅10-10 Ganeev et al. 2005

Au Al2O3 D = (0.6 – 1.0)⋅1017 RZ-scan τ = 55 Re[χ(3)] = -(0.8 – 1.2)⋅10-8 [29]
J = 10 ν=2 2006 [30]
T = 800 - 1100, 1 h I0 = (1.8 - 2.3)⋅109 Stepanov et al.
2005 [94]
2006 [95]

μA/cm2 Hz W/cm2
E = 60 λ = 568 Nonlinear dielectric Takeda et al. 2006
Au Al2O3 D = 2.0⋅1017 PPTNS τ = 0.2 functions [96]
J = 10 ν = 103 2007 [97]
E = 2.75⋅103 λ = 532 n2 = (1.0 - 8.9)⋅10-10 Haglund et al.

Au SiO2 D = (0.3 – 1.5)⋅1017 DFWM τ = 6 and 35 β = (3.7 - 4.8)⋅10-5 1994 [45]
T = 600 - 1100, 2.2 h Z-scan ν = 3.8 and 10 |χ(3)| = (1.0 – 1.7)⋅10-10 Yang et al. 1996
I0 = 4.5⋅108 [49]
Magruder et al.
1993 [98]
White et al. 1994
[99]
E = 1.5⋅103 λ = 532 |χ(3)| = (0.12 – 5.0)⋅10-8 Fukumi et al. 1991
Au SiO2 D = 5.6⋅1016 DFWM τ = 5⋅103 [100]
J = 0.7 I0 = 1.0⋅109 1994 [101]
T = 700 - 1200
E = 3.0⋅103 λ = 532 |χ(3)| = 6.5⋅10-7 Ila et al. 1998 [50]
Au SiO2 D = 1.2⋅1017 Z-scan τ = 4.5
J = 2.0 ν = 76⋅106
T = 1200, 0.5-1 h
μA/cm2 Hz W/cm2
E = 2.75⋅103 λ = 532 |χ(3)| = (0.3 – 1.3)⋅10-7 Lepeshkin et al.
Au SiO2 D = 1.5⋅1017 DFWM τ = 4⋅103 1999 [102]
T = 400 I0 = 1.9⋅106 Safonov et al. 1999
[103]
E = 60 λ = 554 and 568 Nonlinear dielectric Takeda et al. 2006

Au SiO2 D = (1.0 – 2.0)⋅1017 PPTNS τ = 0.2 functions, positive absorption [96]
J = 10 -17 ν = 103 in 500 – 650 nm 2007 [104]
I0 = (0.7 – 0.9)⋅109
E = 2.0⋅103
λ = 532 n2 = -2.0⋅10-8 Torrres-Torres et
Au SiO2 D = 2.8⋅1016 VSD τ = 7⋅103 Re[χ(3)] = 1.9⋅10-9 al. 2007 [105]
T = 1100, 1 h P = 0.14 β = -5.0⋅10-6
Im[χ(3)] = -1.6⋅10-9
|χ(3)| = 2.2⋅10-9
E = 1.5⋅103 λ = 532 n2 = -1.5⋅10-11 Ghosh et al. 2008
Au SiO2 D = (0.3 - 1.0)⋅1017 Z-scan τ = 7⋅103 Re[χ(3)] = 1.5⋅10-8 [71]
T = 400, 1 h ν = 0.1 β = -(2.6 - 8.0)⋅10-8 2009 [106]
I0 = 1.2⋅1010 Im[χ(3)] = -1.5⋅10-10
|χ(3)| = 1.5⋅10-8
Isat = (1.9 – 2.6)⋅107

μA/cm2 Hz W/cm2
E = 250 - 300 λ = 532 n2 = -(1.2 – 1.4)⋅10-10 Wang et al. 2008
Au SiO2 D = 1.0⋅1017 Z-scan τ = 38 Re[χ(3)] = -1.2⋅10-7 [107, 108]
J = 2.5 ν = 10 β = -(9.7 - 21.0)⋅10-10
I0 = 0.9⋅109 Im[χ(3)] = -3.6⋅10-8
|χ(3)| = (1.3 – 1.6)⋅10-7
E = 250 - 300 λ = 1064 n2 = -0.4⋅10-10 Wang et al. 2008
Au SiO2 D = 1.0⋅1017 Z-scan τ = 38 Re[χ(3)] = -(4.3 - -1.2)⋅10-8 [107, 108]
J = 2.5 ν = 10 |χ(3)| = (0.1 – 4.3)⋅10-8
I0 = 3.8⋅108
E = 90 and 100 λ = 770 |χ(3)| = 6.8⋅10-10 Falconieri et al.
Cu-Ni SiO2 D = 6⋅1016 and 6⋅1016 Z-scan τ = 0.13 1998 [27]
ν = 76⋅109 Cattaruzza et al.
I0 = 9.8⋅109 2002 [28]
E = 90 and 100 λ = 532 n2 = 1.5⋅10-10 Cattaruzza et al.
Cu-Ni SiO2 D = 6⋅1016 and 6⋅1016 Z-scan τ=6 |χ(3)| = 5.0⋅10-12 2002 [28]
ν = 0.5 - 1 Battaglin et al.
I0 = 2.0⋅109 2000 [109]
μA/cm2 Hz W/cm2
E = 160 and 305 λ = 570 n2 = (0.1 - 1.6)⋅10-9 Magruder et al.
Cu-Ag SiO2 D = 1.2⋅1016 Z-scan τ=6 β = -(1.4 - -3.8)⋅10-5 1994 [110]
J = 1.3 - 3 ν = 3.8⋅106
I0 = 4.0⋅108
E = 30 and 43 λ = 790 n2 = -(3.8 - 4.3)⋅10-12 Wang et al. 2007
Cu-Ag SiO2 D = (1.0 – 2.0)⋅1017 Z-scan τ = 0.15 β = (1.0 - 2.2)⋅10-6 [111]
ν = 76⋅109 |χ(3)| = (0.8 – 1.5)⋅10-8
I0 = 8.8⋅109
E = 180 and 200 λ = 1064 n2 = (0.6 - 3.0)⋅10-10 Wang et al. 2008
Cu-Ag SiO2 D = (1.0 – 2.0)⋅1017 Z-scan τ = 38 |χ(3)| = (0.6 – 2.1)⋅10-7 [112]
J = 1.5 – 2.5 ν = 10 2010 [113, 114]
E = 130 and 190 λ = 572 n2 = -1.6⋅10-10 Cattaruzza et al.
Ag-Au SiO2 D = 9.0⋅1016 Z-scan τ=5 β = 1.3⋅10-5 2003 [115]
J=2 ν=1 |χ(3)| = (0.9 – 1.7)⋅10-8 2005 [116]
T = 800, 1 h I0 = (1.6 -5.0)⋅109

μA/cm2 Hz W/cm2
E = 130 and 190 λ = 525 β = -(3.42 - -1.7)⋅10-4 Cesca et al. 2010
Ag-Au SiO2 D = 3.0⋅1016 Z-scan τ=6 Isat = (0.1 – 3.2)⋅108 [117]
T = 800, 1 h ν=1
I0 = 0.8⋅109
E = 320 and 1.1⋅103 λ = 532 n2 = (0.6 - 1.2)⋅10-9 Magruder et al.
Ti-Au SiO2 D = (0.6 - 2.0)⋅1016 Z-scan τ=6 β = 5.3⋅10-6 1995 [118]
T = 900, 2 h ν = 3.8⋅106
I0 = 4.0⋅108
For comparison some data for ion synthesized nontraditional MNPs are also presented.
The susceptibility χ(3) is a fourth-rank tensor with eighty-one components; however,

material symmetries often reduce the number of non-vanishing components substantially.
For a MNP with a dielectric constant ε(ω) = ε1(ω)+iε2(ω) occupying a relative volume
fraction (filling factor) p << 1in a host of dielectric constant εh, the absorption can be
presented as [45, 119]
ω ωε 3/2 ε2 ω
Im ⎡⎣ χ (1) (ω )⎤⎦ = 9 p h
2
α0 = = p f (ω ) ε 2 , (4)
c (ε1 + 2ε h ) + ε 22
2 1
n0 c n0 c
where the f1(ω) is the local-field enhancement factor. The absorption coefficient α0has a
maximum at the SPR frequency [4] where ε1(ω)+2εh(ω) = 0.
The effective third-order nonlinear optical susceptibility of the dielectric medium with
MNPs χeff(3) can be derived by applying Maxwell’s equations to the first order in the
electromagnetic field to yield [3, 120]
2 2
3ε h ⎛ 3ε h ⎞ (3) 2 2 (3)
χ (3)
=p ⎜ ⎟ χ met = p f1 f1 χ met , (5)
ε1 + 2ε h ⎝ ε1 + 2εh ⎠
eff
where f1 is the same local-field enhancement factor of the polarization describing the χ(1).
This equation shows that the nonlinearity of composites with MNPs comprises two factors:
the nonlinearity due to the MNPs itself, and the enhancement contributed by the host matrix.
Note that whereas the α0 varies as ⎜f1⎜2, the χeff(3) varies as ⎜f1⎜2f12. Hence, it is expected a
significantly greater enhancement due dielectric nonlinearity in the χeff(3).
3. NONLINEAR OPTICAL PROPERTIES OF ION-SYNTHESIZED

NANOPARTICLES NEAR IR-AREA (1064 NM)
3.1. Nonlinear Absorption of MNPs Studied by Z-Scan
In numerous studies, the nonlinear optical characteristics of the composite materials with
MNPs fabricated by various methods were generally studied using lasers operating at
frequencies that correspond to the spectral range of the SPR in particles [120] and Table 1.
One other hand, one should take into account that, when used in practice as optical switches,
optical limiters, and so on, these nonlinear materials have to operate at the wavelengths of the
most frequently used industry available lasers, such as Nd:YAG (λ = 1064 nm), Ti:Al2O3
(λ = 800 nm), and so on. Hence, in order to create new materials promising for practical use
in laser systems and integral optics and to optimize their characteristics, one should study the
nonlinear optical properties of these materials not only in the SPR spectral region, but also at
the frequencies specific for industrial lasers. Materials characterized with nonlinear properties
in near IR are now searching for applications in the field of telecommunication.
Here, recent results on nonlinear optical properties of copper and silver nanoparticles [62-
65], synthesized by ion implantation in glass host matrices studied by the classical Z-method
[121, 122] at the wavelength of a picosecond mode-locked Nd:YAG laser (λ = 1064 nm) are
presented. The used Z-scan setup is shown in Figure 2. Laser pulse duration was 35 ps, pulse
energy 1 mJ and 2-Hz pulse repetition rate. The radiation had a spatial distribution close to
Gaussian and was focused by a 25-cm focal length lens (1) onto the samples (2). The beam-
waist diameter of the focused radiation was measured to be 90 μm using a CCD camera. The
samples were transferred in steps of 2 mm along Z-axis when scanning focal region. The
maximum laser intensity at the focal point was 3⋅1010 W/cm2, whereas the intensities of
optical breakdown were 6⋅1010 W/cm2 and 8⋅1010 W/cm2 for the glasses with copper and
silver nanoparticles, respectively. The fluctuations of the laser energy from pulse to pulse did
not exceed 10 %. The energy of single laser pulses was measured by a calibrated photodiode
(3). The samples were moved by a translation stage (7) along the Z-axis. A 1-mm aperture (9)
with 1 % transmittance was fixed at the distance of 100 cm from the focusing plane (closed-
aperture scheme). A photodiode (5) was kept behind the aperture. The radiation energy
registered by photodiode (5) was normalized relative to the radiation energy registered by
photodiode (3) in order to avoid the influence of non-stability of laser parameters. The
experimental data accepted as normalized transmittance T(z). The closed-aperture scheme
allowed the determination a value of n2 and the open-aperture scheme was used for the
measurements a value of β.
Figure 2. Z-scan setup. (1) focal length lens; (2) sample; (3) and (5) photodiodes; (4) and (6) digital
voltmeters; (7) translation stage; (8) computer; (9) aperture.
The samples with copper were prepared by Cu-ion implantation into amorphous SiO2 and
soda lime silicate glasses (SLSG) as described in details [65]. The energies of 50 keV and
dose 8⋅1016 ion/cm2 and at a beam current density of 10 μA/cm2 were used. The penetration
depth of the MNPs in the glasses for given energy of implantation was not exceed 80 nm.
Optical transmittance spectra of implanted samples Cu:SiO2 and Cu:SLSG are presented in
Figure 3. MNPs such as Cu in dielectric medium show optical absorption determined by SPR
[4]. The spectra are maximized near 565 nm Cu:SiO2 and 580 nm for Cu:SLSG that gives
evidence for formation of the Cu nanoparticles in the glasses. Depending on the ion
implantation conditions, the incorporation of accelerated ions into silicate glasses leads to the
generation of radiation-induced defects, which can initiate reversible and irreversible
Nonlinear
N Optiical Propertiess of Transitionn Metal Nanopparticles … 87
trransformationss in the glass structure [66]. This can result in struuctural imperffections of
diifferent types, such as the generation
g of extended
e and point
p defects, local crystallization and
am morphization, the formationn of a new phaase either from m atoms involvved the glass structure
s or
frrom implanted d ions, etc. Inn particular, thhe formation of
o MNPs in thhe glass bringgs about an
inncrease in its volume
v and thhe generation of internal stresses within an implanted layer. The
raadiation-inducced defects aree responsible for f an increase in the absorrption in the raange of the
U fundamental absorption edge in the sppectrum of thee glass. In ourr case, this efffect can be
UV
obbserved in thhe short-wavelength range of the opticaal transmittannce spectra diisplayed in
Fiigure 3. It shoould be noted that,
t presentedd here nonlineear optical studdy were perfoormed upon
exxposure of thee samples to laaser radiation at a wavelenggth of 1064 nm m, which lies far
f from the
U spectral rannge of the linnear absorptionn attributed too the SPR andd interband traansitions in
UV
M
MNPs and glaasses. For thiis reason, in what follow ws, the contribbutions assocciated with
innterband transiitions and radiation-inducedd defects will be eliminatedd from the analysis of the
exxperimental reesults.
Fiigure 3. Transm
mittance spectraa of (1) SiO2 and
a (3) SLSG before
b and afterr Cu-ion implanntation with
V and dose of 8⋅1016 ion/cm2 (22) Cu:SiO2 and (4) Cu:SLSG [665].
ennergy of 50 keV
Figure 4 sh hows the experimental deppendences of the T(z) measured for booth glasses
coontaining coppper nanoparticcles in the Z-sscan scheme with
w an open aperture
a [65]. Recall that
thhe measuremeents carried outo in this schheme make itt possible to determine thee nonlinear
cooefficient β. Silicate
S glassees did not demmonstrate the nonlinear abssorption at appplied laser
inntensities. It can
c be seen from f Figure 4 that the exxperimental deependences T(z)T exhibit
sppecific featurees inherent inn nonlinear abbsorption: thee T(z) decreasses as the foccal point is
appproached and reaches a minimum
m at Z = 0. Each point
p in the graphs
g was obtained by
avveraging overr the values measured
m for 40 pulses. Soome distributiion of the exxperimental
888 Andreey L. Stepanov
pooints in the grraphs is causeed, to some extent,

e by the energy instabbilities and, foor the most
paart, by the tim
me instabilities of laser radiattion.
Fiigure 4. Normmalized transmiittance as a function

f of thee Z-position of o Cu:SiO2 andd Cu:SLSG
coomposites in th
he z-scan schem
me with an opeen aperture. Saamples fabricateed by Cu-ion implantation
i
w energy of 40
with 4 keV and dosee of 8⋅1016 ion//cm2.Laser intennsity is 8⋅109 W/cm
W 2 and pulsee duration is
355 ps [65].
The nonlinear coefficiient βof com mposite materrials can bee determined from the
reelationship forr the T(z), whiich, in the casee of the schem
me with an opeen aperture, iss written as
[1122, 123]
T(z) = q(z)-1
-
ln(1+q(z)). (6)
Here, q(z) = βI(z)Leff is the laser beam

m parameter, Leff = (1− eα0 L ) / α 0 is thhe effective
opptical path witth MNPs in thhe sample, Lis the sample thhickness, and I(z)
I is the intennsity of the
ligght passed thrrough the sam
mple as a functtion of its possition along thhe Z-axis. Thee parameter
q((z) describes the propagattion of the laaser beam in the material,, because thee following
reelationship hollds
G(z)-2λΔφ/πw2-iλ/πw2,
1/q(z) = 1/G (7)
where G(z) = z[[1+z02/z2]is the radius of thee wave front curvature

w c in thhe Z-direction,, z0 = kw2/2
iss the diffractiion length off the beam, k=k 2π/λis the wave vectorr, Δφ = ΔΦ0/((1+ z02/z2),
ΔΦ0 = (2π/λ)n2I0Leff - phase shift of frequency gained by the radiation passed through the
sample, w(z) = w0(1 + z02/z2)2 is the beam radius at the point Z, and w0 is the beam radius at
the focal point (at a level of 1/e2).
At Z = 0 (focal plane), the parameter q(0) = q0 is defined by the expression
q0 = βI0Leff, (8)
where I0 = I(0) – intensity at the focal point.

Using formulas (6) and (8), it is possible to write
T0 = q0-1ln(1+q0), (9)
where T0 is the minimum of T(z) in the focal plane in the scheme with an open aperture.
Expression (9) permits to determine the nonlinear absorption coefficient β. The values of
βcalculated in this way from the experimental data for the Cu:SiO2 and Cu:SLSG composites
are equal to 9.0⋅10–6 and 3.42⋅10–6 cm/W, respectively (Table 2).
Table 2. Nonlinear optical parameters of silicate glasses with ion-synthesized copper and
silver nanoparticles measured at the wavelength of 1064 nm
Sample n2, β, Reχ(3), Imχ(3), ⎜χ(3)⎜,

-8
10 esu 10-6 cm/W 10-9 esu 10-9 esu 10-8 esu
Cu:SiO2 -13.7 9 -32.0 6.5 3.28
Cu:SLSG 3.6 3.42 8.3 2.5 0.87
Ag:SiO2 1.5 2.5
Ag:SLSG 3.5 5.7
SLSG 8.1⋅10-6 1.4⋅10-6 1.4⋅10-6
As can be seen, the nonlinear coefficients β for these composites differ by a factor of
2.63. However, to compare correctly the coefficients β for the Cu:SiO2 and Cu:SLSG, it is
necessary to take into account the individual linear coefficients α0 for layers with copper
nanoparticles in different glasses ( α 0SiO2 = 9340 and α 0SLSG = 5800 cm–1). By assuming
that the thicknesses of the layers with MNPs in the implanted glasses are virtually identical
(~80 nm) [124], the nonlinear coefficient β to the linear coefficient α0 for the relevant
composite (U = β/α0) can be normalized. As a result, the normalized values of U SiO2 =
9.64·10–10 and U SLSG = = 6.73·10-10 cm2/W, which differ by a factor of 1.432, were obtained.
To account for this discrepancy between the parameters U for different samples, proper
allowance must be made not only for the difference in the linear absorption coefficients but
also for the specific features in the location of the SPR peaks attributed to copper
nanoparticles. As can be seen from Figure 3, the SPR peaks assigned to MNPs is observed at
565 nm (ωp = 17699.1 cm–1) for the Cu:SiO2 composite and at 580 nm (ωp = 17241.4 cm–1)
for the Cu:SLSG composite. In such MNP systems a two-photon resonance related to the SPR
can be assumed [3, 11]. On the other hand, it is known that, in the range of excitations and
their associated transitions in nonlinear medium, the optical nonlinearities become more
pronounced with a decrease in the detuning of the frequency from the resonance (in a case,
two-photon) excitation [125]. In present experiment, the frequency detuning should be treated
as the difference between the SPR frequency and the frequency of two photons of the laser
radiation used ω20 = 18797 cm–1 (532 nm). The difference in the location of the SPR peaks
for copper nanoparticles in the SiO2 and SLSG composites can be estimated from the
following ratio:
M = (ω 20 − ω pCu:SiO2 ) / (ω 20 − ω pCu:SLSG ) =1.42 .

−1 −1
(10)
This value is in qualitative agreement with a ratio of 1.432 between the nonlinear
coefficients βnormalized to the linear coefficients α0 for different glasses.
The most interesting feature in the nonlinear optical properties of glasses with copper
nanoparticles irradiated at a wavelength of 1064 nm is the fact that the doubled frequency of
the laser radiation is close to the SPR peak frequency of copper particles. This is illustrated by
the diagram in Figure 5, which shows the spectral positions of the SPR peaks of the MNPs in
the samples studied and the spectral positions of the fundamental and doubled frequencies of
the laser radiation [63, 64]. Thus, from the above date, it can draw the following conclusions:
(1) In the near-IR range, the large nonlinear absorption coefficients determined
experimentally for glasses containing copper nanoparticles are explained by the SPR in
MNPs; (2) The efficient nonlinear absorption in the composites with copper nanoparticles
considered is associated with both the linear absorption of the material and the effect of two-
photon resonance at the SPR frequency for copper nanoparticles, which leads to the two-
photon transition at the wavelength 1064 nm.
The theoretical realization of two-photon absorption associated with the SPR of colloidal
metal (silver) particles in a solution was previously discussed in [126, 127], but in these
experiments the authors were difficult to analyze this possibility due to the experimental
problems related to the efficient aggregation of colloidal silver under laser irradiation, which
changed the nonlinear optical properties of the samples in time.
When analyzing the results presented here, it is expedient to dwell on the possible fields
of practical application of the studied composites. As is known, media with nonlinear (in
particular, two-photon) absorption are very promising as materials for optical limiters, which
can serve, for example, for the protection of eyes and highly sensitive detectors against
intense optical radiation [128]. Early, the majority of studies in this field have been performed
using nanosecond laser pulses. In this case, the main mechanisms responsible for nonlinear
effects are associated with the reverse saturable nonlinear absorption (fullerenes and organic
and metalloorganic compounds) and nonlinear scattering (solutions of colloidal metal
aggregates). Picosecond and subpicosecond laser pulses have been used only to examine the
optical limiting in media belonging primarily to semiconductor materials (two-photon
absorption and strong nonlinear refraction).
Since two-photon absorption at a wavelength of 1064 nm is observed in the Cu:SiO2 and
Cu:SLSG samples, it is of interest to investigate the optical limiting effect in these composites
in the scheme with an open aperture. Here, it was assumed that the sample is located in the
Nonlinear
reegion correspo onding to a minimum

m transmittance, i.e.,, in the focal plane
p of a beaam (Z = 0).
The nonlinear absorption was w studied exxperimentally at an operatiing intensity from107 to
10011 W/cm2 [62, 63]. With the use of the t linear andd nonlinear (two-photon)
( absorption
cooefficients, thee dependencess of the normaalized T(z) on the laser radiiation intensityy presented
inn Figure 6. It can be seenn from Figuree 6 that, at thhe maximum m intensity, thhe Cu:SiO2
coomposite is chharacterized by
b an approxim mately fifteenn-fold limitingg, whereas thee Cu:SLSG
coomposite exhiibits an approxximately threee-fold limitingg. Consequenttly, these compposites can
seerve as nonlinear materials for
f optical lim miting. It is cleear that the Cuu:SiO2 compossite is more
prreferable fromm the practical standpoint.
Fiigure 5. Diagramm of the SPR frrequencies for the

t glasses withh implanted coppper and silver
naanoparticles [633, 64].
3.2. Nonlinea
ar Refractioon of MNPs Studied byy Z-Scan
Consider thhe nonlinear optical

o refracttion of Cu:SiO
O2 and Cu:SLSG compositees [63, 65].
Fiigure 7 showss the T(z) deppendences of the samples in the Z-scann scheme witth a closed
apperture. Each point on the plot corresponnds to a valuee averaged ovver 40 pulses. A specific
feeature of the samples withh copper nannoparticles is that the plots for differennt types of
suubstrate glasss demonstratte opposite signs of nonlinear refraction under the same
im
mplantation coonditions. Fromm the positionn of the T(z) peak
p in the possitive or negattive Z-scan
reegion (the no onlinearity siign), it can be can concclude that thhe Cu:SiO2 sample s are
chharacterized by
b self-defocuusing of the laser beam (n ( 2 < 0), whilee the Cu:SLS SG sample
deemonstrate a self-focusing
s e
effect (n2 > 0).
To recogniize the reason for the differrent signs of nonlinear
n refraaction in the glasses
g with
coopper nanopaarticles, the observed self-action effeccts has to by b analyzed. Since the
w
wavelength of the laser raddiation used inn this study considerably exceeds the size s of the
M
MNPs synthesiized by the im
mplantation [66, 9], the opticcal properties of the nanopaarticles can
bee considered within
w the fraamework of thhe effective medium
m theoryy [4]. Such ann approach
alllows to conssider the com

mposites as optically homoogeneous matterials, disreggarding the
prresence of MN
NPs in them.
Fuug. 6. Calculateed curves T(z) as

a a function of the incident raddiation intensityy for (1) Cu:SiO
O2 and (2)
Cu:SLSG compo osites [62].
In general,, among nonliinear optical processes

p conntributing to the
t nonlinear part of the
reefractive index, it should be taken intoo account thee optical Kerrr effect, caussed by the
ellectronic resp
ponse of atom ms and moleccules [125] and a associatedd with the presence
p of
reesonance transsitions in the medium [1299]. The nonlinnear index n2 may vary coonsiderably
deepending on the type of o interactionn (resonancee or nonresoonance). Nonnresonance
coontributions too the n2 of suuch medium as a glasses are usually positiive [130]. In the
t case of
reesonance inteeractions invoolving one-phhoton or twoo-photon proccesses, the siign of the
noonlinear indexx n2 is determmined from thhe difference between
b the frequency
f of ana incident
ellectromagneticc laser wave ω10 (or a muultiple frequeency ωi0) and the intrinsic resonance
frrequency of thhe material (ωp in the case of MNPs). Inn particular, the t nonlinear index n2 is
neegative only for
f frequenciees that are sligghtly below thet one-photon resonances or slightly
abbove the two-p photon resonaances [130].
For a hommogeneous conndensed mediium characterrized by the occurrence
o off resonance
trransitions, on
ne can considder the standdard two-levvel energy model m [125]. Then, the
coorresponding equation
e for thhe nonlinear inndex n2 will have
h the form
Nonlinear
4
μi00
n2 = −2π N , (11)
n0η (ωio − ω p )3
where ωp and ωi0 correspondd to the frequuencies of the SPR of MNP

w P and the laserr radiation,
reespectively; th
he subscript i denotes
d one- and
a two-photoon processes; N is the conceentration of
acctive excitatioon centers considered
c to be dipoles (virtually eqqual to the number n of
naanoparticles inn the sample); and μi0 is the transition dippole moment ata the frequenccies ωi0.
As follows from equationn (11), N and μi0 have no efffect on the siggn of the nonliinear index
n2 (the sign of the
t nonlinearitty), which is determined
d onnly by the detuuning from thee resonance
Δi0. Keeping inn mind that χ(3)depends liinearly on n2[125], it can be written thhe relation
deetermining thee sign of the nonlinearity
n as
sgn Re ⎡⎣ χ (3) ⎤⎦ ∝ −(ω 20 − ω p )−3

−
= −sgn Δi 0 , (12)
annd analyze it only

o for the freequency ω20, i.e.,
i for the dooubled frequenncy of the laseer radiation,
w
which lies in th
he vicinity of the
t SPR of thee samples withh copper particcles. In other words,
w it is
coonsidered the effect that thhe frequency detuning
d ween the sum frequencies of two laser
betw
phhotons and thee SPR frequenncy exerts on nonlinear
n opticcal processes.
Fiigure 7. Depend dence of the currves T(z) for (a)) Cu:SiO2 and (bb) Cu:SLSG coomposites in thee Z-scan
sccheme with a close aperture. Saamples fabricatted by Cu-ion im mplantation witth energy of 40 keV and
doose of 8⋅1016 ionn/cm2. Laser inttensity is 8⋅109 W/cm2 and pulse duration is 35 ps [65].
As was meentioned (Figuure 7) the sam mples show diifferent spectrral positions of
o the SPR
m
maxima for MNNPs in glass host
h matrices of o different tyypes. For exam
mple, the SPRR maximum
foor the Cu:SLS SG samples iss in the viciniity of 580 nmm, while the SPPR peak of thhe Cu:SiO2
saamples lies neear 565 nm. Suubstituting thee frequencies of the SPR off copper nanopparticles in
SiiO2 and SLSG a the frequeency ω20 ~ 188797 cm–1 (thhe frequency of
G (Figure 5) and o the two-
phhoton excitatiion of the laser radiation used) into eqquation (12), a negative sign s of the
detuning is obtained, which points to a negative contribution to the nonlinear susceptibility

for the matrices of both types. These conditions correspond to the self-defocusing of laser
radiation, which was experimentally observed for the Cu:SiO2 sample (Figure 7a). Thus, the
two-level model used in this paper gives the proper sign of nonlinearity in the Cu:SiO2 system
excited by laser radiation at a frequency lying outside the SPR region of its particles, namely,
at a frequency about two times lower than the SPR frequency.
A noticeable contribution to the n2 can also be made by the thermal effect, i.e., by the
heat transfer from MNPs and defects of a dielectric host matrix heated by laser radiation
[131]. The rise time τrise of n2 variations is determined by τrise = Rbeam/Vs, where Rbeam is the
beam-waist radius and Vs is the sound velocity in the lattice.In present case (Rbeam = 75 μm,
Vs ≈ 5500 m/s) the time necessary for both the distribution of the density of a material and its
n2 to reach their stationary values — trelax ~ 13–15 ns — is three orders of magnitude longer
than the pulse duration (35 ps). This allows one to exclude from consideration the influence
of the thermal effect on the nonlinear optical properties of the composites at present
experimental conditions and regard the electronic optical Kerr effect in MNPs as the main
factor.
On the other hand, for the Cu:SLSG sample, the self-focusing of the laser radiation
(Figure 7b) was observed [63], which contradicts the conclusions derived from equation (12).
To reveal the reasons for the different self-action effects in the glasses, it is necessary to
consider the influence of the substrate on the nonlinear optical properties of the composites.
For this purpose, the dependences of the T(z) for both types of glasses without MNPs was
measured. The SiO2 substrate shows no noticeable changes in the character of the T(z) under
irradiation with the intensities used in this study; i.e., this glass does not demonstrate
nonlinear refraction and the nonlinearities observed in the Cu:SiO2 samples are evidently
caused by the copper nanoparticles.
At the same time, the SLSG matrix exhibits a self-focusing effect (Figure 8). To estimate
the contribution of the glass substrate to the optical refraction of the Cu:SLSG sample, it was
determined and compared the values of χ(3)for the SLSG and Cu:SLSG samples.
In the general case, when a material simultaneously exhibits both nonlinear refraction and
nonlinearabsorption, the nonlinear susceptibility is a complex quantity
χ (3) = Re⎡⎣ χ (3) ⎤⎦ + iIm ⎡⎣ χ (3) ⎤⎦ (13)
where the real part is related to the nonlinear index n2 and the imaginary part is related to the
nonlinear coefficient β. As was mentioned the used glasses, contrarily to the samples with
nanoparticles, have no nonlinear absorption and, hence, χ(3)for the SLSG substrates is directly
real-valued and can be expressed in terms of n2as
n0
Re ⎡⎣ χ (3) ⎤⎦ = n2 . (14)
3π
This parameter can be experimentally estimated using the known Z-scan relations [122]
Nonlinear
ΔTm−v = 0.404(1− S)
S 0.25 ΔΦ 0 (15)
where ΔTm-v is the differennce between the maximum

w m and the minimum
m (vallley) of the
m
measured T(z),, Sis the percent of radiatiion passing thhrough the apperture and reeaching the
phhotodiode.
Fiigure 8. Depend
dence of the currves T(z) for SL
LSG in the z-scaan scheme with a close aperturre [63].
Applying relations
r (15)) to the expeerimental dataa (Figure 8) obtained for the SLSG
suubstrate, a vallue of n2 = 8.1⋅10–14 esu was
w estimated,, while for thhe Cu:SLSG sample
s this
–8 (3)
paarameter was detected to bee of n2 = 3.6⋅110 esu. Usinng relation (144) for the Re[χ ], it was
f SLSG, whhich shows no nonlinear abssorption, |χ(3)|iis equal to 1.44⋅10–14 esu,
obbtained that, for
(3)
w
while Re[χ ] for
f Cu:SLSG is i equal to 8.3⋅⋅10–9 esu (Tabble 2).
Taking into o account thaat the nonlinear susceptibillity in Cu:SLS
SG is a compplex-valued
paarameter, whoose imaginary part is expressed via the noonlinear coefficient β as
nε c 2
Im ⎡⎣ χ (1) ⎤⎦ = h h β . (16)
ω
Using equaation (13) andd the value off Im[χ(3)] for the
t given meddium, then thee nonlinear
(3) –9
suusceptibility iss |χ | = 8.7⋅100 esu (Table 2) [63].
R (3)] is respoonsible for thee nonlinear reffraction in a material,
Since the Re[χ m it wass compared
too such nonlin near parameterrs (Table 2) forf the SLSG G and Cu:SLS SG samples. In I order to
elliminate the in nfluence of booth the linear absorption annd the differennce in the thiccknesses of
the samples, in practice, one does not compare directly the values of Re[χ(3)], but rather their
normalized values Re[χ(3)]Leff (in this case, Leff includes a correction for the linear absorption).
Using Leff of the wavelength 1064 nm for the samples of both types, it is possible to
getRe[χ(3)] Leff = 4.92⋅10–14 esu⋅cm for Cu:SLSG,Re[χ(3)] Leff = 3.45⋅10–15 esu⋅cm for SLSG.
Therefore, the nonlinear parameters of pure SLSG are lower by an order of magnitude than
the same parameters for the glasses containing nanoparticles.
Discussing the reasons for the self-focusing observed in the experiment (Figure 7), i.e.,
the reasons for the positive contribution to the nonlinear susceptibility of Cu:SLSG, it should
be take into account the considerable (~30%) linear absorption of SLSG in the spectral region
ofthe laser radiation (Figure 3). If a material exhibits the effect of saturation at the laser
wavelength, the total absorption will decrease upon the laser irradiation. However, if a
material is characterized by nonlinear absorption, the total absorption will increase, as is
observed for the glasses with nanoparticles. The nonlinear absorption of Cu:SLSG causes an
additional decrease in the intensity of the transmitted light in the focal plane by approximately
10–12%, while for Cu:SiO2, whose linear absorption is ~15%, this value is equal to 18%.
Irrespective of the conditions of the laser radiation which was choose here, the increase in the
total absorption of Cu:SLSG can be caused by the nonlinear thermal effect predicted early
[132], and observed in [133] for silicate glasses containing radio-frequency sputtered copper
nanoparticles with size of 2.2±0.6 nm irradiation at the wavelength 1064 nm, when positive
nonlinear susceptibility was recorded using trains of picosecond pulses (100 pulses in a train).
Consider nonlinear refraction of glass containing silver nanoparticles. The composites
with silver were prepared by Ag-ion implantation into amorphous SiO2 and soda lime silicate
glasses (SLSG) as described [23]. The energies of 60 keV and dose 4⋅1016 ion/cm2 and at a
beam current density of 10 μA/cm2 were used. The penetration depth of the MNPs in the
glasses for given energy of implantation did not exceed 80 nm [124]. Optical transmittance
spectra of implanted samples Ag:SiO2 and Ag:SLSG are presented in Figure 9. MNPs such as
Ag in dielectric medium show optical absorption determined by SPR with maximum near
415 - 440 nm [4]. Figure 10 shows the experimental dependences of the T(z) of the samples
Ag:SiO2 and Ag:SLSG during Z-scanning in the scheme with a closed aperture. As follows
from Figure 10, both types of glasses with silver nanoparticles demonstrate self-focusing of
laser radiation. The values n2 and Re[χ(3)] are presented in Table 2. The nonlinear absorption
was not detected for these samples.
Estimate the nonlinear optical contributing to both the magnitude and the sign of the
nonlinear susceptibility χ(3). Similarly to the case of sample with copper nanoparticles, the
spectral positions of the SPR bands in the glasses with silver nanoparticles depend on the type
of substrate (Figure 9). The SPR maximum lies at about 415 nm (ωp = 24096.4 cm–1) for the
Ag:SiO2 and at 440 nm (ωp = 22727.3 cm–1) for the Ag:SLSG samples. As can be seen from
the diagram in Figure 5, the frequency of the sum of two photons of the laser radiation is
lower than the SPR frequency for nanoparticles in either matrix, which corresponds to a
positive sign of the detuning and, as a consequence, leads to a positive contribution to the
nonlinear susceptibility. Hence, no two-photon absorption occurs in the samples with silver
nanoparticles.
Nonlinear
Fiigure 9. Transm
mittance spectra of (1) SiO2 andd (2) SLSG befoore and after Agg-ion implantation with
V and dose of 4⋅1016 ion/cm2 (33) Ag:SiO2 and (4) Ag:SLSG [223].
ennergy of 60 keV
Fiigure 10. Depen ndence of the cuurves T(z) for (aa) Ag:SiO2 and (b) Ag:SLSG composites
c in thhe Z-scan
sccheme with a close aperture. Saamples fabricatted by Ag-ion im mplantation witth energy of 60 keV and
doose of 4⋅1016 ionn/cm2. Laser inttensity is 8⋅109 W/cm2 and pulse duration is 35 ps [63].
3.3. RZ-Scan
n Techniquee
There are different apprroaches for thhe study of noonlinear opticcal properties of various
materials, for example,
m e degeenerate four-w
wave mixing [136], nonlineaar optical inteerferometry
[1137], Z-scan [121, 122]). Ass was mentionned the latter technique
t alloows determininng both the
value and the sign of nonlinear optical indexes n2 and β. There are several modifications of
the Z-scan technique, such as transmission Z-scan (TZ-scan) [121, 122], eclipsing Z-scan
[138], two-beams [139], reflection Z-scan (RZ-scan) [140-142], time-resolved Z-scan [143],
etc. The RZ-scan has an advantage with comparing to the others that allows studying the
optical nonlinearities of materials with a limited optical transparency. This technique is based
on the analyze of the surface properties of materials, whereas the others are used for
theinvestigation of bulk characteristics of media. The application of RZ-scan was firstly
presented in [14], where the nonlinear refraction of gallium arsenide was studied in at a
wavelength of 532 nm at which this semiconductor is fully opaque. On the other hand, this
technique can also be applied for transparent materials and can be used for the comparison
with conventional TZ-scan.
Ricently, the RZ-scan technique was applied for measurement of nonlinear characteristics
of low-transparency dielectric layers with MNPs beyond the region of the SPR absorption of
particles [29, 94]. Consider some examples with composites based on dielectric with copper,
silver and gold nanoparticles synthesized by ion implantation. As a substrate for such model
composites an artificial sapphire (Al2O3) was used. Whose surface of the sapphire opposite to
the implanted surface was frosted, because of which the sample was almost nontransparent in
visible and IR-spectral area. Ion implantation was performed with Ag+, Cu+ and Au+
[95, 144]. Experimental conditions of ion implantation used for fabrication of MNPs in Al2O3
are shown in Table 3 [30].
Table 3. Ion implantation conditions and nonlinear optical parameters of Al2O3 with
ion-synthesized silver, copper and gold nanoparticles measured at the wavelength of
1064 nm. * - thermal annealing [30]
Sample No. Energy, Current Ion dose, I0, n2, Re[χ(3)],

keV density, 1017 109 10-11 10-9
μA/cm2 ion/cm2 W/cm2 cm2/W esu
Ag:Al2O3 1 30 3 3.75 4.3 3.40 0.94
Ag:Al2O3 2 30 6 3.75 4.3 3.89 1.07
Ag:Al2O3 3 30 10 3.75 4.3 5.36 1.48
Cu:Al2O3 4 40 2.5 0.54 7.7 -3.75 -1.04
Cu:Al2O3 5 40 12.5 1.0 7.7 -4.96 -1.38
Au:Al2O3 6 160 10 0.6 2.3 -28.15 -7.77
Au:Al2O3 7* 160 10 0.6 2.8 -32.68 -10.0
Au:Al2O3 8 160 10 1.0 2.3 -38.76 -10.7
Au:Al2O3 9* 160 10 1.0 2.8 -44.30 -12.2
The RZ-scan setup for measurement of nonlinear refraction is presented in Figure 11. The
Nd:YAG laser (λ = 1064 nm, τ = 55 ps) operated at a 2 Hz pulse repetition rate was applied.
Laser radiation was focused by a 25-cm focal length lens (1). The maximum intensity and the
beam waist radius in the focal plane were measured to be I0 = 7·109 W/cm2 and 72 μm,
respectively. The sample (2) was fixed on the translation table (7) and moved along the Z-
axis. The angle of incidence of laser radiation on the surface of sample was 30°. A part of
radiation was reflected from the beam splitter (9) and measured by photo-diode (3) to control
Nonlinear
thhe energy of laaser pulses. The radiation reflected from the surface of sample was directed to
thhe mirror (10)) and than colllected by the lens (11) thaat allowed reggistering all thhe reflected
raadiation by ph
hoto-diode (5).. To decrease the
t influence of the instabillity of laser raddiation, the
raatio R(z) betweeen the reflectted signal and the incident one
o was accepted.
Fiigure 11. RZ-sccan setup. (1) foocal lens; (2) sam

mple; (3) and (55) photodiodes;; (4) and (6) diggital
vooltmeters; (7) trranslation stage; (8) computer; (9) beam splittter; (10) mirror; (12) lens.
In the casee of RZ-scan the refractivee nonlinearitiees are measureed without apperture (for
exxample, see [145]).
[ In TZZ-scan schemee, the phase changes are produced by absorptive
noonlinearities and
a the apertture is needeed in this caase. The refraactive nonlineearities are
reesponsible forr the amplitudde changes off reflected raddiation so theere is no needd to use an
apperture beforee the detectorr. The measurrements of thee refractive nonlinearities
n of samples
(tthat are the suubject of preseent studies) weere carried ouut without an aperture,
a thus neglecting
thhe influence off phase changees caused by nonlinear
n absoorption.
The principples of RZ-sccan can be deescribed as foollows. The saample moves during the
exxperiment throough the focaal plane of focusing lens. The T amplitudee and phase of o reflected
beeam change due to the innfluence of nonlinearn refraaction and noonlinear absoorption. No
noonlinear effeccts appear wheen the sample is positionedd far from the focal plane, so s the ratio
R(z) of the refflected and inccident laser raadiation is coonstant. Whenn the sample approaches
a
foocal plane, thee laser intensitty becomes hiigher and the nonlinear effeects occur. In the case of
poositive nonlinear refraction (n2 > 0), the movement
m of sample close to the focus leads
l to the
grrowth of R(z). After crossinng the focal plaane the nonlinnear refractionn diminishes thhat leads to
a decrease of R(z)
R down to previous
p valuee. In the case of
o self-defocussing (n2 < 0) thhe opposite
feeature will be observed withh the valley apppearing in thhe R(z) dependdence. One caan conclude
abbout the sign ofo n2 from the R(z) dependence.
The expresssion for the inntensity of raddiation reflecteed from the suurface of a sam
mple can be
w
written in the fo
orm [140-142]]
(
I R (z ) = I 0 R0V0−1 (z ) + R1 (θ )(n2 − ik2 )I (z )V1−1 (z )(1 − ix ') ).
2
(17)
Here, k2 is the coefficients of nonlinear extinction; R0 is the linear reflection coefficient,

Vm(z) = g(z) – id/dm, g(z) = d/d0x, d is the distance from the sample to the far-field aperture;
dm = kω2m0/2, ω2m0 = ω2(z)/(2m+1), ω2(z) = ω2(1+x2), x = z/z0, z0 = kω20/2 is the diffraction
length of the beam; ω0 is the beam waist radius; z characterizes the sample position:
2n 03 cos(θ ) − 4n 0 cos(θ )Sin 2 (θ ) 2

[ ]
−1 2
R1(θ ) = n − sin 2
(θ ) , (18)
n 04 cos2 (θ ) − n 02 + sin 2 (θ )
0
and θ is the angle of incidence of the beam [145]. Substituting into equation (17) the
parameters given above, it will be obtained the following expression for the normalized
reflection:
R (z,θ ) = 1 −
(4R (θ ) / R )I k x ' + (2R (θ ) / R )I n (x ' + 3) + (R (θ ) / R ) I
1 0 0 2 1 0 0 2
2
1 0
2 2
0 (n22 + k22 )
(x ' + 9 )(x ' + 1)
2 2
(x ' + 9 )(x ' + 1)
2 2
(x ' + 9 )(x ' + 1)
2 2
. (19)
Here, the first expression on the right-hand side is responsible for the nonlinear
absorption, the second expression describes the nonlinear refraction, and the third expression
characterizes their joint effect. It should be noted that equation (18) was derived without
taking into account the effect of thermal processes, which are characteristic of nanosecond
pulses [131] or of radiation with a high pulse repetition rate [131]. To determine the real part
of the third-order nonlinear susceptibility, the expression (14) was used.
For practical purpose the R(z) power could be presented as follows [144] :
∫
∞ 4
E( ρ, z) ρ d ρ
P(z) = 1+ 2Re [ R(n2 + ik )] 0
, (20)
∫
2 ∞ 2
E(ρ, z) ρ d ρ
0
where ρ the radial coordinates, and E(ρ,z) is the incident beam amplitude.
This equation describes the general case, when both nonlinear refraction and
nonlinearabsorption appear simultaneously during the reflection from the sample. However,
the application of open-aperture RZ-scan allowed neglecting the influence of nonlinear
absorption for the measurements of nonlinear refraction [146].
3.3.1. RZ-Scan Study of Ag:Al2O3

The spectra of linear optical reflection for both virgon Al2O3 and Ag:Al2O3 composites
obtained by ion implantation under different conditions presented in Figure 12. Samples 1 - 3
Ag:Al2O3 were implanted at fixed doses and energies but at different ion current densities,
which increases with the sample number (Table 3). The thickness of a substrate layer
containing silver nanoparticles was about 50 nm [124].
Nonlinear
Fiigure 12. Reflecctance spectra of

o Al2O3 before and after Ag-ioon implantationn with energy off 30 keV,
doose of 3.75⋅10177 ion/cm2 and diifferent current densities (1) 3; (2) 6 and (3) 10 μA/cm2 [30]..
As is seen from Figure 12,1 in contrastt to nonimplannted Al2O3, alll the implanteed samples
arre characterizeed by the pressence in the viisible spectrall region of a broad
b selectivee reflection
baand with a maximum
m neaar 460 nm, whose
w intensityy is slightly higher for thhe samples
obbtained at hig gher ion curreents. This refleection band appears
a due too the formatioon of silver
naanoparticles in n the implanteed Al2O3 and corresponds to t the SPR abssorption in MNPs [4]. A
shharp increasee in the refleection intensiity in the shhorter waveleength region beginning
frromapproximaately 380 nm (beyond
( the SP PR band) is caaused by the absorption
a of light
l by the
A 2O3 matrix an
Al nd by interbannd transitions in
i metal NPs.
As was sh hown recentlly [147], an increase in the ion currrent density during the
immplantation off silver ions into
i SiO2 leadds to an increase in the porrtion of the metalm phase
(MMNPs) in the sample. This is explained by an increasse in the tempperature of thee dielectric
irrradiated by hiigh ion currennts and, hence, by a higher diffusion mobbility of implaanted silver
ioons and thus their
t more effficient incorpporation into MNPs.
M In thee general casee, this may
reesult in an inccrease both in the number of o MNPs and in their sizes, which leads to a higher
SP PR absorptionn of MNPs. Therefore,
T the rising in the SPR reflectioon intensity inn Figure 12
shhould be related to a larger portion of metallic silver in i Al2O3 implanted at higheer currents.
Siince the specctral positionss of the SPR band maxim ma almost do not change, hence h it is
poossible to concclude that an increase
i in thee ion current density
d under these
t conditionns of silver
immplantation innto Al2O3 ressults in a higgher concentrration of MN NPs rather thaan in their
diimensions, whhich would im mmediately cauuse a spectral shift
s of the SP
PR reflection maximum.
m
The experiimental R(z) dependences
d f the Ag:Al2O3samples measured
for m by RZZ-scanning
9 2
att the waveleng gth 1064 nm ata the laser raddiation intensity I0 = 4.3⋅10 W/cm are presented
p in
Fiigure 13. Dependences R(z)) for all the saamples have thhe shape of a bell b with the toop directed
uppward, symmeetrical with reespect to Z = 0, 0 and by the positive
p n2. It should be notted that the
toops of the beell-shaped deppendences aree higher for the t samples implanted
i at higher ion
cuurrents, i.e., foor the sampless with a higherr content of metallic silver.
Virgin Al2O3 shows noo such opticall nonlinearityy in experimeents with laseer radiation
inntensity up to the optical brreakdown. Thuus, the nonlineear optical efffects shown inn Figure 13
arre caused by the presence of silver nannoparticles in Al2O3. It is also interestinng that the
opptical nonlineearities of silvver particles are observed at laser irraddiation at a wavelength
w
ouutside the SPR R absorption of
o the MNPs.
Using mod deled R(z) deppendences (Figgure 13) and fitting
f by them m the experim
mental data,
(3)
vaalues of n2and d Re[χ ] in eaach sample weere estimated anda presented in Table 3. The analysis
off the results sh hows that the samples with a higher conccentration of silver
s nanoparrticles have
(
(3)
hiigher values of o n2 and Re[χ ].
Fiigure 13. Depenndence of the cuurves R(z) for Ag:Al

A 2O3 compo osites implantedd with energy of
o 30 keV,
doose of 3.75⋅10177 ion/cm2 and diifferent current densities (1) 3; (2) 6 and (3) 10 μA/cm2. Laseer intensity
is 4.3⋅109 W/cm2 and pulse duraation is 55 ps. Solid line is a fittting [30].
3..3.2. RZ-Scan n Study of Cu u: Al2O3

The second d type of sam
mples is the Al
A 2O3 with coppper nanopartticles. In conttrast to the
prrevious seriess of Ag:Al2O3 samples (1––3) presented in Table 3, in i which the content of
M
MNPs was varried by using different ion current densiities, one of the
t samples with
w copper
naanoparticles (ssample 4) wass obtained by implantation with
w a small dose
d (0.54·1017 ions/cm2)
2
annd a low ion current (2.5 μA/cm
μ ), whille the other saample (sample 5) was impplanted at a
laarger dose (110 ions/cm ) and a higgher current (12.5 μA/cm2). The energgy of ion
17 2
immplantation was equal to 400 keV for both samples (Tabble 3).
Nonlinear
The choicee of ion impllantation regim mes (Table 3)) in the case of copper naanoparticles
alllowed to obtaained samples with a noticeeably differentt filling factorr of the metal phase and,
inn particular, with
w different sizes
s of MNPs. This is illustrated in Figuure 14, whichh shows the
linnear reflectionn spectra of Cu:Al
C 2O3 withh the SPR abbsorption bandds of copper NPs N [148],
w
whose maxima take clearly different
d positiions. Sample 5,
5 which has a higher conceentration of
coopper nanopaarticles, exhibbits the band at a longer wavelength (with the maaximum at
~ 650 nm) than n sample 4 (~ ~ 610 nm), which
w points to the presennce of largerr MNPs in
saample 5 [21, 148].
1 A pronouunced differennce in the porttion of the meetal phase andd in the size
off MNPs also manifests itsself in the inttensity of the SPR bands. The reflectioon intensity
foorsample 5 is noticeably
n higgher than that for
f sample 4.

o Al2O3 before (1) and after Cu-ion implantattion with energyy of 40 keV
o 0.54·1017 ionss/cm2 and 2.5 μA/cm2 (2) and dose of 1.0⋅10177 ion/cm2
annd different parameters: dose of
annd 12.5 μA/cm2 (3) [147].
The experiimental and caalculated depeendences R(z)) for the Cu:A Al2O3 samples are shown
inn Figure 15. Since
S the efficciency of the electronic SPR R excitation in
i copper nannostructures
n films, wires, etc.) is know
(in particular, in wn to be noticeeably lower thhan in silver paarticles [4],
it was chosen a somewhat higher h intensiity of laser raadiation for measuring
m theirr nonlinear
9 2
opptical propertties I0 = 7.7·100 W/cm (Taable 3) than for f Ag:Al2O3. The R(z) deependences
obbtained are alsso bell-shapedd and symmetrrical with resppect to the point Z = 0, whicch points to
n the Cu:Al2O3 samples duee to the presennce of copper nanoparticles. However,
seelf-focusing in
inn contrast to the
t case withh Ag:Al2O3, when w the tops of the bells are directed downward,
d
w
which clearly testifies
t to thee self-defocussing of the lasser beam in thet samples with
w copper
naanoparticles, i.e., to a neggative n2 (Tabble 3). Such a different beehavior of thee nonlinear
opptical propertiies of Ag:Al2O3 and Cu:A Al2O3 samples (a difference in the signs of n2) was
allso observed in transmission Z-scan measurements at the same wavelength w o 1064 nm
of
innSiO2with silv
ver and coppeer nanoparticlees (Table 2). Estimated
E values of n2 andd Re[χ(3)] in
C
Cu:Al 2O3 by sim
mulating the R(z)
R dependennces and compparing them wiith experimenntal data are
prresented in Table 3. It is found
f that thee sample withh a higher conntent of the metal
m phase
(3)
(ssample 5) has higher |n2| andd |Re[χ ]|.
Fiigure 15. Depen ndence of the curves

c R(z) for Cu:Al2O3 com mposites implanted with energyy of 40 keV
(11) dose of 0.544·1017 ions/cm2 and current deensity 2.5 μA/ccm2 and (2) dosse of 1.0⋅1017 ion/cm
i 2
and
cuurrent density ofo 12.5 μA/cm . Laser intensityy is 7.7⋅10 W/ccm and pulse duration
2 9 2
d is 55 ps.
p Solid line
is a fitting [30].
3..3.3. RZ-Scan n Study of Au u:Al2O3

Samples (66–9) describedd in Table 3 are the Al2O3 containinng ion-synthesized gold
naanoparticles, which
w are alsoo characterizedd by efficient SPR absorptioon in the visibble spectral
reegion. As in the case withh copper ionns, two differeent implantattion doses, 0..6·1017 and
0..1·1017 ions/cm
m2, but higher irradiationn energies, 160 keV (sam mples 6 and 8, 8 Table 3)
[994, 95]. Sincee, at such higgh energies, the implantedd impurity acccumulates inn a thicker
suubsurface layeer of the irradiated dielectricc [124], the im
mpurity concenntration necesssary for the
nuucleation of MNPs
M accumuulates over a longer
l time. Inn order to inccrease the sizee of MNPs,
soome of samplles 7 and 9 were w annealedd in a furnace for 1 h at a temperaturee of 800°C
(TTable 3) [94, 95].
9
The spectraa of linear opptical reflection from the Auu:Al2O3 sampples 6–9 are presented in
Fiigure 16. The formation of gold nanopartticles by ion im mplantation iss proved by thhe presence
off SPR reflectioon bands peakked at about 610 nm. Compaaring samples 6 and 8 (curvves 1 and 3,
Fiigure 16), obtained directlyy by ion implaantation, it is possible
p to seee that an incrrease in the
im
mplantation doose (sample 8) 8 results in a slight shift off the maximuum of the SPR R reflection
Nonlinear
(tto ~ 620 nm), which is accoompanied by a noticeable increase

i in thee intensity. Thhis fact, as
innthe previous case with thee implantationn with copperr ions (samplees 4 and 5), points p to a
hiigher filling faactor of the metal
m phase in sample
s 8 (Au::Al2O3). Subseequent thermaal treatment
off these samplees almost doees not change the positions of the maxim ma of the SPR R bands but
leeads to a sharrp increase inn the reflectioon in the longg-wavelength spectral rangee. A broad
reeflection shoulder (sample 9, 9 curve 4 in Figure
F 16) or even an addittional maximuum (sample
7,, curve 2 in Figure
F 16) apppearing near the SPR refllection bands can be assocciated with
o the metal phase in the diielectric volum
reedistribution of me due to the high temperaature of the
m
material and, heence, with thee formation off aggregates off MNPs. Simillar spectral beehavior was
obbserved in exp periments withh fractal aggreegates of silverr particles butt in solutions [149].

o Al2O3 before and after Au-ioon implantationn with energy off 160 keV,
cuurrent density of 10 μA/cm2 wiith different dosses of 0.6·1017 ions/cm
i 2
a 1.0⋅1017 ionn/cm2 (1, 2).
(3, 4) and
Saamples annealed after ion impllantation duringg 1 h at temperaature of 800ºC (2,
( 4) [94, 95].
At present,, there are no data in the liiterature on thhe nonlinear optical

o propertties of gold
naanoparticles in
n a solid matriix in the near--IR region (10064 nm). The first
f experimeental results
foor Au:Al2O3 were
w given in [94, 95] and presented
p in Figure 17. Figuure 17a showss the curves
foor samples 6 and 7, whichh were obtainned directly byy ion implanttation, while Figure 17b
prresents the deependences forr samples 8 and
a 9, obtainedd by ion impllantation and subsequent
thhermal treatmeent. As is seenn, the R(z) dependences have a bell-like shape symmeetrical with
reespect to the point Z = 0,, with the toops directed downward. Thus, T samples (6-9) are
chharacterized by
b self-defocussing, which coorresponds to a negative n2anda Re[χ(3)] whhich values
prresented in Taable 3.
Fiigure 17. Depen ndence of the cuurves R(z) for Au:Al

A 2O3 compo osites implantedd with energy of
o 160 keV
w doses 0.6·10
with 017 ions/cm2 (1, 2) and 1.0⋅10177 ion/cm2 (3, 4) at current density of 10 μA/cm
m2 with
17 2 17 2
diifferent doses of 0.6·10 ions/ccm (3, 4) and 1.0⋅10
1 ion/cm (1, 2). Samplees created by ionn
im
mplantation (1, 3) 3 and samples created by ionn implantation withw subsequentt thermal annealling during
1 h at temperaturre of 800ºC (2, 4).4 Laser intenssity is 2.3⋅109 W/cm
W 2and pulse duration is 55 ps. p Solid
linne is a fiting [944, 95].
3.3.4. Nonlinear Refraction of MNPs Studied by RZ-Scan

For the composites based on Al2O3, the frequencies ωp are equal to 22222 cm–1
(~ 450 nm, Figure 12) for silver nanoparticles, 16393 – 15384 cm–1 (~ 610 – 650 nm,
Figure 14) for cupper nanoparticles, and 16129 cm–1 (~ 620 nm, Figure 16) for gold
nanoparticles. Consider relation (12) for the case of a one-photon process (i = 1), i.e., for the
frequency ω10 = 9398 cm–1 (λ = 1064 nm), which is the fundamental frequency of the laser
radiation used. Substituting the values of ω10 and ωp into relation (12), positive values of
Re[χ(3)] and a negative detuning Δ10 for all the samples can be obtained. The positive Re[χ(3)]
and n2 correspond to the self-focusing of the laser radiation in the sample, which was
observed experimentally for the Ag:Al2O3 samples (samples 1–3, Table 3).
On the other hand, the positive values of the signs of Re[χ(3)] and n2 contradict the self-
defocusing experimentally detected in the samples with cupper and gold nanoparticles
(Figures 15 and 17). Hence, the description of nonlinear processes in the approximation of
one-photon excitation for the Cu:Al2O3 and Au:Al2O3 systems is incorrect. Therefore,
consider the case of two-photon excitation for all the composite systems studied using again
expression (12) but with the doubled frequency of the laser radiation, ω20 = 18797 cm–1
(λ = 532 nm). This frequency lies in the vicinity of the SPR frequencies of MNPs in Cu:Al2O3
and Au:Al2O3. Determine the signs of Δ20 for composites and see how they correlate with the
nonlinear optical processes observed experimentally. In this case, the signs of Re[χ(3)] for the
Cu:Al2O3 and Au:Al2O3 systems are negative, which agrees with the self-defocusing detected
in experiments and suggests the occurrence of two-photon absorption in these samples. For
the Ag:Al2O3 samples, this sign turns out to be positive again, as in the case of one-photon
excitation, and correlates with the self-focusing observed in experiments. However, for silver
nanoparticles in Al2O3, it is difficult to choose between the one-photon and two-photon
excitation mechanisms. Probably, the two mechanisms are simultaneously realized in this
type of MNPs and their manifestation depends on the dominant frequency of laser excitation.
Thus, the two-level model correctly predicts the sign of the nonlinearity in the Cu:Al2O3 and
Au:Al2O3 systems in the case of excitation by laser radiation at a frequency divisible by the
doubled SPR frequency.
As was mention a change in n2 of a composite material can be caused by the thermal
effect due to heat transfer from MNPs or defects of the dielectric host matrix heated by laser
radiation [131]. Despite the duration of laser pulses used was rather short (τ = 55 ns), the
influence of the thermal effect on the nonlinear refraction can be analyzed. Estimate how
large a change in the refractive indexof crystalline sapphire ΔnAl O caused by heating can
2 3
be.
The change in the refractive index due to the thermal effect can be represented in the
form [131]
1 dn
Δn(r, z, t) = ΔΕ (r, z, t) , (21)
Ch ph dT
where Ch and ρh are, respectively, the heat capacity and the density of the host matrix with
MNPs (in the case of sapphire, Ch = 0.419 J/g⋅K and ρh = 3.97 g/cm3); dn/dT is the thermo-
optic coefficient, equal to 13.7⋅10–6 1/K; and ΔE(r, z, t) is the energy of the radiation absorbed
in a unit volume of the material over a time t. The thermo-optic coefficient for sapphire is
positive, and, hence, the thermal effect should lead to the self-focusing of laser radiation in all
the samples.
Since the self-focusing of laser radiation was experimentally observed only for the
samples with silver nanoparticles the thermal effect for such samples were analyzed using
present experimental conditions of nonlinear measurements [94, 95]. Thus, in the case of
Ag:Al2O3, the energy of the absorbed radiation is 3.87⋅10–6 J. For the layer with silver
nanoparticles of 50 nm thickness and the beam waist radius 72 μm, the analyzing volume is
4.88⋅10–10 cm3. In this case, the energy ΔE(r, z, t) is 7.92⋅103J/cm3. Substituting these values
into equation (21), the value of Δn(r, z, t) ≈ 6.53⋅10–2 will be obtained. In same time, the
experimental values are from 4.33⋅10–2to 6.83⋅10–2. Hence, the thermal effect may manifest
itself in the case of samples with silver nanoparticles. However, as it was mentioned the time
τrizenecessary for a change in the medium density and a corresponding change in the refractive
index is determined by the ratio of the beam waist radius to the speed of sound. Taking into
account our experimental conditions (ω0 = 72 μm at the wavelength 1064 nm and Vs~ 5000–
5500 m/s), τrize ≈13–15 ns will be again estimated. This time is three orders of magnitude
longer than the pulse duration used (55 ps), and, hence, the thermal effect caused by the
propagation of an acoustic wave can be excluded from consideration in our case.
In conclusion, RZ-scan method is suited for study of nonlinear refraction of samples
based on dielectrics with MNPs. Although the sensitivity of the RZ-scan method is slightly
lower than that of the classical transmission Z-scan, the RZ-scan method allows one to extend
the spectral range of study to the region of low transparency of composite materials. The sign
of the Re[χ(3)] is analyzed on the basis of the two-level model, and it is shown that Re[χ(3)] of
the samples with copper and gold nanoparticles are determined by the two-photon process. It
is difficult to make similar conclusion for samples with silver nanoparticles.
4. NONLINEAR OPTICAL ABSORPTION OF ION-SYNTHESIZED SILVER

NANOPARTICLES IN VISIBLE RANGE
The silver nanoparticles doped in different dielectrics demonstrate variable nonlinear
optical properties in visible range [120]. The interest on such structures is based on the
prospects of the elaboration of optical switchers with ultrafast response, optical limiters, and
intracavity elements for mode locking. Silver nanoparticles have an advantage over another
metal nanoparticles (i.e., gold and copper) from the point of view that the surface plasmon
resonance energy of silver is far from the interband transition energy. So, in the silver
nanoparticle system it is possible to investigate the nonlinear optical processes caused solely
by SPR contribution. It should be noted that previous studies of nonlinear optical parameters
of silver nanoparticles-doped glasses were mostly focused on determination of third-order
nonlinear susceptibility χ(3).
The saturated absorption in silicate glasses doped with ion-synthesized Ag nanoparticles
at wavelength of 532 nm and their dependence on laser radiation intensity are considered at
present review. As was shown the ion-synthesized silver nanoparticles in Ag:SLSG and
Ag:SiO2 demonstrate the SPR band with minimum transmission in the range of 410–440 nm
(Figure 9). Early, it was predicted that glasses with silver-doped nanoparticles could possess a
nonlinear saturated absorption [150]. The spectral dispersion of the imaginary part of
susceptibility Im[χ(3)] of such glass was detected as negative value in the spectral SPR range
of 385 – 436 nm. The nonlinear coefficient β is also negative in the case of saturated
absorption.
The T(z) dependences of Ag:SLSG and Ag:SiO2 samples measured using open aperture
Z-scan scheme at laser radiation intensity of I0 = 2.5·109 W/cm2 and pulse duration of 55 ps is
presented in Figure 18 [84]. The transmission of samples was increased due to nonlinear
saturated absorption as they approached close to the focal plane. Experimentally estimated
nonlinear parameters of the β are -6.7·10-5 cm/W in Ag:SLSG and -3.6·10-5 cm/W in Ag:SiO2.
Note that the coefficient β can be presented as β = α/Is whereIs is saturated intensity. Then
the values of Is are 1.1·109 and 1.4·109 W/cm-2 and the Imχ(3) are -2.4·10-8 and -1.3·10-8 esu in
Ag:SLSG and Ag:SiO2, respectively.
Figure 18. Normalized transmittance Ag:SLSG (1) and Ag:SiO2 (2) samples at laser radiation intensity
of I0 = 2.5·109 W/cm2. Solis lines show is a fittings [84].
In Figures 19 and 20 values of β in dependence of laser intensity varied from 109 to

2·1010 W/cm2 are presented. As seen from the figures there are a decrease βof for higher
intensities. In particularly, a 21- and 12-fold decrease of β was measured at
I0 = 1.15·1010 W/cm2 for Ag:SLSG and Ag:SiO2, respectively, compared to β detected at
I0 = 1·109 W/cm2.
The variations of nonlinear transmission in MNP structures in dielectrics were early
attributed in some cases to the fragmentation, or fusion of nanoparticles following the their
photothermal melting [151, 152]. It was reported about the alteration of the sign of nonlinear
refractive index of small Ag clusters embedded in SLSG [153]. They noted that thermal
effects could change the properties of nanoclusters. The transparency in these samples was
associated with oxidation of Ag nanoparticles. However, no irreversible changes of
transmittance were observed in present experiments.
Figure 19. Coefficient β of Ag:SLSG in dependence of laser intensity.
Figure 20. Coefficient β of Ag:SiO2 in dependence of laser intensity.

The reverse saturated absorption can be responsible for the decrease of negative nonlinear
absorption of Ag nanoparticles and it could be assume that in the case of picosecond pulses
the reverse saturated absorption starting to play an important role in the overall dynamics of
nonlinear optical transmittance of MNPs contained compounds, taking into account the
saturation of intermediate transitions responsible for saturated absorption.Thus, saturated
absorption in Ag:SLSG and Ag:SiO2 was dominated at small intensities and decreased with
the growth of intensity due to influence of competing effects, whereas the selfdefocusing at
low intensities was changed to self-focusing at high intensities. The possible mechanism of
the decrease of Im[χ(3)] is the influence of nonlinear optical processes with opposite
dependences on laser intensity, also such as two-photon absorption [122]. The wavelength
range corresponded to the interband transitions in Ag is located below 320 nm, so the two-
photon absorption connected with interband transitions can be involved in the case of 532 nm
radiation. The possibility of two-photon absorption due to interband transition of
photoexcited electrons was previously demonstrated for Ag particles [154]. The three-photon
absorption connected with interband transition for Ag nanoparticles was analysed in (Kyoung
et al., 1999). Thus, saturated absorption in Ag:SLSG and Ag:SiO2 was dominated at small
intensities and decreased with the growth of intensity due to influence of competing effects,
whereas the self-defocusing at low intensities was changed to self-focusing at high intensities.
ACKNOWLEDGMENTS
I wish to thank my partners and co-authors from different countries D. Hole,
P.D. Townsend, I.B. Khaibullin, V.I. Nuzhdin, V.F. Valeev, Yu.N. Osin, R.A. Ganeev,
A.I. Ryasnyanskiy, T. Usmanov, M.K. Kodirov, V.N. Popok, and U. Kreibig, Also, I grateful
to the Alexander von Humboldt Foundation and the DAAD in Germany, Austrian Scientific
Foundation in the frame of Lisa Meitner Fellowship and the Royal Society in UK for
financial support. This work was partly supported by the Ministry of Education and Science
of the Russian Federation (FTP “Scientific and scientific-pedagogical personnel of the
innovative Russia” No. 02.740.11.0779).
REFERENCES
[1] Zhang, J. Z. Optical properties and spectroscopy of nanomaterials; Wold Sci. Pub.:
London, 2009.
[2] Optical properties of nanostructured random media; Shalaev, V. M.; Ed,: Springer:
Berlin, 2002.
[3] Flytzanis, C.; Hache, F.; Klein, M. C.; Ricard D.; Rousignol P. Nonlinear optics in
composite materials; Elsevier Science: Amsterdam, 1991.
[4] Kreibig, U.; Vollmer, M. Optical properties of metal clusters; Springer: Berlin, 1995.
[5] Stepanov, A. L. In High-power and Femtosecond Lasers: Properties, Materials and
Applications; Barret, P.-H.; Palmer M.; Eds., NOVA Sci. Publ.: New York, 2009, pp.
27-70.
[6] Townsend P. T.; Chandler P. J.; Zhang, L. Optical effects of ion implantation;
Cambridge Univ. Press: Cambridge, 1994.
[7] Stepanov, A. L. In Metal-Polymer Nanocomposites; Nicolais, L.; Carotenuto, G.; Eds.;
John Wiley & Sons Publ: London, 2004; pp. 241-263.
[8] Gonella, F.; Mazzoldi, P. In Handbook of nanostructured materials and
nanotechnology; Nalwa, H. S.; Ed.; Academic Press: London, 2000.
[9] Stepanov, A. L. Ion-synthesis of metal nanoparticles and their optical properties;
NOVA Sci. Publ.: New York, 2011.
[10] Ricard, D.; Roussignol, P.; Flytzanis, C. Opt. Lett. 1985, 10, 511-513.
[11] Haglund Jr., R. F. In Handbook of optical properties. Vol. II. Optics of small particles,
interfaces, and surfaces; Hummel, R. F.; Wismann, P.; Eds.; CRC Press: London, 1997;
pp. 198-231.
[12] Haglund Jr., R. F.; Osbone, D. H.; Magruder III, R. H.; White, C. W.; Zuhr, R. A.;
Hole, D. E.; Townsend; P. D. Proc. Conf. Science and technology of atomically
engineered materials; Jena, P.; Khanna, S. N.; Rao B. K.; Eds.; World Sci.: Singapure,
1995; pp. 411-418.
[13] von Neumann, J. In Fundamentals of photonics, Saleh B. E. A.; Teich, M. C.; Eds.;
Wiley: New York, 2001; p. 856-903.
[14] Davenas, J.; Perez, A.; Thevenard, P.; Dupuy, C. H. S. Phys. Stat. Sol. A. 1973, 19,
679-686.
[15] Treilleux, M.; Thevenard, P.; Ghassagne, G.; Hobbs, L. H. Phys. Stat. Sol. A. 1978, 48,
425-430.
[16] Arnold, G. W. J. Appl. Phys. 1975, 46, 4466-4473.
[17] Arnold, G. W.; Borders, J. A. J. Appl. Phys. 1977, 48, 1488-1496.
[18] Mazzoldi, P.; Arnold, G. W.; Battaglin, G.; Bertoncello, R.; Gonella, F. Nucl. Instr.
Meth. Phys. Res. B. 1994, 91, 478-492.
[19] Mazzoldi, P.; Arnold, G. W.; Battaglin, G.; Gonella, F.; Haglund Jr., R. F. J. Nonlinear
Opt. Phys. Mater. 1996, 5, 285-230.
[20] Chakraborty, P. J. Mater. Sci. 1998, 33, 2235-2249.
[21] Stepanov, A.; Khaibullin, I. B. Rev. Adv. Mater. Sci. 2005, 9, 109-129.
[22] Meldrum, A.; Lopez, R.; Magruder III, R. H.; Boatner, L. A.; White, C. W. In Material
science with ion beam; arnes, H.; Ed.; Springer: Berlin, 2010; pp. 255-285.
[23] Stepanov, A.L. Rev. Adv. Mater. Sci. 2010, 26, 1-29.
[24] Ganeev, R. A. J. Opt. A.: Pure Appl. Opt. 2005, 7, 717-733.
[25] Ganeev, R. A.; Usmanov, T. Quant. Electr. 2007, 37, 605-622.
[26] Cattaruzza, E.; Gonella, F.; Mattei, G.; Mazzoldi, P.; Gatteschi, D.; Sangregorio, S.;
Falconieri, M.; Salvetti, G.; Battaglin, G. Appl. Phys. Lett. 1998, 73, 1176-1778.
[27] Falconieri, M.; Salvetti, G.; Cattarruzza, E.; Gonella, F.; Mattei, G.; Mazzoldi, P.;
Piovesan, M.; Battaglin, G.; Polloni, R. Appl. Phys. Lett. 1998, 73, 288-290.
[28] Cattaruzza, E.; Battaglin, G.; Gonella, F.; Polloni, R.; Mattei, G.; Maurizio, C.;
Mazzoldi, P.; Sada, C.; Montagna, M.; Tosello, C.; Ferrari, M. Phil. Mag. B. 2002, 82,
735-744.
[29] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Marques, C.; da Silva, R. C.; Alves,
E. Opt. Comm. 2005, 253, 205-213.
[30] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T.; Marques, C.; da Silva,
R. C., Alves, E. Opt. Spectr. 2006, 101, 615-622.
[31] Ryasnyanskiy, A. I. Nonlin. Opt. Quant. Opt. 2005, 33, 17-28.

[32] Plaksin, O.; Takeda, Y.; Amekura, H.; Kishimoto, N.; Plaksin, S. J. Appl. Phys. 2008,
103, 114302-1 - 114302-5.
[33] Ryasnyansky, A. I.; Palpant, B.; Debrus, S.; Khaibullin, R. I.; Stepanov, A. L. J. Opt.
Soc. Am. B. 2006, 23, 1348-1352.
[34] Takeda, Y.; Lee, C. G.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2002, 191, 422-
427.
[35] Takeda, Y.; Lee, C. G.; Bandourko, V. V.; Kishimoto, N. Proc. SPIE, 2002, 4628, 46-
54.
[36] Takeda, Y.; Bandourko, V. V.; Lee, C. G.; Kishimoto, N. Mater. Trans. 2002, 43,
1057-1061.
[37] Kishimoto, N.; Takeda, Y.; Umeda, N.; Okubo, N.; Faulkner, R.G. Nucl. Instr. Meth.
Phys. Res. B. 2003, 206, 643-638.
[38] Plaksin, O. A.; Takeda, Y.; Kono, K.; Umeda, N.; Fudamoto, Y.; Kishimoto, N. Mat.
Sci. Eng. B. 2005, 120, 84-87.
[39] Plaksin, O.A.; Kishimoto, N. Phys. Solid State, 2006, 48, 1933-1939.
[40] Kishimoto, N.; Takeda, Y.; Umeda, N.; Gritsyna, T.; Lee, C. G.; Saito, T. Nucl. Instr.
Meth. Phys. Res. B. 2000, 166-167, 840-844.
[41] Takeda, Y.; Umeda, N.; Gritsyna, V. T.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B.
2001, 175-177, 463-467.
[42] Becker, K.; Yang, L.; Haglund Jr., R. F.; Magruder III, R. H.; Weeks, R. A.; Zuhr, R.
A. Nucl. Instr. Meth. Phys. Res. B. 1991, 59-60, 1304-1307.
[43] Haglund Jr., R.F.; Magruder III, R.H.; Morgen, S.H.; Henderson, D.O.; Weller, R.A.;
Yang, L.; Zuhr, R. A. Nucl. Instr. Meth. Phys. Res. B. 1992, 65, 405-411.
[44] Haglund Jr., R. F.; Yang, L.; Magruder III, R. H.; Wittig, J. E.; Becker, K.; Zuhr, R. A.
Opt. Lett. 1993, 18, 373-375.
[45] Haglund Jr., R. F.; Yang, L.; Magruder III, R. H.; Wittig, C. W.; Zuhr, R. A.; Yang, L.;
Dorsinville, R.; Alfano, R. R. Nucl. Instr. Meth. Phys. Res. B. 1994, 91, 493-504.
[46] Haglund Jr., R. F. Mat. Sci. Eng. A. 1998, 253, 275-283.
[47] Magruder III, R. H.; Haglund Jr., R. F.; Yang, L.; Wittig, J. E.; Zuhr, R. A. J. Appl.
Phys. 1994, 76, 708-715.
[48] Yang, L.; Becker, K.; Smith, F. M.; Magruder III, R. H.; Haglund Jr., R. F.; Yang, L.;
Dorsinville, R.; Alfano, R. R.; Zuhr, R. A. J. Opt. Soc. Am. B. 1994, 11, 457-461.
[49] Yang, L.; Osbone, D. H.; Haglund Jr., R. F.; Magruder III, R. H.; Wittig, C. W.; Zuhr,
R.A.; Hosono, H. Appl. Phys. A. 1996, 62, 403-415.
[50] Ila, D.; Williams, E. K.; Sarkisov, S.; Smith, C. C.; Poker, D. B.; Hensley, D. K. Nucl.
Instr. Meth. Phys. Res. B. 1998, 141, 289-293.
[51] Sarkisov, S.; Williams, E. K.; Curley, M.; Ila, D.; Venkateswarlu, P.; Poker, D. B.;
Hensley, D. K. Nucl. Instr. Meth. Phys. Res. B. 1998, 141, 294-298.
[52] Takeda, Y.; Gritsyna, V.T.; Umeda, N.; Lee, C. G.; Kishimoto, N. Nucl. Instr. Meth.
Phys. Res. B. 1999, 148, 1029-1033.
[53] Takeda, Y.; Zhao, J. P.; Lee, C. G.; Gritsyna, V. T.; Kishimoto, N. Nucl. Instr. Meth.
Phys. Res. B. 2000, 166-167, 877-881.
[54] Olivares, J.; Requejo-Isidro, J.; del Coso, R.; de Nalda, R.; Solis, J.; Afonso, C. N.;
Stepanov, A. L.; Hole, D.; Townsend, P. D.; Naudon, A. J. Appl. Phys. 2001, 90, 1064-
1066.
[55] Takeda, Y.; Lee, C. G.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2002, 190, 797-
801.
[56] Takeda, Y.; Lu, J.; Plaksin, O. A.; Amekura, H.; Kono, K.; Kishimoto, N. Nucl. Instr.
Meth. Phys. Res. B. 2004, 219-220, 737-741.
[57] Takeda, Y.; Lu, J.; Okubo, N.; Plaksin, O. A.; Suga, T.; Kishimoto, N. Vacuum, 2004,
74, 717-721.
[58] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Phys. Stat. Sol. B.
2003, 238, R5-R7.
[59] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Phys. Solid State, 2004,
46, 351-356.
[60] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Quant. Electr. 2003,
33, 1081-1084.
2004, 241, R1-R4.
[62] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Phys. Solid State, 2003,
45, 1355-1359.
[63] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Kodirov, M. K.; Usmanov, T. Opt.
Spectr. 2003, 95, 967-975.
2004, 241, 935-944.
[65] Stepanov, A. L.; Ganeev, R.; Ryasnyanskiy, A. I.; Usmanov, T. Nucl. Instr. Meth. Phys.
Res. B. 2003, 206, 624-628.
[66] Takeda, Y.; Plaksin, O. A.; Kono, K.; Kishimoto, N. Surf. Coat.Technol. 2005, 196, 30-
33.
[67] Ren, F.; Jiang, C. Z.; Wang, Y. H.; Wang, Q. Q.; Wang, J. B. Nucl. Instr. Meth. Phys.
Res. B. 2006, 245, 427-430.
[68] Y.H. Wang, C.Z. Jiang, F. Ren, Q.Q. Wang, D.J. Chen D.J. Fu Physica E. 33 (2006)
444-248.
[69] Wang, Y. H.; Ren, F.; Wang, Q. Q.; Chen, D. J.; Fu, D. J.; Jiang, C. Z. Phys. Lett. A.
2006, 357, 364-368.
[70] Ghosh, B.; Chakraborty, P.; Mohapartra, S.; Kurian, P. A.; Vijayan, C.; Deshmukh, P.
C.; Mazzoldi, P. Mat. Lett. 2007, 61, 4512-4515.
[71] Ghosh, B.; Chakraborty, P.; Singh, B. P.; Kundu, T. Appl. Surf. Sci. 2009, 256, 389-
394.
[72] Torres-Torres, C.; Reyes-Esqueda, J. R.; Cheng-Wong, J. C.; Crespo-Sosa, A.;
Rodriguez-Fernandez, L.; Oliver, A. J. Appl. Phys. 2008, 104, 14306-1 -14306-5.
[73] Wang, Y. H.; Wang, Y. M.; Lu, J. D.; Ji, L. L.; Zang, R. G.; Wang, R. W. Physica B.
2009, 404, 4295-4298.
[74] Wang, Y. H.; Wang, Y. M.; Lu, J. D.; Ji, L. L.; Zang, R. G.; Wang, R. W. Opt. Comm.
2010, 283, 486-489.
[75] Wang, Y. H.; Wang, Y. M.; Han, C. J.; Lu, J. D.; Ji, L. L. Physica B 2010, 405, 2664-
2667.
[76] Takeda, Y.; Lu, J.; Plaksin, O. A.; Kono, K.; Amekura, H.; Kishimoto, N. Thin Solid
Films, 2004, 464-456, 483-486.
[77] Takeda, Y.; Plaksin, O. A.; Lu, J.; Kono, K.; Amekura, H.; Kishimoto, N. Nucl. Instr.
Meth. Phys. Res. B. 2006, 250, 372-376.
[78] Cetin, A.; Kibar, R.; Hatipoglu, M.; Karabulut, Y.; Can, N. Physica B. 405 (2010)
2323-2325.
[79] Stepanov, A. L.; Khaibullin, R. I.; Can, N.; Ganeev, R. A.; Ryasnyanski, A. I.; Buchal,
C.; Uysal, S. Tech. Phys. Lett. 2004, 30, 846-849.
[80] Ryasnyanskiy, A. I.; Palpant, B.; Debrus, S.; Ganeev, R.; Stepanov, A. L.; Can, N.;
Buchal, C.; Uysal, S. Appl. Opt. 2005, 44, 2839-2845.
[81] Ryasnyanskiy, A. I. J. Appl. Spect. 2005, 72, 712-715.
[82] Williams, E. K.; Ila, D.; Darwish, A.; Poker, D. B.; Sarkisov, S. S.; Curley, M. J.;
Wang, J.-C.; Svetchinkov, V. L.; Zandbergen, H. W. Nucl. Instr. Meth. Phys. Res. B.
1999, 148, 1074-1078.
[83] Sarkisov, S. S.; Curley, M. J.; Williams, E. K.; Ila, D.; Svetchinkov, V. L.; Zandbergen,
H. W.; Zykov, G. A.; Banks, C.; Wang, J.-C.; Poker, D. B.; Hensley, D. K. Nucl. Instr.
Meth. Phys. Res. B. 2000, 166-167, 750-757.
[84] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Opt. Quant. Electron.
2004, 36, 949-960.
[85] Stepanov, A. L. In Silver nanoparticles; Perez, D.P.; Ed.; In-tech: Vukovar, 2010; p. 93-
120.
[86] Joseph, B.; Suchand Sandeep, C. S.; Sekhar, B. R.; Mahapatra, D. P.; Philip, R. Nucl.
Instr. Meth. Phys. Res. B. 2007, 265, 631-636.
[87] Rangel-Roja, R.; McCarthy, J.; Bookey, H. T.; Kar, A. K.; Rodriguez-Fernandez, L.;
Cheang-Wong, J.-C.; Crespo-Soso, A.; Lopez-Suarez, A.; Oliver, A.; Rodriguez-
Iglesias, V.; Silva-Pereryra, H. G. Opt. Comm. 2009, 282, 1909-1912.
[88] Rangel-Roja, R.; Reyes-Esqueda, J. A.; Torres-Torres, C.; Oliver, A.; Rodriguez-
Fernandez, L.; Crespo-Soso, A.; Cheang-Wong, J. C.; McCarthy, J.; Bookey, H. T.;
Kar, A. K. In Silver nanoparticles, Perez, D.P.; Ed.; In-tech: Vukovar, 2010; p. 35-62.
[89] Wang, Y. H.; Peng, S. J.; Lu, J. D.; Wang, R. W.; Cheng Y. G.; Mao, Y. I. Vacuum,
2009, 83, 412-415.
[90] Takeda, Y.; Hioki, T.; Motohiro, T.; Noda, S. Appl. Phys. Lett. 1993, 63, 3420-3422.
[91] Takeda, Y.; Hioki, T.; Motohiro, T.; Noda, S.; Kurauchi, T. Nucl. Instr. Meth. Phys.
Res. B. 1994, 91, 515-519.
[92] Takeda, Y.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2003, 206, 620-623.
[93] White, C. W.; Thomas, D. K.; Hensley, D. K.; Zuhr, R. A.; McCallum, J. C.; Pogany,
A.; Haglund Jr., R. F.; Magruder III, R. H.; Yang, L. Nanostruct. Mat. 1993, 3, 447-
457.
[94] Stepanov, A. L.; Marques, C.; Alves, E.; da Silva, R. C.; Silva, M. R.; Ganeev, R.;
Ryasnyanskiy, A. I.; Usmanov, T. Tech. Phys. Lett. 2005, 31, 702-705.
[95] Stepanov, A. L.; Marques, C.; Alves, E.; da Silva, R. C.; Silva, M. R.; Ganeev, R.;
Ryasnyanskiy, A. I. Tech. Phys. 2006, 51, 1474-1481.
[96] Takeda, Y.; Plaksin, O. A.; Wang, H.; Kono, K.; Umeda, N.; Kishimoto, N. Opt. Rev.
2006, 13, 231-234.
[97] Takeda, Y.; Plaksin, O. A.; Wang, H.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B.
2007, 257, 47-50.
[98] Magruder III, R. H.; Yang, L.; Haglund Jr., R. F.; White, C. W.; Yang, L.; Dorsinville,
R.; Alfano, R. R. Appl. Phys. Lett. 1993, 62, 1730-1772.
[99] White, C. W.; Zhou, D. Z.; Budai, J. D.; Zhur, R. A.; Magruder III, R. H.; Osbone, D.H.
Mat. Res. Soc. Proc. 1994, 316, 499-507.
[100] Fukumi, K.; Chayahara, A.; Kadono, K.; Sakaguchi, T.; Horino, Y.; Miya, M.; Fujii,
K.; Hayakawa, J.; Satou, M. Jpn. J. Appl. Phys. 1991, 30, L742-L744.
[101] Fukumi, K.; Chayahara, A.; Kadono, K.; Sakaguchi, T.; Horino, Y.; Miya, M.; Fujii,
K.; Hayakawa, J.; Satou, M. J. Appl. Phys. 1994, 75, 3075-3080.
[102] Lepeshkin, N. N.; Kim, W.; Safonov, V. P.; Zhu, J. G.; Armstrong, R. L.; White, C. W.;
Zuhr, R. A.; Shalaev, V. M. J. Nonlin. Opt. Phys. Mat. 1999, 8, 191-210.
[103] Safonov, V. P.; Zhu, J. G.; Lepeshkin, N. N.; Armstrong, R. L.; Shalaev, V. M.; Ying,
Z. C.; White, C. W.; Zuhr, R. A. Proc. SPIE, 1999, 3788, 34-41.
[104] Takeda, Y.; Plaksin, O. A.; Kishimoto, N. Opt. Express, 2007, 10, 6010-6018.
[105] Torres-Torres, C.; Khomenko, A. V.; Cheang-Wong, J. C.; Rodriguez-Fernandez, L.;
Crespo-Soso, A.; Oliver, A. Opt. Express, 2007, 15, 9248-9253.
[106] Ghosh, B.; Chakraborty, P.; Sundaravel, B.; Vijayan, C. Nucl. Instr. Meth. Phys. Res. B.
2008, 266, 1356-1361.
[107] Wang, Y. H.; Lu, J. D.; Wang, R. W.; Peng, S. J.; Mao, Y. I.; Cheng, Y. G. Physica B.
2008, 403, 3399-3402.
[108] Wang, Y. H.; Lu, J. D.; Wang, R. W.; Mao, Y. I.; Cheng, Y. G. Vacuum, 2008, 82,
1220-1223.
[109] Battaglin, G.; Calvelli, P.; Cattaruzza, E.; Polloni, P.; Borsella, E.; Cesa, T.; Mazzoldi,
P. J. Opt. Soc. Am. B. 2000, 17, 213-218.
[110] Magruder III, R. H.; Osbone, D. H.; Zuhr, R. A. J. Non.-Cryst. Solids, 1994, 176, 299-
303.
[111] Wang, Y. H.; Jiang, C. Z.; Ren, F.; Wang, Q. Q.; Chen, D. J.; Fu, D. J. J. Mat. Sci.
2007, 42, 7294-7298.
[112] Wang, Y. H.; Jiang, C. Z.; Xiao, X. H.; Cheng, Y. G. Physica B 2008, 403, 2143-2147.
[113] Wang, Y. H.; Wang, Y. M.; Han, C. J.; Lu, J. D.; Ji, L. L.; Wang, R. W. Physica B.
2010, 405, 2848-2851.
[114] Wang, Y. H.; Wang, Y. M.; Han, C. J.; Lu, J. D.; Ji, L. L.; Wang, R. W. Vacuum, 2010,
85, 207-210.
[115] Cattaruzza, E.; Battaglin, G.; Gonella, F.; Calvelli, P.; Mattei, G.; Maurizio, C.;
Mazzoldi, P.; Padovani, S.; Polloni, R.; Sada, C.; Scremin, B. F.; D’Acapito, F.
Composites Sci. Technol. 2003, 68, 1203-1208.
[116] Cattaruzza, E.; Battaglin, G.; Gonella, F.; Calvelli, P.; Mattei, G.; Maurizio, C.;
Mazzoldi, P.; Polloni, R.; Scremin, B. F. Appl. Surf. Sci. 2005, 247, 390-395.
[117] Cesca, T.; Pellegrini, G.; Bello, V.; Scian, C.; Mazzoldi, P.; Calvelli, P.; Battaglin, G.;
Mattei, G. Nucl. Instr. Meth. Phys. Res. B. 2010, 268, 3227-3230.
[118] Magruder III, R. H.; Zuhr, R. A.; Osbone, D. H. Nucl. Instr. Meth. Phys. Res. B. 1995,
99, 590-593.
[119] Mie, G. Ann. Phys. 1908, 25, 377-420.
[120] Palpant B. In Non-Linear optical properties of matter; Papadopoulos, M. G.; Ed.;
Springer: Amsterdam, 2006; pp. 461-508.
[121] Sheik-Bahae, M.; Said, A. A.; van Stryland, E. W. Opt. Lett. 1989, 14, 955-957.
[122] Sheik-Bahae, M.; Said, A. A.; Hagan D. J.; van Stryland, E. W. IEEE J. Quan. Elect.
1990, 26, 760-769.
[123] Kwak, C. H.; Lee, Y. L.; Kim, S. G. J. Opt. Soc. Am. 1999, 16, 600-604.
[124] Stepanov, A. L.; Zhikharev, V. A.; Hole, D. E.; Townsend, P. D.; Khaibullin, I. B.
Nucl. Instr. Meth. Phys. Res. B. 2000, 166-167, 26-30.
[125] Reintjes, J. F.Nonlinear-optical parametrical processes in liquids and gases; Academic:

Orlando, 1984.
[126] Karpov, S. V.; Popov, A. K.; Slabko V. V. JETP Lett. 1997, 66, 106-111.
[127] Ganeev, R. A.; Ryasnyansky, A. I.; Kamalov, S. R.; Kodirov, M. K.; Usmanov, T. J.
Phys. D: Appl. Phys. 2001, 34, 56-61.
[128] Tutt, L. W.; Boggess, T. F. Prog. Quant. Electr. 1993, 17, 299-338.
[129] Shen, Y. R. The principles of nonlinear optics; Wiley: New York, 1989.
[130] Owyoung, A. IEEE J. Quant. Electr. 1973, 9, 1064-1069.
[131] Mehendale, S. C.; Mishra, S. R.; Bindra, K. S.; Laghate, M.; Dhami, T. S.; Rustagi, K.
C. Opt. Comm. 1997, 133, 273-272.
[132] Falconieri, M. J. Opt. A: Pure Appl. Opt. 1999, 1, 662-667.
[133] Battaglin, G.; Calvelli, P.; Cattaruzza, E.; Gonella, F.; Polloni, R.; Mattei G.; Mazzoldi,
P. Appl. Phys. Lett. 2001, 78, 3953-3955.
[134] Mizrahi, V.; DeLong, K. W.; Stegeman, G. I.; Saifi, M. A.; Andejco, M. J. Opt. Lett.
1989, 14, 1140-1142.
[135] Rangel-Rojo, R.; Kosa, T.; Hajto, E.; Ewen, P. J. S.; Owen, A. E.; Kar, A. K.; Wherrett,
B. S. Opt. Comm. 1994, 109, 145-150.
[136] Fribers, S. R.; Smith, P. W. IEEE J. Quant. Electr. 1987, 23, 2089-2096.
[137] Moran, M. J.; She, C. Y.; Carman, R. L. IEEE J. Quant. Electr. 1975, 11, 259-263.
[138] Xia, T.; Hagan, D. J.; Sheik-Behae, M.; van Stryland, E. W. Opt. Lett. 1994, 19, 317-
319.
[139] Ma, H.; Gomes, A. S. L.; de Araujo, C. B. Appl. Phys. Lett. 1991, 59, 2666-2668.
[140] Petrov, D. V.; Gomes, A. S. L.; de Araujo, C. B. Appl. Phys. Lett. 1994, 65, 1067-1069.
[141] Petrov, D. V.; Gomes, A. S. L.; de Araujo, C. B. Opt. Comm. 1996, 123, 637-641.
[142] Petrov, D. V. J. Opt. Soc. Am. 1996, 13, 1491-1498.
[143] Kawazoe, T.; Kawaguchi, H.; Inoue, J.; Haba, O.; Ueda, M. Opt. Comm. 1999, 160,
125-129.
[144] Stepanov, A. L. Rev. Adv. Mater. Sci. 2003, 4, 45-60.
[145] Martinelli, M.; Gomes, L.; Horowicz, R. J. Appl. Opt. 2000, 39, 6193-6196.
[146] Ganeev, R. A.; Ryasniansy, A. I. Phys. Stat. Sol. A. 2005, 202, 120-125.
[147] Stepanov, A. L.; Popok, V. N. Surf. Sci. 2004, 566-568, 1250-1254.
[148] Stepanov, A. L.; Kreibig, U.; Hole, D. E.; Khaibullin, R. I.; Khaibullin, I. B.; Popok,
V.N. Nucl. Instr. Meth. Phys. Res. B. 2001, 178, 120-125.
[149] Karpov, S. V.; Popov, F. K.; Slabko, V. V. Izv. Akad. Nauk SSSR Ser. Fiz. 1996, 60,
42-49.
[150] Hamanaka, Y.; Hayashi, N.; Nakamura, A.; Omi, S. J. Luminesc. 2000, 87-89, 859-861.
[151] Link, S.; Burda, C.; Mohamed, M. B.; Nikoobakht, B.; El-Sayed, M. A. J. Phys. Che. A.
1999, 103, 1165-1170.
[152] Mafune, F.; Kohno, J.-Y.; Takeds, Y.; Kondow, T. J. Phys. Chem. B. 2002, 106, 7576-
7577.
[153] Osbone Jr., D. H.; Haglund Jr., R. F.; Gonella, F.; Garrido, F. Appl. Phys. B. 1998, 66,
517-521.
[154] Kyoung, M.; Lee, M.; Opt. Comm. 1999, 171, 145-148.
Chapter 3
SELF-ORGANIZATION OF THE NANOCRYSTALLINE

STRUCTURE AND RADIATION RESISTANCE OF
STRUCTURAL MATERIALS
V. P. Kolotushkin* and A. A. Parfenov

JSC ”VNIINM ” A.A. Bochvar,
Moscow, Russia
ABSTRACT
Radiation resistance of structural materials depends on the ability of their structure to
reduce the rate of accumulation of secondary radiation defects. The introduction of
interstitial or substitutional atoms into the matrix, increasing the density of dislocations
and other external factors, can accelerate the recombination of primary point defects.
We have studied the use of internal structural factors in recombination accelerating
of vacancies and interstitials. The principal difference between the two approaches lies in
the next. In the proposed metastable alloys the traps of point defects forms the matrix
itself but not embedded in a matrix artificial species. The crystal lattice distortions arising
in synergistic effect of neutron irradiation and short-range ordering become the traps of
vacancies and interstitials. Distortions capture vacancies and interstitials, thus occurs a
self-organization of the crystal structure of material.
1. INTRODUCTION
Structural materials of reactor cores are simultaneously impacted the neutron radiation,
high temperatures, and the temperature gradient across the thickness of products, mechanical
stress and chemical interaction with the environment. Under these conditions the materials
must provide the strength of the reactor equipment units, the stability of their geometric
shapes and sizes throughout the campaign [1]. The most important damaging factor is the
neutron irradiation. When impacted into the metal atom a neutron with energy of 1 MeV can
*
Email: kolotush@bochvar.ru
120 V. P. Kolotushkin and A. A. Parfenov
transfer energy to 50 keV sufficient to displace the atom from the lattice site (20-50 eV). The
destruction of the crystal lattice and the mixing of atoms in the displacement cascade alter the
qualitative structure of the metal. The size of a cascade is ∼ 10 nm. In this region is released
an energy of primary knock-on atom. Although most of this energy is released as heat in the
process of Frenkel pair’s recombination, much of them remain creating a microstructure
changes that lead to changes in the phase diagram [2].
Typical values of activation energy of migration of vacancies and interstitials are
respectively EmV = 1 eV and Emi = 0.4 eV. At temperatures around 800 K both types of
defects are mobile. Due to the supersaturating of lattice vacancies and interstitials there are
the clusters of these defects. Accumulation of vacancies leads to the formation of vacancy
pores as well as clusters of interstitial atoms form an additional extra planes bounded by edge
dislocations. These secondary radiation defects (clusters) determine the change in material
properties.
Behavior of point defects imposed into the metal during irradiation depends mainly on
the temperature and material structure. In this case unlike the case of thermal diffusion
vacancies and interstitials are introduced into the material in equal amounts during irradiation.
It is clear that depending on the temperature the effect of irradiation will be different. The low
temperature irradiation can freeze almost all input defects which in subsequent annealing start
migrating and interact with each other and with the available material sinks.
Analysis of experiments shows that due much higher mobility the interstitial atoms are
quickly assembled into clusters and form dislocation loops which rather rapidly grow to
noticeable size in process of irradiation. The formation of vacancy clusters and loops runs
more slowly. This process is temperature dependent; usually the formation of vacancy-type
defects with other things being equal occurs at higher temperatures and these defects are
smaller than the defects of interstitial type.
In order to maintain a stable structure and high mechanical characteristics of materials it
is necessary to create the structure conditions for reducing the rate of accumulation of
secondary radiation defects (dislocation loops, vacancy pores, excess phases, etc.).
Accumulation of secondary radiation defects is determined by the rate of appearance and
recombination of vacancies and interstitials [3]. The morphology of the multiphase structure
under irradiation, ultimately, determined counteraction of dissolution in the displacements
cascades and the phase formation due to freely migrating radiation point defects [4].
Investigations show that the interstitial or substitution atoms doping of austenitic steels
and alloys accelerates the recombination of radiation point defects [5]. On the other hand it
has been found that in the number of transition metal alloys for the increasing of the radiation
resistance it is need not stabilize the structure by means of certain doping, but on the contrary,
to create an unstable, metastable structure, prone to the formation of short-range order [6].
Such alloys showed the functional properties exceeding the analogues properties [7]. In these
alloys at the stage of short-range order nucleation occur crystal lattice distortions, which are
the traps for the vacancies and interstitials and accelerate their recombination [8]. It was also
found that formation of the cluster sub lattice of short-range order with the period ≤ 5 nm in
the solid solution during neutron irradiation is the most effective mechanism for the enhance
of radiation resistance of alloys at temperatures of 573-623 K [9].
Thus on improving the structure and mechanical properties of materials under neutron
irradiation as follows from [3, 10] affects the no equilibrium metastable character of alloys
Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 121
original structure. Studies of the metastable alloys of nickel - chromium basis showed
extremely high radiation resistance of Ni-42Cr-1Mo alloys. Such alloys are not susceptible to
radiation swelling; changes of their mechanical properties are minimal [11]. These features
are caused by the fact that during the formation of short-range order in their structure arise
domains of tension and compression [8], which are lattice distortions and act as centers of
attraction for the vacancies or interstitials, depending on the sign of distortion.
The analysis shows that the reactor structural materials, having transitional from the
ordering to the bundle structure, with near-zero enthalpy of mixing, can be developed on the
basis of transition metal alloys for a number of systems: Fe-Cr, Ni-Cr, Ni-V, Ni-Cr-V, V-Ti,
and V-Ti-Cr etc. Working temperature of alloys of Ni-Cr can be temperature ≤ 623 K, for
alloys of the Fe-Cr ≤ 823 K, for alloys V-Ti-Cr ≤ 1023 K, respectively.
Despite the huge number of works devoted to the physics of radiation damage and the
explaining of the behavior of structural materials under neutron irradiation, a complete
understanding of the nature of radiation damage, as well as the mechanisms and the ways of
its reducing does not exist. This makes it impossible to effectively decide the tasks of reactor
material science. However, lately there have been data that allow us to hope that this situation
can be corrected with the appropriate formulation of tasks. Such a problem is the
establishment of the stability and metastability of materials interrelation. Changes in the
structure of metastable alloys during irradiation is directed toward stability, but this change
stops without a phase transition at the stage of formation of short range order nanodomains in
size ∼ 2.5 nm [9].
It is known that the nanodomains (clusters) represent the intermediate link between
elementary particles (atoms and molecules) and bulk solids. Due to the discrete structure of
energy levels and a large value of the surface ratio to a volume the properties of clusters differ
from the properties of individual atoms and the properties of bulk substance. Clusters with the
number of particles N ≥ 102 represent the nanoparticles [12]. During irradiation of
nanoobjects as well as coarse-grained materials are formed cascades of atomic displacements,
i.e. are formed as the single vacancies and interstitials as their complexes in the form of loops
and vacancy nanopores. If the size of nanoobjects is comparable with the diffusion way of
defects to sinks we can expect a higher radiation resistance of nanomaterials in comparison
with their coarse counterparts that actually observed in most studies [13].
The exceptional interest that represents the formation of short-range order nanodomains,
stems from the fact that the difference in volume and the electronic subsystems of the
component atoms creates during irradiation the ordered static distortions and dimensional
effect whose value is determined by the degree of short-range ordering and can change not
only the mobility of vacancies and interstitials but also the mechanism of their annihilation.
The development of approaches to the creation of radiation-resistant nanocrystalline
materials is a promising problem of metal science. It will allow creating a new class of
materials. Such materials will have a neutron irradiation stable structure and properties and
elevated service life. This paper is devoted to the development and detailing of the
phenomenological model of self-organization of the nanocrystalline structure ensuring the
stability of properties of structural materials of nuclear power plants.
2. EXPERIMENTAL PROCEDURE
In this paper we study the structure, composition and properties of steels and alloys based
on iron and nickel-based alloys with chromium and molybdenum in the states before and after
neutron irradiation (electrons).
To study the dependence of radiation damage of austenitic steel on the parameters of
niobium carbonitrides the samples have been prepared in the form of rings 10 mm high for
structural studies and 2.5 mm for mechanical testing. The samples were annealed in vacuum
horizontal furnace at 1300°C, 1 h. Extent of deformation of the samples was about 67 %. The
deformed specimens were subjected to recrystallization annealing at temperatures of 800-
1250°C for 1 h and additional annealing at 680°C for 2 h. After the annealing the containers
with the samples was cooled in water. Then the samples were irradiated in a reactor «MIR»
with neutrons up to ~ 1.5 dpa at ∼ 330°C.
In order to calculate the concentration of the niobium carbonitrides the particles were
divided by size into 6 groups (from the < 50 nm to ~ 300 nm). In each size group was
determined the number of particles Ki. Concentration of particles (the parameters of the
dislocation loops are calculated the same way) related to a given size group was determined
by the formula
ρi=[КiМ2 ]/[S(t + di)], where M - the picture increase, equal to the product of instrumental
increase the photographic, S - area of the image, on which were count the particles, t -
thickness of the foil, di - size of particles in size group. The total concentration of particles
was determined as the sum of the particle concentrations in all size groups ρ=Σρi.
The average particle size was calculated using the expression: (d = (Σdi ρi)/ρ. The volume
fractions of excess phase particles of each size group were as follows: (ΔV/V)i = 4/3πri3 ρi 100
% = ~ 0,52 d3ρi 100 %. The total volume fraction of particles of excess phase equals the sum
of volume fractions of particles of all size groups ΔV/V=Σ(ΔV/V)i. From here was calculated
amount of the niobium, carbon and nitrogen as part of the niobium carbonitrides: α = (4
ΔV)/Vяч A, β = (2 ΔV)/Vяч A. Here α and β - volume fractions respectively of the niobium and
carbon (nitrogen), ΔV - volume of particles Nb (CN) in 1 m3, Vяч - unit cell volume of Nb
(CN), equal to 0.087366 nm3, A - number of atoms in 1 m3 of austenite, which equals
8,65х1028м-3.
The study of structural phase changes in Ni-Cr alloys was carried out on experimental
nonstoichiometric nickel alloys with chromium 32-47 wt% containing additional ~ 1.3 wt%
molybdenum. Experimental samples were manufactured from metal open-induction melting.
Ingots weighing 10 kg were reformed into billets of thickness 40 mm followed by hot rolling
to a thickness of 5 mm at 1100 - 1250°C. Hot-rolled plates were subjected to cold rolling to a
thickness of 2 mm. From these sheets were produced the specimens for testing and research.
The starting processing of the samples of alloys Ni-Cr-Mo was annealing in an argon
atmosphere at temperatures from 1050 to 1220°C for 30 min to obtain a homogeneous solid
solution. Annealed specimens were quenched in water.
Samples of steel of type Fe-18Cr-20Ni and some of the samples of the alloy Fe-20Cr-
40Ni-5Mo-Nb were irradiated with neutrons in the reactor 27-BM.
Other steels and alloys based on iron were irradiated in the reactor BOR-60 with neutron
dose of 10 dpa.
In BOR-60 were also irradiated specimens of the alloy Ni-42Cr-1Mo with a diameter of
working part 3 mm and 15 mm long and the ring specimens of the alloy Ni-47Cr-1Mo. At the
bottom of the ampoules the temperature was equal to the temperature of sodium at the reactor
inlet. With the rise of the sodium temperature increased, reaching 350º C in the middle of the
ampoule in height. Alloys were exposed to ~ 32 dpa.
As the objects for electron microscopic studies were used the disks diameter of 3 mm,
obtained of foil, rings, and of tensile samples.
Major investigations of the material microstructure were carried out under an electron
microscope EM-301. Thinning of the samples was carried out in installation of jet electro
polishing "Struers" in solution of 4-10 % vol. perchloric acid and 90-96 % vol. icy acetic acid
at ~ -10°C and a voltage of 65 V.
The diffractograms were recorded on a DRON-4, on the copper Cu Kα radiation using a
pyrographite crystal - monochromator. The shooting mode is "on points", the time is 10 s to a
point, step 0.05° of 2θ. The samples of the size 15x8x2 mm were subjected to electrochemical
polishing in a solution of 60 % phosphoric acid and 40 % glycerol to remove the surface layer
of 10-20 microns.
Profile analysis of reflections was performed to estimate the physical broadening of the
reflections of structural imperfections in the phases. In order to determine the hardware
profile of the diffractometer the standard sample of powder monocrystal Ge were used for the
measurements.
The measurements of the density alloys were performed by hydrostatic weighing in water
with preliminary evacuation of air, thermostatic, and after adjusting for buoyancy force of the
suspension and the temperature correction of the water density. The total error in determining
of the density is ± 0.01 g/cm3.
3. EXPERIMENTAL RESULTS
3.1. Influence of Carbide-Forming Elements on the Formation of Secondary
Radiation Defects in the Steels and Alloys under Neutron Irradiation up to
~10 dpa
In order that a structural reactor material maintained its performance it is necessary that
the amount accumulated in the structure of radiation defects did not exceed the critical value
at which the change in the shape of the material becomes more than acceptable, or there is
destruction. It means that it is necessary in the initial material to create non-equilibrium
structure in which the accumulated during neutron irradiation the vacancies and interstitial
atoms are forced to recombine. There are a number of different mechanisms that provide such
an opportunity. First we estimate the dependence of the formation of point radiation defects
complexes from the state of the metal solid solution, which is due to the dissolution of the
niobium carbonitrides enriched in the process of initial thermomechanical treatments with the
interstitial atom.
3.1.1. Features of Radiation Damage of Austenitic Steel, Depending from the

Thermomechanical Treatment at a Dose of Radiation Damage ~1.5 dpa
The standard treatment of steels and alloys as the structural reactor materials involves the
processes of cold deformation and heat treatments. The purpose of the final annealing is to
create a material structure with a certain grain size and excess phases. The atoms, which
create an excess phase in the present case niobium carbonitrides, may be dissolved into
matrix or incorporated into large or small particles. Depending on the position of interstitial
atoms, their influence on the irradiated with neutrons material will vary. Investigation of the
structure of Fe-16Cr-15Ni-3Mo-Nb-0.021C steel (Table 1) was performed before and after
irradiation in the reactor «MIR» with neutron dose ∼ 1.5 dpa at ∼330ºС.
Table 1. Chemical composition of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C in wt%
C Si Mn Cr Ni Mo Nb N Fe Al
0.021 0.080 0.79 16.35 15.30 2.67 0.39 0.010 осн. 0.03
The content of carbon and nitrogen in the solid solution was changed as follows: particles
of Nb (CN) were dissolved in the matrix by homogenizing annealing at 1300°C for 1 h. The
samples were then deformed at room temperature for 67 % (Fig. 1). Cold deformation
increased the dislocation density to ≤ 1x1016 m-2, formed multiple slip planes and micro
twins. After deformation, specimens were subjected to recrystallization annealing at
temperatures 800 - 1250°С.
Figure 1. Structure of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after cold deformation (the deformation
ratio is 67 %).
With increasing the temperature of recrystallization annealing the number of remaining in

solid solution C and N atoms was increased, and after annealing at 1250°C almost all the
atoms of Nb, C and N were in the solid solution. The lattice period of solid solution as the
result of raising the temperature of recrystallization annealing and the amount of carbon and
nitrogen in the matrix increased from 0.35943 to 0.35949 nm.
The study showed that during the recrystallization annealing at temperatures 800-900ºC
the largest number of the niobium carbonitrides was formed. A maximal concentration of
particles Nb (CN) has been found after annealing at 800ºC (Fig. 2). In structure of these
samples along with recrystallized grains are preserved and deformed grains with a high
concentration of particles Nb (CN). In the recrystallized grains behind the front
recrystallization the particle size and concentration are, respectively, ~ 7 nm and ~ 2х1021 m-3.
In the deformed grains are allocated the fine particles Nb (CN) of a higher concentration
(average particle size of ~ 3 nm, the concentration ~4х1021 m-3). The volume fractions of
particles of Nb (CN) are, respectively, 0.05 and 0.005 % in the recrystallized and deformed
regions.
It follows that the passage of the front recrystallization leads to a more intensive release
of particles Nb (CN) from the solid solution and the greater its purification by carbon,
nitrogen and niobium.
Figure 2. Particles Nb (CN) in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after recrystallization annealing

at 800°C.
Dispersed particles of the niobium carbonitrides after recrystallization annealing at 800ºC

are located mainly on the footsteps of the slip planes of the deformed grains (Fig. 2). Chains
of the niobium carbonitrides often pass through the boundary of adjacent grains. Similar
processes occurred at temperatures of 850 and 900ºC. Rising of recrystallization annealing
temperature to 1000ºC and above led to a decrease in the number of particles of Nb (CN) and
the enlargement (Fig. 3). It should be noted that the distribution of precipitated particles of
Nb (CN) sufficiently no uniform, for example, after recrystallization annealing at 1000° C
particles are arranged with an interval from ∼ 30 to ∼ 300 nm.
Depletion of the solid solution of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C of the interstitial
atoms during annealing at 800 and 1000°C occurs in different ways. At 800° C the solubility
of the atoms Nb, C and N into the recrystallization front boundary is higher than in the
matrix, so most of the dissolved in the matrix atoms Nb, C and N swept out the
recrystallization front. On the boundary of the front there is an accumulation of atoms. High
diffusion mobility in the bulk of the moving front recrystallization boundary promotes the
nucleation and growth of Nb (CN). Growing particles inhibit the movement of the front of
recrystallization, but upon reaching a certain critical particle size of Nb (CN) curved
boundary of recrystallization front separates from them (Fig. 2). Behind the boundary
remains depleted on the Nb, C and N matrix, which are interspersed with small and large
particles of Nb (CN).
Figure 3. Particles Nb (CN) in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after recrystallization annealing

at 1000°C.
When the annealing temperature increases, the solubility of Nb, C and N in solid solution
also increases. Therefore, at 1000°C much of the interstitial atoms are not enjoys the front of
the recrystallization, but remains in solid solution. Therefore, an additional annealing at
680°C, 2 h following the recrystallization annealing at 1000°C, even more clean matrix,
binding the atoms of Nb, C and N in the smallest particles of Nb (CN).
Due to differences in the volume fraction of particles of Nb (CN) in the original samples
and the corresponding difference in the enrichment of solid solution of C and N atoms under
neutron irradiation the accumulation of radiation defects in the samples of steel Fe-16Cr-
15Ni-3Mo-Nb-0.021C differed. Irradiation at ∼ 330°C led to the formation in the solid
solution mainly of prismatic dislocation loops (Fig. 4) and, in the some states, vacancy pores.
The distribution of dislocation loops in the matrix is fragmented, apparently in accordance
with inhomogeneity of chemical composition and distribution in the matrix of C and N atoms
and particles Nb (CN). In the various sample grains concentration of loops sometimes
differed by 2-3 times. The size of the loops varies from 1 to 50 nm. The main part of
dislocation loops has a size of less than 10 nm.
Figure 4. Dislocation loops in irradiated alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C.
On the histogram of the dislocation loops distribution in size in irradiated samples of Fe-
16Cr-15Ni-3Mo-Nb-0.021C steel is clearly seen that the temperature increasing of
recrystallization annealing entails an increase in the number of loops (Fig. 5). It is caused by
the increasing an enrichment of solid solution with carbon and nitrogen atoms, which poison
the dislocation loops slowing their growth. Preferential absorption of interstitials by
dislocation loops decreases, respectively, decreasing the growth rate of loops.
Figure 5. Dislocation loop size distribution in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C irradiated

at ∼ 330°C.
The sharp difference in the concentration of dislocation loops in the samples after
recrystallization annealing and the samples after additional annealing at 680°C is formed
mainly due to the dislocation loops with the size of ≤ 10 nm. The concentration of such loops
in the samples with additional annealing is much lower. The difference in the concentration of
larger loops is less significant. In the Fig. s is clearly seen that in the samples not annealed at
680°C (Fig. 6a), dislocation loops are smaller, and their concentration is accordingly higher
than in samples with an additional annealing (Fig. 6b). Thus, additional purification of the
matrix from carbon and nitrogen reduces the possibility of poisoning of dislocation loops and
promotes their growth in the process of neutron irradiation at ∼ 330ºC.
Figure 6. Dislocation loops in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C: a) irradiation following the

recrystallization annealing 1000°C, b) irradiation following the recrystallization annealing 1000°C plus
an additional annealing 680°C.
With the release from the solid solution of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C the
niobium carbonitrides particles is linked another mechanism of reduction the radiation
damage. Particles Nb (CN) create in the lattice during separating from the solid solution the
zones of structural distortions due to lattice period mismatch of the phase and of the matrix.
In relation to point defects such distortions in the initial period of Nb (CN) particle formation
may be the regions of compression or tension, which can serve as traps for vacancies or
interstitials. Fixing of point defects in the neighborhood of distortion zones accelerates their
recombination. As a consequence, the growth of dislocation loops and the formation of
vacancy pores slow. Effectiveness of the latter mechanism is clearly visible when comparing
the concentration of dislocation loops in samples of 1000°C and 1000°C +680°C (Fig. s 5 and
6).
In the structure of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C samples recrystallized at 800 -
950°C and additionally annealed at 680°C, after irradiation were found the vacancy pores
(Fig. 7). The pores are distributed in the matrix unevenly like the dislocation loops. The pore
size does not exceed ∼ 10 nm; the total relative swelling was less than 0.02 %.
Figure 7. Vacancy pores in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C: a) irradiation following the

recrystallization annealing 850°C plus an additional annealing 680°C, b) irradiation following the
recrystallization annealing 800°C plus an additional annealing 680°C.
The analysis shows that the formation of vacancy pores in the steel Fe-16Cr-15Ni-3Mo-
Nb-0.021C samples correlated with depletion of the original solid solution the atoms Nb, C
and N. For example, in the structure of the sample after recrystallization annealing at 800°C
plus an additional annealing at 680°C vacancy pores were found only in areas with the
recrystallized structure, depleted the atoms Nb, C and N. In the deformed grain the pores are
not revealed. Thus, the experiments show that depletion of the matrix with carbon nitrogen
and niobium during the passage of the front recrystallization results in the growth of
dislocation loops and reducing their concentration as well as the appearance of vacancy pores.
Taking into account that the degree of solid solution depletion with carbon, nitrogen and
niobium after recrystallization annealing at 800 and 1000°C is different, and the neutron
irradiation was conducted under the same conditions it may be concluded: decrease in the
amount of carbon and nitrogen in solid solution increases the preferential absorption of
interstitials by dislocation loops. The confirmation of this was found in specimens after
recrystallization annealing at 1000°C, plus an additional annealing 680°C. But there is
appears to be a certain critical concentration of carbon and nitrogen in solid solution. It is
created by recrystallization annealing at 800-850°C plus an additional annealing 680°C. At
the lower concentration than critical the dislocation loops absorb a higher proportion of
interstitials. As a result, the matrix sate by vacancies, the rate of recombination of point
defects is reduced, and vacancy swelling begins.
These experimental results underscore the importance of considering the content of
interstitial impurities in the solid solution of austenitic steels, and ensuring uniformity of their
structure-phase state.
3.1.2. Effect of Interstitial Atoms on the Accumulation of Radiation Defects in Steels

and Alloys Under Neutron Irradiation to 10 dpa
Described in section 3.1.1 results have shown a qualitative dependence of structure
changes of Fe-16Cr-15Ni-3Mo-Nb-0.021C steel after neutron irradiation at ~ 330°C from the
initial processing and content in solid solution of atoms niobium, carbon and nitrogen. In the
present section the quantitative evaluation of the influence of carbide-forming elements in
solid solution of iron-based steels and alloys (Table 2) on radiation damage of materials under
neutron irradiation of higher damage dose is conducted.
Table 2. Chemical composition of materials studied in wt%
Materials C Si Mn Cr Ni Mo Nb N
Fe-16Cr-15Ni-3Mo-Nb-
0.020 0.08 0.94 16.99 15.45 2.73 0.37 0.010
0.020C
Fe-16Cr-15Ni-3Mo-Nb-
0.026 0.31 0.51 16.00 14.97 2.68 0.39 0.040
0.026C
Fe-20Cr-25Ni-Nb 0.013 0.05 1.48 20.1 24.60 - 0.72 0.008
Fe-20Cr-25Ni-Nb-Si 0.012 0.92 1.80 20.1 24.80 - 0.79 0.008
Fe-20Cr-40Ni-5Mo-Nb 0.014 0.09 1.68 19.80 40.80 4.73 0.57 0.020
Initial state of material structure changed during recrystallization annealing (Table 3).
The volume fraction of particles of excess phase varied in accordance with the final heat
treatment. With increasing annealing temperature, as seen from the table, the number of
atoms of carbide-forming elements in solid solution grows, and the volume fraction of
niobium carbonitrides is reduced. A higher content of carbon and nitrogen in the matrix
corresponds to annealing at higher temperature.
Table 3. Distribution of Nb, C and N in the structure of alloys in the initial state
Operation of Parameters of the niobium The content of

recrystallizat carbonitrides elements in the matrix
Materials ion annealing in wt%
Number Size Volume Nb C+N
density (m-3) (nm) fraction,
%
Fe-16Cr-15Ni- 800°С, 1 ч 3х1020 20 0.15 0.17 0.012
3Mo-Nb- 900°С, 30’ 1х1021 10 0.1 0.29 0.018
0.020C 1200°С,1 ч - - <0.01 0.37 0.030
Fe-16Cr-15Ni- 950°С, 30’ 1х1021 180 0.43 0.09 0.010
3Mo-Nb-
0.026C
Fe-20Cr-25Ni- 1000°С, 30’ 2х1018 150 0.45 0.34 <0.010
Nb
Fe-20Cr-25Ni- 1000°С, 30’ ≤1х1019 40 0.05 0.70 0.015
Nb-Si
Fe-20Cr-40Ni- 800°С, 1 ч 2х1019 60 0.20 0.34 0.010
5Mo-Nb 1000°С, 1 ч 1х1018 30 0.01 0.54 0.032
The samples of steels and alloys were irradiated in the BOR-60 reactor with neutrons up
to ~ 10 dpa at ∼ 350°C. In the process of irradiation the phase composition of steels and
alloys has not changed. The results of determining the parameters of secondary radiation
defects are shown in Table 4. These results show a significant effect of changing the quantity
of carbide-forming elements in the solid solution: of niobium, carbon and nitrogen on the
recombination of point radiation defects. In the structure of materials under neutron
irradiation were formed, as a rule, the dislocation loops. In some specimens in addition to
dislocation loops have appeared and the vacancy voids. Dislocation loops were mostly perfect
prismatic loops of embedded type. In specimens of steels and alloys with higher content in
solid solution of atoms Nb, C and N the concentration of dislocation loops was greater and
the average size of loops is less.
Table 4. Parameters of secondary radiation defects in the alloys after irradiation in

BOR-60 reactor with neutrons up to ~ 10 dpa at 350°C
Annealing Parameters of the vacancy Parameters of

temperature, °C pores the dislocation
Materials / Contents (C+N) loops
in the matrix in ρ (1021 d Swelling, ρ d (nm)
wt% m-3) (nm) % (1021
м-3)
Fe-16Cr-15Ni- 800 / 0.012 - - - 12 20
3Mo-Nb- 900 / 0.018 - - - 15 15
0.020C 1200 / 0.030 - - - 20 10
Fe-16Cr-15Ni- 950 / 0.010 3 10 0.20 4 40
3Mo-Nb-
0.026C
Fe-20Cr-25Ni- 1000 / <0.010 0,3 13 0.04 4 30
Nb
Fe-20Cr-25Ni- 1000 / 0.015 - - - 10 20
Nb-Si
Fe-20Cr-40Ni- 800 / 0.010 3 9 0.10 9 30
5Mo-Nb 1000 / 0.032 - - - 30 8
In the samples of Fe-16Cr-15Ni-3Mo-Nb-0.020C steel the temperature raise of

recrystallization annealing increases the amount of niobium, carbon and nitrogen in the
matrix (Table 3). After neutron irradiation, as seen from Table 4, in accordance with the
enrichment of solid solution with atoms of Nb, C and N the concentration of dislocation loops
increases, and their average size decreases.
On the structure and phase composition of steel Fe-16Cr-15Ni-3Mo-Nb-0.026C of
electroslag remelting in the initial state appears to be influenced the peculiarities of its
creation that is the composition (Table 2), the smelting and the processing. Samples were
subjected to recrystallization annealing at a lower temperature of 950°C, compared with the
standard annealing temperature of 1050°C. As a result of this annealing, niobium, carbon and
nitrogen were significantly linked in the particles of niobium carbonitrides (Fig. 8a). In this
case, the total content of carbon and nitrogen in solid solution was decreased to the level of
0.01 wt%. Apparently due to the fact that during exposure in the depleted by interstitial
impurities matrix the interstitials mainly went to major (≥ 40 nm) dislocation loops, in the
solid solution formed an excess of vacancies, which formed the vacancy pores (Fig. 8b).
Figure 8. Structure of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.026C: a) initial state, b) irradiation to ∼10 dpa
at 350°C.
In the samples of steel Fe-20Cr-25Ni-Nb with a silicon content of 0.05 wt% in the
process of recrystallization annealing of the initial samples the carbide-forming elements of
niobium, carbon and nitrogen were mostly linked in the particles of niobium carbonitrides Nb
(CN) (Fig. 9a). Solid solution of these samples was depleted on carbon and nitrogen to
<0.010 wt%. Therefore under neutron irradiation to 10 dpa in clean from introduction
impurities solid solution a separate vacancy pores were formed (Fig. 9c).
In samples of steel Fe-20Cr-25Ni-Nb (Fig. 9b) which had increased silicon content
(Table 2), the solid solution after the recrystallization annealing was enriched in carbon and
nitrogen resulting from the substitution these elements with silicon at the grain boundaries
and in solid solution. Enrichment of solid solution on carbon and nitrogen (0.015 wt%)
probably contributed to the increasing the recombination rate of vacancies and interstitials
and the nucleation of vacancy pores has not been detected (Fig. 9d).
Recrystallization annealing of the alloy Fe-20Cr-40Ni-5Mo-Nb at 800º C for 1 h (Fig.
10a) caused extensive appearance of carbonitrides of niobium and led to the depletion of the
solid solution on carbon and nitrogen. Subsequent neutron irradiation created in the pure on
introduction impurities the solid solution vacancy pores and large dislocation loops (Fig. 10).
Their emergence and rapid growth are due to a decrease in the rate of recombination of point
defects in the equilibrium matrix.
The temperature rise of recrystallization annealing of the alloy Fe-20Cr-40Ni-5Mo-Nb up
to 1000ºC (Fig. 10b) led to a more than threefold (0.032 wt%) enrichment of the matrix on
carbon and nitrogen. As a result the neutron irradiation increased the concentration of smaller
dislocation loops. At the same time the rate of recombination of point defects on the
equilibrium distortions of the solid solution increased, and the vacancy voids during
irradiation were not revealed (Fig. 10d).
Figure 9. Structure of the alloy Fe-20Cr-25Ni-Nb: a, b) initial state: melting with 0,05 and 0,92 % Si,
respectively; c, d) irradiation of 10 dpa at ~ 350 ° C: melting with 0,05 and 0,92 % Si, respectively.
Moreover all the chromium-nickel steels and alloys behave practically identically. In all
materials there is an accumulation of Frenkel pairs to the level of > 1025 m-3 that is 1 - 20 %
of the quantity of Frenkel pairs in the cascade of displacements which equal ∼1027 м-3.
Summarizing the experimental results obtained on effect of interstitial atoms carbon and
nitrogen on the process of recombination of vacancies and interstitials in neutron irradiation
of steels and alloys based on iron it is possible to come to such conclusion: if the solid
solution of steels and alloys is depleted by carbon and nitrogen in the initial heat treatment to
a level ≤ 0,01 wt% (≤ 500 ppm at) there is a stabilization of the structural state of alloy, the
disequilibrium decreases. The location of the structural distortions of the solid solution with
an average linear spacing of more than 12 interatomic distances does not create enough of
traps or sinks for point defects. Therefore the rate of recombination is reduced and neutron
irradiation to 10 dpa at a temperature of ∼ 350°C causes the formation of the vacancy pores
and the large dislocation loops in the solid solution.
Figure 10. Structure of the alloy Fe-20Cr-40Ni-5Mo-Nb: a, b) in its original condition after
recrystallization annealing at: a) 800°C, b) 1000°C, c, d) after neutron irradiation to ~10 dpa at 350°C:
c) 800°C, d) 1000°C.
3.1.3. The Influence of Oversized Substitutional Atoms on the Acceleration of the

Recombination of Radiation Defects
Examined in the previous section, the mechanism of influence of carbide-forming
elements on the radiation damage of steels and alloys outlined the important role of carbon
and nitrogen atoms in a change in the rate of the point defects recombination. If the carbon
and nitrogen atoms there are in the solid solution, they accelerate the recombination of
vacancies and interstitials. Upon binding of carbon and nitrogen in niobium carbonitrides
particles their effect on recombination is reduced. When considering the mechanism of the
effect of carbide-forming elements on the radiation-damage susceptibility was not separately
accounted for the influence of so-called "oversized" atoms of niobium and molybdenum.
The radius of the niobium atoms (the Goldschmidt) by 15%, and molybdenum atoms by
10% larger than that of iron atoms. When replacing the main on the oversized atoms in the
crystal lattice there are distortions that can serve as traps for vacancies and to accelerate the
recombination of point defects. The influence of oversized substitution atoms on the
recombination of point defects was evaluated in the study [5] of the samples of high purity
steel Fe-18Cr-20Ni (Fig. 11a) and complex doped alloy Fe-20Cr-40Ni-5Mo-Nb (Fig. 12a).
Figure 11. Structure of the alloy Fe-18Cr-20Ni: a) initial state, b) irradiation with neutrons with a
fluence of 4.6x1024 n/m2, E > 0.8 MeV.
The steel Fe-18Cr-20Ni in the initial state after recrystallization annealing has a
homogeneous structure of the solid solution. In the structure there is no excess phase and
oversized atoms. The total concentration of carbon and nitrogen in solid solution is about
0.015 wt%. Alloy Fe-20Cr-40Ni-5Mo-Nb, unlike steel Fe-18Cr-20Ni, has an additional 5
wt% oversized atoms of molybdenum and niobium, so the structure of the alloy Fe-20Cr-
40Ni-5Mo-Nb (Fig. 12a) contains also particles of niobium carbonitrides Nb (CN),
concentration and average size equal to ~ 2x1018 m-3 and 0.2 microns.
The samples of steel Fe-18Cr-20Ni and the alloy Fe-20Cr-40Ni-5Mo-Nb were irradiated
with neutrons in a reactor 27VM at 320-340°C for 7400 h up to 1 dpa.
After neutron irradiation up to 1 dpa change in phase composition of materials was not
observed (Fig. s 11b, 12b). In the structure of steel and alloy formed prismatic dislocation
loops, the average size and the concentration, as well as the numbers of displaced atoms in the
loops are shown in Table 2.9. From the results of exposure can be seen that the concentration
of dislocation loops in steel Fe-18Cr-20Ni with an increase in the neutron fluence rapidly
reaches saturation. Already after the fluence 4x1024 n/m2 concentration of loops remains
practically unchanged as the number of displaced atoms in the loops.
Figure 12. Structure of the alloy Fe-20Cr-40Ni-5Mo-Nb: a) initial state, b) neutron irradiation with a
fluence of 6.2 x1024 n/m2, E > 0.8 MeV.
Table 5. Parameters of dislocation loops in neutron-irradiated samples of the alloys Fe-

18Cr-20Ni and Fe-20Cr-40Ni-5Mo-Nb
Флюенс Parameters of dislocation loops

Alloys (1024 n/m2, Mean size Number density Number of atoms in
Е>0,8 MeV) (nm) (1022 m-3) the loops (1024 m-3)
4.0 4.0 3.2 9.0
Fe-18Cr-20Ni 4.6 6.0 3.0 16.0
6.3 5.0 3.2 14.0
1.4 6.0 0.1 0.5
Fe-20Cr-40Ni-
4.9 6.0 0.7 3.2
5Mo-Nb
6.2 6.5 2.0 11.0
In the complex doped alloy Fe-20Cr-40Ni-5Mo-Nb the development and accumulation of

dislocation loops in the initial stages of irradiation is much slower than in steel Fe-18Cr-20Ni.
However, upon reaching the neutron fluence of ~ 5x1024 n/m2 and the hereinafter
concentration of dislocation loops and the number of displaced atoms in the loops in the alloy
increases rapidly and almost reach the level of damage to the steel Fe-18Cr-20Ni in the
studied range of irradiation. The average size of dislocation loops in the alloy Fe-20Cr-40Ni-
5Mo-Nb in the course of irradiation changes little.
The resulting dependence of the accumulation rate of secondary radiation defects on the
amount of impurities in the solid solution shows that the increase in the number of interstitial
atoms in solid solution, especially after the neutron irradiation of small fluences, accelerates
the formation of dislocation loops. A longer incubation period of accumulation of dislocation
loops in the alloy Fe-20Cr-40Ni-5Mo-Nb can, apparently due to the fact that oversized
substitutional atoms Mo and the Nb in solid solution create a traps for the displaced atoms
and the vacancies, accelerating their recombination. However, the difference in the
concentration of dislocation loops and the number of displaced atoms in the loops is almost
eliminated with increasing the neutron fluence up to ~ 6.2x1024 n/m2, i.e. at a dose of damage
≤ 1 dpa.
Furthermore the presence in the solid solution of steel Fe-18Cr-20Ni a comparatively
large amount of carbon and nitrogen promotes more intensive poisoning of dislocation loops.
In the alloy Fe-20Cr-40Ni-5Mo-Nb significant part of the carbon and nitrogen was bound
with niobium, so poisoning of the loop was smaller. As a consequence the dislocation loops
in the alloy Fe-20Cr-40Ni-5Mo-Nb are larger and have a smaller concentration. It should be
noted that the width of the histogram loop size is much larger in the alloy than in the steel.
For example, in neutron-irradiated to a fluence of 6.3x1024 n/m2 (E> 0.5 MeV) samples of
steel Fe-18Cr-20Ni were observed the loop of maximum size 10 nm, and in irradiated at
similar conditions the samples of the alloy Fe-20Cr-40Ni-5Mo -Nb correspondingly 15 nm.
Analysis presented in the last sections of the results displays comparatively higher
efficiency of the influence of carbon and nitrogen atoms on the acceleration of recombination
vacancies and interstitials in steels and alloys. Heat treatments of chromium-nickel steels and
alloys, creating a depletion of the solid solution on the carbon and nitrogen to the level of
≤ 0.01 wt% contribute to the development of during neutron irradiation of vacancy porosity.
When the total content of carbon and nitrogen is > 0.01 wt% vacancy pores are not formed at
the dose of 10 dpa.
Thus, the combined impact of carbide forming and oversized atoms and interstitial atoms
(carbon and nitrogen) increases the duration of the incubation period of radiation damage by
more than one order of magnitude compared with the effect only oversized substitution
atoms.
The traps created by oversized atoms, the interstitial atom in the excess phases or in the
form of interstitial impurities can affect the change in flows of point defects in the incubation
period, but are not the unsaturated traps, i.e. do not possess sufficient effectiveness to provide
a continuous recombination of vacancies and interstitials. The most important shortcoming in
the conduct of such traps in steels and alloys is the change in their morphology and
composition during neutron irradiation. The phase particles, formed during the initial
thermomechanical treatments are destroyed in the displacement cascade and as a result of
radiation-induced segregation become radiation-stable phase. Turning into the stable
formations, they lose the ability to be the traps of point defects. Thus, it can be assumed that
the methods of accelerating the recombination of point radiation defects with the help of a
homogeneous and uniform decay of particles of excess phases, and thereby increasing their
radiation resistance, apparently, are not effective.
3.2. Effect of Short-Range Order on Recombination Accelerating of

Radiation Point Defects
Accumulated to date data on the impact of various factors on the radiation damage of
chromium-nickel steels and alloys have highlighted the crucial role of recombination
accelerating of point radiation defects. To understand the changes in the behavior of steels
and alloys under neutron irradiation it is necessary to understand the influence of non-
equilibrium structure on the kinetics of these changes.
Structural disequilibrium in metals occurs if the rate of cooling after recrystallization

annealing is so high that the diffusion processes in the solid solution did not have time to go,
and quenching structure is fixed. In the basis of their origin virtually all types of non-
equilibrium structures have changing the solubility of the components with temperature
changes. The disequilibrium of structure depends mainly on the doping, quenching rate, the
presence of impurities, etc. The structure with no uniform chemical composition acquire
during the rapid cooling all the construction materials used in nuclear energy sector. In this
connection it is interesting to consider the communication nature of the damage, which
develops in metals during irradiation with the disequilibrium of the structure.
In studying the mechanical properties of the alloy Ni-42Cr-1Mo, irradiated in BOR-60
reactor with neutrons up to 32 dpa, it was surprisingly found that with the accumulation the
dose the mechanical properties and especially the relative total and uniform elongation of the
alloy at temperatures of irradiation and test up to 350°C virtually unchanged. At the same
time in austenitic stainless steels the total elongation becomes < 3 % for neutron irradiation of
lower dose (Fig. 13). This means that the alloy Ni-42Cr-1Mo significantly less susceptible to
radiation damage as compared to austenitic stainless steels [11].
Figure 13. Effect of irradiation on the mechanical properties of the austenitic alloys of type 316, 304
and alloy Ni-42Cr-1Mo.
Studies of the structure of materials whose properties are shown in Fig. 13 using electron
microscopy showed that the size of dislocation loops in the alloy Ni-42Cr-1Mo irradiated
with neutrons up to ∼ 32 dpa, was 2-3 times more, and concentration of loops - one order of
magnitude lower than in austenitic steel Fe-16Cr-15Ni-3Mo-Nb-0.026C (Fig. 14a). The
concentration of dislocation loops in the alloy is ~ 3x1021 m-3 (Fig. 14b), and in the steel ~
3x1022 m-3. It should be noted at the same time that the steel Fe-16Cr-15Ni-3Mo-Nb-0.026C
was irradiated by neutrons in the order of lower dose compared with the alloy.
Figure 14. Structure of alloys after neutron irradiation at ∼ 350°C: a) Fe-16Cr-15Ni-3Mo-Nb-0.026C, ∼

2.5 dpa, b) Ni-42Cr-1Mo, ∼32 dpa.
Larger dislocation loops with a low concentration in the alloy Ni-42Cr-1Mo impede
dislocation motion weaker; therefore the effect of radiation hardening in the alloy respect of
the steels is weak. In the turn, lowering the concentration of secondary radiation defects in the
alloys of Ni-Cr type of Ni-42Cr-1Mo can be, apparently, associated with acceleration of
recombination of vacancies and interstitials in the process of neutron irradiation.
Radiation damage of structural materials under the action of neutron flux begins with the
appearance in the structure of vacancies, interstitials and the formation of their clusters.
Gathering of point defects in complexes: dislocation loops, vacancy pores, the participation of
point defects in segregation processes that alter the phase composition of materials and
mechanical properties, means a change in the stability of the structure and deterioration of the
radiation resistance. Thereby, one of the ways of improving the stability of the structure
material is the recombination accelerating of vacancies and interstitials and lowering the rate
of accumulation of radiation defect.
Therefore the principal goal of this paper was to investigate the possibilities of creating in
the construction-traditional materials such original structure, which accelerates the
recombination of vacancies and interstitials.
3.2.1. Features of Radiation Damage of of Ni-Cr Alloys

Alloys of the system Ni-Cr, which showed significant benefits in neutron irradiation have
been investigated in the connection with the need creation of the material, the complex match
to the requirements of high radiation and corrosion resistance, high mechanical properties and
structural stability at temperatures of 300-350°C.
In studying of alloys of the system nickel-chromium were obtained the first experimental
data on the significant influence of metastable structure on the recombination of point defects.
In the particular, it was found that the concentration of dislocation loops in the alloy Ni-42Cr-
1Mo after irradiation by neutrons up to ∼ 32 dpa at 350°C was almost one order of magnitude
smaller than in the alloy Ni-47Cr-1Mo [3].
The alloys Ni-42Cr-1Mo and Ni-47Cr-1Mo (Table 6) after quenching have FCC lattice
based on nickel. Volume fraction of particles of excess α - phase in the alloy Ni-42Cr-1Mo
(Fig. 15) did not exceed 0.05 %. In the solid solution of tension samples of the alloy Ni-
47Cr-1Mo were remained not dissolved in holding for quenching globular particles of α -
phase based on chromium BCC and inhomogeneously distributed titanium carbide particles
of size ~ 100 nm and the concentration of ~ 8 x 1018 m-3. Volume fraction of particles α -
phase in the alloy was ∼ 0.1 %, the dislocation density ~ 1x1013 m-2.
Table 6. Chemical composition of alloys Ni-Cr-Mo in wt%
Alloys C Si Mn S P Cr Mo Al Fe Ti
Ni-42Cr-1Mo 0.003 0.05 0.05 0.001 0.003 41.65 1.01 0.21 0.23 0.21
Ni-47Cr-1Mo 0.013 0.15 <0.05 0.007 0.007 46.69 1.36 0.23 0.24 0.25
Figure 15. Structure of the Ni-42Cr-1Mo alloy after quenching from a temperature of 1100°C.
Under irradiation in BOR-60 at ~ 350°C by neutrons dose of 10 dpa in the tensile

samples of the alloy Ni-47Cr-1Mo were formed dislocation loops, vacancy pores and the
linear dislocations (Fig. 16). In addition to the globular precipitates of α - phase in the
structure were observed the titanium carbide particles (Fig. 16a) with the lattice constant
0.435 nm, the size of 100 nm and the concentration ≤ 8x1018 m-3. Concentration of dislocation
loops reached ~ 2x1021 m-3, the average size of ~ 16 nm. Vacancy pores (Fig. 16b) had a size
of ~ 9.5 nm and a concentration of ~ 3x1021 m-3 and the swelling was ~ 0.14 %. There were
near the grain boundaries depleted zones in the pores of a width of 100 nm.
Figure 16. Structure of the alloy Ni-47Cr-1Mo samples after neutron irradiation to ~ 10 dpa at ~350°С:
a) α - phase and titanium carbides, b) dislocation loops, voids and linear dislocations.
In the ring samples of the alloy Ni-47Cr-1Mo after irradiation in BOR-60 reactor at a
temperature of 350ºC by neutrons dose of ~ 32 dpa vacancy pores were not detected.
Concentration of dislocation loops was ~ 3x1022 m-3 (Fig. 17a), the average size of loops -
7.5 nm. In the structure were observed the linear dislocations, carbides of titanium and
randomly distributed particles α - phase (Fig. 17b).
Figure 17. Structure of the alloy Ni-47Cr-1Mo samples after neutron irradiation to ~ 32 dpa at ~350ºС:
a) dislocation loops and line dislocations, b) α - phase and titanium carbides.
Analysis of the structural features of the irradiated samples of the alloy Ni-47Cr-1Mo
shows that his damage is analogous to by neutrons damage of austenitic steels and alloys
(Section 3.1.2). In the samples in tension of this alloy during the initial hot repartition the
solid solution was depleted of interstitial impurities. Therefore under neutron irradiation dose
of 10 dpa interstitial atoms are arranged in the large size of dislocation loops and dislocation
network, as well vacancy - in the pores. In the ring samples irradiated up to ~ 32 dpa,
interstitials are located in the higher concentration dislocation loops (~ 3x1022 m-3) and the
smaller size, as well vacancies are located in the vacancy loops d < 10 nm, ρ ~2x1022 m-3.
In such a way, the radiation damage of the alloy Ni-47Cr-1Mo affects the content of
interstitial impurities in solid solution. Reducing the number of carbon atoms in solid solution
reduces the decorating of the dislocation loops, which increase in size by absorbing the
interstitials. As a result, the recombination rate of Frenkel pairs slows down. The
concentration of radiation-induced vacancies in the matrix increases and causes the
appearance of porosity in the samples in tension of the alloy Ni-47Cr-1Mo. Under the carbon
content in the ring samples of the alloy Ni-47Cr-1Mo at the level of the original concentration
the dislocation loops are screened by carbon, the growth of loops slows down. The increased
amount of interstitial atoms in the matrix accelerates the recombination of point defects. Not
exchanged radiation vacancies can be united into vacancy dislocation loops.
In the samples for tensile of the alloy Ni-42Cr-1Mo, irradiated in the BOR-60 at ∼ 350°C
by neutrons dose of ~ 32 dpa, dislocation loops were formed and the linear dislocations (Fig.
18). The volume fraction of particles of excess phase (Fig. 18a) does not exceed 0.05 %.
Diffraction contrast of the matrix has a tweed structure (Fig. 18b) showing the homogeneous
formation of the short-range ordering. Homogeneous short-range ordering in the alloy matrix
manifested brighter after heating of the irradiated samples for mechanical testing: in the
electron diffraction patterns - in the form of diffuse streaks around the main reflections (Fig.
19a) as well in the microphotographs in the form of clusters of dark spots, whose
concentration was ≤ 1024 m-3. An increase the sizes of short-range ordering regions is not
large (∼ 2 nm, Fig. 19b) due to the short duration of heating of samples for tensile testing.
Figure 18. Structure of the alloy Ni-42Cr-1Mo after neutron irradiation to ~ 32 dpa: a) the grain
boundary, and b) the dislocation structure.
A tendency to developing of short-range order means that in conditions of neutron

irradiation the atoms of a disordered after quenching solid solution are rebuilt to form clusters
of the ordered structure. Occurring during the nucleation of clusters the lattice distortions
increase the probability of recombination of vacancies and interstitials. Accelerating of the
recombination of vacancies and interstitials reduces the amount of secondary radiation defects
including dislocation loops and vacancy pores. After irradiation under identical conditions,
the concentration of dislocation loops in the disposed to the short-range ordering alloy Ni-
42Cr-1Mo was several times lower than in the alloy Ni-47Cr-1Mo. Accordingly, uniform and
total elongation of the alloy Ni-42Cr-1Mo after neutron irradiation dose of 32 dpa ∼ was 2 - 3
time higher.
Figure 19. Short-range ordering in the alloy Ni-42Cr-1Mo, irradiated at ~ 350ºС to ~ 32 dpa after
mechanical tests: a) electron diffraction pattern, b) structure after tensile testing at 500ºС.
Now we shall return to the problem of different radiation damage of austenitic stainless
steel Fe-16Cr-15Ni-3Mo-Nb-0.026C and alloy Ni-42Cr-1Mo, which had been irradiated by
neutrons in a factor of 10 the higher fluence and at the same time had a factor by 10 smaller
concentration of dislocation loops than steel. In this connection there appeared one more
unexpected experimental fact. Alloy Ni-47Cr-1Mo alloy was different from the Ni-42Cr-1Mo
only the fact that had the content of chromium in ∼ 5 % more (Table 6). However under
neutron irradiation a dose of 32 dpa this alloy has accumulated secondary radiation defects,
not as a nickel alloy with ∼ 42 % chromium, but as austenitic steel Fe-16Cr-15Ni-3Mo-Nb-
0.026C. Despite the slight differences in chemical composition, the concentration of
dislocation loops in the nickel alloy with 42 % chromium was an order of magnitude smaller
and the number of not recombine defects - 3 times less.
The recombination rate, the concentration of dislocation loops, longer incubation period
of damage show that the structure of the alloy Ni-42Cr-1Mo under neutron irradiation is
changed according to some different mechanism than in austenitic stainless steels and alloys
and nickel alloy with 47 % chromium.
Study of the mechanisms and laws of point defects recombination accelerating in alloys
of the system Ni-Cr is discussed in the next section.
3.2.2. The Short-Range Ordering Nanodomains of the Ni-Cr System

To elucidate the mechanism of accelerating of point defects recombination in the alloy
Ni-42Cr-1Mo under neutron irradiation were carried out comprehensive studies of the
structure, resistivity, lattice parameters, density and other features of the experimental alloys
of the Ni-Cr system (supplemented with. ∼ 1 at% Mo, table 7 ) in the initial state and after
thermal and radiation exposure.
Table 7. Chemical composition of experimental alloys Ni-Cr-Mo in wt%
Alloys C Ni Cr Cr* Mo S
Ni-32Cr-1Mo 0.027 осн. 32.11 34.94 1.28 0.006
Ni-38Cr-1Mo 0.027 осн. 37.85 40.90 1.30 0.005
Ni-39Cr-1Mo 0.022 осн. 38.90 42.00 1.30 0.005
Ni-41Cr-1Mo 0.028 осн. 41.35 44.49 1.30 0.005
Ni-43Cr-1Mo 0.025 осн. 43.06 46.24 1.30 0.005
Ni-44Cr-1Mo 0.026 осн. 44.48 47.69 1.30 0.005
* at%.
The starting state for the alloys investigated [7] is the state after quenching from the
single-phase γ - region of state diagram. Alloys for the investigations were quenched from the
single-phase γ - region of state diagram, and then annealed at temperatures of 300-450°C
(points on the graph show the position of alloy before quenching and with aging, Fig. 20).
The typical structure of alloys in the initial state is shown in Fig. 21. The structure is a
homogeneous solid solution of nickel. Significant differences in the structural-phase state of
alloys after the quenching occur with increasing chromium content of more than 38 wt%. In
the body of grains of alloys with such a chromium content remain did not dissolved by
annealing for quenching particles of α - phase of chromium with the volume fraction ≤ 0,1 %
(Fig. 21a. At the grain boundaries are observed seldom selections of chromium carbides
M23C6 (Fig. 21b).
Figure 20. The alloys investigated in the phase diagram of the system Ni-Cr.
Figure 21. Structure of the alloy Ni-41Cr-1Mo after quenching: body (a) and grain boundary (b).
In the microstructure of quenched alloys is observed diffraction tweed contrast (Fig. 22a.
Tweed contrast becomes sharper detected after the annealing at 450°C for 9 000 h (Fig. 22b).
Oscillation period of the fragments of contrast is ∼ 5 nm.
Study of the kinetics of structural features in the annealing process at 300 - 450°C for up
to about 40 000 hours spent on the experimental samples of nickel alloys with chromium, has
shown that annealing in the temperature range 300 - 400°C did not cause significant structural
and phase changes which are practically not detected by electron microscopy [14].
At 450°C in the alloys there are structural-phase changes in accordance with the
chromium content in the matrix. The increase in chromium content stimulates grain boundary
precipitation of α - phase, especially if the chromium content > 41 wt% (Fig. 23).
In the alloys with 32 and 38 wt%. of chromium on the high-angle grain boundaries were
formed chromium carbides type M23C6 [6]. In the alloy Ni-38Cr-1Mo having a larger amount
of chromium the grain-boundary processes were developed more intensively. Further increase
in amount of chromium (alloy Ni-39Cr-1Mo) is even more intensified phase transformation at
grain boundaries. There were formed the plates of M23C6 carbides and the plates of α - phase
that is the beginning of discontinuous disintegration. Apparently due to the chemical no
uniformity the phase decomposition at the grain boundaries occurs uneven. On some sections
of the grain boundaries were formed carbides M23 C6; on the others - there was the beginning
of discontinuous disintegration.
Figure 22. Tweed contrast in the alloy Ni-42Cr-1Mo: a) after quenching, b) after quenching and
annealing at 450°С, 9 000 h.
Figure 23. Structure of grain boundaries in alloys of Ni-Cr-Mo after annealing at 450°С, 40 000 h.
In the alloy Ni-41Cr-1Mo at the grain boundaries is observed occasional precipitation of

carbides M23C6 and plates α - phase. Increasing the chromium content to 43 wt% leads at
450°C to intensive phase decomposition of frontier regions of the alloy Ni-43Cr-1Mo
emitting chromium-rich particles. There is the development of discontinuous disintegration
and precipitation of carbides M23C6. In the alloys with more than 43 wt% chromium the
discontinuous disintegration covers most of the grain body.
Fine structure of alloys at long (40 000 h) annealing varies in accordance with the
equilibrium phase diagram. Fig. 24 shows that in the alloy near the stoichiometric
composition at 450°C for 40 000 h were formed Ni2Cr domains of superstructure with a
concentration > 7x1021 m-3 and the size of 4 - 10 nm. In the electron diffraction pattern in
addition to the matrix reflections are present reflections from the superstructure, in the light of
which was shown dark-field image of long-range ordering domains. Long-range order
develops in the whole volume of the matrix.
In the alloy Ni-38Cr-1Mo concentration and size of the domains of the superstructure
constitute respectively 1.2x1023 m-3 and 1-2 nm. Closer to the grain boundaries, on which is
allocated the phase based on chromium, the amount of long-range ordering domains more,
and their concentration is lower ( d ≥2 nm, ρ = 5x1022 m-3. The smaller size of the long-range
order domains, which according to their size have been called "nanodomains", in the alloy Ni-
38Cr-1Mo, apparently due to lower nickel content.
Figure 24. Structure of the alloys Ni-Cr-Mo (32, 38 and 39 wt% Cr) after annealing at 450°С, 40 000 h.
With increasing chromium content up to ~ 39 wt% intensity of superstructure

precipitation is reduced (Fig. 24). In the matrix of the alloy Ni-39Cr-1Mo, as in the matrix of
alloy Ni-38Cr-1Mo homogeneous nucleation of superstructure nanodomains Ni2Cr occurs.
Their concentration and size constitute are 1.4x1023 m-3 and 1-2 nm, respectively.
The parameters of phases after the aging at 450°C show that increase in the chromium
content with increasing distance from the stoichiometric gradually lowers the amount of long-
range ordering superstructure. The intensity of the reflections from the superstructure Ni2Cr
nanodomains in the electron diffraction patterns decreases. And finally, in the alloy with
content of chromium ∼ 41 wt% during aging at 450°C appears to be formed only the short-
range order. Reflections from the superstructure Ni2Cr nanodomains in the electron
diffraction patterns of the alloy Ni-41Cr-1Mo did not detected (Fig. 25). In such a way, in the
fine structure of the alloy with 41 wt% of chromium after the prolonged aging at 450°C
occurs only the short-range order, phase transitions are not observed.
In the kinetics of transformation of the solid solution of the alloy Ni-44Cr-1Mo at 450°C
was clearly demonstrated the effect of chromium. At the grain boundaries were formed the
fields of discontinuous decomposition (Fig. 25) size up to 5 microns. The precipitation of
chromium carbides M23C6 was observed at grain boundaries. In the alloys with 43 and
especially 44 wt% chromium the discontinuous disintegration with the formation of α - phase
of chromium in the form of plates occurs very rapidly, at the same time due to of enrichment
in nickel the matrix adjacent to the - α phase domains forms large domains of the
superstructure Ni2Cr. The domains of superstructure have a size of 2 nm far away from grain
boundaries to 70 nm closer to precipitates, which are enriched with chromium.
Figure 25. Structure of the alloys Ni-Cr-Mo (41, 43 and 44 wt% Cr) after annealing at 450°С, 40 000 h.
An important feature of the restructuring of the atoms of nickel and chromium at the long
range ordering of FCC solid solution by type Ni2Cr lies in the fact that after formation of a
superstructure Ni2Cr the slip planes {111} become structurally not equivalent. The
arrangement of atoms in the two systems {111} planes corresponds to planes of type I (Fig.
26), in two other systems - planes of type II.
Figure 26. Location of atoms in different planes {111} of superstructure Ni2Cr [8].
Another important aspect in the formation of domains and the nucleation of the
superstructure nanodomains is a distortion of values of the matrix lattice parameters. In the
crystal lattice of the matrix (Fig. 27) the lattice parameters in the directions [110] [111]
increase while in the directions [311] and [331] decrease as compared with the original cubic
lattice parameters. At the same time in the crystal lattice of the matrix appear tetragonal
distortions.
Figure 27. The unit cell of superstructure Ni2Cr in the fcc lattice based on nickel [15].
The crystal lattice spacings of experienced alloys of the system Ni-Cr calculated from the
reflections [111] and [331] are shown in Fig. 28. It is seen that the lattice spacings of all the
alloys determined from the reflection of [111] is greater, as well from reflection of [331] -
smaller than the spacing of the original cubic lattice аcube (Table 8).
Figure 28. The lattice spacings of Ni-Cr alloys after aging at 450°C, 40 000 h, calculated from the main
reflections (111) and (331).
The values of changes of the matrix lattice parameters for different basic reflections
compared with the parameters of the original cubic lattice, also shown in Table 8.
Table 8. Changes in the lattice parameters of Ni-Cr alloys as a result of short-and long-
range ordering during annealing 450°C, 40 000 h
Changes of lattice parameters upon annealing The lattice period

Alloys (d450 - dcube)/ d450, % of initial alloys
Δd220 Δd111 Δd311 Δd331 аcube (nm)
Ni-32Cr-1Mo +0.07 % +0.07 % -0.19 % -0.27 % 0.35726
Ni-38Cr-1Mo +0.11 % +0.11 % -0.14 % -0.11 % 0.35860
Ni-39Cr-1Mo +0.11 % +0.12 % -0.08 % -0.05 % 0.35888
Ni-41Cr-1Mo +0.04 % +0.21 % -0.05 % -0.05 % 0.35927
Ni-43Cr-1Mo +0.09 % +0.06 % -0.08 % -0.02 % 0.35948
Ni-44Cr-1Mo -0.03 % +0.03 % -0.08 % -0.05 % 0.36010
With the results of structural studies agree well the changes in the mechanical and physical
properties of experimental alloys of the system Ni-Cr. So, the occurrence of tetragonal
distortions in the solid solution due to the long-range order decreases the maximum impact
strength in exactly those alloys in which there is the highest degree of long-range order - in the
alloys with 35 and 48 at% chromium (Fig. 29). Fig. 29 also shows that when the aging time is
≤ 10 000 h the toughness of alloys with elevated chromium content (~ 43 and ~ 44 wt%) is
higher than that in alloys with lower chromium content (~ 38 and ~ 39 wt%), but after
exposure 40 000 h the situation is reverse. It is connected, apparently, with the formation the
regions of long-range ordering around of precipitates the α - phase.
Figure 29. Dependence of impact strength Ni-Cr alloys from chromium content after annealing
at 450°C [6].
Character of the electrical resistivity changes of the system Ni-Cr alloys also confirms the
results of electron microscopic studies [16], which showed that the no equilibrium state of the
system Ni-Cr alloys manifests itself during aging in different ways. If in the alloys with 32
and 44 wt% chromium at 450°C occur drastic structural changes, in the alloys with ∼ 41 wt%
chrome like as if nothing happened. To elucidate the structural transformations have been
conducted experimental determinations of the electrical resistivity of alloys in the initial state
and after aging at 450°C for 4000, 10000 and 40000 h [17]. Electrical resistivity was
measured at room temperature for the same samples before and after aging.
The results of electrical resistance measurements are shown in Fig. 30. The analysis
shows that the electrical resistivity is in good agreement with the structural features of alloys
Ni-Cr-Mo. The higher after quenching in comparison with other alloys electrical resistivity of
the alloy Ni-32Cr-1Mo is connected, apparently, with higher degree of short-range ordering.
In accordance with this assumption in solid solution of the alloy Ni-32Cr-1Mo should be
more pairs of unlike atoms after quenching than in the alloys with higher amounts of
chromium. The significant and monotonic decrease in the electrical resistivity with increasing
of aging time at 450°C of the alloy Ni-32Cr-1Mo is caused by increasing the long-range order
extent in solid solution.
Figure 30. Resistivity of alloys Ni-Cr-Mo after quenching and aging at 450°C [17].
As far as the distance from the stoichiometric Ni2Cr grows the character of electrical
resistivity changes in the system Ni-Cr alloys is complicated by competition between short-
and long-range ordering and discontinuous decomposition with the formation of α - phase.
Long-range order of alloys with approaching to the boundary of the «cupola» of ordering in
the process of aging is becoming less and less intensive, and in these alloys occurs only short-
range order. In the alloys outside the "cupola" of ordering apparently due to the changes the
mechanism of disintegration of solid solution, the course of the electrical resistivity curves is
more complicated. A significant role in the changes of the electrical resistivity starts to play
the decomposition. The elucidation more details of these changes is not the purpose of this
study. One can only note a few facts. Reduction of resistivity in the alloys with higher
chromium content is due to intensive precipitation α - phase and the subsequent nucleation of
long-range order domains in interlamel space. Somewhat unexpected increase in the values of
resistivity in the alloy Ni-44Cr-1Mo for the first 10 000 h of aging may be caused by short-
range ordering connected with the intense precipitation α - phase. In further with increasing
the aging time up to 40 000 h the resistance of the alloy Ni-44Cr-1Mo decreases during the
formation of the Ni2Cr superstructure in the interlamel space.
For further investigation, it should be noted that the degree of long-range order, which
was estimated on the decrease of electrical resistivity, is minimal in the alloys, which are on
the content of chromium are close to the right boundary of the "cupola" ordering on phase
diagram of the system Ni-Cr. Significance and meaning of this phenomenon will be clarified
during the discussion the results of further research.
The changes of the electrical resistivity (Fig. 31) associated with structural changes at
450°C, are apparently caused by dependence of the electron density of the system Ni-Cr
alloys from chromium content. In alloy, which is close to stoichiometric, electrical resistivity
during the aging has dropped after 4 000 h of exposure due to long-range ordering. In alloys
with higher chromium content character of changes of the electrical resistivity is more
complicated because it is influenced by several factors, in particular, the need a more

prolonged exposure for the beginning of long-range ordering.
Annealing time:
♦ - 4 000 h,
■ - 10 000 h,
Δ - 40 000 h
Figure 31. Relative change of alloys Ni-Cr-Mo resistivity after aging at 450°C.
In the paper [18] have been suggested that the change in electrical resistance with the
formation of alloys based on transition metals is determined by the redistribution of electrons
between atoms. According to this hypothesis, the chromium atoms give a portion of their
conduction electrons, which pass to d - subshells of nickel atoms. Such a transition should
lead to an increase in the binding energy of atoms.
During the short-range ordering in solid solution increases the number of pairs of unlike
atoms. The free energy of the electron cloud decreases due to the transfer of electrons in a
stable state, this is accompanied by the release of energy ΔHmix<0. Number of conduction
electrons decreases, as well the electrical resistivity increases.
If we increase the content of chromium in the alloys, then due to increasing tendency of
alloys to the disintegration with the formation of pairs of like atoms, the relative amount of
chromium, transferred their valence electrons to the nickel atoms is reduced. Accordingly, the
number of conduction electrons increases as well the electrical resistivity of the alloy
decreases.
In the process of long-range ordering in solid solution alloys Ni-Cr-Mo is formed not a
pairs of Ni-Cr, but superstructure, based on its triad of Ni-Ni-Cr. In this case, the number of
atoms of chromium, referred from solid solution to the superstructure is less than during the
formation of short-range ordering. In this case, respectively, the number of conduction
electrons increases and the electrical resistivity of alloys decrease.
Decrease in the electrical resistivity due to aging at 450°C for 40 000 h was found in all
the experimental alloys Ni-Cr-Mo, but the minimum relative change in the electrical
resistivity occurs in alloys with chromium content in the interval ∼ 38 - 41 wt%.
So the results of structural studies and the definition of the electrical resistivity showed in
the good agreement with the hypothesis of exchange interaction of electrons of the nickel and
chromium atoms the minimum relative structural and physical changes in alloys with
chromium content in the interval ∼ 38 - 41 wt%.
3.2.3. Crystal Lattice Distortions and Recombination of Point Defects

Since the purpose of this study is to understand the role of changes in the structure in
improving of radiation resistance of materials, as well as the causes and mechanisms that
cause such an increase it is necessary to clarify the changes of physical properties with the
peculiarities which arise with rearrangement of atoms in the crystal lattice.
The appearance of tetragonal distortions in the crystal lattice of the Ni-Cr alloys in the
process of prolonged annealing at 450°C have been reliably confirmed by X-ray studies of
structure and measuring the density of alloys. First of all, it was found that the absolute values
of the lattice constant in all the alloys after annealing at 300° C have higher values than after
aging at 450° C (Fig. 32 [8]). This means that in all the studied alloys of the system Ni-Cr,
which more or less display a tendency to short-range ordering and long-range ordering in the
process of the formation of order there is a decrease of the atomic volume or the lattice
contraction. The difference of the lattice periods after annealing at 300 and 450° C is maximal
for close-stoichiometric alloys and decreases with increasing chromium content up to ∼ 42
at%.
▲ - matrix, aging at 300 °C;

◆,■ - the matrix, aging at 450 °C;
× - superstructure Ni2Cr
Figure 32. The lattice periods of alloys Ni-Cr-Mo.

Aging at 300°C for 40 000 h of studied alloys Ni-Cr-Mo, as was shown in [3, 6],
practically does not change their phase composition as compared to the state after quenching.
Was found only the initial γ - phase. However, in the solid solution of alloys, apparently in
connection with the annealing of quenched vacancies, there were the signs of short-range
ordering [8], as indicated by the comparison of the Bragg peaks (331) for the alloy Ni-41Cr-
1Mo at two temperatures (Fig. 33). It is seen that the lattice parameter of the alloy as a result
of short-range ordering at 450°C decreased Δd/d ≈ (4x10-4) and the width of the reflections
increased (∼ 20 %). Qualitatively such changes manifest themselves in all other samples.
Figure 33. Comparison of the alloy Ni-41Cr-1Mo (331) reflections after annealing at 300 and 450°C,
40 000 h.
The lattice compression was also discovered [19] by hydrostatic weighing in water with
preliminary evacuation the air, thermostatting, and with correction for buoyant force of the
suspension and the temperature correction to the density of water. The total error of
determining the density is ± 0,01 g/cm3. The density of experimental alloys after quenching
and after prolonged aging was determined (Table 9). In the alloys with chromium content
from 41 to 44 wt% the density increase due to short- and long range ordering was
compensated by its decrease due to precipitation of α - phase.
Effect of annealing temperature on the density is observed more clearly in alloys with 32
and 39 wt% Cr (Table 9). In the Ni-32Cr-1Mo alloy located near the stoichiometric phase
Ni2Cr the raising of annealing temperature from 300 to 450°C led to a significant increase in
density due to the formation of a superstructure Ni2Cr. In the alloys with 43 and especially 44
wt% chromium discontinuous disintegration of solid solution occurs at the grain boundaries.
At the first stage of disintegration in some parts of the grain boundaries there is a formation of
α - phase in the form of plates. The plates of α - phase are formed to the discontinuous
disintegration cell. The formation of cells occurs very rapidly, and in adjacent with plates of α
- phase enriched by nickel interlamel space the particles of phase Ni2Cr are formed.
Table 9. Density of Ni-Cr alloys after annealing at 300-450°C, 40 000 h
Alloys Annealing Sample Weight Alloy density ρ (g/cm3)

temperature, °С in air (g)
Никель - - 8.91
Хром - - 7.20
300 0.47505 8.22
Ni-32Cr-1Mo 400 1.15615 8.23
450 0.58670 8.34
300 0.58625 8.09
Ni-39Cr-1Mo 400 0.59115 8.11
450 0.45520 8.13
300 0.36330 8.08
Ni-41Cr-1Mo 400 0.95355 8.02
450 0.52045 8.00
Ni-44Cr-1Mo 400 0.45730 7.99
450 0.44530 8.00
Increasing the chromium content from ~ 32 to ~ 44 wt% in the investigated alloys is

accompanied during annealing at 300 and 450° C uniform increasing in the lattice parameter
(Fig. 32. An increase the parameter is accompanied by decrease in the density because the
density of chromium less than the density of nickel (Table 9), and the size of chromium atom
by about 2.4 % larger than the size of the nickel atom.
Figure 34. Dependence of relative changes in density and lattice constants of alloys Ni-Cr-Mo on the
content of chromium with increasing aging temperature from 300 to 450°C, 40 000 h.
With increasing chromium content from about 32 to ∼ 41 wt% the propensity of alloys
Ni-Cr-Mo to long range ordering decreases [3, 6, 8]. Simultaneously with the decrease in the
propensity to long range ordering increases the propensity to the disintegration of solid
solution with the formation of α - phase. Character of change in the lattice parameter and the
density of alloys Ni-Cr-Mo with aging (Fig. 34) confirm these trends. The increase in the
density (Δρ > 0) due to the formation of long-range ordering domains, with increasing
chromium content decreases and becomes minimum at short-range order alloys. Since the
beginning of the selection α - phase the density become lower than the initial (Δρ <0). At the
simultaneous formation of discontinuous disintegration cells and concomitant formation of
long-range ordering domains in the transition from ordering to disintegration region in which
long-range order does not occur, i.e. stage of short-range ordering is not transferred to the
stage of the long-range ordering the change in density close to zero.
Thus, the chromium content in the range ~ 39 - 41 wt% for alloys of Ni-Cr at ∼ 450°C is
a transition or critical. Within this interval, at reasonable times of aging there is only short-
range ordering. In the microstructure of these alloys is observed only diffraction tweed
contrast which is evidence of short-range order. At this stage, oscillation period of the
fragments of contrast, i.e. zones of enrichment and depletion of nickel in the matrix is ∼ 5 nm.
It is known that in solid solutions, whose formation is accompanied by the increase in the
number of unlike pairs of atoms, i.e. ordering, there is the release of heat (negative deviations
from Raoult's law). In solid solutions whose formation is accompanied by a decrease in the
number of unlike pairs i.e. disintegration of solid solutions, there is the heat absorption
(positive deviations from Raoult's law). For this reason, the enthalpy of mixing Hmix is
sometimes called the enthalpy of ordering if it is negative or enthalpy of decomposition if it is
positive. In the critical range of the chromium content the enthalpy of mixing Hmix should be
close to zero.
The aging process at a temperature of ~ 450°C in alloys with chromium content ~ 39 - 41
wt% stops at the stage of formation of crystalline domains size ∼ 2.5 nm i.e. at the stage that
is intermediate between the homogeneous and micro domain short-range order. This step
should be to call, according to the size of areas, "nanodomain short-range order". A
characteristic feature of the nanodomain short-range order is close to zero enthalpy of mixing
Hmix. The nanodomain short-range order should have a positive impact on improving the
radiation resistance of alloys by increasing the recombination of vacancies and interstitials in
the border zones of the nanodomains.
This also implies that with a glance the heterogeneity of chemical composition, the alloys
in the concentration range of ~ 39-41 wt% chromium are in a no equilibrium metastable state.
Solid solution of these alloys has the concentration and density of components fluctuations,
availability and the development of which is crucial for increasing radiation resistance of
materials.
To determine the effect of short-and long-range order on the recombination of point
defects was conducted 5 MeV electron irradiation [20] of nickel alloy with 32 wt% chromium
in the states after quenching (short-range order) and after annealing at 450°C for 40 000 h
(long-range order). In analyzing the structure was used the method of positron annihilation by
measuring the angular distribution of annihilation photons. Changes in the shape of the
spectra due to the capture of positrons by defects were characterized by standard S - and W -
parameters. S - and W - parameters were determined as the ratio of the coincidence rate sum
in the angle range of θ from 0 to 3.5 mrad and 10 to 20 mrad to the total rate of coincidences,
respectively. When positrons are trapped by vacancy-type defects or dislocations, the value of
S - parameter increases and W decreases, i.e. increases the probability of annihilation of

positrons with conduction electrons, and decreases the probability of annihilation with the
electrons of the ion core.
Fig. 35 shows the dependence of parameter S, proportional to the number of vacancies in
the matrix of the irradiated alloy from the electron fluence.
○ - long-range ordering
■ - short-range ordering [20]
Figure 35. Effect of short-and long-range ordering on the accumulation of vacancies in the irradiated at
200° C 5 MeV electrons alloy Ni-32Cr-1Mo:
It is seen that with increasing electron fluence the number of vacancies in which the
positrons annihilate is increased. However for the alloy in a state of short range ordering at a
fluence of ~ 2x1022 m-2 the growth of S - parameter is slowing, and the values of S -
parameters reach saturation. This means that the emerging vacancies during irradiation of the
alloy in a state of short-range ordering recombine with the interstitial atoms. At the same time
for the alloy in a state of long-range ordering the growth of values S - parameter at irradiation
continues, i.e. vacancies in the matrix continues to accumulate.
This experiment shows that the tetragonal distortions that occur in the matrix during the
formation of short-range order nanodomains are effective traps for point defects. From this
experiment should also be an important conclusion: when the alloy is given in a stable state,
for example by long-range ordering, the alloy can not provide the high recombination of
vacancies and interstitials.
At the same time the recombination accelerating of vacancies and interstitials is
observed, as determined by the study of experienced Ni-Cr alloys in no equilibrium
metastable alloys, removed from the composition of the stoichiometric phase Ni2Cr and
having approximately the same inclination as to ordering and to phase separation, i.e. near to
zero enthalpy of mixing of solid solution. Due to nonstoichiometric of composition and near-
zero enthalpy of mixing in the structure of these alloys during neutron irradiation does not
occur long-range ordering and is observed only short-range order.
Study of physical mechanisms of radiation damage of materials and the ways of
increasing resistance to embrittlement and swelling is the most important problem of radiation
material science, and in this regard, understanding of dependence the recombination of point
defects on the effects of short-range ordering is of considerable interest.
In the process of the study of ordering alloys of system Ni-Cr with near-zero enthalpy of
mixing was found that their evolution during neutron irradiation is stopped at the stage of
formation of tweed contrast with the period of oscillation of zones nickel enriched ∼ 5 nm. It
is known that due to the high surface energy such small particles have high catalytic activity
[21]. The number of constituent atoms in an isolated metal particle is small, so the distance
between the energy levels of electrons δ = EF/N (EF — Fermi energy, N — the number of
atoms in a particle) comparable to the thermal energy kBТ. Activity of small metal particles
begins to appear when δ in size close to kBТ. This allows us to estimate the size for which
show catalytic properties of the particle.
In accordance with the algorithm proposed in [22], were determined for metals used in
nuclear industry (Table 10), parameters for calculating the number of atoms in a particle: the
number of electrons in 1см3
Zρm
n = 0,6022⋅1024
A (1),
where Z - number of conduction electrons, ρm - bulk density (g/cm3), А - relative atomic mass;
radius of a sphere whose volume is equal to the amount paid for a conduction electron
1
⎛ 3 ⎞ 3
rS = ⎜ ⎟
⎝ 4πn ⎠ (2)
and the Fermi energy of metals
50,1эВ
EF =
(rS a0 )2 (3),
where а0 - Bohr radius = 0.529 Å.
Table 10. Initial data for calculating the number of atoms in the particle [9]
Element Z ρ (g/cm3) n, 1022 cm-3 rs, Å rs/ а0 ЕF, eV

Ti 2 4.51 11.34 1.28 2.42 8.55
V 2 6.1 14.42 1.18 2.23 10,07
Cr 1 7.19 8.33 1.42 2.68 6.98
Fe 2 7.87 16.97 1.12 2.12 11.15
Ni 2 8.9 18.26 1.09 2.06 11.81
Calculating the number of atoms N = EF /kBT in the isolated metal particle from the atoms
of transition elements gives, in accordance with the Fermi energy, defined by (3), the values
shown in Table 11.
Table 11. Assessment of the number of atoms for some transition metals in accordance
with the catalytic activity
The number of atoms in a particle (at temperature*, °C), = EF / kBT

Temperature* 20 100 200 300 400 500 600 700 800
Ti 342 267 214 174 147 128 114 102 93
V 423 330 264 216 182 158 141 126 115
Element
Cr 279 218 174 142 120 104 93 83 76

Fe 446 348 279 228 192 166 149 133 121
Ni 472 369 295 241 204 176 157 141 128
With such quantity of the atoms a linear particle size is 2 - 4 nm and, therefore, in this
size range should significantly change the physical and the catalytic properties of small
particles of these atoms.
The evaluation shows that short-range order nanodomains with an average size ∼ 2 -3 nm
formed in alloys of nickel and chromium under irradiation with neutrons are the particle of
size at which is actively manifest catalytic properties. Short-range order nanodomains form
homogeneously distributed in the matrix system or a sub lattice of the catalytically active sites
that interact with vacancies and interstitials. With the linear size of the nanodomains ∼ 2 - 3
nm, the number of the atoms in them in the system Ni-Cr amounts 150 - 250 for a
temperature of 600 K [9]. One can assume that consolidation of point defects in the zone of
influence of nanodomains short-range ordering is an effective factor in the recombination
accelerating and increasing radiation resistance of the alloys.
4. DISCUSSION: SELF-ORGANIZATION OF THE NANOCRYSTALLINE

STRUCTURE OF TRANSITION METALS
Now back to the unusual results of the experiment on neutron irradiation, in which was
discovered a more long incubation period to maintain a stable structure of the alloy Ni-42Cr-
1Mo compared with other materials. On the diagram state of the system Ni-Cr figurative
point of radiation-resistant alloy Ni-42Cr-1Mo is located in the region of metastable alloys,
which have enthalpy of mixing close to zero (Hmix ∼ 0). Due to this the alloy Ni-42Cr-1Mo
affects only short-range order during prolonged radiation and thermal aging. Less radiation
resistant alloy Ni-47Cr-1Mo alloy lies in the region of alloys which subjected to
discontinuous disintegration at exposed to prolonged thermal aging and therefore in
conditions of the reactor are more inclined to transition to stable structural condition. Over the
stabilization of the structure there should be accelerated accumulation of dislocation loops.
Mechanism of the recombination accelerating in alloys of system Ni-Cr of type Ni-42Cr-
1Mo with near-zero enthalpy of mixing is as follows. In the alloys with the structure of short-
range order (38 - 41 wt% Cr) the changes in the displacement cascade of the composition of
matrix entails the formation of the local areas short-range ordering. If in the local region
begins short-range ordering, then the adjacent areas of the matrix are enriched with
chromium. In the chromium-enriched areas begins to form discontinuous disintegration. In
this case, the surrounding matrix is enriched with nickel. In these areas begins to form short-
range ordering, etc. Short-range ordering and the short-range disintegration help each other,
and the as a result no one phase is not formed, which corresponds to the spinodal condition.
This mechanism suggests that the processes in the metastable structure, leading to the
appearance of nuclei of new phases are competing. However, it seems obvious that if for the
nucleation of short-range order is necessary only tendency to minimize of the system free
energy, for the formation of clusters should be further upward diffusion. From this point of
view, the formation of clusters (zones of Guinier - Preston) are less likely than the emergence
of short-range order nanodomains, since during the nucleation of short-range order
nanodomains the energy gain will be greater..
However, the tetragonal distortions move over the matrix due to the fact that in the
displacement cascades the formed nanodomains of short-range ordering and disintegration are
destroyed and re-formed in another place. As a result of differences in lattice constant and the
density of the FCC phase and the nanodomains short-range order in the alloys appear the
mobile local distortions that significantly accelerate the recombination of the surrounding
radiation-induced point defects.
Ordered arrangement of the short-range order nanodomains with an interval of ∼ 5 nm
allows evaluate them as an ordered structure of traps of vacancies and interstitials.
The short-range order nanodomains form crystalline structure, but do not have time to
form long-range order domains of the superstructure due to failure in displacement cascades
and the near-zero enthalpy of mixing. During the formation of nanodomains the surrounding
volume is depleted with one of the components, creating a periodic change in chemical
composition. Such zones are constantly shuffled and placed on a matrix, which ultimately
ensures the presence of traps and recombination of point defects in any point of the matrix,
where the formation of displacement cascade would not have happened with the
corresponding appearance of an excess concentration of vacancies and interstitials. In these
processes, the dynamic equilibrium of ordering and disordering is the decisive factor that
controls the structural transformations.
Such is the concept of maximal radiation resistance of the metastable alloys.
It is known that in the presence of distortions in the crystal lattice the interstitial atoms
tend to get into the stretched spaces, and vacancies on the contrary, in tight. Therefore,
existing and emerging after quenching and aging in the alloys Ni-Cr-Mo fluctuations of
concentration and density represent a system or sub lattice of short-range order nanodomains
- traps for vacancies and interstitials.
In the process of neutron irradiation the primary knocked atoms destroy the integrity of
the nanodomains, takes place a process similar to hardening of the alloy - there is a local
disordering. Alloy tends to decrease the free energy and again is locally ordered; then again in
the displacement cascade is destroyed etc. Thus, the behavior of the atomic structure of the
alloy under neutron irradiation becomes in the local points the character of the continuous
reversible change from ordering to disordering and vice versa, i.e. the character of dynamic
equilibrium.
The orientation and shift of the dynamic equilibrium of the metastable alloy in the
direction of the order or disorder is determined by the alloy composition, i.e. electron density
and other physical characteristics, as well as the parameters of an open system. With the
change in the physical characteristics of the alloy appears to be changed the effectiveness of
interaction of vacancies and interstitials with the crystal lattice. We can assume that the rate
of ordering of the alloy must be equal to the rate of disorder in the neutron field or be a few
below it. Such a preponderance of the rate of disorder in the neutron field is required in order
to prevent the transformation of the metastable solid solution through the ordering in the
stable.
Calculating the number of displaced atoms in the dislocation loops according to the
formula N=0,141d2ρ, where d - the average size of dislocation loops, ρ - the average
concentration showed: in the alloy Ni-42Cr-1Mo after neutron irradiation dose of ~ 32 dpa
the number of displaced atoms in the loops, i.e. the number of the not recombined interstitials
was approximately two times less than in the alloy Ni-47Cr-1Mo.
One can with certainty assume that the advantages of alloys of Ni-42Cr-1Mo, as a stable
during neutron irradiation material, are based on the metastability of the structure derived
from a tendency to short-range order. The above analysis also suggests that the development
of the traps associated with the short-range ordering nanodomains, is the most effective
mechanism for improving radiation resistance at temperature of 350°C.
Thus, the analysis of the results of neutron and electron irradiation clearly demonstrates
that the alloys in a metastable state having a tendency to the short-range order much more
slowly accumulate radiation damages compared to the more stable alloys in the state of long-
range ordering, and especially in comparison with the austenitic steels.
The obtained experimental facts indicate that in assessing the number of secondary
radiation defects must be taken into account as the conditions for the appearance of point
defects and the effectiveness of the conditions for their recombination. The higher the rate of
the creation the displacements in the core, the greater number of vacancies and interstitials
per unit of time are created in the crystal lattice of the alloy. And, in its turn, the higher the
rate of ordering of the structure, the greater amount of point defects recombines in a time unit.
The equality of these rates will provide the dynamic equilibrium of the structure during
neutron irradiation.
The analysis of own and literature data shows that the established mechanism of
accelerated recombination of point defects is effective not only in radiation-resistant alloys
system of Ni-Cr, but also in the alloys with the others system components. The use of
radiation-resistant alloys of different systems is predetermined by operating temperature
range in which in structure of the alloy are formed the short-range order nanodomains.
Different classes of materials of active zones have the different temperature ranges of
use. For example, alloys based on nickel-chromium are suitable to ∼ 400°C, iron-based alloys
with the chromium - approximately 550°C. At higher temperatures, are perspective ternary
alloys based on vanadium with titanium and chromium, which can provide a more stringent
operating conditions arising from the 2 - 3-fold reduce the amount of the core of fast reactors
per unit of installed capacity.
Thus in accordance with the proposed phenomenological model the alloys that are
resistant to neutron irradiation in a specific temperature range necessary to select in the range
of compositions with the enthalpy of mixing, which is close to zero. This implies that the
alloys have the metastable structure of short-range ordering and about the same penchant for
ordering and phase separation, i.e. structure that as the swing periodically inclined then to
ordering then to the disintegration.
The distinctive feature of short-range ordering nanodomains as the traps for vacancies
and interstitials is that they are formed from atoms of the components of the matrix, however,
such atoms can be either in the a disordered state or in a state of short-range order. And the
transition from one state to another in the open system of neutron irradiation is carried out
continuously. Under the influence of the temperature the matrix is ordered, creating the traps
and under the influence of the neutron flux - becomes disordered, losing the traps. And these
"the swing" is working as long as the active zone works. This feature of the behavior of solid
solution of the metastable alloys with the near-zero enthalpy of mixing we call "the self-
organization of the nanocrystalline structure" of transition metal alloys under the influence of
temperature and radiation.
CONCLUSION
The analysis of experimental results of the study the structure-phase state of the austenitic
steels, nickel-based alloys after quenching and aging, neutron irradiation at temperatures of
300 - 350°C and by electrons with the 5 MeV allows us to make the following conclusions.
1) The formation in the solid solution of nickel-based alloys of the short-range order
nanodomains as the traps of vacancies and interstitials with the period ∼ 5 nm and
concentration ≥ 1024 m-3 is the most effective way to ensure the radiation resistance.
2) The crystal structure of the short-range order nanodomains is formed in the process
of the neutron irradiation under the influence of radiation enhanced temperature,
while under the influence of irradiation is destroyed.
3) The effect of "the self-organization of the nanocrystalline structure" of alloys,
inclined to short-range ordering during neutron irradiation consists in the permanent
formation in the solid solution of the short-range order nanodomains, being destroyed
in the displacement cascades.
4) In accordance with the proposed phenomenological model the alloys that are
resistant to neutron irradiation in the specific temperature range should be selected in
the range of compositions with the enthalpy of mixing which is close to zero. This
implies that the alloys have the metastable structure of short-range order and about
the same penchant to the ordering and phase separation.
5) A necessary condition for the minimal accumulation of secondary radiation-induced
defects in the alloys is the lagging speed of short-range ordering from the rate of
disorder in the neutron field, which prevents the formation of stable phases and the
shift of the solid solution state to the stability.
6) The choice of alloy components with the metastable structure for the operation in
conditions of specific open system should be determined by its parameters, that is the
temperature and intensity of irradiation, as well as the relevant physical
characteristics of the material.
REFERENCES
[1] S. N. Votinov, V. I. Prokhorov, and Z. E. Ostrovskii, Irradiated Stainless Steels (Nauka,
Moscow, 1987) [in Russian].
[2] Russell K.C. //Acta Met. (1978). Vol. 26, 1615-1630.
[3] V. P. Kolotushkin, //Fiz. Met. Metalloved. (2004) 97 (2), 63–73; Phys. Met. Metallogr.
97, 177–187 (2004)].
[4] H. Wollenberger //Journ. of Nucl. Mater. (1991) Vol. 179-181, Part 1, 76-80.
[5] V. P. Kolotushkin and S. N. Votinov //Metalloved. Term. Obrab. Met. (2006) 10(616),
27–31.
[6] V. P. Kolotushkin, V. P. Kondrat’ev, A. V. Laushkin, and V. N. Rechitskii
//Metalloved. Term. Obrab. Met. (2003) 11, 7–10.
[7] V. P. Kolotushkin, V. P. Kondrat’ev, and V. N. Rechitskii //Perspektivnye Materialy,
(2004) 1, 36–45.
[8] V. P. Kolotushkin, A. A. Chernyshev, and A. A. Veligzhanin //Materialovedenie,
(2006) 1, 18–24.
[9] V.P. Kolotushkin, A.A. Parfenov //Russian Metallurgy (Metally) (2010) 3, pp. 197–
206.
[10] V. P. Kolotushkin and V. N. Rechitskii //Vopr. At. Nauki Tekh., Ser. Materialoved.
Nov. Mater. (2004) 1(62), 131–138.
[11] M. I. Solonin, V. P. Kondrat’ev, S. N. Votinov, V. N. Rechitskii, Yu. I. Kazennov, A.
B. Alekseev, and V. P. Kolotushkin //Vopr. At. Nauki Tekh., Ser. Materialoved. Nov.
Mater. (1995) 1 (52), 13–20.
[12] G.N. Makarov //Uspekhi Fizicheskikh Nauk. (2008) 178, No 4, 337-376.
[13] R.А. Andrievskii // Fiz. Met. Metalloved, (2010) 110, No 3, 243-254.
[14] V. P. Kolotushkin, V. P. Kondrat’ev, A. V. Laushkin, and V. N. Rechitskii //Vopr. At.
Nauki Tekh., Ser. Materialoved. Nov. Mater. (2005) 1(64), 348–353.
[15] Yu. A. Bagaryatskii //Dokl. Akad. Nauk SSSR (1958) 122 (5), 806–809.
[16] V. P. Kolotushkin, V. N. Rechitskii, O. B. Ermolova, and A. V. Laushkin //Vopr. At.
Nauki Tekh., Ser. Materialoved. Nov. Mater. (2003) 1(61), 94–104.
[17] S. N. Votinov and V. P. Kolotushkin //Metalloved. Term. Obrab. Met. (2006) 1(607),
33–37.
[18] I. Ya. Dekhtyar //Dokl. Akad. Nauk SSSR (1952) 85 (3).
[19] V. P. Kolotushkin, S. N. Votinov, and V. I. Sorkoin //Materialovedenie, (2007) 6(123),
40–46.
[20] A.P. Druzhkov, V.P. Kolotushkin, V.L.Arbuzov et al. //The Physics of Metals and
Metallography, (2006) 101, No. 4, 369-378.
[21] A.I. Gusev. Nanomaterials, Nanostructures, and Nanotechnologies. – Moscow:
FIZMATLIT, 2005.
[22] N. Ashcroft and N. Mermin, Solid State Physics (Holt, New York, 1976; Mir, Moscow,
1979).
Chapter 4
TRANSITION METAL COMPLEXES OF SCHIFF BASE

LIGANDS OF 3-FORMYLSALICYLIC ACID:
SYNTHETIC PATHWAYS AND USEFUL PROPERTIES
Saikat Sarkar1 and Kamalendu Dey2

1
Department of Chemistry, Santipur College, Santipur,
Nadia, West Bengal, India
2
Department of Cheistry, University of Kalyani, Kalyani,
Nadia, West Bengal, India
ABSTRACT
The contributions of transition metal complexes of 3-formylsalicylic acid and
varieties of Schiff base ligands based on it have been vividly reviewed and discussed.
The mode of reactions along with the structural topologies with such variety of ligands
having a wide range of donor atoms such as N, S, O, P are typically commented. The
metal complexes of such ‘privileged ligands’ show many interesting polymeric /
supramolecular coordination architectures involving different weak forces e.g. C-H….π,
π….π etc. interactions. The synthesis and practical properties of the complexes of various
nuclearities of the Schiff bases derived from 3-formylsalicylic acid with monoamines,
diamines, polyamines and substituted amines are discussed systematically. Such
transition metal coordination complexes, due to their intriguing topologies, have found
their applications in magnetism, catalysis, biological activities, solid state properties,
charge transfer and useful materials. A few non-transition metal complexes have also
been disussed for comparison.
1
E-mail addresses: saikat_s@rediffmail.com (S. Sarkar)
2
Email address: kdey_chem@rediffmail.com (K.Dey) Former Professor of Chemistry and UGC Emeritus Fellow.
166 Saikat Sarkar and Kamalendu Dey
1. INTRODUCTION
In 1864 Hugo Schiff [1] first described the reaction between an aldehyde and an amine
lead to a condensation product called Schiff base according to his name. Modern chemists
still prepare Schiff bases, and now-a-days active and well-designed Schiff bases are being
prepared. Schiff bases may also act as ligands to form metal complexes coordinating metal
centres through imine nitrogen(s) and other groups usually linked to aldehyde, and they can
also stabilize them in various oxidation states, enabling the use of such complexes for a large
variety of useful catalytic transformations and recently they are considered as “privileged
ligands” [2].
Many simple organic aldehydes were used to react with variety of amines to produce a
large number of Schiff base ligands. 3-Formylsalicylic acid (Figure 1.1), first synthesized by
Duff and Bills [3], has been extensively utilized as an efficient precursor for the synthesis of
numerous multidentate Schiff base ligands. 3-Formylsalicylic acid, itself, may also act as a
ligand for the synthesis of many metal complexes.
Figure 1.1.
2. METAL COMPLEXES OF 3-FORMYLSALICYLIC ACID

3-Formylsalicylic acid, owing to the presence of three different binding groups (viz. -
COOH, -CHO and -OH) may act as monobasic bidentate (like salicylaldehyde), dibasic
bidentate (like salicylic acid) or dibasic phenoxy oxygen bridged tridentate ligand [4-6].
Dey et al. [6] had synthesized anionic complexes of V(IV)O and V(V)O with H2fsa of the
types (NH4)2[VO(fsa)2].2H2O and NH4[VO(fsa)(OH)2(H2O)].
The IR spectra [4,7] of the complexes suggest that both OH and COOH groups
participate in chelate formation after deprotonation and the ligand behaves as a dibasic
bidentate fashion. The electronic spectra of the V(IV)O and V(V)O have been measured and
compared with the previously reported low-symmetry oxovanadium complexes [8,9] of
hydroxy acids. Qualitative band assignments suggest that the geometry of these V(IV)O and
V(V)O complexes are intermediate between square pyramid and bi-pyramid.
Binuclear Cu(II) complexes of the types Cu2Cl2(fsa)H2O, Cu2Cl2(Hfsa)2H2O,
Cu2(CH3COO)2(Hfsa)2.H2O and Cu2(fsa)2.3H2O were prepared and characterized by Dey and
coworkers [10]. Binuclear Ni(II) complexes of H2fsa are also known [11].
Encapsulation of metal complexes inside microporous supports has emerged as a general
technique to increase and control selectivity of catalysis [12]. Zeolites can play as effective
and attaractive supports for encapsulation as they are thermally and chemically stable having
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 167
a regular, crystalline framework. Besides, because of their similarities with the

metalloenzymes, the encapsulated complexes are expected to mimic enzyme active site for
catalytic reactions such as oxidation [13,14], hydrogenation [15], dehalogenation [16], etc.
Considering the above characteristics Xavier et al. [17] synthesized and characterized Y
zeolite encapsulated Co(II), Ni(II) and Cu(II) complexes of 3-formylsalicylic acid which were
used as a novel solid catalysts for the partial oxidation of benzyl alcohol and ethyl benzene.
Encapsulated Cu(II) complexe has been found to be more efficient than the other two
complexes for the oxidation reaction.
However, thorough investigations on the metal complexes of H2fsa are yet to be done.
3. METAL COMPLEXES OF LIGANDS DERIVED FROM

3-FORMYLSALICYLIC ACID
The formyl group (-CHO) of H2fsa can easily be condensed with different monoamines,
aminoalcohols, aminophenols, aminothiol, aminothiophenol, suphanilamides, diamines and
polyamines leading to different types of Schiff bases. Most of these Schiff bases were
synthesized and their versatility as ligands has been investigated over the past several years
by different group of workers. The accounts of which are given below under appropriate
headings covering the salient features of the topics.
3.1. Mono-, Bi- And Polynuclear Complexes of the Schiff Base Ligands
Derived by the Condensation of 3-Formylsalicylic Acid with
Monoamines, Aminoalcohols, Aminoacids, etc.
Condensation reactions of appropriate amino compounds and 3-formylsalicylic acid (1:1

molar ratio) lead to the formation of corresponding Schiff base ligands (Scheme 1.1).
Scheme 1.1.
Depending on the nature of R, the Schiff base ligands can act as a monobasic bidentate
(Figure 1.2), dibasic tridentate (Figure 1.3) and phenoxo-bridged dibasic tridentate (Figure
1.4) ligand. Most of the transition and non-transition metals form these types of complexes
[18-23].
Figure 1.2.
Figure 1.3.
Figure 1.4.
Magnetic moment values of the Fe(II) and Fe(III) complexes of H2fsaan and H2fsaana
show that the complexes belong to the ionic or outer-level covalent category [7]. Some
V(IV)O and V(V)O complexes of dibasic tridentate Schiff bases, H3fsagly and H2fsaana have
also been prepared and characterized [9]. The complexes synthesized are of the types,
[(Hfsagly)VO(H2O)], [(Hfsagly)VO(H2O)(Py)], [(Hfsaana)VO(H2O)], [(Hfsaana)VO(H2O)
(OH)] and [(Hfsagly)VO(OH)]2. The structures of the complexes have been discussed on the
basis of elemental analyses, magnetic moments and spectroscopic (IR, UV-Vis.) data. The
V(IV)O complexes are paramagnetic with magnetic moment ranging from 1.77-1.81 B.M.,
which is close to the spin-only value of 1.73 B.M. for a d1 system. A square-pyramidal
geometry has been assigned to the [(Hfsagly)VO(H2O)] and [(Hfsaana)VO(H2O)] complexes
and their electronic spectra are interpreted using the ordering of vanadium d orbitals, i.e.
dxy<dxz, dyz<dx2-y2<dz2 proposed by Vanquickenborne and McGlynn [11,24]. The other
complexes found to be diamagnetic. The electronic spectrum of the dimeric compound in

nujol mull shows one broad band around 17000 cm-1 which may be considered as metal
ligand charge transfer [18,25].
Dey et al. [10] reported the synthesis and characterization of Cu(II) complexes of
H2fsama, H2fsaan and H2fsaeao. All of these complexes except one are binuclear with
subnormal magnetic moments at room temperature. Using gav = 2.2 and a value of 6 x 106
c.g.s. units for TIP (temperature independent paramagnetism), the energy separation between
singlet and triplet states, i.e. –2 J, have been calculated using Bleaney and Bowers equation
[19,26] which support the occurrence of strong antiferromagnetic spin-exchange interaction
between the two Cu(II) centres. Similar Cu(II) complexes have also been described by
Tanaka et al. [11,27].
Sugar borne Schiff bases and their metal complexes can play wide variety of roles in
different fields like, metal-base affinity chromatography materials [28], chiral homogeneous
catalysts [29], metal chelators for clinical use [30], etc. Inspite of the above facts, the field of
sugar-metal chemistry is still unexplored vividly. Keeping the facts in mind, Adam and Hall
synthesized a new sugar containing Schiff base ligand and its Cu(II) complex [31]. Methyl
3,4,6-tri-o-actyl-2-amino-2-deoxy-β-D-glucopyranoside hydrobromide on condensation with
H2fsa gives the Schiff base which on reaction with copper(II) acetate afforded Cu(II) complex
in alcoholic solution. From detail study of mass spectrometry and ESR spectra it has been
concluded that the complex has binuclear Cu(II) structure. The overall reactions are shown in
Scheme 1.2.
Scheme 1.2.
Other complexes of this type with first and second row transition metal ions have also
been synthesized. Some boron derivatives of this ligand are also known [32]. Amine
containing polysaccharides on reaction with such aldehydes also produce Schiff base which
on treatment with the metal salts also give metal complexes [33].
3-Formylsalicylic acid (H2fsa) on reaction with 2-aminothiophenol in methanol yielded
benzothiazoline [34-36], (H2chpbzn) which remains in equilibrium with its corresponding
Schiff base form, H3mpcsalim, in solution (Figure 1.5).
However, in the solid state the benzothiazoline structure has been suggested from the
infrared spectroscopic data. The absence of νCHO, νC=N and νSH at 1660 cm-1, ~1600 cm-1 and
~2600 cm-1 respectively support the benzothiazoline structure [37].
Figure 1.5.
Some complexes of Cu(II), Ni(II), Zn(II), Pd(II) and U(VI)O2 have been synthesized by
the treatment of the benzothiazoline solution with the corresponding metal salts [34]. In these
complexes, the Schiff base actually functions as a tridentate NSO donor ligand. Based on
physico-chemical data the authors proposed following monomeric structures for Zn(II) and
U(VI)O2 complexes (Figure 1.6) but sulphur-bridged dimeric structures for Cu(II), Ni(II) and
Pd(II) complexes (Figure 1.7) [34]. Crystallographic studies of such complexes will be of
much interest.
Figure 1.6.
Figure 1.7.
Scheme 1.3.
Scheme 1.4.
Recently Dey et al. synthesized many new metal complexes and organometallic
compounds by the reaction of benzothiazoline (H2chpbzn) with (π-C5H5)2TiCl2, (π-C-
5H5)2ZrCl2, CrCl3.6H2O, FeCl3, VOSO4.2H2O, VOCl3, Ni(OAc)2.4H2O, Na2PdCl4, Me2TlCl,
Ph2TlCl, BiCl3 and SbCl3 under varied reaction conditions [36]. During complexation, the
Schiff base (H3mpcsalim) involves in its dianionic form utilizing NSO donor set of atoms,
except in case of Bi(III) and Sb(III), where the benzothiazoline acts as a unidentate neutral N-
donor ligand. Such Lewis basic behaviour of benzothiazoline is very rarely encountered in
literature [35,38-40]. The reactions are summarized in the Schemes 1.3-1.5.
Scheme 1.5.
Scheme 1.6.
As proposed by Nag et al. [34] sulphur-bridged dimeric structures have been proposed
for Ni(II), Pd(II) and V(IV)O complexes. Corresponding molybdenum (III, IV, V, VI)
complexes are also known [41].
The reaction of [(Hmpcsalim)Ti(π-C5H5)2Cl] with Me3SiE (where E stands for SMe,
NMe2, N3 and C≡CPh) affording new organotitanium(IV) compounds have also been
discussed (Scheme 1.6).
Due to immense importance of benzothiazoline type of ligand in coordination chemistry,
Dey and co-workers [42] have shown interest to synthesize a new benzothiazolidine
compound and studied similar types of reactions with different metal salts. The reaction of 3-
formylsalicylic acid with 2-aminoethanethiol produces the thiazolidine (H2chptz) compound
which shares equilibrium in solution with its corresponding Schiff base form (H3mcsalim)
(Figure 1.8).
Figure 1.8.
The reaction of this thiazolidine with Me2SnCl2 is very interesting. It gives NSO chelated
organotin(IV) compound having trigonal bipyramidal geometry (Figure 1.9). Similar type
organotin(IV) complex with benzothiazoline (Figure 1.10) has also been reported.
Figure 1.9.
Figure 1.10.
The 1H NMR spectra of organotin(IV) complex [(Hmcsalim)SnMe2] (Figure 1.9)

displays the Sn-CH3 protons as one sharp singlet at δ 0.89 ppm. The observed 3J (119Sn-CH3),
2
J (117Sn-CH3) and 3J (119Sn-N=CH+) values (74.5, 72.1, 38.8) respectively are within the
ranges reported for other trigonal bipyramidal (CH3)2Sn(IV) chelate complexes with two
methyl groups in the cis-configuration [43].
The dimeric Cu(II) complex also draws our attention. The ESR data of the complex in
polycrystalline and solution phase (DMF) at room temperature (300 K) exhibits four lines
(63Cu, I = 3/2) slightly anisotropic spectra at higher magnetic field. At liquid nitrogen
temperature (77 K) the spectrum shows axial type with g║ (2.280) and g┴ (2.091) with respect
to DPPH marker. The trend g║ > g┴ > ge (2.0048) suggests that the unpaired electron is
localized in dx2-y2 [44,45].
The cyclic voltammogram (CV) of the Cu(II) complex exhibits one quasi-reversible
redox couple at E1/2 = 0.16 V (∆Ep = 150 mv) and an irreversible peak at 0.8 V vs. SCE. First
response is reductive due to CuII→ CuI and the second one is oxidative CuII→ CuIII.
Dey et al. [46] very recently synthesized a new hydrazone ligand, 3-carboxy-2-
hydroxybenzaldehydemorpholine N-thiohydrazone (H2chbmth) by the condensation of H2fsa
and morpholine N-thiohydrazide (Hmth) and studied its reactions with 3d and 4d transition
metal salts. The thiohydrazone ligand remained as thioketo form in the solid state. However,
in solution, thioketo and small amount of thiolo tautomeric forms (H2chbmth and H3chbmthol
respectively) may remain in equilibrium (Figure 1.11). Depending on the pH’s of the reaction
medium and the nature of the metal salts used, the ligand is found to act as monobasic
tridentate, dibasic tridentate, monobasic bidentate and neutral bidentate fashion.
Figure 1.11.
The dimeric Cu(II) complex, [Cu(Hchbmthol)]2 (scheme 1.7) is found to show low
magnetic moment (1.44 B.M.) which might be due to spin-coupling resulting from super
exchange through the bridging sulphur (oxygen) atom or metal-metal bonding as observed
earlier on similar such complexes [47-49]. The decrease in the magnetic moment with the
decrease in the temperature indicates the presence of antiferromagnetic coupling between the
two centres.
Scheme 1.7.
Using the idea of an easy route for the synthesis of immobilized transition metal
complexes by the reaction of polymer-anchored ligand with metal ions, recently, Syamal et
al. [50,51] have reported the synthesis and characterization of Cu(II), Ni(II), Co(II), Fe(III),
Zn(II), Cd(II), Mn(II), Mo(VI), Zr(IV) and U(VI)O2 complexes of polystyrene supported
resin containing Schiff base derived by the reaction of chloromethylated polystyrene, 3-
formylsalicylic acid and ethanolamine (Scheme 1.8).
The reaction of PS-Cl and H2fsa in 1:4 molar ratio leads to the 100 % conversion to PS-
FSal, which does not contain any chlorine. But the same reaction in the ratio 1:<4 always
resulted the product containing chlorine. These types of polymer-assisted complexes might
have wide range of applications [52-54] based on their physico-chemical properties.
The same group of workers extended their idea to synthesize polystyrene-anchored mixed
Schiff bases and their coordination complexes [55,56,57] in view of their numerous
applications in organic synthesis [58], biological systems [53], catalysis [59] and analytical
chemistry [60]. They designed the mixed Schiff base having H2fsa as one component fixed
which are shown in Scheme 1.9.
Scheme 1.8.
Scheme 1.9.
The Maurya group of researchers also synthesized many polymer bound Schiff base
metal complexes and studied their immense catalytic applications [61-64]. Schiff bases have
been derived by the condensation reaction of 3-formylsalicylic acid with 2-aminoethanol, 3-
aminoethanol, 2-amino-2-methylpropanol, β-alanine, D,L-alanine, L-isoleucine and o-
hydroxybenzylamine. Then, the polymer bound oxovanadium, oxomolybdenum and copper
complexes have been synthesized, characterized and employed as efficient catalysts in
various oxidation reactions. The recycling studies also indicated the reusability of such
catalysts for atleast three times without any significant loss in their potential catalytic activity.
Recent research of Maurya et al. has shown a new gateway for the desulfurization of
various organo-sulfur compounds to their corresponding sulfones using polymer bound
oxovanadium(IV) and oxovanadium(V) complexes [65]. The desulfurization process is
deadly required in petroleum industry. The general mechanism (Scheme 1.10) of oxidation
has also been proposed based on UV-Vis, EPR, 51V NMR and DFT study.
Scheme 1.10.
Scheme 1.11.
The immobilization of H2fsa on the surface of amino group containing silica gel phases
and the use of such phases for the extraction of different metal ions from aqueous solution
using batch equilibrium has been reported by Mahmoud et al. [66,67]. The synthesis of silica
gel bound H2fsa has been shown in the Scheme 1.11.
The selectivity of the different phases is evaluated by atomic absorption spectroscopy and
found with highest exchange capacity of 0.95-0.96 mmol/g for Fe(III) ion. A method for the
recycling of immobilized silica gel after metal extraction has also been demonstrated for
practical utility.
The synthesis and reactivity of a Cu(II) complex of N-4-acetophenyl-3-carboxy-

salicylaldimines (Figure 1.12) has been studied [68] to build up a hierarchy for similar type
metal complexes of N-substituted salicylaldimine.
Figure 1.12.
Further condensation of the ketone parts of the Schiff base and its Cu(II) complex
generates new ketimine center which leads to transamination reaction. The reaction involves
exchange of amine parts in the Schiff bases with the added amines and in situ complexation
of the freshly generated Schiff bases with Cu(II) ion present in solution.
Mononuclear complexes of Co(II), Ni(II) and Cu(II) with the Schiff base derived from
H2fsa and hydroxylamine hydrochloride have been characterized by infrared spectra, thermal
analysis and molar conductance studies [69]. The Co(II) and Cu(II) complexes are found to
be paramagnetic while Ni(II) exhibits diamagnetism.
The Schiff base ligand formed by the condensation of H2fsa and 2-
(aminomethyl)pyridine have been first investigated by Coppola et al. [70] by fast atom
bombardment mass spectrometry and metastable ion studies.
Monomeric [Cu(Hfsagly)].2H2O and trimeric [Cu3(fsagly)2].6H2O are prepared by the
reaction of CuCl2.2H2O, H2fsa, gycine and Na2CO3 in Cu: H3fsagly as 1:1 and 2:1 ratio
respectively. The spectroscopic (IR, UV-Vis.) and magnetic studies proposed the trimeric
Cu(II) complex as [Cu(H2O)6][Cu2(fsagly)2] with uncoordinated glycinato ‘O’. A strong
antiferromagnetic coupling is observed in [Cu2(fsagly)2]2- unit with J = -185 cm-1 [71].
The coordination chemistry of alkaline earth metals with such ligands received far less
attention than that with transition metal ions. Keeping this in view Erxleben and co-workers
[72,73] tried to synthesize Mg (3s2) complex with the Schiff base ligand, H3fsagly. The
Mg(II) complex is prepared by the substitution reaction of the corresponding Zn(II) complex
in DMSO. It is found that Zn(II) is susceptible to substitution by Mg(II) when DMSO is used
as the non-aqueous solvent. But the presence of small amount of water decrease the yield of
the Mg-complex mainly owing to the high affinity of Mg(II) for aqua ligand. The whole
observation (Scheme 1.12) has been monitored by 1H NMR spectroscopy.
Presently the homo- and heteropolymetallic complexes are of much interest due to their
unique physico-chemical properties associated with metal-metal interactions [74,75]. Several
synthetic routes have been proposed for their synthesis, one being consists of the ingenious
use of compartmental ligands. The newly synthesized unsymmetrical polydentate Schiff base,
3-[N-2-(pyridylether)fomimidoyl]salicylic acid (H2fsapea), derived by the reaction of H2fsa
and 2-(2-aminoethyl)pyridine in ethanol in 1:1 molar ratio, belonging to this compartmental
behaviour category, is used to synthesize a series of bi-[76-79] and tri-nuclear [77,78] Cu(II)
complexes. The 3d-4f hexanuclear cluster compounds [76] are also cited using dinuclear
species as precursor.
Scheme 1.12.
In all these complexes ligand utilizes two different adjacent coordination sites, N2O and
O2 and favours the formation of polymetallic systems containing phenoxo groups as
exogenous bridges.
Variable temperature magnetic susceptibility measurements for the chloro- bridged
dicopper complex, [Cu(Hpefdsa)2Cl2], show the presence of very weak ferromagnetic
coupling between the Cu(II) ions with J = 0.15 cm-1. But the antiferromagnetic coupling
between the two Cu(II) centres is observed in [Cu2(pefdsa)2] (J = -617 cm-1) and trimeric
Cu(II) complex [Cu3(pefdsa)2](ClO4)2 with J = -228 cm-1. The Scheme 1.13 shows synthetic
routes for preparation of some of the bi- and tri-nuclear complexes.
But to explain the magnetic behaviour of the hexanuclear clusters {Cu4Ln2}, the clusters
may be taken as two individual {CuIILnIIICuII} triads. A weak antiferromagnetic Cu(II)-Cu(II)
interaction through the closed shell rare earth ion is noticed for {Cu4La2} complex having
JCuCu = -3.13 cm-1. Inspite of antiferromagnetic coupling, the {Cu4Gd2} complex shows
ferromagnetic Gd(III)-Cu(II) interaction with JGdCu = 6.0 cm-1, which is attributed to the
coupling between the Gd(III)Cu(II) ground configuration and the Gd(III)Cu(II) charge-
transfer excited configuration in which the electron is transferred from the slightly occupied
3d type copper orbital towards an empty 5d type gadolinium orbital. The Gd(III)-Cu(II)
interaction is quite peculiar in the sense that owing to the contraction of 4f orbitals, the usual
mechanisms involving 4f-3d overlap densities are inoperative [76,77].
In this connection the work of Tuna et al. [79] may be mentioned, who for the first time
reported a pentanuclear complex of {CuIICuIIMnIICuIICuII} moiety with the ligand H2fsapea
having novel magnetic properties. The IR spectrum of the complex shows two bands at 1564
and 1439 cm-1, attributed to the νCOO stretching modes, which are characteristic of the
bridging carboxylate groups.
The variable temperature magnetic susceptibility measurements indicate the presence of
antiferromagnetic interactions within the {CuIICuIIMnIICuIICuII} pentanuclear entity. The
bridging capability of the phenolic oxygen between the Cu(II) and Mn(II) ions in {Cu4Mn}
system might be responsible for the most probable exchange pathway for the
antiferromagnetic coupling. On the basis of the above discussion and considering the
electronic spectra the following structure for the pentanuclear complex may be proposed
(Figure 1.13). However, only x-ray structure can say the last word.
Scheme 1.13.
Figure 1.13.
In continuation of this study, a new oxalato bridged dinuclear Cu(II) complex of the same
ligand, H2fsapea (Figure 1.14), and phenolato bridged dinuclear Cu(II) complex of the ligand
derived from H2fsa and N,N-dimethyl-1,3-propanediamine (Figure 1.15) has been reported
[80]. Both the complexes are crystallographically characterized and show strong
antiferromagnetic coupling interaction between the two Cu(II) centres.
Figure 1.14.
Figure 1.15.
Two dinuclear Zn(II) complexes (Figure 1.16) of unsymmetrical binucleating Schiff base
ligand 3-{N-[2-(dimethylamino)ethyl]iminomethyl}salicylic acid (H2fsadmen) (Figure 1.17)
have been synthesized by the reaction of ZnX2 (X = NO3-, CH3COO-) with H2fsa and N,N-
dimethylethylenediamine at neutral or slightly acidic pH [81]. In the nitrate complex,

[Zn2(Hfsadmen)2(H2O)2](NO3)2.2H2O the centrosymmetric Zn(II) ions are bridged by two
phenolato oxygens. Further coordination sites of the ligand are the imine nitrogen and
carboxylate oxygen, while the amino nitrogens of the ligand side arms are protonated. The
basic structure of the acetato analogue, [Zn2(Hfsadmen)2(CH3COO)2].6H2O is identical to
that of nitrate complex except the water ligands coordinated to Zn(II) ions in the former have
been replaced by acetate ion in the later.
Figure 1.16.
Figure 1.17.
On dissolution in DMSO or DMF these dizinc complexes are converted into mononuclear
species [Zn(Hfsadmen)]+ and the cleavage is accompanied by migration of the ammonium
proton to the carboxylate group and coordination of the amino nitrogen to zinc. Reaction of
[Zn2(Hfsadmen)2(CH3COO)2].6H2O with 1(N) NaOH at pH 9.9 produces yellow cubes of
tetranuclear zinc complex, [Zn4(fsadmen)4].6.5H2O that is found to show asymmetry in
coordination around the four zinc centres having N2O3 and N2O4 coordination environments
and located at the corners of a nearly square-planar rectangle.
In contrast to H2fsadmen the Schiff base 3-[N-(2-pyridylmethyl)iminomethyl]-salicylic
acid (H2fsapma) (Figure 1.18) (formed by H2fsa and 2-picolylamine) forms the mononuclear
complex with zinc in acid medium (Figure 1.19). The ligand H2fsapma bind Zn(II) via
deprotonated phenolic oxygen, the imine nitrogen and pyridine nitrogen while the carboxylate
group remains free.
Figure 1.18.
Figure 1.19.
When a solution of the above zinc complex is brought to pH 8.9 with 0.5(N) NaOH,
deprotonation of the carboxyl (-COOH) group results to form a tetranuclear compound
[Zn4(fsapma)4].4.5H2O with a cubane like {Zn4(o-phenolato)4} core situated around a
crystallographic two-fold axis of symmetry.
Two tetranuclear Cu(II) assembly complexes comprised of one dimetallic di(3-
iminomethylsalicylato)dicopper(II) core and two monometallic Cu(II) auxiliaries attached to
the imino nitrogens of the dinuclear core through an alkane chain have been reported [82].
The synthetic route to the preparation is shown by the Scheme 1.14. One Cu(II) complex,
[Cu4(LigA)](PF6)4.2CH3CN.3H2O has one di(2-pyridylethyl)amine copper(II) as the
monometallic auxiliary and the other Cu(II) complex [Cu4(LigB)](ClO4)4.CH3OH has
1,4,8,11-tetraazacyclotetradecanecopper(II) as the monometallic auxiliary.
The cryomagnetic property suggests that the bimetallic core and the monometallic
auxiliaries are magnetically independent of each other, and a strong antiferromagnetic
interaction operates within the bimetallic core to achieve a perfect coupling above 100 K.
This is also supported by the previous magnetic studies of the similar complexes [83].
[Cu4(LigA)](PF6)4.2CH3CN.3H2O in acetonitrile shows a two-electron reduction at –0.08
V (vs. SCE) followed by a one electron reduction at –0.42 V. Together with EPR studies for
electrolyzed solutions, it is shown that the two monometallic auxiliaries are reduced at –0.08
V, followed by an intramolecular electron transfer from one of the reduced auxiliaries to the
bimetallic core and by the second reduction at the resulting monometallic Cu(II) centre at –
0.42 V: {Cu(II)-Cu2(II,II)-Cu(II)}/ {Cu(I)-Cu2(II,II)-Cu(I)}→{Cu(I)-Cu2(I,II)-Cu(II)}/
{Cu(I)-Cu2(I,II)-Cu(I)}. The cyclic voltammogram (CV) of [Cu4(LigB)](ClO4)4.CH3OH in

DMSO shows two couples at–0.68 and –0.99 V attributable to the stepwise reduction:
{Cu(II)-Cu2(II,II)-Cu(II)}/{Cu(II)-Cu2(I,II)-Cu(II)}/{Cu(I)-Cu2(I,II)-Cu(I)}. The tetranuclear
complex, [Cu4(LigA)](PF6)4 is reduced with ascorbic acid to {Cu(I)-Cu2(I,II)-Cu(I)} species,
whereas [Cu4(LigB)](ClO4)4 does not undergo reduction with ascorbic acid.
Scheme 1.14.
The syntheses and structure determination of mixed valence pentanuclear manganese

complex [{MnIIMnIII(fsatren)}2MnII(H2O)4].n(sol) where, H6fsatren is tris-[(2-hydroxy-3-
carboxybenzylidene)aminoethyl]amine and ‘sol’ is H2O or MeOH and hexanuclear cobalt
complex [Co4IICo2III(fsaea)2(OMe)4(NO3)2(OAc)2(MeOH)2] where, H3fsaea is 3-[N-(2-
hydroxyethyl)formimidoyl]salicylaldehyde by T. Shiga and H. Oshio is also worth
mentioning [84]. It is clear from the crystal structure that [Mn3IIMn2III] complex has a linear
pentanuclear core bridged by phenoxo and carboxyl group and [Co4IICo2III] complex has a
face shared incomplete tetra cubane core bridged by μ3-MeO-, phenoxo, alkoxo and carboxyl
groups. An antiferromagnetic interaction between the Mn(II) ions in [Mn3IIMn2III] complex
and a ferromagnetic interaction between Co(II) ions in [Co4IICo2III] complex have been
proved by magnetic susceptibility studies. The structures of both the complexes are show
below (Figure 1.20).
Figure 1.20.
The technique ‘complex as a ligand’ was also successfully used by R-J. Tao et al. [85] to
synthesize a 1D chain coordination polymer having chemical formula {[Cu4L2(H2O)].H2O}n
where, H4L is 2-hydroxy-3-[(E)-({2-[(2-hydroxybenzoyl)imino]ethyl}imono)methyl]benzoic
acid. The polymer has been synthesized by the assembly reaction of precursor complex
K2CuL. 1.5 H2O and Cu(CH3COO)2. H2O in 1:1 molar ratio. The x-ray crystal structure has
shown that the polymeric chain structure has been formed by dissymmetrical tetranuclear
units and the Cu-Cu antiferromagnetic interactions have also been observed.
Double stranded monohelical complexes with exclusive M-helicity of divalent iron,
nickel, cobalt and zinc have been synthesized from an unsymmetrical chiral Schiff base
ligand, prepared by a two-step reaction of 3-formylsalicylic acid and (1R, 2R)-
diaminocyclohexane in alcoholic solvents [86]. The 1:1 condensation product was shown to
exist as a zwitterion in the solid state having pleated weak hydrogen bonding interactions.
The chiral ligand behaves as a monobasic tridentate donor system having carboxylic acid
group remains free in all the complexes. But the same ligand reacts in distinctly different way
to bind with divalent copper, in which the ligand was shown to be transformed into a
symmetric tetradentate ‘salen’ type ligand with uncoordinated carboxylic acid groups.
Another most interesting diazine tetratopic helicand ligand (H4L) was synthesized by the
condensation of 3-formylsalicylic acid and hydrazine and the ligand was used to synthesize a
novel chiral coordination polymer which was built up from tetranuclear helicates connected
by Na ions [87]. The anionic helicates results from the self-assembly process involving the
heterotopic helicand and Co(II) and Fe(III) ions. It was reported that the tetratopic helicand
offers two different types of binding domains: one with only oxygen donor atoms and the
other one with N and O donor atoms. The two metal ions were connected by the phenoxo
bridging oxygen atoms which belong to the two chelating moieties and the oxygen of the
carboxyl group helps to build the helical motif through subsequent coordination to a third
metal ion. The crystal structure of the coordination polymer shows that the polymer consists
of triple-stranded dianionic helicates, [L3Co2IIFe2III]2-, and the three ligands twisted along N-N
single bonds. The variable temperature magnetic moment values indicate the spin states of
different metals ions. The perspective view [Figure 1.21 (a)] and the space-filling
representation [Figure 1.21 (b)] of the coordination polymer with M helicity is shown below.
Figure 1.21.
3.2. Binuclear Complexes of 3-Formylsalicylic Acid Oxime
Metal condensed compounds are of much interest due to their physico-chemical

properties arise from the interaction of the metal centres in close proximity. Generally
complex ligands having one or more sites capable of donating other metal ions are used to
synthesize metal-condensed compounds. Complex ligands with cis-dioximate groups within
the molecular framework are of particular interest [88-99] because the dioximate-bridge is
known as a good magnetic mediator between a pair of metal ions.
3-Formylsalicylic acid oxime (H3fsaox) is obtained [100] by the reaction of 3-
formylsalicylic acid and hydroxylamine hydrochloride in presence of NaHCO3.
The ligand H3fsaox on reaction with Cu(II) and Ni(II) salts gives the following binuclear
complexes [Cu2(Hfsaox)2]0.5H2O, Na[Cu2(Hfsaox)(fsaox)].3H2O, [Ni2(Hfsaox)2].2.5H2O,
[Ni2(Hfsaox)2(H2O)4].8H2O. The x-ray structure shows that Na[Cu2(Hfsaox)(fsaox)].3H2O
has a cis-arrangement of the two ligands providing dissimilar {CuN2O2} and {CuO4}
chromophores sharing the two phenolic oxygen atoms. The N2O2 cavity has a hydrogen-
bonded N-O….H….O-N linkage as the lateral chain and the Cu(II) in this site has a square-
pyramidal geometry with a water molecule at the axial site. The Cu(II) at O4 cavity has a
planar geometry.
[Ni2(Hfsaox)2].2.5H2O has a trans- configuration with respect to its two ligands and each
Ni(II) has a six-coordinate geometry with two H2O molecules at the axial sites. The
interconversion among the dinuclear Cu(II) and Ni(II) complexes have been established by
pH adjustment (Scheme 1.15 & 1.16).
Scheme 1.15.
Scheme 1.16.
3.3. Mononuclear Complexes of the Schiff Base Ligands Derived by the

Condensation of 3-Formylsalicylic Acid with Diamines
3-Formylsalicylic acid (H2fsa) on reaction with diamines in 2:1 molar ratio produces
different types of Schiff base ligands as shown in the Scheme 1.17.
Scheme 1.17.
These Schiff bases are capable of acting as dibasic tetradentate ligands having N2O2
donor with –COOH groups being remained free in the complexes except in the complexes of
U(VI)O2 and Eu(III) ions. For these ions the ligands generally act as a tetrabasic tetradentate
O2O2 donor system. Such ligands form numerous numbers of mononuclear complexes with
different transition, non-transition and lanthanide metal ions [101-117]. The corresponding
disodium salt has also been reported [118]. The general structures have been shown below in
the Figures 1.22-1.25.
Figure 1.22. Figure 1.23. Figure 1.24. Figure 1.25.
The complexes have been characterized by the help of elemental analyses, molecular
weights, magnetic moments, and molar conductance, UV-Vis., IR, ESR, CD and 1H NMR
spectral data [119-156]. The x-ray crystal structures of some of the complexes have also been
determined [157-160].
Mononuclear complexes of Cu(II), Ni(II) and U(VI)O2 with the Schiff base, H4fsadmtp,
derived by the condensation H2fsa and 1,5-diamino-3-thiapentane (dmtp) have been
synthesized and properly characterized. In the complexes, Ni(II) and Cu(II) lie in inner N2SO2
site while U(VI)O2 takes the outer O2O2 site.
It is interesting to mention here that Kahn and co-workers [161,162] studied some spin
crossover, high-spin, low-spin Co(II) complexes with Schiff base derived from H2fsa and
ethylenediamine (en). The magnetic behaviour of [Co(H2fsaen)L] [161,162] and
[Co(H2fsaen)L2] [161,163] species clearly suggests that, in both kinds of compounds, the
lowest high-spin (S = 3/2) and low-spin (S = 1/2) states are very close in energy. Indeed,
though the χM.T products (χM = molar magnetic susceptibility) related to
[Co(H2fsaen)(EtOH)] and [Co(H2fsaen)(4-t-BuPy)] (where, 4-t-BuPy is 4-tert-butylpyridine)
follow, in a wide temperature range, a Curie-law characteristic of low-spin form, the slight
increase of χM.T with temperature that is observed above ~200 K for the former complex and
~250 K for the later seems to indicate the beginning of an occupation of excited high-spin
levels. Likewise in the six-fold coordinated complexes, the ligand field appeared to
approximate the conditions suitable for the pairing of electrons: in [Co(H2fsaen)(3-MePy)2],
Co(II) is found to retain an essentially high-spin state from 300-4 K, while in [Co(H2fsaen)(
Py)2] and [Co(H2fsaen)(H2O)] it exhibited thermally induced quartet ↔ doublet spin
transitions. It is worth nothing that these transitions are very abrupt, in contrast to the
previously reported for other Co(II) complexes, which are generally of the continuous type
[164-173].
Again Thuery and Zarembowitch show the influence of the apical Lewis bases on the
spin state of the metal ion in order to forecast the nature of the L ligands that would likely to
spin-crossover compounds [174]. The Co(II) complexes of the type [Co(H2fsaen)Ln] (where L
is a substituted pyridine) shows a wide range of magnetic properties . The Five-coordinate (n
=1) species with L = 2-MePy recognized a spin-quartet ground state, and its magnetic
property was described using a rhombic spin Hamiltonian ((D2 + 3E2)1/2 = 16.7 cm-1, g = 2.04)
with additional temperature independent paramagnetism (Nα = 211 x 10-6 cm3 mol-1). The L =
3-OHPy adduct has undergone a kinetically controlled S = 3/2 ↔ S = 1/2 crossover, while
retaining an essentially high-spin character and the cobalt complex with L = 4-MePy is in the
low-spin state even at room temperature.
The six-coordinate species (n = 2) with L = 3-MePy, 3-NH2Py and 3,5-Me2Py present a
predominant high-spin character. The effect of the nature of the apical ligands on the spin-
state of Co(II) is discussed in terms of σ-donor ability, orientation of the pyridine ring and
steric requirements [173,175-180].
Recently Tuna et al. [181] has reported a five-coordinate Co(II) complex containing a
photosensitive ligand which displays a thermally-induced S = 1/2 ↔ S = 3/2 conversion at
high temperature. The schematic representation of the preparation of the complex is shown
(Scheme 1.18).
The coordination of trans-1-(4-methylphenyl)-2-(4-pyridyl)ethene (t-MeSPy) is proved
by electronic spectral data which corresponds to the t-MeSPy π-π* absorption in the room
temperature around 315 nm (~31750 cm-1) [182,183].
Like other transition metal ions [112] a stable Hg(II) complex of the ligand H4fsapnol has
been formed by the reaction of HgCl2 solution with the corresponding Schiff base H4fsapnol.
But the elemental anlyses show metal-ligand ratio as 2:1. This 2:1 complex, further on
treatment with KI solution, a transient red colouration is formed which ultimately gives a
greenish-yellow solution (with excess of KI solution) with the separation of a yellow
crystalline compound, identified as [Hg(H2fsapnol)] [19].
Scheme 1.18.
The above observation may be explained by assuming that each Schiff base molecule in
these metal chelates is also associated with one HgCl radical by displacing a hydrogen atom
in the free hydroxyl group. The Hg-O bond thus formed in the 2:1 complex is not so strong as
Hg-N bond [184,185] and as such the (>CHO.HgCl) group may easily be effected by KI
solution producing K2HgI4 and [Hg(H2fsapnol)] (Scheme 1.19).
Scheme 1.19.
H4fsaen may act as compartmental ligand; the inner compartment consists of N2O2 and
outer compartment O2O2 donor atoms. For transition elements it uses generally the inner
N2O2 coordination site while for lanthanoids (e.g. Eu(III)) it can form complexes using outer
O2O2 site [113,186]. Recently both Cu(II) and Eu(III) complexes have been investigated
[186] by photo-acoustic (PA) and fluorescence spectroscopy. The ‘outside’ and ‘inside’
coordination sphere shows different ligand field strength. The emission spectrum of
[Eu(H2fsaen)(H2O)2]Cl.H2O (Figure 1.26) shows four characteristic emissions of Eu(III) (λ =
594, 614, 650 and 701 nm) attributable to the 5D0 to 7F1, 7F2, 7F3 and 7F4 transitions
respectively.
Figure 1.26.
The Schiff bases derived from 3-formylsalicylic acid and diamines also formed
heterochelates [106], involving quadridentate Schiff base ligands and bidentate ligands (L-L)
of the type, [M(Lig)(L-L)] (where M = Co(III), Cr(III) or Mn(III) and L-L = acac-, gly-, etc.)
(Scheme 1.20).
The same workers also reported some mixed ligand complexes of Co(III) of the type
[Co(H2fsaen)L2]X.2H2O. All the mixed ligand complexes were characterized with the help of
elemental analyses, molar conductances, magnetic moment values, UV-Vis., IR and 1H NMR
spectroscopic data [187-202].
From the above observations it may be concluded that the reaction of [Co(H2fsaen)] with
bidentate chelating agents and oxygen to give Co(III) mixed ligand chelates in which the
dibasic quadridentate Schiff base has been rearranged from a planar to a twisted conformation
by the displacement of only one oxygen atom from equatorial plane to the planar isomer.
The Schiff bases H4fsaen and H4fsatn do not give any mixed ligand complex with Co(II)
ions, instead they produce square planar Co(II) chelates of the type Na2[Co(fsaen)] and
Na2[Co(fsatn)] respectively. These compounds are characterized with help of elemental
analyses, magnetic moment value and spectroscopic data [203-206].
Scheme 1.20.
The Schiff bases have been employed to synthesize varieties of oxomolybdenum (V and
VI) complexes. Detailed characterization data are also available [207-213].
Non-planar configurations of the quadridentate Schiff bases are also observed in the
Mo(VI)O2 complexes (Figure 1.27) as discussed above.
Figure 1.27.
The tendency of the group MoO2 to assume a cis-configuration forced the essentially
planar ligand to occupy the non-planar geometry. This aspect had been discussed earlier
[209,214]. The 1H NMR spectral data also support this view [209-214]. 3-Formylsalicylic
acid (H2fsa), on treatement with boric acid, formed 3-formylsalicylato salt [215]. Thus the
Schiff bases H4fsaen and H4fsatn yielded tri-coordinated boron complexes [216]. These
complexes might have some importance in view of their industrial utility [217], biological
uses [218] and activities [219-221]. The syntheses are depicted in the Scheme 1.21.
Scheme 1.21.
The compound as shown above is interesting in the sense that it has potentiality of being
used as a precursor for further novel syntheses. Thus it smoothly reacts with Ph2BCl (1:1
molar ratio) in thf at around 5o C in di-nitrogen atmosphere and yielded a new organo boron
derivative (Scheme 1.22).
Scheme 1.22.
The compound on reaction with Ni(OAc)2.4H2O in thf at room temperature, yielded

another novel organoboron derivative containing Ni(II) (Scheme 1.23). The study of the
reaction of Ni(II) complex with lanthanide ions will be of much interest.
Scheme 1.23.
Analogously Pd(II) and Pt(II) derivatives were also synthesized [222]. The corresponding
compound [Na(H2fsatn)B(OH)2 ] had also been prepared (Figure 1.28).
Figure 1.28.
All these compounds are solid and coloured. They are stable in air and also in their
solutions. However, the aqueous solutions of the complexes are hydrolysed on prolonged
standing and the solution turned strongly basic probably due to liberation of NaOH upon
hydrolysis.
Scheme 1.24.
Scheme 1.25.
The low values of molar conductance for boron chelates in the solvents suggest their non-
electrolytic nature. However, the conductance value in water, measured after 2 h of
dissolution, increased sufficiently indicating thereby extensive hydrolysis.
The electronic absorption spectral band positions and their molar extinction co-efficients,
when compared with the spectra of the ligands, suggest for complex formation [220,223].
The complex [Ni(fsaen){B(OH)2BPh2}] is characterized with the help of elemental
analyses, magnetic moment, UV-Vis., IR and 1H NMR spectroscopic data [224-231].
Dey and Nandi [232] have successfully synthesized a new 1,2,3 trisubstituted benzene
derivative by using mononuclear Ni(II) complex of the Schiff base ligand, H4fsaen. Here
metal ions play the vital role in protecting the reactive groups.
Dey et,al. [233,234] and Dilworth et al. [235] have synthesized lithio and silyl-
derivatives of several quadridentate Schiff base ligands and also studied their reactions
leading to new synthesis of coordination complexes, organo-derivatives of boron, titanium,
zirconium, tin and organo-oxoderivatives of phosphorus (see later discussion).
Lithio or silyl derivative of mononuclear complex, N,N'-ethylenebis{(3-

carboxy)salicylideneiminato}nickel(II) is easily converted to different organic compounds
and are shown in the following scheme (Scheme 1.24):
The free carboxylic acid group of mononuclear complex [Ni(H2fsaen)] had also been
converted to the corresponding acyl chloride functionality, which on Fridel-Craft acylation
with suitable substrates followed by normal work-up produced different organic compounds
which is shown in the Scheme 1.25.
3.4 Organoderivatives of the Schiff Base Ligands Derived From 3-

Formylsalicylic Acid and Diamines
Cobalt-carbon σ-bond [236,237] is found in vitamin B12-coenzyme. The Co(III) ion

containing a coordinated carbanion [238] in such organometallic complexes stimulated the
interests to synthesize and characterize a wide variety of organocobalt complexes with other
ligands [239-242]. Organoderivatives of dibasic tetradentate ligand with different metal ions
are also known [102,105]. Dey et al. synthesized organotin(IV) [102] and organocobalt(III)
complexes [105] of dibasic tetradentate ligands H4fsaen and H4fsapnol having general
formula shown below (Figure 1.29).
Figure 1.29.
The organoderivatives are hydrolyzed easily with aqueous mineral acids, and the light
remarkably accelerates this. This ‘photo lability’ represents connection between the present
complexes and that of the corrinoids [243,244]. All the diamagnetic Co(III) complexes are
characterized by elemental analyses, thermogravimetric analysis, magnetic moments and
spectroscopic (electronic and IR) data [102,105,245-247].
3.5 Electrochemical Behaviour of the Complexes of Schiff Base Derived

From 3-Formylsalicylic Acid and Diamine
Complexes in which a ligand can bind two metal centres in close proximity are of much
interest in particular in electrochemical field. Such complexes have attracted growing
attention because of their ability to illuminate the redox properties of such complexes, which,
for instance are connected with the function of metalloenzymes incorporating two metal ions
in close proximity to the active site.
The electrochemical behaviour of a series of mononuclear and dinuclear complexes of

Ni(II), Cu(II) and U(VI)O2 ions have been studied with the Schiff base H4fsaen. The
hexadentate H4fsaen ligand has an outer O2O2 and an inner N2O2 coordination site. The redox
properties of the metal ions in these two different and adjacent chambers have been
investigated [248].
It is observed that the reduction of metal centre in the N2O2 compartment is greater than
that of in the O2O2 compartment. The redox properties of such complexes have also been
compared with the ligand H4aapen derived by the condensation of o-acetoacetylphenol and
ethylenediamine and it has been seen that the H4fsaen complexes are in general easier to
reduce than the corresponding H4aapen complex [249,250].
3.6. Binuclear Complexes of the Schiff Base Ligands Derived from

3-Formylsalicylic Acid and Diamines
The chemistry of polymetallic Schiff base complexes is subject of considerable interest.

Ligands derived from the reaction of 3-formylsalicylic acid (H2fsa) and different diamines
have one inner N2O2 core and outer O2O2 coordination site capable of binding two similar or
dissimilar metal ions in these two closely placed chambers. Such homo- or heterobimetallic
complexes are useful in homogeneous catalysis [251] and biochemical field [252,253],
particularly in connection with metalloenzymes which involve two metal ions at their active
site [254]. Specially, the recognition that super oxide dismutase [255] and cytochrome
oxidase [256] contain two kinds of metal ions has stimulated an interest in heterodinuclear
complexes.
Two magnetic centres whenever brought into close proximity our natural inclination is to
assume that, like bar magnets, they will arrange themselves so that they couple
antiferromagnetically, and thus reduce the overall magnetism of the dimer. This spin-
exchange phenomenon is thus common to such bimetallic complexes [74].
Another interest in heterodinuclear complexes is to find new reactivities or functions
associated with such hetero centres where distinct features of the constituting metal ions are
accumulated or amplified to give rise to unprecedented cooperative effects [257,258]. The
potential of this polynuclear area can be gauged from the appearance of many reviews in the
literature [259-261]. All these considerations have led the investigators to investigate the
synthesis and characterization of polynuclear metal complexes with special emphasis on
hetero-polynuclear complexes.
The hydrolysis of bis(p-nitrophenyl phosphate) (BNPP) and p-nitrophenyl phosphate
(NPP) was observed to be catalyzed by the heterodinuclear Cu(II)-La(III) complex in 50%
aqueous DMSO at 35 °C [262]. It was also reported that the Cu(II)-La(III) complex exhibited
a relatively higher catalytic function on NPP hydrolysis, while the hydrolysis of BNPP was
slightly more efficient in the presence of mononuclear La(III) complex.
The Schiff base H4fsaen and its homologous ligands having two dissimilar coordination
sites, N2O2 and O2O2 can form dinuclear complexes [11,263-272] sharing the bridging
phenolic oxygens [11,263]. When only transition metal ions participate in the heterodinuclear
complex, then those transition metal ions, which are higher in the Irving-Williams order,
occupy the N2O2 site and those metal ions that are lower in that series occupy the outer O2O2
site [265-272]. Further, during the synthesis of heterodinuclear complexes containing
transitions metal ions and lanthanoids, the O2O2 site prefer to bind with the lanthanoids
[273,274].
The synthesis of Co-Ln [275] complexes (Ln = La, Nd or Gd) has been carried out by a
step-wise reaction, that is mono-nuclear Co(II) complex is isolated as [Co(H2fsaen)(Py)2] and
subject to reaction with a Ln(III) ion. The Co(II)-Ln(III) complexes are
[CoLa(fsaen)(CH3OH)(NO3)], [CoNd(fsaen)(H2O)2(NO3)], [CoGd(fsaen)(H2O)(NO3)]. In
these complexes the cobalt ion is bound at the N2O2-site and the lanthanoid ion at the O2O2
site. All these complexes are quite stable in air and fully characterized with the help of
elemental analyses, molar conductivity, UV-Vis. and IR spectroscopic data [276-285].
At liquid nitrogen temperature the configuration around the cobalt is dependent upon the
nature of the base. It is suggested that substrates possessing N- and O-donor groups such as 2-
aminoethanol is specifically bind at the cobalt-lanthanoid centre via 'N' to the cobalt and 'O' to
the lanthanoid ion.
Cu(II) salts also give Cu(II)-Ln(III) hetero-binuclear complexes (Ln = La, Pr, Nd, Sm,
Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb or Lu) with the Schiff base ligands such as H4fsaen and
H4fsapn [273] . These complexes have also been fully characterized with the help of physico-
chemical and spectroscopic data [27,286-292].
The frequencies of ligand field bands, due to Cu(II) ion bound to the N2O2 site i.e.
[CuN2O2] chromophore, on forming a binuclear complex with a lanthanide ion at the
coordination site O2O2, are higher than those of mono-nuclear complexes of Cu(II) with same
ligand [263]. Such a blue shift of the d-d band may be attributed to the enhanced planarity of
the [CuN2O2] chromophore on forming a binuclear complex with a lanthanoid ion at the
coordination site.
When the complexes are dissolved in Py, DMSO or DMF, the d-d band frequency
decreases in order of the solvent DMSO>DMF>Py for the binuclear complexes whereas it
decreases in order of DMF>DMSO>Py for mononuclear complexes [273]. These trends is
due to the different affinities of solvent molecules for Cu(II) and Ln(III) ions.
The absorption spectra and circular dichroism (C.D.) spectra of Cu(II)-Gd(III) [282, 293]
hetero-binuclear complexes suggest that substrates with a nitrogeneous and oxygeneous
groups (amino alcohols, amino acids, 8-quinolinol, amino acid esters) were specifically bound
to Cu(II)-Gd(III) centre, with the nitrogen to the copper and with the oxygen to the
gadolinium.
The V(IV)O also gives different binuclear complexes with rare earth(III) ions with the
Schiff base ligand H4fsaen [294]. The general formula of these complexes is
[VOLn(fsaen)(NO3)(H2O)n ](m-n)H2O. where Ln = La, Pr, Eu, Gd, Tb.
The V(IV)O ion and Eu(III) ion in the respective mono-nuclear complexes is bound at the
O2O2 site of the ligand, where as in the V(IV)O-Ln(III) complexes V(IV)O ion is bound at the
N2O2 site and Ln(III) ion at the O2O2 site because Ln(III) ion is more hard than V(IV)O ion,
strongly prefers oxygen donor atoms.
Dinuclear Cu(II)-M(II) (where M = Co, Ni, Cu, Zn, Mg, Ca and Ba) and Cu(II)-Fe(III)
heterodinuclear complexes [287] of N,N'-bis(3-carboxysalicylidene)-1,1-dibenzyl-
ethylenediamine, (H4fsadb) have been prepared and characterized [26,195, 264,265,269,295].
Other complexes of the series are also known. e.g. [CuM(fsadb].nH2O where M = Co, Ni, Cu,
Zn, Mg, Ca, Ba and [CuFe(fsadb)].3/2H2O. The magnetic susceptibilities, measured in the
temperature range 78-300K, indicate antiferromagnetic spin-exchange interactions operating
between metal ions. The Cu(II/I) redox potentials of the hetero metal complexes are much
lower as compared to that of [Cu(H2fsadb)H2O].
The binucleating ligand H4fsaen has formed Cu(II)-Me2Sn(IV) and Co(II)-Me2Sn(IV)
complexes of the type [MSn(CH3)2(fsaen)] (M = Cu, Co), where the Cu(II) or Co(II) ion is
bound at the inner N2O2 site and the Sn(IV) ion at the outer O2O2 site with two methyl groups
at the axial positions. Both complexes are fairly stable towards atmospheric moisture in the
solid state but decomposes into a mononuclear complex [M(H2fsaen)] by a trace amount of
water when dissolved in solution. Spectroscopic investigations on the Cu-Sn complex in
pyridine reveals that the coordination of pyridine to the Cu(II) is sterically hindered by the
methyl groups attached to the neighbouring Sn(IV) ion. In the case of Co-Sn complex such a
steric effect of methyl groups is not pronounced enough to hinder the coordination of pyridine
to the axial site of the Co(II). ESR spectra at liquid nitrogen temperature reveals that the
Co(II) ion adopts a penta-coordinate structure at room temperature and a hexa-coordinate
structure near liquid nitrogen temperature with pyridine molecule at the axial site [296].
Recently a side-off septadentate Schiff base ligand has been synthesized by the reaction
of H2fsa and bis(2-aminophenyl)disulphide (apds) [297]. Though the ligand contains eight
donor atoms (N2S2O4), it, however, acts as a septadentate side-off ligand leaving one
disulphide sulphur atom. Thio-ether is not a good ligand to bind class ‘a’ metal ions [298] and
in this ligand it is located in an internal position within the complexing side chains as shown
in the Scheme 1.26.
Scheme 1.26.
This ligand forms several complexes with the inner N2SO2 with copper ions and outer
O2O2 site having transition/non-transition metal ions. The dinuclear copper complex exhibits
subnormal magnetic moment due to spin-exchange. The complexes have been characterized
by the usual physico-chemical methods and the proposed structures are given in the Figures
1.30 to 1.32.
Figure 1.30.
Figure 1.31.
Figure 1.32.
Nag et al. [299] has also synthesized some mono and heterodinuclear transition metal
complexes with a polydentate Schiff base ligand derived from H2fsa and 1,2-bis(o-
aminophenylthio)ethane.
The complexes [CoMn(fasen)(Py)3], [CoMn(fsapn)(Py)3] and [CoFe(fsapn)(Py)3] [Figure
1.33] have been synthesized and characterized [268]. Cryomagnetic data indicate no spin-
exchange interaction operating between the low-spin Co(II) and the high-spin Mn(II) or Fe(II)
ions.
Figure 1.33.
Scheme1.27.
Dey et al. have shown that [Ni(H2fsaen)] has been successfully silylated or lithiated [224]
to get [Ni{(SiMe3)2fsaen}] and [{(Li)2fsaen}] which in turn react with R2MX2 (R = CH3,
C6H5, π-C5H5; M = Sn, Ti; X = Cl), R2BCl (R = C6H5), RPCl2 (R = CH3, C6H5) and POCl3 to
yield the complex of the type [Ni(M)2R2fsaen], [Ni(BR2)2fsaen], [Ni(PR)fsaen] and
[Ni(POCl)fsaen] (Scheme 1.27). All the complexes have been properly characterized.
Similarly mononuclear complexes of Ni(II), Pd(II) and Sn(IV) upon silylation coupled
with desilylation and reaction with R2SnCl2 afforded many new organotin(IV) complexes
[300] (Figure 1.34).
Figure 1.34.
A magnetically important Cu(II)-V(IV)O heterodinuclear complex [CuVO(fsaen)CH3OH]

has been synthesized and confirmed by molecular structure [301]. In this complex copper ion
is five-fold coordinated to two nitrogens, two phenolic oxygens and the oxygen of methanol
molecule and the vanadium ion is also five-fold coordinated to two phenolic oxygens, two
carboxylic oxygens and the oxygen of the vanadyl group. The metallic ions and the oxygen of
the methanol and of the vanadyl group are in a mirror plane σ for the two square-pyramids
CuN2O3 and VO5. These pyramids point in the same direction. The nature of intramolecular
interaction has been explained easily by the orthogonality of the magnetic orbitals centered on
Cu(II) and V(IV)O metallic ions, antisymmetric and symmetric respectively, with regard to
mirror plane σ. The magnetic behaviour of the complex is studied in the temperature 4-300 K
which reveals an intramolecular ferromagnetic coupling characterized by a ground triplet
state separated by around J = 118 cm-1 from the excited singlet state. The magnitude of the
ferromagnetic interaction is interpreted from considerations of overlap density between the
magnetic orbitals (Figure 1.35).
Figure 1.35.
Casellato et al. has reported [302] the synthesis and characterization of a new
heptadentate compartmental Schiff base ligand (H4fsadmtp) synthesized by the condensation
of H2fsa and 1,5-diamino-3-thiapentane (dmtp) in methanol. The ligand contains an inner
N2SO2 and an outer O2O2 sites and gives homo- and heterodinuclear complexes with Cu(II),
Ni(II) and U(VI)O2. The syntheses of the complexes have been shown in the Scheme 1.28.
Perovskite type oxides (LaxMOy) are known to be efficient in catalysis for oxidation
reactions [303-307]. Initially, they have been synthesized by grinding a stoichiometric
mixture of rare earth oxide and a metal oxide, and heating subsequently at 800-1000 ºC [308].
Unfortunately, this method generates highly heterogeneous solids with a poorly controlled
stoichiometry. An improvement for the synthesis of such perovskite compounds has been
observed by using the process of thermal decomposition of heterodinuclear complexes with
Schiff base as a ligand [309]. Cations of the heterodinuclear complexes of the type
[LaM(fsaen)]NO3.H2O (M = Ni(II), Co(II), Fe(II)) is first exchanged with the interlamellar
cation of montmorillonite, and subsequent thermal decomposition of the derivative under
oxygen at ca. 500-600 ºC produces a clay-perovskite oxide (LaxMOy) type nano-composite
[310-312].
Scheme1.28.
3.7. Mono- and Binuclear Complexes of the Schiff Base Ligands Derived by
the Condensation of 3-Formylsalicylic Acid with Polyamines
Cassellato et al. [21,313] have reported the synthesis of some new potentially
heptadentate compartmental ligands by the reaction of 3-formylsalicylic acid (H2fsa) with
diethylenetriamine (H4fsadien) (Figure 1.36) or bis-3-aminopropylphenylphosphine
(H4fsaappp) (Figure 1.37).
Figure 1.36.
Figure 1.37.
Both the ligands form mononuclear, homo- and heterodinuclear complexes with some
metal salts. The schematic representations of the preparation of such metal complexes with
H4fsadien are given below (Scheme 1.29 & 1.30).
The potentially heptadentate H4fsaappp ligand contains an inner N2O2P and outer O2O2
coordination sites which can bind two similar or dissimilar metal ions in close proximity. This
Schiff base ligand forms mononuclear complexes with Ni(II) while analogous compounds of
Cu(II) and U(VI)O2 are not formed. But in any case the binuclear species have been obtained.
The structures of the homo- and heterodinuclear complexes are shown in Figures 1.38 and
1.39.
Weak and strong antiferromagnetic spin-exchange has been observed in homodinuclear
Ni2 and Cu2 complexes respectively. The homodinuclear Cu2 complexes have also been
employed in the oxidation of 3,5-di-t-butylcatechol (3,5-DTBC) to 3,5-di-t-butylquinone (3,5-
DTBQ). The electrochemical behaviour of the homo- and heterodinuclear complexes has also
been recorded.
Scheme 1.29.
Dey et al. [314] synthesized and studied some mononuclear complexes of some oxo-
cations like U(VI)O2, V(IV)O and V(V)O with the Schiff base ligand H4fsadien. All the
V(IV)O complexes are paramagnetic with the μeff ranging from 1.67-1.73 B.M., which are
quite close to spin-only value for one unpaired electron with no significant interaction
between the neighbouring vanadium ions [315,316]. On the contrary V(V)O and U(VI)O2 are
found to be diamagnetic as expected for these ions having d0 configuration [315,316].
Scheme 1.30.
Figure 1.38.
Figure 1.39.
The U(VI)O2 complex, [(H4fsadien)UO2(NO3)2] is non-conducting in DMSO (ΛM = 5.8

ohm-1cm2mol-1) but on prolonged standing (about 3 days) the molar conductance value is
increased and attained value of 58.5 ohm-1cm2mol-1. This is rationalized by the following
equation and it shows the formation of a 1:2 electrolyte in solution.
From these observations the structure of the V(IV)O and U(VI)O2 complexes have been
proposed as in Figures 1.40 and 1.41.
Figure 1.40.
Figure 1.41.
Recently the same group of researchers thoroughly discussed the formation of

mononuclear [317], homo- and heterodinuclear [318] complexes with the same Schiff base
ligand H4fsadien. It has been observed that the reaction of H4fsadien with CoCl2.6H2O,
Ni(OAc)2.4H2O, Cu(OAc)2.H2O, Zn(OAc)2.2H2O, Na2MoO4.2H2O, WO2(acac)2,
(NH4)2[MoOCl5], (PyH)2[Mo(SCN)6], FeSO4.7H2O and FeCl3.6H2O under varied reaction
conditions led to the formation of mononuclear complexes.
On the basis of elemental analyses, molecular weights, magnetic moment values, molar
conductances and spectroscopic (IR, UV-Vis. and 1H NMR) data the structure of the
complexes of [(H2fsadien)M] has been proposed as shown in Figure 1.42.
Figure 1.42.
The presence of cis-MoO2/WO2 moiety in the complexes [(H2fsadien)MoO2] and

[(H2fsadien)WO2] (Figure 1.43) is confirmed by the presence of bands around 910-940 cm-1
and 900-930 cm-1 region respectively in the IR spectrum [319].
Figure 1.43.
The formation of homo- and heterodinuclear complexes has been achieved by reacting
the mononuclear Co(II) complex, [(H2fsadien)Co] as precursor with suitable metal salts.
The silylation and lithiation of the complex [(H2fsadien)Co] having two free COOH
groups with Me3SiCl or trimethylsilyl N,N/-diphenylurea (TDPU) and LiOH yielded
disilylated and dilithiated product which then smoothly reacts with (π-C5H5)2TiCl2, (π-
C5H5)2ZrCl2, Me2SnCl2, Ph2SnCl2 and MX2.nH2O (where, M = Ni(II), Cu(II), Co(II), Pd(II),
V(IV)O and X = Cl- or CH3COO-) leading to the formation of some homo- and
heterodinuclear complexes including some organo-derivatives. The reaction of H4fsadien with
FeCl3.6H2O and Co(NO3)2.6H2O in access of oxygen also yields diiron and dicobalt
complexes. In all the mononuclear complexes the ligand functions either as dibasic
tetradentate (N2O2 donor) or pentadentate (N3O2 donor) ligand. On the other hand, in the
homo- and hetero-dinuclear complexes the ligand functions either as dibasic hexadentate
(N2O2 inner and O2O2 outer compartment) ligand. The Scheme 1.31 shows the sequences of
the reactions.
Coordination supramolecules of Mn(II), Ni(II) and Cd(II) with a new symmetrical N4O2
hexadentate Schiff base ligand has been reported by Sarkar et al. [320]. The hexadentate
ligand was synthesized by the condensation of 3-formylsalicylic acid and triethylenetetramine
in 2:1 molar ratio and the metal complexes was synthesized using in situ condensation
reaction. The crystal structures shows that the 1D, 2D and 3D supramolecules have been
formed by different weak force interactions like H-bonding, π….π stacking and C-H….π
interactions. Solid-state properties (e.g. electrical conductivity at different temperatures and
optical properties) of the Ni(II) and Mn(II) complexes have also been studied and depending
on the temperature, the conductivity of the complexes is found to be insulating and
semiconducting (intrinsic and extrinsic) in nature. The optical band gap (Egd) of Mn(II) and
Ni(II) complexes was found to be 2.57 and 2.30 eV, respectively. The representative 1D and
2D crystal structures and the perspective view of the Mn(II) complex are shown below
[Figure 1.44, 1.45 and 1.46].
Scheme 1.31.
Figure 1.44.
Figure 1.45.
Figure 1.46.
Some other mononuclear transition and non-transition metal complexes have also been
synthesized and reported by the same group of researchers [321]. The Schiff base ligand and
most of the complexes have been screened in vitro to judge their antibacterial (Escherichia
coli and Staphylococcus aureus) and antifungal (Aspergillus niger and Pencillium
chrysogenum) activities and was found as efficient agent.
ACKNOWLEDGMENT
S.S. is thankful to UGC, ERO, Kolkata for providing financial assistance (No. F. PSW-
107/09-10 (ERO) dt. 08-10-09.) and K.D is thankful to the UGC, New Delhi for awarding
Emeritus Fellowship and Financial grants.
REFERENCES
[1] H. Schiff, Ann. Suppl., 3 (1864) 343.
[2] T.P. Yoon, E.N. Jacobsen, Science, 299 (2003) 1691.
[3] J.C. Duff, E.J. Bills, J. Chem. Soc., (1932) 1987.
[4] D.M.H. Bovey, E.R. Clark, J. Inorg. Nucl. Chem., 29 (1969) 755.
[5] K. Dey, R.K. Maiti, Indian J. Chem., 14A (1976) 602.
[6] K. Dey, R.K. Maiti, A.K. Sinha Roy, Indian J. Chem., 22A (1983) 580.
[7] M.S.C. Flett, J. Chem. Soc., (1951) 962.
[8] J. Selbin, L. Morpurgo, J. Inorg. Nucl. Chem., 27 (1965) 673.
[9] N.D. Chasteen, R.L. Belford, I.C. Paul, Inorg. Chem., 8 (1969) 408.
[10] K. Dey, S.K. Sen, J.K. Bhar, J. Indian Chem. Soc., 52 (1975) 666.
[11] M. Tanaka, H. Okawa, I. Hanaoka, S. Kida, Chem. Lett., (1974) 71.
[12] P.K. Dutta, J. Inclus. Phenom. Mol. Recognition Chem., 21 (1995) 215.
[13] I.F.J. Vankelecom, R.F. Patron, M.J.A. Casselaman, J.B. Uylterhoeven, P.A. Jacobs, J.
Catal., 163 (1996) 457.
[14] N. Herron, J. Coord. Chem., 19 (1988) 25.
[15] D. Chatterjee, H.C. Bajaj, A. Das, K. Bhatt, J. Mol. Catal., 92 (1994) L235.
[16] R. Raja, P. Ratnaswamy, J. Catal., 170 (1997) 244.
[17] K.O. Xavier, J. Chacko, K.K.M. Yusuff, J. Mol. Catal. A: Chemical, 178 (2002) 275.
[18] S.N. Poddar, Z. anorg. allg. Chem., 322 (1963) 326.
[19] S.N. Poddar, K. Dey, J. Indian Chem. Soc., 47 (1970) 909.
[20] S.N. Poddar, K. Dey, Z. anorg. allg. Chem., 327 (1964) 104.
[21] U. Caselato, D. Fregona, S. Sitram, S. Tamburini, P.A Vigato, Inorg. Chim. Acta, 95
(1984) 309.
[22] K. Dey, K.K. Chatterjee, S.K. Sen, J. Indian Chem. Soc., L (1973) 167.
[23] K. Dey, J. Sci. Indus. Res., 33 (1974) 76.
[24] L.G. Vanquickenborne, S.P. McGlynn, Theo. Chim. Acta, 9 (1968) 390.
[25] H.J. Bielig, E. Bayer, Annalen, 584 (1953) 96.
[26] B. Bleaney, K.D. Bowers, Proc. Roy. Soc., London, A214 (1952) 451.
[27] M. Tanaka, H. Okawa, T. Tamura, S. Kida, Bull. Chem. Soc. Japan, 47 (1974) 1669.
[28] J.P. Lebreton, FEBS Lett., 80 (1977) 351.
[29] W.R. Cullen, Y. Sugi, Tet. Letts., (1978) 1635.
[30] W.F. Anderson, M.C. Miller (Eds.), ‘Proceedings of symposium on development of iron
chelators for clinical use’, U.S. Department of Health, Education and Welfare (1975).
[31] M.J. Adam, L.D. Hall, Can. J. Chem., 60 (1982) 2229.
[32] K. Dey, A. Ganguly, Unpublished work.
[33] L.D. Hall, M. Yalpani, Carbohydr. Res., 83 (1980) C5.
[34] J.K. Nag, D. Das, B.B. De, C. Sinha, J. Indian. Chem. Soc., 75 (1998) 496.
[35] K. Dey, K. Chakraborty, R. Bhowmick, S.K. Nag, in ‘Advances in Metallo Organic
Chemistry’, Ed. R. Bohra, Jaipur (1999) 307.
[36] K. Dey, R. Bhowmick, S. Sarkar, Synth. React. Inorg. Met-Org. Chem., 32 (2002)
1393.
[37] Y.M. Issa, H.M. Abdel-Fattah, M.M. Omar, A.A. Soliman, Indian J. Chem., 33A
(1994) 959.
[38] K. Dey, D. Bandyopadhyay, J. Indian Council Chem., 11 (1995) 75.

[39] H.P.S. Chauhan, G. Srivastava, R.C. Mehrotra, Indian J. Chem., 23A (1984) 436.
[40] K. Dey, R. Bhowmick, S.K. Nag, K. Chakraborty, S. Biswas, J. Indian Chem. Soc., 76
(1999) 427.
[41] R. Bhowmick, ‘Metal complexes of ligands derived from 3-formylsalicylic acid’, Ph.D.
thesis, University of Kalyani, India (2003).
[42] K. Dey, S. Sarkar, S. Mukhopadhyay, S. Biswas, B.B. Bhaumik, J. Coord. Chem., 59
(2006) 565.
[43] M.F. Iskander, L. Labid, M.M.Z. Nour-Ed-Din, M. Tawfik, Polyhedron, 8 (1990) 2755
and references cited there in.
[44] B. Singha, B.P. Yadava, R.C. Agarwal, Indian J. Chem., 23A (1984) 441.
[45] R.P. Bonamo, E. Rizzarelli, N.B. Pahor, G. Nardin, J. Chem. Soc. Dalton Trans.,
(1982) 681.
[46] K. Dey, S. Sarkar, S. Mukhopadhyay, A.K. Mallick, S. Biswas, B. B. Bhaumik, J.
Coord. Chem., 59 (2006) 1233.
[47] A. Syamal, K.S. Kale, Indian J. Chem., 16A (1978) 46.
[48] J.F. Weither, L.R. Melby, R.E. Benson, J. Am. Chem. Soc., 86 (1964) 4329.
[49] B.N. Keshari, L.K. Mishra, Indian J. Chem., 20A (1981) 883.
[50] A. Syamal, M.M. Singh, Indian J. Chem., 32A (1993) 42.
[51] A. Syamal, D. Kumar, A.K. Singh, P.K. Gupta, Jaipal, L.K. Sharma, Indian J. Chem.,
41A (2002) 1385.
[52] T.M. Suzuki, T. Yokoyama, H. Matsunga, T. Kimura, Bull. Chem. Soc. Japan, 59
(1986) 865.
[53] M.S. Hutchins, T.K. Chapman, Tet. Letts., 35 (1994) 4055.
[54] R.A. Vaino, K.D. Janda, J. Comb. Chem., 2 (2000) 579.
[55] A. Syamal, M.M. Singh, D. Kumar, React. Funct. Polymers, 39 (1999) 27.
[56] D. Kumar, P.K. Gupta, A. Syamal, J. Chem. Sci., 117 (2005) 247.
[57] D. Kumar, A. Syamal, Jaipal, L.K. Sharma, J. Chem. Sci., 121 (2009) 57.
[58] C. Arunan, V.N.R. Pillai, Tetrahedron, 56 (2000) 3005.
[59] D.C. Sherrington, Stud. Surf. Sci. Catal., B130 (2000) 1655.
[60] N. Pesavento, R. Biesuz, F. Baffi, C. Gencco, Anal. Chim. Acta, 401 (1999) 265.
[61] M.R. Maurya, U. Kumar, P. Manikandan, Dalton Trans., (2006) 3561.
[62] M.R. Maurya, M. Kumar, A. Kumar, J.C. Pessoa, Dalton Trans., (2008) 4220.
[63] M.R. Maurya, S. Sikarwar, M. Kumar, Cat. Commun., 8 (2007) 2017.
[64] M.R. Maurya, U. Kumar, P. Manikandan, Eur. J. Inorg. Chem., (2007) 2303.
[65] M.R. Maurya, A. Arya, A. Kumar, M.L. Kuznetsov, F. Avecilla, J.C. Pessoa, Inorg.
Chem., 49 (2010) 6586.
[66] M.E. Mahmoud, E.M. Soliman, Talanta, 44 (1997) 15.
[67] M.E. Mahmoud, E.M. Soliman, M. Ezzat, A. El-Dissouky, Anal. Sci., 13 (1997) 765.
[68] R.L. De, I. Banerjee, S. Guha, A.K. Mukherjee, Indian J. Chem., 41A (2002) 1380.
[69] R.K. Verma, B.K. Mishra, K.C. Satpathy, A. Mahapatra, Asian J. Chem., 9 (1997) 365.
[70] M. Coppola, S. Catinella. P. Traldi, P. Guerriero, S. Tamburini, P.A. Vigato, Org. Mass
Spectr., 29 (1994) 566.
[71] M. Tanaka, H. Okawa, Ken. Hokoku-Kagawa Dai. Kyoik., Dai-2-bu, 31 (1981) 33.
[72] A. Erxleben, D. Schumacher, Eur. J. Inorg. Chem., (2001) 3039.
[73] J. Hermann, D. Schumacher, A. Erxleben, Eur. J. Inorg. Chem., (2002) 2276.
[74] O. Kahn, Struct. Bonding (Berlin), 68 (1987) 89.

[75] L.K. Thompson, S.K. Mandal, S.S. Tandson, J.N. Bridson, M.R. Park, Inorg. Chem., 35
(1996) 3117.
[76] M. Andruh, I. Ramade, E. Codjovi, O. Guillou, O. Kahn, J.C. Trombe, J. Am. Chem.
Soc., 115 (1993) 1822.
[77] F. Tuna, L. Patron, Y. Journaux, M. Andruh, W. Plass, J.C. Trombe, J. Chem. Soc.
Dalton Trans., (1999) 539.
[78] F. Tuna, G. Grasa, L. Patron, M. Andruh, Rev. Roum. Chim., 42 (1997) 793.
[79] F. Tuna, L. Patron, M. Andruh, Inorg. Chem. Commun., 6 (2003) 30.
[80] F. Tuna, G.I. Pascu, J-P. Sutter, M. Andruh, S. Golhen, J. Guillevic, H. Pritzkow, Inorg.
Chim. Acta, 342 (2003) 131.
[81] A. Erxleben, Inorg. Chem., 40 (2001) 208.
[82] S. Yamanaka, H. Okawa, K. Motoda, M. Yonimura, D.E. Fenton, M. Ebadi, A.B.P.
Lever, Inorg. Chem., 38 (1999) 1825.
[83] P. Zanello, S. Tamburini, P.A. Vigato, G.A. Mazzochim, Coord. Chem. Rev., 77 (1987)
165 and references cited there in.
[84] T. Shiga, H. Oshio, Polyhedron, 26 (2007) 1881.
[85] R-J. Tao, F-A. Li, Y-X. Cheng, S-Q. Zang, Q-L. Wang, J-Y. Niu, D-Z. Liao, Inorg.
Chim. Acta, 359 (2006) 2053.
[86] A. Lalehzari, J. Desper, C.J. Levy, Inorg. Chem., 47 (2008) 1120.
[87] P. Cucos, M. Pascu, R. Sessoli, N. Avarvari, F. Pointillart, M. Andruh, Inorg. Chem.,
45 (2006) 7035.
[88] A. Chakravorty, Coord. Chem. Rev., 13 (1974) 1.
[89] Luneau, H. Oshio, H. Okawa, S. Kida, Chem. Lett., (1989) 443.
[90] H. Okawa, M. Koikawa, S. Kida, D. Luneau, H. Oshio, J. Chem. Soc. Dalton Trans.,
(1990) 469.
[91] Luneau, H. Oshio, H. Okawa, M. Koikawa, S. Kida, Bull. Chem. Soc. Japan, 63 (1990)
2212.
[92] Luneau, H. Oshio, H. Okawa, S. Kida, J. Chem. Soc. Dalton Trans., (1990) 2282.
[93] C.B. Singh, B. Sahoo, J. Inorg. Nucl. Chem., 36 (1974) 1259.
[94] Z.J. Zhong, H. Okawa, N. Matsumoto, H. Sakiyama, S. Kida, J. Chem. Soc. Dalton
Trans., (1991) 497.
[95] R. Ruiz, M. Julve, J. faus, F. Lloret, M.C. Munoz, Y. Journaux, C. Bois, Inorg. Chem.,
36 (1997) 3434.
[96] Colacio, J.M. Dominguez-Versa, A. Escuer, R. Kivekas, A. Romerosa, Inorg. Chem.,
33 (1994) 3914.
[97] C. Krebs, M. Winter, T. Weyhermuller, E. Bill, K. Wieghardt, P. Chaudhuri, J. Chem.
Soc. Chem. Commun., (1995) 1913.
[98] C.N. Verani, E. Rentschler, T. Weyhermuller, E. Bill, P. Chaudhuri, J. Chem. Soc.
[99] N. Fukita, M. Ohba, H. Okawa, J. Chem. Soc. Dalton Trans., (2000) 64.
[100] K. Ikeda, M. Ohba, H. Okawa, J. Chem. Soc. Dalton Trans., (2001) 3119.
[101] K. Dey, R.K. Maiti, J.K. Bhar, Trans. Met. Chem., 6 (1981) 346.
[102] K. Dey, J. Inorg. Nucl. Chem., 32 (1970) 3125.
[103] A. Zarembowitch, O. Kahn, Inorg. Chem., 23 (1984) 589.
[104] K. Dey, Indian J. Chem., 9 (1971) 600.
[105] K. Dey, R.L. De, J. Indian Chem. Soc., 51 (1974) 374.

[106] K. Dey, R.L. De, Z. anorg. allg. Chem., 402 (1973) 120.
[107] K. Dey, K.K. Chatterjee, Z. anorg. allg. Chem., 383 (1971) 199.
[108] K. Dey, Z. anorg. allg. Chem., 376 (1970) 209.
[109] K. Dey, J. Indian Chem. Soc., 48 (1971) 641.
[110] S.N. Poddar, N.R. Sengupta, K. Dey, Science and Culture, (1963) 257.
[111] S.N. Poddar, N.R. Sengupta, K. Dey, Indian J. Chem., 2 (1964) 12.
[112] K. Dey, R.L. De, K.C. Ray, Indian J. Chem., 10 (1972) 864.
[113] M. Sakamoto, M. Hashimura, Y. Nakayama, Bull. Chem. Soc. Japan, 65 (1992) 1162.
[114] K. Dey, Indian J. Chem., 9 (1971) 887.
[115] K. Dey, A. Gangopadhyay, A.K. Biswas, J. Indian Chem. Soc., 66 (1989) 512.
[116] K. Dey, R.L. De, J. Inorg. Nucl. Chem., 37 (1975) 843.
[117] S.N. Poddar, K. Dey, J. Indian Chem. Soc., 43 (1966) 359.
[118] S. Fritzsche, P. Lonnecke, T. Hocher, E. He-Hawkins, Z. anorg. Allg, Chem., 632
(2006) 2256.
[119] B. N. Figgis, J. Lewis, ‘Modern Coordination Chemistry’, Interscience Publisher Inc.,
New York (1960).
[120] A. Vandenbergen, K.S. Murray, M.J. O’Connor, B.O. West, Aust. J. Chem., 22 (1969)
39.
[121] R. Dingle, Acta. Chem. Scand., 20 (1966) 33.
[122] R.W. Kolaczkowski, R.A. Plane, Inorg. Chem., 3 (1964) 322.
[123] M.J. O’Connor, B.O. West, Aust. J. Chem., 22 (1969) 369.
[124] P. Coggon, A.T. McPhail, F.E. Mabbs, A. Richards, A.S. Thornley, J. Chem. Soc. A,
(1970) 3296.
[125] C.J. Ballhausen, W. Mafitt, J. Inorg. Nucl. Chem., 3 (1956) 178.
[126] R.A.D. Wentworth, T.S. Piper, Inorg. Chem., 4 (1965) 202,709.
[127] K.I. Legg, D.W. Cooke, Inorg. Chem., 4 (1965) 1576.
[128] K.I. Legg, D.W. Cooke, Inorg. Chem., 5 (1966) 594.
[129] K. Kuroda, P.S. Gentile, J. Inorg. Nucl. Chem., 27 (1965) 155.
[130] J.H. Dunlop, R.D. Gillard, Mol. Phys., 7 (1963) 493.
[131] M. Gerloch, J. Lewis, F.E. Mabbs, A. Richards, J. Chem. Soc. (London) Sec. A, (1968)
112.
[132] J.S. Griffith, Mol. Phys., 8 (1964) 213.
[133] J. Lewis, F.E. Mabbs, A. Richards, Nature (London), 207 (1965) 855.
[134] M. Gerloch, F.E. Mabbs, A. Richards, Nature (London), 212 (1966) 809.
[135] J. Lewis, F.E. Mabbs, H. Weigold, J. Chem. Soc. A, (1968) 1699.
[136] R.W. Asmussen, H. Soling, Acta. Chem. Scand., 11 (1957) 1331.
[137] J. Lewis, R.A. Walton, J. Chem. Soc. A, (1966) 1559.
[138] R. Belford, T. Piper, Mol. Phys., 5 (1962) 251.
[139] R.S. Downing, F.L. Urbach, J. Am. Chem. Soc., 91 (1969) 5977.
[140] L. Sacconi, M. Ciampolini, J. Chem. Soc., (1964) 276.
[141] L. Sacconi, M. Ciampolini, F. Maggio, F.P. Cavasino, J. Inorg. Nucl. Chem., 19 (1961)
73.
[142] F.A. Cotton, G. Wilkinson, ‘Advanced Inorganic Chemistry’, Interscience Publisher
Inc., New York (1966).
[143] J. Ferguson, J. Chem. Phys., 34 (1961) 1612.
[144] T. Tanaka, J. Am. Chem. Soc., 80 (1958) 4108.

[145] G. Basu, S. Basu, Z. Phys. Chem. (Leipzig), 213 (1960) 158.
[146] S.M. Crawford, Spectrochim. Acta, 19 (1963) 255.
[147] S.V. Sheat, T.N. Waters, J. Inorg. Nucl. Chem., 26 (1964) 1221.
[148] T.N. Waters, D. Hall, J. Chem. Soc., (1959) 1200.
[149] J.M. Waters, T.N. Waters, J. Chem. Soc., (1964) 2489.
[150] T.S. Kanan, A. Chakroborty, Inorg. Chem., 9 (1970) 1153.
[151] R.H. Holm, J. Am. Chem. Soc., 82 (1960) 5632.
[152] S. Yamada, Coord. Chem. Rev., 1 (1966) 415.
[153] W. Manch, W.C. Fernelius, J. Chem. Edu., 38 (1961) 192.
[154] R.J.H. Clark, ‘The Chemistry of Titanium and Vanadium’, Elsevier Publishing
Company, Amsterdam (1968) 201.
[155] L.J. Boucher, T.F. Yen, Inorg. Chem., 8 (1969) 689.
[156] H.P. Jensen, Acta. Chem. Scand. A, 34 (1980) 469.
[157] L.J. Boucher, D.E. Bruins, T.F. Yen, D.L. Weaver, J. Chem. Soc. Chem. Commun.,
(1969) 363.
[158] D.E. Bruins, D.L. Weaver, Inorg. Chem., 9 (1970) 130.
[159] M. Mathew, A.J. Carty, G.J. Palenik, J. Am. Chem. Soc., 92 (1970) 3197.
[160] F.E. Dickson, L. Petrakis, J. Phys. Chem., 74 (1970) 2850.
[161] O. Kahn, R. Claude, H. Coudanne, Nouv. J. Chim., 4 (1980) 167.
[162] J. Zarembowitch, O. Kahn, Inorg. Chem., 23 (1984) 589.
[163] J. Zarembowitch, R. Claude, O. Kahn, Inorg. Chem., 24 (1985) 1576.
[164] R.C. Stoufer, D.W. Smith, E.A. Clevenger, T.E. Norris, Inorg. Chem., 5 (1966) 1167.
[165] D. Willams, D.W. Smith, R.C. Stoufer, Inorg. Chem., 6 (1967) 590.
[166] A. Earnshaw, P.C. Hewlett, E.A. King, L.F. Larkworthy, J. Chem. Soc. A, (1968) 241.
[167] P.S.K. Chia, S.E. Livingstone, Aust. J. Chem., 22 (1969) 1825.
[168] C.M. Harris, T.N. Lockyer, R.L. Martin, H.R.H. Patil, E. Sinn, I.M. Stewart, Aust. J.
Chem., 22 (1969) 2105.
[169] L.G. Marzilli, P.A. Marzilli, Inorg. Chem., 11 (1972) 457.
[170] R. Morassi, F. Mani, L. Sacconi, Coord. Chem. Rev., 11 (1973) 343.
[171] M.G. Simmons, L.J. Wilson, Inorg. Chem., 16 (1977) 126.
[172] S. Kremer, W. Henke, D. Reinen, Inorg. Chem., 21 (1982) 3013.
[173] B.J. Kennedy, G.D. Fallon, B.M.K.C. Gatehouse, K.S. Murray, Inorg. Chem., 23
(1984) 580.
[174] P. Thuery, J. Zarembowitch, Inorg. Chem., 25 (1986) 2001.
[175] M. Calligaris, G. Nardin, L. Randaccio, J. Chem. Soc. Dalton Trans., (1974) 1903.
[176] M.A. Hitchman, Inorg. Chim. Acta, 26 (1977) 237.
[177] M. Calligaris, D. Mminichelli, G. Nardin, L. randaccio, J. Chem. Soc. A, (1970) 2411.
[178] R. Delasi, S.L. Holt, B. Port, Inorg. Chem., 10 (1971) 1498.
[179] D.K. Geiger, Y.J. Lee, W.R. Scheidt, J. Am. Chem. Soc., 106 (1984) 6339.
[180] W.R. Scheidt, Y.J. Lee, D.K. Geiger, K. Taylor, K. Hatano, J. Am. Chem. Soc., 104
(1982) 3367.
[181] F. Tuna, L. Patron, E. Riviere, M-L. Boillot, Polyhedron, 19 (2000) 1643.
[182] C. Roux, J. Zarembowitch, B. Gallois, T. Granier. R. Claude, Inorg. Chem., 33 (1994)
2273.
[183] M-L. Boillot, C. Roux, J.P. Audiere, A. Dausse, J. Zarembowitch, Inorg. Chem., 35
(1996) 3975.
[184] T.H. Wirth, N. Davidson, J. Am. Chem. Soc., 86 (1964) 4314.
[185] M. Ali, D.V. Ramana, J. Indian Chem. Soc., 43 (1966) 583.
[186] Z. Zude, S. Yan, Z. Tao, S. Qingde, J. Mol. Struct., 440 (1998) 9.
[187] A. Bigatto, G. Costa, G. Mestroni, Inorg. Chim. Acta Rev., 4 (1970) 41.
[188] S.N. Poddar, D.K. Biswas, J. Inorg. Nucl. Chem., 31 (1969) 565.
[189] L.J. Boucher, Inorg. Chim. Acta, 6 (1972) 29.
[190] A.B.P. Lever, ‘Inorganic Electronic Spectroscopy’, American Elsevier, New York
(1968) 306.
[191] L.J. Boucher, D.R. Herington, J. Inorg. Nucl. Chem., 33 (1971) 4349.
[192] J. Lewis, R.F. Long, C. Oldham, J. Chem. Soc. (London) Sec. A, (1965) 6740.
[193] R.J. York, W.D. Bonds (Jr), B.P. Cotsoradis, R.D. Archer, Inorg. Chem., 8 (1969) 789.
[194] K. Ueno, A.E. Martell, J. Phys. Chem., 59 (1955) 998.
[195] S.J. Gruber, C.M. Harris, E. Sinn, J. Inorg. Nucl. Chem., 30 (1968) 1805.
[196] J.E. Kovacic, Spectrochim. Acta, 23A (1967) 183.
[197] P.C. Hewlett, L.F. Larkworthy, J. Chem. Soc. (London), (1965) 882.
[198] K. Nakamoto, ‘Infrared Spectra of Inorganic and Coordination Compound’, John
Willey and Sons Inc., New York (1963).
[199] B.J. Hathaway, A.E. Underhill, J. Chem. Soc. (London), (1961) 3091.
[200] S. Buffagni, L.M. Vallarino, J.V. Quagliano, Inorg. Chem., 3 (1964) 671.
[201] R.D. Archer, B.P. Cotsoradis, Inorg. Chem., 4 (1965) 1584.
[202] E. Cara, A. Cristini, A. Diaz, G. Ponticelli, J. Chem. Soc. Dalton Trans., (1972) 527.
[203] G.W. Everett (Jr), R.H. Holm, J. Am. Chem. Soc., 88 (1966) 2442.
[204] H. Nishikawa, S. Yamada, Bull. Chem. Soc. Japan, 37 (1964) 8.
[205] C.J. Hipp, W.A. Baker (Jr), J. Am. Chem. Soc., 92 (1970) 792.
[206] M. Hariharan, F.L. Urbach, Inorg. Chem., 8 (1969) 556.
[207] F.N. Moore, R.E. Rice, Inorg. Chem., 7 (1968) 2510.
[208] P.C.H. Mitchel, Quart. Rev., 20 (1966) 103.
[209] J.R. Dilworth, C.A. McAuliffe, B.J. Sayle, J. Chem. Soc. Dalton Trans., (1977) 849.
[210] M. Calligaris, G. Manzini, G. Nardin, L. Randaccio, J. Chem. Soc.
[211] R.J. Cozens, K.S. Murray, Aust. J. Chem., 25 (1972) 911.
[212] C. Florini, M. Puppis, F. Calderazzo, J. Org. Met. Chem., 12 (1968) 209.
[213] H.A.O. Hill, K.G. Morllee, G. Pellizer, G. Costa, J. Org. Met. Chem., 12 (1968) 167.
[214] S. Yamada, K. Yamanouchi, Inorg. Chim. Acta, 9 (1974) 83,161.
[215] K. Dey, A. Gangopadhyay, A.K. Biswas, J. Bangladesh Acad. Sci., 11 (1987) 55.
[216] K. Dey, A. Gangopadhyay, A.K. Biswas, J. Indian Chem. Soc., 66 (1989) 512.
[217] A. Hebeish, J. Appl. Polym. Sci., 20 (1976) 2631.
[218] M.F. Hawthorne, R.J. Wiersema, J. Med. Chem., 15 (1972) 449.
[219] K. Dey, R.K. Maiti, J.K. Bhar, R.D. Banerjee, G.M. Sarkar, A. Malakar, S. Dutta, P.
Banerjee, Agents and Actions, 11 (1981) 762.
[220] K. Dey, A. Gangopadhyay, A.K. Biswas, C. Bhattacharyya, S. Sarkar, J. Bangladesh
Acad. Sci., 12 (1988) 45.
[221] K. Dey, S.B. Ray, P.K. Bhattacharyya, A. Gangopadhyay, A.K. Biswas, R.D. Verma,
J. Indian Chem. Soc., 62 (1985) 809.
[222] K. Dey, A. Gangopadhyay, A.K. Biswas, Unpublished Work.

[223] A.K. Biswas, ‘Compounds of Boron. Synthesis, characterization and biological
actvity’, Ph.D. thesis, University of Kalyani, India (1983).
[224] K. Dey, A.K. Biswas, A.K. Sinha Roy, Indian J. Chem., 20A (1981) 848.
[225] K. Nakamoto, P.J. McCarthy, ‘Spectroscopy and Structure of Metal Chelate
Compounds’, Wiley, New York (1968).
[226] R.M. Silverstein, C.C. Bassler, T.C. Morril, ‘Spectrometric Identification of Organic
Compounds’, 3rd Edn., Wiley, New York (1974).
[227] W. Fedler, F. Umland, E. Hohaus, Z. anorg. allg. Chem., 471 (1980) 77.
[228] F.K. Butcher, W. Gerrad, E.F. Mooney, H.A. Wielis, Spectrochim. Acta, 20 (1964) 79.
[229] A.T. Balaban, C.W. Rentea, M. MoCaunparaschiv, E. Romas, Rev. Roum. Chim., 10
(1965) 849.
[230] L.J. Bellamy, W. Gerrard, M.F. Lappert, R.L. William, J. Chem. Soc., (1953) 2412.
[231] H. Junge, H. Musso, Spectrochim. Acta Part-A, 24 (1965) 1219.
[232] K. Dey, K.K. Nandi, Indian J. Chem., 35B (1996) 318.
[233] K. Dey, A.K. Biswas, D. Koner, S.B. Roy, J. Chem. Soc. Dalton Trans., (1982) 911.
[234] K. Dey, S.B. Roy, D. Koner, Proc. Indian Acad. Sci. (Chem. Sci.), 92 (1983) 257.
[235] J.R. Dilworth, C.A. McAuliffe, B.J. Sayle, J. Chem. Soc. Dalton Trans., (1977) 849.
[236] P.G. Lenhert, D.C. Hodgkin, Nature, 192 (1961) 937.
[237] P.G. Lenhert, Proc. Royal Soc. (A), 303 (1968) 45.
[238] J.A. Hill, J.M. Pratt, R.J.P. Williams, J. Chem. Soc., (1964) 5149.
[239] R. Bonnett, Chem. Rev., 63 (1963) 573.
[240] J. Halpern, J.P. Maher, J. Am. Chem. Soc., 87 (1965) 5361.
[241] G.N. Schranzer, Acc. Chem. Res., 1 (1968) 97.
[242] G. Costa, G. Mestroni, G. Tauzher, J. Chem. Soc. Dalton Trans., (1972) 450.
[243] D. Dolphin, A.W. Hohnson, R. Rodrigo, J. Chem. Soc., (1964) 3184.
[244] J.M. Pratt, J. Chem. Soc., (1964) 5154.
[245] G. Costa, G. Mestroni, L. Stefaini, J. Org. Met. Chem., 7 (1967) 3184.
[246] G. Costa, G. Mestroni, G. Tauzher, L. Stefaini, J. Org. Met. Chem., 6 (1966) 181.
[247] G. DeAlti, U. Galasso, A. Bigatto, Inorg. Chim. Acta, 6 (1972) 129, 153
[248] P. Zanello, S. Tamburini, P.A. Vigato, G.A. Mazzocchin, Trans. Met. Chem., 9 (1984)
176.
[249] P. Zanello, P.A. Vigato, U. Casellato, S. Tamburini, G.A. Mazzocchin, Trans. Met.
Chem., 8 (1983) 294.
[250] P. Zanello, P.A. Vigato, G.A. Mazzocchin, Trans. Met. Chem., 7 (1982) 291.
[251] G. Fachinetti, C. Floriani, P.F. Zanazzi, J. Am. Chem. Soc., 100 (1978) 7405.
[252] D.E. Fenton, R.L. Lintvedt, J. Am. Chem. Soc., 100 (1978) 6367 and references therein.
[253] R.R. Gagne, C.L. Spiro, T.J. Smith, C.A. Hamann, W.R. Thies, A.K. Shiemke, J. Am.
Chem. Soc., 103 (1981) 4073.
[254] G.L. Eichorn, ‘Inorganic Biochemistry’, 1 & 2, Elsevier, New York (1973).
[255] J.S. Richardson, K.A. Thomas, B.H. Rubin, D.C. Richardson, Proc. Natl. Acad. Sci.
(USA), 72 (1975) 1349.
[256] G. Palmer, G.T. Badcock, L.E. Vickery, Proc. Natl. Acad. Sci. (USA), 73 (1976) 2206.
[257] S. Gambarotta, F. Arena, C. Floriani, P.F. Zanazzi, J. Am. Chem. Soc., 104 (1982)
5082.
[258] F. Arena, C. Floriani, A. Chiesi-Villa, C. Guastini, Inorg. Chem., 25 (1986) 4589.
[259] P. Zanello, S. Tamburini, P.A. Vigato, G.A. Mazzocchin, Coord. Chem. Rev., 77 (1987)
165.
[260] P. Guerriero, S. Tamburini, P.A. Vigato, Coord. Chem. Rev., 139 (1995) 17.
[261] V. Alexander, Chem. Rev., 95 (1995) 273.
[262] B-Y. Jiang, J. Du, C-W. Hu, X-C. Zeng, Trans. Met. Chem., 29 (2004) 361.
[263] Tanaka, M. Kitaoka, H. Okawa, S. Kida, Bull. Chem. Soc. Japan, 49 (1976) 2469.
[264] H. Okawa, Y. Nishida, M. Tanaka, S. Kida, Bull. Chem. Soc. Japan, 50 (1977) 127.
[265] N. Torihara, H. Okawa, S. Kida, Inorg. Chim. Acta, 26 (1976) 97.
[266] N. Torihara, H. Okawa, S. Kida, Chem. Lett., 185 (1978) 1269.
[267] M. Mikuriya, H. Okawa, S. Kida, I. Ueda, Bull. Chem. Soc. Japan, 51 (1978) 2920.
[268] N. Torihara, H. Okawa, S. Kida, Chem. Lett., (1979) 683.
[269] H. Okawa, W. Kanda, S. Kida, Chem. Lett., (1980) 1281.
[270] Morgenstern-Badarau, M. Rerat, O. Kahn, J. Jaud, J. Galy, Inorg.
Chem., 21 (1982) 3050.
[271] S. Desjardins, I. Morgenstern-Badarau, O. Kahn, Inorg. Chem., 23 (1984) 3833.
[272] Y. Journaux, O. Kahn, J. Zarembowitch, J. Galy, J. Jaud, J. Am. Chem.
Soc., 105 (1983) 7585.
[273] M. Sakamoto, M. Takagi, T. Ishimori, H. Okawa, Bull. Chem. Soc. Japan, 61 (1988)
1613.
[274] J.P. Veale, J.A. Cunningham, D.J. Phillips, Inorg. Chim. Acta, 33 (1979) 113.
[275] Y. Aratake, H. Okawa, E. Asato, H. Sakiyama, M. Kodera, S. Kida, M. Sakamato, J
Chem. Soc. Dalton Trans., (1990) 2941.
[276] H. Nishikawa, S. Yamada, Bull. Chem. Soc. Japan, 37 (1964) 8.
[277] S. Yamada, Coord. Chem. Rev., 1 (1966) 415.
[278] Y. Nishida, S. Kida, Chem. Lett., (1973) 57.
[279] Y. Nishida, S. Kida, Coord. Chem. Rev., 27 (1979) 275.
[280] Y. Nishida, S. Kida, Bull. Chem. Soc. Japan, 45 (1972) 461.
[281] Y. Nishida, S. Kida, Bull. Chem. Soc. Japan, 51 (1978) 143.
[282] G.H. Dieke, ‘Spectra and Energy Levels of Rare Earth Ions in Crystals’, Interscience,
New York (1968).
[283] E. Cesarotti, M. Gullotti, A. Pasini, R. Ugo, J. Chem. Soc. Dalton Trans., (1977) 757.
[284] K. Nakamoto, H. Oshio, H. Okawa, W. Kanda, H. Horicuchi, S. Kida, Inorg. Chim.
Acta, 108 (1985) 231.
[285] M.A. Hitchman, Inorg. Chem., 16 (1977) 1985.
[286] H. Okawa, M. Tanaka, S. Kida, Chem. Lett., (1974) 987.
[287] W. Kanda, M. Nakamura, H. Okawa, S. Kida, Bull. Chem. Soc. Japan, 55 (1982) 471.
[288] H. Okawa, S. Kida, Bull. Chem. Soc. Japan, 45 (1972) 1759.
[289] F.A. Miller, C.H. Wilkins, Anal. Chem., 24 (1952) 1253.
[290] K.K. Abid, D.E. Fenton, Inorg. Chim. Acta, 109 (1985) L-5.
[291] R.B. King, P.R. Heckley, J. Am. Chem. Soc., 96 (1974) 3118.
[292] A.B.P. Lever, E. Mantovani, B.S. Ramaswamy, Can. J. Chem., 49 (1971) 1957.
[293] M. Sakamoto, T. Ishimori, H. Okawa, Bull. Chem. Soc. Japan, 61 (1988) 3319.
[294] M. Sakamoto, M. Ohsaki, K. Yamamoto, Y. Nakayama, A. Matsumoto, H. Okawa,
Bull. Chem. Soc. Japan, 65 (1992) 2514.
[295] W.J. Stratton, D.H. Busch, J. Am. Chem. Soc., 82 (1960) 4883.
[296] K. Shindo, H. Okawa, Y. Aratake, S. Kida, Inorg. Chim. Acta, 180 (1991) 47.
[297] J.K. Nag, D. Das, S. Pal, C. Sinha, Proc. Indian Acad. Sci. (Chem. Sci.), 113 (2001) 11.
[298] A. Syamal, D. Kumar, A. Ahmad, Indian J. Chem., 21A (1982) 634.
[299] J.K. Nag, S. Pal, C. Sinha, Trans. Met. Chem., 26 (2001) 237.
[300] K. Dey, S.B. Ray, D. Bandyopadhyay, Proc. Nat. Indian Acad. Sci., LIX (1989) 367.
[301] Kahn, J. Galy, Y. Journaux, J. Jaud, I. Morgenstern-Badarau, J. Am. Chem. Soc., 104
(1982) 2165.
[302] U. Casellato, D. Fregona, S. Sitran, S. Tamburini, P.A. Vigato, Inorg. Chim. Acta, 110
(1985) 161.
[303] J. Choisnet, N. Abadzhieva, P. Stefanov, D. Klissurski, J.M. Bassat, V. Rives, L.
Minchev, J. Chem. Soc. Faraday Trans., 90 (1994) 1987.
[304] L.G. Tejuca, J.L.G. Fierro, J.M.D. Tascon, in ‘Advances in Catalysis’, Ed. D.D. Eley,
H. Pines, P.B. Weisz, Academic Press, 36 (1989) 237.
[305] T. Seiyama, Catal. Rev. Sci. Eng., 34 (1992) 281.
[306] B. Viswanathan, in ‘Properties and Applications of Perovskite-Type Oxides’, Ed. L.G.
Tejuca, J.L.G. Fierro, Marcel Dekker, New York (1992) 271.
[307] R.J.H. Voorhoeve, in ‘Advanced Materials in Catalysis’, Ed. J.J. Burton, R.L. Garten,
Academic Press, New York (1977) 129.
[308] A. Wold, B. Post, E. Banks, J. Am. Chem. Soc., 79 (1957) 4911.
[309] S.P. Skaribas, P.J. Pomonis, A.T. Skouvos, J. Mater. Chem., 1 (1991) 781.
[310] S. Moreau, J. Choisnet, F. Beguin, J. Phys. Chem. Solids, 57 (1996) 1049.
[311] S. Moreau, V. Balek, F. Beguin, Mater. Res. Bull., 34 (1999) 503.
[312] A.K. Ladavos, F. Kooli, S. Moreno, S.P. Skaribas, P.J. Pomonis, W. Jones, G. Poncelet,
Appl. Clay Sci., 13 (1998) 49.
[313] U. Casellato, D. Fregona, S. Sitran, S. Tamburini, P.A. Vigato, P. Zanello, Inorg. Chim.
Acta, 95 (1984) 279.
[314] K. Dey, A.K. Sinha Roy, A.K. Mallick, K.K. Nandi, Synth. React. Inorg. Met-Org.
Chem., 22 (1992) 145.
[315] U. Casellato, P.A. Vigato, M. Vidali, Coord. Chem. Rev., 23 (1977) 31.
[316] K. Dey, R.K. Maiti, S.K. Sen, Inorg. Chim. Acta, 20 (1976) 197.
[317] K. Dey, R. Bhowmick, S. Biswas, D. Koner, S. Sarkar, Synth. React. Inorg. Met-Org.
Nano Met. Chem., 35 (2005) 285.
[318] K. Dey, S. Sarkar, R. Bhowmick, S. Biswas, D. Koner, Indian J. Chem., 44A (2005)
1995.
[319] P.C.H. Mitchell, Coord. Chem. Rev., 1 (1966) 315.
[320] S. Sarkar, S. Biswas, M-S. Liao, T. Kar, Y. Aydogdu, F. Dagdelen, G. Mostafa, A.P.
Chattopadhyay, G.P.A. Yap, R-H. Xie, A.T. Khan, K. Dey, Polyhedron, 27 (2008)
3359.
[321] S. Sarkar, K. Dey, Spectrochim. Acta A, 77 (2010) 740.
Chapter 5
STRUCTURAL AND MAGNETIC CHARACTERIZATION

OF CU-PICOLINATE AND CU-QUINALDINATE
MOLECULAR SYSTEMS
Bogumiła Żurowska*
Faculty of Chemistry, University of Wroclaw, Wroclaw, Poland
ABSTRACT
Review article concerns information on a synthesis, structural and magnetic
characterization of the copper(II) compounds based on two classes of carboxylate ligands
containing heterocyclic nitrogen atom of pyridine and quinoline, e.g. pyridine-2-
carboxylate (2-picolinate, 2-pic) and quinoline-2-carboxylate (2-quinaldinate, 2-qic),
respectively. Such compounds are products of a direct reaction of picolinate or
quinaldynate acids with copper(II) salts and hydrolytic or non hydrolytic decomposition
of the some ligands. Picolinate ion forms polymeric compounds of the general formula
{[Cu(2-pic)2]·2H2O}n, [Cu(2-pic)2Br2][(2-picH)2], {[Cu2(2-pic)3(H2O)]X}n, where X =
ClO4, BF4 or NO3. The compound of the formula [Cu(2-pic)2] exists in three
polymorphic forms: monomeric with Cu(N2O2) chromophore and two polymeric (1D) of
the same Cu(N2O4) chromophore. With halide ions isostructural polymeric (2D)
compounds of the formula [Cu(2-pic)X], X= Cl or Br are formed of Cu(N2O2X
chromophore. However, quinaldynate ion forms compounds of the stoichiometries: two
isomeric forms of [Cu(2-qic)2·H2O], which involve the same CuN2O3 chromophore
(distortion isomers), and [Cu(2-qic)X], X = Cl or Br. The chloride and bromide
polymeric (2D) [Cu(2-qic)X] compounds, which crystal structure consists of two
different chromophore [Cu(N2O2X] and Cu(O2X2) are isostructural. Crystal structure of
these copper-picolinate and copper-quinaldinate systems, indicate that carboxylate group
in both ligands offers a variety of coordination modes leading to the formation of
mononuclear and polynuclear compounds. The monomeric form of [Cu(2-pic)2] is an
example of a square-planar copper(II) compound in which structure is achieved by
important π-π stacking intermolecular interaction, which leads to 1D network. Polymeric
Cu-picolinate and Cu-quinaldynate systems, based on syn-anti or out-of-plane
carboxylates (COO) and di- or monohalogenes bridges (Cl, Br) are interesting material to
*
E-mail: zurowska@wchuwr.pl
222 Bogumiła Żurowska
magnetic investigations and magneto-structural correlations, because included

magnetically couplet copper(II) centers. This work presented also the role of non-
covalent interactions (π-π stacking, hydrogen bonds), stabilizing structures, in
transmission of the magnetic interactions. The magnitude of the exchange interactions
between copper(II) centers are discussed on the basis of the molecular and crystal
structures, in terms of bond properties and well-known theories and thesis of the
exchange being base explanation of the magnetic properties.
INTRODUCTION
The structure, bond properties, and magnetic behavior of copper(II) compounds are
continuous interest in inorganic and bioinorganic chemistry [1-5]. The copper ions as centers
of the active sites of various metaloproteins, play an essential role in biological processes
such as electron transfer, oxidation catalysis and dioxygen transport [6-8]. Generally, the
research of the relationship between structure and magnetic properties are important for the
understand of the fundamental factors responsible for magnetic properties [9-13] and,
furthermore, allows for modeling and understanding of the mechanisms of many bioinorganic
processes. The copper(II) complexes are the best systems to investigation the magnetic
interaction between metal centers, because of the d9 (one unpaired electron) electronic
structure.
The copper(II) complexes characterize a structural diversity, largely related to a Cu(II) d9
system. It enables the creation the compounds with different coordination number i.e. 4, 5 and
6, and stereochemistry [14-17]; (distorted) octahedral, distorted trigonal bipyramidal,
(distorted) square pyramidal, (distorted) square planar, (distorted) tetrahedral complexes have
been observed [for example 18-26]. However, because of the influence of the Jahn-Teller
effect square-planar-based geometries are usually preferred [27]. Steric constraints are
known to generate tetrahedral geometries. Copper(II) with regard on “plasticity effect” and
results from the Jahn-Teller distortion of coordination sphere, yields a polymorphic and
isomers forms [16, 26, 28]. Generally, the symmetry of the coordination polyhedron around
Cu(II) appears to be determined by subtle factors. The shape of the coordination polyhedron
is determined to a much greater extent by ligand constraints, steric hindrance, or the donor
properties of the ligand.
Copper(II) complexes are well-known from the ability of the creation of interesting
structurally and magnetically di- and polynuclear species with poli- (for example e.g. COO-,
CO32- C2O42- and NCS-) [for example 29-35] and monoatomic bridges (for example e.g. μ-
OH, OCH3 and Cl) [for example 36-39]. These compounds provide a substantial knowledge
to several scientific areas, including bioinorganic chemistry, solid-state physics, molecular
magnetism and material science. Particularly interesting is the phenomenon of interaction
between metal centers, which is important for physics of magnetic materials [40, 41]. On the
other hand, the study of the molecular magnetism in correlation with the structure of the
mono- and polynuclear complexes allow to know of the role of the mono- and polymetallic
active sites in biological systems [42, 43]. Many polynuclear complexes relevance as models
for active sites of biomolecules.
Among copper (II) complexes synthesis, structural and magnetic investigations of
copper(II) carboxylates have been the object of special interest [44-48]. The chemistry of
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 223
these compounds, particularly those including N-heterocyclic donor atom has been in recent
years the subject of many studies [44,45]. The reason of this interest are their numerous
applications in diverse areas such as pharmaceuticals, fungicides, catalysts, gas occlusion
compounds and solvent extraction processes. Moreover, the attention of, bioinorganic
chemists has been directed towards the synthesis and characterization of copper(II)
carboxylates with N-donor ligands to model the active sites in metalloenzymes [49].
The carboxylate groups are the versatile ligands, able to generate diverse compounds,
mono-, di- and polynuclear] with interesting magnetic properties. The study of the magnetic
interactions in these compounds permit, on the one hand, the creation of the new magnetic
materials and building of the model systems, on the other hand. These models serve the
explanation of the role of the mono- and polymetallic active sites in protein, because some
carboxylate group play essential role as the ligands in many metalloenzymes.
It is worth to mention that the study of the magnetic interactions between the copper
centers occurring in the crystal network through non-covalent bonds (π-π, hydrogen bonds)
permit the knowledge of the mechanism of this interactions in the biological molecules. In
addition, polynuclear metal carboxylates are good candidates for the investigation of
exchange-coupling interaction between adjacent metal ions.
The structurally and magnetically interesting group of the d9 carboxylate systems with
low molecular weight are the copper(II) complexes, derivatives of pyridine and quinoline, e.g.
pyridine-2-carboxylate (2-picolinate, 2-pic) and quinoline-2-carboxylate (2-quinaldinate, 2-
qic), respectively. Among these species, polymeric compounds have in their structure rare
conformations of the carboxylate group (syn-anti and out-of-plane). It is worth to mention,
that the including in the copper picolinate and quinaldynate systems, the halogene bridges is
unusual and leads to structurally and magnetically interesting polymeric complexes.
This review article presents and summarize, known in literature until now, the results of
the synthetic study, structural and magnetic analysis of the mono- and polinuclear copper(II)-
picolinate and the copper-quinaldynate systems. Magneto-structural correlations, based on
known theories and thesis, explain character of the magnetic interactions occurring through
the carboxylate and halogene bridges, as well as through weak non-covalent bonds (π-π
stacking, hydrogen bonds) in presented systems.
1. THE PICOLINATE AND QUINALDINATE COMPLEXES

1.1. Coordination Properties of the Picolinate and Quinaldinate Acids
Among the carboxylate compounds, containing heterocyclic donor atom, the interesting
group are (stanowią), 2-picolinate (pyridine-2-carboxylate, 2-Hpic)) and 2-quinaldinate
(quinoline-2-carboxylate, 2-Hqic) acids (Figure 1), which contain both O- and N- donor
atoms. These acids coordinated usually in deprotonated form.
N COOH N COOH
2- Hpic 2-Hqic
Figure 1. Scheme of the structure of picolinate (2-Hpic) and quinaldinate (2-Hqic) acids.
The broad spectrum of the physiological effects of 2-picolinic acid and its derivatives on
the activity functions of both animal and plant organisms has been attributed to their ability to
form complexes with transition metals. The picolinate acid is known to form complexes of
the type M(2-pic)2·(H2O)n with n = 0, 2 or 4 and M = Mn, Fe, Co, Ni, Cu, Zn, Cd, Mg and Hg
[50-60]. The X-ray crystal analysis of these compounds shows that the ligand acts
predominantly as N,O-chelating agent with water molecule occupying the crystal lattice
(Figure 3). Also a number of Mn-2-picolinate complexes with high nuclearity have been
reported [61].
Figure 2. Crystal structure of the Cu(2-pic)2⋅2H2O (1) [52].
O O M O
N N C N C
C
O O O M
M M
M
O M O
N C N C
O M O M
M M
Figure 3. Scheme of the coordination mode of the picolinate anion.

The multidentate picolinate ion is versatile ligand, coordinating in variety modes, namely
acts as N,O-, O,O-chelate, or O,O-bridge. (Fig 3). Despite its coordination modes, a chelating
five-membered ring is invariably formed.
The O,O-chelate carboxylate group forms symmetric and asymmetric chelate, and finally
monodentate complexes (Figure 4).
O O O M
M
N C M N C N C
O O O
Figure 4. Coordination modes of the carboxylate.
The 2-quinaldynic acid (2-Hqic) shows also a strong N,O-chelating properties [62-71].
The 2-picolinate and 2-quinaldinate acids indicate the ability of the existing not only in
deprotonated form but also as zwitterion (Figure 5) [72, 73]. In this case the negative charge
is spread over the O-C-O group while the positive charge, formally located on the nitrogen
atom, is delocalized over the pyridine ring. The ligands acting as zwitterions coordinate to
one carboxylic oxygen, however, nitrogen atom interacts with oxygen atom through hydrogen
N-H…O bonds [73].
O O
N C N C
H H
O O
2-Hpic 2-Hqic
Figure 5. The 2-picolinate and 2-quinaldinate acids as zwitterions.
The neutral acid molecule is demonstrated in the structure [Cu(2-pic)2Br2][(2-pic)2-H] in

which nitrogen atom from [(2-pic-H)2]2+ cation interacts with [Cu(2-pic)2Br2]2- through
intermolecular N-H…Br hydrogen bond (Figure 6) [74].
The X-ray analysis of the Cu-picolinate and Cu-quinaldinate systems indicate not only a
strong N,O-chelating ability these ligands but also ability the carboxylate -O-C-O- group to
bridge between metal centers [75-81]. The inclusion in the structure containing the bridging
carboxylate groups also the bridging halogene ions (Cl, Br) leads to structurally and
magnetically interesting polymeric complexes (Part 3) [75, 76, 79].
Figure 6. The molecular structure of [Cu(2-pic)2Br2][(2-picH)2] (3) [74].
1.2. Synthesis of Copper (II) Picolinate and Quinaldinate Complexes
The literature survey indicate that the picolinate and quinaldinate complexes of the
Cu(II) are formed not only in the direct reaction of the copper(II) salts with appropriate
carboxylate acid [50, 53, 69, 74, 77] but also are the product of the hydrolytic and non
hydrolytic processes of the degradation of the some ligands [52, 82-84].
In Table 1 known in the literature 2-picolinate and 2-quinaldinate complexes of Cu(II)
are presented.
The complex of the stoichiometry {[Cu(2-pic)2]·2H2O}n is the product of the direct
reaction [50, 53] of the Cu(II) salt with 2-picolinic acid (1) or hydrolytic degradation
pyridyne-2-carbonitrile (2) [52]. The picolinate 3, 5, 10 and 11, and quinaldinate 12, 14 and
15 complexes are the products of the direct reaction of copper(II) salts with picolinic (2-Hpic)
or quinaldinic (2-qic) acids, respectively. However, the picolinate (4, 6) and quinaldinate (13)
complexes are the product of the oxidative P-dephosphorylation reaction of R-CH2P(O)(OEt)2
phosphonate ligand leading to transformation of this ligand to R-COOH, according to
scheme [83]:
R-CH2-P(O)(OEt)2 → R-COOH + OHP(OEt)2,
where R = C5H4N or R = C9H6N. Final products of this process are copper(II) complexes with
2-pic or 2-qic ligands.
These complexes cannot be obtained directly in the reaction of the copper(II) salts with
picolinic and quinolinic acid. These complexes are formed only in the oxidative degradation
of the phosphonate ligands. However, the complexes 10, 12 and 14 are formed in both above
reactions. The complexes 7, 8 and 9 of formula {[Cu2(2-pic)3(H2O)]X}n, where X = ClO4,
BF4 or NO3, were prepared by taking advantage of the carboxylate bridge of the
“metalloligand” [Cu(2-pic)2].
Table 1. Cu(II) complexes with pyridyne-2-carboxylate and quinoline-2-carboxylate
Compounda Structure Chromophore Ref.

1 {[Cu(2-pic)2]·2H2O}n polimer (1D) Cu(N2O4) [50, 52]
2 {[Cu(2-pic)2]·2H2O}n polimer (1D) Cu(N2O4) [53]
3 [Cu(2-pic)2Br2][(2-pic-H)2] monomer Cu(N2O2Br2) [74]
4 [Cu(2-pic)2] monomer Cu(N2O2) [83]
5 [Cu(2-pic)2]n polimer (1D) Cu(N2O2O2) [77]
6 [Cu(2-pic)2]n polimer (1D) Cu(N2O2O2) [78, 83]
7 {[Cu2(2-pic)3(H2O)]ClO4}n polimer (2D) CuO4, CuN2O3 [80]
CuN2O4
8 {[Cu2(2-pic)3(H2O)]BF4}n polimer (2D) CuO4, CuN2O3 [80]
CuN2O4
9 {[Cu2(2-pic)3(H2O)]NO3}n polimer (1D) CuNO4, CuN2O4 [80]
10 [Cu(2-pic)Cl]n polimer (2D) Cu(N2O2Cl) [75, 81, 83]

11 [Cu(2-pic)Br]n polimer (1D) Cu(N2O2Br) [79]
12 [Cu(2-qic)2·H2O] monomer Cu(N2O3) [69]
13 [Cu(2-qic)2·H2O] monomer Cu(N2O3) [83]
14 [Cu(2-qic)Cl]n polimer (2D) Cu(N2O2Cl) [76, 83]
Cu(O2Cl2)
15 [Cu(2-qic)Br]n polimer (1D) Cu(N2O2Br) [79]
Cu(O2Br2)
1.3. Polymorphic and Isomeric Forms
The polymeric complexes 1 and 2 of formula {[Cu(2-pic)2]·2H2O}n (Figure 2 and 7) are

polymorphic forms, in which the copper(II) ions are a doubly out-of-plane carboxylate
bridged along the a axis. The adjacent polymeric chains are joined by the lattice water chains
leading to a 2D sheet. The crystallographic parameters for both polymorphic forms are
presented in Table 2.
Figure 7. Crystal structure of the [Cu(2-pic)2⋅2H2O]n (2) [53].
Table 2. Crystallographic parameters for polymorphic forms of the {[Cu(2-

pic)2]∙2H2O}n [52, 53]
Compounds {[Cu(2-pic)2]·2H2O}n (1) {[Cu(2-pic)2]·2H2O}n (2)

Crystal system triclinic triclinic
Space group P1̅ P1̅
a(Å) 5.090(2) 5.172(1)
b(Å) 7.480(4) 7.654(2)
c(Å) 9.067(6) 9.175(2)
α(o) 75.89(5) 74.92(3)
β(o) 84.94(5) 84.22(3)
γ(o) 71.96(4) 71.69(3)
Z 1 1
The complexes 4, 5, and 6 are polymorphic forms of the [Cu(2-pic)2]. The

crystallographic parameters are presented in Table 3.
Table 3. Crystallographic parameters for polymorphic forms of the

Cu(2-pic)2 [77, 78, 83]
Compounds Cu(2-pic)2 (4) [Cu(2-pic)2]n (5) [Cu(2-pic)2]n (6)

Space group P21/c P21/c P1̅
Crystal system monoclinic monoclinic triclinic
a(Å) 3.6975(7) 5.163(1) 5.178(3)
b(Å) 11.9890(19) 24.658(1) 7.614(6)
c(Å) 11.8886(19) 8.452(1) 8.109(6)
o
α( ) 90 90 67.06
β(o) 91.108(14) 92.22(1) 73.81(6)
γ(o) 90 90 71.74(6)
Z 2 4 1
The structure of 4, 5 and 6 is shown in Figure 8 and 9.
C6
C5
N1
C4
Cu1
C2
C3
O1 C1
O2
(A) (B)
Figure. 8. (a) The molecular structure of the [Cu(2-pic)2] (4); (b) π-π stacking interactions in the crystal
lattice of the compound 4 [83].
The [Cu(2-pic)2] (4) compound is monomeric. The crystal packing is mainly due to short
stacking (3.27 Å) between pyridine rings belonging to different molecules giving rise to a
mono-dimensional polymeric network arrangement, resulting the Cu-Cu contacts of
3.8975(7) Å. The structures of 5 and 6 are the one-dimensional polymeric chains. Each Cu(II)
ion is connected to the two adjacent metal ions by two out-of-plane carboxylate bridges,
creating a polymeric chain along the a axis in which the Cu…Cu distance within the chain is
3.6975(7) and 5.163(1)Å for 5 and 6 respectively. The Cu(2-pic)2 molecule as a whole, are
nearly planar and forms obliquely stacked planes. The essential difference between structures
5 and 6 results from the Cu-O apical distances, which are 2.745(8) - 2.770(8), 2,737(4) Å,
respectively. These differences in distances are responsible for observed magnetic properties
(see Part 5.1.1 )
(A) (B)
Figure 9. The molecular structure of the [Cu(2-pic)2]n 5 (a) and 6 (b) [77, 78].
These compounds are the coordination isomers, with the different coordination number,
which are 4 for 4, and 4+2 for 5 and 6, and these last are also called polymeric isomers [16].
Figure 10. The molecular structure of Cu(2-qic)2·H2O (12) [69].
The monomeric compounds with quinaldinate ion 12 and 13 of formula [Cu(2-qic)2·H2O]

are isomeric forms, in which 5-coordinated copper centers (CuN2O3) differ from each other
the geometry of the coordination sphere (geometrical distortion). This is the result of the
“plasticity” coordination sphere of the copper(II) and their ability to receive differ
stereochemistry.
2. INTRODUCTION TO THE MAGNETISM OF THE MAGNETIC

EXCHANGE COUPLED SYSTEMS
In transition metal complexes containing more than one metal atom with unpaired
electrons, the observed magnetic behavior often differs from the predicted sum of the
properties of the component units. This phenomenon is due to a coupling of the electron spins
and is termed intramolecular anti- or ferromagnetism, depending upon whether antiparallel or
parallel spin coupling, respectively, is found in the ground state.
In numerous transition metal complexes magnetic interactions between metal centers is
transmitted through mono-(e.g. Cl, Br, μ-OH, OCH3) or multiatomic bridges (e.g. OCO, N3
XCN, X=O, S, Se). In these compounds metal-metal distance is 3-5 Å. For monoatomic
bridges this distance is about 3 Å, and for polyatomic bridges is about 5 Å [85]. Therefore
magnetic interactions do not result from direct metal-metal interaction, but occur through
bridging ligand. These intramolecular interactions, because of the large distances, are often
termed as superexchange.
In experimental studies, the energy of the magnetic interaction of magnetic centers
through the bridge for copper(II) dimers between the local spins Si and Sj for atoms i and j is
given by Heisenberg Hamiltonian [69, 88]: H = -2JSi·Sj, where J is exchange parameter,
called also isotropic interaction parameter. Positive values of J indicate a triplet ground state
(ferromagnetic coupling), while for negative values, the singled state is lower in energy
(antiferromagnetic coupling). Generalizing, this expression for many interacting of the
magnetic centers within a molecule is received: H = -2Σ Jij Si·Sj.
Much experimental and theoretical works in recent decades have been done on the
mechanism of this exchange coupling. Mechanism of magnetic coupling have been described
by Goodenougha [87] in terms of the overlap of the d orbitals on one metal ions with the s
and p orbitals on a bridging anion and with the d orbitals on the other metal. According to the
conception of Kahn [9] and Alvarez [88], on strength of the observed antiferromagnetic
coupling decides the magnitude of the overlap of the magnetic orbitals (build up from the d
orbitals of the metal and p orbitals of the ligand atom on the appropriate symmetry). Maximal
overlap leads to strong antiferromagnetic coupling. When the overlap between magnetic
orbitals is zero, the antiferromagnetic contribution is also zero and the coupling is purely
ferromagnetic. The overlap criterion of the orbitals is confirmed by Hay theory [89], which
on the basis of the calculations for Cu(II) dimers, based on theory of molecular orbitals, state,
that the increase of the electron density on the orbital bridging ligand leads to increase of the
antiferromagnetic coupling (increase of the value |J|). However, decrease of the electron
density leads to decrease antiferromagnetic coupling`(decrease of the value |J|). This
conclusion confirms Hodgson, Hatfield and other [90]. According to Kahn theory, the
exchange coupling is the sum of the ferromagnetic (F) and antiferromagnetic (AF)
contributions i.e. J = JF + JAF. In this model the value of JAF is proportional to the square of
the integral overlap (S2) [91, 92]. Therefore, the magnitude of antiferromagnetic interaction is
governed primarily by the overlap of two magnetic orbitals centered on the nearest neighbor
copper(II) ions. The magnitude of the antiferromagnetic interaction is more sensitive on
change of the structural parameters, deciding on degree of the overlap of the magnetic.
orbitals. At very unfavorable structural conditions of the overlap, the coupling will be
ferromagnetic (JAF ≅ 0).
Summing up, mechanism superexchange interactions between metal centers through
bridging ligands for coupled systems is based on concept overlap of the two magnetic orbitals
and delocalization of the electron density unpaired electron in direction of the orbital of the
bridging ligands. This factors decides on the sign and magnitude of interactions expressed by
J parameter. In other words, the magnitude of the ground spin with regard to the excited spin
is explained in a topologic way from the map of the overlap density. The symmetry of the
metal orbitals, that contains the unpaired electron density, and the symmetry of the bridging
atom about this overlap decides.
3. MAGNETO-STRUCTURAL CORRELATIONS
Magneto-structural correlation based on investigation of the influence a topological way
(geometry of the bridge, stereochemistry of the central ion) occurring between metallic
centers through the bridged ligand, permits to determine magnetic orbitals of the central ions
and the ligands involved in magnetic interaction. Knowledge of the geometry of the
superexchange permits the explanation of the sign and magnitude of the magnetic exchange
parameter, J.
Due to known of the plasticity of the coordination sphere, the Cu(II) adopts in the
complexes different stereochemistry with coordination number: 4, 4+1 or 4+2 with four
atoms in plane and eventually with one or two in axial position, leading to square-planar or
tetragonal pyramid (SP) structure or tetragonal distortion octahedron, respectively. In these
three cases, unpaired electron is on a d(x2-y2) orbital however, for 4+1 trigonal bipyramid
(TBP), on dz2orbital. For geometry between SP and TBP, unpaired electron is on a d(x2-y2)
orbital with some admixture of a dz2. Stereochemistry of the copper(II) ions as well as
geometry of the bridge have essential meaning for explanation of the magnetic properties for
coupled systems.
4. ROLE OF THE CARBOXYLATE AND HALOGENE BRIDGES

IN TRANSMISSION OF MAGNETIC EXCHANGE
4.1. The Conformation of the Carboxylate Bridges
Copper(II) carboxylates are structurally a very diverse group of coordination compounds

due to the various coordination behavior displaying distinct bonding modes towards metal
centers such as monodentate and chelate, as well as bridging ligands (Figure 3). Different
coordination behavior of the carboxylato group lead to the formation of the mono- di- and
polynuclear structures. Carboxylate can assume many types of bridging conformations, the
most important being monoatomic and triatomic syn-syn, syn-anti and anti-anti (Figure 11).
Different conformations are responsible for observed magnetic properties which are from
strongly coupled to moderate or weak antiferromagnetic and even ferromagnetic ones.
Copper(II) compounds in which carboxylate group adopts syn-syn conformation, exhibit
strong antiferromagnetic coupling (singlet-triplet distance is about 300 cm-1) [29]. The
classical example is dimeric copper(II) acetate [Cu(CH3COO)·H2O]2 [93], for which singlet-
triplet distance is -284 cm-1. Weak antyferro- or ferromagnetic interactions are observed for
complexes, in which carboxylate group adopts syn-anti conformation [see e.g. 75, 76, 79, 85,
94-97]. For anti-anti conformation weak or moderately antiferromagnetic coupling is
observed [98-100]. For the coupling through monoatomic bridge interactions are very weak
antiferromagnetic [101, 102]. It is worth to mention, that in spite of large Cu-Cu distances in
the complexes with syn-anti conformation, anti-anti is more favorable for transmission of the
coupling. This shows that the 2p orbitals of the oxygens are favorable oriented to give more
effective overlap with magnetic copper orbitals. It is interesting, that the complexes with
bridging carboxylate group in syn-anti and anti-anti conformation are ever rare, because anti
electron pair on the oxygen atom indicates a lower basicity than the syn ones [103, 104].
Therefore, the largest group are these, which adopt syn-syn conformation.
R R R O R
C
C C Cu Cu Cu
C
O O O O O
O O
Cu Cu Cu Cu
Cu
R R
R O R
C
C
C C
syn_syn syn _ anti anti_ anti wiazanie

monoatomowe
Figure 11. Conformations of the carboxylate group.
4.2. The Carboxylate Bridges Syn-Anti Type
Generally, the weak ferro- and antyferromagnetic interactions observed in copper(II)

complexes, which copper centers are connected carboxylate bridges in syn-anti conformation,
is result this conformation leading to poor overlap of the magnetic orbitals. The structural
features of the bridge, geometry of the coordination sphere and manner of the coordination,
which may be (Fig 12): equatorial-equatorial (Type I), axial-equatorial (Type II) and axial-
axial (Type III) type, are additional factors responsible for the kind and magnitude of the
magnetic interactions.
O Cu O O
Cu
R R R
Cu C C C
O O O
Cu Cu
Cu
Typ I Typ II Typ III
Figure 12. Relative orientation of d(x2-y2) magnetic orbitals of copper(II) and 2p orbitals of oxygen for
carboxylate bridge in syn-anti conformation.
Generally, as it has been stated by several authors and also substantiated by DFT
calculation [32] syn-anti Cu-O-C-O-Cu carboxylate bridge leads to weak magnetic
interactions because 2p orbitals of oxygen atoms belonging to the magnetic orbitals centered
on Cu(II) ions are unfavorably oriented to give a significant overlap.
Figure 12 presents mutually orientation of the magnetic orbitals of Cu(II) and 2p orbitals
of oxygen resulting into weak antyferromagnetic (I), weak ferromagnetic (II) and near zero
interactions.
Very important factor which has an influence on magnitude of superexchange coupling is
non-planarity of the Cu-O-C-O-Cu bridge (an out-of-phase exchange pathway), measured by
the dihedral angle. For high dihedral angles the overlap of the magnetic orbitals is reduced,
which implies a reduction of the antiferromagnetic contribution and, consequently,
ferromagnetism is dominant. The strongest ferromagnetic coupling is expected for a dihedral
angle of 90o [80].
4.3. The Carboxylate Bridge Out-of-Plane Type
The interesting group of the copper(II) carboxylate are rare complexes in which
carboxylate group bridges in out-of-plane type (Figure 13) leading to very weak
antiferromagnetic interactions. [77, 78, 105].
Cu
Cu O
O
C R
C R
O O
Cu Cu
(A) (B)
Figure 13. (a) Single carboxylate bridge of out-of-plane type; (b) Relative orientation of the d(x2-y2)
magnetic orbitals of Cu(II) and 2p orbitals of oxygen atoms of carboxylate group.
In this type of complexes, the magnetic orbitals of the Cu(II) interact through orthogonal
2p orbitals of the oxygen atom. Generally, magnetic coupling for all known out-of-plane
polynuclear compounds is relatively weak, because of the near-orthogonality of magnetic
orbitals, as it has been shown for carboxylato [77, 78], chlorido- [37, 106], carbonato- [107]
or oximato- [108] bridged compounds. In this case of the magnetic interactions in apical-
equatorial bond modes, the orthogonality of magnetic orbitals leads to a coupling which must
be very weakly antiferromagnetic or weak ferromagnetic and even near zero.
4.4. Halogene Bridges (Cl, Br)
The halogene bridges, beside the carboxylate bridges, play essential role in transmission
of the magnetic interactions. These bridges included in the structure of the carboxylate
derivatives of the pyridine and quinoline, build interesting polymeric structures (Part.5.2.1. )
[76, 79].
In the past two decades the copper(II) complexes containing single (μ-Cl) and double (μ-
Cl)2 bridges have been the object of numerous theoretical analysis [89] and magneto-
structural correlations [37, 106, 109]. In the majority of known halogene-bridges di- and
polinuclear Cu(II) complexes, the bridges are out-of-plane type (apical-equatorial bond mode)
with bridging angle about 90o. (Figure 14, Type I). This conformation leads to very weak
ferro-and antyferromagnetic interactions, characterizing small value of the coupling
parameter |J | [37, 106].
Cu
Cl Cu
Cu
Cl
Cl
Cu
Cu Cu
Type I Type II Type III
Cu
Cl
Cu
Type IV
Figure 14. Bridging type for Cu(μ-Cl)Cu system.
Exceptional in respect of topology of chlorobridge, reported so far, are three structurally
and magnetically characterized copper(II) complexes with linear and near linear Cu-Cl-Cu
bridge of apical-apical mode ( Figure 14, Type II) [110, 111], which leads to weak
ferromagnetic interactions and these with equatorial-apical bridge (Figure 14, Type III) [76]
for which moderately strong antiferromagnetic coupling is observed. The type IV (equatorial-
equatorial bridge) is rare and rather characterize other bridging ligands [112].
5. STRUCTURE AND MAGNETIC PROPERTIES OF THE POLYMERIC CU-

PICOLINATE AND CU-QUINALDINATE SYSTEMS
Structures of the polymeric picolinate and quinaldinate complexes presented in the
literature are based on, depending on the compounds (Table 1), carboxylate bridges out-of-
plane (5 and 6) and syn-anti type (7, 8, 9, 10, 11, 14, and 15). Additionally, in the structure
of 10, 11, 14 and 15 halogene bridges (Cl or Br) are included.
5.1. Picolinate Complexes
5.1.1. Structure and Magnetic Exchange through Out-of-Plane Carboxylate Bridges

Molecular structure of 5 and 6 compounds of formula Cu(2-qic)2·H2O as it is seen from
Figure 9 and as mentioned in Part 1.3. is an infinite linear one-dimensional (1D) polymeric
chains [Cu(2-pic)2]n results from the fact that the copper(II) ions are sequentially doubly
bridged by carboxylate groups [77, 78]. The structures are stabilized by weak C-H…O
hydrogen bonds (Part 6). Coordination polyhedron around the copper can be described as a
strongly distorted octahedron (4+2). Both compounds are parallel-planar type with out-of-
plane carboxylate bridges (Figure 14, Type I). The magnetic behavior of these picolinate
complexes can be explained as a results of the magnetic exchange within the chains through
long Cu-O axial bond (2.737(4) Å and 2,745(8)-2.770(8) Å for 5 and 6, respectively).
The small values of the exchange parameters J for 5 and 6 of -0.73 and -1.04 cm-1,
respectively, are in accordance with the expection for this out-of-plane type bridges with the
orthogonality of the orbitals (Figure 15).
Cu Cl
Cl
Cu
Cu(2)
Figure 15. Bridging type for Cu(μ-Cl)Cu system.
On magnitude values of J obtained decides not only topology of the bridges, causing the
weak delocalization of the spin density unpaired electron located on the dx2-y2 orbital in
direction an axial position of the bridging oxygen, but also significant axial bond Cu-O
distance. Sequence of |J | (5) < |J | (6) is in accordance with difference of the Cu-O axial
distance (dcu-o (5) > dcu-o (6)) observed. Both compounds are example of the influence the
axial bond on the magnetic properties and indicates that the magnetic interactions may be
transmitted, through long apical ligand distance. Weak interactions between copper(II)
centers through out-of-plane carboxylate bridge has been observed for other complexes (J
from ∼0.5 to ∼-1 cm-1) with long axial distance (2.28-2.68 Å) [108]. Comparison between the
J values for [Cu(2-pic)2]n (5 and 6) and for out-of-plane single carboxylate bridged
compounds [105], reveals that the monocarboxylato-bridged series exhibit weaker
antiferromagnetic coupling. This is consistent with the simple orbital model proposed by
Kahn et al. [116, 117], in which magnetic coupling is proportional to the square of the
overlapping integral. So, for mono-out-of-plane bridged copper(II) compounds, the values of
coupling constant are smaller due to a decreasing number of the bridging groups.
5.1.2. Structure and Magnetic Exchange through Syn-Anti Carboxylate and Halogene
(Cl, Br) Bridges
Molecular structure of the polynuclear complexes of formula: {[Cu2(2-pic)3(H2O)]ClO4}n
(7) , {[Cu2(2-pic)3(H2O)]BF4}n (8), {[Cu2(2-pic)3(H2O)]NO3}n (9) contains syn-anti
carboxylate bridges [80]. These complexes were synthesized by taking advantage of the
carboxylate bridge of “metalloligand” [Cu(2-pic)2] building block. Isomorphous 7 and 8
complexes are constructed by “fish backbone” chains through syn-anti (equatorial-equatorial)
carboxylate bridges, which are linked to one another by syn-anti (equatorial-axial)
carboxylate-bridges, giving rise to a rectangular grid-like two-dimensional net [80] (Figure
16, 17).
Figure 16. Metallocycle formed in the complex 7 and 8 [80].

Figure 17. Two-dimensional layer in the complex 7 [80].
The magnitude of the magnetic coupling in 7 and 8 through carboxylate bridges defines
the exchange parameters J (chain) and J′ (side), respectively, according to scheme (Figure
18):
Figure 18. Magnetic exchange scheme in the complexes 7 and 8 [80].
The values of the superexchange parameters, assuming J = J′ = J′′, are J = 1.74 cm-1, J′
= 0.19 cm-1 for 7, and J = 0.99 cm-1, J′ = 0.25 cm-1 for 8. The difference between two values
J and J′ for 7 and 8 is a result of the difference of the dihedral angles in the Cu-O-C-O-Cu
carboxylate bridge. Because, in the backbone of the chain (J) the dihedral angle (48.5o),
which is measure of non-planarity bridge, is greater from this (31.6o) in the side chain (J'), the
stronger ferromagnetic coupling (J > J′) in 7 is observed. The same arguments explain the
stronger exchange coupling (J > J′) observed in 8, where the dihedral angle is 48.0o and 31.8o,
respectively.
The structure of 9 is one-dimensional polymeric chain formed by alternating syn-anti
carboxylate-bridges (Figure 19).
Figure 19. Alternating chain in 9 [80].
The geometry of the Cu(1) is intermediate between square pyramid and trigonal
bipyramid (Adison parameter [115] τ is 0.47). In contrast, the arrangement about Cu(2) is an
elongated octahedral. Therefore, it was assumed, that both copper(II) atoms are connected
through equatorial-equatorial syn-anti carboxylate bridges [80].
The magnitude of the magnetic coupling in 9 through carboxylate bridges defines the
exchange parameters J and J′, according to scheme (Figure 20):
Figure 20. Magnetic exchange scheme in complex 9 [80].
The obtained the value of the parameter J and J′ is 1,19 cm-1. This value is very close to
that observed for compounds 7 and 8, where very similar syn-anti carboxylate bridges are
present [80].
The structure of the polymeric complex [Cu(2-pic)Cl]n (10) is presented in Figure 21
[75]. The element of the structure is the Cu4 cluster. Namely, each carboxylate group links in
syn-anti conformation two copper centers, forming a 16-membered ring (-Cu-O-C-O-)4. Each
copper(II) ion of an individual tetrameric units is connected to others through a
dichlorobridge (μ-Cl2) resulting in the layer (2D) structure. The copper is five- coordinate
with CuNO2Cl2 chromophore (4+1). Consideration of the O(1a) atom, included in
semicoordination leads to 4+1+1* type coordination. Local CuNO2Cl2 geometry involves a
very distorted five-coordinate stereochemistry, intermediate between two idealized
geometries: square-pyramidal and trigonal-bipyramidal, as indicates structural index τ = 0.39
[115].
C5
C4
C6
C2 C3
Cl1a
N1 C1
O2
Cl1 Cu1
O1
O2a O1a
(A) (B)
Figure 21. The fragment of Cu(2-pic)Cl structure (10); (b) The view of the layer structure (2D) of
[Cu(2-pic)Cl]n [75].
The [Cu(2-pic)Br]n complex (Figure 22) is izostructural with [Cu(2-pic)Cl]n. Hydrogen

contacts of C-H-X (X = Br or Cl, respectively)) type stabilize the structure of 10 and 11.
(A) (B)
Figure 22. The fragment of [Cu(2-pic)Br]n structure (11); (b) The view of the layer structure (2D) of
[Cu(2-pic)Br]n [79].
The bridges Cu-O-C-O-Cu in 10 and 11 indicate the same structural features. The τ
parameter is 0.39, indicating the same stereochemistry. However, reliably some structural
differences in halogene bridges, essential with magnetic point of view, are observed. Namely,
The Cu-Cu distances in dimeric units are 4.446(2) and 3.676(2) Å for 10 and 11,
respectively. The bridging distances Cu-Br (2.390(1) and 2.849(1) Å) are longer than these
Cu-Cl (2.242(4) and 2.756(4) Å). Bridging angle Cu-X-Cu are 90.79(2)o and 87.9(1)o for
X=Cl and Br, respectively. The magnitude of the magnetic coupling through dihalogene and
carboxylate bridges defines the exchange parameters J and J′ , respectively, according to

scheme presented in Figure 23.
Figure 23. Scheme of magnetic exchange in complexes 10 and 11.
They are J = 15 and 8.31 cm-1 for 10 and 11, respectively, and J′ = 0.38 and 0.34 cm-1
for 10 and 11, respectively. The results obtained indicates that the magnetic interactions
inside of the layer is ferromagnetic, and ferromagnetic interaction through chloride-bridge is
larger than through bromido-bridge, according to sequence: J(Cl) > J(Br).
Weak ferromagnetic interactions through the carboxylate bridge observed for 10 and 11
complexes is results of the syn-anti conformation and low site symmetry of the chromophore
group (C2v), which causing a weak delocalization of the spin density towards the 2p oxygen
orbital of the COO bridge. Additionally, non-planarity of the Cu-O-C-O-Cu bridge leads to
stronger ferromagnetic coupling.
5.2. Quinaldinate Complexes
5.2.1. Magnetic Exchange through Syn-Anti Carboxylate and Halogene (Cl, Br)
Bridges
The crystal structure of the [Cu(2-qic)Cl]n (14) consist of copper(II) ions sequentially
bridged through carboxylate groups in the syn-anti conformation forming an infinite one-
dimensional zigzak chain with two alternating non-equivalent copper(II) chromophores:
CuO2Cl2 on square-planar geometry and CuN2O2Cl on geometry involves a very distorted
five-coordinate stereochemistry, intermediate between two idealized geometries: square-
pyramidal and trigonal-bipyramidal, as indicates structural index τ = 0.64 [115]. The
neighbouring chains are linked by linear mono-chloride atoms (bridging angle Cu-Cl-Cu is
180o) link adjacent chains, forming a ribbon type structure (1D).
(A)
Figure 24. Continued.

(B)
Figure 24. (a) The fragment of [Cu(2-qic)Cl]n structure (14); (b) View of ribbon type structure (1D) of
[Cu(2-qic)Cl]n [76].
The planes of the quinoline rings are stacked, and additionally, the contacts C-H…Cl
stabilize the crystal structure (Figure 25).
Figure 25. Arrangement of the [Cu(2-qic)Br]n (14) ribbons of the compound 14 in the crystal lattice .
Hydrogen contacts of C-H··O and C-H···Br type are shown with dashed lines [79].
The [Cu(2-pic)Br]n (15) is izostructural with [Cu(2-pic)Cl]n (14). Similarly as in the case
picolinate complexes (10 and 11) the some structural differences in halogene bridges are
observed. The distances Cu-Cu in bridged unit Cu(μ-X)Cu is 4.860(3) Å (X=Cl) and 5.149(2)
Å (X=Br). The bridging distances Cu-X are 2.376(2) and 2.515(4) Å (X=Cl), and 2.490(2)
and 2.659(2) (X=Br).
The crystal structure of Cu(2-qic)Cl suggests that two kinds of coupling parameters must
be considered to interpret the magnetic properties, according to the scheme presented in Fig
26.
J2 J2 J2
Cu Cu
J1 J1
Cu Cu
J2 J2 J2
Figure 26. Scheme of the magnetic exchange in complexes 14 and 15.
where J1 and J2 are the constants for exchange coupling via the mono-μ-chlorobridge (or
bromide bridge) in the dimeric unit and the carboxylate bridge in the chain, respectively. The
values parameters coupling are for Cu(2-qic)Cl) (14): J1 = -57 cm-1, J2 = 0.37 cm-1, and for
Cu(2-qic)Br) (15): J1 = -102,5 cm-1, J2 = 0.37 cm-1.
5.3. Magneto-Structural Correlation for Halogene Bridges
As it is seen from the Table 2, the coupling between metallic centers in the complexes 14
and 15 in the chain (carboxylate bridge) is ferromagnetic, however, between the chains
(halogene bridge) is moderately antiferromagnetic and |J| (Cl) > |J| (Br) sequence is
observed.
One of the major problem that remains open in magnetochemistry research is to discover
the factors which determine whether the magnetic interactions in singly and doubly
chlorobridged copper systems will be antiferromagnetic or ferromagnetic. For such systems
some theoretical analyses [91] have been presented.
5.3.1. Monohalogene Bridges

From the Table 3 it is seen, that antiferromagnetic coupling between copper(II) centers
through mono-chloride and bromide bridges is dominating in Cu(2-pic)Cl (10) and Cu(2-
pic)Br (11). It is worth to emphasize that the antiferromagnetic coupling is the strongest one
observed for halogeno-bridged systems up to now. The structures of the complexes with
linear Cu-Cl-Cu bridges are known, but besides carboxylate compound 14 [78], only two
with other ligands including linear 16 [11o] and near linear (177.35o) (17) [111] were
characterized magnetically.
For the complexes including linear Cu-Cl-Cu systems with bridging angle of 180o
moderately strong antiferromagnetic (14) and very weak interactions are observed. As results
with Table 4, presented structural parameters for linear and nearly linear Cu(μ-Cl)Cu bridges
in correlation with coupling parameters J, bridging angle Φ directly not determined
magnitude of the coupling through chloride-bridge. Also such parameters as Cu-Cu and Cu-
Cl distances and structural parameter τ, have not larger influence on value of J parameter.
Table 4. Coupling parameters J and symmetry of the chromophore group for the chloride (10, 14) complexes and its
bromide analogs (11, 15)
Type of bridgea) Chromophore Group Symmetry Reference

Compound Coupling parameter J (cm-1)
(μ-X)2 (μ-X) OCO

J1 (cm -1) J2 (cm-1)
Cu(2-pic)Cl (10) 15.0 0.38 Cu(N2O2Cl) C4v ↔ D3h (C2v) [75]
Cu(2-pic)Br (11) 8.31 0.34 Cu(N2O2Br) C4v ↔ D3h (C2v) [79]
Cu(2-qic)Cl (14) -57.0 0.37 Cu(N2O2Cl) C4v ↔ D3h (C2v) [76]
Cu(O2Cl2) D4h
Cu(2-qic)Br (15) -102.5 0.37 Cu(N2O2Br) C4v ↔ D3h (C2v) [79]
Cu(O2Br2) D4h
X= Cl lub Br;
Table 5. Structural and magnetic parameters for complexes with linear

bridge Cu(μ-Cl)Cu
Compounda Cu⋅⋅⋅Cu R Cu-Cl-Cu τ J Ref.

(Å) (Å) Φ (o) symmetry (cm-1)
Cu(2-qic)Cl (14) 4.86 2.51, 2.65 180 0.64b (C2v) -57.0 [76]
[Cu(tach)2Cl]5+ (16) 5.3 2.34, 2.65 180 0.07 (D4h) -0.86 [110]
Cu2(μ-Cl)(L)2(ClO4)3 (17) 2.75, 2.71 177.35 0.06 (D4h) -1.30 [111]
0.03 (D4h)
a) R- Cu-Cl distance, τ- Adison parameter [119]
b) concern of Cu(2)
c) Φ -bridging angle
Chloride bridges in 16 and 17 compounds belong to II type (axial-axial), however, the

compound 14 to type III (axial-equatorial) (Figure 14). Fig 27 shows the scheme of the
bridges and mutual orientation of the copper(II) magnetic orbitals and 2p ligand orbitals for
above complexes.
Cl
Cl
O O
Cu(1) N N N
Cu N
Cu(1) Cu
O
O N N
Cl N N
Cl Cl
Cl
O N N
Cu(2)
O
N N
N N
Cu
N Cu
O N Cu(2) N
N O N N
Cu(2-qic)Cl (14) [Cu(tach)2Cl]5+ (16)
Figure 27. Relative orientation of magnetic orbitals in Cu(2-qic)Cl (14) and [Cu(tach)2Cl]5+ (16).
According to Kahn’s theory [116, 117] the sign and magnitude of the magnetic exchange
coupling are very sensitive to the orientation of the unpaired electrons on metal ions.
Different geometries usually result in different energies (and orientation). Such a different
orientation of the d orbitals in the cited compounds must be responsible for the magnetic
behavior.
The explanation of the magnetic properties of the 14 and 16 and 17 is based on
determination of the superexchange geometry and topology of the spin density of the
unpaired electron. From Adison structural parameters [115] it is evident, that the geometry of
the copper(II) coordination sphere in 16 and 17 is near square pyramid (D4h), in which axial
position occupy chloride atom. In this case weak delocalization of the spin density in
direction of the axial position is expected. So, in spite of bridging angle of 180o, in 16 and 17
compounds of an axial(apical)-axial(apical) type only weak antiferromagnetic coupling
through chloro-bridge is observed. Stronger coupling observed in 14 is a result of
significantly delocalization of the spin density of the copper magnetic orbital in direction of
the equatorial position occupied by a chloride atom. Then, the Cu(1)-Cl(1)eq pathway in 14 is
more effective in allowing for the spin delocalization than Cu-Clax, pathway in the mono-
chloro-bridged dimers 16 and 17 of an axial(apical)-axial(apical) type, an increase of the
exchange transmitted through the bridging chloride ion in 14 is expected. On the other hand,
the distortion from a square-pyramidal towards a trigonal-bipyramidal copper coordination
geometry (τ = 64) is expected to increase the spin density on the bridge. For this distortion,
magnetic orbital of copper(II), on which is localized the spin density of the unpaired electron,
is dx2-y2 with admixture of the dz2. Then partial delocalization of the spin density on 2p
orbital of the chloride atom in axial position occurs. This is consistent with relationship
between Addison structural parameter τ and the magnitude of the constant coupling |J|,
observed for other systems with chloride-bridged connecting five-coordinated copper centers
[37, 106]. Generally, the Adison parameter τ plays an important role in determination of
magnetic interaction. It has been pointed out that the greater is this parameter, the higher is
the spin delocalization on the bridge, consequently, the stronger is the antiferromagnetic
coupling and vice-versa. Namely, this confirms the Hay’s theory [89], which on the basis of
calculations on a hypothetical mono-chloro-bridged copper(II) dimer predicts an increase of
the antiferromagnetic coupling as such a distortion proceeds. However, the parameter τ has a
minor influence on the relatively superexchange interaction in 14 compound. Mutual
orientation of the equatorial plane of Cu(1) and Cu(2) (Fig 27) is mainly responsible for the
observed strength of the magnetic interaction.
In summary, for 14 compound better overlap of the copper magnetic orbitals with ligand
orbitals leads to, the stronger antiferromagnetic coupling, compared with 16 and 17
compounds. So, the electronic and structural features of the linear Cu-Cl-Cu bridge in 14 are
favorable for the propagation of strong interaction. These features also explain strong
antiferromagnetic coupling observed in bromide analog Cu(2-qic)Br (15), J = -102.5 cm-1.
5.3.2. Dihalogene Bridges

Although there is not simple correlation in the case of chloride bridges, Hatfield [109]
has obtained interesting magneto-structural correlations which show that the sign and the
strength of coupling occurring through the bridging chloride ions in di- and polynuclear
copper(II) complexes depend critically on the structural parameter Φ/Ro, where Φ is the Cu-
Cl-Cu bridging angle and Ro the longer Cu-Cl distance (out-of-plane) within the bridge. For
bromide bridges this correlation is not observed [79, 118, 119]. Alves et all. [120] presented
correlation in a variety of chloro-bridged copper(II) dimers. The empirically established
correlation between J and Φ/Ro leads to conclusion that for the values lower than 32.6oÅ-1,
and higher than 35oÅ-1 the antiferromagnetic magnetic exchange is observed, whereas the
ferromagnetic coupling appears when the value of this structural parameter is intermediate
between these two values. Ferromagnetic coupling through dichloro-bridge in Cu(2-pic)Cl
(14) is well correlated with the calculated structural parameter (J = 15 cm-1, Φ/Ro =33.2 oÅ-1).
However, in the case of dibromo-bridged copper(II) compound Cu(2-pic)Br (11) the
exchange value J does not correlate with Φ/Ro. Namely, for Φ/Ro < 32.6, i.e. 31.9 oÅ-1
ferromagnetic exchange was found (J = 8.32 cm-1). Thus, values of the exchange coupling do
not correlate with the bridging angle or bridging distance Ro. It is in accordance with earlier
observations [118, 119] which indicate that there is no simple magneto-structural correlation
for bromo-bridged dimmers as it was found for dichloro-bridged copper(II) complexes.
5.3.3. Correlation between J(Br) and J(Cl)

The larger antiferromagnetic interaction in [Cu(2-qic)Br]n (15) through the bromide
bridge (J = -102.5 cm-1) than that observed in [Cu(2-qic)Cl]n (14) through the chloride bridge
(J = -57 cm-1), in spite of a longer Cu…Cu distance (5.149(2) Å) in the bromide bridging unit
than that of the chloride compound (4.860(3) Å), may be explained on the basis of the fact,
that the magnetic orbital of bromide atom contacts easier with the copper atom than that of
chloride (the orbitals 3p of the bromide atom, in contrary to 2p orbitals of chloride atom are
energetically nearier of the 3d orbitals of copper atom). In other words, the contribution of the
orbital overlap between Cu(II) and bridging chloride atom, suggesting that the spin density
localized on the bridging Br atom is a larger than that on the bridging Cl atom. Relationship |J
| (Br) > |J | (Cl) is consistent with the value of the exchange constant observed for other
antiferromagnetic monohalide bridging compounds [118, 119].
The dihalido-bridges (μ-Cl)2 transmit the ferromagnetic exchange with J = 8.31 and 15.0
cm-1 in [Cu(2-pic)Cl]n (10) and [Cu(2-pic)Br]n (11), respectively. Thus, in contrary to
relation |J| (Br) > |J | (Cl) obtained for [Cu(2-qic)Br]n (15) and the chloride analog, the
sequence |J | (Cl) > |J| (Br) is observed for 10 and 11. According to Kahn theory: J = JF + JAF
[91-94]. Because the magnetic orbital of bromide atom contacts easier with copper atom than
chloride, the antiferromagnetic contribution JAF in J should be larger in the case of bromide
compounds. This model may explain the observed increase of |J| along the sequence Cl, Br
of briding atoms in Cu(2-pic)X and, Br, Cl of bridging atoms in Cu(2-qic)X. Concluding, the
superexchange pathway Cu-Br-Cu is more favorable for propagation of magnetic interactions
than Cu-Cl-Cu, and generally relationship is observed [79, 125], for the antiferromagnetic
coupling: 2JAF(Cl) ≅ JAF(Br), and for ferromagnetic interaction: JF(Cl) ≅ 2JF(Br).
6. MAGNETIC INTERACTIONS THROUGH NON-COVALENT

INTERACTIONS (H-BOND AND π-π STACKING)
Studies of very weak non-covalent intermolecular interactions, such as hydrogen bonds
[126, 127], π-π stacking of aromatic rings [128-131] are of fundamental importance not only
for further development of inorganic supramolecular chemistry and prediction of crystal
structure, but these contacts also generate interesting supramolecular properties, such as
electrical, optical and magnetic ones [132], and play a major role in the functioning of
biological macromolecules [133, 134]. Tabl. 6 shown exchange coupling parameters zJ′ (z is
the number of nearest neighbors) obtained for Cu(2-pic)2 (4, 5, 6) and Cu(2-qic)2·H2O (12,
13) complexes.
Table 6. Parameters of the magnetic coupling in 4, 5, 6, 12 and 13 complexes
Compound Type zJ′ (cm-1) Oddziaływanie Ref.

interactions poprzez mostek
out-of-plane
-O-C-O-
J (cm-1)
Cu(2-pic)2 (4) π-π stacking -0.76 [83, 135]
C-H⋅⋅⋅O -0.47
[Cu(2-pic)2]n (5) C-H⋅⋅⋅O -0.06 -0.73 [77]
[Cu(2-pic)2]n (6) C-H⋅⋅⋅O 0.34 -1.04 [78, 83]
Cu(2-qic)2·H2O (12) O-H⋅⋅⋅O -0.25 [83, 135]
Cu(2-qic)2·H2O (13) O-H⋅⋅⋅O -0.23 [135]
6.1. Mononuclear Systems
The crystal structures of the [Cu(2-pic)2Br2][(2-pic-H)2] picolinate complex (3) (Fig 6)

indicate that the molecules are isolated in the crystal lattice and for that reason the magnetic
interactions between copper centers are not observed.
As it was mentioned earlier (Figure 8) intermolecular short (3.27 Å) π-π stacking
interactions in Cu(2-pic)2 (4) lead to one-dimensional (1D) network arrangement (Fig 8),
resulting a Cu-Cu contacts of 3.6975(7) Å. Further hydrogen bonds, additionally stabilizing
structure, link Cu(2-pic)2 molecule leading to three-dimensional network. Crystal packing of
4 is presented in Figure 28.
Figure 28. The crystal structure of Cu(2-pca)2 (4). Hydrogen bonds are shown with dashed line [83].
The obtained exchange coupling constants J = -0.76 cm-1, responsible for the π-π
stacking and zJ’ = -0.47 cm-1, responsible for the hydrogen bonds interactions, indicate
stronger antiferromagnetic coupling through the π-π stacking. In 4 an interaction through an
offset π-π stacking (1.73 Å) between the pyridine molecules occurs (Figure 29) with a
perfectly planar copper complex, allowing for the optimal stacking interaction. The mutual
positions of coplanar pyridine rings show a very small value of the interplane distance (3.27
Å) and often observed centroid-centroid distance of 3.70 Å. However, the angle between the
centre-centre line and the normal to the plane, of about 30o, is large. For centroid-centroid
distances up to 3.8 Å, being approximately the maximum distance for which π-π interactions
are accepted, this displacement angle, observed for pyridine molecule, lies around 20o. This
angle corresponds to a horizontal displacement of 1.30 Å.
Magnetic interaction through π-π stacking can have very weak antiferromagnetic [135-
138] or weak ferromagnetic [139, 140] character. Influence of the structural factor, such as
Cu-Cu (R) distance, centroid-centroid distance R, distance between planes R2, offset R1 and
displacement angle Θ, as also influence of electronic factors (participation of π and σ
electrons of the aromatic rings and dπ copper(II) ions) on magnitude and sign of J has been
for several complexes the subject of the discussion [135]. Analysis of the structure and
magnetic interactions in these complexes suggests that the interplane and offset distances are
substantial parameters which could influence on the strength of magnetic exchange coupling
between copper(II) centers. So, both short interplane and relatively large offset distances
could be responsible for a larger antiferromagnetic exchange through π-π stacking interaction
observed in 4.
R1
N Cu
R2 R
R
θ) N Cu
Figure 29. Geometry of the pyridyl rings in Cu(2-pca)2 (4); R = 3.70 Ǻ, R1 = 1.73 Ǻ, R2 = 3.27 Ǻ, θ =
30o [134].
The crystal structure of the Cu(2-qic)2·H2O (12) (Figure 30), which molecular structure is
depicted on Figure 10, present the layer (2D), created by strong O-H···O hydrogen bonds
(O···O The spectroscopic studies of the complexes 12 and isomer 13, for which lack of the X-
ray data, indicate that the structure of 13 is also stabilized by strong O-H…O hydrogen
bonds.
Figure 30. The crystal structure of Cu(2-qic)2·H2O (12). Hydrogen bonds are shown with dashed line
[141].
The coupling parameters of zJ’ = -0.25 (12) and -0.23 cm-1 (13) indicate the weak
antiferromagnetic coupling transmitted by H-bonds [141].
Polynuclear systems. The molecular structures of isomeric forms of [Cu(2-pic)2]n 5 and 6
are one-dimensional chains (1D) formed by double out-of-plane carboxylate bridges (Figure
9). The weak C-H…O hydrogen bonds and contacts link the chains forming two-dimensional
(2D) network (Figure 31, 32).
(A) (B)
Figure 31.The crystal structure of Cu(2-pic)2 (5). (a) Corrugated layers formed by planar molecules of
Cu(2-pic)2 of adjacent chains; (b) The layer (2D). Hydrogen bonds of C-H⋅⋅⋅O type are shown with
dashed lines [77].
Exchange coupling parameters indicate weak antiferromagnetic (zJ’= -0.06 cm-1) in 5 and
weak ferromagnetic (zJ’= 0.34 cm-1) in 6 interactions through hydrogen bonds. These
interactions are weaker than those transmitted through out-of-plane bridges (Table 5).
The role that hydrogen bonds play in the transmission of magnetic interactions is still not
completely understood. For many years, hydrogen bonds have been reported to propagate
essentially antiferromagnetic interactions between metal centers in variety of transition metal
complexes [142]. Even Cu dimer with O-H···O distance of 2.32 Å with high J value of -90
cm-1 has been reported [143]. Recent theoretical studies have been able to rationalize the
antiferromagnetic coupling between copper(II) complexes mediated by hydrogen bonds
[143].
(A) (B)
Figure 32. The crystal structure of Cu(2-pca)2 (6);(a) Layers formed by planar molecules of Cu(2-pca)2
of adjacent chains; (b) The layer (2D). Hydrogen bonds of C-H⋅⋅⋅O type are shown with dashed line
[78].
In recent years, ferromagnetically coupled hydrogen bond systems are growing

exponentially, either some supramolecular copper structures, or even some organic radicals
interactions has been observed but the mechanism of these interactions is not completely
understood [143-148].
Although the ligands (2-pic) are the same in 5 and 6 complexes and the Cu(II) ions are
doubly bridged by carboxylate out-of-plane bridges, the packing of the two complexes is
different (Figure 31, 32). In these compounds difference in H-bond networks are responsible
for different magnetic properties (F and AF). Both compounds show C-H···O intermolecular
hydrogen bonds with similar O···H distance in the range 2.43-2.49 and 2.40-2.49 Å in 5 and
6, respectively. However, the relative C…O donor…acceptor separations in C-H…O
hydrogen bonds in 5 are shorter (3.161-3.278 Å) than those (3.287-3.419 Å) in compound 6.
The shorter Cu-O distance in 5 (1.944(7 Å) than this in 6 (1.957(3) Å) is also observed. On
the other hand, the relative bond angles C-H···O in 5 of 150o and 166o are more favourable
for transmission of the magnetic interaction through the H-bonds than those in compound
6 (140o, 137o, 143o). The above structural factors could explain the differences in the sign of
the superexchange coupling observed in compounds 5 and 6, because the stronger coupling
correspond to the shorter hydrogen bonded donor…acceptor distance [W] and shorter
distance between copper ions and oxygen atom included in H-bond. These conclusions
confirm earlier investigations [143, 144].
The crystal structure of the [Cu(2-pic)2Cl] (9) and izostructural [Cu(2-pic)Br] (11) (Fig
25) indicates that the magnetic interactions may be transmitted through non-covalent
interactions (H-bond network and π-π stacking). However, lack of model do not permit the
calculation of J parameter, characterizing these interactions.
REFERENCES
[1] Murphy, B.P., & Hathaway, B.J. (1993). Copper. Coord. Chem. Rev. 124 (1,2), 63-106.
[2] Hathaway, B.J., (1987). Copper. In G. Wilkinson, R. D. Gillard, & J. A. McCleverty,
(Eds.). Comprehensive Coordination Chemistry, Vol. 5,( pp. 534-774). Oxford:
Pergamon Press.
[3] Nelson, J. (2010). Copper, Annu. Rep. Prog. Chem., Sect A: Inorg. Chem., 106, 235-
254.
[4] Hathaway, B.J. (1984). A new look at the stereochemistry and electronic properties of
complex of the copper(II) ion. Structure and Bondings, Vol. 57 (pp. 55-118) Berlin-
Heidelberg: Springer-Verlag.
[5] Carlin, R.L. & Block, R. (1978). Magnetochemistry of copper(II). J. Chem. Sci. 98 (1-
2), 79-97.
[6] Solomon, E.I., Baldwin, M.J., & Lowry, M.D. (1992). Electronic structures of active
sites in copper proteins: contribution to reactivity. Chem. Rev. 92 (21), 521-542
[7] Karlin K.D., & Tyeklar, Z. (1993). Bioinorganic Chemistry of Copper, London:
Chapman & Hall.
[8] Hughes, M.N.( 1981). The Inorganic Chemistry of Biological Processes, 2nd ed., New
York: Wiley
[9] Kahn, O. (1993). Molecular magnetism, New York: Wiley-VCH.
[10] Kahn, O. (1985). Dinuclear complexes with predictable magnetic properties. Angev.
Chem., Int. Ed. Engl., 24 (10), 834-850.
[11] Kahn, O. (1987). Magnetism of the heteropolymetallic systems. Structure Bonding, 68
89-167. Berlin: Springer.
[12] Gatteschi, D., Kahn, O., & Willett, R. D. (1984) Magneto-Structural Correlations in
Exchange Coupled Systems, Dordrecht: Reidel,
[13] Coronado, E., Georges, R., & Tsukerblat, B.S. (1996). Exchange Interactions. In E.
Coronado, P. Delhačs, D. Gatteschi, & J. S. Miller, (Eds.) Mechanism Molecular
Magnetism: from Molecular Assemblies to the Devices; NATO ASI E 321, pp. 267-
279. Dordrecht: Kluwer.
[14] Gažo, J., Bersuker, I.B., Garaj, J., Kabešová, M., Kohout, J., Langfelderová, H.,
Melník, M., Serátor, M., & Valach, F. (1976). Plasticity of the coordination sphere of
copper(II) complexes, its manifestation and causes. Coord. Chem. Rev., 19 (3), 253-
297.
[15] Murphy, B., & Hathaway, B. (2003). The stereochemistry of the copper(II) ion in the
solid-state – some recent perspectives linking the Jahn-Teller effect, vibronic coupling,
structure correlation analysis, structural pathways and comparative X-ray
crystallography. Coord. Chem. Rev., 243 (1-2), 237-262.
[16] Melník, M. (1982). Structural isomerism of copper(II) compounds. Coord. Chem. Rev.,
47 (3), 239-261.
[17] Melník, M., Kabešova, M., Koman, M., Macaškova, L. & Holloway, C.E. (2000).
Copper(II) coordination compounds: Classification and analysis of crystallographic and
structural data V. Polymeric compounds. J. Coord. Chem., 50 (3-4), 177-322.
[18] Ivarsson, G. (1973). Metal complexes with mixed ligands. Acta Chem. Scand., 27 (9),
3523-3530.
[19] Quiroz-Castro, M.E., v. Albada, G.A., Mutikainen, I., Turpeinen, U. & Reedijk, J.
(2000). The crystal structure, spectroscopy and EPR of tetragonal bis(2-
(aminomethyl)pyridine) Cu(II) compounds. Rare cases of the absence of Cu(II)
plasticity. Inorg. Chim. Acta, 297 (1-2), 129-133.
[20] McFadden, D.L. , McPhail, A.T.. Garner, C.D., & Mabbs, F.E. (1976). Crystal and
molecular structure, electron spin resonance, and electronic spectrum of
tetrakis(imidazole)dinitratocopper(II) J. Chem. Soc., Dalton Trans. (1), 47-52.
[21] Burke, P.J., Henrick, K. D. & McMillin, R. (1982). Crystal and molecular structures of
bis(4,4',6,6'-tetramethyl-2,2'-bipyridyl)copper(I) perchlorate, bis(4,4',6,6'-tetramethyl-
2,2'-bipyridyl)copper(II) diperchlorate, and bis(4,4',6,6'-tetramethyl-2,2'-
bipyridyl)copper(II) diperchlorate dihydrate. A search for copper(II) and copper(I)
complexes with a common ligand environment. Inorg. Chem., 21 (5), 1881-1886
[22] Nieminen, K. (1981). Crystallographic and magnetic study of "tetraisothiocyanato-
cuprate(I)-bis( μ-(2-[(3-aminopropyl)amino]ethanolato)-N,N',μ-O)dicopper(II) polymer
thiocyanate. Acta Scand., ser. A, 35 (10), 753-757.
[23] Haanstra, W.G.,.van der Donk, W.A.J.W., Driessen, W.L., Reedijk, J., Wood, J.S., &
Drew, M.G.B.. (1990). Unusual behaviour of the thioether function of the ligand 1,8-
bis(3,5-dimethyl-1-pyrazolyl)-3,6-dithiaoctane (bddo) towards transition-metal salts. X-
Ray structures of a green and a red modification of [Cu(bddo)Cl2]. J. Chem. Soc.,
Dalton Trans. (10), 3123-3128.
[24] Kelly, P.F. Slawin, A.M.Z., & Waring, K.W. (1997). Preparation and crystal structures
of two forms of trans-[CuCl2{N(H)SPh2}2]; an unusual example of square
planar/pseudotetrahedral isomerism in a neutral copper(II) complex. J. Chem. Soc.
Dalton Trans., (17), 2853-2854.
[25] Broughton, V. Bernandirelli, G. & Williams, A.F. (1998). Tetrahedral coordination by a
seven-membered chelate ring. Inorg. Chim. Acta, 275-276 (1-2), 279-288.
[26] van Albada, G.A., Smeets, W.J.J., Spek, A.L. & Reedijk, J. (1999). Synthesis,
characterization, spectroscopy, magnetism and X-ray structures of red and green Cu(II)
chloride adducts with bis(2-benzimidazolyl)propane. Inorg. Chim. Acta, 288 (2), 220-
225.
[27] Greenwood, N.N., Earnshaw, A. (1997). Chemistry of the Elements, second ed.,
Oxford: Butterworth-Heinemann.
[28] Flizner, K. Stassen, A.F., Mills, A,M., Spek, A.L., Haasnoot, J.G., & Reedijk, J.
(2003). The chelating ligand 1,3-bis(pyrazol-1-yl)propane (Bpp) Enforces a tetrahedral
geometry in both CuII and CuI species. Eur. J. Inorg. Chem. (4), 671-677.
[29] Doedens, R.J. (1976). Structure and metal-metal interactions in copper(II) carboxylate
complexes. In S.J. Lippard (Ed.). Progress in Inorganic Chemistry, Interscience
Publishers: John Wiley & Sons, 29, 209-229.
[30] Ruiz-Perez, C, Sanchiz J, Molina M.H., Lloret F., & Julve M., Ferromagnetism in
Malonato-Bridged Copper(II) Complexes. Synthesis, Crystal Structures, and Magnetic
Properties of {[Cu(H2O)3][Cu(mal)2(H2O)]}n and {[Cu(H2O)4]2[Cu(mal)2(H2O)]}
[Cu(mal)2(H2O)2]{[Cu(H2O)4][Cu(mal)2(H2O)2]} (H2mal = malonic Acid) (2000).
Inorg.Chem.,39, (7), 1363.
[31] Ruiz-Perez, C, Hernandez-Molina M., Lorenzo-Luis P, Lloret F. & Julve, M. (2000).
Magnetic coupling through the carbon skeleton of malonate in two polymorphs of
{[Cu(bpy)(H2O)][Cu(bpy)(mal)(H2O)]}(ClO4)2 (H2mal = malonic acid; bpy = 2,2‘-

bipyridine). Inorg. Chem. 39 (17), 3845-3852.
[32] Rodríguez-Fortea, A., Alemany, P., Alvarez, & S. Ruiz, E. (2001). Exchange coupling
in carboxylato-bridged dinuclear copper(II) compounds: A density functional study.
Chem. Eur. J., 7 (3), 627-637.
[33] Konar, S. Mukherjee, P.S. Drew, Ribas, M.G.B., & Chaudhuri, J. N.R. ( 2003). .
Syntheses of two new 1D and 3D networks of Cu(II) and Co(II) using malonate and
urotropine as bridging Ligands: Crystal structures and magnetic studies. Inorg. Chem.
42 (8), 2545-2552.
[34] Żurowska, B. Mroziński, J. Julve M. , Lloret, F. Maslejova, A. & Sawka-Dobrowolska,
W. (2002). Structural, spectral and magnetic properties of end-to-end di-μ-thiocyanato
bridged polymeric complexes of Ni(II) and Co(II). X-ray crystal structure of di-μ-
thiocyanato-bis- imidazole)nickel(II). Inorg. Chem. 41 (7) 1771-1777.
[35] Youngame, S., Chaichit, N. Kongsaeree, P., van Albada, G.A., & Reedijk, J. (2001).
Synthesis, structure, spectroscopy, and magnetism of two new dinuclear carbonato-
bridged Cu(II) complexes. Inorg. Chim. Acta, 324 (1-2), 232-240.
[36] E. Ruiz, Alemany, P., Alvarez, S., & Cano, J. (1997). Toward the prediction of
magnetic coupling in molecular systems: Hydroxo- and alkoxo-bridged Cu(II) binuclear
complexes. J. Am. Chem. Soc, 119 (6), 1297-1303.
[37] Hernández-Molina, M., González-Platas, J., Ruiz-Pérez, C., Lloret, F., & Julve, M.
(1999). Crystal structure and magnetic properties of the single-μ-chloro copper(II)
chain [Cu(bipy)Cl2] (bipy=2,2′-bipyridine). Inorg. Chim. Acta, 284 (2), 258-265.
[38] Ruiz, E., Alemany P., Alvarez S.,& Cano., J. (1997). Structural modeling and magneto-
structural correlations for hydroxo-bridged copper(II) binuclear complexes. Inorg.
Chem., 36 (17), 3683-3688.
[39] Rodríguez-Fortea, A., Ruiz, E., Alvares, S., & Alemany, P. (2005). Exchange coupling
in di-μ-hydroxo dinuclear cu(II) compounds: a density functional study. Dalton Trans.
(15), 2624-2629
[40] Turnbull, T. & Sugimoto, L.K. (1996). In M.M. Turnbull, T. Sugimoto, L.K.
Thompson. (Eds). Molecule-based Magnetic Materials: Theory, Techniques, and
Applications. (pp 1-352); ASC Symposium Series, Vol. 644; American Chemical
Society: Washington, D.C.
[41] Magnetism: Molecules to Materials; J.S. Miller, M. Drillon., (Eds).; Wiley-VCH: New
York, 2000-2005; Vols. 1-5.
[42] Law, N.A., Caudle, M. T. & Pecoraro, V. L. (1998). Manganese Redox Enzymes and
Model Systems: Properties, Structures, and Reactivity. Adwances in Inorganic
Chemistry, 46, 305-440.
[43] Wieghardt, K., (1989). The active-sites in manganese-containing metalloproteins and
inorganic model complexes. Angev. Chem. Int. Ed. Engl. 28, 1153-1172.
[44] Melník, M. (1981). Mono-, bi-, tetra and polynuclear copper(II) halogeno-carboxylates.
Coord. Chem. Rev., 36 (1), 1-44.
[45] Kato, M., & Muto, Y. (1988). Factors affecting the magnetic properties of dimeric
copper(II) complexes. Coord. Chem. Rev., 92, 45-83.
[46] Sundberg, M.R., Uggla, R. & Melnik, M.( 1996). Comparison of the structural
parameters in copper(II) acetate-type dimers containing distorted square pyramidal
CuO4O and CuO4N chromophores. Polyhedron, 15 (7), 1157-1163.
[47] Oldham, C. (1987). Carboxylates, Squarates and Related Species, In G. Wilkinson
(Ed.). Comprehensive Coordination Chemistry., Oxfort: Pergamon Press.
[48] Mehrotra, R.C., & Bohra, R. (1983). Metal Carboxylates, London: Academic Press.
[49] Holz, C.R., Bradshaw, J.M. , & Bennet, B. (1998). Synthesis, Molecular Structure, and
Reactivity of Dinuclear Copper(II) Complexes with Carboxylate-Rich Coordination
Environments. Inorg. Chem., 37 (6), 1219-1225.
[50] Faure, R., Loiseleu. H., & Thomas-David, G., (1972). New refining of crystalline-
Structure of hydrated bis(pyridine-2-carboxylato)copper(II). Acta Crystallogr. B, 28
(9), 1890-1893.
[51] Faure R., & Loiseleu.H. (1998 ). Structure of zinc 2-pyridylacetate dihydrate . Acta
Crystallogr. B, 28 (25-26), 811-812.
[52] Segl’a, P., Jamnický, M., Koman, M., Šima, J., & Głowiak, T. (1998). Metal(II)-
promoted hydrolysis of pyridine-2-carbonitryle to pyridine-2-carboxylic acid. The
structure of [Cu(pyridine-2-carboxylate)2]·H2O. Polyhedron, 25 (26), 4525-4533.
[53] Dutta, D., Jana, A. D., Ray, A., Marek, J., & Ali, M. (2008). Synthesis of a new
polymorph in [Cu(pyridine-2-carboxylate)2] system. Ind. J. Chem., 47 (11), 1656-1660.
[54] Loiseleur, H., (1972). Structure du pyridyl-2-acétate de zinc, dehydrate. Acta
Crystallogr., Sect. B, 28 (3), 811-815.
[55] Deloume, J.P., & Loiseleur, H. (1974). Structure crystalline du pyridine-2 carboxylate
de cadmium. Acta Crystallogr. B, 30 (3), 607- 609.
[56] Deloume, J.P., Loiseleu, H., & Thomas, G., (1973). Structure du picolate de magnesium
dehydrate. Acta Crystallogr. B, 29 (4), 668-673.
[57] Deloume, J.P., & Loiseleu, H. (1974). Structure of zinc 2-pyridylacetate dehydrate
Acta Crystallogr., B, 30 (3), 607-609.
[58] Takenaka, A. Utsumi, H., Yamamoto, T, Furusaki, A., & Nitta, I. (1970). Crystal and
molecular structure of trans-bis(picolinato)copper(II) dihydrate, Cu(pc)2.2H2O. Nippon
Kagaku Zasshi, 91(10), 928-929.
[59] Takenaka A. Utsumi H, Ishihara N, Furusaki A, & Nitta I. (1970). Molecular and
crystal structures of trans-diaquo-bis-(picolinato)nickel(II) dehydrate. Nippon Kagaku
Zasshi, 91 (10), 921-922.
[60] Lumme, P., Lundgrem, G., & Mark, W. (1969). The crystal structure of zinc picolinate
tetrahydrate Zn(C6H4O2N)2(H2O)4. Acta. Chem. Scand., 23, 3011-3022.
[61] Huang, D., Wang, W., Zhang, X., Chen, Ch., Chen, F., Liu, Q., Liao, D., Li, L., & Sun,
L. (2004 ). Synthesis, Structural characterizations and magnetic properties of a series of
mono- di- and polynuclear manganese pyridinecarboxylate compounds. Eur. J. Inorg.
Chem. (7), 1454-1464.
[62] Lamprecht, G.J., Leipoldt, & J.G., Roodt, A., (1991). Structure of carbonyl(2-
quinolinecarboxylato)-kN,kO)-(triphenylphosphite-kP)rhodium(I). Acta Crystallogr.,
Sect C, 47, Part 10, 2209-2211.
[63] Lamprecht, G.J., Beetge, J.H., Leipoldt, J.G., & De Waal, D.R. (1986). The structure
of 2-carboxyquinolinato-bis(triphenylphosphite)-rhodium(I). Inorg. Chim. Acta, 113
(2), 157-160.
[64] Graham, D.E., Lamprecht, G.J., Potegieter, I.M., Roodt, A., & Leipoldt, J.G. (1991).
Observed trans influence of donor atoms in monocharged bidentate ligands – Crystal
structure of the acetone solvate of 2-carboxyquinolinato-carbonyltriphenyl
phosphinerhodium(I). Trans. Met. Chem., 16, (2), 193-195.
[65] Li, W., Olmstead, M.M., Miggins, D., Fish, & R.H. (1996). Synthesis and structural
studies of metal complexes of the biological ligand 2-quinaldic Acid: Utilization of the
polymer pendant analog PS-2-QA for selective aluminum ion removal from aqueous
solution. Inorg. Chem., 35, (1), 51-55.
[66] Cano, M., Heras, J.V., Lobo, M.A., Pinilla, E., Gutierrez, E., & Monge, M.A. (1994).
Mononuclear and binuclear quinaldinate complexes of rhodium with (P-P) donor
ligands – crystal structure of [RH2(quin)2(CO)2(μ-DPPM)] - oxidative addition-
reactions. Polyhedron, 13 (10), 1563-1573.
[67] Haendler, H.M. (1996). A managanese quinaldinate complex: trans-[diaquabis(2-
quinolinecarboxylato)managanese(II)]-water-ethanol (1/2/2). Acta Crystallogr., Sect. C,
52 (Part 4), 801-803.
[68] Goher, M.A.S., & Mautner, F.A. (1993). Preparation, crystal-structure and
spectroscopic study of azido(N,O-quinaldato)triaquamanganese(II) monohydrate and
thiocyanato(N,O-quinaldato)-(O-quinaldic acid)diaquamanganese(II),
[Mn(NC9H6COO)(N3)(H2O)3].H2O and Mn(NC9H6COO)(NC9H6COOH)(NCS)(H2O)2].
Polyhedron, 12 (15), 1863-1870.
[69] Haendler, H.M. (1986). Copper quinaldinate monohydrate [aquabis(2-
quinolinecarboxylato)copper(II); pentacoordinate copper. Acta Crystallogr, Sect. C, 42
(Part 2), 147-149.
[70] Dobrzyńska, D., Duczmal, M., Jerzykiewicz, L.B., Warcholska, J., & Drabent, K.
(2004). Synthesis, spectroscopy, and magnetic properties of FeII and CoII quinoline-2-
carboxylates-crystal structure of trans-bis(quinoline-2-carboxylato)bis(propanol)iron
(II). Eur. J. Inorg. Chem., (1), 110-117.
[71] Żurowska, A., & Brzuszkiewicz, A., (2008). Co(II) promoted transformation of
diethyl(quinolin-2-ylmethyl)phosphonate to quinoline-2-carboxylate (2-qca): Synthetic,
structural and magnetic studies of [Co(2-qca)2(EtOH)2], Polyhedron, 27 (6),1623-1630.
[72] Prasad, L., Gabe, E.J., & Smith, F.E. (1982). Chlorotriphenyl(pyridinium-2-
carboxylato)tin(IV). Acta Cryst. B, 38, 1325-1327.
[73] Gabe, E.J., Lee, F.L., Khoo, L.E., & Smith, F.E., (1985). Chlorotriphenyl(quinolinium-
2-carboxylato)tin(IV) monohydrate. Inorg. Chim. Acta, , 105, 103-106.
[74] Żurowska, B., & Kochel, A. (2008 ). Synthesis, characterization and crystal structure
of [Cu(2-pic)2Br2][(2-pic-H)2]. J. Mol. Struct., 877 (1-3), 100-104.
[75] Żurowska, & B. Mroziński, J. (2003). Ferromagnetic exchange coupling in a two-
dimensional copper(II) compound: Cu(pyridine-2-carboxylate)Cl. Inorg. Chim. Acta,
342, 23-28.
[76] Żurowska, B., Mroziński, J. & Ciunik, Z. (2007). Structure and magnetic properties of a
coper(II) compound with syn-anti carboxylato- and linear Cu-Cl-Cu chloro-bridges.
Polyhedron, 26 (13), 3085-3091.
[77] Żurowska, B., Mroziński, J. & Ciunik, Z. (2007). One-dimensional copper(II)
compound with a double out-of-plane carboxylato-bridge-Another polymorphic form of
Cu(pyridine-2-carboxylate)2. Polyhedron, 26 (6), 1251-1258.
[78] Żurowska, B., Mroziński, J., & Ślepokura, K. (2007). Structure and magnetic
properties of a double out-of-plane carboxylato-bridged Cu(II) compound with
pyridine-2-carboxylate. Polyhedron, 26 (13) 3379-3387.
[79] Żurowska, B., & Ślepokura, K. (2008). Structure and magnetic properties of
polynuclear copper(II) compounds with syn-anti carboxylato and bromo-bridges. Inorg.
Chim. Acta, 361 (5), 1213-1221.
[80] Biswas, C., Mukherjee, P., Drew, M.G.B., Gómez-Garcia, C.J., Clemente-Juan, J.M.,
& Ghosh, A. (2007). Anion-directed synthesis of metal-organic frameworks based on 2-
picolinate Cu(II) complexes: a ferromagnetic alternating chain and two unprecedented
ferromagnetic fish backbone chains. Inorg. Chem., 46 (25), 10771-10780.
[81] Goher, M.A.S., Hafez, A.K., Abu-Youssef, M.A.M., Popitsch, A., Fritzer, H.P. &
Mautner, F.A. (1994). Synthesis and spectral and structural characterization of a
bridging chloropicolinatocopper(II) complex, Cu(C5H4NCOO)Cl Monatsh. Chem., 125
(8-9), 833-840.
[82] Belokon, Y.N., Tararov, V.I., Savel’eva, T.F., Vitt, S.V., Paskonova, E.A. Dotdayev,
S. Ch., Borisov, Y.A., Struchkov, Y.T., Batasanov, A.S., & Belikov, V.M. (1988).
Copper(II) ion promoted direct hydrolysis of 2-cyanopyridine to picolinic acid.
Intramolecular catalysis by the coordinated N-β-hydroxyethyl group. Inorg. Chem., 27
(22), 4046-4052.
[83] Żurowska , B., Ochocki, J., Mroziński, J., Ciunik, Z., & Reedijk, J. (2004). Synthesis,
spectroscopic and magnetostructural evidence for the formation of Cu(II) complexes of
pyridyl-2-carboxylate (2-pca) and quinolyl-2-carboxylate (2-qca) as a result of a novel
oxidative P-dealcylation reaction of diethyl 2-pyridylmethylphosphonate (2-pmpe) and
diethyl 2-quinolilmethylphosphonate (2-qmpe) ligands. Inorg. Chim. Acta., 357 (3),
755-763.
[84] Barandika, M.G., Serna, Z.E., Urtiaga, M.K., de Larramendi, J.I.R., Arriortua, M.I. &
Cortes, R. (1999). Crystal structure and magnetic properties of two metal-picolinate
systems obtained from degradation of bis(2-pyridylketone) through reaction with
Mn(II) and Cu(II). Polyhedron 18 (8-9), 1311-1316.
[85] Colacio, E., Costes, J.P., Kivekäs, R., Laurent, J.P., Ruiz, J., & Sundberg, M. (1991). A
new hydrogen-bonded dinuclear complex involving copper(II) ions in a
pseudotetrahedral N3O environment: molecular and crystal structure and magnetic and
spectroscopic properties. Inorg. Chem., 30 (7), 1475-1479.
[86] Carlin, R.L., van Duyneveldt, A.I. (1977). Magnetic properties of transition metal
compounds, New York: Springer-Verlag,
[87] J.B. Goodenough, (1963). Magnetism and the Chemical Bond, New York: Interscience,
165-184.
[88] Ruiz, E., Alemany, P., Alvarez, S., & Cano, J. (1997). Structural modeling and
magneto-structural correlations for hydroxo-bridged copper(II) binuclear complexes, J.
Am. Chem. Soc., 119 (6), 1297-1303.
[89] Hay, P.J., Thibeault, J.C., & Hoffman, R. (1975). Orbital interactions in metal dimer
complexes. J. Am. Chem. Soc., 97 (17), 4884.
[90] Jeter, D.Y., Lewis, D.L., Hempel, J.C., Hodgson, D.J., & Hatfield, W.E. (1972).
Magnetic properties of the complex di-µ-hydroxo-bis[2-(2-ethylamino-
ethyl)pyridine]dicopper(II) perchlorate. Inorg. Chem., 11, (8), 1958-1960.
[91] Kahn,O. (1982). Molecular Engineering of coupled polynuclear systems: orbital

mechanism of the interaction between metallic centers. Inorg. Chim. Acta, 62 (1) 3-14.
[92] Girerd, J.J., Charlot, M. F., & Kahn, O. (1977). Orbital interaction in one-dimensional
magnetic compounds. Mol. Phys. 34 (4), 1063-1076.
[93] Figgis, B.N., & Martin, R.L., (1956). Magnetic studies with copper(II) salts .1.
Anomalous paramagnetism and σ-bonding in anhydrous and hydrated copper(II)
acetates. J. Chem. Soc., 3837-3846.
[94] Colacio, E., Dominguez-Vera, J.M., Costes, J.P., Kivekäs, R., Laurent, J.P., Ruiz, J.,
& Sundberg, M. (1992). Structural and magnetic studies of a syn-anti carboxylate-
bridged helix-like chain copper(II) complex. Inorg. Chem., 31 (5), 774-778.
[95] Colacio, E., Dominguez-Vera, J.M., Kivekäs, R. & Ruiz, J. (1994). Preparation, crystal
structures and magnetic properties of a syn-anti carboxylate-bridged dinuclear
copper(II) complex and its precursor, a hydrogen-bonded polynuclear copper(II)
complex. Inorg. Chim. Acta, 218 (1-2), 109-116.
[96] Colacio, E., Costes, J.P., Kivekäs, R., Laurent, J.P. & Ruiz, J. (1990). A quasi-
tetrahedral tetracopper cluster with syn-anti bridging carboxylate groups: crystal and
molecular structure and magnetic properties. Inorg. Chem., 29 (21), 4240-4246.
[97] Colacio, E., Dominguez-Vera, J.M., Kivekäs, R., Moreno, J.M., Romerosa, A., & Ruiz,
J. (1993). Structure and magnetic properties of a syn-anti carboxylate bridged linear
trinuclear copper(II) complex with ferromagnetic exchange. Inorg. Chim. Acta, 212 (1-
2), 115-121.
[98] Inoue, M., & Kubo, M., (1970). Superexchange interaction in anhydrous copper(II)
formate. Inorg. Chem., 9 (10), 2310-2314.
[99] Youngme, S., Pakawatchai, C., Somjitsripunya, W., Chinnakali, K., & Fun, H.-K.
(2000). Preparation, crystal structure, spectroscopic and magnetic characterisation of
acetatobis(di-2-pyridylamine)copper(II) tetrafluoroborate and μ-carbonato-tetrakis(di-2-
pyridylamine) dicopper(II) bistetrafluoroborate tetrahydrate. Inorg. Chim. Acta, 303 (2),
181-189.
[100] Colacio, E., Domínguez-Vera, J.M., Ghazi, M., Kivekäs, R., Klinga, M., & Moreno,
J.M. (1999). Singly anti-anti Carboxylate-Bridged Zig-Zag Chain Complexes from a
Carboxylate-Containing Tridentate Schiff Base Ligand and M(hfac)2 [M = MnII, NiII,
and CuII]: Synthesis, Crystal Structure, and Magnetic Properties. Eur. J. Inorg. Chem.,
(3), 441-445.
[101] Costes, J.P., Dahan, F., & Laurent, J.P. (1985). A further example of a dinuclear
copper(II) complex involving monoatomic acetate bridges. Synthesis, crystal structure,
and spectroscopic and magnetic properties of bis(μ.-acetato)bis(7-amino-4-methyl-5-
aza-3-hepten-2-onato(1-))dicopper(II). Inorg. Chem., 24 (7), 1018-1022.
[102] Chiari, B., Helms, J.H., Piovesana, O., Tarantelli , T.& Zanazzi, P.F. (1986). Exchange
interaction in multinuclear transition-metal complexes. 8. Structural and magnetic
studies on bis(acetato)bis(N-methyl-N'-(5-methoxysalicylidene)-1,3-propanediaminato)
dicopper dihydrate, a novel "structural" ladderlike compound with "magnetic"
alternating-chain behavior. Inorg. Chem., 25 (6), 870-874.
[103] Gandour, R.D. (1981). On the importance of orientation in general base catalysis by
carboxylate. Bioorg. Chem., 10 (2), 169-176.
[104] Wiberg, K.B., & Laidig, K.E.( 1987). Barriers to rotation adjacent to double bonds. 3.
The C-O barrier in formic acid, methyl formate, acetic acid, and methyl acetate. The
origin of ester and amide “resonance”. J. Am. Chem. Soc., 109, 5935-5943.
[105] Levstein, P.R., & Calvo, R. (1990). Superexchange coupling mediated by carboxylate
and hydrogen bridges in copper amino acid complexes. Inorg. Chem. Soc., 29, 1581-
1583.
[106] Grove, M., Sletten, J., Julve, M., & Lloret, F. (2001) Solid-State polymerization causing
transition to a ferromagnetic state. Crystal structures and magnetic properties of
[Cu2(dpp)(H2O)(dmso)Cl4]·dmso and [Cu2(dpp)Cl4]n (dpp = 2,3-bis(2-pyridyl)pyrazine.
J. Chem. Soc. Dalton Trans., (17) 2487-2493.
[107] Youngme, S., Chaichit, N., Kongsaeree, P., van Albada, G.A. & Reedijk, J. (2001).
Synthesis, structure, spectroscopy, and magnetism of two new dinuclear carbonato-
bridged Cu(II) complexes. Inorg. Chim. Acta, 324, (1-2), 232-240.
[108] Cervera, B., Ruiz, R. Lloret, F., Julve, M., Cano, J., Faus, J., Bois, C. & Mroziński, J.
(1997 ). Tuning the nature of the exchange interaction in out-of-plane oximato-bridged
dinuclear copper(II) complexes. J. Chem. Soc. Dalton Trans., (3), 395-401.
[109] W.E. Hatfield, (1985). Magneto-Structural Correlation’s in Exchange Coupled
Systems, In R.D. Willett, D. Gatteschi, O. Kahn ((Eds). Dordrecht: D. Reidel.
[110] Seeber, G., Kariuki, B.M., Cronin, L., & Kögerler, P. (2005). Synthesis, structure and
magnetism of a linear Cu–Cl–Cu entity found in [(Cu(tachH)(tach))2(μ-Cl)]5+
Polyhedron, 24, 1651-1655.
[111] Du, M., Guo, Y.M., Bu, X.H., Ribas, J., & Monfort, M. (2002). Structural and first
magnetic characterization of unique mono-μ-chloro bridged dinuclear CuII complexes
with heterocycle-functionalized diazamesocyclic ligands. New J. Chem., 26, 939-945.
[112] Chou, J.L., Chyn, J.P., Urbach, F.L., & Gervasio, D.F. (2000). Dinuclear copper(II)
complexes incorporating a novel pyrazolo-based ligand with S- and N-rich coordination
spheres. Polyhedron, 19 (20-21), 2215-2223.
[113] Kahn, O., & Charlot, M.F. (1980). Overlap density in binuclear complexes - A
topological approach of the exchange interaction. Nouv. J. Chim. 4, 567-576.
[114] Kahn, O., & Briat, B., (1976). Exchange interaction in polynuclear complexes. J. Chem.
Soc., Faraday Trans., 2, 268-285.
[115] Addison, A.W., Rao, T.N., Reedijk, J., van Rijn, J., & Verschoor, G.C. (1984).
Synthesis, structure, and spectroscopic properties of copper(II) compounds containing
nitrogen–sulphur donor ligands; the crystal and molecular structure of aqua[1,7-bis(N-
methylbenzimidazol-2′-yl)-2,6-dithiaheptane]copper(II) perchlorate. J. Chem. Soc.
Dalton Trans., (7), 1349-1349.
[116] Kahn, O., Claude, R.,& Coudanne, H. (1978 ). Ferromagnetic coupling and electron-
transfer in CoCu(ben).3H2O [H4ben = NN'-bis(2-hydroxy-3-carboxybenzylidene)-1,2-
diaminoethane]. J. Chem. Soc., Chem. Commun., (23), 1012-1013.
[117] Kahn, O., Tola, P., Galy, J., & Coudanne, H. (1978). Interaction between orthogonal
magnetic orbitals in a copper(II)-oxovanadium(II) heterobinuclear complex. J. Am.
Chem. Soc., 100, 3931-3933.
[118] Lee, Y-M., Lee, H.-W., & Kim, Y-I. (2005). Structural and magnetic characterization
of copper(II) halide complex with 2-(dimethylaminomethyl)-3-hydroxypyridine
Polyhedron, 24 (2), 377-382.
[119] Towle, D.K., Hoffmann, S.K., Hatfield, W.E., Singh, P., Chaudhuri, P., & K.
Wieghard, (1985). Ferromagnetic intramolecular interactions in a bis(μ-bromo)-bridged
copper(II) dimeric compound: crystal structure and molecular structure determination,
electron paramagnetic resonance studies, and magnetic susceptibility measurements on
bis(μ-bromo)bis(diethylenetriamine)copper(II)] perchlorate. Inorg. Chem., 24 (25),
4393-4397.
[120] Alves, W.A., de Almeida Santos, R.H., Paduan-Filho, A., Becerra, C.C. Borin, A., & da
Costa Ferreira, A.M. (2004). Molecular structure and intra- and intermolecular
magnetic interactions in chloro-bridged copper(II) dimers. Inorg. Chim. Acta, 357 (8),
2269-2278.
[121] Folgado, J.V., Coronado, E., Beltran-Porter, D., Burriel, R., Fuertes, A., & Miravitlles,
C. (1988 ). Crystal structures and magnetic properties of the mono-µ-halogeno-bridged
copper(II) chains Cu(pcpci)X [pcpci =N-(2′-pyridylcarbonyl)pyridine-2-carboximidate,
X = Cl or Br]. J. Chem. Soc. Dalton Trans., (12), 3041-3045.
[122] van Ooijen, J.A.C., & Redijk, J.( 1978 ). Magnetic exchange in some polynuclear
bis(azole)dihalogenocopper(II) complexes. J. Chem. Soc. Dalton Trans., (9), 1170.
[123] van Ooijen, J.A.C., & Reedijk, J. (1977). Linear-chain anti-ferromagnetism and
spectroscopy of compounds CuX2L2, with X = Cl, Br and L = substituted pyridine.
Inorg. Chim. Acta, 25, 131-140.
[124] Estes, W.E., Gavel, D.P., & Hatfield, W.E., ( 1978). Magnetic and structural
characterization of dibromo- and dichlorobis(thiazole)copper(II). Inorg. Chem., 17 (6),
1415-1421.
[125] Jeter, D.Y., & Hatfield, W.E. (1972). Out-of-plane chain interactions in
dichlorobis(pyridine)copper(II) and dibromobis (pyridine)-copper(II). J. Inorg. Nucl.
Chem., 34, 3055-3060.
[126] Jeffrey, G.A., & Saenger, W. (1991). Hydrogen Bonding in Biological Structures;
Springer: Berlin.
[127] Jeffrey, G.A., (1997) An Introductioon to Hydrogen Bonding; Oxford: New York.
[128] Fisher, B.E., & Sigel, H. (1980). Ternary complexes in solution. 35. Intramolecular
hydrophobic ligand-ligand interactions in mixed ligand complexes containing an
aliphtic amino acid. J. Am Chem. Soc., 102, 2998-3008.
[129] Sugimori, T., Shibakawa, Masuda, K. H., Odani, A., & Yamauchi, O. (1993). Ternary
metal(II) complexes with tyrosine-containing dipeptides. Structures of copper(II) and
palladium(II) complexes involving L-tyrosylglycine and stabilization of copper(II)
complexes due to intramolecular aromatic ring stacking. Inorg. Chem., 32 (22), 4951-
4959.
[130] Costa-Filho, A.J., Munte, C. E., Barberato, C., Castellano, E.E., Mattioli, M.P.D. Calvo,
R., & Nascimento, O.R. (1999). Crystal Structures and Magnetic Properties of
CuX2(pdmp)2 Complexes (X = Br, Cl). Inorg. Chem., 38 (20), 4413-4421.
[131] Janiak, Ch. (2000 ). A critical account on π–π stacking in metal complexes with
aromatic nitrogen-containing ligands. J. Chem. Soc. Dalton Trans., (21), 3885-3896.
[132] Roesky, H.W., & Andruh, M. (2003). The interplay of coordinative, hydrogen bonding
and π-π stacking interactions in sustaining supramolecular solid-state architectures. A
study case of bis(4-pyridyl)- and bis(4-pyridyl-N-oxide) tectons. Coord. Chem. Rev.,
236 (1-2), 91-119.
[133] Brill, A.S. (1977). Transition Metals in Biochemistry, Berlin: Springer Verlag.
[134] S.J. Lippard, & J.M. Berg. (1994) Principles of Bioinorganic Chemistry, California,
University Science Books; Mill Valley.
[135] Żurowska, B., & Mroziński, J. (2007). Magnetic interaction in Cu(pyridine-2-
carboxylate)2. Pol. J. Chem., 81, 403-410.
[136] Madalan, J., Kravtsov, V., Pajic, Ch., Zadro, D., Simonov, K., Stanica, Y. A., Ouahab,
N. Lipkowski, L., & Andruch, M. (2004). Chemistry at the apical position of square-
pyramidal copper(II) complexes: synthesis, crystal structures, and magnetic properties
of mononuclear Cu(II), and heteronuclear Cu(II)–Hg(II) and Cu(II)–Co(II) complexes
containing [Cu(AA)(BB)]+ moieties (AA=acetylacetonate, salicylaldehydate; BB=1,10-
phenanthroline, Me2bipy=4,4′-dimethyl-2,2′-bipyridine). Inorg. Chim. Acta, 357 (14),
4151-4164.
[137] Policar, C., Lambert, F., Cesario, M., & Morgenstern-Badarau, I. (1999). An Inorganic
Helix [Mn(IPG)(MeOH)]n[PF6]n: Structural and Magnetic Properties of a syn-anti
Carboxylate-Bridged Manganese(II) Chain Involving a Tetradentate Ligand. Eur. J.
Inorg. Chem. (12), 2201-2207.
[138] Stachová, P., Korabik, M., Koman, M., Melnik, Mroziński, M.J. Głowiak, T.,Mazur,
M.,& Valigura, D. (2006). Synthesis, spectral and magnetical characterization of
monomeric [Cu(2-NO2bz)2(3-pyme)2(H2O)2] and polymeric [Cu{3,5-(NO2)2bz}2(3-
pyme)2]n. Inorg. Chim. Acta., 359 (4), 1275-1281.
[139] Yamauchi, O., Odani, A., & Masuda, H. (1992). Weak interactions in metal complexes
of amino acids with a phosphorylated side chain. Conversion of aromatic ring stacking
to electrostatic bonding by tyrosine phosphorylation. Inorg. Chim. Acta, 200-198, 749-
761.
[140] Brondino, C.D., Calvo, R., Atria, A.M,. Spodine, E., & Peña, O.( 1995). Polynuclear
complexes with hydrogen-bonded bridges. 4. Structure and magnetic properties of
dinuclear copper(II) complexes of amino alcohols. Inorg. Chim. Acta, 228 (2), 261-266.
[141] Żurowska, B., & Mroziński, J., (2005). Isomeric forms of Cu(quinoline-2-
carboxylate)2·H2O. Spectroscopic and magnetic properties. Mater. Sci-Poland., 23 (3),
737-744.
[142] Xie, Y. Liu, Q., Jiang, H., Du, C., Xu, X., Yu, M., & Zhu, Y. ( 2002). An unusual
alternating ferro- and antiferromagnetic 1D hydrogen-bonded μ2-1,3-azide-bridged
copper(II) complex: a dominant ferromagnetic coupling New. J. Chem., 26 (1), 176-
179.
[143] Desplanches, C., Ruiz, E., Rodríguez-Fortea, A., Alvarez, S. (2002). Exchange
coupling of transition-metal ions through hydrogen bonding: A theoretical
investigation. J. Am. Chem. Soc., 124 (18), 5197-5205.
[144] Desplanches, C., Ruiz, E., & Alvarez, S., (2002). Early-late transition metal
ferromagnetic coupling mediated by hydrogen bonding. Chem. Commun., (22), 2614-
2615.
[145] Bertrand, J.A., Fujita, E., & VanDerveer, D.G. (1980). Polynuclear complexes with
hydrogen-bonded bridges. 4. Structure and magnetic properties of dinuclear copper(II)
complexes of amino alcohols., Inorg. Chem., 19, (7), 2022-2028.
[146] Tercero, J., Diaz, C., Ribaz, J., Machia, J., & Maestro, M.A. (2002). New oxamato-
bridged Trinuclear CuII−CuII−CuII complexes with hydrogen-bond supramolecular
structures: Synthesis and magneto−structural studies. Inorg. Chem., 41, (21), 5373-
5381.
[147] Maspoch, D., Catalá, L., Gerbier, P., Ruiz-Molina, D., Vidal-Gancedo, J., Wurst, K.,
Rovira, C., & Veciana, J. (2002). Radical para-benzoic acid derivatives: transmission
of ferromagnetic interactions through hydrogen bonds at long distances. Chem. Eur. J.,
8 (16), 3635-3645.
[148] Paine, T.K., Weyhermuller, T., Wieghardt, K., & Chaudhuri, P., (2002). The
methanol−methanolate CH3OH···OCH3- Bridging ligand: Tuning of exchange coupling
by hydrogen bonds in dimethoxo-bridged dichromium(III) complexes. Inorg. Chem., 41
(25), 6538-6540.
Chapter 6
REVIEW: TRANSITION METALS IN MEDICINE
Hanan F. Abdel-Halim
Pharmaceutical Chemistry Department, Faculty of Pharmacy,
Misr International University, Cairo, Egypt
INTRODUCTION
Opportunities exist to exploit inorganic chemistry in the discovery and development of
pharmaceuticals. Preparation of model compounds, synthesis of potential medicinal agents
and imaging agents are the new area of pharmaceutical researches[1]. This involves the
synthesis of metal complexes, usually of relatively small molecule ligands, which in some
way mimic the naturally occurring metallomolecules, or which have desirable properties such
as solubility, stability in vivo, selective absorption into certain tissues, are the main core of
studying metals in medicine.
Fear of metal toxicity is a limiting factor, but may be, in part, a matter of perception. Not
all metals are bad and not all metals are "heavy metals", yet, even essential metals are toxic at
certain levels and in some chemical forms [2,3]. The key is to understand and to control the
interaction of the metal with the living system. Metal metabolism is emerging as an exciting
area of cell biology and a potential site for therapeutic interventions where normal metal
metabolism appears to maintain free metal ion concentrations at a very low level and to
deliver metals very selectively to their sites of action, while maintaining tight control over
their reactivity [3].
The unique properties of metal complexes may offer advantages in the discovery and
development of new drugs. These unique properties include redox activity, Lewis acidity,
electrophilicity, access to cationic/anionic/radical species, flexible bond orders, unique
geometries, easily accessed structure/activity variations, and magnetic, spectroscopic, and
radioactive signatures. The fundamental properties of metals and of metal-ligand chelation
chemistry remain an important area for research. Examples include regulation of spin
relaxation processes, complex stability, ligand exchange kinetics, and other physico- chemical
properties (electrochemical potentials, fluorescence quantum yields, ligand pKa values,
etc.).[3] Metals can be useful probes of cellular function. Understanding these interactions is
264 Hanan F. Abdel-Halim
paving the way toward rational design of metallopharmaceticals and implementation of new
co-therapies.
Metal complexes can be potent and highly selective ligands of cell surface receptors. As
metal complexation is the basis for chelation therapy and to rectify abnormal metal
accumulations or toxic metal exposures (e.g., iron overload; lead, cadmium, and mercury
poisoning),improving chelator designs are needed to enhance selectivity, affinity, stability,
renal clearance, and oral activity, while maintaining low toxicity and low cost.
Ligand must be designed to optimize desired metal complex properties (e.g:
thermodynamic and kinetic stability, hydrolytic stability, catalytic activity, molecular weight,
charge, lipophilicity, water solubility, targeting functionalization, and ligand metabolism).In
addition, the essential transition metal ions are accumulated by cells, to be used as required
cofactors, and to catalyze cytotoxic reactions in which several families of proteins are
emerging to control the activity of intracellular metal ions and to help confine them to vital
roles. These include integral transmembrane transporters, metalloregulatory sensors, and
metallochaperone proteins [soluble metal receptor proteins] that protect and guide metal ions
to targets [3].
In this review we try to present the importance of some examples of transition metals in
the treatment of certain diseases and their role in avoid these diseases.
METTALOENZYMES
Metals play roles in approximately one-third of the known enzymes. Metals may be a co-
factor or they may be incorporated into the molecule, and these are known as
metalloenzymes. Amino Acids in peptide linkage posses groups that can form coordinate-
covalent bonds with the metal atom , the free amino and carboxyl group bind to the metal
affecting the enzymes structure resulting in its active conformation [4].
The metalloproteins are part of enzymatic systems, have structural functions, and use the
protein to be transported to their target site in the organism. In enzymes, the metals participate
in catalytic processes as:
• constituents of enzyme active sites.

• stabilizers of enzyme tertiary or quaternary structure.
• contributors in forming weak bonding complexes with the substrate that can carrying
out the orientation of the substrate for reactions.
• Stabilizers for charged transition states.
As constituents of active sites, metal cations with unpaired electrons mediate oxidation–
reduction (redox) processes by reversible changes in their oxidation state, transferring or
receiving electrons to or from the substrate and co-factor. For example, human superoxide
dismutases reduce one superoxide anion to hydrogen peroxide, and oxidize a second
superoxide anion to generate molecular oxygen by means of either Cu or Mn present in the
active site of the cytosolic or mitochondrial enzyme, respectively. The presence of metals
bound to lipids, nucleic acids, and carbohydrates is well documented, but the biochemical
functions of the metals present in these molecules is unclear.
R
Review: Transiition Metals inn Medicine 265
Because metals
m resemblle protons (H+) in that theyy are electrophhiles that are capable of
acccepting an ellectron pair too form a chem mical bond, thhey may act as a general aciids to react
w
with anionic anda neutral liigands. This characteristicc of metals is i helpful in enzymatic
sttructure and fuunction but makes
m the enzyyme it is part of pH dependdent. Changess in pH can
diisrupt this eleectron flow thhat the metal would
w normallly help facilitate and thus inhibit the
ovverall effectivveness of the metalloenzyme
m e.
Nucleases which are meetalloenzymess that have a wide w variety of
o active site motifs and
thhat contain a variety of different
d metaal ions, therefore, design and synthesiss of metal
coomplexes, which can mediaate phosphodieester bond cleeavage via hyddrolytic pathw ways, are of
immportant signiificance in eluucidation of the t catalytic mechanisms
m f the naturall nucleases
for
annd in the deveelopment of the t biomacrom molecule - tarrgeted drugs. Despite the difficulty
d to
prropose a simpple mechanism m for these ennzymes due too the variationn of metal ionns that they
coontain, recent progress has extended
e to thhe design of syynthetic multinnuclear metalllonucleases
coontaining two or more Fe (IIII), Zn (II), Cu (II), Co (II/IIII), or Ln (IIII/IV) ions. Thee ligands in
thhese complex xes include natural andd non-naturall organic molecules, m i.ee., mainly
beenzimidazolyll- and pyridyll-based organiic molecules, azamacrocyclic and aminoocarboxylic
deerivatives, andd their conjuggates to polyppeptides or oligonucleotidees. Owing to be able to
unnderstand thee differences in structure and composition betweenn natural andd synthetic
m
multinuclear metallonucleaases; the design straategies of synthetic multinuclear
m
m
metallonuclease es; the relaationship betw ween the struuctures and nucleolytic
n acctivities of
syynthetic multiinuclear metallonucleases; and the coooperativities between b metall sites, and
beetween metal sites and liggands in the courses c of phhospodiester linkage hydrolysis, deep
sttudies and com mparison mustt be illustratedd. Indeed, therre are featuress that converge about the
chhemistry that provides
p insigght into how chhanges in mettal ions and liggands of both natural
n and
syynthetic metalllonucleases may
m lead to thee same overalll outcome of phosphodieste
p r backbone
clleavage (Fig gure 1).In addition,
a thee solvation effect of synthetic multinuclear
m
m
metallonuclease es and the chaallenges that shhould be facedd toward the development
d o synthetic
of
m
multinuclear metallonuclease
m es with DNA A sequence or structure seleectivity by appplying the
prrinciples of cooordination annd enzymatic chemistry
c [5,6].
Fiigure 1. DNA hydrolytic

h cleavvage catalyzed by
b synthetic muultinuclear metallonucleases.
Transition state is a keyy role in the competitive inhibition of metalloenzym

m mes because
thhey mimic thee structure off the substrattes transition state in the reaction
r of ennzyme and
suubstrate. Metaal's larger sizee relative to protons
p is com
mpensated for by their abiliity to react
w more thann one ligand. Metals
with M typically react with two, four, orr six ligands. A ligand is
w
whatever moleccule the metall interacts withh. If a metal iss bound with tw
wo ligands it will
w form a
linnear complex. So that, if the metal reactss with four ligaands the metal will be set inn the center
off a square thatt is planer or it will form a tetrahedral
t struucture, and whhen six ligandds react, the
m
metal sits in th
he center of ana octahedronn. Amino acidds in their pepptide linkage in proteins
poossess groupss with the abillity to bind too the metal reesulting in cooordinate-covallent bonds.
The free amino o and carboxyl groups in a protein
p can biind to the mettal and this maay bind the
prrotein to a sp pecific, activee conformationn. The fact thhat metals binnd to several ligands is
immportant in thhat metals plaay a role in bringing
b remoote parts of thhe amino acidd sequence
toogether and heelp establish ann active confoormation of thee enzyme.
As transition metal cataalysis is recoggnized as beinng integral too the generatioon and the
reeactions of acttivated oxygenn species (parrtially-reducedd forms of diooxygen or “oxxy-radicals”
(ssuperoxide, ; hydrogen perroxide H2O2; hydroxyl radiical OH) ,factoors such as
pH H and chelatioon govern thee reactivity of the transitionn metals as wee mentioned before,
b with
diioxygen and “oxy-radicals” and therefoore influence the apparentt mechanisms by which
oxxidative damaage to phosphholipids, DNA A, and other biomolecules is i initiated. Inn biological
syystems the co oncentrations of redox-active transitionn metals capaable of catalyyzing these
reeactions appeaars to be relattively low. Hoowever, underr certain condditions metal storage
s and
trransport proteeins (ferritin, transferrin, ceruloplasmin,
c , etc.) may furnish
f additioonal redox
acctive metals [7].Antioxidan
[ nt has been described
d as any
a substance that interferees with the
reeaction of any y substance with
w dioxygenn. The more mechanistic definition
d stattes that an
a substance that hinders a free radical reeaction
anntioxidant is any
CHROMIUM
H
Chromium is not only an a essential ellement required for normall carbohydratee and lipid
metabolism, buut also, its diettary intake is often sub opttimal in the prrevention and alleviation
m
off risk factors associated
a withh diabetes andd cardiovascullar diseases.
Insufficient dietary intakke of chromiuum leads to inccreases in riskk factors assocciated with
diiabetes and cardiovasculaar diseases including eleevated circullating insulinn, glucose,
trriglycerides, tootal cholesterool, reduced HDDL-cholesteroll, and impaired immune funnction.
Severe sig gns of diabettes including weight loss, glucose intoolerance and peripheral
neeuropathy thatt were refractoory to insulin were
w treated byb supplementtal chromium [8, 9].
Chromium improves innsulin function by increasing insulin binding b to cells, insulin
reeceptor numbeer, and phospphorylation off the insulin receptor leading to increassed insulin
seensitivity [10--12]. Researchh has shown that chromiuum(III) picolinnate (Figure 2) 2 helps to
prrevent weight gain associatted with the use u of the diabbetic drug as chromium
c polynicotinate
iss better absorbbed than otheer forms, in which,
w chromiium is bound to vitamin B3,B known(
niicotinic acid). Other forms of chromium,, such as chroomium glycinaate chelate, may work as
w
well. Chromiu um is an esseential nutrientt forming thee active com mponent of the "glucose
toolerance factorr." Despite thhis, chromium m remains the only essentiall transition metal
m whose
m
mechanism of action
a is not known
k [13-16].
R
Fiigure 2. Chromiium (III) picolinnate.
While the toxicity

t of chrromium comppounds are varried due to thee oxidation state and the
soolubility , Cr (VI)
( compounnds, which are powerful oxiddizing agents appear to be much m more
tooxic systemicaally than Cr (III) compounds. Although mechanisms of biological interaction
arre uncertain, thhis variation in
i toxicity mayy be related too the ease withh which Cr (VVI) can pass
thhrough cell membranes andd its subsequeent intracellulaar reduction too reactive inteermediates,
annd the difficuulty of absorbbing Cr(III) by any route. The toxicity of chromium m is mainly
atttributable to the Cr(VI) formf as the reduction
r of CrC (VI) is coonsidered to serve as a
deetoxification process
p when it occurs at a distance from m the target sitte for toxic orr genotoxic
efffect. While reeduction of Crr(VI) may serrve to activate chromium toxicity if it takkes place in
orr near the cell nucleus of tarrget organs[177-20] .
If Cr (VI) is reduced too Cr (III) exttracellularly, this
t form of the
t metal is not n readily
trransported intto cells and so toxicity iss not observeed[21]. As Cr(VI) C enters cells very
effficiently by an
a anion transpport system it is reduced insside the cells tot Cr(III) which binds to
prroteins and DN NA, this creattes adducts invvolving the sixx coordinationn sites of Cr(IIII) with the
phhosphate backkbone of DNA A, N-7 of guannine, and aminno acids, such as cysteine, glutathione,
g
annd larger pepttides and proteein molecules. These ternarry DNA compplexes are veryy stable but
caan be dissociaated with chelaators, such as EDTA.
E
COPPER
Copper is an essential trace
t elementt present in thhe diet and inn the human body. It is
neeeded to abso orb and utilizze iron. It iss also part off the antioxiddantenzyme, superoxide
diismutase (SOD D) [22]. Coppper is needed to make adennosine triphospphate (ATP), the energy
thhe body runs on. Synthesiss of some hoormones requiires copper, as a does the syynthesis of
coollagen (the "glue" that holds connecctive tissue together). t In addition, the enzyme,
tyyrosinase, whiich plays a rolle in the produuction of skin pigment (melanin), requires copper to
fuunction.
Copper com mbines with certain
c proteinns to produce enzymes
e that act as catalystts to help a
nuumber of bodyy functions, others help to formf cross-linnks in collagenn and elastin and
a thereby
m
maintain and reepair connectiive tissues [233]. Referencess and further reading
r may be
b available
foor this article. To view referrences and furrther reading youy must purcchase this article. This is
esspecially impoortant for the heart
h and arterries. Research suggests that copper deficieency is one
faactor leading to
t an increasedd risk of develloping coronarry heart diseasse.
It appears clear that the decrease in antioxidant
a prrotection caused by copper deficiency
gooes beyond a decrease in thhe activity of copper-depend
c dent antioxidaant enzymes by
b inducing
a wide range of o disturbances in other anttioxidant enzyyme systems. as well as inccreases the
suusceptibility of
o lipoproteinss and heart tissue to peroxiddation, providding strong evidence that
coopper plays a vital role in the protectioon of the carddiovascular syystem from frree -radical
m
mediated damaage and diseasee.
Copper hass also been ussed as a mediccine for thoussands of yearss including thee treatment
off chest wound ds and the puurifying of driinking water. Recently, ressearch has inddicated that
coopper helps prrevent inflamm mation in arthhritis and simillar diseases. Research
R is going on into
annti-ulcer and anti-inflammaatory medicinees containing copper, and its use in raddiology and
foor treating co onvulsions andd epilepsy. With
W the know wledge that many
m copper complexes
poossess anti-in nflammatory activity,
a and the finding that t these coopper complexxes almost
allways have significantly
s stronger activity and havve lower toxxicity than thheir parent
coompounds, it hash been hypoothesized that the active forrm of many poopular anti-infflammatory
drrugs are their copper chelatees[24].
It has beenn demonstratedd that copper complexes
c such as copper aspirinate
a (Figgure 3) and
coopper tryptop phanate (Figurre 4), markeddly increase healing rate of ulcers annd wounds.
Fuurther, it has been shownn that, whereaas non-steroiddal anti-inflam mmatory druggs, such as
ibbuprofen and enefenamic acid a suppress wound healinng, copper coomplexes of these t drugs
prromote normaal wound healiing while at thhe same time retaining
r anti-iinflammatory activity.
Fiigure 3. Copperr aspirinate.
Copper hass a role in the prevention off seizures. It was

w discoveredd that organic compounds
c
thhat are not themselves anti-cconvulsants exxhibit anticonvulsant activitty when compplexed with
coopper [25]. The
T hypothessis that coppeer complexess facilitate orr promote tisssue repair
prrocesses invollving copper-ddependent enzzymes and thaat arthritis, ulccers, seizures,, neoplasia,
annd diabetes arre diseases off specific tissuues in disrepair. The corollary to this hyypothesis is
R
thhat the loss or reduction of

o copper-depeendent enzym me-mediated processes
p leadds to tissue
dyysfunction thaat may be reveersed with coppper complex therapy
t [26].
Fiigure 4. Copperr tryptophanate..
Treating foor facial epithhelioma with a mixture of copper

c chloridde and lecithinn has been
suucceeded. Reccently researchh on the treatm ment of solid tuumors with noon-toxic dosess of various
orrganic compleexes of copper markedly decreased tum mor growth anda metastasis and thus
inncreased surviival rate. Thesse copper com mplexes did noot kill cancer cells but caussed them to
reevert to normaal cells.
Copper meetallo-organic complexes have h been shoown to have radiation
r prottection and
raadiation reco overy activitties. They are capable of causingg rapid reccovery of
immmunocompettence and recoovery from raadiation induced tissue channges. The mecchanism of
thhis activity ap
ppears to be tiied to the abiility of certainn copper com mplexes to deaactivate the
suuperoxide, or "free," radicalls liberated byy ionizing radiation. In addiition, since raadiation has
thhe capability of
o breaking thhe bonds of natural copper enzymes in the t body, suppplementing
thhese with non--toxic doses ofo pharmaceutiical copper coomplexes restoores the lost tiissue-repair
caapability. Sincce these complexes may also have anticarrcinogenic acttivity, it is sugggested that
thhere would be merit in usinng copper com mplexes in the treatment of cancer and inn particular,
trreating patients undergoing ionizing radiaation therapy forf their canceer, accidental exposure
e to
raadiation, and astronauts
a unddertaking spacee travel.
Copper haas also a direct effect on the t control of cholesterol, a metabolic imbalance
beetween zinc and
a copper - with w more empphasis on coppper deficiencyy than zinc exxcess - is a
m
major contributting factor to the
t etiology ofo coronary heart disease. Suubsequent work by other
innvestigators has
h shown thhat copper coomplexes alsoo can have a valuable role r in the
m
minimization o damage to the aorta and heart musclee as oxygenateed blood repeerfuses into
of
tissues followin ng myocardiall infarction. This
T action is based
b on the anti-inflamma
a atory action
off copper comp plexes. These and other stuudies suggest thet use of coppper dietary suupplements
ass a means of preventing and controlling such diseases as atheerosclerosis (a ( form of
arrteriosclerosis), coronary heeart disease, aoortic aneurysm
ms and myocarrdial infarctionn [27].
Ceruloplasmin is the major copper-carrying proteiin in the bloood. Ceruloplassmin as an
ennzyme that oxidizes Fe2+ (ferrous iron)) into Fe3+ (fferric iron), thherefore assissting in its
trransport in thee plasma in asssociation witth transferrin, which carriees iron in the ferric state
thhroughout the body ,thereffore, if copperr levels are too t low, iron deficiency annemia may
reesult. Due to its broad rannge of activitties in the boody, copper deficiency
d cann result in
nuumerous symp ptoms. The most
m common symptom of copper deficieency is anemiia and as a
caause of myelo odysplasia (wwhen a blood profile has inndicators of possible
p futuree leukemia
deevelopment). Other symptooms include weakness andd fatigue, poor immune and a thyroid
fuunctions, dimiinished pigmeent in skin andd hair, osteoporosis, probleems with jointts, ruptured
bllood vessels, irregular
i heartt beat , increaased levels of LDL cholesteerol and decreased levels
of HDL cholesterol, resulting in an increase in cardiovascular disease risk [28,29]. It has also
been demonstrated that copper deficiency significantly increases the susceptibility of
lipoproteins and cardiovascular tissues to lipid peroxidation, thus increasing the risk of
cardiovascular disease [30-34]. and breathing problems.
Copper is also involved in normalized function of many enzymes, such as cytochrome c
oxidase, which is complex IV in mitochondrial electron transport chain, ceruloplasmin, Cu/Zn
superoxide dismutase, and in amine oxidases[35,36]. These enzymes catalyze reactions for
oxidative phosphorylation, iron transportation, antioxidant and free radical scavenging and
neutralization, and neurotransmitter synthesis, respectively [37].
It has long been suspected that free radicals may play a role in iron- and copper-induced
cell toxicity because of the powerful prooxidant action of iron and copper salts in vitro. In the
presence of available cellular reductants, iron or copper in low molecular weight forms may
play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have
the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates, resulting in
wide-ranging impairment in cellular function and integrity. However, cells are endowed with
antioxidants, scavenging enzymes, repair processes that act to counteract the effects of free
radical production. Thus, the net effect of metal-induced free radicals on cellular function will
depend on the balance between radical production and the cytoprotective systems As a result,
there may be a rate of free radical production that must be exceeded before cellular injury
occurs.
Despite the importance role of Cu (II) complexes as we mentiond above, we must clarify
that copper (II)ion has a critical role in chronic neurologic diseases. The amyloid precursor
protein (APP) of Alzheimer's disease or a synthetic peptide representing its copper-binding
site reduced bound copper (II) to copper (I). This copper ion-mediated redox reaction led to
disulfide bond formation in APP, which indicated that free sulfhydryl groups of APP were
involved. Neither superoxide nor hydrogen peroxide had an effect on the kinetics of copper
(II) reduction. The reduction of copper (II) to copper (I) by APP involves an electron-transfer
reaction and could enhance the production of hydroxyl radicals, which could then attack
nearby sites. Thus, copper-mediated toxicity may contribute to neurodegeneration in
Alzheimer's disease [38].
Zinc and vitamin C supplements are strong antagonists of copper status and absorption.
In the case of zinc, numerous studies have shown that relatively small increases in dietary
zinc significantly lower copper absorption [39, 40]. This antagonism has been utilized as a
treatment of Wilson's disease.
Copper complexes like copper salicylate have been extensively studied for their anti-
inflammatory and antioxidant activity, as well as their ability to mimic the superoxide-radical
scavenging activity of superoxide dismutase.
Numerous researchers have examined the paradoxical role of copper in the process of
inflammation, and they have determined that the increase in serum copper is a physiological
response to inflammation, rather than a promoter of it [41]. In fact, the main copper
containing enzyme, ceruloplasmin, is significantly elevated in inflammatory conditions and
has anti -inflammatory activity [42] .Additionally, it has been shown that copper deficiency
increases the severity of experimentally-induced inflammation,[43] and that dietary copper
must be increased to maintain adequate copper status [44] .
The therapeutic potency and safety of the copper complexes of aspirin (acetyl-salicylic
acid) and salicylic acid is much better than for aspirin itself or for other copper compounds
Review: Transition Metals in Medicine 271
such as copper acetate. These complexes are 5 to 8 times more effective than aspirin but less
toxic. The therapeutic index (the margin between effectiveness and toxic effects) has been
stated as being significantly greater than for other anti-inflammatory drugs.
While aspirin and other anti-inflammatory drugs cause or aggravate ulcers and gastro-
intestinal bleeding and distress, the copper complexes have a better ulcer-healing effect than
commonly used anti-inflammatory ulcer drugs. Harmful effects of aspirin, salicylic acid and
similar drugs apparently arise because they bind copper in the stomach and intestines wall and
cause a localised copper deficiency in these tissues. This then causes connective tissue
disintegration with bleeding and ulcers. Copper salicylate supplies the necessary copper in a
useable form to heal these lesions. Then we can say that patients who are allergic to
salicylates are mainly reacting because of copper deficiency.
In addition copper salicylate has also good anti-cancer and anti-convulsive properties
suitable for treatment of epilepsy and possibly Parkinson's disease. After the liver the brain is
the second-highest copper-containing organ. There are at least 6 important copper-dependent
enzymes in the brain.
Experimental evidence showed that copper complexes can cause established tumor cells
to re-differentiate into normal cells and it has been suggested that the future use of copper
complexes to treat neoplastic diseases has some exciting possibilities [45].
Wearing copper bracelets is a time-tested anti-inflammatory, in contrast, copper
salicylates were found to be the best copper complex for the treatment of arthritic pain [46,
47].
Prion diseases such as Creutzfeldt-Jakob or "mad cow" disease, and also Alzheimer’s and
Parkinson’s disease are related to the accumulation of wrongly folded and entangled prion
proteins. It has now been shown that this may be due to a copper deficiency in the brain, and
that copper stabilises prions and helps them to fold correctly [48].
In addition to copper salicylate complexes also a salicylate complex with zinc and boron
is a good healing remedy. This has been called the Schweitzer Formula, and is formed from
zinc (oxide or carbonate), boron (boric acid) and salicylic acid. It has been used as an
antibiotic, disinfectant, fungicide, and anti-inflammatory agent.
The Schweitzer Formula was developed 1915, in addition to any kind of infection or
inflammation, it has been used in cancer treatment, to improve the immune response and
blood oxygenation. Applied externally it is claimed to heal injuries and skin diseases,
including acne, scarring varicose veins and varicose ulcers.
The decrease in antioxidant protection caused by copper deficiency goes beyond a
decrease in the activity of copper-dependent antioxidant enzymes by inducing a wide range of
disturbances in other antioxidant enzyme systems. Copper plays a vital role in the protection
of the cardiovascular system from free -radical mediated damage and disease.[49] Thus, it
appears clear that adequate copper is vital for optimal functioning of many antioxidant
enzymes, both copper dependent and otherwise, in varied organs and tissues.
Lysyl Oxidase, which is involved in the synthesis of the collagen that constitutes much of
bone and connective tissue, is a copper dependent enzyme. Insufficient copper intake has also
been shown to lower bone calcium levels during long-term deficiency [50].
With the essential role that copper plays in maintaining bone health, it is surprising how
little attention has been given to copper's role in bone diseases, estrogens, which have a
beneficial effect on preventing post-menopausal bone loss, have been shown to raise the level
of ceruloplasmin (the main copper transport protein) two to three fold, providing a possible
explanation for how estrogen positively influences bone health, as well as cardiovascular
health [51].
Copper plays another role in the development of cancer in which is somewhat similar to
its role in cardiovascular disease. Numerous copper complexes that demonstrate SOD-
mimetic properties, including copper salicylate, have been shown to possess anticancer,
anticarcinogenic, and antimutagenic effects both in vitro and in vivo [52].
With cancer copper serum levels behave similar to those described for atherosclerosis.
Various studies show a beneficial effect of copper on cancer. However, if growing tumours
are present, then copper is needed to form new blood vessels. Therefore one form of cancer
therapy creates artificial copper deficiency by removing copper with a molybdenum
compound, and high amounts of zinc may be used to prevent the absorption of copper. It has
now been shown that in the long-term this so-called anti-angiogenesis therapy does more
harm than good by stressing tumours and inducing them to spread [53].
The main metabolic defect of cancer cells, according to researchers, is a deficiency of the
enzyme cytochrome oxidase. This causes a blockage in the cellular respiration or oxidative
energy production of the affected cells. Cytochrome oxidase is a copper dependent enzyme
and additional copper might be beneficial. In the final stages of this oxidative energy
production cytochrome oxidase transfers electrons to copper (II) and iron (III) to form copper
(I) and iron (II). In the last step these electrons are then transferred to oxygen, which now can
attract hydrogen ions to form water. In cancer cells this electron transfer is blocked and
energy is inefficiently produced by converting glucose into lactic acid.
Due to copper deficiency this electron transfer is defective in Menkes disease, a genetic
disorder of early childhood. This is sometimes called Menkes kinky hair disease because such
babies have very fragile hair; they also have abnormal brain development and a low body
temperature. They are very floppy, lack energy and usually will not survive beyond 3 years of
age.
ZINC
Zinc (Zn) is a trace element essential for cell proliferation and differentiation. It is a
structural constituent of enzymes and proteins, including metabolic enzymes, transcription
factors, and cellular signaling proteins. There is increasing evidence for a direct signaling
function of Zn at all levels of cellular signal transduction [54]. Zinc is an important element in
preventing free radical formation, in protecting biological structures from damage and in
correcting the immune functions. Zinc deficiency produces growth retardation, anorexia,
delayed sexual maturation and iron-deficiency anemia [55].
Zinc is often used for the prevention or treatment of common colds and sinusitis
(inflammation of sinuses due to an infection), ulcers, sickle cell disease, celiac disease,
memory impairment and acne [56,57 ].
Zinc is found in many common vitamin supplements and is also found in denture creams
[56, 58]. There is also increasing evidence that zinc plays an important role in protein
biosynthesis and utilization. The addition of small amounts of zinc to a diet containing
suboptimal amounts of a vegetable protein causes a pronounced increase in protein utilization
and growth. This defect may result from a failure in adequate RNA synthesis. Zinc apparently
inhibits the enzyme ribonuclease. Thus, in zinc deficiency, excessive destruction of RNA
could occur. Zinc-binding proteins, such as metallothioneins (MTs), belong to the family of
intra-cellular metal binding proteins that are present in virtually all living organisms and they
play a key role in the Zn effect upon the immune system. Metallothioneins are protective
against stress and increase in ageing [59]. Zinc plays major biological roles in the organism
such as its role as catalyst, and as structural and regulatory ion [60]. The dysregulation of
apoptosis is central to pathogenic mechanisms in many diseases such as neurodegenerative
disorders, acquired immune deficiency syndrome, autoimmune disease and cancers [61, 62].
Increased apoptosis in vivo may occur as direct or indirect consequence of a decrease in
intracellular Zn concentrations. Therefore, cellular Zn is described as an inhibitor of
apoptosis, while its depletion induces death in many cell lines [63]. In ageing MTs
preferentially bind Zn rather than copper and they are unable to release Zn. Indeed, during
ageing the stress like-condition is persistent provoking sequester of intracellular Zn with
subsequent low Zn ion bioavailability for immune efficiency and for the activity of Zn-
dependent enzymes and proteins [60, 64]. Low Zn ion bioavailability and high MTs levels are
present in aging and stress . A low Zn ion bioavailability may also trigger impaired cognitive
functions, via altered thyroid hormones turnover [60].
Unlike other first-row transition metals (e.g., Sc2+, Ti2+, V2+, Cr2+, Mn2+, Fe2+, Co2+, Ni2+
and Cu2+), the zinc ion (Zn2+) contains a filled d orbital (d10) and therefore does not
participate in redox reactions but rather functions as a Lewis acid to accept a pair of electrons
[65].
This lack of redox activity makes Zn2+ a stable ion in a biological medium whose
potential is in constant flux. Therefore, the zinc ion is an ideal metal cofactor for reactions
that require a redox-stable ion to function as a Lewis acid–type catalyst [66] such as
proteolysis and the hydration of carbon dioxide. Furthermore, due to the filled d-shell
orbitals, Zn2+ has ligand-field stabilization energy of zero [67].
In all liganding geometries, and hence no geometry is inherently more stable than
another. This lack of an energetic barrier to a multiplicity of equally accessible coordination
geometries can be used by zinc metalloenzymes to alter the reactivity of the metal ion and
may be an important factor in the ability of Zn2+ to catalyze chemical transformations
accompanied by changes in the metal coordination geometry. Nevertheless, in all zinc
metalloenzymes studied to date, the binding geometry observed most often is a slightly
distorted tetrahedral (Scheme 1) with the metal ion coordinating three or four protein side
chains. However, five-coordinate distorted trigonal bipyramidal geometry has been observed
in the metal sites of Zn-substituted astacin [68].
A final important property of Zn2+ that makes it well suited as a catalytic cofactor is that
ligand exchange is rapid [69], allowing for the rapid product dissociation required for
efficient turnover.
Zinc is classified as a "borderline" metal, meaning that Zn2+ does not consistently act
either "hard" (not very polarizable) or "soft" (highly polarizable) and does not have a strong
preference for coordinating with oxygen, nitrogen or sulfur atoms [70]. In protein zinc-
binding sites, the zinc ion is coordinated by different combinations of protein side chains,
including the nitrogen of histidine, the oxygen of aspartate or glutamate and the sulfur of
cysteine.
In zinc prooteins, the majjor role of thee zinc ion can be catalytic, cocatalytic orr structural.
Inn a catalytic ziinc site, the ziinc ion directlyy participates in the bond-m
making or -breeaking step.
Inn a cocatalyticc zinc site, thhere are severral metal ionss bound in prroximity to onne another,
w
where one playys a catalytic role
r and the other metal ionns enhance thee catalytic actiivity of the
siite [71].
Finally, in structural zinnc sites, the zinnc ion mainlyy stabilizes thee tertiary struccture of the
ennzyme in a maanner analogoous to disulfidee bonds. In alll cases, removval of the bounnd zinc can
leead to a loss of
o enzymatic activity.
a A systematic analyysis of the strructure and function of a
nuumber of zincc proteins has established diistinct features of catalytic and structurall zinc sites,
ass described latter [72,73] .
As undersstanding of thhe biochemicaal role of zincc in these bioological macroomolecules
inncreases, the connection between
b the detailed
d biochhemical functtions and phhysiological
phhenotypes cann be establisheed.
A unique feature
f s is the exisstence of an oppen coordination sphere;
for a catalytic zinc site
thhat is, the zincc-binding polyyhedron contaains at least onne water moleecule in additiion to three
orr four protein ligands act as powerful elecctrophilic cataalyst by providding all or a coombination
off [74-77]:
• an activated water molecule

m for nuucleophilic atttack.
• polarizzation of the caarbonyl of thee scissile bondd .
• stabilizzation of the negative
n chargge in the transition state.
Sccheme.1. Zinc mettaloenzymes

m s.
In structurral zinc sites, the metal ion is coordinaated by four amino a acid siide chains,
ussually in a tetrrahedral geommetry, so that solvent is excluuded as an innner sphere ligaand [78].
Cysteine iss by far the liggand observedd most frequeently in these sites, with hisstidine also
beeing present inn many cases and aspartate being present in one case [775, 79].
In contrastt to catalytic zinc
z sites, thesse sites contain no regular pattern of spaacer length
beetween the pro otein zinc ligaands, and the ligands
l can bee located on a flexible loop rather than
inn a rigid seccondary struccture. The higgh stability constants
c of these tetradeentate zinc
coomplexes enssure both locaal and overalll structural stability
s simillar to that prrovided by
R
diisulfides [78].This enables proteins

p contaaining structurral zinc atoms to perform a widew range
off functions.
Zinc deficiiency can causse retardation,, cessation of growth, impaired wound heealing, hair
looss or defects leading to reeproductive faailure. Zinc suupplementatioon has successsfully been
ussed as a treatmment of manyy illnesses andd disorders, inncluding dwarffism, sexual immaturity,
accrodermatitis enteropathicaa (inflammatioon of the skiin and the sm mall intestine)), anorexia
neervosa and bu ulimia nervosa [80].Catalyttic zinc sites provide convvenient targetss for drugs
beecause a widde range of functional groups g (i.e., sulfonamides
s or hydroxam mates) can
cooordinate directly to the meetal, displacingg the zinc-watter in the activve site and inhhibiting the
ennzyme.
Zinc has been
b shown inn numerous syystems to antaagonize the caatalytic properties of the
reedox-active trransition metaals iron and copper with respect to thheir abilities to t promote
foormation of ·OH
O from H2O2 and superoxxide. There iss a well know wn requiremennt for trace
ammounts of iron or copper too catalyze forrmation of ·OH H from H2O2 and O2- throuugh Fenton
chhemistry accorrding to the foollowing reactiions [81].
(1)
(2)
(3)
(4)
(5)
(6)
Reaction 2 is commonlyy known as thee Haber-Weisss reaction andd is relatively slow. s It has
beeen suggestedd that trace amounts
a of sooluble iron orr copper in thhe presence ofo reducing
aggents (AH2), such as ascoorbate, can catalyze c the formation off hydroxyl raddical from
suuperoxide via the metal-cataalyzed Haber-Weiss reactionn (Fenton reacction (reactionn 6).
The processs of protein oxidation is initiated
i by thhe binding off a reduced reedox-active
trransition metall to an enzymee to form a cooordination com mplex that cann then react with H2O2 to
·
foorm OH .
Zinc can also
a perform a different rolle in enzymess like the role it performs in i carbonic
annhydrase. Herre the metal biinds H2O and makes it aciddic enough to lose l a proton and form a
Zn-OH group. The zinc meetal serves as a nucleophilee to the substtrate. Since ziinc has the
abbility to act ass an electrophiile or as the soource of a nuccleophilic group it is incorpporated and
ussed by many enzymes
e [81].
Recent clinnical and expeerimental findiings have reinforced the linkk among zinc deficiency,
m
malnutrition an
nd diarrheal diisease. Becausse there is a sttrong associattion between protein
p and
ziinc content in virtually all types
t of foodss, insufficient protein intakee may often bee the cause
off zinc deficieency. Compensatory mechhanisms operaating in monnogastric speccies during
malnutrition are less effective for the absorption of transition divalent elements such as zinc,
which remain bound to ligands of dietary or endogenous origin. Both protein and zinc
deficiencies are strong negative determinants for normal cellular immunity. Zinc deficiency
may impair the absorption of water and electrolytes, delaying the termination of normally
self-limiting gastrointestinal disease episodes.
As zinc has an antioxidant and anti-inflammatory action in the uterus. Improvement in
micro-vessel circulation by zinc may help prevent cramping and pain. Since strong uterine
contractions temporarily reduce or stop the blood supply to the uterus, thus depriving the
uterus of oxygen resulting in contractions and pain, perhaps improvement in micro-vessel
circulation by zinc treatment is sufficient to prevent cramping and pain. Ischemia is partly
caused by reperfusion, which results in the release of much active oxygen species which can
cause tissue damage and pain. Thus, much of the discomfort of dysmenorrhea is likely to be
due to these free oxygen radicals. The enzyme which inactivates these oxygen species is
dismutase. Copper–zinc dismutase is present in the uterus [82] and zinc treatment allows for
more adequate levels of this enzyme – which in turn could relieve cramping and pain. Zinc is
an effective anti-inflammatory and antioxidant agent, and it can readily down regulate
inflammatory cytokines [83]. Zinc protects plasma cell membranes preventing damage to
cells by a wide variety of cytotoxic agents in a dose dependent manner extending far above
physiologic concentrations.
GOLD
For decades, gold salts have been utilized for the treatment of inflammatory rheumatoid
arthritis [84].Although their exact mechanism of action is not clearly understood, gold salts
decrease the inflammation of the joint lining, thereby preventing destruction of bone and
cartilage. It is quite likely that the mechanism by which gold anti-rheumatic drugs modulate
the immune response is multifactorial. Their therapeutic activity may be derived from an
ability of gold to undergo facile ligand exchange with biological thiolates, particularly those
with low pKa values, resulting in the inhibition of activity of several different enzymes. Gold
(I) can chelate thiol peptides with two or more cysteine residues thus affecting antigen
presentation [85].While some gold compounds can affect the cellular redox balance.
Additionally, it has also been proposed that gold’s anti-arthritic activity may be due to its
ability to release peptides from major histocompatibility complex-class II (MHC-II) proteins
[86].
Among the non-platinum antitumor drugs, gold complexes have recently gained
considerable attention due to their strong antiproliferative potency. In many cases the cell
growth inhibiting effects could be related to anti-mitochondrial effects making gold species
interesting drug candidates with a mode of action different from that of the platinum agents.
The spectrum of gold complexes described as antiproliferative compounds comprises a broad
variety of different species including many phosphine complexes as well as gold in different
oxidation states[87].
Auranofin - Au - oral rheumatoid arthritis drug (Figure 5) , has a triethylphosphinegold
unit, is just as effective, as Disodium aurothiomalate AuSCH(CO2Na)CH2CO2Na (Figure 6)
is a coordination complex used to treat rheumatoid arthritis.The injectable thiolate complexes
R
arre polymers containing

c linnear Au (1) and bridging thiolate sulffurs, in chainn or cyclic
sttructures Au-S S-Au-S- withh succinoyl grroups attachedd to the sulfurr atoms.[88]. Formulated
F
auurothiomalate usually contaains a slight excess
e of thiollate over goldd. None of thee injectable
thhiolate drugs have been crrystallized, buut the X-ray crystal structture of a relaated cyclic
heexameric 1 : 1 Au(1) thiolaate complex has h been repoorted [89]. Gold(1) has a much m higher
afffinity for thio
olate S comparred to thioetheer S, and a muuch lower affinnity for N andd 0 ligands.
Therefore Au(1 1) binds to DNA very weaakly and is noot usually carcinogenic or mutagenic.
Thiolate exchan nge reactions on Au(1) are facile [90] and therefore the administeredd drugs are
prrobably not th he pharmacologically-active species.
Fiigure 5. Aurano
ofin.
Fiig 6. Disodium aurothiomalatee.
Albumin can
c transfer Au(1)
A into cellls,specific meetal transport proteins, [91]], transport
Au(1) in the cy
A ytoplasm. Gluttathione is knoown to bind too intracellular Au(1) [92] annd the gold
iss mobile within the cell duee to dynamic exchange
e reacttions. This complex can inhhibit the Se
ennzyme glutathhione peroxidaase by bindinng to the activve site selenoccysteine residuue forming
G
GSH-Px-Se-Au u-SG [93].
Under the oxidative conditions that exist in inflamed joints, oxidation of Au(1) to Au(III)
is likely formed. The formation of Au(III) may be responsible for some of the side-effects of
gold therapy [94]. Gold(III) has a remarkable ability to deprotonate peptide amide bonds even
at highly acidic pH values. The tripeptide Gly-Gly-His, for example, readily forms a square-
planar complex with Au(III) at (pH 2) via binding to the terminal amino group, two
deprotonated amide nitrogens and imidazole N of His. [95]. Ultimately much gold is
deposited in lysosomes of cells but the chemical form of it is not known. It is not metallic Au,
but probably a protein complex. Here gold may inhibit lysosomal enzymes which are
responsible for destruction of joint tissue [96].
As Gold(III) is isoelectronic and isostructural with Platinum (II), it was suggested that
gold compounds may also be useful as anticancer. Although the screening of Auranofin and
Auranofin analogues yielded a limited spectrum of activity [97,98] organogold(III)
DAMP(DAMP = o-C6H4CH2NME2) complexes[99,100] and triphenylphosphine-gold (I)
complexes have shown significant activity . The work conducted on the latter compounds led
to the development of bis(diphos)gold(I) complexes [101,102]. Mononuclear gold(III)
complexes, organogold(III) compounds and dinuclear oxobridged gold(III) complexes were
evaluated in several human tumor cell-lines [103]. and novel targets proposed include the
mitochondrial membrane, cysteine proteases (notably caspases and cathepsins) and
thioredoxin reductase [104,106].
In 2011 researchers synthesis and study new gold(III) complexes 5-aryl-3-(pyridin-2-yl)-
4,5-dihydropyrazole-1- carbothioamide . The cytotoxicity was tested by MTT assay. The
results indicate that some complexes have higher cytotoxicity than cisplatin against HeLa cell
line. The study suggests that the substituent groups on benzene have important effect on
cytotoxicity [107].
VANADIUM
Vanadium is a curious trace element which seems to be required by the body in relatively
tiny amounts. There is nevertheless increasing excitement about its potential therapeutic
value. Low blood levels of vanadium have been associated with increases in cholesterol and
blood sugar, and it is also believed by some researchers that the mineral may play a role in
maintaining the vital balance between sodium and potassium in cells. These characteristics of
vanadium have led to speculation that it may act as a protector against heart disease, cancer
and especially diabetes.
Some nutritional therapists have rushed to embrace vanadium's potential, insisting that
high dose vanadium supplements can reduce levels of fasting blood sugar and reducing
cellular inflammation [108,109 ], as well as those of low density lipids (LDLs), the so-called
"bad cholesterol" which is strongly associated with atherosclerosis (hardening of the arteries)
[110].
The initial use of vanadium to treat diabetes was in 1899 [111]. The ability of sodium
vanadate (NaVO3) to lower blood glucose levels has been tested. The result was very
promising in lowering sugar levels, with no side effects [112].
Vanadyl sulfate (VOSO4) soon replaced sodium vanadate in animal testing due to the
decreased toxicity of vanadyl compared to vanadate . Also, much of the vanadate
R
addministered iss found in thee vanadyl form m [111]. The discovery of insulin in 19222 took the
foocus off of vannadium complexes for treattment of diabeetes, as hormoone supplemennts became
thhe major treatm ment for the disease
d [111,1113]. Bis(malttolato)oxi-vannadium (BMO OV) (Figure
7)) was the firstt vanadium coomplex prepareed that has inccreased effecttiveness against diabetes.
There is also ana increase in uptake and tolerability
t asssociated with the complex [113,114].
There are differrences in distrribution of ionnic verses com
mplex forms off vanadyl.
Fiigure 7. Bis(maaltolato)oxovanaadium (BMOV)).
Vanadium became popuular with boddybuilders lasst decade beccause of its potential p to
inncrease cell voolume and thuus was hoped to also boost muscle mass .Due to its potential p to
m
mimic the hormmone insulin in the body, vanadium
v is believed
b to heelp shuttle nuttrients, like
am mino acids annd blood sugaar, into our muuscle cells, which
w leads to greater cell volume.
v By
inncreasing cell volume, vanaadium has beeen suggested by b some experts to not onlyy make the
m
muscles look bigger
b and fulller but even result in musscle growth. SomeS evidencce suggests
vaanadium may also be imporrtant for bone formation, whhich could hellp maintain boone density
annd fight age-rrelated loss ofo bone. This effect seems to be due too an enzyme-sstimulating
caapacity and abbility to enhance calcium meetabolism [1155-117].
Vanadium salts and com mplexes have been widely investigated
i fo their anticaarcinogenic
for
prroperties in experimental
e carcinogenesis. Vanadyl sulfate, cysteeine and V(IIII)-cysteine
coomplex exerted antitumor effects in tuumor bearingg rats. The V(III)-cysteine
V e complex,
hoowever exertss much moree potent . Thhese beneficiaal effects of the above coomplex, in
coombination with
w its low tooxicity providde evidence suuggest its posssible applicaation in the
trreatment of huuman malignannt diseases [1118].
Most of the biological im mportance of vanadium is associated
a witth the +5 oxiddation state
(vvanadate) probbably due to similarities between the phhosphate and vanadate cheemistries in
soolution. In vannadium (+5) solutions diffferent oligomeeric (n=1 to 10) vanadate speciess can
occcur simultaneeously in equiilibrium such as monomeric (V1), dimerric (V2), tetram meric (V4)
annd decameric (V10) and, in same cases, with differrent states of protonation and a forms,
deepending on vanadium
v conccentration, pH
H and ionic streength. Many of o these vanaddate species
arre not taken in n consideratioon in the majoority of the biological studiies, although iti is known
thhat, particularlly V10, they may
m also influuence enzymee activity not only in vitro but also in
viivo [119]. In vitro effects can be convveniently anaalysed combinning kinetic with w NMR
sppectroscopy sttudies. Allegoorically, vanaddate studies inn biological syystems can bee compared
too the iceberg phenomena: there is alwayys an invisiblle part that probably is noot the most
innteresting onee, but clearlyy it is the esssential part needed
n to precisely charaacterize the
vaanadium speccies and the innteractions wiith the system m before attem mpting to undeerstand the
prromoted effects.
Among vanadate oligomers, decameric vanadate (V10), which may occur upon medium
acidification, is considered as the vanadate oligomer with more biochemical relevance.
Although unstable at physiologic pH, the slow rate of decameric vanadate decomposition
allows studying its effects in biochemical systems [119,120]. In fact, it was suggested that
even at physiological pH values an eventual local acidification of a vanadate solution will
induce the formation of (V10) species. Once formed, decameric vanadate disintegration is in
general slow enough to allow the study of its effects even in the micromolar range. Besides, it
may become inaccessible to decomposition due to their stabilization upon binding to target
proteins such as sarcoplasmic reticulum Ca2+ -ATPase or actin [121]. Additionally, recently
described in vivo toxicological studies demonstrated that decameric vanadate species are
responsible for a strong increase in lipid peroxidation and oxidative stress markers, thus
contributing to oxidative stress responses upon vanadate intoxication and pointing out to the
importance of vanadate speciation on the evaluation of vanadium toxicity . The degree of
toxicity depends on the mode of administration such as intraperitoneal or intravenous, and of
course to the vanadate species such as decavanadate [122,123]. Other studies included the use
of decavanadate as a probe in comprehension of muscle contraction and calcium homeostasis
[119]. Actually, we are investigating the mechanisms of cell death induced by vanadate [122]
and the effects of insulin-mimetic vanadium compounds in the activity of sarcoplasmic
reticulum calcium pump . We believe that these recent advances in vanadium toxicology and
pharmacology allow a better understanding of the role of the versatile vanadium in biological
systems [124].
Vanadium is widely known for its toxic effects; however it is vestigial in muscles and
other tissues and is considered an essential oligoelement for humans. Its biological role is far
from a clear identification. Vanadium is present in petroleum, coal and gasoline, used as
alloys and catalysts for industry and is well known for its environmental and biological
impact (Nriagu, 1998). In spite of the emerging interest in the pharmacological effects of
some vanadium compounds, for instance as an insulin-mimetic in the treatment of diabetes,
the toxicology of vanadium constitutes an area of increasing interest (Aureliano, 2007).
Recently, it was reviewed some medicinal applications of vanadium focusing structure-
activity relationship of antidiabetic vanadium complexes, vanadium compounds as anti-
tumour drugs and anti-parasitic agents, and osteogenic action of vanadium complexes in order
to make vanadium compounds available and safe for clinical use. Milestones in the history of
Vanadium Biochemistry are also the review chapters about the redox profile of vanadium, the
biological role of vanadium in bromoperoxidases and the oxovanadates interactions with
lipidic structures (Aureliano, 2007).
Most of the biological importance of vanadium is associated with the +5 oxidation state
(vanadate) probably due to similarities between the phosphate and vanadate chemistries in
solution. In vanadium (+5) solutions different oligomeric (n=1 to 10) vanadate species can
occur simultaneously in equilibrium such as monomeric (V1), dimeric (V2), tetrameric (V4)
and decameric (V10) and, in same cases, with different states of protonation and forms,
depending on vanadium concentration, pH and ionic strength. Many of these vanadate species
are not taken in consideration in the majority of the biological studies, although it is known
that, particularly V10, they may also influence enzyme activity not only but also (Aureliano,
2007). effects can be conveniently analysed combining kinetic with NMR spectroscopy
studies. Allegorically, vanadate studies in biological systems can be compared to the iceberg
phenomena: there is always an invisible part that probably is not the most interesting one, but
clearly it is the essential part needed to precisely characterize the vanadium species and the
interactions with the system before attempting to understand the promoted effects.
Among vanadate oligomers, decameric vanadate (V10), which may occur upon medium
acidification, is considered as the vanadate oligomer with more biochemical relevance.
Although unstable at physiologic pH, the slow rate of decameric vanadate decomposition
allows studying its effects in biochemical systems (Aureliano and Gândara, 2005, Aureliano
2007). In fact, it was suggested that even at physiological pH values an eventual local
acidification of a vanadate solution will induce the formation of V10 species. Once formed,
decameric vanadate disintegration is in general slow enough to allow the study of its effects
even in the micromolar range. Besides, it may become inaccessible to decomposition due to
their stabilization upon binding to target proteins such as sarcoplasmic reticulum Ca 2+-
ATPase or actin (Ramos et al, 2006). Additionally, recently described toxicological studies
demonstrated that decameric vanadate species are responsible for a strong increase in lipid
peroxidation and oxidative stress markers, thus contributing to oxidative stress responses
upon vanadate intoxication and pointing out to the importance of vanadate speciation on the
evaluation of vanadium toxicity (Soares et al, 2007a). The degree of toxicity depends on the
mode of administration such as intraperitoneal or intravenous, and of course to the vanadate
species such as decavanadate.
One of the most important recent results was the observation that decameric vanadate
also affects mitochondrial oxygen consumption at the nM range of concentration (Soares et
al, 2007b). In another line of research, the effects of vanadate on the mineralization of a fish
bone-derived cell line were studied and compared to that of insulin, being suggested that it
stimulates growth and prevents mineralization through multiple processes involving
regulation that may or may not depend upon the activation of insulin stimulated pathways
(Tiago et al, 2008). Other studies included the use of decavanadate as a probe in
comprehension of muscle contraction (Tiago et al, 2004, 2007) and calcium homeostasis
(Aureliano et al, 2007). Actually, we are investigating the mechanisms of cell death induced
by vanadate (Soares et al, 2008) and the effects of insulin-mimetic vanadium compounds in
the activity of sarcoplasmic reticulum calcium pump (Aureliano et al, 2008). We believe that
these recent advances in vanadium toxicology and pharmacology allow a better understanding
of the role of the versatile vanadium in biological systems (Kustin et al, 2007).
IRON
Hemoglobin, which is the principal oxygen carrier in humans has four sub-units in which
the iron(II) ion is coordinated by the planar, macrocyclic ligand protoporphyrin IX and the
imidazole nitrogen atom of a histidine residue[125].
Each ferrous iron within hemoglobin provides one binding site for O2 (Figure 8) . Thus a
single hemoglobin molecule has the capacity to combine with four molecules of oxygen.
Hemoglobin binds oxygen in a cooperative fashion; occupation of one binding site enhances
the affinity of another binding site for oxygen in the molecule[126,127].
Fiigure 8. Structu
ure of Heme b, in
i the protein.
The sixth coordination

c siite contains a water molecuule or a dioxyggen molecule. myoglobin
haas only one suuch unit. The active site is located
l in an hydrophobic
h p
pocket. This iss important
ass, without it, thhe iron(II) woould be irreverrsibly oxidisedd to iron(III). The
T equilibriuum constant
foor the formatio on of HbO2 is such that oxyygen is taken up u or released depending onn the partial
prressure of ox xygen in the lungsl or in muscle.
m In heemoglobin thee four sub-units show a
coooperativity effect whichh allows forr easy oxyggen transfer from hemooglobin to
m
myoglobin[128 8].A combinaation of a hyydrophobic binding b pockeet, which inccreases the
soolubility and prevents
p aggreegation of hem min, tentative donation
d of ann axial ligand to
t the Fe3+
ceenter and the presence of a relatively polar p site closse to the ironn-oxo center presumably
p
faacilitates the peroxidation
p reeaction.
In both hemmoglobin and myoglobin it is sometimes incorrectly sttated that the oxygenated
o
sppecies containns iron(III). It is now knownn that the diam magnetic naturre of these speecies is due
too the fact that the iron(II) is in the low-sppin state. In oxxyhemoglobinn the iron atom m is located
inn the plane of the
t porphyrin ring, but in thhe paramagnettic deoxyhemooglobin ,
iron atom lies
l above the plane of the ring. r The channge in spin staate is a cooperaative effect
off higher crystaal field splittinng and smallerr ionic radius ofo Fe2+ in the oxy-
o moiety [128].
Fiigure 9. Rubreddoxin.
Rubredoxin metabolizing bacteria and arrchaea. The

n is an electroon-carrier founnd in sulfur-m
acctive site conttains an iron ion which is coordinated by b the sulphurr atoms of fouur cysteine
residues forming an almost regular tetrahedron. Rubredoxins perform one-electron transfer

processes. The oxidation state of the iron atom changes between the +2 and +3 states. In both
oxidation states the metal is high spin, which helps to minimize structural changes.
Iron is transported by transferrin (Figure 10) whose binding site consists of two tyrosines,
one aspartic acid and one histidine[129].
Figure 10.The Amino Acids that bind and hold iron in a N-terminus Transferrin lobe.
Iron tris(bipyridine) Polymeric Metal Complexes is useful in biological applications

because they are labile and may alter their inner coordination sphere in response to changes in
pH and temperature or the presence of reactive oxygen species [130]. This presents a new
triggered release because an iron PMC system that is initially inert when it is delivered can
become labile when it interacts with cells or tissues with appropriate oxidizing environments.
Additionally, some metals can function as molecular probes because they are chromophores
or have properties that can be detected through analytical methods [130]. This allows the
movement of the metal and its interactions with its environment and cells to be monitored.
The regulation of iron metabolism (Bioiron) uses both DNA and RNA as targets, which
contrasts with oxygen metabolism where DNA is the target.
The molecular assembly of polytopic systems containing clathrochelate fragments was
used to design novel antioxidants based on sterically hindered phenols. 2,6-Di(tert
butyl)phenols are well known antioxidants which are widely used in various fields of food
industry and pharmaceutics. Their antioxidant activity is determined by stability of the
phenoxyl radicals formed upon their oxidation, the redox potential value, and the mechanism
and reversibility of the electron transfer [131]. The incorporation of a metal ion in a phenol
containing molecule is known to be an efficient way for stabilizing the phenoxyl radical
formed upon its oxidation. The effect of the metal ion on
the physicochemical characteristics of radical reaction products is determined by two
main factors, steric factor (an increase in the structural rigidity of the molecule and steric
hidrance of the reactive radical centers) and electronic factor (a decrease in the spin density
on the radical fragment as a result of delocalization of the unpaired electron within the
common electronic system of the complex) [132]. In addition, the central metal ions in these
complexes can initiate oxidation (in particular, through coordination of molecular oxygen and
catalysis of hydroperoxide homolysis). Comparative study of the antioxidant activity was
carried out for macrocyclic square bipyramidal iron(II) bis_dioximate and cage
macrobicyclic iron(II) and tris-dioximates [133]. Two series of macrocyclic and
macrobicyclic iron dioximate differing in the molecular geometry and the number of 2,6-
di(tert_butyl)phenol substituents in them were prepared. Specifically, the macrocyclic iron
bis_dioximate, FeD2(BF2)2Py2,where D2 is the methyl[3,5-di(tertbutyl) 4-
hydroxyphenyl]glyoxime dianion, contained two fragments of this type, whereas the
molecules of cage iron trisdioximates contained one or six sterically hindered phenolic groups
[134].
Oleic acid was used as the substrate as a model of autoxidation of lipids by molecular-
oxygen.
The liquid phase oxidation of oleic acid is a radical chain process giving hydroperoxide
as the primary product, which then decompose to yield oxidative destruction products
(mainly, carbonyl compounds). Iron(II) tris_dioximate clathrochelate exhibits a much higher
antioxidant activity than bis_dioximate macrocycles [135].
Thus, encapsulation of the metal ion in macrobicyclic iron(II) trisdioximate results in
inhibition of accumulation of hydroperoxides and their decomposition products.The most
pronounced antioxidant properties were observed for the complexes containing six
2,6_di(tertbutyl)phenol residues.
The level of peroxidation of unsaturated fatty acids was measured based on accumulation
of carbonyl compounds formed upon hydroperoxide decomposition ,and the effect of
macrobicyclic phenol containing iron trisdioximate on the lipid peroxidation was studied in
vitro .
The high antioxidant activity of the clathrochelate iron trisdioximate compared to their
macrocyclic bis_dioximate analogs is attributable to the possibility of incorporating additional
antioxidant phenolic groups into the molecules of macrobicyclic complexes (Figs 11,12).
Figure 11. General view of the iron(II) hexaphenolic clathrochelate.

The encapsulated metal ion provides high stability of the phenoxyl radicals formed, and
the steric hindrance of the metal ion encapsulated in the cavity of the macrobicyclic
clathrochelate tris_dioximate ligand prevents its involvement in dioxygen coordination and
activation. In addition, the efficiency of inhibition of oxidation processes in the cells is
determined by inclusion of clathrochelates with lipophilic peripheral substituents into the
lipid bilayer of the cell membrane .Complexes with an encapsulated metal cation (in
particular, radioactive ion) can be used as radiopharmaceutical and pharmaceutical agents for
diagnostics and therapy.
Figure 12. General view of the iron(II) monophenolic clathrochelate.
It is important that the formation of the clathrochelate bridging fragment, whose stability
is comparable with a covalent bond stability, between the boronic linkers according to
Scheme 20 does not affect other functional fragments (amino, thiol, and carboxy groups).
This system can be used for immobilization and affinity binding of macromolecules,
antibodies, and enzymes, substrate linking to the active sites of these enzymes, and
fluorescence probes.A promising application of clathrochelate linkers is mimicking of ligases
and binding of nucleotide sequences to a single stranded DNA template.
Macrobicyclic cobalt(II) polyamine complexes with apical groups functionalized with
polycyclic aromatic substituents were synthesized as a new type of DNA intercalators. It was
assumed that these systems would demonstrate a synergistic effect in DNA binding both
through intercalation of planar apical fragments and through electrostatic interaction of the
cationic macrobicyclic complex with the DNA poly-anion [136,137].
The use of clathrochelate complexes as protease inhibitors , probably, the ellipsoidal
shape of their molecules allows one to inhibit the HIV protease active site. Analysis of the
shape of molecules and crystal packings for adamantly containing clathrochelates in which
the formation of their crystal lattices is mainly governed by the dispersion van der Waals
interactions between the hydrophobic peripheral parts of the molecule and depends primarily
on the overall geometry of the molecule [138].
PLATINUM
Metal complexes which undergo ligand substitution and redox reactions is likely to mean
that the active species are biotransformation products of the administered complex.
Iddentification of
o these activee species will lead to the more effective use
u of metal compounds
c
ass drugs.
Resistance mechanism which
w have beeen recognizedd are as following:
• reduceed transport accross the cell membrane.

m
• strong binding to innactivating thhiolate ligandss inside the cell, e.g. glutaathione and
metalloothionein.
• repair of
o platinated lesions
l on DN NA by enzymess .
The drug cisplatin

c (Figuure 13 ) contains a square-pplanar platinum m(II) center coordinated
c
too two ammoniia ligands andd two chloride ligands with a cis-ligand conformation.
c Its activity
w discovered
was d by chance in i an experim ment looking at a the effect of electric fieelds on the
grrowth of bacteeria and using platinum elecctrodes.[139 ]
Under physiological connditions cisplaatin does not attack
a the DNNA base thymiine (T), but
chhanging the ligands on Pt(lI) to am mino phosphhines allows this to be achieved.
A
Aminophosphin ne ligands binnd strongly too Pt(II) but inn bischelated cis complexees the Pt-N
boond is relativeely labile on account of thhe high trans influence of P and steric interactions
i
beetween the sub bstituents on the
t N atoms. Thus
T chelate riing opening inn these compleexes can be
coontrolled by thhe substituentss on N ,by the size of the chhelate ring, by the pH [140]..
Fiigure 13. Structture of Cis-platiin.
Fiigure 14. Structture of Pt(II)diaaminocyclohexaane.
I’st way off acting is as follows

f ,one of
o the chloridee ligands is sloowly displaceed by water
(aan aqua ligaand), in a process
p termeed aquation. The aqua ligand in thee resulting
[PPtCl(H2O)(NH H3)2]+ is itselff easily displaaced, allowingg the platinumm atom to binnd to bases
[1138]. Of the bases on DNA,, guanine is prreferred. Subssequent to form mation of [PtC Cl(guanine-
+
D
DNA)(NH 3)2] , crosslinking can occur via a displacementt of the other chloride
c ligandd, typically
by another guanine. Cisplatin crosslinks DNA in several different ways, interfering with cell
division by mitosis. Cellular resistance to cisplatin (cis diamminedichloroplatinum(II)) can be
overcome by changing the ammine ligands to 1,2-diaminocyclohexane (DACH) and Pt(lV)
analogues It is therefore of much interest to investigate how the structures of amine ligands
affect the reactivity of platinum complexes [141].
Intracellular hydrolysis has long been thought to be an important process for the
activation of chloro Pt anticancer diamine complexes (Figure 14). Changing the ammine
ligands can markedly affect the rate of hydrolysis and the pK, values of the resulting aqua
complexes.
['H,I5N] NMR spectroscopy allows the detailed pathways of reactions of cisplatin (and
other ammine and amine complexes) to be followed. The GG chelate is known to be an
important adduct in cells. The selectivity of Pt for GG sequences is related to the high
electron density at such sites (most easily oxidized sites of DNA). Molecular modeling
studies demonstrate that H-bonding between the NH3 ligands and carbonyl groups on DNA
play a major role in determining the orientation of the Pt-Cl bonds and their accessibility.
Molecular mechanics calculations show that although the chloride ligand in the
monofunctional adduct faces outward, away from the helix, the aqua ligand which replaces it
after hydrolysis faces inwards on account of its strong H-bonding properties.
cisplatin does not attack the DNA base thymine (T), but changing the ligands on Pt(lI) to
amino phosphines allows this to be achieved. Aminophosphine ligands bind strongly to Pt(II)
but in bischelated cis complexes the Pt-N bond is relatively labile on account of the high trans
influence of P and steric interactions between the substituents on the N atoms. Thus chelate
ring opening in these complexes can be controlled by the substituents on N, by the size of the
chelate ring, by the pH.
The mechanism of action of Pt is that DNA is the target. In another word platinum-
containing anticancer drugs are alkylating agents which means that they react with the
nitrogenous bases in DNA strands to form crosslinkges within and between strands.
The primary biological target appears to be the interaction with nucleic acids, and
therefore studies of the interaction of platinum amine compounds (both active and inactive
ones) with nucleic acids and nucleic acid fragments are of great interest. Studies on
mononucleotides have made clear that a strong preference exists for platinum binding at
guanine-N7 sites. Investigations on oligonucleotides have shown that, when two neighboring
guanines are present, chelation of the cis-Pt(NH3)2 unit (cisplatin) is strongly preferred above
all other possibilities. Studies on DNA ( in vivo and in vitro) have made clear that similar
binding modes occur in DNA and oligonucleotides, and that after cisplatin binding the DNA
structure is distorted in the same way as double-stranded oligonucleotides.
Some of the most promising compounds, considered today, are Pt(NH)2(CBDCA),
(CBDCA = 1,1-dicarboxylatocyclobutane), now also called paraplatin, and CHIP (cis,cis-
,trans-dichlorodihydroxobis(isopropylamine)platinum(IV).)
Some examples are presented in (Figure 15). Especially the CBDCA derivative is
promising because of its low toxicity.
Figure 15. Structure of Cisplatin derivatives.
During the last decade large number of Pt(II) and Pt(IV) compounds were prepared, they
have made clear that Pt compounds with anti-tumor activity have to fulfil all of the following
structural requirements:
• The two amine ligands in the Pt-compound should be in a cis-orientation. In a

didentate chelating ligand, this geometric requirement is automatically fulfilled. The
general formulae should be cis-Pt(II)X2(Am)2 and cis-Pt(IV)Y2X2(Am)2. However,
the number of variations studied in the case of Pt(IV) is still limited.
• The ligands X, usually anions, should consist of groups that have intermediate
bindingstrength to Pt(II), or that are - for other reasons - easily leaving (i.e. by
enzymatic action). Examples are:Cl-, S042- ,citrate(3-), oxalate(2-) and other
carboxylic acid residues. For the Pt(IV) compounds, the Y group is often OH. The
amine ligands, either monodentate or didentate, should have at least one N-H group,
i.e. possess a hydrogen-bond donor function . All compounds with both amine
ligands lacking such a H-bond donor property, were found to be inactive. The role of
this N—H group in the biological activity, however, is far from being understood. It
could be either kinetic (i.e. play a role in the approach of the DNA), or
thermodynamic (e.g. give an additional (de)stabilization after binding to the
biological target DNA;vide infra). However, also steric effects and/or a role in
transport through the cell wall cannot be excluded.
Molecular modelling studies demonstrate that H-bonding between the NH3 ligands and
carbonyl groups on DNA play a major role in determining the orientation of the Pt-Cl bonds
and their accessibility. In addition molecular mechanics calculations show that although the
chloride ligand in the monofunctional adduct faces outward, away from the helix, the aqua
ligand which replaces it after hydrolysis faces inwards on account of its strong H-bonding
properties[142].
In 2004, a further platinum drug, oxaliplatin (Figure 16) achieved worldwide clinical
acceptance. The clinical advantage of oxaliplatin is that it has a different spectrum of activity,
in particular, it is effective against colorectal cancer, a disease not treatable using cisplatin or
carboplatin(Figure 17) [143], in addition to its activity against some cisplatin-resistant
cancers. The alternate diamine ligands used in heptaplatin and lobaplatin do not confer these
same effects.
Figure 16. Structure of Carboplatin and Oxaliplatin.
Figure 17. Structure of Nedaplatin (top right) and Lobaplatin (bottom).
It is clear from the activity of oxaliplatin, satraplatin, and picoplatin that modifying those
ligands on platinum that are retained in the DNA adduct can affect the way the compound
acts in the biological system.
SUMMARY
The equilibrium of metal ions is critical for many physiological functions, particularly in
the central nervous system, where metals are essential for development and maintenance of
enzymatic activities, mitochondrial function, myelination, neurotransmission as well as
learning and memory. Due to their importance, cells have evolved complex machinery for
controlling metal-ion homeostasis. However, disruption of these mechanisms, or absorption
of detrimental metals with no known biological function, alter the ionic balance and can result
in a disease state, including several neurodegenerative disorders such as Alzheimer's disease.
Understanding the complex structural and functional interactions of metal ions with the
various intracellular and extracellular components of the central nervous system, under
normal conditions and during neurodegeneration, is essential for the development of effective
therapies. Accordingly, assisting the balance of metal ions back to homeostatic levels has
been proposed as a disease-modifying therapeutic strategy for Alzheimer's disease as well as
other neurodegenerative diseases [144].
Metal metabolism is emerging as an exciting area of cell biology and a potential site for
therapeutic interventions. Normal metal metabolism appears to maintain free metal ion
concentrations at a very low level and to deliver metals very selectively to their sites of
action, while maintaining tight control over their reactivity.
Trials to reduce metal toxicity by delivering metal compounds to the tissues, cells and
receptors are rapidly emerging. To better understanding the progressing happened in the field
of pharmaceuticals[145,146].
REFERENCES
[1] M. Gerken. Chemistry 2810 Lecture Notes : Metal ions in biology and medicine.
[2] P., J. Sadler ; Z., Guo. Metal complexes in medicine: Design and mechanism of action.
Pure & Appl. Chem., 70, 1998, 863-871.
[3] Metals in Medicine: Targets, Diagnostics, and Therapeutics, Natcher Conference
CenterNational Institutes of HealthBethesda, Maryland, U.S.A. 2000, 28-29.
[4] B., George; E., E., Conn; R., H., Doi; and P., K., Stumpf. Outlines of Biochemistry.
New York: John Wiley and Sons, Inc., 1978.
[5] C., Liu and L., Wang .Dalton Trans., 2009, 227-239
[6] M., Chandra; A., Sachdeva; S., K., Silverman . DNA-catalyzed sequence-specific
hydrolysis of DNA .Nature Chemical Biology 5, 2009 ,718 – 720.
[7] S., D., Aust; L., A., Morehouse; C., E., Thomas. Role of metals in oxygen radical
reactions. J. of Free Radicals in Biology & Medicine. 1, 2003, 3-25.
[8] L., A., Finney; T. V. O'Halloran. Transition Metal Speciation in the Cell: Insights from
the Chemistry of Metal Ion Receptors. Science. 300 , 2003, 931-936.
[9] C.,Davis; J.B.Vincent. Chromium in carbohydrate and lipid metabolism. J. Biological
Inorganic chemistr, 2,1997,675-679.
[10] R., A., Anderson. Nutrient Requirements and Functions Laboratory, USDA Beltsville
Human Nutrition Research Center, Beltsville, Maryland, USA, 20705. Chromium as a
Dietary Supplement.
[11] B., Stoecker. Ph.D .Essentials of Chromium Bioavailability.

[12] J. Challem. Stop Prediabetes Now: The Ultimate Plan to Lose Weight and Prevent
Diabetes .
[13] JB.,Vincent. Elucidating a biological role for chromium at a molecular level. Acc Chem
Res. 33,2000, 503–510.
[14] W., Cefalu; A.D.,Bell-Farrow; Z.Q., Wang. Effect of chromium picolinate on insulin
sensitivity in vivo. J. Trace Elem. Exp. Med. 12, 1999 ,71-83.
[15] S.,Davies; J., McLaren-Howard; A., Hunniset; M., Howard. Age-related decreases in
chromium levels in hair, sweat, and serum samples from 40,872 patients implications
for the prevention of cardiovascular disease and type II diabetes mellitus. Metabolism,
46, 1997 ,469-473.
[16] R.A.,Anderson;N.,Cheng; N.A.,Bryden. Beneficial effects of chromium for people with
diabetes. Diabetes. 46, 1997,1786-1791.
[17] AD., Dayan; AJ., Paine .Mechanisms of chromium toxicity, carcinogenicity and
allergenicity: review of the literature from 1985 to 2000. Hum. Exp. Toxicol. 20, 2001.
439-451.
[18] U.S. EPA (U.S. Environmental Protection Agency). 1984. Health Assessment
Document for Chromium. Environmental Criteria and Assessment Office, U.S.
Environmental Protection Agency, Research Triangle Park, NC. EPA 600/8-83-014F.
NTIS PB 85-115905.
[19] U.S. Air Force. 1990. Chromium. In: The Installation Restoration Program Toxicology
Guide.Wright-Patterson Air Force Base, OH, pp. 72-1 to 72-81.
[20] P.,Nettesheim; M., J., Hanna; D., Doherty; R., Newell; A.,Hellman. Effect of calcium
chromate dust,influenza virus, and 100 R whole-body X-radiation on lung tumor
incidence in mice. J Natl Cancer Inst. 47, 1971,1129-1138.
[21] M.,Costa; K., Salnikow; W.,Peng; J., Sutherland; M., Tang; C., Huang; X. Shi.National
Institute of Occupational Safety and Health, Morgantown, West Virginia.
[22] T.,Suksrichavalit;S.,Prachayasittikul;C.,Nantasenamat;C.,Isarankura;V.,Prachayasittiku
l. Copper complexes of pyridine derivatives with superoxide scavenging and
antimicrobial activities. European Journal of Medicinal Chemistry, 44, 2009, 3259-
3265.J., A., Drewry ; P., T., Gunning. Recent advances in biosensory and
medicinal therapeutic applications of zinc(II) and copper (II) coordination complexes .
Coordination Chemistry Reviews. 255, 2011, 459-472 .
[24] Y., Rayssiguier ; E., Gueux ; L., Bussiere . J Nutr. 123, 1993, 1343-1348.
[25] J.,R.,J., Sorenson. Prog Med Chem. 26 , 1989, 437-568.
[26] H.,H.,A., Dollwet; J.,R.,J., Sorenson. Historic uses of copper compounds in medicine,
Trace Elements in Medicine 2, 1985, 80 - 87.
[27] [27] J., J., Sorenson; L., W., Oberley; R., K., Crouch; T., W., Kensler; V., Kishore; S.,
W., C., Leuthauser; T., D., Oberley; A., Pezeshk. Pharmacologic activities of copper
compounds in chronic diseases Biological Trace Element Research, 5 , 257-273.
[28] H.H.A. Dollwet and J.R.J. Sorenson, Historic uses of copper compounds in medicine,
Trace Elements in Medicine. 2, 1985, 80 - 87.
[29] L.M. Klevay; L. Inman; L.K. Johnson. Metabolism 33,1984,1112-1118. L.M. Klevay.
Med Hypothesis,. 24,1987, 111-119.
[30] L.M. Klevay, Med Hypothesis, 1987; 24: 111-119.
[31] Y. Rayssiguier; E. Gueux; L. Bussiere. J. Nutrition.123,1993, 1343-1348.

[32] L.M. Klevay. Biol. Tr. Elem. Res. 16,1988 51-57.
[33] E.,Broun;A., Greist ;G., Tricot;R., Hoffman . Excessive zinc ingestion. A reversible
cause of sideroblastic anemia and bone marrow depression. J.AMA,264, 1990,1441-3.
[34] R., Jacob; J., Skala ; S., Omaye; J.,Turnlund. Effect of varying ascorbic acid intakes on
copper absorption and ceruloplasmin levels of young men. J. Nutr,117, 1987,2109-15.
[35] S. Aiser ; G. Winston. Copper deficiency myelopathy. [Review]. Journal of Neurology,
257, 2010, 869-881.
[36] M. Johnson; J. Fischer; S. Kays; Crit Rev Food Sci Nutr , 32,1992, 1-31.
[37] P. Baleuska; E. Russanov; T. Kassabova; Int J Biochem. 13, 1981, 489-493.
[38] G., Multhaup; A., Schlicksupp; L., Hesse; D., Beher; T., Ruppert; C., L., Masters; K.,
Beyreuther. The Amyloid Precursor Protein of Alzheimer's Disease in the Reduction of
Copper(II) to Copper(I). Science. 271 ,1996, 1406-1409
[39] L,.J., Taylor; M.,L., Hinners; S.,J., Ritchey. Am J Clin Nutr . 33,1980, 1077-1082.
[40] H.H., Sandstead. Requirements and toxicity of essential trace elements, illustrated by
zinc and copper. Am. J. Clin. Nutr. 61, 1995 (suppl):62S-4S.
[41] J.R., J., Sorenson. J. Pharm. Pharmac. 2, 1977, 450-452.
[42] E., Frieden. Clin. Physiol. Biochem. 4,1986,11-19.
[43] J.,R.,J., Sorenson ; V. Kishore. Tr. Elem. Med. 1,1984, 93.
[44] R., Milanino; A., Conforti; L., Franco. Agents and Actions .16,1985, 504-513.
[45] A.,S., Gissen. Copper: The Maligned Mineral. 1994 issues of VRP's Newsletter.
[46] J.,Bland: Copper Salicylates and Complexes in Molecular Medicine. Int Clin. Nutr.
Review, 4, 1984, 130-134.
[47] J.,R.,J., Sorenson. Copper Chelates as possible Active Metabolites in the Antiarthritic
and Antiepileptic Drugs. J. Applied Nutrition 32, 1980,4-25.
[48] M.,Hodak; R., Chisnell. Cu2+ Binding to the Prion Protein: Functional Implications
and the Role of Copper. Online publication in Proceedings of the National Academy of
Sciences. SCIENCE BLOG 2009.
[49] Y. Rayssiguier ; E. Gueux ; L. Bussiere. J. Nutr. 123,199 ,1343-1348.
[50] L.,G., Strause; P., Hegenauer; R.,C., Saltman. J. Nutr. 116,1986, 135.
[51] E., Frieden. Caeruloplasm. In: "Biological Roles of Copper." CIBA Foundation
Symposium-79. Exerpta Medica. Amsterdam. 1980. 93.
[52] R.,J.,R., Sorenson. (ed.), Biology of Copper Complexes. Humana Press, Clifton, NJ.
1987.
[53] R.,Moss: Shadow Falls on Anti-Angiogenic Drugs. Cancer Decisions Newsletter, 2009.
[54] D., Beyersmann. Effects of carcinogenic metals on gene expression. Toxicol Lett.
127,2002 , 63-8.
[55] D. G.,Barceloux. Manganese Review. J. Toxicol. Clin. Toxicol. 37,1999, 293-307.
[56] N., Kumar. Copper deficiency myelopathy (human swayback). Mayo Clinic
Proceedings. 81, 2006,1371-1384.
[57] C.,Guo; P., Chen;, M.,Yeh,; D., Hsiung; C., Wang.Cu/Zn ratios are associated with
nutritional status, oxidative stress, inflammation, and immune abnormalities in patients
on peritoneal dialysis. Clinical Biochemistry. 44, 2011, 275-280.
[58] P.,Hedera; A., Peltier; J. K., Fink; S., Wilcock; Z., London; G. Brewer. Myelopoly-
neuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown
origin II. The denture cream is a primary source of excessive zinc. [Article].
Neurotoxicology (Amsterdam), 30, 2009,996-999.
[59] E., Mocchegiani; R., Giacconi; C., Cipriano. Zinc-bound metallothioneins as potential
biological markers of ageing Review. Brain Res Bull. 55, 2001,147-53.
[60] E.,Mocchegiani; M.,Muzzioli; R.,Giacconi. Zinc, metallothioneins, immune responses,
survival and ageing. Biogerontology Review. 1, 2000,133-43.
[61] N.,A.,Thornberry; Y.,Lazebnik. Caspases: enemies within. Science Review. 281,
1998,1312-6.
[62] H.,Tapiero; K.,D., Tew. Trace elements in human physiology and pathology: zinc and
metallothioneins Review. Biomed Pharmacother. 57, 2003 ,399-411.
[63] M.,Seve; F.,Chimienti; A.,Favier. Role of intracellular zinc in programmed cell death
Review.. Pathol Biol. 50, 2002, 212-21.
[64] E.,Mocchegiani; R .,Giacconi; C., Cipriano. Metallothioneins (I+II) and thyroid-thymus
axis efficiency in old mice: role of corticosterone and zinc supply. Mech Ageing Dev.
123, 2002 ,675-94.
[65] R.J.P .,Williams. The biochemistry of zinc. Polyhedron. 6, 1987, 61-69.
[66] A.,Butler. Acquisition and utilization of transition metal ions by marine organisms.
Science, .281, 1998,207-209.
[67] E., A., Keiter; R., L., Keiter. Inorganic Chemistry: Principles of Structure and
Reactivity 4th ed., vol. 1 1993 Harper Collins College Publishers New York.
[68] W., Bode; F. X., Gomisruth; R., Huber; R.,Zwilling; W.,Stocker. Structure of astacin
and implications for activation of astacins and zinc-ligation of collagenases. Nature
(Lond.) 358, 1992,164-167
[69] F., A.,Cotton; G.,Wilkinson. Advanced Inorganic Chemistry: A Comprehensive Text
5th ed., vol. 1. 1988 John Wiley & Sons New York.
[70] R., G., Pearson. J. Am. Chem. Soc. 85, 1963m3533-3539.
[71] B., L., Vallee; D., S., Auld. Cocatalytic zinc motifs in enzyme catalysis. Proc. Natl.
Acad. Sci. U.S.A. 90, 1993a ,2715-2718.
[72] F., H., Arnold; B., L., Haymore. Engineered metal-binding proteins: purification to
protein folding. Science . 252, 1991,1796-1797.
[73] J., E., Coleman. Zinc proteins: enzymes, storage proteins, transcription factors, and
replication proteins. C .,Richardson; J. N. Abelson; A.,Meister; C.,Walsch T. eds.
Annual Review of Biochemistry 1992:897-946 Annual reviews Inc Palo Alto, CA.
[74] B., L.,Vallee; D., S.,Auld. Zinc coordination, function, and structure of zinc enzymes
and other proteins. Biochemistry. 29, 1990b,5647-5659.
[75] D., W.,Christianson; J., D., Cox. Catalysis by metal-activated hydroxide in zinc and
manganese metalloenzymes. Annu. Rev. Biochem.68,1999,33-37.
[76] B.,Lovejoy; A.,Cleasby; A., M., Hassell; K.,Longley; M., A., Luther; D.,Weigl;
G.,McGeehan; A., B., McElroy; D.,Drewry; M., H., Lambert; S., R ., Jordan. Structure
of the catalytic domain of fibroblast collagenase complexed with an inhibitor.
Science.263, 1994,375-377.
[77] D., N., Silverman; S.,Lindskog. The catalytic mechanism of carbonic anhydrase:
implications of a rate-limiting protolysis of water. Acc. Chem. Res. 21, 1988.30-36.
[78] B., L., Vallee; A .,Galdes. The metallobiochemistry of zinc enzymes. Adv. Enzymol.
Relat. Areas Mol. Biol. 56 ,1984,283-430.
[79] B., L., Vallee ; J., E., Coleman ; D., S., Auld. Zinc fingers, zinc clusters, and zinc twists
in DNA-binding protein domains. Proc. Natl. Acad. Sci. U.S.A. 88, 1991, 999-1003.
[80] J., C., Spurlino ; A., M., Smallwood; D., D., Carlton; T., M., Banks ; K. J.,Vavra; J., S.,
Johnson ; E., R., Cook; J., Falvo; R. C., Wahl; T. A., Pulvino; J. J., Wendoloski; D., L. ,
Smith .1.56 Å structure of mature truncated human fibroblast collagenase. Prot. Struct.
Funct. Genet. 19,1994 ,98-109.
[81] D ., S.,Bryce. Zinc-deficiency: the neglected factor. Chem. Br. 25, 1989,783-786.
[82] R. Powell . The Antioxidant Properties of Zinc Saul. Journal of Nutrition. 130,
2000,1447-1454.
[83] N .,Sugino; A.,H.,Karube; A., Sakata; S.,Takiguchi ; H.,Kato. Different mechanisms for
the induction of copper-zinc superoxide dismutase and manganese superoxide
dismutase by progesterone in human endometrial stromal cells. Hum Reprod.
17,2002,1709–14.
[84] A. Prasad; B.,Bao; F.,Beck; O.,Kucuk; F.,Sarkar. Antioxidant effect of zinc in humans.
Free Radic Biol Med .37,2004, 1182–90.
[85] S.,L.,Best ; P.,J., Sadler. Gold Bulletin, .29,1996, 87-93.
[86] P.,Greim;K.,Takahashi; H.,Kalbacher; E.,Gleichman. The antirheumatic drug disodium
aurothiomalate inhibits CD4+ T cell recognition of peptides containing two or more
cysteine residues. Journal of Immunology. 155,1995,1575–1587.
[87] I., Ott .Review On the medicinal chemistry of gold complexes as anticancer drugs.
Coordination Chemistry Reviews. 253, 2009, 1670-1681.
[88] R.,Hewer; M., Coyanis;T., Traut; M., Mphahlele; J., Coates; E.,Van Der Lingen.
Investigating the biomedical applications of gold. World Gold Conference 2009, The
Southern African Institute of Mining and Metallurgy.
[89] Bau, R. "Crystal Structure of the Antiarthritic Drug Gold Thiomalate (Myochrysine): A
Double-Helical Geometry in the Solid State". Journal of the American Chemical
Society, 120, 1998, 9380–1.
[90] I. Schroter and J. Strahle. Chem. Ber. 124, 1991,2161-2164.
[91] A.A. Isab and P.J. Sadler. J. Chem. Soc., Dalton Trans. 135-141 ,1982.
[92] J.R. Roberts, J. Xiao, B. Schleisman, D.J. Parsons and C.F. Shaw 111. Inorg. Chem. 35,
1996,424-433.
[93] M.T. Razi, G. Otiko and P.J. Sadler. ACS Sym. Ser. 209, 1983,371-384 .
[94] J. Chaudiere and A.L. Tappel. J. Inorg. Biochem. 20, 1984,313-325.
[95] D. Schuhmann, M. Kubickamuranyi, J.Mirtschewa, J. Gunther, P. Kind and E.
Gleichmann. J. Immunol. 145, 1990,2132-2139.
[96] S.L. Best, T.K. Chattopadhyay, M.I. Djuran, R.A. Palmer, P.J. Sadler; K. Varnagy. JCS
Dalton Trans. 1997, 2587-2596.
[97] P., J., Sadler and Z., Guo. Metal complexes in medicine: Design and mechanism of
action. Pure & Appl. Chem. 70, 1998, 863-871.
[98] C.J.,Mirabelli; R.K., Johnson; C.M., Sung; L.,Faucette; K.,Muirhead; S.T.,Crooke.
Evaluation of the in vivo antitumor activity and in vitro cytotoxic properties of
auranofin, a coordinated gold compound, in murine tumor models. Cancer Research.
45, 1985, 32–39.
R
[999] C.J.,Miraabelli; R.K.,Joohnson; D.T.,Hill; L.,Fauccette; G.R.,G Girard; G.Y.,K Kuo; C.M.,
Snug; S.T T.,Crooke. Coorrelation of thhe in vitro cytootoxic and in vivo antitumoor activities
of gold(I))coordination complexes. Joournal of Meddicinal Chemisstry, 29, 19866.213–216.
[1100] R.V.,Pariish; B.P., Howe;
H J.P.,W
Wright; J.,Maack; R.G.,Prritchard; R.G G.,Buckley;
A.M.,Elsome; S.P.,F Fricker. Chem mical and biological studies s of dichloro(2
((dimethyylamino)methyyl)phenyl)goldd(III). Inorgannic Chemistry. 35, 1996. 1659 .
[1101] R.G.,Bucckley; A.M.,Elsome; S
S.P.,Fricker; G.R.,Hendeerson; B.R..,Theobald;
R.V.,Pariish; B.P.,Hoowe; L.R.,K Kelland. Anntitumor prooperties of some-2-
[dimethyllamino)methyyl]phenylgold((III) complexxes. J. of Meedicinal Chem mistry. 39,
1996. 52008 .
[1102] C.F.,Shaw w; A., Beeryy; G.C.,Stocco. Anti-tumoor activity off two binucleear gold(I)
complexees with bridgging dithiolatte ligands. In norganica Chhimica Acta, vol. 123,
1986.pp. 213–216.
[1103] T.,Amagaai; T.K., Miyaamoto;H., Ichhida; Y.,Sasakki. Preparationn and crystal structure
s of
new gold d(I) complexees linked to pyrimidines. Bulletin of thhe Chemical Society of
Japan. 622, 1989, 1078––1080.
[1104] A., Casin ni; Kelter; C.,Gabbiani,
C C
C.,Cinellu;M.A A.,Minghetti;G G.,F regona; D.,Fiebig;
H.H.; L.,Messori. Chhemistry, anttiproliferative properties, tumor selecttivity, and
moleculaar mechanismss of novel goldd(III) compouunds for cancer treatment: a systematic
study. J. Biol.Inorg.
B Chhem., 2009, inn press.
[1105] S.P., Friccker. Metal based
b drugs: from serendippity to designn. Dalton Traansactions,
2007, 49 903–4917.
[1106] C.,Gabbiani; A.,Casinni; L.,Messorri. Gold com mpounds as anticancer
a drrugs. Gold
Bulletin. 40, 2007, 73––81.
[1107] R.,Hewerr; M.,Coyaniss; M.,Traut; T., T M phahlele; M., Coatess; J., and E.,V VAN DER
LINGEN N. Investigatinng the biomeddical applicatiions of gold.W World Gold Conference
C
2009, The Southern Affrican Institutee of Mining annd Metallurgy.
[1108] S., Wan ng; W., Shaao ; H., Li ; C., Liu ; K., K Wang ; J., Zhang . Synthesis,
characterrization and cyytotoxicity of the gold (III) complexes off 4,5-dihydroppyrazole-1-
carbothiooamide derivattives European Journal of Medicinal
M Cheemistry, in Preess,2011
[1109] D., Jockeers. Reverse degenerative diabetes natuurally (Opinion) .Natural news.com,
2011.
[1110] H.,Sakuraai. A new cooncept: The use of vanaddium complexxes in the treeatment of
diabetes mellitus.
m The Chemical
C Reccord. 2,2002,237-248 .
[1111] A K.,Sriv vastava; M. Z.
Z Mehdi. Insuulino-mimetic and anti-diabetic effects off vanadium
compoun nds. Diabetic Medicine.
M 22, 2004, 2-13.
[1112] K.H.,Tho ompson; C., Orvig.
O Vanadiuum in diabetes: 100 years fromf phase 0 to phase 1.
J. of Inorrg. Biochem. 100, 2006,19255-1935.
[1113] S.,Vermaa; M.C.,Cam; J.H.,McNeill. Nutritional faactors that cann favorably influence the
glucose/in nsulin system: Vanadium. J. J of the Amer.. College of Nutrition.
N 17, 1998,11-18.
[1114] A.B.,Goldfine; et al., "Metabolic Effects
E of Vanadyl Sulfatee in Humans with Non-
Insulin-DDependent Diaabetes Mellituus: In Vivo annd In Vitro Studies,"
S Metaabolism, 49
,2000 ,4000-10.
[1115] G.S.,Kellly. "Insulin Resistance:
R Liffestyle and Nutritional
N Inteerventions," Altern
A Med
Rev. 5, 20000, 109.
[116] R. B.,Kreider. "Dietary Supplements and the Promotion of Muscle Growth with
Resistance Exercise," Sports Med. 27,1999, 97-110.
[117] R.,Liasko; A.,Kabonsot; S.,Karkabounas;M.,Malamas; A.J.,Tasiopoulos ; D.,
Stefanou; P.,Collery ; A.,Evangelou. Beneficial effects of a Vanadium complex with
cysteine, administered at low doses on benzo(α)pyrene-induced leiomvosarcomas in
Wistar rats. Anticancer Reaserch, 18, 1998, 3609-3613.
[118] Aureliano, M. (Ed), Vanadium Biochemistry, Research Signpost, Kerala, 2007.
[119] Aureliano, M. and Gândara, R. (2005) Decavanadate contribution to vanadium toxicity,
J. Inorg. Biochem. 99: 979-985.
[120] Ramos, S., Manuel, M., Tiago, T., Duarte, R. O., Martins, J., Gutiérrez- Merino, C.,.
Moura, J.J.G., Aureliano, M. (2006) Decavanadate interactions with actin inhibit G-
actin polymerisation, J. Inorg.Biochem.100, 1734-1743.
[121] Soares, S.S. Henao, F., Aureliano, M, Gutiérrez-Merino C. (2008) Vanadate induces
necrotic cell death in neonatal rat cardiomyocytes through mitochondrial membrane
depolarization, Chem. Res. Toxicol. 21, 607-618.
[122] Tiago, D.M., Cancela, M.L, Aureliano M., and Laize, V. (2008) Vanadate proliferative
and anti- mineralogenic effects are mediated by MAPK and PI-3K/ras/Erk pathways in
a fish chondrocyte cell line, FEBS Lett., 582, 1381-1385.
[123] Kustin, K., Pessoa, J.C., Crans, D.C. (Eds.) Vanadium: The versatile metal, 974 ACS
Symposium Series, Washington, DC., 2007.
[124] Anderson BF, Baker HM, Dodson EJ, et al. (April 1987). Structure of human
lactoferrin at 3.2-A resolution. Proc. Natl. Acad. Sci. U.S.A. 84 , 1769–73.
[125] Dickerson, R. E., and Geis, I. (1983). Hemoglobin: Structure, Function and Evolution.
Menlo Park, CA: Benjamin/Cummings.
[126] H. R.Horton; L. A .,Moran; R. S.,Ochs,; J. D .,Rawn; and K. G. Scrimgeour, (2002).
Principles of Biochemistry , 3rd edition. Upper Saddle River, NJ: Prentice Hall.
[127] E.W. Dijk, B.L. Feringa, G. Roelfes Top. Organomet. Chem. 25, 2009,1.
[128] Transferrin Structure". St. Edward's University. 2005. Retrieved 2009.
[129] P. S Corbin.; M. P.Webb,; J. E McAlvin,.; , C. L Fraser. “Biocompatible Polyester
Macroligands: New Subunits for the Assembly of Star-Shaped Polymers with
Luminescent and Cleavable Metal Cores” Bio-macromolecules, 2, 2001,223-232.
[130] V. A. Roginskii. Phenolic Antioxidants: Reactivity and Efficiency, Nauka, Moscow,
1988 .
[131] E. R. Milaeva; Ross. Khim. Zh. Mendeleev Chem.J., 20 ,2004 .
[132] E. R. Milaeva; Izv. Akad. Nauk. Ser. Khim., 2001,549. Russ. Chem. Bull., Int. Ed.,
2001, 50, 573].
[133] D. B. Shpakovskii; E. R. Milaeva; A. V. Fionov; A. V. Dolganov; T.
V.Magdesieva;A.S.Belov;Ya.Z.,Voloshin.Abstrs.Int.Conf."KLASTERY2006"("CLUS
TERS 2006), Astrakhan, 2006, P: 90.
[134] N. M. Emanuel; E. T. Denisov; Z. K. Maizus. Chain Oxidation of Hydrocarbons in the
Liquid Phase, Nauka, Moscow, 1965.
[135] R. J. Geue; B. Korybut_Daszkiewicz; A. M. Sargeson. Chem. Commun., 1996, 1569.
[136] P. M. Angus; A. M. T. Bygott; R. J. Geue; B. Korybut_Daszkiewicz; A. W. H. Mau; A.
M. Sargeson; M. M. Sheil; A. C. Willi. Chem. Eur. J., 3,1997, 1283.
[137] Y. Z. Voloshin; O. A. Varzatskii; A. S. Belov; A. Y. Lebedev; I. S. Makarov; M. E.

Gurskii; M. Y. Antipin; Z. A. Starikova; Y. N. Bubnov. Inorg. Chim. Acta, 360, 2007,
1543.
[138] B. Rosenberg. In Cisplatin, Chemistry and Biochemistry of a Leading Anticancer
Drug,B. Lippert (Ed.), Wiley-VCH, Weinheim 1999.
[139] N. Margiotta; A. Habtemariam; P.J. Sadler. Angew. Chem. Int. Ed. Engl. 36,
1997,1185-1 187
[140] L.R. Kelland; C.F.J. Barnard; I.G. Evans; B.A. Murrer; B.R.C. Theobald; S.B. Wyer;
P.M. Goddard; M. Jones; M. Valenti;A. Bryant; P.M. Rogers; K.R. Harrap. J. Med.
Chem. 38, 1995,3016-3024.
[141] F. Reeder; F. Gonnet; J. Kozelka; J.C., Chottard. Chem. Eur. J.. 2, 1996, 1068-1076 .
[142] P. Beale; I. Judson; A. O’Donnell. Br. J. Cancer 88, 2003,1128.
[143] J. Holford; S. Y. Sharp; B. A. Murrer; M. Abrams; L. R. Kelland. Br. J. Cancer, 77,
1998, 366 .
[144] J. A., Duce; A. I., Bush. Biological metals and Alzheimer's disease: Implications for
therapeutics and diagnostics.Progress in Neurobiology,92, 2010, 1-18.
[145] P. J., Sadler ; Z., Guo .Metal complexes in medicine: Design and mechanism of action.
Pure & Appl. Chem., 70, 1998, 863-871.
[146] E., Luk;L.T., Jensen; V.C., Culotta. The many highways for intracellular trafficking of
metals. J. Biol. Inorg. Chem. 8, 2003,803–809.
Chapter 7
APPLICATION OF TRANSITION METALS AS ACTIVE

COMPOUNDS IN SEPARATION TECHNIQUES
Iwona Rykowska* and Wiesław Wasiak

Faculty of Chemistry, Adam Mickiewicz University,
Grunwaldzka, Poznań, Poland
INTRODUCTION
Among important factors related with an efficiency of analytical methods, a possibility of
selective determination and preconcentration of the analytes makes it possible to determine
the compounds at very low concentration levels (ppb, ppt, or even ppq). While determining
the most adequate separation system, one must take into consideration several criteria towards
optimum choice of both mobile and stationary phase according to physico-chemical
properties of the analytes under study.
Recently, separation techniques using transition metals as active compounds are of
growing importance. This chapter is a survey of such applications of transition metals,
divided to the following four parts:
• metal complexes as components of column packings as well as liquid stationary

phases in gas chromatography,
• optical-active complexes of transition metals in the determination of the enantiomers
by means of chromatographic methods,
• sorbents containing metals to be applied for the SPE (Solid Phase Extraction)
technique,
• immobilized Metal Ion Affinity Chromatography IMAC applied for a separation of
the proteins and peptides.
Electron-donor complexes (EDA), known also as charge-transfer complexes, are created

in both liquid phase and in a solution with some organic compounds, by cations of transition
*
Corresponding Author
300 Iwona Rykowska and Wiesław Wasiak
metals characterized by a deficit of electrons. The metal cations creating above-mentioned

EDA complexes were successfully applied to the modification of packings for gas
chromatography. Such packings may be categorized as the two below-described groups, later
described in detail:
• liquid super-selective phases, for which an inorganic salt or a complex is dissolved in

one of classical liquid stationary phases (e.g., AgNO3 in glycol ethylene, HgBr2 in
glycol polyethylene, etc.),
• super-selective adsorbents, for which transition metals are applied as:
1) a salt or another compound deposited at carrier surface,
2) porous inorganic salt,
3) an oxide of a transient metal,
4) metal-organic polymer,
5) salt of transition metal chemically bonded to the carrier surface.
The second part of the chapter is devoted to the optical-active metal complexes. Such
complexes are of growing importance in the chemistry, from both analytical and preparative
points of view, in particular in the analysis of pharmacological preparations. Among the
techniques capable of a separation of enantiomers as well verification of their optical purity,
chiral chromatography is one of the most effective. This technique has been developed
rapidly since an introduction of chiral stationary phases (CSP). A separation of enantiomers
by means of chromatographic techniques and chiral stationary phases is based on a creation of
transition diastereoisomeric complexes of a selector molecule, being a part of CSP or chiral
mobile phase, and a molecule of the compound under separation (a selectand).
Ligand-exchange chromatography LEC is a technique capable of a separation of
enantiomers of free amino acids and their derivatives, amino-alcohols, hydroxyl-acids as well
as some other classes of chiral compounds, which, in turn, are capable of a creation of
complexes with ions of transition metals (M) and ligands (L) rooted in the stationary or
mobile phase. The coordination complexes are created only in the case the ligand is a donor
of the electrons, to fill unfilled orbitals d of transition metals. The most frequently applied for
LEC ions are the following: Cu, Ni, Co, Zn, Mg, and Cd, due to the fact that their complexes
are kinetically labile. Some examples of optically active complexes of metals for the
separation of enantiomers by means of the chromatography will be given in the text.
The third part of the chapter is devoted to applications of Solid Phase Extraction SPE.
SPE is a method of growing-importance for an isolation and concentration of organic micro-
pollutants and metals from water samples. Most of the currently used sorbents are based on
silica modified with n-alkyl groups, including C8 and C18 ones. Current research is
concentrated on more and more perfect sorbent, to be applied in SPE for a better
determination of the analytes from complex matrices, and a higher recovery rate. By means of
an immobilization of transition metals on a polymer or silica-gel, it is possible to
preconcentrate the compounds that are able to create strong covalent bonds with metals. A
desorption of an analyte is provoked by a change of pH or an introduction of a ligand that, in
turn, creates a stronger bond with a metal in comparison with the compounds analyzed. Some
examples of such sorbents will be given in the text.
The last part of the chapter is devoted to applications of Immobilized Metal Ion Affinity
Chromatography (IMAC). The isolation and separation of protein and peptide mixture is not
Application of Transition Metals as Active Compounds in Separation Techniques 301
an easy procedure. IMAC is increasingly often applied to perform this task. Affinity
chromatography relies on the specific interactions between amino acids, their reactive groups
in peptides and transition metal ions. Those ions are immobilized by chelating compound on
the bed, forming specific adsorbents that bind proteins and peptides.
The chapter presents both theoretical and practical information about a possibility of an
application of metals as active elements in the separation techniques. It is demonstrated that
such metals may be effectively applied for chemistry, medicine, environmental research, and
any other field characterized by a need for a selective determination and preconcentration of
the analytes. As such, the proposed subject is very important and thus merits complex
research and discussion.
METAL COMPLEXES AS COMPONENTS OF COLUMN PACKINGS AS

WELL AS LIQUID STATIONARY PHASES IN GAS CHROMATOGRAPHY
Transition-metal complexes, chemically bonded with the carrier surface or dissolved in a
liquid stationary phase, can create labile complexes with selected organic compounds. These
complexes are also called charge-transfer complexes [1, 2]. The capability of some cations to
form complexes with the molecules showing electron-donor properties is widely used in
chromatographic separations. Such a capability may be interpreted on the grounds of the
standard acid-base theory. From the point of view of the chromatographic analysis, the
interactions among the analytes and the packings are of great importance. In case of liquid
stationary phases, two basic mechanisms of the molecular-based interactions are identified:
unspecific interactions by means of van der Waal’s forces, and specific interactions that in
turn require a transfer of electrons between interacting molecules. In general, the origin of the
adsorption interactions between an adsorbate molecule and the solid surface of an adsorbent
are similar. A creation of covalent bonds or interactions among strong acids and bases, with
resulting durable and stable products, is of no practical importance in case of
chromatographic process. Only quite weak interactions, with bonding energy at the level of a
few kcal/mol, are suited to this goal [3].
All the specific interactions taking place either in a liquid phase or on a solid surface can
be explained on the basis of updated concept of Lewis acid-base interactions. Bases (electron
donors) are species that can donate an electron pair to acids (electron acceptors). In terms of
molecular orbital theory, electron donor-acceptor interactions can be classified according to
the interacting molecular orbitals (Table 1), where n are nonbonding orbitals (e.g., unshared
electron pairs, σ and π are bonding (occupied) orbitals, and σ* and π* are antibonding
(empty) orbitals. The underlined interactions in Table 1 play an important role in
chromatographic separations of organic compounds [3].
Table 1. Classification of EDA interactions
Donor orbital Acceptor orbital

N σ* π*
n n–n n - σ* n - π*
σ σ-n σ - σ* σ - π*
π π-n π - σ* π - π*
In electron-donor-acceptor complexes, the metal stands for the acceptor, while the
organic compounds containing π bond or free electrons n become the donors. Some examples
of donors and acceptors of electrons are classified in Table 2.
Table 2. Examples of donors and acceptors of electrons
Compounds Examples
n-Donors Aliphatic amines, pyridine, sulfides, ketones, ethers, and all
neutral organics with nonbonding electron pairs
π -Donors Olefines, aromatics, azaarenes alkanes, peralylpolysiloxanes
σ-Donors Alkanes, peralylpolysiloxanes
n-Acceptors Monoatomic cations (e.g., Pd+2, Ag+2, Cu+2, etc.)
π -Acceptors Alkynes, alkenes, or aromatics with electron-withdrawing
substituents (e.g., CN, Cl, etc.)
σ-Acceptors Halogenes, halogenated alkanes (e.g., CH2Cl2, CHCl3)
In this review of the application of EDA (electron-donor-acceptor) interactions to

chromatography, we stay apart from organic complexes (e.g., π-π* or n-n*) and put stress on
coordination complexes of some metal cations with organic ligands. The role of the d-block
metal may be explained according to the charge-transfer theory [3]. The metal must be
coordinatively unsaturated, and as such it may interact with an adsorbate showing electron-
donor capabilities.
Besides the stability of complexes created, complexation kinetics is important as well.
Chromatographic retention depends on the stability of EDA complexes formed between
the stationary phase and the solute. Ideas about the formation of EDA complexes in the gas
phase or dilute solutions are based on Mulliken’s theory of charge-transfer complexes [3].
Despite the fact that the energy of formation of the complexes is of order of a few kcal·mol-1
and the retention is a result of several types of intermolecular interactions, such as, for
example, the formation of EDA complexes, the formation hydrogen bonds, and the influence
of steric effects, one can point out the cases where complexation is the process that
determines the retention of the analyte.
Some examples of electron donors and acceptors were given by Nondek [3].
The molecular complexes are substances with well-defined stochiometry and geometry.
Such complexes are formed by the interaction of two or more component molecules or ions
(Figure 1). Since the complex formation is highly selective, depending on the structure of the
complexing species as well as on the temperature or polarity of environment (as for the HPLC
case), the utilization of such complexes in chromatography has resulted in many selective
separations of mixtures of species of similar chemical structure and boiling point, such as
constitutional, configurational, isotopic, and optical isomers.
CH 3
C O Cl
SiO 2 SiCH 2 CH 2 CH 2 C M
C O
CH 3
Figure 1. Schema of a packing with chemically bonded metal complexes.
The factors influencing the stability of a complex with respect to selected ligands are the
following:
• valence, electronic structure, and radius of central metal ion,

• spatial arrangement of overlapping orbitals of central ion and ligands,
• basicity of ligands,
• “internal” electric effects or ligands transmitted through the central ion,
• steric effects due to direct contact between the atoms of different ligands,
• “external” effects due to changes in the outer coordination sphere.
A large number of the above-mentioned factors makes it possible to control the retention
in order to obtain the required separations. In many cases, depending on the circumstances,
the same molecules may play the role of either donor or an acceptor. Polycyclic aromatic
hydrocarbons (PAH) are an example of such behavior: PAHs are donors of the electrons
towards picrinian acid and tri-nitro-benzene, while acceptors towards N-dimethyloaniline. In
large molecules, such as pharmaceuticals, biologically active compounds and synthetic
colorants, few independent acceptor and donor centers may be pointed out. Low-molecule
unsaturated and aromatic hydrocarbons are usually weak donors and very weak acceptors.
Their capability of acting as donor/acceptor is increasing together with the number of double
bonds > C = C <, or, as in case of WWA, number of aromatic rings. Multi-ring aromatic
hydrocarbons are good electron donors. A substitution of a hydrogen atom by a substituent
capable of increasing a density of electrons in the ring, such as alkylo-, alkoxylo- or amino
group, increases a capability of a molecule to act as a donor of π electrons. On the other hand,
aromatic or unsaturated compounds containing few substituents removing the electrons from
the ring, such as -NO2, -CN and -Cl, are good acceptors, e.g., 1,3,5-trinitrobenzene,
tetracyjanoethylene and similar compounds. A difference between the complexing in liquid
stationary phase and at the surface of liquid sorbent aims in the fact, that:
• large surface concentration of the complexing ligands may be a reason for creation of
the complexes of “extraordinary” geometry or stechiometry,
• limited mobility of the adsorbed or chemically bonded with carrier surface acceptors
and donors of the electrons is a reason of existence of steric hindrance in turn
troubling the process of complex creation.
In gas chromatography, organic and coordination complexes are being enumerated (e.g.,
π- π* or n-n*), created among cations of the metals and organic ligands. Besides the stability
of the created complexes, kinetics of the complexing process is important as well. A
capability of an easy and fast disassembly of the complexes and their fast rebuilding is a
necessary condition for the application of such complexes in separation processes. Besides
the fact that the energy of the creation of the complexes is at the level of a few kcal/mol, and
the retention is a combined result of few types of interactions among molecules, such as a
creation of EDA complexes, hydrogen bonds and steric effects, some cases may be pointed
out when the complexation is the key process for the retention of an analyte.
Metal cations creating electron-donor-acceptor complexes can be applied as modifiers for
gas chromatography packings. Such modified packings are classified into the following two
groups.
1) Liquid super-selective phases, where inorganic salt or a complex is dissolved in one

of the classic liquid stationary phases, such as AgNO3 in ethylene glycol;
2) Super-selective adsorbents, where a transition metal is applied in the form of [3]:
• salt or another compound present on the carrier surface,
• porous inorganic salt,
• transition metal oxide,
• organometallic polymer,
• salt of a transition metal chemically bonded to the silica surface.
The above-mentioned super-selective phases and adsorbents are usually applied to the
separation of compounds differentiated by small structural changes, i.e., cis-trans isomers.
As already mentioned, cations of the transient metals, capable of EDA complexation,
may be applied as an active compound of a stationary phase in gas chromatography. The very
first work devoted to this topic was published by Bradford, Hervey and Chalkey [4]. These
authors applied a solution of AgNO3 in polyethylene glycol to separate butene-1 and
isobutane. Cation Ag+ creates a π complex with olefin. Due to the fact that the stability of
such complex depends (among others) on the steric factor, it is possible, by means of this
method, to separate the compounds of the same or similar boiling temperatures, on condition
that these compounds differ by geometric architecture (even in the minimum way).
Among several metals, silver is the metal most widely used in gas chromatography. The
systems with Ag as an active metal have been widely investigated and described. Based on
the research results, the following conclusions may be drawn [5, 6]:
• Usually, one olefin molecule coordinates at a single silver ion, forming a planar
complex with triangular structure.
• Alkyl substitution at the double bond usually decreases the stability of complexes
despite if the basicity of olefin is enhanced. The steric effects are predominating for
trans-olefins.
• The deuteration of a > C = C < bond increases its basicity and consequently the
stability of the complex.
• The most stable diene complexes are formed by 1,5-diene systems.
• With endo-cycloolefins, the stability constant increases with increasing ring strain of
olefin, which is released via complexation.
• The stability of silver-olefin complexes also depends on the anion of silver salt -
BF4- > ClO4- >> NO3- in concentrated solutions.
According to Dewar [7], the bond between an olefinic ligand and metal ion, such as Ag+ ,
is formed by donation of electrons from the filled π−orbital of the olefin to the vacat s orbital
of Ag+ and back donation of d electrons from the metal ion to the antibonding π*-orbital of
the olefin. The bonding in the complex will be affected by the availability of electrons in the
filled π−orbital and the ease of overlap of these orbitals. So both polar and steric factors
determine the stability of the silver ion-olefin complexes. In fact, the steric effects have been
found to be strong and in many cases are sufficient to explain the influence of structure on the
stability constants.
According to these basic principles, the chromatographic applications of silver-olefin
complexing, they can be classified as follows:
1) Chromatographic separations of hydrocarbon mixtures (saturates, olefins, aromatics).

2) Selective separations of olefins:
• monounsaturated hydrocarbons,
• polyunsaturated hydrocarbons: dienes,
• terpenes,
• pheromones.
Many examples of argentation chromatography are presented and discussed by D.

Cagniant in his book entitled Complexation Chromatography [3].
A separation of cis and trans isomers is a well-described example of the usability of the
Ag compounds in gas chromatography [8, 9]. By means of column packed with saturated
solution of AgNO3 in polyethylene glycol over Celit, Cope at al. [10] separated a mixture of
cis- and trans- olefins. By an application of a solution of AgNO3 in tetraethylene glycol, it
was possible to determine equilibrium of cis- and trans- cyclenes (C9-C12) [11]. However, an
application of a higher temperature for this experiment is difficult to explain, as it is widely
known that such column is not stable in the temperatures above 65 °C.
Besides Ag+ cation, an application of some other cations of transient metals was also
investigated, with the metals as solutions creating stationary phases for the gas
chromatography. Such cations as Hg2+, Cu2+, Ni2+, Pd2+, Pt4+, Rh+ and Rh2+ may be
enumerated there. Compounds of mercury were detected as of particular importance towards
a separation of oxygen-containing compounds, such as ethers, esters, and ketones [12]. The
compounds of nickel, palladium, platinum and copper are characterized by especially strong
interactions with organic compounds containing nitrogen. Capronines of nickel, copper and
other metals have been applied to separate methyl esters of the amino acids and their
N-trifluorooctanes [12]. Complexes of Ni, Pd, Pt and Cu with N-dodecylosalicyloaldimine we
proposed to separate primary and secondary amines and paraffins [12]. Stearates of Mn, Co,
Ni, Cu and Zn we also applied to separate amines [13, 14]. Very interesting results in the area
of a separation of olefins were reported by Gil-Av and Schurig. They proposed an application
of rhodium (I) β-diketonate as a solution in squalane [15-17].
Different compounds of lantanes were also applied to the separation of some organic
compounds. The authors of the work [18], while taking a research on packings containing β-
diketonate of Eu3+ dissolved in squalane, reported a affinity of such systems to such
compounds as n-alkens-1, alcohols, ketones, esters and ethers. Kowalski determined a
polarity and selectivity of polydimethylsiloxane stationary phases containing organic chelates
of the following lanthanides [19]: Pr, Eu, Dy, Ho and Yb. The phases under study were
characterized by a high selectivity towards nucleophilic compounds containing the following
functional groups:
-N=, -OH, ≡C-O-C≡
The second group of super-selective packings is based on adsorbents. The metal

compounds are present there in the solid form [12] as (1) a salt or another compound present
on the carrier surface, (2) porous inorganic salt, (3) transition metal oxide, (4) organometallic
polymer, or (5) salt of a transition metal chemically bonded to the silica surface.
Corresponding groups of super-selective adsorbents are enumerated below.
Salt and metal complexes present on the carrier surface have been used in gas
chromatography since 1962 [20]. Sawyer et al. published several results of the research
devoted to a separation of compounds by means of salts and such carriers as Porasil and
Al2O3. Different salts have been applied, both of transient metals and main groups (CoSO4,
Cr2(SO4)3, LaCl3, NaCl, Na3PO4, Na2SO4). The authors put special attention to specific
interactions of olefins and aromatic compounds with inorganic salts, drawing a conclusion
that such compounds in particular interact strongly with the packings containing transient
metals [21].
Interesting separation capabilities are shown in case of complexes of such transient
metals as Fe, Ni, Co, Cr, Zn, Cu with phthalocyanate, to be applied as adsorbents. Such
compounds are characterized by high thermal resistance, and thus may be applied to separate
the compounds of high boiling temperature [22, 23].
Porous salts used as adsorbents are prepared in a thermal process, removing a part or a
whole of the complexing element from the complexing salt. For example, Cu(Py)2(NO3)2 is
synthesized from Cu(Py)4(NO3)2 in the temperature up to 85°C, and Cu(Py)SO4 from
Cu(Py)4SO4 in 100°C. A similar method is applied to remove ammonia, water, dipyrydyl and
o-phenanthroline from the complexing salts of copper, and water from the hydrated salts of
cadmium and magnesium [21].
The above-described adsorbents, characterized by high uniformity of the pores and high
thermal resistance, have been applied to separate compounds belonging to different groups.
Cation of copper (II) interacted more strongly with non-bonding pair of electrons of a
nitrogen molecule, more weakly with the pair of electrons of an oxygen molecule, and created
π complexes with olefins. To separate alkanes, alkenes and alkines, anhydrous chlorides of
vanadium, manganese, and cobalt have been applied [24].
Transition metal oxides have been applied as adsorbents mainly in the separation of light
hydrocarbons and permanent gases. These oxides were applied as:
• fractions of the granulation adequate for the chromatographic packings,

• porous adsorption layers at the internal surface of a capillary column,
• surface adsorption layers on a glass or metal balls of adequate granulation,
• adsorption layers at the carrier surface (Al2O3).
A lot of effort has been devoted to the application of iron oxides to separate light
hydrocarbons. It was shown that α-Fe2O3 may be applied to a fast separation of isomers of
such group of organic compounds. Cr2O3 has been proposed to separate oxygen and nitrogen
[21]. Research on adsorption of benzene, pentane, hexane and other compounds showed high
energetic homogeneity of the surface of Ni(OH)2 and Co(OH)2 as well as hydrogenised
derivatives of these compounds. Also, an application of Fe(OH)3 to separate the blasy-furnace
gases has been investigated [12].
Zeolites with cations of transient metals, being crystallic aluminosilicate, are
characterized by high ordering of their structure and a capability of ion exchange. These
compounds were mainly applied, in the area of gas chromatography, to separate low-boiling-
temperature hydrocarbons. These zeolites strongly interact with olefins. Irreversible
adsorption of H2,CO and unsaturated hydrocarbons was detected on AgX zeolite as a result
of chemisorption on reduced molecules of silver [21]. The zeolites with ions Na+ replaced by
Ag+ or Cd+ strongly interacted with carbon monoxide and olefins [21]. Zeolites substituted
with Ni+2 cations are characterized by high affinity for carbon monoxide, thus may be applied
to complete separation of this gas from a mixture of inert gas. Other research was
concentrated on an application, for gas chromatography, of the zeolites containing cations of
zinc, cadmium, and manganese [25, 26].
Metalloorganic polymers are a group of adsorbents with high potential impact taking into
account selectivity and thermal resistance. In case of that group of compounds, it is possible
to obtain a packing with required pore size, specific volume, and other physical parameters.
An introduction of a metal to an organic molecule may increase the selectivity of the
adsorbent towards given groups of compounds. For example, an introduction of a molecule of
silver or mercury may increase the affinity for olefins, while an introduction of nickel -
affinity for amines [12].
The last group of super-selective adsorbents comprises salts of a transition metal
chemically bonded to the silica surface. Authors of the review [27] summarized current state-
of–the-art and recent advances in the application of metal complexes as adsorbents and liquid
stationary phases in gas chromatography. Particular stress was put on stationary phases with
β-diketonate group, and nitrogen-containing functional groups (e.g., ketoimine, amine). Such
groups show electron-acceptor properties, and due to this fact, they can be permanently
bonded to metal cations. Such packings can be used as selective stationary phases for analysis
of electron-donor compounds.
β-Diketonates were a subject of many research projects in field of chromatography.
Complexes of transition metals and β-diketonates are used in gas chromatography for two
basic purposes. On one hand, metal β-diketonates, due to their high volatility, are used for the
analysis of metals [28,29] and, on the other hand, due to their ability to form adducts with
additional ligands, β-diketonates can be used as selective adsorption centers in complexation
gas chromatography.
β-Diketonate complexes of transition metals are of great interest to complexation gas

chromatography. In Table 3, are sample applications of β-diketonates for the separation of
nucleophilic compounds.
Table 3. Sample applications of β-diketonates for the separation of nucleophilic

compounds [27]
Reference
No Packing Separated compounds
No
alkenes, aromatic
n-nonylo-β-diketonate
1 hydrocarbons, ketones, [30,31,]
M=Cu(II), Ni(II), Al(III), Zn(II), Be(II)
alcohols
2 Rh (CO)2 β-diketonates Olefins [32]
(CO)2 trifluoroacetylcamphorate olefins, esters, alcohols,
3 [33,34,35]
M=Rh aldehydes
p-, o-, m-nitroaniline,
4 [36]
M=Cu(II), U(II), Fe(III) herbicides,
Eu Eu
O O O O
C C C C ketones, aldehydes,
5 F7C 3 C C C 3F 7 [37, 38]
esters, ethers, thioethers
H H
[Eu(dihed)]x
R
O O ethers, ketones, [39]

6
X Eu X alcohols, esters
O O
O O
R1 R2
R2 O O R1 alcohols, ketones,
7 O O [40, 41]
ethers, esters
Ln
O O
R1 R2
No Packing Separated compounds Reference No
O O
M
O O
amines, alcohols,
R ketones, esters, ethers,
8 R [42- 44]
compounds containing
O O sulphur
M M = Ni(II), Cu(II), La(III), Zn(II)
O O
R = CH3, CF3, C3F7, C6H5
SiO 2 O Si CH2CH2C 6H 4PPh 2 . Cu (acac) 2

alkenes, ketones, ethers,
9 or [45,46]
nitroalkanes
SiO 2 O Si CH2CH 2C 6H 4PPh 2 . Ni (acac) 2
R1 R2
H3C CH3
10 N N ketones, amines, [47]
Ni alcohols
O O
H3C CH3
CH 3
OEt
Si O C O
O Si(CH2)3C MX
ketones, cyclic and
Si O C O
11 aromatic hydrocarbons, [48-56]
CH 3 ethers and tioethers
MX= Co(acac) 2, Co(hfac) 2, Ni(acac) 2, Ni(hfac)2
O O
C3F 7 nitro aromatic, nitrate

12 F7C3 ester, piroxide [57]
explosives
O O
M=La(III), Cu(II), Zn(II)

Apart from the applications of β-diketonates discussed above, another group of gas
chromatography packings came into attention, namely those based on ketoimines.
Iminoketonates are one of the possible products of acetylacetone reactions with different
reagents. Complexes of transition metals with β-ketoimines formed in such a way are
characterized by high volatility, and this fact enables efficient use of iminoketonates in the
analysis of metals by gas chromatography [58, 59]. Due to coordinative unsaturation,
additional ligands can be inserted in the unoccupied coordinative positions of metal
iminoketonates. They form adducts with Lewis bases through intermolecular bonds. Pyridine
bases were separated by the use of nickel (II) N,N’-ethylene-, N,N’-trimethylene-, and N,N’-
phenyl-bis(acetylacetimine) dissolved in squalane [60]. Complexes of copper (II) with bis(β-
diketone) were applied by Zhang et al. [61] to separations of position isomers of selected
aromatic hydrocarbons.
Silica modified by ketoimino groups bonded to chlorides of copper (II) and nickel (II)
were used by Wawrzyniak and Wasiak as adsorbents for capillary PLOT (porous layer open
tubular) columns [62,63].
The specific interactions between the adsorbent and adsorbate molecules (linear and
branched hydrocarbons, cyclic and aromatic hydrocarbons) were characterized by retention
parameters.
Rykowska and Wasiak, in a series of publications [64-70], have presented results of their
studies of the application of complexes of copper(II) and chromium(III) chemically bonded
with silica surface by ketoimino groups. Structures of such packings are presented in Figure
5. The packings were investigated from the point of view of characterization of specific
interactions, as well as determination of the influence of the interactions on retention
parameters. Since electron-donor interactions are influenced by several factors, both
originated from the packings and from adsorbate molecules, several adsorbates differing in
their electron-donor abilities and configurations were tested. These adsorbates included,
among others, aliphatic hydrocarbons, both linear and branched [65, 66, 69], aromatic and
cyclic hydrocarbons [66, 69, 70], halogenated hydrocarbons, ethers and thioethers [64, 67,
69]. While investigating the influence of the structure and the configuration of the adsorbate
molecules on the specific interactions, particular attention was paid to the following factors:
quantity, types and positions of unsaturated bonds in a molecule, number and types of
substituents and the presence of heteroatoms (S, O) in the molecule. In Table 4 are sample
applications of β- ketoimines for the separation of nucleophilic compounds.
Chemically bonded phases containing amine groups are of great importance to GC and
HPLC [71-73]. They show electron-donor-acceptor properties, and, therefore, they can form
stable complexes with metal cations. Chemically bonded chelates have been used as selective
adsorbents in complexation reactions in gas chromatography in order to separate different
organic compounds such as hydrocarbons, alcohols, and amines. Khuhawar et al. [74] used
Ni(II) chelate complexes to separate saturated aromatic hydrocarbons, heteroaromatic
aldehydes, amines, ketones and alcohols. Dithiocarbamates bound to the support surface have
also been used as chemically bonded phases [75]. The complexes of dithiocarbamates and
such metals as cadmium, copper, and zinc were studied with the aim of applying them to the
separation of dialkyl sulfides.
Table 4. Sample applications of β-ketoimines for the separation of

nucleophilic compounds
Reference
No
Ni (II) N,N’-ethylene-, N,N’-trimethylene-,
1 and N,N’-phenyl-bis(acetylacetimine) Pyridine bases [60]
dissolved in squalane
Isomers of selected
2 Complexes of Cu (II) with bis(β-diketone) [61]
aromatic hydrocarbons
Linear and branched
The silica modified by ketoimino groups hydrocarbons, cyclic
3 [62,63]
bonded to chlorides of Cu (II) and Ni (II) and aromatic
hydrocarbons
Aliphatic
hydrocarbons, both
linear and branched,
Complexes of Cu (II) and Cr (III) chemically
aromatic and cyclic
4 bonded with silica surface by ketoimino [64-70]
hydrocarbons,
groups
halogenated
hydrocarbons, ethers
and thioethers
In [76, 77] some results of research on using polyamine complexed with copper(II) and
chromium(III) for analysis of nucleophilic compounds by complexation gas chromatography
were described. These packings were tested in order to verify their usefulness for the analysis
of aliphatic and aromatic nucleophilic compounds [76], aliphatic and aromatic halogenated
hydrocarbons, ethers, thioethers and esters [77]. Results of the retention studies as well as
chromatographic analysis have proved that the phases investigated can be successfully
applied to complexation gas chromatographic analyses of mixtures of organic compounds
including geometric isomers [76].
Cu(II) and Co(II) chelates of dithiooxamide, linked via propylene ether to silica, were
prepared, and their application to separation of C1–C4 hydrocarbons was reported by Akapo
[78], who claimed that the Co(II) complexes enable a better separation of olefins than for the
Cu(II) chelates. Akapo has also determined and characterized retention parameters for such a
group of light hydrocarbons. In Table 5 are sample applications of amine groups for the
separation of nucleophilic compounds.
Separation of higher olefins (C5 and higher) and their isomers have been carried on
transition metal complexes of bonded silica with the carrier groups –CN, -SH, -NH2, and
PPh2 [79-84].
Table 5. Sample applications of amine groups for the separation of

nucleophilic compounds
Reference
No
aromatic hydrocarbons,
heteroaromatic
1 Ni(II) chelate complexes [74]
aldehydes, amines,
ketones and alcohols
The complexes of dithiocarbamates and such
2 dialkyl sulfides [75]
metals as cadmium, copper, and zinc
aliphatic and aromatic
nucleophilic
compounds , aliphatic
3 Polyamine complexed with Cu (II) and Cr (III) and aromatic [76, 77].
halogenated
hydrocarbons, ethers,
thioethers and esters
4 Cu (II) and Co (II) chelates of dithiooxamide C1–C4 hydrocarbons [78]
OPTICAL-ACTIVE COMPLEXES OF TRANSITION METALS

IN THE DETERMINATION OF THE ENANTIOMERS BY MEANS
OF CHROMATOGRAPHIC METHODS
The separation of enantiomers by gas chromatography can be performed in two modes.
1. Indirect Methods
Enantiomers are converted off-column into diastereomeric derivatives by a chemical

reaction with an enantiomerically pure resolving agent; further subsequent gas
chromatographic separation of the diastereomers is achieved using a conventional chiral
stationary phase.
2. Direct Method
Gas chromatographic separation of the enantiomers is achieved using a chiral stationary

phase (CSP) containing a resolving agent of high (but not necessarily 100%) enantiomeric
purity.
While the indirect method involves the formation of diastereomers before separation, the
direct method relies on the different diastereomeric molecular association between the chiral,
non-racemic stationary phase (named selector) and the chiral analyte (selectand). Since
diastereomers usually possess different physical properties, an unintended discrimination may
arise during detection when using the indirect method. Also, fractionation may occur as the
result of incomplete recovery, decomposition and losses during work-up, isolation and sample
handling. Furthermore, the racemization and kinetic resolution must be absent in the
formation of diastereomers by the indirect method.
Enantiomer separation by gas chromatography is mainly performed on three types of
CSPs:
• chiral amino acid derivatives via hydrogen bonding [85-88],

• chiral metal chelates via coordination (complexation gas chromatography) [89-91],
• cyclodextrin derivatives via inclusion [92,93].
Three principal CSPs, distinguishable by the mode of selector-selectand interaction (i.e.,

hydrogen bonding, coordination and inclusion), have been thoroughly investigated using GC
[94]:
• chiral separation on non-racemic chiral amino acid derivatives via hydrogen-

bonding,
• chiral separation on non-racemic chiral metal coordination compounds via
complexation,
• chiral separation on biogenic cyclodextrin derivatives via (inter alia) inclusion.
Pioneering work in the field of chiral separation by the gas chromatography in general
was done by Gil-Av and co-workers [95]. They developed the first chiral GC phases based on
an amino acid derivative, N-trifluoroacetyl – L – isoleucine lauryl ester [96] and
N-trifluoroacetyl – L – valyl – L – valine cyclohexylester and resolved N-trifluoroacetyl
amino acids on these columns (Figure 2).
O COOR'
F 3C C N *C H
H R
R = sec-butyl R' = dodecyl
Figure 2. Structure of N-trifluoroacetyl – L – isoleucine lauryl ester.
At the beginning, the selectors were based on non-volatile liquids or some compounds
dissolved in squalane or polysiloxane. Later, these compounds were chemically bonded to
polysiloxane (such type of a stationary phase is usually known under common name
Chirasil). The method of chemical bonding of a selector has been applied for the first time in
the synthesis of Chirasil-Val [97-99] (Figure 3). Recently, this approach has been broadened
for the complexation gas chromatography by the synthesis of Chirasil-Metal [100] (Figure 4),
and, for the inclusive gas chromatography by the synthesis of Chirasil-Dex [101,102] (Figure
5).
A valine diamide was linked to polysiloxanes yielding Chirasil-Val phase [103], which
found broad application for chiral separation of amino acids and other compounds after
transformation into volatile derivatives.
Me Me
Si O Si O
CH2 Me
n
Me CH O H
O C C NH t Bu
HN *C H
Figure 3. Structure of Chirasil-Val.
CH3 CH3
O Si O Si O
CH2 CH3
n
CH2
O
Ni / 2
C3F7
Figure 4. Structure of Chirasil-Metal.
Schurig [104] introduced the principle of complexation gas chromatography using a

dicarbonyl rhodium(I)-3-trifluoroacetyl-(1R)-camphorate (Figure 6) dissolved in squalane as
CSP (Chiral Stationary Phases) and resolved (used for the enantiomeric separation of the
chiral olefin) 3-methylcyclopentane on this phase. Later, a series of 1,3-diketonate bis
chelates of manganese(II), cobalt(II) and nickel(II) derived from perfluoroacetylated terpene-
ketones were investigated as CSPs [105]. A limiting factor of coordination-type CSPs is the
low temperature range of operation 25 to 120°C. To increase the thermal stability, an
immobilized polysiloxane-based phase (Chirasil-Nickel) was developed [106].
Applicatiion of Transitiion Metals as Active Compounds in Sepaaration Techniiques 315
CH
H3 CH 3
O Si O Si O
CH
H3 (CH2)
n 8
(CH3O)) O
6
β - CD
(CH3O
O) (OC
CH3)
7 7
Fiigure 5. Structu
ure of Chirasil-D
Dex.
Dicarbonyl rhodium(I)-33-trifluoroacettyl-(1R)-campphorate
Fiigure 6. Coordinnation-type chirral stationary phhases.
Many chiraal phases succcessfully appliied in HPLC or o GC chromaatography havee been also
innvestigated in super- and subb-critical fluidd chromatograaphy [106-1099].
Lipkowitz discusses thheoretical aspects of different separatioon principles based on
attomic-level molecular modeeling [110].
A compreh hensive surveyy of differentt techniques used
u in enantiioselective commplexation
gaas chromatography was peerformed by Schurig S in 20002 [111]. Otther studies inn this area
innclude those by Schurig et e al., who successfully
s a
applied metall-β-diketonatee polymers
coontaining optically active liggands to the seeparation of enantiometric pairs
p [33-35].
A good surrvey of differeent techniquess used in gas chromatograph
c hy for the sepaaration and
chharacterization
n of inorganicc complexes wasw made by Shepherd
S [1122]. The revieww covers the
addvances in in norganic chroomatography that took plaace from 19992 through early e 2003,
concerning separations of isomers, chiral complexes, or species that bind to metal complexes
via molecular recognition that affects their migration rates.
Table 6. Surveys and other important publications in the field of optical-active

complexes of transition metals in the determination of the enantiomers by means of
chromatographic methods
Authors Title Ref.

1 W. Linder Recent development in HPLC enantioseparation—a [113]
selected review
2 V. Schurig Enantiomer analysis by complexation gas [114]
chromatography: scope, merits and limitations
3 V. Schurig Separation of isotopic and enantiomeric [115]
compositions by complexation gas chromatography
4 G. Gűbitz Separation of drug enantiomers by HPLC using [116]
chiral stationary phases—a selective review
5 V. Schurig Enantiomer separation by gas chromatography on [117]
chiral stationary phases (Review)
6 J. Bojarski, Hassan Recent applications of chromatographic resolution [118]
Y. Aboul-Enein of enantiomers in pharmaceutical analysis
6 S. Allenmark, Chromatography on chiral carriers [119]
V. Schurig
7 J. Bojarski Recent progress in chromatographic [120]
enantioseparations
8 H.Y. Aboul-Enein, M.I. Application of thin-layer chromatography in [121]
El-awady, C.M. Herda, enantiomeric chiral analysis—an overview
P.J. Nicholas
9 V. Schurig Separation of enantiomers by gas chromatography [122]
10 F. Gasparrini, D. Misiti, HPLC chiral stationary phases based on low- [123]
C. Villani molecular-mass selectors
11 G. Gűbitz, M. Schmid Chiral separation by chromatographic and [124]
electromigration techniques. A review
12 V. Schurig Chiral separations using gas chromatography [125]
13 V. Schurig Practice and theory of enantioselective complexation [111]
gas chromatography
14 G. Gűbitz, M. Schmid Chiral separation principles. [126]
15 Oi Naobumi Development of practical Chiral stationary phases [127]
for chromatography and their applications
16 H. Lingfeng, T. Beesley Applications of enantiomeric gas chromatography: [128]
A review
17 V. Šunjić Separation of enantiomers by chromatography as a [129]
vehicle for chiral catalysis. Abridged review
18 K.K. Chandrul, Enantiomeric separation in pharmaceutical analysis: [130]
B. Srivastava A chromatographic approach
In Table 6, a list of the references is given, related with surveys and other important
publications in the field of optical-active complexes of transition metals in the determination
of the enantiomers by means of chromatographic methods.
SORBENTS CONTAINING METALS TO BE APPLIED FOR THE SPE

(SOLID PHASE EXTRACTION) TECHNIQUE
These sorbents contain some metals immobilized on a carrier surface, i.e., a polymer or a
silica gel. They are characterized by a high selectivity, and they are usually applied for the
isolation and preconcentration of the compounds of similar chemical structure.
Some organic compounds can form very strong covalent bonds with metal ions. To trap
these compounds, the metal ions can be dissolved in aqueous solution, but a more
advantageous approach is to immobilize them on a polymer or silica gel-type support. A
covalent bond between the internal orbitals of a metal ion and the functional groups of the
support can serve for this immobilization. Other orbitals of the metal ion must remain free
after its immobilization, to bind the ligands from the mobile phase. Besides accumulated
analytes, other competitive ligands and metal ions as well as inorganic ions are usually also
present in the aqueous sample. This fact has to be taken into account to establish the sorption
conditions properly.
Analytes will be eluted by change of pH value and introduction of a ligand, which forms
stronger bonds with the metal ions into the system. Another possibility is to flush the analytes
out with a solution of a competitive metal ion.
The main sorbents used for trace enrichment purposes have been enumerated in a survey
[131] and some other publications [132,133].
Metal-loaded sorbents are a suitable tool when the selectivity is of prime importance.
Unfortunately, they can be used only for classes of compounds that can form covalent bonds
with metal ions. As for SPE technique, and similar–liquid chromatography, these sorbents
have their “dedicated” application areas. Continuously, the research is undertaken to broaden
these areas.
IMMOBILIZED METAL ION AFFINITY CHROMATOGRAPHY IMAC

APPLIED FOR A SEPARATION OF THE PROTEINS AND PEPTIDES
In 1975, Porath et al. [134] introduced a new type of chromatography, at the beginning
named “metal chelate chromatography,” but later renamed to “immobilized metal (ion)
affinity chromatography” (IMAC). The authors described the use of immobilized zinc and
copper metal-ions for the fractionation of proteins from humana serum.
Since the set of work was published describing the immobilization of metal ions using a
chelating agent covalently attached to a stationary support, to purify proteins [134, 135], there
have been several modifications and adaptations of this technique over the years.
IMAC is a group-specific affinity separation technique, based on specific interactions
between molecules in solution and metal ions fixed to solid support. This technique is based
on the principle of coordinate covalent bonding chemistry. Metal ions (e.g., Ag+ Al3+, Ca2+,
318 Iw
wona Rykowsska and Wiesłaaw Wasiak
Cr3+, Ni2+, Cu2+

C 2
, Zn2+, Co2++ , Eu3+ , Fe3+, Hg2+, La3+, Mn M 2+ ), being electron accepptors, react
w ligands an
with nd electron-donnor groups off biomoleculess. In biomoleccules, electron donors are
suurface-exposed d atoms of nitrogen, suulfur and oxxygen, potenttially phosphhorous. As
biiomolecules are bound to metal m chelates, weakly boundd ligands are displaced
d fromm the metal
chhelate complex x.
The classiffication system m cited by most
m authors in the IMAC field is that of Pearson
[1136], who posstulated that metal
m ions can be divided innto three categgories: hard, inntermediate
annd soft, based on their prefeerential reactivvity towards nucleophiles.
n T hard metall ions (e.g.,
The
A 3+, Ca2+, Fe3+) show a preference
Al p forr oxygen-conttaining groupps such as caarboxyls or
phhosphates fou und in phosphorylated proteeins. Soft mettal ions such as a Cu2+, Ag+, Hg2+, etc.,
2+
+ 2+ 2+ 2+
prrefer sulfur. In
ntermediate metal
m ions Ni , Cu , Zn , Co C , coordinaate nitrogen, oxygen
o and
2+ 2+
suulfur. The mo ost commonly used metal-ioons are the transition ones,, Cu , Ni , Zn Z , Co2+,
2+
3+ 2+
annd Fe , espeecially Ni , which w providees a coordinaation number of six, electrochemical
sttability underr chromatograaphic conditioons, borderlinne polarizabillity and redoox stability
[1137].
Electron-do onor atoms nitrogen, oxyggen and sulfurr present in thhe chelating compounds c
thhat are attachhed to the chromatographicc support aree capable of coordinating metal-ions
(eelectron-pair acceptors)
a forrming metal chelates, which can be biidentate, trideentate, etc.,
deepending on thhe number off occupied cooordination bonnds. The remaiining metal cooordination
siites are normaally occupied by b water moleecules and cann be exchangeed with suitablle electron-
doonor groups frrom protein.
As a chroomatographic technique, the IMAC procedure p relies on the ability of
immmobilized metal-ion
m chelaate complexes to interact with
w the side-chhain moieties of specific
am mino acids acccessible at thhe surface of protein
p via cooordinative intteractions. Foor chelating
aggent, multideentates are most populaarly used inn research works w and commercial
c
chhromatographic products. Four F differentt types of denntates: bidentaate, e.g., saliccylaldehyd,
trridentate, e.g.,, iminodiacetic acid (IDA),, tetradentate, e.g., nitrilotrriacetic acid (N NTA), and
peentadentate, e.g., N,N,N’-yrris-carboximetthyl ethylene diamine (TED D), have been thoroughly
innvestigated sinnce immobilizzed metal affinnity chromatoggraphy was exxploited [138, 139]. IDA,
N
NTA and TED D are by far the t most widdely used chellating compouunds. Figure 7 shows a
scchematic repreesentation of the octahedraal coordinationn of metal ionn Me with thee chelectors
IDDA, NTA annd TED, illusstrating the decrease d in avvailable proteein-binding siites as the
deentation of thee chelator incrreases.
IDA
A (Iminodiacettic acid) Trideentate; three reemaining coorrdination sites
Fiigure 7. Continu
ued.
NTA (Nitrilotracetic acid) Tetradentate; two remaining coordination sites
TED (Tris(carboxymethyl)ethylenediamine Pentadentate); one remaining coordination site
* Indicates coordination sites available for protein binding
Figure 7. Schematic representation of IDA, NTA and TED metal chelation.
A very simplified representation of the capacity and selectivity of various chelating

ligands and intermediate metal ions is shown in Figure 8 [140].
Selection of the supporting matrix is the first important consideration in affinity systems.
To be adequate for IMAC, the matrix must show the following characteristics [138,139]:
• easy to derivatize,
• high hydrophilic character and extremely low non-specific adsorption,
• high porosity to allow high amount of ligand immobilization,
• fairly large pore size and narrow pore size distribution,
• functional surface groups (hydroxyl, carboxyl, amide, etc.),
3220 Iw
wona Rykowsska and Wiesłaaw Wasiak
• physically, chemicaally, thermallyy, and mechannically stable under a widde range of

conditiions,
• allow the
t use of highh flow rates,
• permit regeneration of columns without
w degeneration of the matrix,
m
• provide a stable bed with no shrinnking or swelliing during the chromatograpphic run.
Fiigure 8. Chelatiing ligands and metal ions: speecificity vs. adsoorption [140].
Two charaacteristics of thet metal-ligaand bond can be used for successful sepparation of
diifferent ligandds. First, the strength
s of thee metal-ligandd bond varies from ligand-lligand, and
seecond, bindingg between the immobilized metal ions annd the ligand is i reversible. The
T elution
caan be carried outo by changing the conditiions and thereefore breakingg the metal-liggand bonds.
Three differentt elution princciples are used in IMAC: competitive
c ellution, strippiing elution,
annd pH adjustm ment. Ligand retention
r usingg Fe, Co, Cd and
a Ni as imm mobilized metaals has been
innvestigated [141-144], but most studies have examinned Cu-binding ligands. Moost authors
asssumed that th he value of thhe conditionall stability connstant with Cuu is the dominant factor
innfluencing the retention of liigand on the IMAC
I columnn [141-146].
Since its inntroduction byy Porath in 19775, IMAC hass developed innto a robust annd versatile
toool. The numb ber of uses is large and incluudes the isolattion of metal-bbinding compoounds from
seeawater, separration of enanttiomeric form ms of amino accids, tetracycliine removal frrom animal
prroducts and prrotein purificaation.
In recent years, IMAC has h experienceed a rapid expaansion into a variety
v of envvironmental
appplications. IMMAC has beenn employed inn combination with hyphenaated techniquees to isolate
annd characterize natural organic
o ligandd from aquattic environm ments and othher natural
m
macromolecule es [141-147]. Hundreds
H of papers
p have sinnce been published, describbing the use
off this principlee in not only group
g separatioons, but also as
a highly selecctive purificatiion tool for
taarget proteins from
f complexx biological saamples [140].
In Table 7 are some refferences are giveng to the literature (maiinly surveys) devoted to
IMMAC.
Table 7. IMAC-related publications
Authors Title Ref.

1 J. Porath, B. Olin Immobilized metal ion affinity adsorption and [148]
immobilized metal ion affinity chromatography
of biomaterials: serum protein affinities for gel-
immobilized iron and nickel ions
2 E. Sulkowski Purification of proteins by IMAC [149]
3 A.J. Fatiadi Affinity chromatography and metal chelate [150]
affinity chromatography
4 J. Porath IMAC—Immobilized metal ion affinity based [151]
chromatography
5 E. Sulkowski The saga of IMAC and MIT [152]
6 J. Porath Amino acid side chain interaction with chelate- [153]
liganded crosslinked dextran, agarose, and TSK-
gel, A mini review of recent work
7 F.H. Arnold Metal-affinity separations—A new dimension in [154]
protein processing
8 J.W. Wong, R.L. Albright, Immobilized Metal Ion Affinity Chromatography [155]
N.H. Wang (IMAC) Chemistry and Bioseparation
Applications
9 J. Porath Immobilized metal ion affinity chromatography [136]
10 T.T. Yip, T.W. Hutchens Immobilized metal ion affinity chromatography [156]
11 R.D. Johnson, F.H. Arnold Multipoint binding and heterogeneity in [157]
immobilized metal affinity chromatography
12 S.A. Lopatin, A new trend toward using metal chelates in [158]
V.P. Varlamov affinity chromatography of proteins (review)
13 Ki Gedal L. Immobilized metal ion affinity chromatography [159]
14 J. Zouhar Affinity Chromatography of Proteins on [160]
Immobilized Metal Ions
15 G.S. Chaga Twenty-five years of immobilized metal ion [140]
affinity chromatography: past, present and future
16 V.Garberc-Porekar, Perspectives of immobilized-metal affinity [161]
V. Menart chromatography
17 N.T. Mrabet, M.A. Immobilized metal-ion affinity chromatography: [162]
Vijayalakshmi, from phenomenological hallmarks to structure-
based molecular insights
18 E.K.M. Ueda, P.W. Gout, L. Current and prospective applications of metal [137]
Morganti ion-protein binding
19 S.Y. Suen, Y.C. Liu, Review: Exploiting immobilized metal affinity [139]
C.S. Chang membranes for the isolation or purification of
therapeutically relevant species
Authors Title Ref.

20 E. Zatloukalova Immobilized metal ion affinity chromatography [163]
and its application
21 X. Sun, J.F. Chiu, Q.Y. He Application of immobilized metal affinity [164]
chromatography in proteomics
22 J. Arnau, C. Lauritzen, G.E. Current strategies for the use of affinity tags and [138]
Petersen, J. Pedersen tag removal for the purification of recombinant
proteins
23 R. Gutiẽrreze, E.M. Martin Immobilized metal-ion affinity Chromatography: [165]
del Valle, M.A. Galản status and trends
24 D.V. Kurek, S.A. Lopatin, Prospects of application of the chitin-binding [166]
V.P. Varlamov domains to isolation and purification of
recombinant proteins by affinity chromatography
25 Rex E. Shephard Chromatographic and related electrophoretic [112]
methods in the separation of transition metal
complexes or their ligands
CONCLUSION
The chapter presents both theoretical and practical information about a possibility of an
application of metals as active elements in the separation techniques. Such topics were
described: metal complexes as components of column packings as well as liquid stationary
phases in gas chromatography, optical-active complexes of transition metals in the
determination of the enantiomers by means of chromatographic methods, sorbents containing
metals to be applied for the SPE (Solid Phase Extraction) technique, and Immobilized Metal
Ion Affinity Chromatography (IMAC) applied for a separation of the proteins and peptides.
It was demonstrated that such metal compounds may be effectively applied for chemistry,
medicine, environmental research, and any other field characterized by a need for a selective
determination and preconcentration of the analytes.
REFERENCES
[1] E.N. Gurjanowa, I.P. Goldsztajn, I.P. Romm, Donoro-akceptornaja zwjaz., Izd.
Chemia, Moscow 1973. (in Russian)
[2] I.J. Krickaja, J. Usp. Chim. 41 (1972) 2160.
[3] D. Cagniant (Ed.) Complexation Chromatography, Marcel Dekker Inc., New York,
1992.
[4] W.B. Bradford, D. Harvey, D.E. Chalkey, J. Inst. Petroleum, 4 (1955) 80.
[5] H. Hosoya, S. Nagakura, Bull. Chem. Soc. Jpn., 37 (1964) 249.
[6] M.A. Muhs, F.T. Weiss, J. Am. Chem. Soc., 84 (1962) 4697.
[7] M.J.S. Dewar, Bull. Soc. Chim. Fr., 18 (1951) C71.
[8] J.S. Shabtai, J. Herling, E. Gil-Av, J. Chromatogr., 2 (1959) 406.
[9] J. Herling, J.S. Shabtai, E. Gil-Av, J. Chromatogr., 8 (1962) 349.

[10] A.C. Cope, E.M. Acton, J Am. Chem. Soc., 80 (1958) 355.
[11] A.C. Cope, P.T. Moore, W.R. Moore, J. Am. Chem. Soc., 82 (1960) 1744.
[12] W. Szczepaniak, J. Nawrocki, Chemia Analityczna (Poland), 19 (1974) 375.
[13] D.W. Barber, C.S.G. Philips, G.F. Tusa, A. Verdin, J. Chem. Soc., (1959) 18.
[14] R.C. Castells, J.A. Cataggio, Anal. Chem., 42(1970) 1268.
[15] V. Schurig, E. Gil-Av, Anal. Chem., 3 (1971) 2030.
[16] V. Schurig, J.L. Bear, A. Zlatkis, Chromatogr., 5 (1972) 301.
[17] V. Schurig,, R.C. Chang, E. Gil-Av, F. Mikes, Chromatogr., 6 (1973) 223.
[18] E.T. Kowalska, W.J. Kowalski, J. Chromatogr., 19 (1984) 301.
[19] W.J. Kowalski, Chromatographia, 34 (1992) 266.
[20] C.G. Scott, Gas Chromatogr., Intern. Symp., 4 (1962) 36.
[21] W. Szczepaniak, J. Nawrocki, W. Wasiak, Chromatogr. 12 (19790 559.
[22] J.J. Franken, C. Vidal-Madjar, G. Guichon, Anal. Chem., 43 (1971) 2034.
[23] C. Vidal-Madjar, G. Guichon, J. Chromatogr. Sci., 9 (1971) 664.
[24] R.L. Grob, E.J. Mc Gonigle, J. Chromatogr., 59 (1971)13.
[25] F. Wolf, H. Schmidtke, Z. Phys. Chem.. (Leipzig), 257 (1976) 1061.
[26] F. Wolf, H. Schmidtke, Z. Phys. Chem.. (Leipzig), 257 (1976) 1073.
[27] I. Rykowska, W. Wasiak J. Chromatogr., 1216(2009)1713.
[28] S. Dilli, E. Patsalides, Aust. J. Chem. 29 (1986) 2369.
[29] K. Robards, E. Patsalides, S. Dilli, J. Chromatogr. A, 411 (1987)1.
[30] D.J. Mc Ewen, Anal. Chem., 38(1966) 1047.
[31] G.P. Cartoni, A. Liberti, R. Palombari, J. Chromatogr. A, 20(1965) 278.
[32] V. Schurig, E. Gil-Av, Anal. Chem., 3 (1971) 2030.
[33] V. Schurig, Chromatographia, 13 (1980) 263.
[34] V. Schurig, R.C. Chang, E. Gil-Av, F. Mikes, Chromatographia, 6 (1973) 223.
[35] V. Schurig, R.C. Chang, A. Zlatkis, J. Chromatogr. A, 99 (1974) 147.
[36] T. Seshardi, V. Kampschultz, A. Kettrup, Fresenius, Z. Anal. Chem., 360 (1980) 124.
[37] J.E. Picker, R.E. Sievers, J. Chromatogr. A, 203 (1981) 29.
[38] J.E. Picker, R.E. Sievers, J. Chromatogr. A, 217 (1981) 275.
[39] E.T. Kowalska, W.J. Kowalski, Chromatographia, 19 (1984) 301.
[40] W. J. Kowalski, J. Chromatogr. A, 349(1985) 457.
[41] W. J. Kowalski, Chromatographia, 31(1991) 168.
[42] T.J. Wenzel, W. Lawrance, J. Chromatogr. A, 396 (1987) 51.
[43] T.J. Wenzel, P.J. Bonasia, T. Brewitt, J. Chromatogr. A, 637 (1989) 171.
[44] T.J. Wenzel, K.J. Towsend, J. Chromatogr. A, 637 (1993) 187.
[45] W. Wasiak, J. Chromatogr. A, 547 (1991) 259.
[47] M.Y. Khurawar, A. Memon, M.I. Bhanger, J. Chromatogr. A, 715 (1995) 366.
[48] W. Wasiak, W. Urbaniak, I. Obst, R. Wawrzyniak, Acta Chromatogr. 1 (1992) 56.
[49] I. Rykowska, R. Wawrzyniak, W. Wasiak, Chem. Anal. (Warsaw), 39 (1994) 335.
[50] W. Wasiak, I. Rykowska, Chem. Anal. (Warsaw) 40 (1995) 731.
[51] W. Wasiak, I. Rykowska, J. Chromatogr. A, 723 (1996) 313.
[52] W. Wasiak, I. Rykowska, J. Chromatogr. A, 773 (1997) 209.
[53] W. Wasiak, I. Rykowska, Acta Chromatogr., 7 (1997) 88.
[54] Wasiak, I. Rykowska, Chromatographia, 48 (1998) 284.
[55] I. Rykowska, W. Urbaniak, Chem. Papers, 62 (2008) 268.

[56] W. Wasiak, A. Voelkel, I. Rykowska, J. Chromatogr. A, 690 (1995) 83.
[57] S.D. Harvey, T.J. Wenzel, Chromatogr., 1192 (2008) 212.
[58] S. Dilli, E. Patsalides, Aust. J. Chem. 29 (1986) 2369.
[59] K. Robards, E. Patsalides, S. Dilli, J. Chromatogr. A, 411 (1987)1.
[60] J. Masłowska, G. Bazylak, Collect. Czech. Chem. Commun., 54 (1985) 1530.
[61] H. Zhang, X. Yuan, R. Fu, J. Chromatogr. A, 809 (1998) 65.
[62] R. Wawrzyniak, W. Wasiak, J. Sep. Sci., 28 (2005) 2454.
[63] R. Wawrzyniak, W. Wasiak, Chromatographia, 59 (2004) 205.
[64] W. Wasiak, I. Rykowska, Anal. Chim. Acta, 378 (1999) 101.
[65] I. Rykowska, W. Wasiak, Chem. Anal. (Warsaw), 46 (2001) 489.
[66] I. Rykowska, W. Wasiak, J. Chromatogr. Science, 39 (2001) 1.
[67] I. Rykowska, W. Wasiak, Anal. Chim. Acta, 451 (2002) 271.
[68] W. Wasiak, I. Rykowska, A. Voelkel, J. Chromatogr. A, 969 (2002) 133.
[69] I. Rykowska, W. Wasiak, Chem. Anal. (Warsaw), 48 (2003) 495.
[70] Rykowska, W. Wasiak, Chem. Anal. (Warsaw), 49 (2004) 707.
[71] O. Bordelanne, M.H. Delville, G. Felix, Chromatographia, 52 (2000) 51.
[72] A.G.S. Prado, C. Airoldi, J. Coll. Interface Sci., 236 (2001) 161.
[73] C.R. Silva, I. Jardim, C. Airoldi, J. High Resolut. Chromatogr., 22 (1999) 1030.
[74] M.Y. Khuhawar, A.A. Memon, M.I. Bhanger, J. Chromatogr. A, 715 (1995) 336.
[75] C.F. Yeh, S.D. Chyuch, W.S. Chen, I.D. Fang, C.Y. Liu, J. Chromatogr. A, 630 (1993)
275.
[76] I. Rykowska, S. Smyka, W. Urbaniak, W. Wasiak, J. Chromatogr. A, 844 (1999) 239.
[77] Rykowska, W. Wasiak, Chromatographia, 51 (2000) 623.
[78] S.O. Akapo, Anal. Chim. Acta, 341 (1997) 37.
[79] W. Wasiak, W. Szczepaniak, Chromatographia, 18 (1984) 205.
[80] W. Wasiak, Chromatographia 22 (1986) 147.
[84] W. Wasiak, W. Urbaniak, J. Chromatogr. A, 757 (1997) 37.
[85] W.A. Kőnig, J. High Resolut. Chromatogr., 5 (1982) 588.
[86] R. Straub, M. Pfister, H. Arm, J. Chromatogr., 585 (1991) 195.
[87] D. Chambaz, W. Haerdi, J. Chromatogr., 600 (1995) 203.
[88] V. Vaccher, P. Berthelot, M. Debaert, J. Chromatogr., 715 (1995) 361.
[89] V. Schurig, Chromatographia, 13 (1980) 263.
[90] V. Schurig, J. Chromatogr., 441 (1988) 135.
[91] Ch. Boberg, T. Norin, L. Rakos, J. Chromatogr., 585 (1991) 111.
[92] M. Jang, V. Schurig, J. High Resolut. Chromatogr., 16 (1993) 289.
[93] V. Schurig, H.P. Nowotny, J. Chromatogr., 441 (1988) 155.
[94] P. Schreier, A. Bernreuther, M. Huffer, Analysis of Chirac organic molecules, Walter
de Gruyter, Berlin, Germany, 1995.
[95] E. Gil-Av, B. Feibush, R. Charles-Sigler, Tetrahedron Lett., 8 (1966) 1009.
[96] E. Gil-Av, B. Feibush, Tetrahedron Lett., 9 (1967) 3345.
[97] H. Frank, G.J. Njcholson, E. Bayer, J. Chromatogr. Sci., 15 (1977) 174.
[98] T. Saeed, P. Sandra, M. Verzele, J. Chromatogr., 186 (1980) 611.
[99] H. Rotzche, Stationary phases in gas chromatography, Elsevier, Leipzig 1991.

[100] W.A. Kőnig, I. Benecke, J. Chromatogr., 209 (1981) 91.
[101] V. Schurig, D. Schmalzing, J. High Resolut. Chromatogr., 13 (1990) 713.
[102] M. Jung, V. Schurig, J. Microcol. Sep., 5 (1993) 11.
[103] H. Frank, G.J. Nicholson, E. Bayer, Angew. Chem. Int. Ed Engl., 17 (1978) 363.
[104] V. Schurig, Angew. Chem. Ed Engl., 16 (1977) 110.
[105] V. Schurig, W. Burkle, K. Hintzer, R. Weber, J. Chromatogr. A, 475 (1989) 23-44.
[106] V. Schurig, D. Schmalzing, M. Schleimer, Angew. Chem. Int. Ed Engl., 30 (1991) 987.
[107] G. Terfloth, J. Chromatogr. A, 906 (2001) 301.
[108] K.L. Williams, L.C. Sander, J. Chromatogr. A, 785 (1997) 149.
[109] P. Petersson, K.E. Markides, J. Chromatogr. A, 666 (1994) 381.
[110] K. B. Lipkowitz, J. Chromatogr. A, 906 (2001) 417.
[111] V. Schurig, J. Chromatogr. A, 965 (2002) 315.
[112] Rex E. Shepherd, Coord. Chem. Rev. 247 (2003) 147.
[113] W. Linder, Chromatographa, 24 (1987) 97.
[115] V. Schurig, Anal. Proceedings (London) 26 (1989) 202.
[116] G. Gűbitz, Chromatographia, 30 (1990) 555.
[118] J. Bojarski, Hassan Y. Aboul-Enein, Biom. Chromatogr., 10 (1996) 297.
[119] S. Allenmark, V. Schurig, J. Mater. Chem. 7 (1997) 1955.
[120] J. Bojarski, Chem. Anal., 42 (1997) 139.
[121] H.Y. Aboul-Enein, M.I. El-Awady, C.M. Herda, P.J. Nicholas, Biomem. Chromatogr.,
13 (1999) 531.
[123] F. Gasparrini, D. Misiti, C. Villani, J. Chromatogr. A, 906 (2001) 35.
[124] G. Gűbitz, M. Schmid, Biopharm. Drug Dispos., 22 (2001) 291.
[125] V. Schurig, Trends Anal. Chem. (TRAC), 21 (2002) 647.
[126] G. Gűbitz, M. Schmid, Methods in Molecular Biology, 243 (2003) 1.
[127] Oi Naobumi, Chromatography, 26 (2005) 1.
[128] H. Lingfeng, T. Beesley, J. Liq. Chrom. & Related Technol., 28 (2005) 1075.
[129] V. Šunjić, Croat. Chem. Acta, 82 (2009) 503.
[130] K.K. Chandrul, B. Srivastava, J. Chem. Pharm. Res., 2 (2010) 923.
[131] I. Liška, J. Krupčik, P.A. Leclerc, J. High Res. Chromatogr., 12 (1989) 577.
[132] C.E. Goewie, P.K. Kwakman, R.W. Frei, U.A. Th. Brinkman, W. Maasfeld, T.
Seshadri, A. Kettrup, J. Chromatogr. A, 284 (1984) 73.
[133] M.W. Nielen, R. Bleeker, R. W. Frei, U.A. Th. Brinkman, J. Chromatogr. A, 358
(1984) 393.
[134] J. Porath, J. Carlsson, I. Olsson, G. Belfrage, Nature, 258 (1975) 598.
[135] J.R. Everson, H.E. Parker, Bioinorg. Chem., 4 (1974) 15.
[136] J. Porath, Protein Expression Purif., 3 (1992) 263.
[137] E.K.M. Ueda, P.W. Gout, L. Morganti, J. Chromatogr. A, 988 (2003) 1.
[138] J. Arnau, C. Lauritzen, G.E. Petersen, J. Pedersen, Protein Expr. And Purificat., 48
(2006) 1.
[139] S.Y. Suen, Y.C. Liu, C.S. Chang, J. Chromatogr. B, 797(2003) 305.
[140] G.S. Chaga, J. Biochem. Biophys. Chromatogr., 49 (2001) 313.
[141] I. Paunovic, R. Schulin, B. Nowack, J. Chromatogr. A, 1100 (2005) 176.

[142] S. Sharma, G.P. Agarwal, Anal. Biochem., 288 (2001) 126.
[143] F.C. Wu, R.D. Evans, P.JJ. Dillon, Anal. Chim. Acta, 452 (2002) 85.
[144] F.C. Wu, R.D. Evans, P.JJ. Dillon, Anal. Chim. Acta, 464 (2002) 47.
[145] A.R.S. Ross, M.G. Ikonomou, K.J. Orians, Mar. Chem., 83 (2003) 47.
[146] R.W. Vachet, M.B. Callaway, Mar. Chem., 82 (2003) 31.
[147] R.G. Pearson, In: Rearson, R.G., editor. Hard and soft acids and bases. Stroudsburg,
PA: Hutchington & Ross; 53 (1973) 67.
[148] J. Porath, B. Olin, Prot. Express. Purif., 3 (1983) 263.
[149] E. Sulkowski, Trends Biotechnol., 3 (1985) 1.
[150] A.J. Fatiadi, Crit. Rev. Anal. Chem., 18 (1987) 1.
[151] J. Porath, TRAC-Trends Anal. Chem., 7 (1988) 254.
[152] E. Sulkowski, Bioessays, 10 (1989) 170.
[153] J. Porath, J. Mol. Recognit., 3 (1990) 123.
[154] F.H. Arnold, Bio-Technol., 9 (1991) 151.
[155] J.W. Wong, R.L. Albright, N.H. Wang Sep. Purif. Methods 20 (1991) 49.
[156] T.T. Yip, T.W. Hutchens, Mol. Biotechnol., 1 (1994) 151.
[157] R.D. Johnson, F.H. Arnold, Biotechnol. Bioeng., 48 (1995) 437.
[158] S.A. Lopatin, V.P. Varlamov, Prikl. Biokhim. Microbiol., 31 (1995) 259.
[159] Ki Gedal L., Immobilized metal ion affinity chromatography. In: Janson J-C, Rydĕn L,
eds. Protein Purification: Principles, High-Resolution Methods, and Applications. 2nd
ed. New York: John Wiley & Sons, Inc., (1998) 311.
[160] J. Zouhar, Chem. Listy, 93 (1999) 683.
[161] V. Garberc-Porekar, V. Menart, J. Biochem. 49 (2001) 335.
[162] N.T. Mrabet, M.A. Vijayalakshmi, Immobilized metal-ion affinity chromatography:
from phenomenological hallmarks to structure-based molecular insights. In:
Vijayalakshmi M.A. ed. Biochromatography: Theory and Practice. London: Taylor &
Francis, Ltd., (2002) 272.
[163] E. Zatloukalova, Chemicke Listy, 98 (2004) 254.
[164] X. Sun, J.F. Chiu, Q.Y. He, Expert Rev. Proteomics, 2 (2005) 649.
[165] R. Gutiẽrreze, E.M. Martin del Valle, M.A. Galản, Separ. & Purf. Reviews, 36 (2007)
71.
[166] D.V. Kurek, S.A. Lopatin, V.P. Varlamov, Applied Biochem. and Microbiol., 45 (2009)
1.
Chapter 8
CHROMIUM PIGMENT
Mohammad Fikry Ragai Fouda1 , Hanan F. Abdel-Halim2

and Samia Abdul Raouf Mostafa3
1
Professor of Inorganic Chemistry, National Research Center,
Cairo, Egypt
2
Ph.D Inorganic Chemistry, Faculty of Pharmacy, Misr International University,
Cairo, Egypt
3
Associate Professor Inorganic Chemistry, National Research Center,
Cairo, Egypt
INTRODUCTION
Discovery of the Chromium
Chromium is the 21st element in the earth's crust in relative abundance, ranking with V,
Zn, Ni, Cu, and W, with atomic numder 24, It belongs to Group VI B of the periodic table
whose other members are molybdenum and tungsten. Its neighbors are vanadium and
manganese. It was first isolated and identified as a metal by the French chemist, Vauquelin, in
1798 working with a rare mineral, Siberian red lead (crocoite, PbCrO4). He chooses to name
it chromium, from the Greek word chroma meaning color, because of the wide variety of
brilliant colors displayed by compounds of the new metal. Chromium metal in its purest form
(99.96% chromium) is produced in limited quantities by vapor deposition from anhydrous
chromium iodide. Commercial chromium metal is produced either by electrolysis of a
chromium-containing electrolyte or by aluminothermic reduction of pure chromic oxide.
Nowadays, the chromium metal, different chromium alloys and chromium compounds
were produced, on a large scale, for uses in various industrial applications [1].
1
E.mail address: mfrfouda@yahoo.com
2
Email address: hanan.farouk2@yahoo.com
3 Email address: Samia_Abdulraouf@yahoo.com
328 Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al.
Occurrence and Mining of Chromite Ore
The only commercial ore, chromite, has the ideal composition FeO.Cr2O3, i.e. 68%
Cr2O3, 32% FeO or ca. 46% chromium- Actually the Cr/Fe ratio varies considerably and the
ores are better represented as (Fe,Mg)0.(Cr,Fe,Al)2O3.
Table 1 gives the classification of chromite ores.
Table 1. Composition of chromite ores[1]
Grade Composition Ratio Cr:Fe

metallurgical, high Cr 46% Cr2O3 min. >2:1
chemical, high Fe 40 to 46% Cr2O3 1.5 to 2:1
refractory, high Al >20% Al2O3
>60% A12O3 + Cr2O3
Chromite deposits occur in olivine and pyroxene type rocks and their derivatives.
Geologically they appear in stratiform deposits several feet thick covering a very wide area
and are usually mined by underground methods.
Podiform deposits, i.e. isolated lenticular, tabular, or pod-shaped bodies ranging in size
from a kilogram to several million tons are mined by both surface and underground methods,
depending on size and occurrence. Most chrome ores are rich enough for hand sorting.
However, fines or lower-grade ore can be effectively concentrated by gravity separation
methods yielding products as high as 50% Cr2O3 with the Cr/Fe ratio of the original ore
usually unchanged.
Decreasing world supplies [2] of high-grade lumpy ore and increasing availability of
high-grade fines and concentrates has increased the use of three agglomeration methods, (a)
briquetting with a binder, (b) production of an oxide pellet by kiln firing, and (c) production
of aprereduced pellet by furnace treatment.
Manufacture of Chrome and Chrome Compounds
The two primary industrial compounds of chromium made directly from chromite ore are
sodium chromate and sodium dichromate. Secondary chromium compounds produced in
substantial quantity include potassium chromate and dichromate, ammonium dichromate,
chromic acid (chromium (VI) oxide), and various formulations of basic chromic sulfate used
principally for leather tanning. The production processes of chromium and different
chromium alloys; and chromium compounds (such as potassium chromate and dichromate,
ammonium dichromate, chromic acid, basic chromic sulfate) from different grades of
chromite ores were extinsively studied by numerous authers[3, 4].
Uses of Chromium Compounds
Chromite ore used for production of some inorganic chemicals and pigments. These
compounds are widely used in various industrial purposes such as metal finishing and
Chromium Pigment 329
corrosion control pigments, allied products, leather tanning, textiles, wood preservation,
drilling muds, catalysts and intermediates.
Chromium compounds are essential to many industries. The major uses are metal
finishing and corrosion control, pigments and allied products, leather tanning and textiles ,
wood preservation, drilling muds and other uses ( e.g: catalysts, intermediates) [5].
METAL FINISHING AND CORROSION CONTROL

The most important use of chromium compounds in metal finishing is that of chromic
acid in chromium plating [6,7]which consumes most of the chromic acid produced.
Unlike most metals, chromium is best plated from solutions in which it is present as an
anion in a high oxidation state. The use of the lower oxidation states is confined to the
electrolytic production of chromium metal.
Chromate performs two major applications in corrosion control. The first is conversion
sealing pretreatments for metal alloys of iron, aluminum, zinc, copper, and magnesium.
The second application is as leachable inhibitive pigments in many primer formulations.
Both of these uses of chromate compounds produce strong corrosion inhibiting effects.
Trialkoxysilanes and similar silicon compounds are currently the subject of intensive research
due to the need of “green” technology in the metal-finishing and the adhesive industries.
PIGMENTS
Chromium pigments can be further classified into chromate color pigments based on lead
chromate, chromium oxide greens and corrosion inhibiting pigments based on difficulty
soluble chromate. An excellent discussion of these pigments is given in a recent encyclopedia
[8]; an older reference is also useful [9].
Lead Chromate Pigments
The Chemical compositions of these pigments in addition to their analytical

specifications are summarized in the Table2. PbCrO4 PbMoO4 PbSO4 also known as
chromium-molybdenum, molybdenum red, orange molybdenum, Pigment Red 104. The main
compounds are lead chromate acid and a small amount of lead and molybdenum lead sulfate
solution formation of the orange-red approximate composition of inorganic pigments for
PbCrO4 69%:80%, PbSO49%:15%. Look for the light orange-red powder, molybdenum
(chromium) bright red. The impermeability of a better color and fragmentation. Hiding and
excellent brightness, high crushing strength worse. For sodium, sodium molybdenum, sodium
nitrate and lead to raw materials, crystal formation of the mixed precipitation making it stable,
according to that system in molybdenum lead chromate, adjusting the ratio of raw materials,
control of the reaction temperature and time, the different colors available products. Mainly
used in the coatings, plastics and inks, but there are restrictions on heavy metals in the area
not to be applied.
Table 2. Chemical composition and analytical specifications for chromate color

pigments [11,12]
PbCrO4, % PbSO4, % Other components, %

Primrose chrome yellow
theoretical 77.3 22.7
ASTM spec, min 50
actual
min 52.0 4.2
max 82.7 25.9
Lemon chrome yellow
theoretical 72.7 27.3
ASTM spec, min 65
actual
mm. 52.4 17.4
max. 68.8 39.0
medium chrome yellow
theoretical 100.0
ASTM spec, min 87
actual
mm. 82.4 nd
max. 98.2 nd
chrome orange
theoretical 59.2 PbO.40.8
ASTM spec, min 55
actual 58.2 PbO, 39.4
molvbdate orange
theoretical 82.3 2.8 PbMoO4, 14.9
ASTM spec, min 70
lead silicochromate
theoretical 50.0 SiO2, 50.0
Chromium Oxide Greens
These pigments comprise both the pure anhydrous oxide Cr2O3, and hydrated oxide, or
Guignet's green [13]
Corrosion Inhibiting Pigments
These pigments derive their effectiveness from the low solubility of chromate. The major
pigment of this group is zinc chromate or zinc yellow; others include zinc tetroxychromate,
basic lead silicochromate, strontium chromate, and barium potassium chromate [14].
The chemical composition of some of these pigments is shown in Table 3.
Table 3. Analytical specification and composition (percent by weight) of corrosion inhibiting pigments [12,14]
H2O
CrO2 ZnO Other MO SO3 Other
combined
zinc chromate
type I, low sulfate
theoretical 45.8 37.2 10.8 K2O 6.2
ASTM spec. 41min. 35-40 max. K2O 0.2 max. 0.1 max. Cl
typical 45.0 36.0 10.0 6.0 0.05
type n, regular
ASTM spec. 41min. 35-40 13max. K2O 3.0 max. 0.8 max. C1
typical 44.0 38.0 10.0 6.0 1.0
zinc tetroxychromate
typical 17.0 71.0 10.0 0
strontium chromate
theoretical
ASTM spec. 44min. 47min. SrO 0.2 max. 0.1 max. C1
typical 47.0 49.0 0.2
Basic lead silicochromate
ASTM spec. 5.1-5,7 46-49 PbO 0.2 max. 45.5- 48.5

SiO2
typical 5.4 47.0 47.0
LEATHER TANNING
Although compounds of chromium (VI) are the most important commercially chromium
compounds the bulk of the applications in the textile and tanning industries depend on the
ability of chromium (III) to form stable complexes with proteins, cellulosic materials,
dyestuffs, and various synthetic polymers. The chemistry is complex and still imperfectly
understood in many cases. The common denominator is the coordinating ability of chromium
(III).
The chromium tanning of leather is one step in a complicated series of operations leading
from the raw hide to the finished product. Chrome tanning is the most important tannage for
all hides except heavy cattle hides, which are usually vegetable, tanned. In heavy shoe uppers
and soles, chrome tanned leather is frequently given a vegetable retan to produce chrome
retan leather. The annual consumption of hides by the leather industry appears to be
decreasing [15].
Some thermoresistant pigments having spinel and tin sphene structure were synthesized
using as chromophore (Cr3+) source leather wastes with 6.5% Cr2O3 content. This particular
chromium source brings a series of advantages, as: burning of the organic components
supplies in situ a part of the necessary energy of the synthesis and the chromophore is well
dispersed in the reaction mixture. The complete burning of the wastes without the emission of
polluting compounds requires the reaction mixture to be introduced in the oven at
temperatures above 800 °C [16].
IN TEXTILE INDUSTRY
Sodium dichromate and various chromic salts are employed in the textile industry [17,
18]. The former compounds are used as an oxidant and as a source of chromium; for example,
to dye wool and synthetics with mordant acid dyes, oxidize vat dyes and indigosol dyes on
wool, after-treat direct dyes and sulfur dyes on cotton to improve washfastness and oxidize
dyed wool. Premetallized dyes are also employed. These are hydroxyazo or azomethine dyes
in which chromium or other metals are combined in the dye.
A typical premetallized dye is designated Chromolan Black NWA (CI 15711). The
commercial product also contains some-of the 1:1 chelate.
There are numerous patents covering dark pigment compositions containing iron and
chromium. For example, U.S. Pat. No. 2,187,822 (I. G. Farben) relates to a process of
producing a brown pigment having the formula 3K2O.11Fe2O3 .16CrO 3 .12H2 O. In this
pigment, the weight ratio of the oxides of chromium and iron is approximately 1:1.
U.S. Pat. No. 3,561,989 (Bayer) relates to a black enamel having a corundum structure in
the form of Fe 2 O 3 and containing 66 to 95 parts by weight of Cr2O3 per 100 parts of Fe2O3.
No mention is made of its possible use in vinyl or other polymers for house siding. Instead its
suggested uses are limited to enameling and glazing.
U.S.Pat. No. 3,528,839 (Bayer) covers a black pigment containing copper, iron, and
chromium in a spinel structure and having higher temperature stability, high tinting strength,
good light fastness and resistance to weathering. The atomic weight ratio of copper to chrome
and iron is 0.25-0.5 and the ratio of iron to chrome is 0.25-0.5 [19]. Another use of chromium
compounds is in the production of water- and oil resistant coatings on textiles, plastic, and
fiberglass. Trade names are Quilon, Volan, and Scotchgard [20,21].
CHROMIUM PIGMENTS AS WOOD PRESERVATION

The recent increase in the use of chromium compounds in wood preservation may be
largly due to the excellent results achieved by chromated copper arsenate (CCA), available in
three modifacations under a variety of trade names. The treated wood is free from bleeding, is
paintable and of an attractive olive-green color. Thus CCA is widely used, especially in
treating utility poles,building lumber, and wood foundations.
Chromium compounds are also used in fire- retardant formulations where their function
is to prevent leaching of the fire retardant from the wood and corrosion of the equipment
employed.[22].
CCA protects wood used aboveground, in contact with the ground, or in contact with
freshwater or seawater. Wood treated with CCA (commonly called green treated) dominated
the treated wood market from the late 1970s until 2004. Chromated copper arsenate has been
phased out voluntarily for most applications around residential areas and where human
contact is prevalent. The allowable uses for CCA are discussed in more detail in the
Recommended Guidelines section.
The three standardized formulations are: CCA Type A, CCA Type B, and CCA Type C.
CCA Type C (CCA–C) is the formulation used by nearly all treatment facilities because of its
resistance to leaching and its demonstrated effectiveness. CCA–C is comprised of 47.5
percent chrom-ium trioxide, 18.5 percent copper oxide, and 34.0 percent arsenic pentoxide
dissolved in water.
CCA–C has decades of proven performance. It is the reference preservative used to
evaluate the performance of other waterborne wood preservatives during accelerated testing.
Because it has been widely used for so many years, CCA–C is listed in AWPA standards for
a wide range of wood products and applications. The minimum retention of CCA–C in wood
ranges from 0.25 pounds per cubic foot (4 kilograms per cubic meter) in aboveground
applications to 2.5 pounds per cubic foot (40 kilograms per cubic meter) in marine
applications. Most ground-contact applications require minimum retentions of 0.4 pounds per
cubic foot (6.4 kilograms per cubic meter). Critical structural applications require minimum
retentions of 0.6 pounds per cubic foot (9.6 kilograms per cubic meter). It may be difficult to
obtain adequate penetration of CCA in some difficult-to-treat species. The chromium serves
as a corrosion inhibitor.
CHROMIUM PIGMENTS AS CATALYSTS

A more important minor use of chromium compounds is in the manufacture of catalysts,
consuming about 1500 metric tons of sodium dichromate equivalents annually. Chromium
catalysts are used in a great variety of reactions, including hydrogenations, oxidations.and
polymerizations. Most of the details are proprietary and many patents are available [23-25]
Chromia-alumina catalysts are prepared by impregnating y-alumina shapes with a solution of
chromic acid, ammonium dichromate, or chromic nitrate, followed by gentle calcination. Zinc
and copper chromites are prepared by coprecipitation and ignition, or by thremal
decomposition of zinc or copper chromates, or organic amine complexes therefore many
catalysts have spinel-like structures [26].
Back in the 1940s as well as in the paint industry of today, the term Zinc Chromate does
not refer to a paint color, but rather a protective coating. Another route of preparation of these
compounds by heating the nitrates of chromium and the desired metal at 1000 c. A Through
investigation were carried out by monitoring reaction products at numerous temperatures.the
products were tested as pigments according to the usual method of testing in that respect[27].
Zinc chromate is a corrosion resistant agent that is added to certain coatings. Even today,
chromate finishes including zinc chromate provide superior corrosion resistance.
Additionally, zinc chromate is highly toxic thus protecting the surface from proliferation of
organic matter.
In the aircraft industry of the 1940s, zinc chromate was used as an anti-corrosive barrier
primer; it could be described as a sort of painted-on galvanizing. It has been developed by
Ford Motor Company by the late 1920s, subsequently adopted in commercial aviation and
later by the US Military. Official USAAC notes mention successful application of zinc
chromate primer starting from 1933, but it has not been adopted as standard until 1936.
Because zinc chromate is all about corrosion protection, the precise coloring of it is and
has not been considered as important as the chemical composition. In the official notes of the
period, the name zinc chromate is often accompanied by the name of particular manufacturer,
thus mentioning Ford zinc chromate, DuPont zinc chromate or Berry Brothers zinc chromate.
This means that the actual color of zinc chromate coating may have varied from batch to
batch or manufacturer to manufacturer without it being viewed as an issue.
The 'native' tone of zinc chromate crystalline salt is a bright greenish-yellow. When put
into a vehicle with binders to make paint, this color would be the raw result.
Such raw zinc chromate primer would also give a semi-translucent coating, not very
opaque like a pigmented paint or lacquer. This property becomes especially interesting when
we consider that aircraft factory instructions often called for just one protective coat of
primer. As a consequence, the color of the underlying surface might have a significant effect
on the final appearance. For example, raw zinc chromate applied on the white background
would look yellow, while applied to bare metal aluminum it would look more like apple
green.
Similarly, any pigment might be added to the raw paint mixture to go with the zinc
chromate, thereby modifying the color. Some of today's mixtures use iron oxide -- giving that
rusty red appearance you can often see on prefabricated steel beams in highway and building
construction.
Sometimes, zinc chromate was mixed with Lamp Black paste to give a bit more UV
resistance (zinc chromate is very sensitive to photolitic reactions) and more durability in high
wear areas.
Mixing with black gave greener tones, which, depending on the amount of black added
could run from apple greens to medium olive greens[28].
Thermochromism of art-known compositions of rubies d-elements (Al2-xCrxO3) and
spinels (MgAl2-xCrxO4), as well as of the claimed ones, is stipulated not by the phase
transition with the temperature changes, but with the change in ligands field force. Color
change takes place with chromium concentration increase on account of aluminium atoms
with chromium atoms substitution, which is accompanied by lattice deformation due to

greater radius of chromium atoms against aluminium atoms. Hereupon, the phenomenon of
such thermochromism is known for chromium only.
If chromium concentration in these compounds is not high, they have pink color. At high
chromium concentrations the color of these compounds is green. Pink crystals have
thermochromism : upon heating their color gradually changes from pink at low temperatures
to green at high temperatures. However, this change takes place very slowly within wide
range of temperatures from 200 to 900 ◦C. Within the range of temperatures from room
temperature to about 400 ◦C, which is the most substantial for warning a customer, change of
color in rubies and spinels is not sufficient for using them as thermochromic components of
the coatings.
Spinel Structured Pigments
Spinels are ternary oxides with the general formula AB2O4, where A and B are cations
occupying tetrahedral and octahedral sites respectively. These oxides exhibit interesting
electric, magnetic and catalytic properties [29-32], depending on their nature, charge, and
distribution of ions at interstices [33]. CuCr2O4 crystallizes as a tetragonally distorted spinel
structure. Its distortion is related to the cooperative Jahn-Teller effect of Cu2+ at the
tetrahedral sites [34]. The substitution of tetrahedral Cu2+ ions by any bivalent cation does not
affect the distribution of cations in the substituted spinel oxides [35,36]. Site preference
energies for oxide spinels indicate that Ni2+ and Cr3+ occupy octahedral sites, although Cr3+ is
also capable of forcing Ni2+ into tetrahedral positions [35].
The most widely used method for the preparation of spinels involves solid-state reaction
of mechanically mixed metal oxides at high temperatures [37,38]. The Pechini
method[39,40], based on polymeric precursors, can be used to prepare spinels and it does not
require high temperature calcinations and permits good stoichiometric control as well as
reproducibility. This method consists of the formation of a polymeric resin between a metallic
acid chelate and polyhydroxide alcohol by polyesterification.
This study is focused on the preparation of solid solutions of copper chromites doped
with nickel by the Pechini method, and the investigation of the effect of heat treatment on
particle size and morphology. X-ray diffraction (XRD) and Fourier Transform Infrared
Spectroscopy (FTIR) patterns were used to reveal the structural properties of the materials
formed.
According to group theory, spinel type oxides should exhibit four IR bands υ 1- υ 4
[41,42]. In this investigation measurements were carried out up to 500 cm-1, thus limiting the
study to the high frequency bands (υ 1 and υ2) of the IR spectrum. Since these bands are
nearly insensitive to changes in the bivalent cation [37], they should not be significantly
affected when Cu2+ from CuCr2O4 is substituted by another bivalent cation. The infrared
spectra are shown in( Figure 2) Both, υ 1 at 665 cm-1, and υ 2 at 580 cm-1 are related to bonds
of the internal tetrahedra and octahedra of the structure of Cu0.8Ni0.2Cr2O4. The broadening of
these bands is probably due to the presence of more than one type of cation [42].
Figure 1. Infrared absorption pattern of the polymeric precursor and powders calcined at 500oC, 700oC
and 900oC for 4 hours.
Due to their excellent resistance to temperature, light, weather and chemicals, spinel
black pigments are eminently suitable for pigmenting highly heat resistant lacquers (e.g.
based on silicone resins) and Coil-Coat-Lacquers. For these applications they are sometimes
mixed with white pigments for obtaining a variety of grey shades. They are also suitable for
colouring plastics, porcelain enamels and ceramic glazes.
Oxidic mixed phase pigments having a spinel structure have been known for a long time.
The crystal structure of the colourless mineral spinel, MgAl2O4,offers numerous possibilities
of substitution of the magnesium and aluminium, in particular by colour producing transition
metals such as vanadium, chromium, manganese, iron, cobalt, nickel and copper, mixed
oxides of the general formula AB2O4 being thereby obtained in a wide variety of colour
shades .Mixed phase pigments are normally produced by subjecting an intimate mixture of
the metal oxides, or of compounds which form the metal oxides when heated, to a solid state
reaction at temperatures of from 800° to 1400° C. and then grinding the product.
Black pigments based on copper-chromium spinels CuCr2O4 have achieved particular
technical importance. They are frequently modified by the incorporation of iron and/or
manganese in the spinel lattice[43].
The black pigments according to the invention are distinguished by the fact that they have
substantially lower brightnesses L* when brightened by a white pigment than pigments which
have been produced by conventional processes. This brightness L* may serve as measure of
the tinting strength of the pigments. A low L* value indicates that the black pigment has a
high absorption capacity for visible light and is therefore particularly efficient in imparting
colour to other substances.
The preparation of spinel black pigments by annealing a mixture of oxides, hydroxides

and/or carbonates of copper, chromium and manganese, optionally with the addition of
mineralizing agents, at temperatures of from 750° to 900° C has been invented.
After the addition of the copper and chromium component, a homogeneous suspension is
prepared with intensive stirring and the reaction time increased by decreasing the
temperature.
Production and characterisation of pigments by using less expensive raw materials such
as limonite and chromite was undertaken. The resulting pigments were characterised by using
X-ray diffraction (XRD) and UV-Vis spectrophotometer. The colour of glazed tiles
containing 3 wt.% pigment change from dark brown to light brown depending on the
calcination temperature and limonite content. With pigments prepared with 50% limonite
content calcined at 1250 °C, the chocolate brown colour was obtained corresponding to the
commercial brown pigments. An iron-chromium black pigment was synthesised from a
mixture of pure chromium (III) oxide (Cr2O3) and iron (III) oxide (Fe2O3) powders and was
used to determine possible interactions between a pigment and a transparent glaze. The
interactions were studied using a scanning electron microscope (SEM) attached with an
energy dispersive X-ray spectrometer (EDX). The results showed that black pigment particles
give brown colour to the glaze. EDX analysis on pigment crystals embedded in the glaze
clearly showed that Zn and Mg diffused into pigment crystals and caused a change of colour
from black to brown [44].
Brown ceramic pigment has also been studied. The pigment was synthesized by adding
Al2O3 and MgO dopants in small quantities, below 3 wt%. Analysis has shown the
stabilization of two corundum structures with a compositions close to Cr0.50Fe1.50O3 and
Al0.30Cr1.70O3, plus a spinel structure with composition close to MgCr2O4. This new way of
preparation may lead to significant savings in costs [45].
Another invention in the preparation of a mixed-phase pigment was based on iron oxide
and chromium oxide by heating a mixture of the oxides, hydroxides or oxide hydroxides of
iron and of chromium at from 600° to 1100° C .The essential feature of this invention is that a
mixture of transparent α-iron oxide having an orthorhombic bipyramidal crystal structure and
a chromium(III) hydroxide, which has been applied onto the transparent iron oxide by
precipitation with an alkali, preferably sodium carbonate, is heated. The pigments according
to the invention give deep colorations and are readily dispersible. Mixed-phase pigments
based on iron oxide and chromium oxide belonging to the (Fe,Cr)2O3 are used in the form of
chrome iron brown, and demand for them in the plastics industry for coloring construction
components, eg. window profiles, is growing since they possess excellent fastness properties.
However, the tintorial properties, such as particLe fineness, dispersibility and color yield, of
the chrome iron brown pigments commercially available to date have not so far completely
met the high requirements set by the plastics industry.
Mixed-phase pigments are manufactured in general by reacting the oxide components in
the solid state at from 800° to 1400° C. This method of production results in pigments which
have a very large particle diameter and extensive sintered fractions .The use of particularly
finely divided oxides, hydroxides, or other compounds to produce a good mixture in aqueous
suspension did not result in any substantial improvement, nor were sufficient improvements
achieved by using mixtures, such as hydroxides or carbonates, which were prepared by co-
precipitation of aqueous salt solutions.
Processes which lead to homogeneous brown products of the general composition (Fe,
Cr)2 O3 , in which decomposed iron and chromium compounds are ignited at fairly high
temperatures, are also known .The mixture of the transparent α-iron oxide and the
chromium(III) hydroxide is obtained by precipitating a solution of a chromium(III) salt in the
presence of the iron oxide with an alkali, preferably sodium carbonate or potassium
carbonate. Precipitation is carried out at from room temperature to 95°C., preferably from 40°
to 80° C.
The precipitate (the mixture) is filtered off, washed and dried, and the dry mixture is then
heated in a conventional manner at from 600° to 1100° C. Heating is effected by a
conventional method, for example in a bogie hearth furnace, a rotary tube furnace or a similar
furnace.
The hue of the pigments is altered from pale brown through medium brown to deep dark
brown shades by increasing the amount of chromium oxide.
To a lesser extent, the tinctorial properties of the products are also influenced by the
temperature during heating (calcining temperature). In the system ZnO–Fe2O3–Cr2O3 the
ability of iron to occur on both the tetrahedral and octahedral sites of the spinel structure leads
to a versatile system yielding a variety of related shades [46,47].
Brown spinel pigments based on zinc chromite which are iron-free and exhibit an atomic
ratio of chromium to zinc in a range of 1 to greater than 0.5 up to 2 are disclosed. Preferred
pigments additionally contain manganese, in which instance the atomic ratio of Mn to Cr is a
maximum of 0.2. The production of the pigments involves a firing process of a powder
mixture consisting of the oxides the metals, or precursors thereof, contained in the pigment.
Instead of previously known grayish-brown unattractive products, attractive brown pigments
are obtained by means of the selected molar ratio and a baking temperature above 1200° C.
The novel pigments can be used in the presence of glass frits even at firing temperatures
above 1200° C. to 1500° C. and are suitable for a common firing of ceramic carrier and
decoration. The novel brown spinel pigments based on zinc chromite which, in contrast to
previously known pigments of this type, are iron-free. The production of the pigments of the
invention is carried out in a manner which is generally known for spinel pigments but in
which the baking temperature of the powder mixture is above the known range. The novel
pigments can be used for ceramic decorations which can be fired or baked on in a high-
temperature firing.
Spinel pigments based on zinc chromite are known; however, in many respects they do
not meet the qualities desired by manufacturers of ceramic decorations. Zinc chromite of the
formula ZnCr2O4 is a spinel in which the Zn 2 + ions occupy the tetrahedral positions and the
Cr 3+ ions the octahedral interstices of the cubically densest packing of oxygen atoms.
ZnCr2O4 is normally a greenish-gray product and is coloristically unattractive. This brown
pigments are obtained by means of the insertion of iron into the spinel lattice of the zinc
chromite. A disadvantage of these brown spinel pigments is their limited temperature stability
in the presence of glass frits, which also applies to many other iron-containing spinels. Such
pigments discolor during the firing on of decorative colors produced from them onto ceramic
products with increasing firing temperature. Such pigments are therefore not satisfactorily
suitable for applications which require firing temperatures above 1200° C., especially above
1300° C. to 1500° C., such as e.g. new porcelain firing methods in which the unfired ceramic
carrier and a decorative layer applied onto it are fired in a single firing cycle. It is assumed
that chromium is partially in the tetravalent form in the lattice of the spinels of the present
invention and that zinc ions occupy positions of the chromium for the purpose of the charge
equalization. Normally, the zinc oxide which is not bound in the spinel lattice does not result
in any disturbances when the pigments are used. However, excess ZnO can be dissolved out
or leached out of the pigment with an acid wash as required.
The pigments can additionally contain other metals in a limited amount in the spinel
lattice aside from the components Cr2O3 and ZnO for modifying the shade and/or for
stabilizing the shade in the case of very high firing temperatures, with the stipulation that the
brown color remains preserved. The term "limited amount" denotes an atomic ratio of these
other metals to chromium of a maximum of 0.2. These modifying metals are preferably
manganese, but metals inserted in the spinel such as Mg, Ti, Al, Sn, Ni, Co and V can also
modify the shade.
Pigments of the invention which essentially contain only Cr 2 O 3 and ZnO exhibit a slight
color shift toward green in glazes as the firing temperature increases--this can be recognized
by an "a" value in the L, a, b colorimetric system which decreases and, if applicable, becomes
negative. This color shift can be eliminated by means of the insertion of manganese into the
spinel lattice. Especially preferred pigments of the invention contain essentially only oxides
of chromium, zinc and manganese and exhibit an atomic ratio of Cr to Zn to Mn of 1:0.75 up
to 2:0.01 up to 0.15. The term "precursors of metal oxides" denotes compounds which are
converted into oxides below the firing temperature, e.g. sulfates, oxide hydrates, carbonates,
oxalates.
Preferred pigments which do not exhibit any color shift to green even at the high firing
temperatures of decorative systems containing these pigments and glass frits can be produced
in that the powder mixture to be fired consists essentially of Cr 2 O3 , ZnO and an Mn
compound from the series MnO , MnO2 , Mn2O3 or a permanganate with the atomic ratio of
Cr to Zn to Mn being 1:0.75 up to 2:0.01 up to 0.15. The term "essentially" signifies that the
powder mixture can additionally contain mineralizers which are not inserted into the spinel
lattice as well as impurities stemming from the raw materials used [48].
A gray vinyl polymer material having improved tolerance to sunlight and other sources of
infra red radiation. The vinyl polymer contains an inorganic pigment composed of chromium
oxide (Cr2O3) and iron oxide (Fe2O3) wherein the weight ratio of the oxides is about 3:1. The
pigment may be blended with titanium dioxide (TiO2) to give a continuous spectrum of
shades ranging from dark gray to light gray. The pigment is prepared by co-calcining the
oxides of chromium and iron in finely divided form (-325 mesh) at a relatively low (900°-
950° C.) temperature followed by grinding of the co-calcined product to 99% -325 mesh. The
pigment useful in the present invention contains between 40 and 60% by weight of
chromium, present in oxide form and between 25 and 12% by weight of iron, also present as
the oxide. A more preferred range is between 48 and 52% chromium and between 19 and
16% iron. In a highly preferred embodiment of the invention, the chromium is present as
49.8% and the iron as 17.6%. This represents 73.91% as Cr 2 O 3 and 26.09% as Fe 2 O3 [49] .
Grayish-green ZnCr2O4 spinel that an attractive brown spinel pigment is obtained by
means of the elevation of the firing temperature and the selection of the molar ratios of the
initial components. It was also surprising that the incorporation of a small amount of
manganese into the pigment distinctly increases the color stability at very high temperatures.
The novel brown spinel pigments obtainable in accordance with the method of the
present invention can be used for coloring and decorating ceramic products known in the art
such as porcelain, earthenware and stoneware in the presence of glass frits which are known
in the art. The firing temperatures can be in the customary range of usually 700° to 1100° C.
or above thereby. The temperature is a function in particular of the pigment composition and
also the softening range of the glass frits present in the decoration system used. The
temperature stability and glaze stability of the pigments of the present invention also permit
firing temperatures above 1200° C. and especially above 1300° to 1500° C. This unexpected
advantage makes it possible to also use the pigments in so-called high-temperature firing
methods, in which the ceramic carrier and the decoration are fired simultaneously in a single
firing procedure [50].
Valences of chromium were directly related to the color of the pigments. The valences
were dependent on the Ti/Sn ratio in sphene-type (CaTiSiO5-CaSnSiO5), perovskite-type
(CaTiO3-CaSnO3) and rutile-type (TiO2-SnO2) matrices mother crystals . Results of XPS
showed that chromium ions doped in CaSnSiO5 and CaSnO3 matrices existed Cr4+, causing
reddish purple color. With substitution of Ti for Sn in these matrices, the fraction of trivalent
chromium increased and the color changed from reddish purple through purple red, red brown
and finally to brown. A similar valence change of chromium was observed in the rutile-type
pigments that changed lilac through brown to ocar colors. Purple red color was achieved in
2mol% Cr-doped sphene- and perovskite-type pigments containing 20mol%Ti [51].
The tie-lines delineating intercrystalline ion-exchange equilibria between MgAl2O4-
MgCr2O4 spinel solid solution and Al2O3-Cr2O3 solid solution with corundum structure have
been determined at 1473 K by electron microprobe and X-ray diffraction (XRD) analysis of
equilibrated phases. The tie-lines are skewed to the solid solution 0.7MgAl2O4-0.3MgCr2O4.
The lattice parameters and molar volumes of both the solid solution series exhibit positive
deviations from Vegard's and Retger's laws, respectively. Activities in the spinel solid
solution are derived from the tie-line information and thermodynamic data on Al2O3-Cr2O3
solid solution available in the literature. Activities of Mg0.5CrO2 and Mg0.5AlO2 in the spinel
solid solution exhibit strong positive deviations from Raoult's law over most of the
composition range. However, activity of Mg0.5CrO2 exhibits mild negative deviation for
compositions rich in Mg0.5CrO2. The activity-composition relationship in the spinel solid
solution is analyzed in terms of the intracrystalline exchange of cations between the
tetrahedral and octahedral sites of the spinel structure. The intracrystalline ion exchange is
governed by site preference energies of the cations. The difference between the Gibbs energy
of mixing calculated using the cation mixing model and the experimental data is taken as a
measure of the strain contribution arising from the difference in the radii of Al3+ and Cr3+
ions. The large positive strain enthalpy suggests the onset of immiscibility in the spinel solid
solution at low temperatures. The computed critical temperature and composition for phase
separation are 802 (±20) K and XMgCr2O4 = 0.46 (±0.02), respectively[52].
Solid Solution Pigments
An investigation of the reaction products of aluminium hydroxide-chromium nitrate

mixtures at 200° and 1000°C with molar ratios 9:1, 8:2, 7:3, 6:4, 5:5 and 4:6 was carried out.
The products resulting at 200°C were characterized by XRD, IR and diffuse reflectances
spectra (DRS) as mixtures ofhexavalent chromium compounds with general formula
Al2O3Aln(OH)3n−2-iCrO4, Al2(OH)4CrO4,Al2CrO4)2Cr2O7, and Al2O3Cr2(CrO4)2-Cr2O7. Upon
heating at 1000°C for 12 h transformation into (Al1−x CrxO3 ) solid solutions took place. The
compositions were estimated from plots of lattice parameter values versus compositions of
mixed crystals. The solid solutions were examined in order to test their suitability as pigments
in comparison with the well-known green chromium oxide pigments. They showed a high
degree of stability towards water, organic solvents, acids, alkalis, light and heat and had in
addition reasonable hiding power. Their good properties indicate that they can be used as
satisfactory pigments for coating applications [53].
The presence of these hexavalent chromium compounds was verified by the presence of a
charge transfer band in the UV region in addition to the presence of characteristic vibrational
bands in the IR region.
The chromates and dichromates are converted into definite solid solutions of Cr2O3 in
A12O3 and vice versa on heating above ca. 480°C. The composition of such crystalline solid
solutions is estimated from the plot of lattice parameter values versus composition of
AlxCr2−xO3 mixed crystals [54-56].
Thermal decomposition of aluminium nitrate and chromium nitrate was carried out. The
decomposition products of these salts at 250, 350, 500, 750 and 1000 ° C were characterized
by means of chemical analysis, IR, diffuse reflectance and X-ray diffraction. The same
studies were also carried out on three mixtures of aluminium and chromium nitrates with
molar ratios 3 :1, 1:1 and 1:3, where two intermediates were produced from each mixture in
the temperature range 375–475 °C. These were AlCrO3Al(OH)CrO4, Al2O3Al3(OH)7CrO4
Al0.67Cr1.33O3Al2(CrO4)2Cr2O7, Al2(OH)4CrO4 Al1.33Cr0.67O3Cr2(CrO4)2Cr2O7, AlCrO3Al
(OH)CrO4.The dichromates or chromates with an Al/Cr ratio of less than 1 are transformed to
corresponding solid solutions of Al2O3, in Cr2O3 at about 500 °C, whereas those with an
Al/Cr ratio of more than 1 are transformed to solid solutions of Cr2O3 in Al2O3 at
temperatures above 750 °C. The corresponding solid solutions of the above-mentioned
dichromates and chromates are (Al0.5Cr0.5)2O3, (Al0.83Cr0.17)2O3 (Al0.33Cr0.67)2O3,
(Al0.67Cr0.67)2O3 (Al0.17Cr0.832O3, (Al0.5Cr0.5)2O3 [57].
TOXICITY OF CHROMIUM COMPOUNDS
Chromium (Cr)-doped materials have been widely investigated as ceramic pigments.

Malayaite pigment chemical formula (CaSnSiO5) is one of the important red pigments used in
the ceramic and polymer industries. These industries use Cr ions as the active chromosphere
agent. (1) Cr(VI) is recognized as a carcinogenic and mutagenic agent. In addition, Cr(VI)
leads to liver damage, pulmonary congestion, and causes skin irritation, resulting in ulcer
formation. Because of its high toxicity (acute and chronic) and carcinogenicity, Cr (VI) needs
to be controlled. Cr-containing waste is recycled as a secondary raw material in the ceramic
industry, which could help reduce the quantity. In the literature, many solutions are indicated
for reuse of the wastewater; most of them are the preparations of green chromium oxide
(Cr2O3) and lead chromate (PbCrO4) [58].
The toxicity associated chromium (VI) is mainly due to generation of reactive oxygen
species (ROS) with subsequent oxidative deterioration of biological macromolecules. Both
nickel and chromium can generate free radicals (FR) directly from molecular oxygen in a two
step process to produce superoxide anion and in continued process, produce highly toxic
3442 Mohammadd Fikry Ragai Fouda,
F Hanann.F.Abdel-Haliim et al.
hyydroxyl radical. The pro-ooxidative effeccts are compoounded by fact that they also a inhibit
anntioxidant enzzymes and depplete intracelluular glutathionne [59,60].
Also they differentially inhibit macroomolecular syyntheses in BKH B cells, thaat of DNA
beeing always th he most affectted. Among Cr C (III) compoounds, which generally havve very low
cyytotoxicity, chhromite is partticularly active, and inhibitss cell growth anda DNA synthesis even
m
more than the poorly soluble Cr(VI) com mpounds. Preinncubation in growth
g mediuum, with or
w
without metabo olizing cell cultures,
c solubbilizes considerable amounnts of Cr(VI) from zinc
yeellow and chhromite, but significant
s am
mounts are alsso obtained from fr the most insoluble
C
Cr(VI) pigmentts. When BHK K cells are treeated with such preincubated solutions, reeduction of
sooluble Cr(VI) to Cr(III) by cell
c metabolitees is seen withh all Cr(VI) coompounds, acccompanied
by y decreased cytotoxicity.
c T same diffferences betw
The ween Cr(VI) and Cr(III) compounds
c
appply to the cy ytotoxic effectts on mitosis of HEp cellss and the clastogenic effectts on CHO
vity of chromitte, the only Crr(III) pigment capable of siggnificantly inccreasing the
ceells. The activ
frrequency of SCE, is due too contaminatioon with solublle Cr(VI). In contrast to the very low
cyytotoxicity of Cr(III), muchh higher chrom mium levels arre detected in the cells incuubated with
sooluble Cr(III) than with thhe same conncentrations of soluble Cr((VI). 50% annd 75% of
chhromium accu umulated in thhe cells durinng treatments with Cr(VI) and Cr(III) reespectively
reemains firmly bound to thee cells, even when w they aree incubated foor up to 48 h in normal
grrowth medium m. Chromium m accumulatedd in the cells after treatmeent with Cr(IIII) is most
prrobably boundd to the cell membrane,
m whereas some off the Cr(VI) iss transported through
t the
ceell membrane and reduced in i the cell nuccleus. The results of the preesent investigaation are in
aggreement with h those obtained with the saame Cr(VI) annd Cr(III) com mpounds in muutagenicity
asssays in bacteria and carcinnogenicity testts in rodents. A re-evaluatioon of the mechanisms of
chhromium carcinogenisis is proposed.
p
Hexavalentt chromium Cr(VI)
C is a reespiratory toxxicant and carrcinogen, withh solubility
pllaying an impportant role inn its carcinogeenic potential . Zinc chrom mate a water innsoluble or
paarticulate Cr(VVI) compoundd, has been shoown to be carccinogenic in epidemiology
e studies and
too induce tumoors in experim mental animals, but its gennotoxicity is poorly underrstood. Our
sttudy shows th hat zinc chrom mate induced concentrationn-dependent inncreases in cyytotoxicity,
chhromosome daamage and DN NA double strrand breaks inn human lung cells. c In respoonse to zinc
chhromate-inducced breaks, MRE11M expreession was inncreased and ATM and ATR A were
phhosphorylatedd, indicating thhat the DNA double strandd break repairr system was initiated in
thhe cells. In adddition, our datta show that zinc
z chromatte -induced doouble strand breaks
b were
onnly observed in the G2/M phase populaation, with noo significant amount a of douuble strand
brreaks observeed in G1 annd S phase cells. c These data will aidd in understaanding the
m
mechanisms off zinc chromate toxicity and carcinogenes is [61].
Lead chrom mates are resppiratory carcinnogens in expeerimental anim mals and suspected to be
soo in humans. It induces neeoplastic transsformation in cultured cells but the mecchanism of
geenotoxicity iss unknown. Examination
E t effect of lead chrom
the mate on the inntegrity of
chhromosomes of o Chinese ham mster ovary (C CHO) and hum man foreskin fibroblasts (H HFF) after a
244-h exposure. At 0.4 μg/cm m2, 0.8 μ/cm2, 2 μg/cm2 and a 8 μg/cm2 lead chromatte particles
reeduced survivaal of CHO cellls to 86%, 62% %, 2% and < 1% respectiveely. These conncentrations
innduced a dosee-dependent 4–19-fold
4 incrrease in the percent metaphhases with daamage. The
H cells exhib
HFF bited higher seensitivity in booth cytotoxicitty and clastoggenicity. The spectrum
s of
daamage observ ved for both ceell types was primarily achhromatic lesions affecting one o or both
chhromatids [62].To test for particle
p dissoluution effects, CHO cells weere treated forr 24 h with
Chrom
mium Pigmennt 343
eiither clarified medium thatt had been inncubated for 24 2 h with leadd chromate particles,
p or
cllarified mediu um that had beenb pre-condditioned by CHO cells treaated with leadd chromate
paarticles for 24 2 h. No dam mage was dettected in thesse cells, indiccating that exxtracellular
diissolution intoo ionic lead and chromatee did not conntribute to thhe genotoxicitty. This is
coonsistent with h a previouss study in which w scanniing electron micrographs illustrated
innternalization of the particlees. These resuults suggest thhat clastogenessis may be a mechanism
m
foor lead chromaate induced caarcinogenesis [63]. [
Lead chromate caused dose-related increases in chromosomee aberration and sister-
chhromatid exchhange in hum man lymphocyttes. No increaase in DNA damage d was observed
o in
C
CHO cells, po ossibly due too the relativee insensitivityy of the CHO O cells and thet limited
soolubility of lead chromate in i tissue cultuure medium. TheT mutagenicity of lead chromate in
huuman lympho ocytes appearrs to be entirrely due to the t chromate ion since chhromosome
abberrations werre induced by potassium chrromate but nott lead chloridee [64].
However,C Cr(VI)-inducedd inflammatoory/immunoloogical responnses, and altteration of
suurvival signaliing pathways. Cr(VI) enters the cell throough non-speccific anion chaannels, and
iss metabolically y reduced by agents includding ascorbatee, glutathione, and cysteinee to Cr(V),
C
Cr(IV), and Cr((III). Cr(III) has
h a weak mem mbrane permeeability capaciity and is unabble to cross
thhe cell membrrane, thereby trapping
t it witthin the cell where
w it can biind to DNA annd produce
geenetic damagee leading to genomic g instaability. Structtural genetic lesions
l producced by the
inntracellular reduction of Crr(VI) include DNA adductts, DNA-strannd breaks, DN NA-protein
crrosslinks, oxidized bases, abasic sites, and DNA innter- and intrrastrand crossslinks. The
daamage induceed by Cr(VI) can lead to dysfunctionall DNA repliccation and traanscription,
abberrant cell cycle checkppoints, dysregulated DNA A repair mechanisms, microsatelite
m
innstability, infllammatory responses, and the disruptioon of key reggulatory genee networks
reesponsible forr the balance of o cell survivaal and cell deeath, which may all play ann important
roole in Cr(VI)) carcinogeneesis. Several lines of eviddence have inndicated that neoplastic
prrogression is a result of connsecutive geneetic/epigenetic changes that provide cellullar survival
addvantages, and d ultimately leead to the connversion of noormal human cellsc to malignnant cancer
ceells. This review is based on o studies thatt provide a glimpse into Crr(VI) carcinoggenicity via
m
mechanisms inncluding Cr(V VI)-induced death-resistanc
d ce, the involvvement of DNAD repair
m
mechanisms in
n survival afteer chromium exposure, andd the activatioon of survivaal signaling
caascades in resp ponse to Cr(VVI) genotoxicitty.
There is an n intracellularr redox pathwway in the mettabolism of thhe carcinogen chromate
assThe capacity of glutathionee (GSH) to redduce Cr(VI) too Cr(III) in vittro was investiigated. The
reeaction was deetermined specctrophotometrrically by folloowing the absorption of Cr((VI0 at 370
nm m. At stoichio ometric condittions (molar raatio Cr(VI)/GSH of 1:3) thee reduction was w strongly
deependent on th he solution's pH.
p It was muuch slower at pH p 7.4 than att pH values beelow 5. An
exxcess of GSH H (100- or 10000-fold) accelerated the reaaction. In any case, 3 GSH molecules
w
were required to reduce 1 molecule of chromate. Incubation I off human red blood
b cells
(RRBC) with an excess of of Na N 2CrO4 (10 mM)m decreased the GSH coontent of the ceells to 10%
off the original amount. This depletion of GSH was sim milar to that obbtained when RBC were
inncubated with 62 mM diethyylmaleate (DE EM), a well knnown GSH deppleting agent.
Sephadex G-100G chromaatography of lyysates from huuman RBC inncubated with radioactive
chhromate (51Cr((VI)) showed a strong affinnity of 51Cr forr hemoglobin: 97% of the appplied dose
w bound to hemoglobin whilst only minor amounnts of 51Cr were
was w found inn the low-
m
molecular fracttions. However, incubationns of preparedd lysates (as opposed to inntact cells)
3444 Mohammadd Fikry Ragai Fouda,
F Hanann.F.Abdel-Haliim et al.
with 10 mM Na
w N 251CrO4 maarkedly raised the chromium m content of low-moleculaar fractions
(pprobably GSH H-Cr-complexees), probably indicative off a role of GSH G in the inntra-cellular
reeduction of Crr(VI) to Cr(IIII), the latter beeing regarded as the ultimaately toxic species of this
m
metal.
The toxic effects of Cr have been sttudied on thee photosynthettic activity off Spirodela
poolyrhiza by means
m of the chlorophyll
c a (Chl a) fluorrescence transsient O-J-I-P. The Chl a
fluorescence trransients werre recorded in i vivo with high time resolution
r andd analyzed
acccording to th he JIP-test whhich can quantify the photoosystem II behhavior. Cr treated plants
shhow a decreasse in yield forr primary phootochemistry, Po. The perfformance indeex of PSII,
PIIABS, which iss the combinattion of the inddexes of threee independent parameters, (1) the total
nuumber of acctive reactionn centers peer absorption (RC/ABS), (2) yield of o primary
phhotochemistryy ( Po) and (33) efficiency withw which a trapped
t excitoon can move an a electron
innto the electroon transport chhain (ψ0), deccreased due too Cr treatmentt. Chromate sensitivity
vaaries within pllant populations. The main targets of Cr, according to the t JIP-test, caan be listed
ass a decrease in i the numberr of active reaaction centerss and damage to the oxygeen-evolving
coomplex [65]. Breathing
B highh levels of chrromium (VI) can
c cause irritaation to the noose, such as
ruunny nose, nosebleeds, and ulcers and hooles in the nassal septum. Inggesting large amountsa of
chhromium (VI)) can cause stoomach upsets and ulcers, convulsions,
c k
kidney and liver damage,
annd even deathh. Skin contacct with certainn chromium (V VI) compoundds can cause skin s ulcers.
Soome people arre extremely sensitive
s to chhromium (VI) or chromium m (III). Allergiic reactions
coonsisting of seevere redness and
a swelling of o the skin havve been noted..
Cr (VI) is not
n a very stabble state whenn compared too Cr (III). Thee Cr (VI) is a veryv strong
oxxidizing agentt (therefore veery fast in reaccting, unlike Cr
C (III) and likeely to form coomplexes).
The main reason
r why Crr (VI) is so tooxic is that onee of the reducction products of Cr (VI)
iss Cr (V). Chro ome (V) is a known
k carcinoogen and will lodge in any tissue
t to form
m cancerous
grrowths. In the body, the aciddity and actionn of enzymes on Cr (VI) wiill promote thee formation
inn small quantitties of Cr (V). However, ass the size of thhis is normallyy too large to be adopted
by y a tissue, thee Cr (V) will pass
p out. The only place whhere the Cr (V V) is likely to lodge is in
soome of the fine capillaries inn the kidneys, intestines or lungs.
l
During the passage out, Cr (VI) will continue
c to oxxidize anythingg it can, leavinng deposits
off the relativelyy safe Cr (III) and completely unsafe Cr (V)( behind [666].
Animal stu udies also show that Cr (VII) is generallyy more toxic than t Cr (III), but neither
oxxidation state is very toxic by the oral route.
r Chromium(VI) causees hepatotoxiccity in both
m and laboraatory animals [67]. Studies of
man o workers in the chrome piigment industrry revealed
a correlation beetween exposuure to Cr (VI) and lung canccer [68]. Chroomium (VI) caan act as an
oxxidant directly y on the skin surface or it can be absorbbed through thhe skin, especcially if the
skkin surface is damaged.
d
REFFERENCESS
[11] J. L. Morrning, Chromiuum, U. S. Burr. Mines Rpt. MCP-1,1977.
M
[22] P. R. Graabfield, "Chrom
me Ore Sourcces and Availaability with Em
mphasis on Meetallurgical
Use", Ironn and Steel Metallurgy,
M 19775, 16-26; 19775, 27-35.
A
A. H. Sully-and E. A. Braandes, Chromiuum, Plenum Publ.
P Corp. Neew York, 2nd ed., 1967 .
B. L. Rollinson, The Chemistry of Chromium, Molybdenum and Tungsten, 21, Pergamon

Texts in Inorganic Chemistry ,1975.
[3] O. Kirk, Encyclopedia of Chemical Technology, 3rd ed., part 6 John Wiley& sons.
New York, 1979.
[4] W. H. Hartford, Chromium, in A. J. Bard, ed.. Applied Electrochemistry of the
Elements, Marcel Dekker, New York, Oct. 1977 .
[5] F. A. Loewenheim and M. R. Moran Faith, Keys, and dark's Industrial Chemicals. 4th
ed., Wiley-mterscience, New York, 716-721,1975 .
[6] T. C. Patton, Pigment Handbook, 1, Wiley-mterscience, New York, 1947 .
[7] C. H. Love, Important Inorganic Pigments, Hobart, Washington, D. C.1947 .
[8] Inorganic Chemicals, Report M28A (76)-14, U. S. Bureau of the Census, Washington,
D. C. (1977) .
[9] Ref.9.pp., 357-389.
[10] W. H. Hartford in F. D. Snell and L. C. Ettre, eds., Encyclopedia of Industrial Chemical
Analysis, part 17, John Wiley & sons. New York, 197- 201,1973 .
[11] Ref 9, pp., 351-357.
[12] Ref.9, pp., 843-861.
[13] R. A. Smith, Quo Vadis Chromium, Producers Council of Canada, Toronto, (copies
available from Allied Chemical Corp.) Syracuse, New York, (1976).
[14] R.I. Lazău, Cornelia Păcurariu , D. Becherescu and R. Ianoş. Ceramic pigments with
chromium content from leather wastes .J. of the European Ceramic Society 2007, 27,
1899-1903.
[15] M. J. Udy, Chromium, Chemistry of chromium and its compounds, vol 1, Reinhold
Publishing Co., New York, pp., 283-301, 1956 .
[16] H. A. Lubs, The Chemistry of Synthetic Dyes and Pigments, Robert E. Krieger
Publishing Co., Huntington, N. Y., pp. 153, 160, 161, 247, 258, 261, 284, 426, (1972).
[17] Brown spinel pigments based on zinc chromite, method of their production and use
[18] United States Patent 5254162
[19] R. F. Her, Wemer-type chromium complexes. U. S. 2,683, 1954.156 .
[20] T. S. Reid, Chromium coordination complexes of saturated perfluoromono- carboxylic
acids. U. S. 2,662,835, 1953.
[21] Ernst and Ernst, Proc. Am. Wood Preservers Assoc. 73, 186,1977.
[22] Ref. 18, pp.283-422.
[23] Chemical Sources USA, Directories Publishing Co., Flemington, N. J., 1977.
[24] Chemical Week 1979 Buyers'Guide Issue, McGraw-Hul, New York, 1978.
[25] 1976-1977 OPD Chemical Buyers' Directory, SchneU Publishing Co., New York,
(1976).
[26] M.F.Fouda,R.S.Amin and S.A.Moustafa,E.A.Yousseff and A.Ismail;Preparation and
Characterization of Chromites As Safe Pigments Suitable For Practical Applications,To
be published elsewhere.
[27] Combustion and Flame. Rubies and Spinels As Chromium Coloring, Materials, 1970,
14,73-83.
[28] P.,Nathawan; VS.,Darshane . Structural, Transport, magnetic and infrared studies of the
oxidic spinels Co2-XTi1-XFe2XO4. Journal of Physics. 1988, 21,3191-3203.
[29] VM.,Vlasenko; VL.,Chernobrivets. Methane chlorination on spinel copper-chromium

catalyst in the presence of oxygen. Russian Journal of Applies Chemistry. 1998;
71,1393-1396.
[30] E.,Erran; F.,Trifino; A.,Vaccari ; M.,Richter . Structure and reactivity of Zn-Cr mixed
oxides Role of non-stoichiometry in the catalytic synthesis of methanol. Catalysis
Letter. 1989, 3,65-72.
[31] MSC., Câmara; PN., Lisboa-Filho; MD., Cabrelon; L., Gama; WA., Ortiz; CO., Paiva-
Santos; ER., Leite; et al. Synthesis and characterization of Li2ZnTi3O8 spinel using the
modified polymeric precursor method. Materials Chemistry and Physics. 2003, 82,68-
72.
[32] McClure D. The distribution of transition metal action in spinels. Journal of Physical
Chemistry Solids. 1957, 3,311-317.
[33] Roy S, Ghose J. Synthesis and studies on some cooper chromite spinel oxide
composites. Materials Research Bulletin. 1999, 34,1179-1186.
[34] Jendrzejewska I. Influence of nickel substitution on the crystal structure of CuCr2Se4.
Journal of Alloys Compounds. 2000, 305.90-92.
[35] I.,O., Kozlowska ; J.,Kopyczok; HD.,Lutz; TH.,Stingl. Single-crystal structure
refinement os spinel-type CuCr2Se4. Acta Crystallographica Section C - Crystal
Structure Communications. 1993, 49,1448-1449.
[36] Preudhomme J, Tarte P. Infrared studies of spinels-III. The normal II-III spinels.
Spectrochimica Acta Part A: Molecular Spectroscopy. 1971, 27,1817-1835.
[37] S.,Chokkaram ; R.,Srinivasan;,DR., Milbrun ; HB.,Davis .Conversion of 2-octanol over
nickel-alumina, cobalt-alumina, and alumina catalysts. Journal of Molecular Catalysis
A: Chemical. 1997, 121,157-169.
[38] M P .,Pechini. US Patent. 3330697, 1967.
[39] PA .,Lessing .Mixed-cation powders via polymeric precursors. American Society
Ceramic Bulletin. 1989, 68,1002-1007.
[40] HD., Lutz; G.,Waschenbach; G.,Khiche; H., Hacuseler . Latice vibration-spectra .33.
far-infrared reflection spectra, to and lo phonon frequencies, optical and dielectric-
constants, and effective charges of the spinel-type compounds MnCr254, FeCr254,
CoCr254, ZnCr254, CdCr254, HgCr254, ZnCr25E4, CdCr25E4, HgCr25E4, MnIn254,
FeIn254, CoIn254, NiIn254, CdIn254, HgIn254. Journal of Solid State Chemistry.
1983, 48,196-208 .
[41] D.,Basak; J ,Ghose. Infrared studies on some substituted copper chromite spinels.
Spectrochimica Acta Part A: Molecular Spectroscopy. 1994, 50,713-718.
[42] P. A. Lewis. Pigment Handbook, John Wiley & Sons, New York 1988, 2nd Edition,
Volume 1, 777-784.
[43] E., Ozel and S., Turan. Production and characterisation of iron-chromium pigments and
their interactions with transparent glazes . Journal of the European Ceramic Society, 23,
2003, 2097-2104 .
[44] Á. G. De la Torre; M. A. G. Aranda ; L., León-Reina; J. Pérez.International Journal of
Applied Ceramic Technology Ceramic Pigments and the European REACH
Legislation: Black Fe2O3–Cr2O3, a Case Study.2010
[45] S., H., Murdock ;R., A., Eppler. Zinc Iron Chromite Pigments. J. American Ceramic
Society. 1988 71,212–214.
mium Pigmennt
Chrom 347
[446] Preparatio on of a mixedd-phase pigmeent based on irron oxide and chromium oxxide United
States Patent 4643772.
[447] Brown sppinel pigmentts based on zinc z chromite, method of thheir productioon and use
United Sttates Patent 52254162.
[448] Pigment consisting of a mixture of chromium
c oxiide and iron oxide
o useful inn high infra
red reflecctance gray vinnyl compositioon. United Staates Patent 46224710.
[449] Brown sp pinel pigmentts based on zinc z chromite,method of thheir productioon and use
.United States
S Patent 5254162.
[550] K.,MASA AHIRO;U.,HIDERO;T., MIINORU.Colorr Modificationn of Chromium m-Tin Pink
Pigment by Substitutiion of Ti forr Sn. Journall of the Ceraamic Society of Japan.
2000,108 8,478-481.
[551] K.,T., Jaacob ;C.K.,Beehera. Spinel-corundum eqquilibria and activities
a in the
t system
MgO-Al2O3-Cr2O3 at 1473 K. Meetallurgical annd materials transactions.
t B Process
B,
metallurggy and materiaals processing,, Science 20000, 31, 1323-1332 .
[552] M. F. R. Fouda ; R. S.. Amin;M. A. Abd El-Ghafffar . Preparatiion and physiccochemical
characterrization of (All1−xCrx)2O3 sollid solutions as
a inorganic grreen pigmentss. Dyes and
Pigmentss. 1991, 15,2999-306.
[553] M.F.R. Fouda,
F R.S. Ammin and M.M.. Selim. Therm mal and spectrroscopic charaacterization
of reaction products of aluminium m hydroxyaceetate-chromium m nitrate inteeraction at
different temperaturess. Thermochimica Acta. 1989,144, 141-150. 1 [55]]review of
hexavalen nt chromium.. CAS No. 18540-29-9,
1 T
Toxicological Profile for Chromium.
C
Agency forf Toxic Subbstances, U.S S. Public Health Service, Report
R No. ATSDR/TP-
A
88/10, 19989.
[554] EPA web bsite. Toxicollogical U.S. Environmental
E l Protection Agency,Washi
A ington DC,
1998.
[555] M. F. R. R Fouda, R. R S. Amin and M. M. Selim. Therrmal and speectroscopic
characterrization of reeaction produucts of al-nitrrate-Cr-nitratee interaction at various
temperatu ures, Thermocchimica Acta. 1989, 141, 2777-291.
[556] Z., Le; P.,
P Zhenbang;; Y., Chao; T., T Xike; Z., Suxin.Synthessis of Chrom mium-doped
malayaitee pigments fromfr wastewaater containinng low chrom mium(VI).(TECHNICAL
PAPER)((Report) Journnal of the Air & Waste Mannagement Assoociation, 2010.
[557] Al Ame.A Comprehennsive Review w on Nickel (II) ( And Chrromium VI Toxicities
T –
Possible Antioxidant (Allium Sativvum Linn) Defenses.Kusall K.Das. en J Med Sci.
2009, 2 ,443 -50.
[558] P., T. LaPPuma; J., M., Fox and E., C. C Kimmel. Chhromate Conccentration Bias in Primer
Paint Parrticles .Regulaatory Toxicoloogy and Pharm macology, 20001,33, 343-3449. H., Xie;
A., L., Ho olmes ;J. L. Young
Y ;Q., Qinn ;K., Joyce; S.
S C., Pelsue ;C
C., Peng ;S.,SS., Wise ;A.
S. Jeevarrajan; W., T., Wallace; D., Hammond annd J. P. Wise . Zinc chromaate induces
chromoso ome instabilityy and DNA doouble strand brreaks in humaan lung cells .T Toxicology
and Appllied Pharmacoology, 2009, 2334, 293-299 .
[660] [62] J.J. McAughey, A.M.A Samuel, P.J. Baxter anda N.J. Smith. Lead, Chroomium and
Thalliumm: Toxicity, Environmental
E l and Health Impact, and Regulation Sources S of
human exxposure. Bioloogical indicator Biological monitoring of o occupationaal exposure
in the chhromate pigm ment productiion industry. Science of The T Total Ennvironment,
1988, 71,, 317-322.
[61] J., Wise; J., Leonard and S., R. Patierno. Clastogenicity of lead chromate particles in
hamster and human cells. Mutation Research/Genetic Toxicology, 1992, 278, 69-79 .G.,
R. Douglas; R.D.L. Bell; C.E. Grant; J.M. Wytsma and K.C. Bora. Mutation
Research/Genetic Toxicology, 1980, 77,157-163.
[63] Effect of lead chromate on chromosome aberration, sister-chromatid exchange and
DNA damage in mammalian cells in vitro. K.,J. Appenroth, J. Stöckel, A. Srivastava
and R. J. Strasser. Environmental Pollution, 2001, 115, 49-64 .
[65] Multiple effects of chromate on the photosynthetic apparatus of Spirodela polyrhiza as
probed by OJIP chlorophyll a fluorescence measurements. Combustion and Flame.
1970,14, , 3-83.
[67] P .,Nettesheim; Jr.,Hanna; DG.,Doherty ; RF.,Newell; A.,Hellman .Effect of calcium
chromate dust, influenza virus, and 100 R whole-body X-radiation on lung tumor
incidence in mice. J Natl Cancer Inst. 1971, 47, 1129-1138.
[68] R ,Frentzel-Beyme. Lung cancer mortality of workers employed in chromate pigment
factories. A multicentric European epidemiological study. J Cancer Res Clin
Oncol,1983. 105, 183-188.
Chapter 9
TRANSITION METALS: BIOINORGANIC AND REDOX

REACTIONS IN BIOLOGICAL SYSTEMS
Marisa G. Repetto1* and Alberto Boveris2

1
General and Inorganic Chemistry
2
Laboratory of Free Radical Biology (PRALIB; UBA-CONICET),
School of Pharmacy and Biochemistry, University of Buenos Aires,
Buenos Aires, Argentina
ABSTRACT
Transition metals are elements located in the middle section of the periodic table
within groups 3 and 12 that have incomplete inner electron shells and are, in terms of the
outermost electron shell, intermediate between the most and the least electropositive in
the series of elements. All the transition metals have certain properties in common: they
have a partially filled d-shell, as elements and in their compounds, except Zinc (Zn); they
are all metals, malleable and ductile; they have high melting and boiling points; and their
ions form complexes and colored compounds (except scandium, and Zn) with various
coordination numbers and geometries. These elements have more than one electron shell
capable of acting with different oxidation numbers, they can accept or give various
numbers of electrons per atom. This wealth of electron mobility is highly effective in
conducting electricity, so transition metals are good conductors either as pure metal or as
alloys. Physically mixed with silica, transition metals generate semiconductors, the
essential part of transistors and chips. Due to their strong atom bonding, these metals are
useful in metallurgy for their ductility and malleability and in industrial catalysis, where
the transition metals participate with their mobile electrons in the reaction without
affecting the metal lattice. A limited amount of transition metals is present in biological
organisms, where they are part of essential and vital proteins and enzyme active centers.
In this way, small amounts of the transition metals constitute minerals necessary for life.
The more important processes and reactions in mammals derived directly from their
aerobic life, i. e., oxygen transport in blood, cellular respiration and inactivation of the
*
Corresponding Author: Prof. Dr. Marisa G. Repetto. Department of General and Inorganic Chemistry. School of
Pharmacy and Biochemistry. University of Buenos Aires. Junin 956. Buenos Aires 1113AAD,
Argentina.TEL: 54-11-4964-8249; FAX: 54-11-4508-3653; E-mail: mrepetto@ffyb.uba.ar
350 Marisa G. Repetto and Alberto Boveris
radical superoxide and hydrogen peroxide, occur at transition-metal centers. However,

transition metals became toxic to cells at elevated tissue concentrations. The
understanding of the metabolism of oxygen free radicals in mammalian cells has shown
that transition metals, notably iron (Fe) and copper (Cu), and in a lower proportion
Chromium and vanadium, undergo redox cycling, involving the Fenton-like production
of superoxide anion, hydrogen peroxide and hydroxyl radicals, while cadmium, mercury,
and nickel deplete the endogenous cytosolic antioxidants, reduced glutathione and
protein-bound sulphydryl groups, resulting in both cases in toxicity of the transition
metals. The cytoxicity of the transition metals is currently explained by the sequential
stages of reversible oxidative stress and irreversible oxidative damage. Oxidative
breakdown of biological phospholipids and protein macromolecules occurs in most
cellular membranes including mitochondria, microsomes, peroxisomes and plasma
membrane. The toxicity of transition metals in mammals generally involves
neurotoxicity, hepatotoxicity and nephrotoxicity. Specific differences in the toxicities of
metal ions derive from the differences in chemical properties, electronic configuration
and oxidation-reduction potentials. The two more important redox-active biometals, Fe
and Cu, promote lipid peroxidation by hydrogen peroxide decomposition and direct
homolysis of endogenous hydroperoxides. The understanding of the effects of transition
metal ions on biomolecules is relevant to prevent oxidative damage and toxicity in
biological systems. In this chapter, we highlight the current understanding and some of
the new insights into bioinorganic chemical reactions and into the functions and toxicity
of transition metals.
INTRODUCTION
The transition metals are the group of metals in the middle section of the Periodic Table
of Elements, in groups 3 to 12. They are considered as divided in three groups: the first row,
the second row and the third row transition metals. There are in total 38 transition metals,
including such common metals as iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), silver (Ag),
gold (Au), and mercury (Hg). These metals have similar chemical properties, easily alloy with
other metals, and have useful properties for metallurgy and industrial catalysis [1-4] (Figure
1).
Figure 1. Transition metals’ classification in the Periodic Table. Elements in white background are trace
and essential elements, necessary for living organisms; in dark gray, very toxic elements; in
intermediate gray, moderate toxic; in clear gray, low toxic; and in black, radioactive elements.
Transition Metals 351
Due to their malleability and ductility, conductive electrical properties, and catalytic
properties, transition metals are used in building construction, as electricity conductors, and
as industrial catalysts.
TRANSITION METALS: PHYSICAL PROPERTIES AND USES

Transition metals have useful structural properties. Elements such as Cu and Fe can be
bent into different shapes, while remaining strong enough to support significant weights. This
makes the transition metals good to be used in building and appliance construction. The
bonding of the atoms in the metal lattice is very strong in transition metals. As a result,
transition metals are strong metals, with high melting and boiling points, and high density.
Well-known and representative transition metals are Fe, Cu, Ag, Au and Hg [1]. The ease of
bending and the property of stretching without breaking are advantages of transition metals.
These metals are known for being ductile (they can be stretched) and malleable (they can be
hammered into various shapes) [1]. Transition metals are commonly used to create alloys,
which are combinations of metals and/or non-metallic substances. Many well-known
substances are alloys made of transition metals. Fe is combined with carbon and a variety of
other substances to make steel, and the inclusion of chromium (Cr) makes it stainless steel.
Cu makes up several well-known alloys: it is mixed with Zn to create brass, combined with
tin to form bronze and mixed with Ni to form cupro-Ni, which is often made into coins [2].
Transition metals have a wealth of electrons in inner electron layers that are also
incomplete, in such way that the atoms easily take or release a number of electrons per atom.
The easy electron mobility in transition metals is the property that gives the basis for their two
main uses: electricity and heat conductors and industrial catalysts. Transition metals such as
Cu, Zn and Au can be stretched out into wires to transmit electricity. Conducting wires in the
power lines are commonly made of Cu. Additionally, many light bulbs have filaments made
of tungsten, which has a very high melting point [3].
Three transition metals, in particular Fe, cobalt (Co) and Ni, are capable of producing a
magnetic field; the metals and their compounds are paramagnetic; and they are affected by
magnetic fields. Given this versatility, transition metals are used to create materials that are
intentionally responsive or unresponsive to magnetic fields. Furthermore, Fe, Co and Ni are
used to create ferromagnetic solids, objects that create a magnetic field. Compass needles and
bar magnets, for example, are ferromagnetic [4].
Transition metal compounds (often oxides) of Cu, Fe, Cr and Co are used as pigments for
artwork; they give bright colors to stained glass and ceramics and pottery glazes. Unlike
alkali metals like potassium and sodium, many of the transition metals are not reactive to
water or oxygen. When they do form salts, the resulting substance is often colored. The
compounds used in making pigments and other coloration involve transition metals oxides
and salts. Fe, Cu, Cr and titanium (Ti) are transition metals used widely in the pigmentation
of substances, such as foods and artistic supplies. For example, Ni chloride is green, and Ti
chloride is purple [2, 3].
Transition metals are widely used in the production of semiconductors. A semiconductor
is a material with electrical conductivity due to electron flow (as opposed to ionic
conductivity), intermediate in magnitude between that of a conductor and that of an insulator.
They are used for manufacturing modern electronics, including computers, telephones, radio,
TV sets and many other devices, such as transistors, solar cells, many kinds of diodes
including the light-emitting diode, the silicon controlled rectifier, and digital and analog
integrated circuits. Recent studies have increased our understanding of the nanotoxicity of the
metal oxide particles used in semiconductor materials. People who work in the production or
in recycling computers are at the greatest risk for a toxic exposure to heavy and transition
metals, such as lead (Pb), Cr, Cd (Cd) and Hg. The toxic chemicals in computers are linked to
many health problems: Hg can cause permanent brain damage, and reproductive and
developmental harm; Cd is known to cause cancer. The oxides of the transition metals of the
fourth period are widely used in industry and biotechnology. Recent studies and reports
indicate that the toxicity of the nanoparticles of these metals is compellingly related to
oxidative stress and oxidative damage. The phase of oxidative stress and damage is followed
by alteration of calcium (Ca) homeostasis, by inflammatory responses, and by abnormal
cellular signaling and gene expression. The precise physicochemical properties that make the
toxicity of nanoparticles have yet to be defined, but may include element-specific surface
catalytic activity (e.g., metallic or semiconducting properties), and nanoparticle uptake or
dissolution. Nanoparticles are frequently applied directly on human body for purposes such as
diagnostics. Toxicological literature reveals a trend, including several transition metal oxides
(TiO2, CuO and ZnO, oxides of Cr, manganese (Mn), Fe, Co, Ni, Cu, and Zn), which are
widely used in industry [5].
Some transition metals and transition metal oxides and compounds are used as industrial
catalysts to speed up reaction rates. Due to their strong atom bonding, transition metals
participate in the catalyzed reactions forming adducts with their mobile electrons without
affecting the metal lattice, with catalyst recovered from the process. In the hydrogenation of
vegetable oils to turn them into saturated fats (with higher melting point), Ni is used as a
catalyst so the hydrogen molecule can effectively join a carbon-carbon double bond [4].
Another example is given by automobiles that have an emissions-control device called a
catalytic converter. This device contains a screen of platinum or palladium, along with the
metal rhodium. The presence of the transition metal, along with the heat of combustion
generated by the automobile engine, causes the exhaust coming from the internal combustion
engine to be broken down from partially burned hydrocarbon compounds into less harmful
compounds such as water vapor and carbon dioxide [2].
THE ABUNDANCE OF THE FIRST ROW TRANSITION METALS

IN THE EARTH’S CRUST
Transition metals are present in the solid crust of the planet at significant levels. Fe is the
fourth most abundant element in the earth crust (after oxygen, silicon, and aluminium) at
6.2% or 62000 ppm, making it the commonest transition metal. V and Cr are present at the
similar levels of 126 and 122 ppm, respectively. About 19.4 and 9.5 million tonnes are
produced annually of Cr and V. Mn is the twelfth most abundant element, and the fourth most
abundant transition element at 1060 ppm in the earth crust. Over 300 minerals contain Mn, of
which 12 are important commercially. Ni is the seventh most abundant transition metal and
twenty-second most abundant element at 99 ppm. Zn is present at 76 ppm, and about six
million tonnes are produced each year. Cu is present at 68 ppm in the earth crust and has
several important ores, as well as being found native. About eight million tonnes are produced
annually. Co is present at 29 ppm and is only the thirtieth most abundant element and apart
from scandium (Sc), at 25 ppm, is the most rare of the first row transition elements. Only a
few important ores exist, although over 200 Co-containing minerals are known, and about
33,000 tonnes are produced annually. About 30% of this is used to produce chemicals for the
ceramic and paint industries [2].
ELECTRONIC CONFIGURATION AND CHEMICAL PROPERTIES

OF TRANSITION METALS
All the transition metal atoms in a row of the Periodic Table have the same arrangement
of electrons in the outer orbital shell of the metal atom, and an inner orbital of the metal atom
fills with electrons moving from left to right across the row. The outer orbital is already filled,
so the atom adds or loses electrons without greatly changing properties such as atomic radius
[2]. The most commonly studied transition metals are the first row transition metals, and their
electronic configuration is given in Table 1. Cr and Cu are particularly popular ones, as they
do not fill the outer shell in the order one would expect. When forming ions, they all start by
losing the 4s electron first, then the 4d electrons.
Table 1. Electronic configurations of the transition metals of the first row

of the Periodic Table of Elements
Name Atomic Number Electronic Configuration

Sc Scandium 21 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d1
Ti Titanium 22 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d2
V Vanadium 23 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d3
Cr Chromium 24 1s2, 2s2, 2p6, 3s2, 3p6, 4s1, 3d5
Mn Manganese 25 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d5
Fe Iron 26 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d6
Co Cobalt 27 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d7
Ni Nickel 28 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d8
Cu Copper 29 1s2, 2s2, 2p6, 3s2, 3p6, 4s1, 3d10
Zn Zinc 30 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d10
Transition metals are, according to their standard reduction potentials (Table 2), good
reducing agents (except Cu). These ions transfer 2 electrons of the subnivel s, and additional
electrons of the incomplete subnivel d (Table 1). The standard reduction potential of the first
row transition elements is given in Table 2.
Table 2. Standard reduction potentials of the transition metals of the first row of the
Periodic Table of Elements (298 K). The ionic aqueous concentrations of ions are 1 M
Name E0
(V)
Sc (3+) - 2. 08
Ti (2+) - 1. 63
V (2+) - 1. 18
Cr (2+) - 0. 91
Mn (2+) -1. 19
Fe (2+) - 0. 44
Co (2+) - 0. 28
Ní (2+) - 0. 25
Cu (2+) + 0. 34
Zn (2+) - 0. 76
BIOLOGICAL PROPERTIES OF TRANSITION METALS

Twenty-three elements of the Periodic Table are present in the bodies of humans and
mammals, have known physiological functions and hence, they can be considered as
bioelements. From these bioelements, eleven are classified as trace elements (V, Cr, Mn, Fe,
Co, Cu, Zn, molybdenum (Mo), selenium (Se), fluoride (F), iodine (I)) because of their
limited quantity in humans and their essentiality for life. Seven of these elements belong to
the period 4 of the periodic table (Cr, Mn, Fe, Co, Cu, Zn, Mo), indicating an optimal
relationship between nucleus size and electron availability of the elements to interact with
bioorganic molecules in living systems (Figure 1). All of these elements are considered as
micronutrients, which are needed by the human body in small concentrations (less than 100
mg/day) and are essential components of biological structures [6].
Transition metals of the first row account for a good part of the trace elements, indeed six
out of eleven elements, and all of them have known biochemical and physiological functions.
Fe plays a decisive role in the most important functions of the aerobic life of mammals and
humans participating in oxygen delivery to the tissues by blood haemoglobin, oxygen
utilization in cell mitochondria by cytochromes and cytochrome oxidase, and hydrogen
peroxide removal by catalase. Fe is found in four classes of proteins: hemoproteins
(hemoglobin, myoglobin, cytochromes, catalase), Fe-sulfur enzymes (aconitase, fumarate
reductase), proteins for Fe storage and transport (transferrin, lactoferrin, ferritin,
hemosiderin), and other enzymes that contain Fe or –Sfe, such as activated NAD(P)H
dehydrogenase, succinate dehydrogenase, alcohol dehydrogenase, cyclooxigenases) [7]. Cu is
in way similar to Fe, an essential part of the active center of essential enzymes: cytochrome
oxidase for cell and tissue respiration and Cu,Zn-superoxide dismutase (Cu,Zn-SOD), where
the reversible redox change Cu2+- Cu1+ is the mechanism for the dismutation reaction. Cu has
been recognized as necessary for the development of connective tissue, nerve coverings, and
bone [8]. Zn is involved in the activity of about 100 enzymes, for example, RNA polymerase,
carbonic anhydrase, angiotensin I and superoxide dismutase, in the latter case with a
structural role [9]. Manganese is the active redox component of mitochondrial superoxide
dismutase (Mn-SOD). It has been associated with bone development and with amino acid,
lipid and carbohydrate metabolism [10].
In enzymes, the transition metals participate in catalytic processes as constituents of
enzyme active sites; as stabilizers of enzyme tertiary or quaternary structure; or associated in
forming complexes with the substrate. Metal cations are effective as intermediates in
oxidation-reduction processes by reversible changes in their oxidation state, transferring or
receiving electrons to or from the substrate or cofactor [6].
A free radical is “any chemical species capable of independent existence that possesses
one or more unpaired electrons” [11]. Stable compounds have even numbers of electrons,
paired in orbital with opposite spins, the magnetic fields of which cancel each other out. A
free radical has either an odd number of orbital electrons, with one unpaired or pairs of
electrons of the same spin isolated singly in separate orbital. The presence of one or more
unpaired electrons causes physically that the species is slightly attracted to a magnetic field
and chemically that exhibits a high reactivity. Molecular oxygen is, in fact, a biradical, having
two unpaired electrons with parallel directions of the spin in these unpaired electrons.
Molecular oxygen, in spite of the biradical nature, is quite unreactive and is kwon as a
sluggish radical. Cations of the bioelements Cu, Fe and Mn have unpaired electrons that allow
their participation in redox reactions involving mostly one electron loss (oxidation) or gain
(reduction). This condition would allow classifying these bioelements as free radicals’
however, when the concepts of one unpaired electron and high reactivity are linked, the free
radical concept applies to organic molecules and not to metal ions. Most of the toxic effects
of these transition metals are related to their capacity of catalyse the initiation of free radical
reactions by the decomposition of hydroperoxides, allowing the propagation of free radical
chain reactions and tissue damage [6, 11, 12].
The role of the biometal depends on its chemical structure and on the reaction medium:
Fe and Cu ions act as pro-oxidants and as antioxidants; Co and Zn are, in general,
antioxidants, preventing the catalytic participation of redox metals in free radical reactions, by
replacing these metals [6-14].
Other trace transition metals that are important for human physiology are Co (component
of cobalamine or vitamin B12) [15], Mo (electron transfer agent in enzymes such as xanthine
oxidase and sulphite reductase) [16]; and Cr and V, related to glucose and lipid metabolism
and ion pumps [17]. In biological systems, these bioelements are mostly conjugated or bound
to proteins forming metalloproteins, or to smaller molecules, such as phosphates, phytates,
polyphenols and other chelating compounds [6].
THE TOXIC EFFECTS OF TRANSITION METALS

Transition metals at increased levels are clearly toxic and sometimes lethal for biological
systems from isolated cells to whole organisms. There are no metabolic pathways for the
detoxification of transition metals and it is not easy to establish clear separations among
essentially, health benefits and toxicity [6].
The metals Fe and Cu are considered trace elements, and the metals Co and Ni are known
as ultra-trace elements, considering their presence in low and very low quantities,
respectively, in humans. The biological activity of these transition metals is associated with
the presence of unpaired electrons that favour their participation in redox reactions. They are
part of important enzymes involved in vital biological processes. However, these transition
metals (Fe, Cu, Co and Ni), as all the other transition metals, become toxic to cells when they
reach elevated tissue concentrations, mainly producing cellular oxidative stress and damage
[12].
Recent studies have shown that some transition metals, for instance, Fe, Cu, Cr, and V,
undergo redox cycling, involving the production of reactive oxygen species (superoxide
anion, hydrogen peroxide and hydroxyl radicals), while other metals, for instance, Cd, Hg,
and Ni, deplete the cytosolic endogenous antioxidants, such as reduced glutathione and
protein-bound sulphydryl groups, resulting in both cases in toxicity of the metals. Irreversible
oxidative damage to biological macromolecules, such as proteins, RNA and DNA, and to
cellular membranes is considered the mechanism of the cellular and tissue toxicity of the
transition metals. In all cases, the irreversible phase of oxidative damage is preceded by the
reversible phase of oxidative stress, in the reduction level of key redox pairs (NADH/NAD;
NADPH/NADP; GSH/GSSG) is shifted towards oxidation. Some transition metal ions,
notably those of Fe and Cu, catalyze Fenton-like reactions with homolysis of the
hydroperoxide –O-O- bond and generation of hydroxyl radical (HO. ) especially in the
membranes of subcellular fractions, such as mitochondria, microsomes, plasma membranes
and peroxisomes. Biological systems have developed proteins that have the ability to
recognize and combine with the toxic metal, not allowing it to participate in toxic reactions,
with a second function of transporting and delivering it at distance [6, 12].
Concerning transition metal toxicity, there are clear examples and evidences. Fe
intoxication produces oxidative damage to biomolecules, cells, tissues and organs. Increased
Fe storage has been associated with colorectal cancers in humans, genetic hemochromatosis
and hepatocellular tumors [7]. Cu toxicity is associated with liver damage, neurodegenerative
disease, and gastrointestinal effects characterized by abdominal pain, cramps, nausea,
diarrhea, and vomiting [18]. Zinc toxicity, which includes interference with Cu and Fe status
and functions, reduces immune function, promotes neurodegeneration, increases cell
hydroperoxide concentrations, and reduces the levels of HDL [19]. Manganese toxicity as
been reported in human brains, and as a cause of Parkinson-type syndrome [20].
Metal toxicity is used with chemotherapeutic purposes: the drug cis-Platinum is utilized
in treatment of cancer [2].
OXIDATIVE DAMAGE ASSOCIATED WITH TRANSITION METALS

The mechanism of biological damaged caused by oxygen free radicals and related species
has been the focus of scientific interest for many years [11, 21-34]. The spectrum of reactive
oxygen species that are considered responsible for biological toxicity include the
intermediates of the partial reduction of oxygen, superoxide radical (O2-), hydrogen peroxide
(H2O2), and hydroxyl radicals (HO.), peroxyl radical (ROO.), the intermediate of lipid
peroxidation process, and singlet oxygen (1O2) [12]. Superoxide radical exhibits low chemical
reactivity in vitro [11] by itself is not a deleterious agent, but rather serves as a source,
through its dismutation product, H2O2, of secondary highly reactive and toxic species, such as
HO. radicals, and even singlet oxygen [27]. Hydroxyl radicals are formed mainly by the
Haber-Weiss reaction that implies the homolytic scission of hydrogen peroxide (Eq. 1):
O2- + H2O2 → O2 + HO· + HO- (1)
However, the in vitro data indicate that this reaction would not proceed significantly in
vivo because the rate constant of the reaction is lower than that of the dismutation reaction.
Nevertheless, a modification of the Haber-Weiss reaction, as Fenton-like reactions, in which
O2- and H2O2 are bound to a Fe-hemoprotein and that utilizes the redox cycling ability of Fe
to increase the rate of reaction, is more feasible in vivo [11, 27, 30]. This type of reaction
mechanism is frequently used to explain the toxic effects of redox-active metals where M(n)+
is usually a transition metal ion. The original Fe-catalyzed Haber-Weiss mechanism has been
extended to other transition metals (Fe, Co, Cr, Co and others) as chemical pathways that lead
to HO. radical formation (Eq. 2 and 3):
M(n) + + O2- → M(n-1) + + O2 (2)
M(n-1) + + H2O2 → M(n) + + HO· + HO- (3)
The in vivo production of HO· in a Haber-Weiss reaction, with M(n)+ as an ionic form of
Fe, Co, Cr, Co, is the current hypothesis in the field [20]. Interestingly, the intracellular
2+
concentration of redox active transition metals is either low or negligible: free Fe is 0. 2 to
2+
0. 5 μM and the pool of free Cu is about a single ion per cell. However, trace (nM) levels of
cellular and circulating active transition metal ions seem enough for the catalysis of a slow
Fenton reaction in vivo at the physiological levels of hydrogen peroxide (H2O2, 0. 1-1. 0 μM)
[27]. As said, the Haber-Weiss reaction, a well-known abiotic reaction, affords the current
hypotheses in the field [19]. Hydroxyl radical (HO. ) production is the From a molecular point
of view hydroxyl radical (HO·) generation, formed from H2O2 and Fe2+ by the Fenton
reaction, has been considered for a long time as the likely rate-limiting step for physiological
process of lipid peroxidation [11, 25, 27]. This process involves free radical-mediated
reactions, in which the initiation reaction is provided by HO. attack to allylic carbons in
unsaturated phospholipids with hydrogen abstraction and generation of alkyl radicals (R.).
The propagation reactions are given by the addition of molecular O2 to the alkyl and carbon
centered free radical (R.) to form oxyradicals (ROO.) and the reaction in which ROO. abstract
another hydrogen from another allylic carbon, yielding stable hydroperoxide (ROOH) and the
R. radical, with the capacity to keep the chain process as long as unsaturated fatty acids and
oxygen are present. The stable products of the lipid peroxidation process are the
hydroperoxides (ROOH), a series of aldehydes, among them, 4-HO-nonenal and
malonaldehyde; this latter, is usually measured by its reaction with thiobarbituric acid
(TBARS). The toxicity of the sum of reactive oxygen species comes from their ability to
oxidize a large number of cellular constituents, such as phospholipids, proteins and DNA.
The role of metal transition ions in promoting lipid peroxidation by H2O2 homolysis has
been recently studied in phospatidylcholide and phospatidylserine mixed (PC/PS).
Phospholipid oxidation was assessed by TBARS production [12]. The Fe2+-H2O2-mediated
lipid peroxidation takes place by a pseudo-second order process, and the Cu2+-mediated
process by a pseudo-first order reaction. Co2+ and Ni2+ by themselves do not induce lipid
peroxidation. Nevertheless, when they are combined with Fe2+, a Fe2+-H2O2-mediated lipid
peroxidation process is stimulated (Ni) or inhibited (Co) [12].
Iron
Fe is the most abundant transition metal in the body (about 4 g in human adults), almost
all in the form of hemoproteins and Fe-sulfur centers. Free Fe concentrations are particularly
low (0. 2 to 0. 5 μM) [31], mainly as Fe2+ due to the biological reduction by O2- and ascorbic
acid [28]. Superoxide radicals are able to reduce the Fe3+ of ferritin and some Fe-sulphur
centres to Fe2+, making Fe2+ readily released [11].
It has been considered for a relatively long time that the main source of HO· formation in
aerobic cells is the Fenton reaction (ΔEº = + 0. 307 V), with H2O2 homolyzed and reduced
(Eq. 4):
Fe2+ + H2O2 → [Fe(II)H2O2] → Fe3+ + HO- + HO (4)
An alternative explanation for the Fenton reaction postulates the formation of an

oxidizing Fe(IV) species, as FeO2+ or Fe(IV)=O. These perferryl intermediates are thought of
as powerful oxidants, similar to HO· but distinguishable from it. In the Fenton reaction, HO.
derives exclusively from H2O2 and not from H2O [35].
2+
Transition metal ions also stimulate Fe -mediated lipid peroxidation by the reductive
cleavage of endogenous lipid hydroperoxides (ROOH) of membrane phospholipids to the
corresponding alkoxyl (RO·) and peroxyl (ROO·) radicals in a process that is known as
ROOH-dependent lipid peroxidation (Eqs. 5 and 6):
Fe2+ + ROOH → RO· + OH- + Fe3+ (5)
Fe3+ + ROOH → RO2· + H+ + Fe2+ (6)
The mechanisms of these two reactions appear to involve the formation of Fe(II)-Fe(III)
or Fe(II)-O2-Fe(III) complexes with maximal rates of HO· radical formation at a ratio
Fe(II)/Fe(III) of 1 [11]. At low level of H2O2, Fe2+ induces lipid peroxide decomposition,
generating peroxyl and alkoxyl radicals and favouring lipid peroxidation [12].
Copper
Cu is an essential element, as it is part of the active center of cytochrome oxidase, the

enzyme responsible for O2 uptake in mammalian cells [27], with a content of about 80 mg in
human adults. The Cu+ ion is considered an effective catalyst for the Fenton reaction (Eq. 5),
and Cu2+ and Cu+ are known for their capacity to decompose organic hydroperoxides
(ROOH) to form RO. and ROO· (Eqs. 7 to 9) [11, 12, 36].
Cu+ + H2O2 → [Cu(I)-H2O2] → Cu2+ + HO- + HO (7)
Cu+ + ROOH → RO· + OH- + Cu2+ (8)
Cu2+ + ROOH → RO2· + H+ + Cu+ (9)
Cu+, as well as Fe2+ promoted lipid peroxidation in phospholipid liposomes by homolysis

of H2O2 with HO· generation and by scission of ROOH with RO. and ROO. production and by
altering liposome surface structure [12].
The process of lipid peroxidation has been recognized as free radical-mediated and
physiologically occurring [11, 27] with the supporting evidence of in situ organ
chemiluminescence [37]. The main initiation reaction is understood to be mediated by HO·
(Eq. 2) or by a ferryl intermediate, both with the equivalent potential for hydrogen abstraction
from an unsaturated fatty acid and formation of an alkyl radical (R·) (Eq. 10):
HO· + RH → H2O + R (10)
2+ 2+
The metal ions Fe and Cu , which are bound to proteins, are reduced by ion O2-,
yielding the reduced metal-protein complex. This reduced complex reacts with H2O2 in a
Fenton reaction to yield locally the secondary HO· radicals. These HO· radicals react at the
specific site with the protein, impairing its activity. In this site-specific mechanism, the O2-
radical ion plays a dual role: reduction of the protein bound metal ion and production of H2O2
by dismutation [11].
Cu forms high affinity complexes with amino acids, short oligopeptides, and proteins,
and the role of Cu, as Cu+-macromolecule complexes in enhancing biological damage has
been suggested [38]. Reduced Cu ions in the complex react with H2O2 in a Fenton reaction
(Eq. 11):
Cu+-protein + H2O2 → [Cu(I)-protein-H2O2] → Cu2+-protein + HO- + HO (11)
The site-specific Fenton mechanism explains the enhancement of biological damage due
to transition metal ions by reducing agents [11, 12, 37, 38]. The toxicity of Cu and Fe in
biological systems may come clearer by increasing the concentration of the ions and by
providing reducing agents (for instance, ascorbate).
Recent experiments by the authors (unpublished results) show that the property of Fe2+
and Cu2+ of promoting lipid peroxidation, as shown by Figure 2, is reproduced in vivo. The
two transition metals, Fe2+ and Cu2+ were injected to rats (FeCl2, 0. 3-60 mg/kg rat; CuSO4, 5-
30 mg/kg rat; i. p.), and in situ liver chemiluminescence was determined after 16 hs. The
intensity of surface organ chemiluminescence, expressed as counts/second (cps) indicates and
measures the steady-state concentration of 1O2 in the organ. For the physiological condition,
the measured photon emission corresponds to 10-16 M 1O2. Singlet oxygen is by-product of
lipid peroxidation and its level directly measures the rate of lipid peroxidation. Both transition
metal ions were able to increase in situ and in vivo liver chemiluminescence: Fe2+ by a factor
of 4. 9 and Cu2+ by a factor of 1. 6. These effects depended on the transition metal content of
the organ (Figure3). Thus, the two transition metals increased the physiological rate of lipid
peroxidation. Cu and Fe toxicity primarily affect the liver because it is the first site of these
metals deposition after they enter the blood. Other organs, notably the brain, are later reached.
Figure 2. Phospholipid oxidation and lipid peroxidation (expressed as TBARS) on phospholipid

liposomes (0. 5 mg/mL, PC/PS) in the metal and H2O2-promoted process at different Fe2+ and Cu2+
concentrations (H2O2=10 μM). For statistical analysis, p<0. 05 with respect to control was used.
Figure 3. Dependence of the in situ chemiluminecence emission with Fe 2+ and Cu2+ liver content, after
16 hours of acute treatment with the metal. The data show mean ± SEM. For statistical analysis, p<0.05
with respect to control was used.
The spontaneous chemiluminescence of in situ organs provides a quantitative

determination of the steady-state concentrations of molecules in excited states, since these
molecules give off photons in the process of returning to the ground state. Photons are
quantitatively determined at the organ surface by the single photon counting. The spectral
analysis of organ chemiluminescence and the effects of trap and quenchers indicate that the
light emission from mammalian organ under physiological and in pathological situation of
oxidative stress is mainly related to singlet oxygen (dimol emission) and secondarily to
excited carbonyl groups [25, 27].
Inactive redox metals, such as Hg and Cd, displace Fe and Cu from their intracellular
binding sites and accelerate, in a Fenton reaction, the production of reactive oxygen species.
Nickel and Cobalt
The divalent cations of Ni and Co are able to promote, similarly to Fe2+ and Cu2+, in the
metal-catalyzed peroxidation of cellular phospholipids. Although not clear yet, it is generally
considered that Fenton-type reactions may be involved in the toxic effects of these metals in
vivo.
The oxidative effects are ascribed to the Ni(III)-Ni(II) complex and to the oxene species
(NiO)2+ that are formed at neutral pH [39]. Ni2+ does not promote lipid peroxidation in the
presence of hydroperoxides but it does in the presence of Fe2+/H2O2 mixtures, in such
conditions is oxidized to Ni3+ and reduced back to Ni2+ by cellular reductant as O2-, in a
Haber/Weiss-type reaction [40, 41].
Co ions, Co2+, do not promote phospholipids peroxidation directly and showed an almost
negligible pro-oxidant effect in the presence of Fe2+/H2O2. Co2+ may act as pro-oxidant
through its capacity to replace redox-active metals from in their binding sites in
hemoproteins. The possibility that Co2+-mediated free radical generation contributes to cobalt
toxicity was studied by EPR spin trapping, and it was found that O2- is formed in the reaction
of H2O2 with Co2+, a reaction inhibited when Co2+ was chelated with ADP, EDTA or citrate
[26].
The observed effects of Co2+ and Ni2+ in vivo are better explained by their structural
binding to liposomes and cell surfaces. The current hypothesis is that ions with redox capacity
stimulate Fe2+-initiated lipid peroxidation, but ions without redox capacity increase Fe2+-
initiated lipid peroxidation by increasing lipid packing, bringing phospholipid acyl chains
closer together, thus favoring the propagation steps of lipid peroxidation [12, 42].
Recent results showed that Co2+ and Ni2+ by themselves do not induce lipid peroxidation.
Nevertheless, when they are combined with Fe2+, Fe2+-H2O2-mediated lipid peroxidation is
stimulated in the presence of Ni2+ and inhibited in the presence of Co2+ [12].
The concept of oxidative stress describes an imbalance between the physiological rate of
oxidant production and the velocity of antioxidant defence system. The whole purpose of the
antioxidant defence is the maintenance of biological oxidative damage at a minimum [21-23].
A difference is made between oxidative stress as a reversible situation and oxidative damage
as an irreversible situation, but the limit is not clear. The difference is similar to the one
between reversible and irreversible cell injury in classic cell pathology [24].
In free radical-mediated chain reactions, the increase in the steady state concentration of
any intermediate species produces: (a) an increase in the reaction rate of all the reactions that
are downhill; (b) an increase in the steady state concentrations of all downhill intermediates;
and (c) a decrease in the steady state concentration of the antioxidants in the system. An
alternative and more chemical definition is the consideration of intracellular oxidative stress
as a situation where increases in the steady state concentrations of any intermediate produces
an increase in oxidant intermediates, an increase in the chain reaction rate, and a decrease in
intracellular antioxidants [23].
A growing body of evidence indicates that transition metal cytotoxicity is likely exerted
through oxidative stress and oxidative damage as precursors of cellular damage leading to
apoptosis or necrosis [11, 12, 19, 25-28].
The physiological generation of the products of the partial reduction of oxygen, O2- and
H2O2, constitute the biological basis of the process of lipid peroxidation in mammalian cells.
The lipid peroxidation of membrane phospholipids induced by reactive oxygen species leads
to membrane damage and is considered one of important mechanisms for the onset of several
pathologies [12].
Oxidative damage and the triggering of oxidant-responsive transcription factors could be
involved in the neurotoxicity of certain metals. Zn, Fe and Cu are essentials elements required
for the functions of various enzymes and cellular proteins in the central nervous system [11].
High Zn levels in the brain have been implicated in the oxidative damage to cell
components, with an effect that is initiated by the increase in intracellular oxidant
concentrations. In a second step, the reactive oxygen species trigger redox-sensitive
transcription factors involved either in cell proliferation mechanisms or in apoptosis [19].
Even though the mechanism is not elucidated, mitochondria may have a central role in the
neuronal death caused by Zn toxicity, enhancing mitochondria O2- and H2O2 production that
leads to cell death. Apoptotic or necrotic neuronal death will depend on the amount of oxidant
generated. Moderate production of oxidants seems to lead to apoptosis while high amounts of
oxidants trigger the necrotic pathways [29, 30].
TRANSITION METALS, NEURODEGENERATION

AND TUMOR PROMOTION
Neurodegeneration and Neurodegenerative Diseases
Increasing evidence indicates that multiple biochemical and cellular factors are involved
in metal-induced toxicity. Two main mechanisms are currently considered: a Haber-Weiss
reaction, likely to be the mechanism for redox active metals; and a depletion of major
sulfhydryls, reduced glutathione and protein –SH groups, likely to be the mechanism for the
metals that are redox active.
The cellular and tisular levels of transition metals are apparently determined by
regulatory proteins and metallochaperons that control metal capture, transport and storage.
The major consequences of metal dyshomeostasis are mitochondrial dysfunction, oxidative
stress, and mitochondrial genomic damage, which enhanced activation of the apoptotic
machinery [43].
Oxidative stress and oxidative damage have been reported in familial amyotrophic lateral
sclerosis, Alzheimer’s, and Parkinson’s diseases. The series of observed changes include
glycation, protein oxidation, lipid peroxidation, depletion of antioxidants, and nucleic acid
oxidation [44-49].
There are also consistent observations of the impaired functioning of mitochondrial
complex I (NADH CoQ10 reductase), with consequent aggregation and accumulation of α-
synuclein [49]. Mitochondria are targets of metal toxicity, and in many cases, a close link
between metal-induced oxidative stress and damage and mitochondrial dysfunction has been
established [33, 51-53]. The mitochondria of Fe-treated rats show lower respiratory control in
association with higher resting (state 4) respiration. The mitochondrial uncoupling elicited by
Fe-treatment does not affect neither the phosphorylation efficiency nor ATP levels, indicating
a mild degree of uncoupling in Fe overload [54].
Alzheimer’s disease is characterized by a selective loss of neurons in hippocampus and
frontal cortex and by the presence of neurofibrillary tangles, neutrophil threads, and β-
amyloid peptide (Aβ)-rich senile plaques. The brains of Alzheimer’s-diseased patients are
characterized by the accumulation of Fe within senile plaques and neurofibrilary tangles, and
also by lowered expression of the transferrin receptor. As a consequence, these brains are
subject to high levels of oxidative stress. It has been claimed that Fe promotes Aβ amyloid
deposition and affects the enzymatic processing of the amyloid precursor protein [43, 55].
As for Parkinson’s disease, dopaminergic cell loss and disease progression are
accompanied by the accumulation of high Fe levels, associated with aggregation of α-
synuclein (especially the mutated form found in familial Parkinson’s disease). The Fe
accumulation in substantia nigra (with up to 255% increases) results in oxidative stress,
oxidative damage, decreased reduced glutathione levels, and increased dopamine neuronal
toxicity [43]. The Fe-induced oxidative damage to mitochondria contributes to the cellular
death mechanisms, arising from a diminished respiratory chain activity and ATP production.
The significant reduction in transferrin levels, observed in patients with Alzheimer’s and
Parkinson’s diseases, is a contributory factor to increased Fe concentrations [43, 56].
Increased contents of Cu in the human body, especially in the central nervous system,
exert toxic effects with metabolic disturbances. The increased Cu levels have been implicated
in many diseases, including microbial infections, cancer and neurodegenerative disorders.
These copper metabolism disorders include Menkes and Wilson diseases, and
neurodegenerative disorders like familial amyotrophic lateral sclerosis, Alzheimer’s and
Parkinson’s diseases [43].
The aggregation of Aβ is promoted by Cu, and its neurotoxicity depends on catalytically
generated H2O2 by Aβ-Cu complexes. Moreover, the characterization of Cu2+ interacting with
α-synuclein demonstrated that this metal is effective in accelerating protein aggregation at
physiologically relevant concentrations without altering the resultant fibrillar structures [43].
The Cu2+-complex is reduced by ascorbate, GSH or NADPH and reacts with H2O2 to generate
HO. (recognized by immediate amino acid oxidation).
Another proposed mechanism is that Aβ aggregation promoted by Cu inhibits
cytochrome oxidase α-ketoglutarate dehydrogenase activities in mitochondria. The higher
reduction state increases superoxide production through a single-electron transfer to
molecular oxygen, particularly at respiratory complex I. Both the Cu deficiency and the Cu
overload are associated with neurodegeneneration and result in oxidative stress and oxidative
damage. These effects are associated with mitochondrial dysfunction due to decreased
activity of cytochrome c oxidase and to the increased production of reactive oxygen species,
which, in turn, triggers mitochondria-mediated apoptotic neurodegeneration [56, 57].
Membrane-bound α-synuclein may play a role in fibril formation. Over expression of α-
synuclein impairs mitochondrial function and increases oxidative stress. The prion protein has
a neuroprotective function by acting as antiapoptotic factor that inhibits the mitochondria-
mediated apoptosis, by preventing the formation of the permeability pore of the inner
mitochondrial membrane [43, 50]. Oxidative stress promotes aggregation and accumulation
of Aβ and α-synuclein, both characteristics of Alzheimer’s and Parkinson’s diseases,
respectively [43, 50].
Oxidative stress and damage induce chemically modified forms of Aβ (generation of
soluble covalently-linked oligomers of the protein). Interaction of these oligomers and Cu,
further promote the aggregation of Aβ, which is the core component of extracellular amyloid
plaques, a central pathological hallmark of Alzheimer’s disease. Cu deregulation is also
implicated in the hyperphosphorylation and aggregation of tau, the main component of
neurofibrillary tangles, which is also a pathological hallmark of this disease [43, 50-52].
Oxidative damage has been proposed to favour the aggregation of α-synuclein in
sporadic Parkinson’s disease. Inhibition of complex I creates an environment of oxidative
stress that ultimately leads to aggregation of α-synuclein with the consequent neuronal death.
Complex I dysfunction, also called “complex I syndrome” results in complex I inactivation,
reduced O2 uptake and ATP formation, increased O2- formation, oxidative stress and lipid
peroxidation, events that lead to neuronal depolarisation and contribute to excitotoxic
neuronal injury [43, 50, 52].
In the brain, Zn is found at higher concentrations in hippocampus and frontal cortex, with
lesser amounts in cerebellum. This metal is associated with glutamate in excitatory neurons.
Upon stimulation, glutamate and Zn are released into the synapse, where Zn is thought to play
a role in stabilizing the neurotransmitter, reaching high levels at the synaptic area and
entering post-synaptic neurons via Ca channels, competing with Ca [58]. Several diseases,
such as global ischemia or epilepsy, are related to Zn-mediated neuronal death, and they
induce a rapid delivery of Zn from storage vesicles in excitatory pre-synaptic buttons and
bounds to metallotionein. The binding of Zn to this enzyme is thought to be one of the most
important mechanisms of Zn homeostasis.
The mechanism involved in Zn-induced neuronal degeneration is not completely
elucidated. Increasing evidence suggests that Zn toxicity induces cell death by impairing
mitochondrial function and decreasing cell energy production through different mechanisms:
inhibition of the electron transport chain by Zn [59], inhibition of energy production and
induction of mitochondrial depolarisation [60], inhibition of the α-ketoglutarate complex of
the tricarboxylic cycle in rat liver mitochondria [61], reversible inhibition of electron
transport chain at the bc1-complex [62], and inhibition of oxygen consumption and reduction
of transmembrane potential in brain mitochondria [63]. Neuronal death due to Zn toxicity
mainly involves the mobilization and redistribution of this metal located in the brain, rather
than a participation of exogenous Zn [43, 58].
In familial amyotrophic lateral sclerosis, the general concept is that upon mutation, SOD1
(Cu,Zn-SOD) is partially misfolded and binds copper improperly. Inadequately buffered
copper ions trigger aberrant metal chemistry leading to oxidative stress and to induction of
cell death [48, 64, 65]. Considering the organs affected, the toxicities produced by transition
metals are mainly associated with apoptosis and generally involve neurotoxicity,
hepatotoxicity, and nephrotoxicity [43].
Tumor Promotion
Increased Fe levels promote already-initiated hepatocarcinogenesis, enhance cell

proliferation and deplete intracellular antioxidants, such as ubiquinone [29].
Cu toxicity is associated with liver injury by generating reactive oxygen species and
causes tumour promotion, possibly by inducing oxidative DNA damage. Oxidative stress-
related effects are involved in Cu-induced tumour promotion and Fe-induced enhancement,
causing cytokine imbalance and enhanced lipid peroxidation [29].
Many carcinogenic metals, including Cd, Cr, and to a lesser extend Ni, form complexes
with thiols preferentially to any other functional group. The proposed mechanisms of
carcinogenesis associated with toxic metals involve free radical generation by Fenton-like
reactions, metal-induced thiyl radical generation, metal-induced DNA damage and inhibition
of DNA repair, and impairment of phosphorylation/desphosphorylation controlled by signal
transduction, involving nuclear factor-kappa β, activator protein-1 and mitogen-activated
protein kinases [66]. Cr and Cd are well-known carcinogens. Cr is an essential transition
metal that reacts with H2O2 and other organic hydroperoxides to form reactive oxygen
species. Due to its ability to change oxidation numbers from +2 to +6, Cr has a complex
redox chemistry and can participate in a multitude of cellular interactions. Hexavalent Cr
(Cr6+) is a potent teratogen and is considered the most carcinogenic form of Cr. The
hexavalent form of Cr is a potent inducer of apoptosis. The hexavalent form is easily reduced
in cells to the trivalent state by ascorbate, NADPH and GSH; the trivalent form is redox
active and able to interact with peroxides. For example, Cr5+ interacts with H2O2, generating
HO. in a Fenton-type reaction [31]. Partially reduced Cr is able to interact with DNA and
cellular macromolecules.
Cd is frequently associated with lung cancer in humans. Cd is an abundant, non-essential
element that increases lipid peroxidation in tissues soon after Cd exposure, but does not
appear to generate free radicals by itself [31]. Ni is a long-term recognized human carcinogen
that forms compounds with oxidation states –1 to +4, with the prevalent form of +2. The main
recognized biochemical effects of Ni2+ are the interference in DNA repair [66] and the
promotion of lipid peroxidation and protein carbonyl formation [63, 66].
CONCLUSION
The toxicity of transition metal ions in biological systems is a complex process that
involves Haber-Weiss-like production of reactive oxygen species with the participation of
redox active metals as Fe, Cu, Cr, and V. However, for redox inactive toxic metals, such as
Cd, Zn, Co, Ni, and Hg, depletion of cells’ major antioxidants, reduced glutathione and
protein-bound sulfhydryls provide the molecular mechanism for the overall toxic
manifestations. Mounting evidence indicates that multiple mechanisms participate in
production of free radicals and reactive oxygen species in the toxicity of transition metals.
Concerning the cellular mechanisms for transition metal toxicity, increased production of free
radicals, decreased reduced thiol status, increased lipid peroxidation, and impairment of the
cellular antioxidant defense systems have been proposed, and it seems that all of them, redox
active and inactive metals, participate in the phenomenon. The bulk of the studies on the
relationship of transition metals with the protein markers of the most common
neurodegenerative diseases strongly support the hypothesis that an aberrant redox reactivity
of these metals may be implicated in neuronal death. A tight regulation of neuronal transition
metal homeostasis is essential to the integrity of normal brain functions. The understanding of
the effects of physiological and pathological levels of transition metal ions on neurons is
relevant to prevent oxidative damage in highly sensitive brain areas (hippocampus and frontal
cortex).
REFERENCES
[1] Chang, R. Chemistry. Ninth edition. Mexico: McGraw Hill; 2007.
[2] Housecroft, C.E. & Sharpe A.G. Inorganic Chemistry. Second edition. United
Kingdom: Pearson Education; 2006.
[3] Atkins, P. & Jones, L. Chemical principles. The quest for insights. Third edition. United
States, New York: Freemand and CO; 2005.
[4] Orgel, L.E. An introduction to transition-metal chemistry. Ligand field theory. Second
edition. United Kingdom, London: Methuen and CO; 1975.
[5] Wern Huang, Y. Wu, Chi-heng. & Aronstam, R. (2010) Toxicity of transition metal
oxide nanoparticles: recent insights from in vitro studies. Materials, 3, 4842-4859.
[6] Fraga, C.G. (2005) Relevance, essentially and toxicity of trace elements in human
health. Mol Asp Med, 26, 235-244.
[7] Fraga, C.G. & Oteiza, P. (2002) Iron toxicity and antioxidant nutrients. Toxicol, 180,
23-32.
[8] Vir, S. & Rana, S. (2008) Metals and apoptosis: recent developments. J Trace Elem
Med Biol, 22, 262-284.
[9] Zago, M. Verstraeten, S. & Oteiza, P. (2000) Zinc in the prevention of Fe2+-initiated
lipid and protein oxidation. Biol Res, 33,143-150.
[10] Davis, C.D. & Greger, J.L. (1992) Longitudinal changes of manganese-dependent
superoxide dismutase and other indexes of manganese and iron status in women. Am J
Clin Nutr, 55, 747-752.
[11] Halliwell, B. & Gutteridge, J. (1984) Oxygen toxicity, oxygen radicals, transition
metals and disease. Biochem J, 219, 1-14.
[12] Repetto, M.G. Ferrarotti, N.F. & Boveris, A. (2010) The involvement of transition
metal ions on iron-dependent lipid peroxidation. Arch Toxicol, 84, 255-262.
[13] Oteiza, P.I. Olim, K.L. & Fraga, C.G. (1995) Zinc deficiency causes oxidative damage
to proteins, lipids and DNA in rat testes. J Nutr, 123, 823-829.
[14] Oteiza, P.I. Clegg, M.S; Zago, M. & Keen, C.L. (2000) Zinc deficiency induces
oxidative stress and AP-1 activation in 3T3 cells. Free Radic Biol Med, 28, 1091-1099.
[15] Kobayashi, M. & Shimizu, S. (1999) Cobalt proteins. Eur J Biochem, 261, 1-9.
[16] Rajagoplan, K.V. (1988) Molybdenum: an essential trace element in human nutrition.
Annu Rev Nutr, 8, 401-427.
[17] Vincent, J.B. (2004) Recent advances in the nutritional biochemistry of trivalent
chromium. Proc Nutr Soc, 63, 41-47.
[18] Waggoner, D.J. Bartnikas, T.B. & Gittin, J.D. (1999) The role of copper in
neurodegenerative disease. Neurol Dis, 6, 221-230.
[19] Oteiza, P.I. Mackenzie, G.G. & Verstraeten, S.V. (2004) Metals in neurodegeneration:
involvement of oxidants and oxidant-sensitive transcription factors. Mol Asp Med, 25,
103-115.
[20] Auschner, M. (2000) Manganese: brain transport and emerging research needs. Environ
Health Perpect, 108, 429-432.
[21] Boveris, A. Repetto, M.G. Bustamante, J. Boveris, A.D. & Valdez, L. (2008) The
concept of oxidative stress in pathology. In: Alvarez S. & Evelson P. (Eds.), Free
Radical Pathophysiology (first edition, 1-17). Kerala, India: Research Signpost.
[22] Sies, H. (1991) Oxidative stress: from basic research to clinical application. Am J Med,
91, 31-38.
[23] Halliwell, B. & Gutteridge, J. (1984) Oxygen toxicity, oxygen radicals, transition
metals and disease. Biochem J, 219, 1-14.
[24] Repetto, M.G. & Ossani, G. (2008) Sequential histopathological and oxidative damage
in different organs in choline deficient rats. In: Alvarez S. & Evelson P. (Eds.), Free
Radical Pathophysiology (first edition, 433-450). Kerala, India: Research Signpost.
[25] Cadenas, E. (1989) Biochemistry of oxygen toxicity. Annu Rev Biochem, 58,79-110.
[26] Carter, D. (1995) Oxidation-reduction reactions of metal ions. Environ Health Perspect,
103, 17-20.
[27] Chance, B. Sies, H. Boveris, A. (1979) Hydroperoxide metabolism in mammalian
organs. Physiol Rev, 59,527-605.
[28] Fang, Y. Yang, S. & Wu, G. (2002) Free radicals, antioxidants and nutrition. Nutrition,
18, 872-879.
[29] Mizukami, S. Ichimura, R. Kemmoci, S. Wang, L. Taniai, E. Mitsumori, K. &
Shibutani, M. (2010) Tumor promoting by copper-overloading and its enhancement by
excess iron accumulation involving oxidative stress responses in the early stage of a rat
two-stage hepatocarcinogenesis model. Chem Bio Int, 185, 189-201.
[30] Repetto, M. Ossani, G. Monserrat, A. & Boveris, A. (2010) Oxidative damage: The
biochemical mechanism of cellular injury and necrosis in choline deficiency. Exp Mol
Pathol, 88, 143-149.
[31] Valko, M. Rhodes, C. Moncol, J. Izakovic, M. & Mazur, M. (2006) Free radicals,
metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact, 160,1-
40.
[32] Boveris, A. & Fraga, C. (2004) Oxidative stress in aging and disease. Mol Aspect Med,
25, 1-4.
[33] Navarro, A. & Boveris, A. (2004) Rat brain and liver mitochondria develop oxidative
stress and lose enzymatic activities on aging. Am J Physiol Reg Comp Integr Physiol,
287, 1244-1249.
[34] Ossani, G. Dalghi, M. & Repetto, M.G. (2007) Oxidative damage and lipid
peroxidation in the kidney of choline-defficient rats. Front Biosci, 12, 1174-1183.
[35] Lloyd, R. Hanna, P. and Mason, R. (1997). The origin of the hydroxyl radical oxygen in
the Fenton reaction. Free Radic Biol Med, 22, 885-888.
[36] Klotz, O. Kronche, D. Buchczyk, D. & Sies, H. (2003) Role of copper, zinc, selenium
and tellurium in the cellular defense against oxidative and nitrosative stress. J Nutr,
133, 1448-1451.
[37] Boveris, A. Cadenas, E. Reiter, R. Filipkowski, M. Nakase, Y. & Chance, B. (1980)
Organ chemiluminescence: noninvasive assay for oxidative radical reactions. Proc. Natl
Acad Sci USA, 177, 347-351.
[38] Shinar, E. Navok, T. & Chevion, M. (1983) The analogous mechanisms of enzymatic
inactivation induced by ascorbate and superoxide in the presence of copper. J Biol
Chem, 25, 14778-14783.
[39] Kasprzak, K. Sunderman, F. & Salnikow, K. (2003) Nickel carcinogenesis. Mut Res,
533, 67-97.
[40] Krezel, A. & Bal, W. (2004) Studies of Zn (II) and Nickel (II) complexes of GSH,
GSSG and their analogs shed more light on their biological relevance. Bioinorg Chem
Appl, 2, 293-305.
[41] Salnikow, K. & Kasprzak, K. (2005) Ascorbate depletion: a critical step in nickel
carcinogenesis. Environ Health Perspect, 113, 577-564.
[42] Verstraeten, S. Nogueira, L. Schreier, S. & Oteiza, P. (1997) Effect of trivalent metal
ions on phase separation and membrane lipid packing: role in lipid peroxidation. Arch
Biochem Biophys, 338, 121-127.
[43] Kozlowski, H. Janck-Klos, A. Brasun, J. Gaggelli, E. Valensin D. & Valensin, G.
(2009) Copper, iron, and zinc ions homeostasis and their role in neurodegenerative
disorders (metal uptake, transport, distribution and regulation). Coord Chem Rev, 253,
2665-2685.
[44] Gatto, E. Carreras, M.C. Pargament, G. Reides, C. Repetto, M. G. Llesuy, S. Fernandez
Pardal, M. & Poderoso, J. (1996) Neutrophil function nitric oxid and blood oxidative
stress in Parkinson’s disease. Mov Disord, 11, 261-267.
[45] Famulari, A. Marschoff, E. Llesuy, S. Kohan, S. Serra, J. Dominguez, R. Repetto, M.
G. Reides, C. & Sacerdote de Lustig, E. (1996) Antioxidant enzymatic blood profiles
associated with risk factors in Alzheimer’s and vascular diseases a predictive assay to
differentiate demented subjects and controls. J Neurol Sci, 141, 69-78.
[46] Gatto, E. Carreras, C. Pargament, G. Riobó, N. Reides, C. Repetto, M.G. Fernandez
Pardal, N. Llesuy, S. & Poderoso, J. (1997) Neutrophyl function nitric oxide and blood
oxidative stress in Parkinson’s Disease. Focus Parkinson’s Dis, 9, 12-14.
[47] Repetto, M. Reides, C. Evelson, P. Kohan, S. Sacerdote de Lustig, E. & Llesuy, S.
(1999) Peripheral markers of oxidative stress in probable Alzheimer’s patients. Eur J
Clin Invest, 29, 643-649.
[48] Fiszman, M. DÉigidio, M. Ricart, K. Repetto, M.G. Llesuy, S. Borodinsky, L. Trigo,
R. Riedstra, S. Costa, P. Saizar, R. Villa, A. & Sica, R. (2003) Evidence of oxidative
stress in Familial Amyloidotic Polyneuropathy Type 1. Arch Neurol, 60, 593-597.
[49] Domínguez, R. Marschoff, E. Guareschi, E. Repetto, M.G. Famulari, A. Pagano, M. &
Serra, J. (2008) Insulin, glucose and glycated haemoglobin in Alzheimer’s and vascular
dementia with and without superimposed Type II diabetes mellitus condition. J Neur
Transm, 115, 77-84.
[50] Opazo, C. Barría, M.I. Ruiz, F.H. & Inestrosa, N.C. (2003) Copper reduction by copper
binding proteins and its relation to neurodegenerative diseases. Biometals, 16, 91-98.
[51] Navarro, A. Bández, M. Gómez, C. Sánchez-Pino, M. Repetto, M. & Boveris, A.
(2010) Effects of rotenone and pyridaben on complex I electron transfer and on
mitochondrial nitric oxide synthase functional activity. J Bioenerg Biomembr, 42, 405-
412.
[52] Navarro, A. Boveris, A. Bandez, M.J. Sanchez-Pino, M.J. Gomez, C. Muntane, G. &
Ferrer, I. (2009) Human brain cortex: mitochondrial oxidative damage and adaptive
response in Parkinson’s disease and in dementia with Lewy bodies. Free Radic Biol
Med, 46, 1574-1580.
[53] Navarro, A. & Boveris, A. (2009) Brain mitochondrial dysfunction and oxidative
damage in Parkinson's disease. J Bioenerg Biomembr, 41, 517-521.
[54] Pardo Andreu, G.L. Inada, N.M. Vercesi, A.E. & Curti, C. (2009) Uncoupling and
oxidative stress in liver mitochpndria isolated from rats with acute iron overload. Arch
Toxicol, 83, 47-53.
[55] Wan, L. Nie, G. Zhang, J. Luo, Y. Zhang, P. Zhang, Z. & Zhao, B. (2011) Amyloid
peptide increases levels of iron content and oxidative stress in human cell and
Caenorhabditis elegans models of Alzheimer disease. Free Radic Biol Med, 50, 122-
129.
[56] Spencer, W. Jeyabalan, J. Kichambre, S. & Gupta, R. (2011) Oxidatively generated
DNA damage after Cu(II) catalysis of dopamine and related catecholamine
neurotransmitters and neurotoxins: Role of reactive oxygen species. Free Radic Biol
Med, 50, 139-147.
[57] Rossi, L. Lombardo, M. Ciriolo, M. & Rotilio, G. (2004). Mitochondrial dysfunction in
neurodegenerative diseases associated with Copper imbalance. Neurchem Res, 29, 493-
504.
[58] Choi, D.W. & Kob, J.Y. (1999) Zinc and brain injury. Annu Rev Neurosci, 21, 347-375.
[59] Dineley, K.E. Votyakova, T.V. & Reynolds, I.J. (2003) Zinc inhibition of cellular
energy production: implications for mitochondria and neurodegeneration. J Neurochem,
85, 563-570.
[60] Sensi, S.L. Yin, H.Z. Carriedo, S.G. Rao, S.S. & Weiss, J.H. (1999) Preferential Zn2+
influx through Ca2+ permeable AMPA/kainite channels triggers prolonged
mitochondrial superoxide production. Proc Natl Acad Sci, USA, 96, 2414-2419.
[61] Brown, A.M. Cristal, B.S. Effron, M.S. Shestopalov, A.I. Ullucci, P.A. Sep, K.F. Blass,
J.P. & Copper, A.J. (2000) Zn2+ inhibits alpha-ketoglutarate-stimulated mitochondrial
respiration and the isolated alpha-ketoglutarate dehydrogenase complex. J Biol Chem,
275, 13441-13447.
[62] Lorusso, M. Cocco, T. Sardanelli, A.M. Minuto, M. Bononi, F. & Papa, S. (1991)
Interaction of Zn2+ with the bovine-heart mitochondrial bc1 complex. Eur J Biochem,
197, 555-561.
[63] Galaris, D. & Evangelou, A. (2002) The role of oxidative stress in mechanisms of
metal-induced carinogenesis. Crit Review Oncol Hematol, 42, 93-103.
[64] Carri, M.T. Ferri, A.B. Cozzolino, M. Calabrese, L. & Rotilio, G. (2003)
Neurodegeneration in amyothropic lateral sclerosis: the role of oxidative stress and
altered homeostasis of metals. Brain Res Bull, 61, 365-374.
[65] Ozcelick, D. & Uzun, H. (2009) Copper intoxication; antioxidant defenses and
oxidative damage in rat brain. Biol Trace Elem Res, 127, 45-52.
[66] Hartwig, A. Asmuss, M. Ehleben, I. Herzer, U. Kostelac, D. & Pelzer, A. (2002)
Interference by toxic metal ions with DNA repair processes and cell cycle control:
molecular mechanisms. Environ Health Perspect, 110, 797-799.
Chapter 10
HYDRODESULFURIZATION OF DIBENZOTHIOPHENE
OVER VARIOUS COMOP/AL2O3 SULFIDE CATALYSTS
PREPARED FROM CO AND MO PHOSPHORIC ACIDS
Masatoshi Nagai*1, Yuki Nakamura1 and Shoji Kurata2

1
Graduate School of Bio-applications and Systems Engineering, Tokyo University
of Agriculture and Technology, 2-24 Nakamachi, Koganei, Tokyo, Japan
2
Criminal Investigation Laboratory, Metropolitan Police Department,
Chiyoda-ku, Tokyo, Japan
ABSTRACT
The activities of the CoMoP/Al2O3 catalysts prepared by different preparation methods
using Mo and Co phosphoric acids were studied for the hydrodesulfurization (HDS) of
dibenzothiophene at 513 K and a total pressure of 2.0 MPa. The sulfided CoMoP/Al2O3
catalyst using the consecutive impregnation method with calcination exhibited a higher
conversion (62 % at 7.5 h) than those prepared by seven other methods. The sulfided catalyst
is prepared by calcination of the catalyst impregnated with a Co phosphoric acid solution after
drying the catalyst impregnated with a Mo phosphoric acid solution on alumina. The sulfided
catalysts, made by the drying method after both a consecutive impregnation and simultaneous
methods using Co and Mo solutions, was less active than the catalysts with calcination during
the HDS. The sulfiding pretreatment of the CoMo phosphorus precursors was more useful for
the HDS than the reduction. From the XPS analysis, the catalysts with calcination and
subsequent impregnation had the higher ratios of Co/(Co+Mo) and S/(Co+Mo) than those
prepared by the other methods. The composition of the active catalyst was CoMo1.4S2.9P0.57
(CoMoS2‧Mo0.4P0.57) before the reaction probably due to the formation of the CoMoS slab
stacking.
Keywords: Dibenzothiophene; HDS; Co and Mo Phosphide; XPS
*
Corresponding author: E-mail address: mnagai@cc.tuat.ac.jp
372 Masatoshi Nagai, Yuki Nakamura and Shoji Kurata
1. INTRODUCTION
Hydrodesulfurization (HDS) has been of considerable attention for the past decade to
reduce the high sulfur levels to below 10 ppm and is being developed as a deep HDS catalyst.
It is generally accepted that the addition of phosphorus promotes the HDS activity of
NiMo/Al2O3 during the HDS of dibenzothiophene and 4,6-dimethyldibenzothiophene
(4,6DMDBT) due to the stacking formation of the active species [1-3,30,31], formation of
strong acid sites [4-8], surface active site distribution [9-12], and decrease in coke formation
[13,14]. The addition of 2.7% phosphorus to NiMo/Al2O3 has been reported to cause the
formation of a highly dispersed NiPS3 of NiMo/Al2O3 [15] and of a "Ni-(thio)phosphate
phase" [16] of CoNiMo/Al2O3. For the CoMo catalysts, the phosphorus-doped CoMo catalyst
acted as a 3-fold more active catalyst compared to the phosphorus-free CoMo catalyst. The
CoMo catalyst prepared using citric acid and phosphoric acid without calcination (only
drying) was reported to be very active during the HDS [17]. Furthermore, the cobalt and
molybdenum phosphides are reported to be active for the HDS and hydrodenitrogenation
[15,18-21]. However, there are few studies regarding the preparation methods of the Co-Mo
phosphide from the compounds of Co and Mo containing phosphorous in the starting material
and their HDS active catalysts. In this study, the CoMo phosphides supported on alumina
were prepared and sulfided using six impregnation methods, such as the consecutive and
simultaneous methods of cobalt and molybdenum phosphoric acids and two subsequent
procedures of drying and calcination. Two reduced catalysts were prepared. The change in the
compositions of the sulfided CoMoP/Al2O3 catalysts before and after the reaction were
discussed on the basis of the obtained X-ray photoelectron spectroscopy (XPS) results.
2. EXPERIMENTAL
2.1. Catalyst Preparation
A cobalt molybdenum phosphide (mole composition, CoO:MoO3:P2O5 = 3.1:17.9:2.7)

supported on Al2O3 was prepared using four different successive impregnation methods and
two simultaneous solutions methods containing the Co and Mo phosphoric acids (Fig. 1). In
the first successive impregnation method (Mo first and Co after), alumina was injected into an
aqueous solution of (NH4)3PO4⋅12MoO3⋅3H2O and dried at 393 K and then oxidized at 773 K
for 5 h. An aqueous solution of Co3(PO4)2⋅8H2O and a 0.1 M HNO3 solution was added to the
solid which was then dried at 393 K (Cat 5) and calcined at 773 K for 5 h (Cat 1). In the
second method (Co first and Mo after), alumina was introduced into the aqueous solution of
Co3(PO4)2⋅8H2O and dried at 393 K, then the aqueous solution of (NH4)3PO4⋅12MoO3⋅3H2O
was added to the dried solid. This precursor was dried at 393 K (Cat 6) and calcined at 773 K
for 5 h (Cat 2). In the third simultaneous method (Co-impregnation of Co and Mo), the
aqueous solutions of (NH4)3PO4⋅12MoO3⋅3H2O and Co3(PO4)2⋅8H2O were mixed with Al2O3,
followed by drying at 393 K (Cat 4) and calcining at 773 K for 5 h (Cat 3). The catalysts were
pretreated by two presulfidation methods of Cat1-Cat6 and pre-reduction of Cats 1 and 5. For
the reduction of the calcined catalysts (Cat 1 and Cat 5 before sulfidation), the catalysts were
cooled in a stream of He from 773 to 623 K (Cat 7) or heated from 393 to 623 K in the stream
Hydrodesulfurization of Dibenzothiophene … 373
of He (Cat 8). The former catalyst (Cat 7) and the latter (Cat 8) were reduced in a stream of
H2 at 623 K for 3 h. All the catalysts (Cat 1-Cat 6) were sulfided in 10% H2S/H2 at 4 L/h and
623 K for 3 h. In a separate experiment, the Mo compound without phosphorus
((NH4)6Mo7O24⋅4H2O) and phosphoric acid were mixed instead of (NH4)3PO4⋅12MoO3⋅3H2O
and then prepared with alumina compared to the activity of Cat 1.
Consecutive and Simultaneous Impregnation

1.C onsecutive C atalyst
S ulf
dry C alc C onsec M oP 1 C at 1
MoP CoP 623 K
773 K R ed
D ry 623 K C at 7
623 K S ulf
C onsec M oP 2 623 K
C at 5
R ed
623 K
dry C alc C at 8
CoP MoP C onsec C oP 1 S ulf
773 K 623 K
C at 2
D ry
623 K S ulf
2.Sim ultaneous C onsec C oP 2 C at 6
623 K
MoP CoP C alc S ulf

＋ 773 K S im ultaneous 3 C at 3
623 K
D ry
673 K S ulf
S im ultaneous 4 C at 4
623 K
Figure 1. Catalyst names based on the consecutive impregnation methods.
2.2. HDS Activity Measurement and Characterization
The HDS of dibenzothiophene was carried out using a fixed-bed microreactor, which was
packed with1.0 g of the sulfided catalyst, in a high-pressure flow system. The solution of 1.0
wt% dibenzothiophene in xylene was introduced into the reactor at the flow rate of 10 mL/h
with flowing hydrogen at 4 L/h, 513 K and a total pressure of 2 MPa. Hydrogen was dried by
passing it through a Linde 13X molecular sieve trap. The feed and reaction products were
quantitatively analyzed using an FID gas chromatograph with a DB-5 (30 m x 0.248 mm,
J&W) capillary culumn.
The changes in the surface compositions of the catalysts before and after the reaction
were determined using XPS. The catalyst was not exposed to air during the procedure from
the catalyst pretreatment to the XPS measurement. The XPS spectra of the Mo3d, Co2p, P2p,
and S2p lines before and after the reaction were obtained using a Shimadzu ESCA 3200
spectrometer with monochromatic MgKα exciting radiation. The binding energy values for
the catalysts were referenced to the Al2p line of Al2O3 at 74.7±0.2 eV. The baseline
corrections for the Co 2p3/2 and Mo 3d peaks were carried out using the Shirely method.
3. RESULTS AND DISCUSSION

3.1. Catalyst Preparation
The HDS of dibenzothiophene on Cat 1-Cat 6 is shown in Fig. 2. Cat 1 exhibited a

conversion of approximately 62% and was similar to or slightly higher than that for Cat 2.
The conversion for Cat 5 and Cat 6, dried in spite of the calcination of Cat1 and Cat 2, were
0.38 and 0.3, respectively, and less active than Cat 1 and Cat 2. This result showed that the
drying process probably neither fully activated the Mo species to combine the phosphorus
with Al2O3 during the incomplete decomposition of (NH4)3PO4⋅12MoO3⋅3H2O nor
decompose Co(PO4)2 to CoP, Co2P or Co with heating [22]. Furthermore, the catalysts from
the drying method did not completely form Co and Mo oxides that produced the low active
species. The catalysts (Cat 3 and Cat 4) based on the simultaneous method were less active.
The Cat 3, based on the simultaneous method, with calcination exhibited a conversion of
15%. The mixture of the aqueous solution of Mo and Co caused the precipitation to form
large particles on alumina on heating. The conversion factor for Cat 5 at 7.5 h was the same
value (38%) as Cat 4. The catalysts made by the drying method had a middle level of activity
between the catalysts formed by the consecutive method with calcination (Cat 1 and Cat 2)
and the simultaneous method with calcination (Cat 3).
1.0
0.8
Conversion / -
0.6
0.4
0.2
0.0
0 2 4 6 8 10 12
Time on stream / h
Figure 2. HDS of dibenzothiophene over various 623 K-sulfided CoMoP/Al2O3 catalysts at 513 K and a
total pressure of 2.0 MPa. (■) Cat 1, (□) Cat 2, (▲) Cat 3, (△) Cat 4 , (●) Cat 5, and (○) Cat 6.
Table 1. Reaction products and selectivity of the desulfurization and

hydrogenation at 8 h
Concentration [mmol/L] Selectivity [-]

BP/(THDBT+
Catalyst BPa Conc. CHBb Conc. THDBTc Conc. BCHd Conc. BP/CHB
CHB+BCH)
Cat 1 34.1 3.49 0 0 9.78 9.78
Cat 5 18.2 4.75 0.624 0.224 3.85 3.25
Cat 2 31.6 3.74 0.200 0.150 8.43 7.70
Cat 6 14.7 2.52 0.553 0.117 5.84 4.61
Cat 3 7.26 0.487 0.324 0 14.9 8.95
Cat 4 19.4 2.33 0.440 0.106 8.32 6.74
a
Biphenyl, b cyclohexylbenzene, c tetrahydrodibenzothiophene, and d bicyclohexyl.
BPN/(CHB+THDBT+BCH) / -
12
0
0 2 4 6 8
Time on stream / h
Figure 3. Selectivity of biphenyl to cyclohexylbenzene, tetrahydrodibenzothiophene, and bicyclohexyl.
(■) Cat 1, (○) Cat 2, (▲) Cat 5, (△) Cat 6.
The selectivities of biphenyl to cyclohexylbenzene, tetrahydrodibenzothiophene, and

bicyclohexyl are shown in Table 1 and Fig. 3. No tetrahydrodibenzothiophene and
bicyclohexyl were observed for Cat 1, but they were formed at about 0.15 and 0.2 mmol/L for
Cat 2. The biphenyl selectivity for Cat 1 and Cat 5 (selectivity for the C-S hydrogenolysis)
was higher than those for the Cat 2 and Cat 6 catalysts as shown in Fig. 3. Based on the
results, the second impregnation of CoP was preferred to the C-S hydrogenolysis due to the
creation of Co on the surface and the binding with the Mo sulfides. Manoli et al. [23] reported
that phosphorus modifies the catalytic behavior in several ways; i.e., increases the Mo4+
abundance [17], increases the number of Lewis acid sites, and subsequent enhancement of the
direct desulfurization rate [4]. Although the dried Cat 5 and Cat 6 catalysts exhibited lower
activities than Cat 1 and Cat 2, they contained a concentration of tetrahydrodibenzothiophene
2-3 times higher than that for Cat 2. The drying method before sulfidation promoted the
hydrogenation activity of the CoMoP/Al2O3 catalysts. Furthermore, phosphorus addition
could promote the hydrogenation pathway of HDS as suggested from the promotion for
NiMo/MCM-41 [24]. Although Cat 3 and Cat 4 exhibited a high biphenyl selectivity of 9, it
might contain a higher error because of the low conversion (below 20%). The simultaneous
mixing of the Co and Mo phosphoric acids likely caused a buildup of the active species or
participated with the Mo and Co phosphoric acid particles to form large particles.
The effect of the reduction treatment instead of sulfidation was carried out using Cat 7
and Cat 8 reduced at 623 K (Fig. 4). These catalysts were less active at conversions below 18
% after a 3-h run. Although the 623 K-reduced catalyst was the most active of the NiMo
phosphorus catalysts reduced at 573-923 K in the dibenzothiophene HDS as reported in a
previous paper [25], the sulfided catalyst was more active than the reduced NiMo/Al2O3
catalysts. Tetrahydrodibenzothiophene and bicyclohexyl were scarcely observed. The
selectivity of biphenyl to cyclohexylbenzene (approximately 10) for the reduced catalysts was
similar to that for the sulfided catalysts, but the conversion for the reduced catalysts was
lower than that for the sulfided catalysts. The reduction treatment was not useful for the
activity improvement due to the hard sulfidation of the CoP and MoP formed by reduction.
The sulfidation treatment should have a good catalyst consisting of a phosphorus containing
CoMo catalyst.
1.0
0.8
Conversion / -
0.6
0.4
0.2
0 2 4 6 8 10 12
Time on stream / h
Figure 4. The effect of the reduction treatment for Cats 1, 2 ,and 3 reduced at 623 K. (■) Cat 7 and (●)
Cat 8.
3.2. Difference between Mo Phosphide and Mo with Phosphorus Addition
In order to determine the difference in the HDS activity between the Mo compound
containing phosphorus ((NH4)3PO4⋅12MoO3⋅3H2O) and the Mo compound without
phosphorus ((NH4)6Mo7O24⋅4H2O) for the preparation procedures of the precursors, the

catalyst to which were separately added Mo and phosphorus ((Mo+P)+ Co) was prepared.
The separately added-phosphorus catalyst had the same high or slightly higher HDS rate than
Cat 1 (Fig. 5A). It appeared that the calcination procedure separated the Mo phosphorus from
phosphorous oxide which probably bonded to the alumina. Lewis and Kylk [7] reported that
molybdena on P/Al2O3 is more easily sulfided than that on Al2O3, in particular molybdena
bonded to the phosphorus-OH group is readily sulfided [7,8]. Furthermore, Quartararo et al.
[6] suggested that the phosphorus addition decreased the activity by the formation of the
AlPO4 or Al2(MoO4)3, phase, but promoted the activity by the formation of Mo-O-P species
in MoP-Al such as heteropolymolybdate species (PMo12O403−) [26]. Based on this result, the
preparation of the catalyst containing both Mo and phosphorus was not related to the HDS
activity, but the second impregnation of Co phosphoric acid and calcination is useful for the
formation of the active species for HDS. In addition, the biphenyl/cyclohexylbenzene
selectivity of Cat 1 had a higher selectivity for biphenyl to cyclohexylbenzene than that for
the catalyst prepared without the phosphorus Mo compound (Fig. 5B).
Tetrahydrodibenzothiophene and bicyclohexyl were not observed for Cat 1, but were
observed for the separately-added phosphorus catalyst. Consequently, the catalyst containing
both Mo and phosphorus (Cat 1) preferred the C-S hydrogenolysis selectivity probably due to
the formation of sulfided (cobalt-decorated) heteropolymolybdate on the Al2O3 surface.
1.0
0.8
Conversion / -
0.6
0.4
0.2
0.0
0 2 4 6 8 10 12
Time on stream / h
Figure 5A. The HDS for the phosphorus-added catalyst vs. Cat 1. (■) Cat 1 and (●) phosphorus-added
((Mo+P)+Co) catalyst.
15
12
BPN/CHB / - 9
0
0 2 4 6 8 10 12
Time on stream / h
Figure 5B. The selectivity for biphenyl to cyclohexylbenzene. (■) Cat 1 and (●) phosphorus-added
((Mo+P)+Co) catalyst.
3.3. Composition of the Catalyst by XPS
The ratios of Co, sulfur, and phosphorus to (Co and Mo) before and after the reaction are
shown in Table 2 and Fig. 6. The catalysts with calcination and the consecutive impregnation
(Cat 1 and Cat 2) had the higher ratios of Co/(Co + Mo) and S/(Co + Mo) before and after the
reaction. The Co/(Co + Mo) ratios for Cat 1 and Cat 2 were higher than those of Cat 5 and
Cat 6. This result indicated that the calcination of the catalysts increased the Co amount on
the surface. From the XPS analysis, the presence of phosphorus on the support surface forced
the formation of octahedral Co2+ species and irregular oxide Mo6+ particles [27] as well as
improved the cobalt phase dispersion in the oxide precursor state of the catalyst [28].
Furthermore, the Co/(Co+Mo) ratio after the reaction was higher than that before the reaction.
The Co atoms of all the catalysts came to the surface from the inside during the reaction. The
catalyst from the second impregnation of CoP contained more phosphorus than the first
impregnation of the CoP catalysts before and after the reaction. The gradual decrease in
phosphorus is due to the release of phosphorus from the Al2O3 surface at the total pressure of
2.0 MPa and hydrogen flow rate of 4 L/h. Furthermore, Cat 1 and Cat 2, by calcination before
sulfidation, exhibited a higher S/(Co+Mo) ratio than Cat 5 and Cat 6 by drying before
sulfidation. This is probably because the Co and Mo oxides were more readily sulfided than
CoP and MoP. The sulfidation of the cobalt promoted catalysts would increase the extent of
stacking of the molybdenum disulfide layers [2,3]. The binding energies of the oxides with
alumina were lowered by compensation of the phosphorus bonded with alumina, and
consequently, the Mo oxides were liberated and readily sulfided by hydrogen sulfide.
Furthermore, after sulfiding at 623 K, the Co-Mo-S phase is most likely still to be associated
with the AlPO4 species [29]. Mangnus et al. [30] reported that the cobalt sulfide species are
formed upon sulfiding of the CoO, Co3O4, cobalt nitrates or cobalt species surrounded by a
small number of phosphates. Co3(PO4)28H2O is also reported to sulfide to a minor extent
below 800 K. The composition of the active Cat 1 was CoMo1.4S2.9P0.57 (CoMoS2·Mo0.4P0.57).
The composition of Cat 1 had decreased Mo, S, and P contents in the catalyst and became
CoMo1.2S1.4P0.4 after the reaction.
Table 2. XPS results for Cats 1, 2, 3 and 4 before and after the reaction
Co/(Co+Mo) Mo/(Co+Mo) S/(Co+Mo) P/(Co+Mo)

br ar br ar br ar br ar
Cat1a 0.425 0.451 0.575 0.549 1.22 0.746 0.244 0.182
Cat2a 0.464 0.512 0.536 0.488 1.14 0.964 0.085 0.044
Cat5b 0.233 0.419 0.767 0.523 0.824 0.791 0.097 0.087
Cat6b 0.317 0.411 0.683 0.589 0.889 0.787 0.081 0.068
a
calcination before sulfidation.
b
drying before sulfidation.
1.6 Co S P
1.4 /(Co+Mo) /(Co+Mo) /(Co+Mo)
1.2
Atomic ratio / -
1.0
0.8
0.6
0.4
0.2
0.0
Catalyst
Figure 6 Surface composition of sulfided CoMoP/Al2O3 prepared by the consecutive methods by XPS.
( ) Cat 1 and ( )Cat 2.
CONCLUSION
The catalysts made by the consecutive impregnation method using Co and Mo
phosphoric acids exhibited higher conversion than those made by the other methods. The
catalysts with drying after the Co and Mo impregnation and the catalysts prepared by the
simultaneous method were less active. From the XPS analysis, the Co/(Co+Mo) ratio after the
reaction was higher than that before the reaction. The Co atoms migrated to the surface from
the inside during the reaction. The Co and Mo oxides in Cat 1 and Cat 2 with calcination
before sulfidation exhibited a high S/(Co+Mo) ratio and were more readily sulfided than CoP
and MoP. The catalysts (calcination) made by the second Co impregnation of phosphoric acid
had a higher ratio of P/(Co+Mo) than the catalysts prepared by the other methods, resulting in
stacking of the CoMoS slabs, which were prepared from the sulfidation of cobalt-decorated
heteropolymolybdate species (PMo12O403−). The catalyst contained CoMo1.4S2.9P0.57 before
the reaction which was active for dibenzothiophene HDS.
REFERENCES
[1] D. Ferdous, A. K. Dalai, J. Adjaye, L. Kotlyar, Appl. Catal. A: Gen. 294 (2005) 80.
[2] D. Frdous, A. K. Dalai, J. Adjaye, J. Mol. Catal. A: Chem. 234 (2005) 169.
[3] M. Villarroel, P. Baeza, F. Gracia, N. Escalona, P. Avila, F. J. Gil-Llambías, Appl.
Catal. A: Gen. 364 (2009) 75.
[4] D. Ferdous, A. K. Dalai, J. Adjaje, Appl. Catal. A: Gen. 260 (2004) 137, 153.
[5] E. J. M. Hensen, V. H. J. de Beer, J. A. R. van Santen J. Catal. 215 (2003) 353.
[6] J. Quartararo, J.-P. Amoureux, J. Grimblot, J. Mol. Catal. A: Chem. 162 (2000) 353.
[7] J. M. Lewis, R. A. Kydd, J. Catal. 136 (1992) 478.
[8] S.M.A.M. Bouwens, J.P.R. Vissers, V.H. J. de Beer, R. Prins, J. Catal. 112 (1988) 401.
[9] T. Koranyi, Appl. Catal. A: Gen. 239 (2003) 253.
[10] J. M. Lewis, R. A. Kydd, P. M. Boorman, P. H. van Rhyn, Appl. Catal. A: Gen. 84
(1992) 103.
[11] S. Sigurdson, V. Sundaramurthy, A. K. Dalai, J. Adjaye, J. Mol. Catal. A: Chem. 291
(2008) 30.
[12] S. Eusbouts, J.N.M. van Gestel, J.A.R. van Veen, V.H.J. de Beer, R. Prins, J. Catal.
131 (1991) 412.
[13] A. Spojakina, S. Damyanova, L. Petrov, Z. vit, Appl. Catal. 56 (1989) 163.
[14] S. K. Maity, G. A. Flores, J. Ancheyta, M. S. Rana, Catal. Today 130 (2008) 374.
[15] A. Andreev, Ch. Vladov, L. Prahov, P. Atanasova, Appl. Catal. A: Gen. 108 (1994)
L97.
[16] M. W. J. Crajé, V. H. J. de Beer, A. M. van der Kraan, Catal. Today 10 (1991) 337.
[17] T. Fujkawa, Top. Catal. 52 (2009) 872.
[18] S.T. Oyama, J. Catal. 216 (2003) 343.
[19] A. W. Burns, K. A. Layman, D. H. Bale, M. E. Bussell, Appl. Catal. A: Gen. 343
(2008) 68.
[20] C. Stinner, R. Prins, Th. Weber, J. Catal. 202 (2001) 187;191 (2000)438:
[21] F. Sun, W. Wu, Z. Wu, J. Guo, Z. Wei, Y. Yang, Z. Jiang, F. Tian, C. Li, J. Catal. 228
(2004) 298.
[22] P. J. Mangnus, J. A. R. van Veen, S. Eijsbouts, V. H. J. de Beer, J. A. Moulijn, Appl.
Catal. 61 (1990) 99.
[23] J.-M. Manoli, P.Da Costa, M. Brun, M. Vrinat, F. Mauge, C. Potvin, J. Catal. 221
(2004) 365.
[24] J. M. Herrera, J. Reyes, P. Roquero, T. Klimova, Microporous Mesoporus Mat. 83

(2005) 283.
[25] M. Nagai, T. Fukiage, S. Kurata, Catal. Today 106 (2005) 201.
[26] D. Nicosia, R. Prins, J. Catal. 234 (2005) 414.
[27] B. Pawelec, T. Halachev, A. Olivas, T. A. Zepeda, Appl. Catal. A: Gen. 348 (2008) 30.
[28] S.M.A.M. Bouwens, A.M. van der Kraan, V.H. J. de Beer, R. Prins, J. Catal. 128
(1991) 559.
[29] P. J. Mangnux, A.D. van Langeveld, V. H. J. de Beer, J. A. Moulijn, Appl. Catal. 68
(1991) 161.
[30] P. J. Mangnux, V. H. J. de Beer, J. A. Moulijn, Appl. Catal. 67 (1990) 119.
Chapter 11
MIXED TRANSITION METAL ACETYLIDES

WITH DIFFERENT METALS CONNECTED
BY CARBON-RICH BRIDGING UNITS:
ON THE WAY TO HETERO-MULTIMETALLIC
ORGANOMETALLICS*
Heinrich Lang† and Alexander Jakob

Technische Universität Chemnitz, Fakultät für Naturwissenschaften,
Institut für Chemie, Lehrstuhl für Anorganische Chemie,
Chemnitz, Germany
ABSTRACT
The chemistry of mono- and bis(alkynyl) transition metal complexes, modified
ferrocenes, functionalized alkynyls, diaminoaryl NCN pincer molecules (NCN =
[C6H2(CH2NMe2-2,6)2]-), and 1,4- and 1,3,5-substituted benzene derivatives towards
diverse metal fragments will be discussed and serves to understand the manifold and
sometimes unexpected reaction behavior of such species. Interesting novel (hetero)bi- to
undecametallic compounds with often uncommon structural motifs are formed in which
the respective transition metal building blocks are connected by carbon-rich p-conjugated
organic and/or inorganic bridging units. The reactions based on the modular molecular
“Tinkertoys” approach depend upon the steric and electronic properties of the metal
centers and ligands involved, which also will be discussed. The electrochemical behavior
of such 1-dimensional molecular wire molecules, coordination polymers, star-like
structured and dendritic oriented transition metal systems, respectively, is presented as
well.
*
A version of this chapter also appears in Organometallic Chemistry Research Perspectives, edited by Richard P.
Irwin, published by Nova Science Publishers, Inc. It was submitted for appropriate modifications in an effort
to encourage wider dissemination of research.
†
Heinrich Lang: E-mail: heinrich.lang@chemie.tu-chemnitz.de
384 Heinrich Lang and Alexander Jakob
INTRODUCTION
The coordinative and covalent linking of modular constructed transition metal building
blocks to generate heteromultimetallic assemblies increasingly gained interest during the last
years because such species may offer diverse applications in, for example, the field of
electroluminescence, information storage materials and photochemical molecular devices [1].
Also, they are of interest since they may be used as representative model compounds in the
fundamental study of electron-transfer and photoinduced energy-transfer processes [1]. One
possibility to synthesize such complexes includes the principle of molecular manufacturing
[2, 3]. This generally requires the prior preparation of multifunctional organic molecules
which allow the stepwise synthesis of multitopic organometallic assemblies. In particular, as
different binding sites of the bridging ligands reactive groups such as acetylides, phosphines,
N,N,(N)-donor systems (N,N,(N) = bi- or tri-dentate Lewis-base), … can be used to control
the synthesis of multimetallic complexes. In this respect, metal-containing alkynyls have been
studied extensively due to their rigid structures, their stability and, for example, their rich
spectroscopic, photophysical and electrochemical properties [1d, 4]. Examples of such
connectivities are 1,4-diethynyl benzene [5, 6], 1,3,5-triethynyl benzene [7, 8], 1-ethynyl-
4diphenylphosphino benzene [9], 5-ethynyl-2,2´-bipyridine [10] and 2,5-bis(alkynyl)
thiophenes [11, 12]. Based on these cores mainly homometallic assemblies have been
synthesized, while only less is known about heteromultimetallic transition metal species.
In context with this background we focuse in this chapter on the synthesis of heterodi- to
heterohexametallic transition metal complexes, a hitherto barely explored class of
compounds, supported by applying multitopic organometallic and organic building blocks.
This article is a continued amendment of recently published reviews in this field of chemistry
by one of the authors including recent developments made in organometallic p-tweezer
chemistry [13].
Bis(alkynyl) transition metal complexes of type RC=C-[M]-C=CR with [M] = 12 - 16
valence electron complex fragment, R = singly-bonded organic or organometallic group [13,
14], have recently been applied as organometallic bidentate chelating ligands (organometallic
p-tweezers) for the stabilization of low-valent metal fragments M'Ln (M' = element of groups
1, 2, 4, or 6 – 12 of the periodic table of the elements; L = neutral or ionic organic or
inorganic 2-electron donor ligand; n = 1, 2, 3, 4) [14]. In the thus accessible heterobimetallic
{[M](µ-s,p-C=CR)2}M'Ln tweezer molecules the alkynyl groups RC=C act as s-donors to M
and as p-donors to M', and hold the metals M (preferentialy an early transition metal atom,
such as Ti, Zr or Hf) and M' (vide supra) in close proximity to each other [14]. Synergistic
and cooperative effects between M and M' are observed and apparently, these complexes
show a versatile reaction chemistry and many applications [14].
Mixed Transition Metal Acetylides with Different Metals Connected … 385
A further extensively investigated chelating ligand in organometallic chemistry is the

potentially η3-chelating, monoanionic diaminoaryl pincer molecule NCN (NCN
=[C6H3(CH2NMe2-2,6)2]-) [13, 15]. Together with related diphosphino- and disulfido-
arylanions many pincer metal complexes are accessible, which possess a remarkable stability,
and at the same time show excellent catalytic properties [15]. Recently, this approach could
be successfully extended to synthesize pincer main-group element compounds [15].
Functionalized ferrocenes can act as bidentate chelating ligands towards many diverse
transition metal and main-group element entities [16]. In addition, the ferrocene moiety is an
exceptional building block in the preparation of, for example, multimetallic coordination
complexes which provide interesting electronic, optical and/or magnetic properties [17].
Moreover, ferrocenes are very robust materials and show a versatile and interesting redox
chemistry associated with, for example, polycarbon or related ligands derived from polyynes,
since ferrocenes are excellent organometallic one-electron reservoirs [17]. Although,
ferrocene celebrated its 50th anniversary six years ago [18], it still is a fountain of youth for
the synthesis of new types of transition metal complexes with specific properties. The concept
of “molecular Lego®” was independently established by Michl [2a] and Stoddart [3a].
Individual functionalized inorganic, organic and/or organometallic molecules can be
considered as modular “Tinkertoys” and can be assembled according to a specific building

design to give new complexes with unique chemical head structures. This construction
process should be reversible. The thus prepared parts can be maintained until the next
“molecular Lego®” process starts anew.
Herein we focus in the following on the use of mainly mono and bis(alkynyl) transition
metal complexes, ferrocenes, NCN pincer molecules, 1,4-/1,3,5-substituted benzenes,
functionalized acetylenes etc. as molecular “Tinkertoys” in the modular synthesis of
heteroatomic multinuclear assemblies with up to six different transition metal atoms. (For
other organic and/or inorganic connecting units, such as carboxylates, halides and
pseudohalides see refs. [13, 15, 18]). In this respect, special attention will be paid to the most
recent rersults from our group and others. We hope that we will be able to give new impetus
to the path-breaking and rapidly developing field of multiheterometallic organometallic
chemistry and applications of the systems. Therefore, this chapter is divided into two sections
(i) 102 Heinrich Lang and Alexander Jakob RECENT DEVELOPMENTS IN
ORGANOMETALLIC π-TWEEZER CHEMISTRY, and
in particular, (ii) MULTIHETEROMETALLIC TRANSITION METAL COMPLEXES.
In all organometallic systems different transition metals are spanned by carbon-rich π-
conjugated organic and/or inorganic units, allowing (more or less) electronic communication
between the metals along the bridging entities. However, clusters, or (linear) transition metal
complexes with direct metal-metal interactions will not be considered [19].
RECENT DEVELOPMENTS IN ORGANOMETALLIC

π-TWEEZER CHEMISTRY
Complexes of type RC≡C-[M]-C≡CR ([M] = 12 – 16 valence electron complex
fragment, R = singly-bonded organic or organometallic group) (type A molecule) [14n] with
their two alkynyl units act towards different metal fragments as organometallic bidentate
chelating ligands, or like the motto “an old principle but a new name” as organometallic π-
tweezers to afford heterobimetallic species of type B – G in which the respective metals M
and M’ are bridged by alkynyl ligands (Scheme 1) [14n].
The structures adopted by complexes B - G strongly depend on the relative affinity of the
metals M and M′ for electron density. If one metal atom (e.g., M) is more electrophilic than
the other (M′), then the alkynyl ligands RCβ≡Cα will preferentially bind to M through the
α atoms. This results in the formation of type B species in which both alkynyl ligands are σ-
bound to M and π-coordinated to the second metal M′. This is the preferred structure for
many early-late heterobimetallic complexes [14n]. In most complexes of the latter type, e. g.,
{[Ti](μ-σ,π-C≡CR)2}M′X ([Ti] = (η5-C5H5)2Ti, (η5-C5H4Me)2Ti, (η5-5H4SiMe3)2Ti,
...; M′= Cu, Ag, Au, ..; X = neutral or ionic inorganic or organic 2-electron donor ligand;
M′ = Ni, Co: X = CO, PR3, ...) the metals M′ within the tweezer framework have
coordination number 3 and possess a planar environment [14].
Scheme 1. Interconversion of alkynyl coordination modes in type A – G molecules [14n].
If the metals M and M′ are competitive in their affinities towards the alkynyl ligands
RC≡C, or if steric factors prevent the formation of type B tweezer complexes, then structural
type C or D species are formed. In these molecules, the ligands RC≡C are more evenly
shared, either with both metals, μ-bridged by both alkynyl ligands (type C) or with each
metal σ-bonded by one alkynyl unit and π-coordinated to the other (type D) [14].
In view of the fact that the two alkynyl ligands in type B molecules are held in close
proximity by [M], coupling reactions between the two RC≡C ligands are possible, forming
molecules of type E and G [14f, r, aa]. Steric and electronic effects appear to play an essential
role in determining the feasibility of the carbon-carbon bond forming reactions, as small
changes in the alkynyl-bonded groups R or in the ancillary ligands of M and M′ can induce
or prevent these reactions.
The state-of-the-art in the field of organometallic π-tweezer chemistry until 2000 is
depicted in Scheme 1. Many examples to date confirm this picture [14n]. While in the
beginning of this chemistry we have been increasingly attracted by the use of type A
molecules as organometallic chelating ligands [14n], we recently became interested in the
application of such systems to study, for example, electron transfer [14i, h, s, v, x], to create
self-assembled monolayers (SAMs) [20], and to prepare 1-dimensional molecular wire

molecules, which can be used in molecular electronics to span metal surfaces/electrodes [20].
Regarding these topics, special attention was drawn to low-valent alkynyl-stabilized
organo-copper(I) and -silver(I) compounds in which the respective metals possess a planar
surrounding [14]. While the use of alkyne- and alkynyl-stabilized inorganic and organic
group-11 metal fragments have lately been reviewed in detail [14], we focus here on recent
results obtained in the field of electron transfer.
Since the path-breaking and pioneering work of Creutz and Taube in early 1969 [21],
there has been a rapidly growing interest in the preparation as well as chemical and physical
properties of homo- and heterobimetallic organometallic and metal organic assemblies in
which the respective transition metals are connected by organic and/or inorganic (carbonrich)
π-conjugated bridging units [22, 23]. As this, many redox-active model compounds have
been synthesized, such as (η5-C5H5)(η5-C5H4)Fe-C≡C-Pt(dppe)(R) (1) [22t] (dppe =
diphenylphosphino ethane; R = aryl), [(η5-C5H5)Fe(η5-C5H4-C≡C-η5-C5H4)Co(η5-
C5H5)]+ (2) [24], trans-(PEt3)2(Ph)Pt-C≡C-C6H4-C≡C-MLn (3a, MLn =
Ru(Cl)(Ph2PCH2PPh2)2; 3b, MLn = Ru(η5-C5H5)(PPh3)2, …) [6b], (η5-C5Me5)(dppe)Fe-
C≡C-C≡C-Fe(η5-C5Me5)(dppe) (4) [22w, y], and [(η5-C5Me5)(NO)(Ph3P)Re-C≡C-
C≡C-C≡Mn(η5-C5H5)(CO)2]+ (5) [23p, 25] in which a molecular wire consisting of an all-
carbon C2-, C4- or C5-chain bridges the two metals M and M′ (M/M′ = Fe/Fe, Re/Mn,
Fe/Co, Fe/Pt), giving rise to an electronic coupling through three, five or even six bonds.
Further examples of molecular wire molecules are, for example,
(R′2PCH2CH2PR′2)(RC≡C)Mn-C≡C-C≡C-Mn(C≡CR)(R′2PCH2CH2PR′2) [26] (6)
(R = SiEt3, SiiPr3, SitBuMe2; R’ = Me, Et), (η5-C5H4Me)
(Me2PCH2CH2PMe2)Mn=C=C=Mn-(Me2PCH2CH2PMe2)(η5-C5H4Me) (7) [27], (η5-C5H5)
(NO)(Ph3P)Re-(C≡C)n-Re(η5-C5H4-Me)(NO)(PPh3) (8) (n = 1 – 10) [28], [trans-(R-4-
C6H4)(Ph3P)2Pd←N∩N→Pd(PPh3)2(C6H4-4-R)]m+ (9) (N∩N = 4,4'-bipy, C6H4-1,4-(C≡N)2,
(C6H4-4-C≡N)2, C5H4N-CH=CH-C6H4-CH=CH-C5H4N, …; R = Me(O)CS, m = 2; R = Ph3P,
m = 4) and [(R-4-C6H2(CH2NMe2-2,6)2)Pt←N∩N→Pt(C6H2(CH2NMe2-2,6)2-4-R]2+ (10)
[20]. In 10 the group-10 platinum redox termini can be adjusted in variable distances to each
other by the connecting entities N∩N [20]. Besides these species, further binuclear assemblies
with two different redox sites in close proximity were synthesized containing the cyano
acetylide ligand as bridging unit.
The isomeric heterobimetallic Fe-Ru complexes (η5-C5H5)(Ph3P)2Ru-C≡C-C≡N-Fe(η5-
C5H5)(dppe) (11) and (η5-C5H5)(dppe)Fe-C≡C-C≡N-Ru(η5-C5H5)(PPh3)2 (12) are readily
available [29], and the electrochemical response of each complex is characterized by two
oxidation waves found at 0.62 and 1.22 V (11) and at 0.66 and 1.37 V (12), respectively [29].
IR spectro-electrochemical investigations of the respective mono cationic species revealed a
noteworthy decrease in the energy of the ν(C≡C, C≡N) vibrations, which is consistent with a
contribution from the ligand to the redox active orbitals. [29] In addition, a intense NIR band
is observed at ν = 9600 cm-1 (ε = 5600 M-1 cm-1) for [(η5-C5H5)(Ph3P)2Ru-C≡C-C≡N-
Fe(η5- C5H5)(dppe)]+, while for [(η5-C5H5)(dppe)Fe-C≡C-C≡N-Ru(η5-C5H5)(PPh3)2]+ a
band at ν = 9600 cm-1 (ε = 5600 M-1 cm-1) is typical [29]. From oxidation potentials of
model alkynyl and cyano complexes featuring the (η5-C5H5)(dppe)Fe and Ru(η5-
C5H5)(PPh3)2 fragments, respectively, it looks like that initial oxidation of these two
assemblies takes place at the iron ion [29]. Examples of another type of binuclear compounds
are shown in Figure 1. It must be noted that since the first generation of the mixed-valence of
diferrocenyl acetylene in 1974 [30], the interest in these sandwich complexes has
significantly increased [31], because the ferrocenyl moiety is robust in its neutral and
oxidized form. It also was shown that oligoyne and polyyne chains can be stabilized next to
the direct linking of sp carbon atoms to the metals (vide supra) by joining the triple-bonded
systems to the ligand periphery as typical for the molecules represented in Figure 1. The
electrochemical response of these systems has been selectively reported with a focus on the
variation of the connecting unit and the nature of the metal groups [32]. There it is found that
the doubly bridged diiron species (ΔE = 0.25 V) exhibit two sequential one electron
oxidations with greater separation in the E1/2 potentials than the singly bridged analogues [32].
From NIR studies it is assumed that the doubly bridged ferrocenes are more strongly coupled
than the singly bridged ones [32]. The binuclear cobalt complex shown in Figure 1 possesses
two potentials at 0.846 and 0.947 V in the cyclic voltammogram [33]. Apparently, in the
radical cationic state the two cobalt atoms interact via the butadiyne chain. Although the
complexes gave no ESR signals, the cyclic voltammetric results are in good agreement with a
valence-trapped species.
Figure 1. Selected oligometallic complexes featuring acetylide-based connecting ligands [32, 33].
Diethynyl di- and triferrocenyls have also been considered as potential connecting units.
[34] Interactions between the remote ferrocenyl redox probes through the Fcn core (n = 1, 2,
3) were investigated [34]. However, it was found that the interpolation of the Fc2 moiety does
not impede electronic communication between the two Fc units, although more attention is
apparent with the Fc3 entity. This means that the terminal groups and the oligo-ferrocene
skeleton act almost independently. For an excellent review on this topic see ref. [29b].
Next to the high variety of late-late transition metal complexes (vide supra), also a
number of early-late species, e.g. (η5-C5H5)(Me3P)2Ru-C≡C-Zr(η5-C5H5)2(Cl) (13) are
known [23l]. Further examples of this family are depicted in Figure 2. Complexes 14 - 16 are
suited to transport electrons along the organic π-system between the redox-active metal
termini.
Figure 2. Organometallic π-tweezer molecules with (benzene tricarbonyl) chromium (14), ferrocenyl
(15, 16) and ruthocenyl (15) (redox-active) termini [14n, v, w, aa, 35 - 38].
Cyclic voltammetric studies of 14 show a reversible wave at E0 = -1.6 V (ΔE = 100 mV)
which can be assigned to the Ti(IV)/Ti(III) redox couple [35]. For the (η6-C6H5)Cr(CO)3 unit
the appearance of irreversible oxidation waves is typical [39]. Replacement of this fragment
in 14 by less electron withdrawing groups such as ferrocenyl or ruthocenyl units affords the
organometallic π-tweezers [Ti][(C≡C)mMc][(C≡C)nM′c] (15a, m = n = 1, Mc = M′c =
Fc; 15b, m = n = 1, Mc = M′c = Rc; 15c, m = n = 2, Mc = M′c = Fc; 15d, [Ti] = (η5-
C5H5)2Ti, m = n = 2, Mc = M′c = Fc; 15e, m = n = 2, Mc = Fc, M′c = Rc; 15f, m = 1, n =
2, Mc = M′c = Fc; 15g, m = 1, n = 2, Mc = Rc, M′c = Fc; Fc = (η5-C5H4)Fe(η5-C5H5),
Rc = (η5-C5H4)Ru(η5- C5H5)) (Figure 2) [14v, x, aa]. Oxidation of 15 leads to an
instantaneously coupling of the acetylide-ferrocenyl or –ruthocenyl entities Mc(C≡C)m and
M′c(C≡C)n to give the appropriate all-carbon complexes by an electron transfer from Ti-
CC≡C to Mc or M′c across the π- conjugated acetylides (C≡C)m and (C≡C)n, respectively.
The oxidatively induced coupling of the Mc(C≡C)m and M′c(C≡C)n moieties is not even
averted when the alkynyl ligands in 15 are η2-coordinated to an additional transition metal
fragment as given in, i. e., {[Ti](μ-σ,π- C≡CFc)2}CuBr (17) and {[Ti](μ-σ,π-
C≡CFc)2}PdPPh3 (18) [14s, ee].
To prevent the metal-carbon cleavage in 15 the titanocene moiety was exchanged by [Pt]
since Pt-C bonds are significant more stable than Ti-C ones. In cis-[Pt](C≡CFc)2 (16a, [Pt] =
(bipy)Pt; 16b, [Pt] = (Ph3P)2Pt; 16c, [Pt] = (dppf)Pt; 16d, [Pt] = (bipm)Pt; bipy = 2,2'-
bipyridine; dppf = 1,1’-bis(diphenylphosphino)ferrocene; bipm = 2,2’-bispyrimidine) a d8-
electron configurated and hence, square-planar coordination of the Pt(II) ion is typical, which
contrasts with the tetrahedral surrounding of the titanium(IV) ion in [Ti]. The electrochemical
response of 16a and 16b shows two reversible one-electron oxidations centered on the Fc
moieties at E0 = -0.1 V (ΔE = 180 mV) and +0.05 V (ΔE = 115 mV) for 16a and E0 = +0.1
V (ΔE = 200 mV) and +0.17 V (ΔE = 200 mV) for 16b. This indicates a moderate
electronic interaction between the iron cores through the connecting organic chains and the
platinum atom. Nevertheless, the electronic interaction found in 16a and 16b is stronger as in
all-carbon Fc-C≡C-C≡C-Fc (ΔE = 100 mV) [37, 38]. Next to the two reversible oxidation
processes, irreversible one-electron reductions are found at -1.55 and -2.19 V for 16b and at -
1.46 V for 16a, which can be assigned to the reduction of Pt(II) to Pt(0). The second reduction
wave for 16a (Pt(I)/Pt(0)) is covered by the reversible reduction of the 2,2'-bipyridine ligand
(bipy/bipy- = -1.78 V (ΔE = 140 mV), bipy-/bipy2- = -2.47 V (ΔE = 180 mV)) [37]. In
addition, the electrochemical properties of cis-(dppf)Pt(C≡CFc)2, (16c) [{cis-(dppf)Pt-
(C≡CFc)2}CuBr] (19a), and [{cis-(dppf)Pt(C≡CFc)2}AgOClO3] (19b) were investigated
[40].Oxidation of 16c gives by an oxidative coupling of the FcC≡C fragments the all-carbon
butadiyne FcC≡C-C≡CFc along with [(dppf)Pt]2+ (Figure 3) [40].
Figure 3. Cyclic voltammogram of 16c in dichloromethane at 25 °C, [nBu4N]PF6 supporting electrolyte

(0.1 M), scan rate = 100 mV s-1. All potentials are referenced to the FcH/FcH+ redox couple (FcH =
(η5-5H5)2Fe) with E0 = 0.00 V (ΔEp = 150 mV) [40].
The oxidatively induced coupling of the FcC≡C units is averted, when the alkynyl
ferrocene ligands in 16c are π-bonded to a low-valent CuBr moiety, i.e., [{cis-(dppf)-
Pt(C≡CFc)2}CuBr] (19a), which differs from the appropriate titanocene species (vide supra)
[40]. When instead of the CuBr moiety the higher homologue of copper is used then again the
coupling of the FcC≡C ligands takes place. Next to the formation of FcC≡C-C≡CFc the
mononuclear cationic platinum compound [(dppf)Pt(L)(OH)]X (L = thf, CH3C≡N; X = Br,
ClO4) along with elemental silver was produced. A detailed mechanism for the formation of
the latter species is presented in ref. [40]. The higher oxidation potentials for the silver
complexes as compared with the copper counter parts suggest that there is less stabilization of
the silver in the bis(alkynyl) platinum complexes than in the copper-platinum-iron assemblies
[40]. A similar behavior was found for cis-(dppf)Pt(C≡CPh)2 [41]. When the Fc units in 16
and 19 are replaced by Rc moities (Rc = (η5-C5H4)(η5-C5H5)Ru), then more stable
compounds are obtained, which most likely is attributed to the higher oxidation potential of
the Rc fragments.
Extending the idea of connecting early-late and late-late transition metal building blocks
from all-carbon to other carbon-rich μ-σ,π-conjugated organic bridging units enables the
synthesis of a large variety of further organometallic compounds by applying the modular
“Tinkertoy” approach.
MULTIHETEROMETALLIC TRANSITION METAL COMPLEXES

Within this Section the modular preparation of multimetallic transition metal compounds
featuring two, three, four, five, or even six different redox active early and/or late transition
metals will be discussed. This idea can be extended even to complexes of higher nuclearity
(undecametallic systems) possessing a variety of two, three or four distinct metal atoms.
Concertedly for all heteromultimetallic species is that the individual metals are bridged by π-
conjugated carbon-rich organic and/or inorganic building blocks. To limit the scope of this
article we focus in the following on the synthesis, reaction chemistry, structure and bonding
of mainly multimetallic complexes based on mono- and bis(alkynyl) transition metal
complexes, functionalized diaminoaryl NCN (NCN = [C6H2(CH2NMe2-2,6)2]-) and NN’N
(NN’N = C5H3N(CH2NMe2-2,6)2) pincer molecules, modified ferrocenes as well as 1,4- and
1,3,5-substituted benzenes.
(HETERO)BIMETALLIC TRANSITION METAL COMPLEXES

Besides early-late organometallic π-tweezer complexes of structural type B (Scheme 1),
also titanocene and zirconocene mono-acetylides enable the synthesis of a series of
heterobimetallic compounds featuring early-late transition metal atoms [42]. Two selected
examples based on a titanocene (η5-C5H4SiMe3)2Ti core are depicted in Figure 4 [44].
Replacement of the C5H4N→{Ru} and C6H4-4-C≡N→{Ru} coordination complex
fragments in 20 and 21 by an organometallic sandwich moiety Fc (Fc = (η5-C5H4)(η5-
C5H5)Fe) leads to [Ti](CH2SiMe3)(C≡CFc) (22). Compound 22 represents a mixed early-late
transition metal molecule with a reasonable electron transfer between the reducible [Ti] and
oxidizable Fc groups via a C≡C connecting unit [44, 45]. A further example is (η5-
C5H5)2(Me3P)2Ru-C≡C-Zr(η5-C5H5)2(Cl) (13) in which the zirconium(IV) ion is directly
linked with a ruthenium(II) fragment by an acetylide unit [46]. Likewise, {Pt}(C≡C-C6H4-4-
C≡N) (23) ({Pt} = (C6H3(CH2NMe2-2,6)2)Pt) can act as starting source for the synthesis of
linear heterobimetallic complexes of type {Pt}-C≡C-C6H4-4-C≡N→M'L (24a, M'L =
{Pt}BF4; 24b, M'L = {Ru}; 24c, M'L = AuCl) [47].
Figure 4. Complexes 20 (left) and 21 (right) [44].
A series of supplementary heterobimetallic complexes based on Fc moieties is accessible

by applying different synthesis methodologies. Sonogashira cross-coupling of
ethynylferrocene (26) with 4-bromobenzonitrile or 5-bromo-2,2'-bipyridine afforded Fc-
C≡C-C6H4- 4-C≡N (27) and Fc-C≡C-bipy (28), respectively. Treatment of 27 and 28 with
{Pt}BF4, {Ru}N≡N{Ru}, (nbd)Mo(CO)4 (nbd = norbornadiene), Mn(CO)5Br, Ru(bipy)2Cl2
or (Et2S)2PtCl2 gave the appropriate binuclear complexes Fc-C≡C-C6H4-4-C≡N→M′L
(29a, M′L = {Pt}BF4; 29b, M′L = {Ru}) and Fc-C≡C-bipy(M′L) (30a, M′L =
Mo(CO)4; 30b, M′L = Mn(CO)3Br; 30c, M′L = Ru(bipy)2(PF6)2; 30d, M′L = PtCl2) in
which a rigid-rod structured alkynyl benzonitrile entity spans the ferrocene and the M′L
building blocks [13, 14a, 48].
Heterobimetallic iron-platinum and iron-palladium complexes based on the pincer
functionalized ferrocene Fc-NCN (NCN = [4-C6H2(CH2NMe2-2,6)2]-) are available by the
synthesis protocol shown in Scheme 3 [49, 50].
Compound 33b possesses the ability to reversibly bind sulfur dioxide and hence, can
successfully be used as a gas sensor for the detection of SO2 (Scheme 3) [49, 50]. Related Fc-
C≡C-NCNH (35) in which the NCNH and the Fc moieties are separated by an acetylide unit
is accessible from FcC≡CH by applying the Sonogashira cross-coupling protocol. Lithiation
of 35 and reaction of 35-Li with stoichiometric amounts of [(Et2S)2MCl2] (M = Pd, Pt)
produced Fc-C≡C-NCN-MCl (36a, M = Pd; 36b, M = Pt) [49, 50]. The introduction of a PdI
unit into ferrocene NCN pincer molecules is realizable by the oxidative addition of the
carbon-iodide bond in Fc-NCN-I or Fc-C≡C-NCN-I to palladium (e. g., [Pd2(dba)3], dba =
di(benzylidene) acetone). After appropriate work-up, complexes Fc-NCNPdI (33c) and Fc-
C≡C-NCN-PdI (35c) could be isolated in good yields.
Scheme 3. Synthesis of heterobimetallic 33a and 33b and their reaction behavior towards SO2
(formation of 34) [49, 50].
The influence of the connecting alkynyl-aromatic moieties has been considered through
electrochemical measurements of closely related complexes (vide supra) with a metal-ligand
combination and a range of ethynyl-aromatic bridging entities.
(HETERO)TRIMETALLIC TRANSITION METAL COMPLEXES

Recent work of our group has been concerned with (hetero)trimetallic complexes derived
from organometallic π-tweezers {[Ti](μ-σ,π-C≡CR)2}M′X and {[Pt](μ-σ,π-
≡CR)2}M′X (R = singly-bonded organic or organometallic fragment; M′X = 12 – 14
valence electron transition metal building block; [Pt] = (bipy)Pt, …) (type B molecule) in
which the M′X unit is complexed by both alkynyl ligands of the bis(alkynyl) transition
metal fragments [Ti](C≡CR)2 and [Pt](C≡CR)2 [14n]. In complexes of type {[Ti](μ-σ,π-
C≡CR)2}M′X the chelated metal atoms M′ and the [Ti](C≡CR)2 fragments are
coplanar, while in {[Pt](μ-σ,π- C≡CR)2}M′X the M′ center is displaced from the
plane defined by the Pt atom and the alkynyl ligands and hence, are non-planar [14n]. Within
these studies a closely related series of diverse complexes with interesting properties could be
prepared.
An approach to transition metal complexes with linear heterotrimetallic assemblies is
given by starting from the alkyne-stabilized copper(I) methyl compound {[Ti](μ-σ,π-
C≡CR)2}CuCH3 (37a, R = SiMe3; 37b, R = tBu). Reaction of 37a and 37b with equimolar
amounts of FcC≡CH produces upon loss of methane the appropriate copper(I) acetylide
{[Ti](μ-σ,π-C≡CR)2}CuC≡CFc (38) in which a rigid-rod structured Ti-Cu-C≡C-Fc
unit is present [14o]. Compounds similar to 38 can be obtained, when FcC≡CH is reacted
with 4- ethynylbenzonitrile or 5-ethynyl-2,2′-bipyridine which contain further N-ligated
sites. Thus formed {[Ti](μ-σ,π-C≡CR)2}CuC≡CR′ (39a, R′ = C6H4-4-C≡N; 39b,

R′ = bipy) reacts with, for example, {Ru}N≡N{Ru} ({Ru} = RuCl2(NN′N); NN′N =
[C5H3N(CH2NMe2-2,6)2]-) or (nbd)Mo(CO)4 to afford heterotrimetallic 40 (Ti-Cu-Ru) and 41
(Ti-Cu-Mo), respectively, (Figure 5) [14j, 48].
Figure 5. Trimetallic 40 (left) and 41 (right) (R = SiMe3, tBu) [14j, 48].
In 40 and 41 three different transition metals (TiCuRu, TiCuMo) are connected via
σ,π- bound acetylides and datively-bound benzonitrile (40) and 2,2′-bipyridine (41)
ligands. In 40 a linear Ti-Cu-C≡C-C6H4-C≡N-Ru-NN′N building block is characteristic
as evidenced by single X-ray structure analysis [LIT]. A further example of a similar
compound is [Ti](μ-
σ,π-C≡CSiMe3)2}Cu-C≡N→Cr(CO)5 (42) which is accessible by treatment of the
copper(I) cyanide {[Ti](μ-σ,π-C≡CSiMe3)2}CuC≡N (43) with the metal carbonyl
Cr(CO)5(thf) in a 1:1 molar ratio [52]. However, the latter molecule could only be
characterized spectroscopically, due to its great instability in solution at room temperature.
A further effort to include metal atoms within organic connecting moieties is possible by
treatment of the early-late titanium-copper and titanium-silver tweezers {[Ti](μ-σ,π-
C≡CSi- Me3)2}M′X (44a, M′X = Cu(N≡CMe)BF4; 44b, M′X = AgFBF3) with
Ph3PAuC≡N in a 1:1 molar ratio [52]. Complex 44a affords upon elimination of MeC≡N
cationic 45 (Figure 6) in which the linear Cu-N≡C-Au-P arrangment is stabilized by the
chelating effect of the organometallic π-tweezer [Ti](C≡CSiMe3)2. However, when 44b is
reacted with the same gold(I) precursor then heterotrimetallic 46 is obtained (Figure 6) [52].
Figure 6. Complexes 45 (left) and 46 (right) (R = SiMe3) [52].
In 45 the copper(I) ion is tri-coordinate and shows a planar surrounding set-up by the η2-
coordinated Ti(C≡CSiMe3)2 unit and the datively-bonded (Ph3P)AuC≡N building block
counting to 16-valence electrons at the copper center, while in 46 the coordination number of
silver(I) expands to four and an 18-valence electron fragment is formed [52]. Complex 46
displays a non-linear Ti-Ag-N≡C-Au array as required by the pseudo-tetrahedral geometry
around silver(I). For the different coordination behavior of copper(I) and silver(I) towards
Lewis-bases see refs. [14] and [53].
Although the reaction of [M](C≡CR)2 π-tweezers ([M] = [Ti], [Pt]; R = singly-bonded
organic or organometallic ligand) with different metal sources in a 1:1 ratio results in the
formation of heterobimetallic structural type B complexes (Scheme 1), an interesting class of
oligometallic species is produced in a straightforward manner, when two equivalents of the
organometallic π-tweezer [M](C≡CR)2 are allowed to react with copper(I) or silver(I) salts
[M′X], forming molecules of type [{[M](μ-σ,π-C≡CR)2}2M′]X (47 – 50) (Table 1).
In these complexes a single metal M′ (M′ = Cu, Ag) is tetrahedrally coordinated by two
organometallic π-tweezer fragments [14]. However, it appeared that the counter-ion X must
be a poor ligand, such as BF4 -, ClO4 - and PF6 - to prevent the formation of structural type B
molecules. Complexes 47 - 50 are summarized in Table 1.
The molecular solid state structures of selected species of multimetallic 47 - 50 were

determined by single X-ray structure analysis. The cationic [{[M](μ-σ,π-C≡CR)2}2M′]+
part is set-up by two almost orthogonal positioned bis(alkynyl) transition metal fragments
[M](μ- σ,π-C≡CR)2 which are connected by a d10 M′+ metal ion. All four RC≡C
ligands are thereby η2-coordinated to M′+ forming a linear M-M′-M assembly. A
characteristic feature of complexes 47 – 50 is the non-equivalent linkages of Cα and Cβ to
M′ (M-Cα≡Cβ), which is even more pronounced as it is the case in type B molecules
[14]. In 49c the copper ion lies only slightly out of the best Pt(C≡CCPh)2 plane to presumably
minimize steric interactions between the phenylethynyl ligands and the dppe chelate, in 50b
an asymmetric structure is typical, which means that the silver(I) ion is more closely situated
to one Pt(C≡CCPh)2 fragment than to the other (Pt(1)–Ag 3.384 Å, Pt(2)–Ag 3.513 Å) [14,
54, 59].
Further possibilities to prepare 49a – 49c are presented in Scheme 4. The reactions shown
there are based on the stoichiometry of the reactants cis-[Pt](C≡CPh)2 and [Cu(N≡CMe)4]X
(X = BF4, PF6, ClO4) as well as on the temperature and the reaction time (Scheme 4) [14gg,
56, 57, 59]. It was found that, when cis-[Pt](C≡CPh)2 is reacted with [Cu(N≡CMe)4]X in
the ratio of 3:2, pentametallic Pt3Cu2 (51) is formed in which three helically arranged cis-
[Pt](C≡CPh)2 building blocks are connected by two copper(I) ions. In 51 the two outer
[Pt](C≡CPh)2 entities are coordinated by only one copper atom. For this, we reacted 51 with
a further type B molecule to obtain even higher oligomeric structures. To our surprise only
trimetallic 49 could be isolated. However, treatment of cis-[Pt](C≡CPh)2 with the copper
Table 1. Synthesis of Complexes 47 – 50
Compound [M] R M` X Refs.

47a (η5-C5H4SiMe3)2Ti Ph Cu BF4 14d, 87
47b (η5-C5H4SiMe3)2Ti Ph Cu PF6 14d, 87
47c (η5-C5H4SiMe3)2Ti F Cu BF4 14d
48a (η5-C5H4SiMe3)2Ti Ph Ag BF4 14d, 87
48b (η5-C5H4SiMe3)2Ti Ph Ag PF6 14d, 87
48c (η5-C5H4SiMe3)2Ti Ph Ag ClO4 14d, 87
48d (η5-C5H4SiMe3)2Ti Fca) Ag PF6 14w
48e (η5-C5H4SiMe3)2Ti Fca) Ag ClO4 14d
48f (η5-C5H5)2Ti C≡CFca) Ag PF6 14w
48g (η5-C5H4SiMe3)2Ti C≡CFca) Ag PF6 14w
48h (η5-C5H4SiMe3)2Ti Rcb) Ag PF6 14w
49a (bipy)Ptc) Ph Cu BF4 55, 59
49b (bipy`)Ptd) Ph Cu BF4 55, 59
49c (dppe)Pte) Ph Cu BF4 55, 59
49d (bppz)Ptf) SiMe3 Cu BF4 55, 59
49e (bipy)Ptc) Fca) Cu Br 61
49f (bipy)Ptc) Fca) Cu BF4 61
49g (dppf)Ptg) Ph Cu BF4 58
50a (bipy)Ptc) Ph Ag BF4 55, 59
50b (bipy)Ptc) Ph Ag PF6 55, 59
50c (bipy)Ptc) Ph Ag ClO4 55, 59
50d (bipy`)Ptd) Ph Ag BF4 55, 59
50e (bipy`)Ptd) Ph Ag PF6 55, 59
50f (bipy`)Ptd) Ph Ag ClO4 55, 59
50g (bipy)Ptc) Fca) Ag ClO4 61
Compound [M] R M` X Refs.

50h (bppz)Ptf) SiMe3 Ag ClO4 55, 59
50i (PPh3)2Pt Ph Ag ClO4 54
50j (PEt3)2Pt Ph Ag ClO4 54
50k (dppe)Pte) Ph Ag ClO4 54
50l (PPh3)2Pt t Bu Ag ClO4 54
50m (dppe)Pte) t Bu Ag ClO4 54
50n (dppf)Ptg) Ph Ag BF4 58
a) Fc = (η5-C5H4)Fe(η5-C5H5). b) Rc = (η5-C5H4)Ru(η5-C5H5). c) bipy = 2,2'-bipyridine. d) bipy' = 4,4'- dimethyl-2,2'-bipyridine. e) dppe = 1,2-
diphenylphosphinoethane. f) bppz = 2,5-bis(2- pyridyl)pyrazine. g) dppf = 1,1'-bis(diphenylphosphino) ferrocene.
source [Cu(N≡CMe)4]X and using the molar ratio of 2:1 at low temperature gave 52, a
compound in which the copper(I) ion is π-bound by one PhC≡C ligand of individual cis-
[Pt]C≡CPh)2 units, thus resulting in a linear alkyne-copper-alkyne arrangement (alkyne =
midpoint of the C≡C triple bond). This complex can be considered as an intermediate in the
formation of 49 (Scheme 4). Slowly warming a tetrahydrofuran solution containing this
species to 45 °C, 52 smoothly rearranges via the formation of 53 and 54 to give 55 as
evidenced by spectroscopic and single crystal X-ray diffraction studies [14gg, 45, 56 57, 58,
59]. When 49 is further reacted with one equivalent of [Cu(N≡CMe)4]X the incoming Cu(I)
adds to the alkynyl ligands of 49 resulting in the formation of 55 (Scheme 4). In 55 two
bis(alkynyl) platinum entities are linked by copper(I) ions, whereby two PhC≡C units, one
associated with each platinum atom, are π-bonded to the group-11 metal copper.
Scheme 4. Reaction chemistry of cis-[Pt](C≡CPh)2 towards [Cu(N≡CMe)4]X; formation of 49 and 51

– 55 [55, 57, 59].
Another possibility to synthesize trimetallic 50a is given by treatment of the

platinumsilver species {cis-[Pt](μ-σ,π-C≡CPh)2}AgFBF3 (56) with stoichiometric
amounts of cis- [Pt](C≡CPh)2 as depicted in Scheme 5 [55, 57, 59]. The first step in the
preparation of 50a involves the elimination of BF4 - from 56 upon addition of the
organometallic chelate cis- [Pt](C≡CPh)2. Initially formed [{cis-[Pt](μ-σ,π-
C≡CPh)2}2Ag]BF4 (57) contains two cis- [Pt](C≡CPh)2 moieties which are η2-coordinated
to a silver(I) cation by all of the PhC≡C ligands. The two cis-[Pt](C≡CPh)2 units are
oriented parallel to the platinum atoms on opposite sites. This complex isomerizes in solution
to produce 58 and then 59, which afterward rearranges to give 50a. IR spectroscopic studies
gave the first hint for the different bonding modes of the alkynyl groups in 56 - 59 and 50a.
Additionally, the molecular solid state structures of these species were confirmed by single
crystal X-ray structure determinations [14gg, 45, 56, 59].
Scheme 5. Synthesis of 50a by reacting 56 with cis-[Pt]C≡CPh)2 [55, 57, 59].
Trimetallic M2M′ compounds of type (M = Fe, M′ = Hg, Cd, Zn, Pd; M = Pd, Pt,
M′ = Fe; …) can be synthesized in a straightforward manner by applying different
synthesis methodologies [60, 61]. Treatment of two equivalents of FcC≡CH with mercuric
acetate (Hg(OAc)2) in different solvents produced (FcC≡C)2Hg (60) along with acetic acid
[60, 61]. The reaction mechanism is discussed in the light of the mercurated and non-
mercurated reaction intermediates (depending on the solvents used), involving
FcC(O)CH2HgX, FcC(OMe)=CH2, FcC(O)Me, and FcC(OAc)=CH2, whereby X appeared to
contain another mercury atom [60a]. For comparison the reaction behavior of ethynylbenzene
witht the same mercurating systems has also been investigated [60, 61].
Isostructural (FcC≡C)2M complexes (61, M = Cd; 62, M = Zn) are accessible in a much
more straightforward reaction when FcC≡CLi is treated with MCl2 (M = Cd, Zn) in a 2:1
molar ratio [61]. After appropriate work-up, these complexes were obtained in good yield. In
the latter molecules group-11 and group-12 transition metal atoms are linking two ferrocene
ethynyl building blocks. Electrochemical studies, however, showed that between the FcC≡C
units no coupling is observed [61].
A Fe2Pd trinuclear complex of composition [(Fc-C≡C-1-C6H4-4-C≡N)2
Pd(PPh3)2](OTf)2 (63) is available by the reaction of Fc-C≡C-1-C6H4-4-C≡N (64) with
Pd(PPh3)2(OTf)2 [62]. Electrochemical studies of 63 showed that only one reversible redox
couple is found for the Fc units and hence, no electron transfer via the connecting metal
palladium atom takes place.
As shown earlier Fc-NCNH pincer molecules can successfully be used in the synthesis of
heterobimetallic complexes. The introduction of a further NCNH unit in Fc-NCNH opens the
possibility to prepare the ferrocene-based trimetallic FeM2 complexes 68 and 69 (M = Pd, Pt)
by starting from ferrocene 65 (Scheme 6). The reactions shown in Scheme 6 include
metallation-transmetallation and oxidative addition processes [49, 63].
Scheme 6. Synthesis of FeM2 complexes 68, 69a and 69b from 65 [49, 63].
Replacing the NCN pincer unit in (η5-C5H4-NCN)2Fe sandwich compounds by diphenyl

phosphino coordinating groups allows the synthesis of a series of trimetallic assemblies of
structural type (η5-C5H4PPh2MLn)2Fe (MLn = M(CO)5: 70a, M = Cr; 70b, M = Mo; 70c, M =
W; 71, MLn = (η6-C6H4-1-iPr-4-Me)RuCl2; 72a, MLn = AuCl; 72b, MLn = AuC≡Cbipy) [64,
65]. Molecules 72a and 72b can be used as starting materials for the preparation of complexes
of higher nuclearity and of, e.g., coordination polymers [64].
Other trimetallic MM′2 metal complexes are {[(η5-C5H4PPh2)2CuCl]Ti(μ-σ,π-
C≡CtBu)2}CuCl (73) [65], Pt[(μ-σ,π-C≡CPh)CdCl2]2 (74) [66], Pt[(C≡C-C6H4-2-C≡C-
C6H4- 2-C≡C)HgCl2]2 (75) [67], (nBu3P)2(L)(CO)Ru(C≡CFc)2 (76a, L = CO; 76b, L = C5H5N;
76c, L = P(OMe)3) [68], (Ph2P(CH2)nPPh2)2Ru(C≡CFc)2 (77a, n = 1; 77b, n = 2) [69],
(R3P)2Pt(C≡CFc)2 (78) [70], (R3P)2Pt(C≡C-Y-C≡CFc)2 (79a, Y = 1,4-C6H4; 79b, Y = 2,5-
thiophene, …; R = alkyl, aryl) [12a, 71], and [(η5-C5H4terpy)Fe(η5-C5H4PPh2)]2MCl2 (80a,
M = Pt; 80b, M = Pd; terpy = terpyridine) [61]. Trimetallic 80b can be used in the preparation
of pentametallic complexes featuring three different transition metals, since it possesses with
the terpy ligands further N-ligated coordination sites (see below). From 77 – 79 detailed
spectroelectrochemical investigations were carried out. These complexes display a degree of
electronic interaction between the metal-based redox groups located at the ligand termini. The
electrochemical response of these systems has been selectively reviewed, with a focus on the
variation in properties that accompany changes in the structure of the bridging ligand and the
nature of the metal groups [69-71].
So far, trimetallic molecules with two different transition metals have been discussed. A
straightforward synthesis method to prepare heterotrimetallic organometallic π-tweezer-
based derivatives with three different metal atoms is depicted in Scheme 7 [14a, 48].
Scheme 7. Synthesis of heterotrimetallic 83 by subsequent treatment of 81 with HC≡CSiMe3 followed

by complexation of 82 with [Cu(N≡CMe)4]ClO4 [14a, 48].
Compound 83 is accessible in a consecutive way by the alkynylation of

FcC≡Cbipy(PtCl2) (81) with HC≡CSiMe3 in presence of diisopropyl amine and catalytic
amounts of [CuI] to give FcC≡C-bipy[Pt(C≡CSiMe3)2] (82) which yields with
[Cu(N≡CMe)4]BF4 the trimetallic Fe-Pt-Cu complex 83 (Scheme 7) [14a, 48]. The cyclic
voltammogramms of 82 and 83 are shown in Figure 7.
For heterobimetallic 82 two redox waves are observed for the bipy ligand at E0,1 = -1.59
V (ΔEp = 120 mV) and E0,2 = -2.24 V (ΔEp = 130 mV) in the cyclic voltammogram (Figure
7, top) which is typical for chelate-bonded bipy ligands in platinum transition metal chemistry
[14a, 48]. The cyclic voltammogram of 82 also exhibits, as 81, a reversible oxidation for the
ferrocene moiety at E0 = 0.17 V (ΔEp = 130 mV) showing that this unit is more difficult to
oxidize than 81 and FcH, taken as standard [72]. Complexation of [CuFBF3] as given in 83
does not influence on the oxidation or reduction potentials of the FcC≡C-bipy[Pt(C≡CSiMe3)
2] moiety (Fe2+/Fe3+: E0 = 0.16 V (ΔEp = 120 mV); bipy: E0,1 = -1.60 V (ΔEp = 130 mV) E0,2
= -2.23 V (ΔEp = 120 mV). The coordinated copper(I) ion shows a irreversible reduction
wave at Ep,red = -1.82 V (Figure 7, bottom). This observation may imply that the copper(I)
reduction occurs initially resulting in fragmentation of FcC≡C-bipy{[Pt((μ-σ,π-
C≡CSiMe3)2]CuFBF3}. A similar phenomenon was found for other organometallic π-
tweezers, i.e. {[Ti](μ-σ,π-C≡CR)2}CuX [14a, 48].
In neutral 83 a Fc-C≡C-bipy unit is chelate-bonded to a Pt-Cu tweezer moiety. A similar
structural motif is also found in [({[Ti](μ-σ,π-C≡CSiMe3)2}M')bipy-C≡CFc]X (85a, M'
= Cu, X = PF6; 85b, M' = Ag, X = ClO4), where the 2,2'-bipyridine entity is coordinated to a
heterobimetallic {[Ti](μ-σ,π-C≡CSiMe3)2}M'+ tweezer fragment [14a, 48]. In this
molecule the group-11 metal ions copper and silver are chelate-bound by the organometallic
π-tweezer [Ti](C≡CSiMe3)2 and the 2,2’-bipyridine ligand resulting in tetra-coordination at
M'. These complexes are accessible by combining the mononuclear ferrocene acetylide
FcC≡C-bipy (84) with heterobimetallic early-late {[Ti](μ-σ,π-C≡CSiMe3)2}M'X (M'X =
Cu(N≡CMe)PF6; M'X = AgOClO3). While trimetallic 85a and 85b are stable in the solid
state, they slowly start to decompose in solution on exposure to air, i. e., 85b gives metallic
silver along with [Ti](C≡CSiMe3)2 [14a, 48].
Exemplary, the solid state structure of 85a was determined by single X-ray structure
analysis. The result thereof is shown in Figure 6 [14a, 48].
Figure 6. ORTEP plot (30 % probability level) of 85a with the atom numbering scheme (the hydrogen
atoms, the PF6 - counter ion, and the distortion of one Me3Si group are omitted for clarity). For selected
bond distances (Å) and angles (°) see ref. [14a, 48].
Figure 7. Cyclic voltammograms of 82 (top) and 83 (bottom) in tetrahydrofuran at 25 °C, [nBu4N]PF6

supporting electrolyte (0.1 M), scan rate = 100 mV s-1. All potentials are referenced to the FcH/FcH+
redox couple (FcH = (η5-C5H5)2Fe) with E0 = 0.00 V (ΔEp = 150 mV) [14a, 48].
Heterotrimetallic 85a shows a pseudo-tetrahedral coordination geometry around Cu1 with

two η2-coordinated Me3SiC≡C groups (C23-C24, C28-C29) and the chelate-bonded bipy
ligand (N1, N2). Noteworthy to mention is the difference between Cu1-N1 (2.225(4) Å) and
Cu1-N2 (2.044(4) Å) which verifies an asymmetrical chelate binding of the bipyridine ligand
to Cu1. The large dissimilarity between Cu1-N1 and Cu1-N2 in 85a most probably can be
ascribed to electronic effects resulting from the electron rich FcC≡C unit. For comparison,
[FcC≡C-bipy{[Ti](μ-σ,π-C≡CSiMe3)2}Cu]PF6 (85a) was subjected to cyclic voltammetric
studies (Figure 8).
Figure 8. Cyclic voltammogram of 85a in tetrahydrofuran at 25 °C, [nBu4N]PF6 supporting electrolyte

(0.1 M), scan rate = 100 mV s-1. All potentials are referenced to the FcH/FcH+ redox couple (FcH =
(η5-C5H5)2Fe) with E0 = 0.00 V (ΔEp = 150 mV) [14a, 48].
The relevant electrode potentials of 85a are for the iron(II) ion E0 = 0.12 V (ΔEp = 150
mV), the reduction of the copper ion at Ep,red = -1.45 V and the reduction process bipy/bipy- at
Ep,red = -2.67 V (Figure 8). The reduction of Cu(I) to Cu(0) is typical in Ti-Cu organometallic
π-tweezer chemistry implying that in such complexes the reduction occurs initially at the
Cu(I) ion resulting in fragmentation of the respective complexes (vide supra) [14a, 48].
However, when the cyclic voltammogram of 85a is measured only between -0.4 and -1.6 V
(Figure 8, inlet) the cathodic reduction of Cu(I) is followed by reoxidation of Cu(0) (E0 = -
1.39 V, ΔEp = 120 mV) obviously without any change of the chemical identity of the
molecule involved. In contrast, this is not the case for isostructural 85b, where instead of
copper(I) a silver(I) ion is present. Next to the redox couples Fe2+/Fe3+ (E0 = 0.13 V, ΔEp =
145 mV) and bipy/bipy- (Ep,red = -2.66 V), respectively, an irreversible reduction peak for
Ag(I)/Ag(0) is found at Ep,red = -1.26 V, i. e., no reoxidation peak is observed. In the second
run the only observable potentials are those ones typical for free FcC≡C-bipy and
[Ti](C≡CSiMe3)2 indicating that 85b fragmented into the starting materials.
Related trimetallic compounds to 83 and 85 can be obtained, when the gold(I) and
ruthenium(II) acetylides Ph3PAu-C≡C-bipy (86) and (η5-C5H5)(PPh3)2RuC≡C-bipy (87) are
reacted with the organometallic π-tweezer {[Ti](μ-σ,π-C≡CSiMe3)2}M'X (M'X =
Cu(N≡CMe)PF6, AgOClO3). After appropriate work-up, complexes [LnMC≡C-
bipy{[Ti](μ- σ,π-C≡CSiMe3)2}M′]X (88a, LnM = (Ph3P)Au, M' = Cu, X = PF6; 88b,
LnM = (Ph3P)Au, M' = Ag, X = ClO4; 89a, LnM = (η5-C5H5)(PPh3)2Ru, M’ = Cu, X = PF6;
89b, LnM = (η5- C5H5)(PPh3)2Ru, M' = Ag, X = ClO4) can be isolated as red solids in
excellent yield [48, 64].
Table 2. Electrochemical Data of 82 – 85a)
Compd. Fe2+/Fe3+ bipy/bipy.- b) bipy.-/bipy2- b) M′+/M′ c)
E0/V E0 (Ep,red)/V E0/V Ep,ox V Ep,red/V E0/V

(ΔEp mV) (ΔEp/mV) (ΔEp/mV) (ΔEp/mV)
82 0.17 (130) -1.59 (120) -2.24 (130) - - -
83 0.16 (120) -1.60 (130) -2.23 (120) - -0.82 -
84 0.10 (194) -2.36 (200) -2.76 (430) - - -
85a 0.12 (150) -2.67 - -1.33 -1.45 -1.39 (120)
85b 0.13 (145) -2.66 - - -1.26 -
a) In tetrahydrofuran. b) For electrode potentials of free bipy see ref. [73]. c) M′ = Cu, Ag.
They are fairly stable molecules, both in the solid state and in solution. The chemical and
physical properties of the latter compounds correspond to those of other gold(I) [74] and
ruthenium(II) [75] acetylides.
Another heterotrimetallic complex with a gold(I) acetylide unit is Ph3PAu-C≡C-NCN-
Pt- C≡C-Fc (91), which can be obtained by combining Ph3PAu-C≡C-NCN-PtCl (90) with
FcC≡CSnMe3 [74k]. Complex 91 represents a rigid-rod shaped molecular wire molecule in
which the transition metals Au, Pt, and Fe are spanned by acetylide, cyclopentadienyl and
phenylene units.
A heterotrimetallic molecule featuring iridium, platinum and rhodium metals is 92, which
is accessible by treatment of (NBu4)[{Ir-Pt}(C≡CSiMe3)2] with [Rh(cod)(acetone)x]+ (cod =
cyclooctadiene) [76]. The molecular solid state structure of 92 proves the presence of the
zwitter ion [(cod)Ir(μ-1κCα:η2-C≡CSiMe3)(μ-2κCα:η2-C≡CSiMe3)Pt-(μ-2κCα:η2-
C≡CSi- Me3)2Rh+(cod)], resulting from the dinuclear anionic fragment [(cod)Ir(μ-
1κCα:η2- C≡CSiMe3)(μ-2κCα:η2-C≡CSiMe3)Pt(C≡CSiMe3)2]- which acts as a
chelating dimetallo bidentate ligand towards the cationic [Rh(cod)]+ building block.
One more heterotrimetallic complex is represented by (dppf)(η5-C5H5)Ru-C≡C-C5H4-

N→W(CO)4PPh3 (93) in which a linear carbon-rich dimetalla Ru-C≡C-C5H4N-W segment is
present [77]. Replacement of the 4-ethynyl-pyridine by a 1-ethynyl-4-diphenylphosphino
benzene entity gives access to a further series of complexes, i. e. (dppf)(η5-C5H5)Ru-

C≡CC6H4PPh2- MLn (94, MLn = AuCl; 95, MLn = (η5-C5Me5)RhCl2; 96, (cod)RhCl) [64].
Other trimetallic complexes featuring the dppf group as a basic building block are
(dppf)Pt(C≡CPPh2MLn)2 (97a, MLn = AuCl; 97b, MLn = (η6-C6H4-1-iPr-4-Me)RuCl2) and
(dppf)Pt[(C≡CPPh2)2MLn] (98a, MLn = PdCl2; 98b, MLn = PtCl2; 98c, MLn = Mo(CO)4)
(Figure 9) which are accessible in consecutive reaction sequences as described in ref. [40].
Complex 98a was used as a catalyst in the Heck reaction of coupling iodobenzene with tert.-
butylacrylate to give E-tert.-butyl cinnamate [40].
The molecular solid state structures of 98a – 98c were established by single X-ray
structure analyses showing that constraint Pt(C≡CP)2M' rings (M' = Mo, Pd, Pt) are present.
This corresponds with the observation made that 98a is a very efficient catalyst in Heck
reactions showing very high activities [40].
Examples of other heterotrimetallic complexes are [(η5-C5H4terpyMLn)Fe(η5-
C5H4PPh2)]2M'Cl2 (M' = Pd: 99, MLn = Mo(CO)4; M' = Pt: 100, MLn = Mo(CO)4) [61].
Another possibility to synthesize heterotrinuclear transition metal assemblies is the use of
(poly)phenyleneethynes as connecting units to span different metal ions [78]. Recently, 1,3,5-
triethynylbenzene was introduced as core in organometallic chemistry to prepare symmetrical
and unsymmetrical bridged transition metal complexes. Due to its geometry and active
coordination sites this molecule allows to extend the core into three directions by using, e. g.
dehydrohalogenation and C-C coupling reactions. In general, there has been symmetric
homo-substitution around the benzene core based on iron, iridium, chromium, gold and
platinum containing metal building blocks (i. e., C6H3-1,3,5-(Fe(η5-C5Me5)(dppe))3 (101))
[5i, 7b 79], while only less is known about unsymmetrical substituted complexes of 1,3,5-
triethynylbenzene featuring, for example, trans-[Ru(dppm)2Cl], trans-[Os(dppm)2Cl],
[Ru(η5-C5H5)(PPh3)2] (dppm = bis(diphenylphosphino)methane), and ferrocenyl end-grafted
moieties [80]. These organometallic species are key molecules for the synthesis of
metallodendrimers, megamers, and nanostructured materials [81], and play an importend role
in homogeneous catalysis and in many electron-transfer processes [81]. However, only two
examples are known in which three different transition metal fragments are unsymmetrical
arranged around the periphery of a 1,3,5-triethynylbenzene core [8c, 82].
A suitable starting material for the preparation of additional heterotrinuclear σ-alkynyl

complexes is the 1,3,5-ethynylbenzene core 1-(Fc-C≡C)-3,5-(HC≡C)2C6H3 (102) because
alkynyl ferrocenes are known to be very robust to further reactions [8c]. Lithiation of 102
with LiN(SiMe3)2 followed by treatment with (bipy´)(CO)3ReCl (bipy´ = 4,4´-di-tert.-butyl-
2,2´-bipyridine) afforded heterobimetallic 1-(FcC≡C)-3-[(bipy´)(CO)3ReC≡C)]-5-
(HC≡C)- C6H3 (103). Complex 103 possesses with the free alkynyl entity a further reactive
site and therefore should have a great potential to introduce a third transition metal building
block and hence, forms oligomeric structures based on a 1,3,5-trisubstituted benzene core.
Thus, the reaction behavior of the disubstituted iron-rhenium assembly 103 towards diverse
transition metal complexes was studied.
The preferred synthetic method for the preparation of heterotrimetallic species was
accomplished by the addition of the organometallic metal chloride (η5-C5H5)(Ph3P)2RuCl to
103 in presence of the ammonium salt [H4N]PF6 and the base KOtBu (Scheme 8). The analog
osmium(II) complex could be prepared by the reaction of 103 with (η5-C5H5)(Ph3P)2OsBr in
refluxing methanol in presence of [H4N]PF6 followed by deprotonation of the vinylidene
intermediate [1-(FcC≡C)-3-[(bipy´)(CO)3ReC≡C)]-5-[(η5-C5H5)(Ph3P)2Ru=C=CH]C6H3]+
(104) by addition of sodium metal. After appropriate work-up, 1-(FcC≡C)-3-
[(bipy´)(CO)3ReC≡C)]-5-[(η5-C5H5)(Ph3P)2MC≡C]C6H3 (105, M = Ru; 106, M = Os)
could be isolated as orange powders in good yield [64]. A possibility to introduce a platinum
building block exists in the reaction of 103 with (PPh3)2PtCl2 in refluxing chloroform in
presence of diethylamine (Scheme 8) [64]. To avoid the formation of the corresponding
platinum bis(acetylide) complex the use of an excess of (PPh3)2PtCl2 is required. 1-(FcC≡C)-
3-[(bipy´)(CO)3ReC≡C)]-5-[Cl(Ph3P)2PtC≡C]C6H3 (107) could be isolated as a yellow
solid.
The influence of connecting alkynyl-aromatic moieties has been considered through
electrochemical measurements and is discussed in detail elsewhere [64].
A further series of trinuclear heterometallic complexes could be synthesized based on the
1,3,5-tri(ethynyl)benzene core as evidenced by [1,3-{Cl(PEt3)2PdC≡C}2-5-{(Me2bpy)(CO)3-
ReC≡C}C6H3] (108) and [1-{Fc-C≡C}-3-{(CO)3Cr(η6-C6H5C≡C)}-5-{Ph3PAuC≡C}C6H3]
(109) [83, 64]. For similar compounds see ref. [64].
Heterotrimetallic complexes based on the diphenylphosphino ferrocene building block
are FcPPh2Au-C≡CRc (110), FcPPh2Au-C≡C[(η6-C6H5)Cr(CO)3] (111), and FcPPh2Au-
C≡Cbipy[Mo(CO)4] (112) (Rc = (η5-C5H4)(η5-C5H5)Ru) [48, 64, 84]. Redox-active
multinuclear ferrocenyl ethynyl phosphanes and their palladium and platinum complexes Ph3-
nP(C≡CFc)n (113, n = 1; 114, n = 2; 115, n = 3) and [Ph3-nP(C≡CFc)n]M′X2 (M′ = Pd, X
= Cl: 116a, n = 1; 116b, n = 2; 116c, n = 3; M′ = Pd, X = I: 117, n = 1; M′ = Pt, X = Cl:

118a, n = 1; 118b, n = 2; 118c, n = 3) were independently described by Baumgartner [85] and
our group [84]. These ferrocenyl ethynyl phosphanes show an increasing number of
ferrocenyl ethynyl units including the corresponding M′X2 complexes.
Scheme 8. Reaction chemistry of 103; synthesis of heterotrimetallic 105 – 107 ((i) 1. LiN(Si-Me3)2,
toluene, 25 °C, 2 h; 2. (bipy’)(CO)3ReCl, toluene, reflux, 5 h. (ii) M = Ru: (PPh3)2(η5-C5H5)RuCl,
[H4N]PF6, KOtBu, CH2Cl2/MeOH, 5 h; M = Os: 1. (PPh3)2(η5-C5H5)OsCl, [H4N]PF6, MeOH, reflux, 3
h; 2. Na, MeOH, 25 °C, 1 h. (iii) cis-(PPh3)2PtCl2, CHCl3/HNEt2, reflux, 3 h) [64].
Solid state structures of this series of complexes were determined by X-ray structure
analysis. The PdI2-based complex shows a favourable trans-configuration with almost linear
alkynyl ligands. The thermal behavior of some of the newly synthesized compounds indicated
their utility as potential precursors for magnetic ceramic nanomaterials [85]. Although they
can successfully be used as catalysts in, for example, the Heck, Suzuki and Buchwald-
Hartwig reaction [84, 86]. Electrochemical investigations of the ferrocenyl ethynyl phosphane
ligands and the appropriate palladium and platinum complexes, respectively, revealed that the
structural motif of the ligands Ph3-nP(C≡CFc)n does not support multistep redox processes
within these materials. All assemblies showed single, reversible redox processes whose
potential is influenced by the substitution pattern of Ph3-nP(C≡CFc)n and the respective

complex geometries [84, 85].
Reaction of 118a with two equivalents of HC≡CFc in diisopropyl amine in presence of
catalyic amounts of [CuI], or treatment of 118c with LiC≡CFc in a 1:2 molar ratio produced
the nonametallic square-planar structured platinum(II) complex [(FcC≡C)Ph2P]2
Pt(C≡CFc)2 (119) in excellent yield [84]. In 119 a total of four ferrocene ethynyl groups are
present.
(HETERO)TETRAMETALLIC TRANSITION METAL COMPLEXES

Organometallic π-tweezer complexes of structural type B (Scheme 1) can also
successfully be used in the preparation of tetrametallic Ti2Ma′Mb′ species (Ma′ = Mb′;
Ma′ ≠ Mb′; Ma′, Mb′ = Cu, Ag) [14, 87]. In this respect, halides, pseudohalides,
dicarboxylates and, for example, nitrogen-based molecules have been utilized to connect
tweezer-chelated copper(I) and silver(I) ions. For a detailed discussion on this topic see ref.
[14b, e, 87]. The respective complexes may display metal-metal interactions, as the inorganic
or organic connecting units permit rapid intramolecular electron transfer. The
electrochemistry of selected complexes was studied by cyclic voltammetry. Semi-empirical
calculations were additionally carried out. [14h] The results indicate a strong intramolecular
interaction between the group-11 metals held in place by the organometallic bis(alkynyl) π-
tweezers.
Other tetrametallic MM′M2′′ compounds are {[M](μ-σ,π-C≡CFc)2}M′X
([M] = (η5- C5H4SiMe3)2Ti: 120a, M′X = Pd(PPh3); 120b, M′X = Ni(CO); 120c, M′X
= CuBr; 120d, M′X = CuCl; 120e, M′X = CuOTf; 120f, M′X = CuCl2; 120g, M′X =
ZnCl2; 120h, M′X = ZnBr2; 120i, M′X = AgCl; 120j, M′X = AgBF4; [M] = (bipy)Pt:
121a, M′X = CuBr; 121b, M′X = CuOTf; 121c, M′X = CuBF4; 121d, M′X = AgNO3;
121e, M′X = AgClO4; 121f, M′X = AgO2CCF3; [M] = [(Ph2PCH2PPh2)2Ru: 122, M′X =
CuI) [14, 61]. They are impressive examples of mixed early-late transition metal complexes
in which reducible and oxidizable groups are present in close proximity to each other. Their
electrochemical behavior is discussed in detail in refs. [14] and [61].
Further heterotetrametallic compounds are 125a and 125b (Figure 10) which are
accessible in a two-step synthesis procedure including the Sonogashira cross-coupling
reaction of 1,1`-bis(ethynyl) biferrocene (123) with I-1-NCN-4-Br and the oxidative addition
of (1,1`-Br-4-NCN-C≡C)2bfc (bfc = biferrocene) (124) to [Pd2(dba)3] and [Pt(tol)2(SEt2)]2,
respectively, [88].
Figure 10. Biferrocene-based molecules 125a (M = Pd) and 125b (M = Pt) [88].
Cyclic voltammetric measurements of 125a and 125b show that the ferrocene moieties
can be oxidized independently. The difference of the potentials of the Fe(II)/Fe(III) redox
couples is 300 mV and is not affected by the NCN transition metal pincer [88].
Similar results are obtained for the biferrocene-based complexes bfc(PPh2MLn)2 (127a,
MLn = Cr(CO)5; 127b, MLn = Mo(CO)5; 127c, MLn = W(CO)5; 128, MLn = (C6H4-1-iPr-4-
Me)RuCl2; 129, MLn = AuCl), a series of complexes which can be prepared by the reaction of
bfc(PPh2)2 (126) with two equivalents of the MLn sources M(CO)5(thf) (M = Cr, Mo, W),
[(C6H4-1-iPr-4-Me)RuCl2]2, or (tht)AuCl [89].
Tetrametallic Fe2Au2 129 affords with HC≡CMc (Mc = Fc, Rc) in presence of [CuI] and
diethylamine in tetrahydrofuran at room temperature bfc(PPh2Au-C≡C-Mc)2 (130a, Mc =
Fc; 130b, Mc = Rc) (Scheme 9, route (i)) [90]. Under identical reaction conditions 129
reacted with a 20 % excess of 5-ethynyl-2,2´-bipyridine to give bfc(PPh2Au-C≡C-bipy)2
(131) (Scheme 9, route (ii)) which contains with the bipy ligand a further N-ligating unit and
hence, was reacted with stoichiometric amounts of the heterobimetallic early-late tweezer
molecule [{[Ti](μ-σ,π-C≡CSiMe3)2}Cu(N≡CMe)]PF6 (Scheme 9, route (iii)). On
replacement of the weakly-bonded acetonitrile in the latter molecule by bipy octametallic 132
is formed which can be isolated after appropriate work-up in acceptable yield [90]. In 132 the
bfc unit links the two heterotrimetallic Au-C≡C-bipy[{[Ti](μ-σ,π-C≡CSiMe3)2}Cu]+
building blocks and hence, represents a further example of a so far only barely discussed class
of heterotetrametallic MM′M′′M′′′ complexes. A detailed investigation of
possible photophysical properties and electronic interactions between the appropriate metal
atoms of 132 is in progress in our laboratory.
Scheme 9. Synthesis of heteromultimetallic 130, 131 and 132. ((i) 1. (tht)AuCl; 2. HC≡CMc,
[CuI]/NEt3. (ii) 1. (tht)AuCl; 2. HC≡Cbipy, [CuI]/NEt3. (iii) [{[Ti]C≡CSiMe3}2Cu(N≡CMe)PF6]) [90].
The development of polynuclear ruthenium(II) terpyridine molecular wire molecules

based on the biferrocene building block bfc were recently reported by Dong et al. [91]. The
multinuclear supramolecules assembled from 1’,1’’’-bis(terpyridyl) biferrocene redox-active
sub-units attached to Ru(II) ions were prepared by, for example, the reaction of bfc-terpy
(133) and bfc(terpy)2 (134), respectively, with LRuCl3 (L = terpy, fc-terpy), LRuCl2(dmso) (L
= bfc-terpy, dmso = dimethylsulfoxide) or RuCl2(dmso) in the appropriate ratios as outlined
in Figure 11 [91]. Complexes Ru(bifc-terpy)(dmso)Cl2 (135), [Ru(terpy)(bifc-terpy)](PF6)2
(136), [Ru(bifc-terpy)2](PF6)4 (137), [bifc(terpy)2(Ru(terpy))2](PF6)4 (138), [bifc-
(terpy)2(Ru(terpy-Fc))2](PF6)4 (139), [bifc(terpy)2(Ru(terpy-bifc))2](PF6)4 (140), [(Ru(terpy))
2(bifc(terpy)2](PF6)6 (141), and [(Ru(terpy-Fc)2(bifc(terpy)2)2](PF6)6 (142) are thereby formed
in good yield. The cyclic voltammograms of the ruthenium(II) coordinated bifc-terpy and fc-
terpy species are dominated by the Ru2+/Ru3+ (E1/2 ≅ 1.35 V), Fe2+/Fe3+ (E1/2 ≅ 0.4 – 0.9 V),
and the terpy (terpy-/terpy2- redox couples (E1/2 ≅ -1.2 – -1.4 V). The appreciable variations
detected in the Fe2+/Fe3+ oxidation potentials indicated that this is an interaction between the
respective spacer and the Ru2+ metal ions [91].
On the coordination of the 1,’1’’’-bis(terpyridyl) biferrocene 133 to a ruthenium(II) ion
there is a red-shifted and more intense 1[(d(π)Fe)6] → 1[(d(π)Fe)5(π*terpy Ru)1] transition
found in the visible region ([Ru(terpy)2]2+, [Ru(terpy)(bifc-terpy)]2+: ca. 510 nm; polynuclear
ruthenium(II) 1,’1’’’-bis(terpyridyl) biferrocenes: ca. 570 nm) [91]. This shift indicates that
there is a qualitative electronic coupling within the appropriate assemblies. The coordination
of Ru(II) ions lowers the energy of the π*terpy orbitals giving a more red-shifted transition.
Further examples of heterotetrametallic MM′M′′M′′′ complexes with four

different metals, based on organometallic π-tweezer units, can be obtained by joining
heterobimetallic titanium-copper or titanium-silver tweezers with Fe-Pt or Fe-Au containing
molecules (Figure 12). Thus, HC≡C-{Pt}-C≡C-Fc (143) ({Pt} = Pt(C6H2(CH2NMe2-2,6)2))
gives with {[Ti](μ- σ,π-C≡CtBu)2}CuCH3 on loss of CH4 complex 144 [51], while
FcPPh2Au-C≡C-bipy affords with {[Ti](μ-σ,π-C≡CSiMe3)2}M′X (M′X =
Cu(N≡CMe)PF6, AgClO4) tetrametallic 145 [92].
Figure 12. Complexes 144 (left) and 145 (right; 145a: M′ = Cu, X = PF6; 145b: M′ = Ag, X =
ClO4) [51, 92].
Complexes 144 and 145 represent the first examples of heterotetrametallic transition
metal complexes in which early and late metals are connected by π-conjugated organic
bridging units. A striking feature of 144 is that all metals possess different coordination
spheres: titanium shows a pseudo-tetrahedral environment, copper possesses a planar
surrounding, platinum is square-planar coordinated and iron is part of a sandwich structure
[51].
Based on the organometallic π-tweezer moiety [{[Ti](μ-σ,π-C≡CSiMe3)2}Cu]+
another heterotetrametallic species could be isolated from the reaction of {[Ti](μ-σ,π-
C≡CSiMe3)2}- CuMe with (η5-C5H4CO2H)Fe(η5-C5H4PPh2Mo(CO)5) (146) [93]. The
latter molecule is accessible by treatment of HO2C-fc-PPh2 (147) (fc = Fe(η5-C5H4)2) with
M(CO)5(thf) [93]. The respective Ti-Cu-Fe-M complexes 148a - 148c (148a, M = Cr; 148b,
M = Mo; 148c, M = W) are, however, very instable molecules both in the solid state and in
solution and hence, can only be handled at low temperature without significant decomposition
[93].
Isostructural systems to 148 can be obtained for the higher homologue of copper by
combining [Ti](C≡CSiMe3)2 with equimolar amounts of the silver(I) salt [AgO2C-fc-PPh2]
to give {[Ti](μ-σ,π-C≡CSiMe3)2}AgO2C-fc-PPh2 (149) [93]. Addition of M(CO)5(thf) to
149 produced the Ti-Ag-Fe-M complexes {[Ti](μ-σ,π-C≡CSiMe3)2}AgO2C-fc-
PPh2M(CO)5 (150a, M = Cr; 150b, M = Mo; 150c, M = W), which are, when compared with
148a – 148c, even more reactive. They readily decompose in solution and on exposure to sun
light on formation of metallic silver, the free π-tweezer [Ti](C≡CSiMe3)2 and other
unidentified materials.
When the FcPPh2Au entity in 145 (Figure 12) is replaced by the (η2-dppf)(η5-C5H5)Ru
building block related tetranuclear complexes of type [(η2-dppf)(η5-C5H5)Ru-C≡Cbipy{[
Ti](μ-σ,π-C≡CSiMe3)2}M′]X (151a: M′ = Cu, X = PF6; 151b: M′ = Ag, X = ClO4)
are accessible [64].
Extending the distance between the remote Fe-Ru and Ti-Cu fragments in 151 by an
C≡C-1-C6H4-4-PPh2-Au moiety opens the possibility to create stable heteropentametallic
transition metal complexes (see below). When the organometallic π-tweezer entity (vide
supra) is substituted by mononuclear transition metal building blocks, such as Mo(CO)4 and
Re(CO)3Cl, then tetrametallic [(η2-dppf)(η5-C5H5)Ru(C≡C)-1-(C6H4)-4-PPh2-Au-
C≡Cbipy( MLn)] (152, MLn = Mo(CO)4; 153, MLn = Re(CO)3Cl) is formed in which four
different metal atoms are bridged by organic carbon-rich connecting units [64].
Compounds of the latter type are formed by treatment of [(η2-dppf)(η5-

C5H5)Ru(C≡C)-1- (C6H4)-4-PPh2-AuCl] (154) with HC≡C-bipy(Re(CO)3Cl) (synthesis of
152) or combining (η2-dppf)(η5-C5H5)Ru(C≡C)-1-(C6H4)-4-PPh2-Au-C≡C-bipy (155)
with (nbd)Mo(CO)4
(synthesis of 153) [64].
An elegant approach to a novel Fe-Ru-Re-Rh tetrametallic complex, based on the 1,3-
diethynyl-5-diphenylphosphino benzene core, is given by using a consecutive reaction
methodology as presented in Scheme 10 including, dehydrohalogenation and carbon-carbon
coupling reactions [64].
Scheme 10. Synthesis of heterotetrametallic 158 via the formation of 156 and 157, ((i)
(bipy’)(CO)3ReC≡CH, [(PPh3)2PdCl2], [CuI], HNiPr2, reflux, 5 h; (ii) [nBu4N]F, thf, 25 °C, 1 h; (iii)
(dppf)(η5-C5H5)RuCl, [H4N]PF6, KOtBu, CH2Cl2/MeOH, 25 °C, 3 h; (iv) [(η5-C5Me5)RhCl2]2, CH2Cl2,
25 °C, 1 h) [64].
Exemplary, the molecular solid state structure of 158 was solved by X-ray structure
analysis, thus confirming the structural assignment made from spectroscopic data [64]. An
ORTEP drawing of this species is depicted in Figure 13.
Figure 13. ORTEP drawing of 158. Thermal ellipsoids are shown at the 50% probability level. For
selected bond lengths (Å) and angles (°) see ref. [64].
(HETERO)PENTA- TO (HETERO)UNDECAMETALLIC TRANSITION

METAL COMPLEXES
Further examples of the modular “Tinkertoy” approach includes the synthesis of
(hetero)penta- to nona-metallic complexes. An important family of “Tinkertoys” are halide-,
pseudohalide-, cyanoacetylide-, heterocyclic- and/or di- and tricarboxylic acid-funtionalized
transition metal building blocks.
There are mainly three methods which can successfully be applied for the preparation of
the title compounds. The first synthesis protocol includes the reaction of {[Ti](μ-σ,π-
C≡CR) 2}CuMe with diverse organic and organometallic di- and tricarboxylic acids, owing
to the instability of the alkyl-copper system, and is based on the preparation of 159 and 160
[14m, 94].
In the latter molecules organometallic π-tweezer units are connected by a 1,1'-

errocenyldicarboxylate (159) or a 1,3,5-benzenetricarboxylic entity (160). However,
electrochemical studies showed that the connecting carboxylates act as an impedance rather
than a transmitter [14m, 94].
The 2nd and hence, more straightforward synthetic route to (hetero)multimetallic π-
tweezer-based complexes is the reaction of {[Ti](μ-σ,π-C≡CSiMe3)2}M′X (M′ = Cu,
Ag; X = ClO4, OTf) with the metal salts [MX2]- (M = Cu, Ag, Au; X = C≡N, OCN)
(synthesis of 161a - 161e) or [Ag(C≡N)4]3- (synthesis of 162) in the ratios of 2:1 and 4:1,
respectively [14h, gg, 52, 56, 87, 95].
Complexes 161a – 161e (161a, M = M′ = Cu, X = C≡N; 161b, M = M′ = Ag, X =

C≡N; 161c, M = M′ = Ag, X = NCO; 161d, M = Ag, M′ = Cu, X = C≡N; 161e, M =
Au, M′ = Cu, X = C≡N) are linear structured and contain the features typical for 1-
dimensional molecular wire molecules. Complex 162 is one of the outstanding examples of a
cross-shaped molecule in which four titanium-silver tweezer parts are linked by a
[Ag(C≡N)4]3- core. In 162 each cyanide is datively-bound to a silver(I) center of an
individual π-tweezer fragment. While the inner silver atom possesses a tetrahedral
environment, the outer silver(I) ions are planar coordinated and hence, possess coordination
number 3 [95].
Multiple π-tweezers can also be linked together by bipyridyl, 2,4,6-tri(2-pyridyl)-1,3,5-
triazine (tpt) or pyridyl-functionalized porphyrin connecting units [96, 97]. With tpt,
complexes 163a – 163d (M′ = Cu, X = PF6: 163a, R = Ph; 163b, R = SiMe3; M′ = Ag, X
= ClO4: 163c, R = Ph; 163d, R = SiMe3) are formed, when {[Ti](μ-σ,π-C≡CR)2}M′X is
reacted with tpt in the stoichiometry of 3:1.
In a similar manner, heptametallic FeAu2Cu2Ti2 and FeAu2Ag2Ti2 molecules Fe(η5-

C5H4PPh2AuC≡Cbipy-M′{(μ-σ,π-C≡CSiMe3)2[Ti]})2 (164a, M′ = Cu; 164b, M′
= Ag) are accessible by treatment of Fe(η5-C5H4PPh2AuC≡Cbipy)2 with two equivalents of
{[Ti](μ- σ,π-C≡CSiMe3)2}M′X (M′X = Cu(N≡CMe)PF6, AgClO4) [64].
Pyridine-functionalized porphyrins allow the linkage of four organometallic π-tweezers
as shown in 165a (M′ = Cu) and 165b (M′ = Ag). However, these molecules show a
tendency to decompose in solution with formation of metallic copper or silver along with
[Ti](C≡CSiMe3) 2 and the free porphyrin [97].
The reaction chemistry of 165a and 165b towards diverse transition and main-group
element salts is in progress in our labortories.
Ferrocene-based multimetallic species of type MxM′y are [Ph((η5-C5H5)Fe(η5-
C5H4))2P]AuC≡CAu[P((η5-C5H5)Fe(η5-C5H4))2Ph] (166) [98], (FcC≡C-C≡CFc)2Os2(CO)6
(167) [32c] and (FcC≡C)2Os3(CO)9 (168) [32c].
As an instance, the pentametallic complex 171, a bipyramidal supramolecular cage based
on rhodium and platinum atoms must be mentioned [99]. This compound is accessible by the
consecutive reaction of 4-ethynyl-pyridine with tBuLi followed by its addition to
(Me3tacn)RhCl3 (Me3tacn = N,N′,N′′-trimethyl-1,4,7-triazacyclononane) giving the
facial octahedral complex (Me3tacn)Rh(C≡Cpy) (169), condensation of which with the
squareplanar species cis-(dcpe)Pt(NO3)2 (170) (dcpe = 1,2-bis(dicyclohexylphosphino)ethane)
results in a self-assembled trigonal-bipyramidal cage with Rh(III) and Pt(II) ions occupying
the vertics. Multinuclear NMR analyses and single X-ray structure determination of 171 are
consistent with the proposed structure.
A star-shaped ruthenium complex (176) with five ferrocenyl end-grafted arms bridged by
the trans- platinum fragments Pt(PEt3)2 represents an example of a undecanuclear Fe5Pt5Ru
assembly containing three different metals [100]. This complex can be synthesized by starting
from the novel heteropolytopic penta(4-ethynyl)cyclopentadiene C5(C6H4-4-C≡C-TIPS)5(Br)
(TIPS = tri(iso-propyl)silyl) (172) (Scheme 11). Ruthenium was subsequently condicted to
172 affording 173 (Scheme 11). Compound 173 reacts with potassium tris(indazolyl)borate
(= KTIB) and than with tetra-butylammonium fluoride (= TBAF) to yield 174, bearing five
free HC≡C terminal groups. These end-grafted units are available for coordination and
hence, 174 was reacted with the ethynyl-ferrocenyl platinum fragment Fc-C≡C-Pt(PEt3)2Cl
(175) in presence of [CuI] in Et2NH as solvent (Scheme 11). In a quintuple coupling of 175
with 174, complex 176 was isolated. Oxidation of the five centers in 176 occurs
simultaneously at a potential of 0.31 V followed by the oxidation of the Ru(II) ion at 0.60 V.
However, the platinum atoms were not oxidized within the potential window of –1.8 to +1.5
V used. Finally, after preforming a partial oxidation of the Fc units, no intervalence transition
between Fe2+/Fe3+ was observed, thus confirming the absence of electronic communication
between the electro-active ferrocenes [100].
Even the synthesis of heteropenta- and heterohexametallic complexes with the metals
rhenium, iron, ruthenium, gold, copper and titanium is possible. Complex [(η2-dppf)(η5-
C5H5)RuC≡C-1-C6H4-4-PPh2-Au-C≡C-bipy{[Ti](μ-σ,π-C≡CSiMe3)2}Cu]PF6 (179) is
accessible in a consecutive reaction sequence by using (η2-dppf)(η5-C5H5)RuC≡C-1-C6H4-
4- PPh2-AuCl (177) as key starting material [64, 101]. The newly synthesized compounds and
the overall synthetic strategy employed are shown in Scheme 12. Compound 177 reacts with
5-ethynyl-2,2´-bipyridine, whereby this compound is added in a 20 % excess, in presence of
[CuI] and diethylamine to give (η2-dppf)(η5-C5H5)RuC≡C-1-C6H4-4-PPh2-Au-C≡C-bipy
(178) (Scheme 12, route (i)). This molecule contains with the 2,2´-bipyridine ligand a
Nligating unit and hence, was reacted with stoichiometric amounts of the heterobimetallic
early-late tweezer molecule [{[Ti](μ-σ,π-C≡CSiMe3)2}Cu(N≡CMe)]PF6 (Scheme

12, route (ii)). On replacement of the copper-bonded acetonitrile in the organometallic π-
tweezer part by bipyridine, complex 179 is formed which could be isolated after appropriate
work-up in 92 % yield. Complex 179 is surprisingly a very stable species in which five
different transition metals are brought in close proximity to each other by connecting
C5H4PPh2, C≡C, C6H4, and bipyridine units.
Scheme 11. Consecutive synthesis of 176 from 172 [100].
Scheme 12. Synthesis of trimetallic 178 and pentametallic 179 (route (i): tetrahydrofuran, 25 °C, 3 h;
(ii): tetrahydrofuran, 25 °C, 2 h) [64, 101].
The formation of heteropentanuclear 179 was evidenced from spectroscopic studies and
ESI-TOF mass spectrometric investigations. The ESI-TOF spectrum shows a prominent ion
peak at m/z 1963.4 (100 %) corresponding to [179-PF6]+. Moreover, comparison of the Mixed
measured isotope pattern of 179 with the calculated one confirms the elemental composition
and charge state (Figure 13).
Figure 13. Comparison of the measured (bottom) and calculated (top) isotope pattern of the ion peak
[179-PF6]+ in the ESI-MS spectrum of 179 [64, 101].
The bipyridine building block in [(η2-dppf)(η5-C5H5)RuC≡C]-1-[(4,4´-tBu2-2,2´-

bipy)(CO)3ReC≡C]-5-[PPh2AuC≡Cbipy]C6H3 (180) as bidentate binding site allows the
preparation of Fe-Ru-Re-Au-Mo- and even Fe-Ru-Re-Au-Cu-Ti-based assemblies as outlined
in Scheme 13. Addition of (nbd)Mo(CO)4 yields heteropentanuclear 181 upon replacement of
nbd by bipy. Heterohexanuclear 182 is formed in a straightforward manner, when 180 is
treated with [{[Ti](μ-σ,π-C≡CSiMe3)2}Cu(N≡CMe)]PF6 [64]. Within this reaction the
coordination number at copper is changed from three (planar) to four (tetrahedral).
The synthesis protocol developed to prepare heteromultinuclear 181 and 182 is directed
to the use of modular shaped organometallic building blocks (vide supra) [64]. This allowed
for the first time the synthesis of such unique complexes in which acetylenic and aromatic
groups are connecting the different metal atoms.
Scheme 13. Synthesis of heteropentametallic 181 and heterohexanuclear 182 [(i) (nbd)Mo(CO)4,
dichloromethane, tetrahydrofuran, 25 °C, 8 h; (ii) [{[Ti](C≡CSiMe3)2Cu(N≡CMe)]PF6, tetrahydrofuran,
25 °C, 2 h] [64].
The reports on the synthesis of transition metal complexes in which five different metals
such as Fe, Ru, Au, Cu and Ti (complex 179), Fe, Ru, Re, Au and Mo (complex 181) or even
six different metal atoms (Fe, Ru, Re, Au, Cu, Ti; complex 182) are spanned by carbon-rich
bridging units demonstrate that such large heteronuclear assemblies can be synthesized in a
straightforward manner by using the modular “Tinkertoy” approach. This procedure allows a
fair control over the structure and composition of such molecules. A detailed investigation of
possible photophysical properties and electronic interactions between the appropriate metal
atoms of 179, 181 and 182 is in progress in our laboratory.
The identities of all described complexes within this article have been confirmed by
elemental analysis, IR, 1H, 13C{1H} and 31P{1H} NMR spectroscopy. From selected samples
the ESI-TOF mass spectra were measured and the solid state structures determined by single
X-ray structure analysis. In this respect, IR and NMR (1H, 31P{1H}) spectroscopy allows to
monitor the progress of the reactions and verifies the structure and composition of the final
assemblies.
CONCLUSION
This chapter addresses the chemistry of mono- and bis(alkynyl) transition metal
complexes, diaminoaryl NCN and NN’N pincer molecules (NCN = [C6H2(CH2NMe2-2,6)2]-;
NN’N = [C5H3N(CH2NMe2-2,6)2]), modified ferrocenes and biferrocenes towards diverse
metal complex fragments and serves to understand the manifold and sometimes unexpected
reaction behavior of such systems. Interesting unique (hetero)bi- to (hetero)undecametallic

compounds with often uncommon structural motifs are formed in which the respective
transition metal building blocks are connected via π-conjugated carbon-rich organic and/or
inorganic bridging units. The reactions based on the modular “Tinkertoys” approach depend
on the steric and electronic properties of the metal atoms and ligands involved. Despite the
large quantity of experimental work carried out in this field of chemistry, the exact factors
which control the formation and/or interconversion of the structures in the
(hetero)multimetallic complexes is still an open question and will continue to stimulate
further work in this field of chemistry. A challenge is the preparation of even larger transition
metal complexes featuring more than six different early-late metals and new functionalities.
This chemistry opens the possibility for creating new materials with innovative electronic,
catalytic, optical, and/or magnetic properties.
ACKNOWLEDGMENT
The very creative and fruitful contributions of Drs. S. Back, W. Frosch, T. Stein, K.
Köhler, M. Al-Anber, and Dipl.-Chem. S. Köcher, M. Lohan, J. Kühnert, A. del Villar, and
D. Friedrich and specially R. Packheiser are gratefully acknowledged. The financial support
from the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and the
VW-Foundation have been essentiell throughout.
REFERENCES
[1] For example: (a) Balzani, V.; Juris A.; Venturi, M.; Campagna, S., and Serroni,
S.(1996). Luminescent and Redox-Active Polynuclear Transition Metal
Complexes.Chem. Rev., 96, 759-833. (b) Balzani, V.; Campagna, S.; Denti, G.; Juris
A.; Serroni, S., and Venturi, M. (1998). Designing Dedrimers Based on Transition-
Metal Complexes. Light-Harvesting Properties and Predetermined Redox Patterns. Acc.
Chem. Res., 31, 26-34. (c) Long, N. J. (1995). Organometallic Compounds for
Nonlinear Optics - The Search for En-light-Enment! Angew. Chem., Int. Ed., 34, 21–38.
(d) Wong, K. M. C.; Lam, S. C. F.; Ko, C. C.; Zhu, N.; Yam, V. W. W.; Roué S.;
Lapinte, C.; Fathallah, S.; Costuas, K.; Kahlal, S., and Halet, J. F. (2003).
Electroswitchable Photoluminescence Activity: Synthesis, Spectroscopy,
Electrochemistry, Photophysics, and X-ray Crystal and Electronic Structures of
[Re(bpy)(CO)3(C≡C-C6H4-C≡C)Fe(C5Me5)(dppe)][PF6]n (n = 0, 1). Inorg. Chem., 42,
7086–7097. (e) Powell C. E., and Humphrey M. G. (2004). Nonlinear Optical
Properties of Transition Metal Acetylides and their Derivatives. Coord. Chem. Rev.,
248, 725-756. (f) Cifuentes, M. P.; Humphrey, M. G; Morall J. P.; Samoc, M.; Paul, F.;
Roisnel, T., and Lapinte C. (2005). Third-Order Nonlinear Optical Properties of Some
Electron-Rich Iron Mono- and Trinuclear Alkynyl Complexes. Organometallics, 24,
4280-4288. (g) Low P. J. (2005). Metal Complexes in Molecular Electronics: Progress
and Possibilities. Dalton Trans., 17, 2821-2824. (h) Long, N. J.; Angela, A. J.; de Biani,
F. F., and Zanello, P. (1998). Synthetic and Electrochemical Studies of Some Metal
Complexes of 1,3,5-Triethynylbenzene J. Chem. Soc., Dalton Trans., 2017-2022. (i)

Koellner, C.; Pugin, B., and Togni, A. (1998). Dendrimers Containing Chiral
Ferrocenyl Diphosphine Ligands for Asymmetric Catalysis. J. Am. Chem. Soc., 120,
10274-10275. (j) Devadoss, C.; Bharathi, P., and Moore, J. S. (1996). Energy Transfer
in Dendritic Macromolecules: Molecular Size Effects and the Role of an Energy
Gradient. J. Am. Chem. Soc., 118, 40, 9635-9644. (k) Hu, Q. S.; Pugh, V.; Sabat, M.,
and Pu, L. (1999). Structurally Rigid and Optically Active Dendrimers J. Org. Chem.,
64, 20, 7528-7536. (l) Paul, F., and Lapinte, C. (1998). Organometallic Molecular
Wires and other Nanoscale-sized Devices: An Approach Using the Organoiron
(dppe)Cp*Fe Building Block. Coord. Chem. Rev., 178-180, 431-509. (m) Brunschwig,
B. S.; Creutz, C., and Sutin, N. (2002). Optical Transitions of Symmetrical Mixed-
Valence Systems in the Class II–III Transition Regime Chem. Soc. Rev., 31, 168-184.
(n) Nelson S. F. (2001). In V. Balzani (Ed.) Electron Transfer in Chemistry (Vol. 1,
Chapter 10). Weinheim, Germany; Wiley-VCH. (o) Kaim, W.; Klein, A., and Glöckle,
M. (2002). Exploration of Mixed-Valence Chemistry: Inventing New Analogues of the
Creutz-Taube Ion. Acc. Chem. Res., 33, 755-763. (p) Ceccon, A.; Santi, S.; Orian, L.,
and Bisello, A. (2004). Electronic Communication in Heterobinuclear Organometallic
Complexes Through Unsaturated Hydrocarbon Bridges. Coord. Chem. Rev., 248, 683-
724. (q) Ward, M. D. (1995). Metal-Metal Interactions in Binuclear Complexes
Exhibiting Mixed Valency; Molecular Wires and Switches. Chem. Soc. Rev., 121-134.
(r) Astruc D. (1997). From Organotransition-Metal Chemistry toward Molecular
Electronics: Electronic Communication between Ligand-Bridged Metals. Acc. Chem.
Res., 30, 383-391. (s) Sarkar, B.; Kaim, W.; Fiedler, J., and Duboc, C. (2004).
Molecule-Bridged Mixed-Valent Intermediates Involving the RuI Oxidation State. J.
Am. Chem. Soc.; 126, 14706-14707. (t) Connelly, N. G., and Geiger, W. E. (1996).
Chemical Redox Agents for Organometallic Chemistry. Chem. Rev., 96, 877-910.
[2] (a) Michl, J., and Magnera F. (2002). Two-dimensional Supramolecular Chemistry with
Molecular Tinkertoys. Proc. Natl. Acad. Sci. U.S.A., 99, 4788-4792. (b) Levin, M.;
Kaszynski, P., and Michl, J. (2000). Bicyclo[1.1.1]pentanes, [n]Staffanes,
[1.1.1]Propellanes, and Tricyclo[2.1.0.02,5]pentanes. Chem. Rev., 100, 169-234. (c)
Kaszynski, P., and Michl, J. (1998). [n]Staffanes: A Molecular-Size "Tinkertoy"
Construction Set for Nanotechnology. Preparation of End-Functionalized Telomers and
a Polymer of [ l.l.l]Propellane. J. Am. Chem. Soc., 110, 5225-5226.
[3] (a) Stoddart, J. F. (1992). Constructing a Molecular LEGO Set. Chem. Soc. Rev., 21,
215-225. (b) Raymo, F. M., and Stoddart, J. F. (1999). Interlocked Macromolecules.
Chem. Rev., 99, 1643-1663; (c) Kessler, V. G. (2003). Molecular Structure Design and
Synthetic Approaches to the Heterometallic Alkoxide Complexes (Soft Chemistry
Approach to Inorganic Materials by the Eyes of a Crystallographer) Chem. Commun.,
1213.
[4] Long, N. J., and Williams, C. K. (2003). Metal Alkynyl Complexes: Synthesis and
Materials. Angew. Chem., Int. Ed., 42, 2586-2617. (b) Yam V. W. W. (2004).
Luminescent Metal Alkynyls – From Simple Molecules to Molecular Rods and
Materials. J. Organomet. Chem., 689, 1393. (c) Bruce, M. I.; Low, P. J.; Frantisek, F.;
Humphrey, P. A.; De Montigny, F.; Jevric, M.; Lapinte, C.; Perkins, G. J.; Roberts, R.
L.; Skelton, B. W., and White, A. H. (2005). Syntheses, Structures, some Reactions,
and Electrochemical Oxidation of Ferrocenylethynyl Complexes of Iron, Ruthenium,
and Osmium. Organometallics, 24, 5241-5255. (d) Low, P. J.; Roberts, R. L.; Cordiner,
R. L., and Hartl F. J. (2005). Electrochemical Studies of Bi- and Polymetallic
Complexes Featuring Acetylide Based Bridging Ligands. Solid State Electrochem., 9,
717-731. (e) Szafert, S., and Gladysz, J. A. (2003). Carbon in One Dimension:
Structural Analysis of the Higher Conjugated Polyynes. Chem. Rev., 103, 4175-4205.
(f) Bruce, M. I.; Low, P. J.; Costuas, K.; Halet, J. F.; Best, S. P., and Heath G. A.
(2000). Oxidation Chemistry of Metal-Bonded C4 Chains: A Combined Chemical,
Spectroelectrochemical, and Computational Study: J. Am. Chem. Soc., 122, 1949-1962.
(g) Narvor, N. L.; Toupet, L., and Lapinte, C. (1995). Elemental Carbon Chain
Bridging Two Iron Centers: Syntheses and Spectroscopic Properties of [Cp*(dppe)Fe-
C4-FeCp*(dppe)]n+·n[PF6]-. X-ray Crystal Structure of the Mixed Valence Complex (n=
1). J. Am. Chem. Soc., 117, 7129-7138; (h) Baumgartner, T., and Reau, R. (2006).
Organophosphorus π-Conjugated Materials. Chem. Rev., 106, 4681-4727. (i) Yam, V.
W. W.; Lo, K. K. W., and Wong K. M. C. (1999). Luminescent Polynuclear Metal
Acetylides. J. Organomet. Chem., 578, 3-30.
[5] Chawdhury, N.; Long, N. J.; Mahon, M. F.; Ooi, L.; Raithby, P. R.; Rooke, S.; White,
A. J. P.; Williams, D. J., and Younus, M. (2004). Synthesis, Characterisation and
Optical Spectroscopy of Platinum(II) Di-ynes and Poly-ynes Incorporating Condensed
Aromatic Spacers in the Backbone. J. Organomet. Chem., 689, 840-847. (b) de
Montigny, F.; Argouarch, G.; Costuas, K.; Halet, J. F.; Roisnel, T.; Toupet, L., and
Lapinte, C. (2005). Electron Transfer and Electron Exchange Between
[Cp*(dppe)Fe]n+(n = 0, 1) Building Blocks Mediated by the 9,10-
Bis(ethynyl)anthracene Bridge Organometallics, 24, 4558-4572. (c) Callejas-Gaspar,
B.; Laubender, M., and Werner, H. (2003). Synthesis and Reactivity of Dinuclear
Rhodium Complexes with Rh=C=CHR and Rh=C=C=CRR′ Units as Building Blocks.
J. Organomet. Chem., 684, 144-152. (d) Klein, A.; Lavastre, O., and Fiedler, J. (2006).
Role of the Bridging Arylethynyl Ligand in Bi- and Trinuclear Ruthenium and Iron
Complexes Organometallics, 25, 635-643. (e) Hurst, S. K.; Cifuentes, M. P.;
McDonagh, A. M.; Humphrey, M. G.; Samoc, M.; Luther-Davies, B.; Asselberghs, I.,
and Persoons, A. (2002). Organometallic Complexes for Nonlinear Optics. Part 25.
Quadratic and Cubic Hyperpolarizabilities of some Dipolar and Quadrupolar Gold and
Ruthenium Complexes. J. Organomet. Chem., 642, 259-262. (f) Hurst, S. K., and Ren,
T. (2002). Synthesis, Characterization and Electrochemistry of Diruthenium Complexes
Linked by Aryl Acetylide Bridges. J. Organomet. Chem., 660, 1-5. (g) Fraysse, S.;
Coudret, S., and Launay, J. P. (2003). Molecular Wires Built from Binuclear
Cyclometalated Complexes. J. Am. Chem. Soc., 125, 5880-5888. (h) Back, S.; Lutz, M.;
Spek, A. L.; Lang, H., and van Koten, G. (2001). Preparation and Electrochemical
Behaviour of Dinuclear Platinum Complexes Containing NCN Ligands
(NCN=[C6H3(Me2NCH2)2-2,6]−). The Crystal Structure of [C6H3(Me2NCH2)2-1,3-
(C≡C)-5]2. J. Organomet. Chem., 620, 227-234. (i) Weyland, T.; Ledoux, I.; Brasselet,
S.; Zyss, J., and Lapinte, C. (2000). Nonlinear Optical Properties of Redox-Active
Mono-, Bi-, and Trimetallic σ-Acetylide Complexes Connected Through a Phenyl
Ring in the Cp*(dppe)Fe Series. An Example of Electro-Switchable NLO Response
Organometallics, 19, 5235-5237. (j) Colbert, M. C. B.; Lewis, J.; Long, N. J.; Raithby,
P. R.; Younus, M.; White, A. J. P.; Williams, D. J.; Payne, N. N.; Yellowlees, L.;
Beljonne, D.; Chawdhury, N., and Friend, R. H. (1998). Synthesis and Characterization
of Dinuclear Metal σ-Acetylides and Mononuclear Metal σ-Allenylidenes.
Organometallics, 17, 3034-3043. (k) Bruce, M. I.; Hall, B. C.; Kelly, B. D.; Low, P. J.;
Skelton, B. W., and White, A. H. J. (1999). An Efficient Synthesis of Polyynyl and
Polyynediyl Complexes of Ruthenium(II). J. Chem. Soc., Dalton Trans., 19, 3719-
3728. (l) Lavastre, O.; Even, M.; Dixneuf, P. H.; Pacreau, A., and Vairon, J. (1996).
Novel Ruthenium- or Iron-Containing Tetraynes as Precursors of Mixed-Metal
Oligomers. Organometallics, 15, 1530-1531.
[6] (a) Lam, S. C. F.; Yam, V. W. W.; Wong, K. M. C.; Cheng, E. C. C., and Zhu, N.
(2005). Synthesis and Characterization of Luminescent Rhenium(I)-Platinum(II)
Polypyridine Bichromophoric Alkynyl-Bridged Molecular Rods Organometallics, 24,
4298-4305. (b) Younus, M.; Long, N. J.; Raithby, P. R., and Lewis, J. (1998).
Synthetic, Spectroscopic and Electrochemical Characterisation of Mixed-Metal
Acetylide Complexes. J. Organomet. Chem., 570, 55-62. (c) Lavastre, O.; Plass, J.;
Bachmann, P.; Guesmi, S.; Moinet, C., and Dixneuf, P. H. (1997). Ruthenium or
Ferrocenyl Homobimetallic and RuPdRu and FePdFe Heterotrimetallic Complexes
Connected by Unsaturated, Carbon-Rich -C≡CC6H4C≡C- Bridges. Organometallics,
16, 184-189.
[7] (a) Fink, H.; Long, N. J.; Martin, A. J.; Opromolla, G.; White, A. J. P.; Williams, D. J.,
and Zanello, P. (1997). Ethynylferrocene Compounds of 1,3,5-Tribromobenzene.
Organometallics, 16, 2646-2650. (b) Weyland, T.; Costuas, K.; Mari, A.; Halet, J. F.,
and Lapinte, C. (1998). [(Cp*)(dppe)Fe(III)]+ Units Bridged Through 1,3-
Diethynylbenzene and 1,3,5-Triethynylbenzene Spacers: Ferromagnetic Metal-Metal
Exchange Interaction. Organometallics, 17, 5569-5579. (c) Tykwinski, R. R., and
Stang, P. J. (1994). Preparation of Rigid-Rod, Di- and Trimetallic, σ-Acetylide
Complexes of Iridium(III) and Rhodium(III) via Alkynyl(pheny1)iodonium Chemistry
Organometallics, 13, 3203-3208. (d) Müller, T. J. J., and Lindner, H. J. (1996).
Palladium-Copper-Catalyzed Coupling of Tricarbonylchromium-Complexed
Phenylacetylene with Iodoarenes. A Facile Access to Alkynyl-Bridged Cr(CO)3-
Complexed Benzenes. Chem. Ber., 129, 607-613. (e) Irwin, M. J.; Manojlovic-Muir, L.;
Muir, K. W.; Puddephatt, R. J., and Yufit, D. S. (1997). Trigold Triacetylides:
Polymerization Through Gold···Gold Bonding or Bridging Ligands. Chem. Commun.,
219-220. (f) Leininger, S.; Stang, P. J., and Huang S. (1998). Synthesis and
Characterization of Organoplatinum Dendrimers with 1,3,5-Triethynylbenzene
Building Blocks. Organometallics, 17, 3981-3987.
[8] (a) Vicente, J.; Chicote, M. T., and Alvarez-Falcon, M. M. (2005). Platinum(II) and
Mixed Platinum(II)/Gold(I) σ-Alkynyl Complexes. The First Anionic σ-Alkynyl
Metal Polymers. Organometallics, 24, 2764-2772. (b) Chong, S. H. F.; Lam, S. C. F.;
Yam, V. W. W.; Zhu, N.; Cheung, K. K.; Fathallah, S.; Costuas, K., and Halet, J. F.
(2004). Luminescent Heterometallic Branched Alkynyl Complexes of Rhenium(I)-
Palladium(II): Potential Building Blocks for Heterometallic Metallodendrimers.
Organometallics, 23, 4924-4933. (c) Long, N. J.; Martin, A. J.; White, A. J. P.;
Williams, D. J.; Fontani, M.; Laschi, F., and Zanello, P. (2000). Synthesis and
Characterisation of Unsymmetrical Metal (RuII, OsII) and Ferrocenyl Complexes of
1,3,5-Triethynylbenzene. J. Chem. Soc., Dalton Trans., 3387-3392. (d) Long, N. J.;
Martin, A. J.; De Biani, F. F., and Zanello, P. (1998). Synthetic and Electrochemical
Studies of some Metal Complexes of 1,3,5-Triethynylbenzene. J. Chem. Soc., Dalton
Trans., 2017-2022.
[9] Lucas, N. T.; Cifuentes, M. P.; Nguyen, L. T., and Humphrey, M. G. (2001).
Ruthenium Cluster Chemistry with Ph2PC6H4-4-C≡CH. J. Cluster Science, 12, 201-
221.
[10] (a) Barbieri, A.; Ventura, B.; Flamigni, L.; Barigelletti, F.; Fuhrmann, G.; Baeuerle, P.;
Goeb, S., and Ziessel, R. (2005). Binuclear Wirelike Dimers Based on Ruthenium(II)-
Bipyridine Units Linked by Ethynylene-Oligothiophene-Ethynylene Bridges. Inorg.
Chem., 44, 8033-8043. (b) Newkome, G. R.; Patri, A. K.; Holder, E., and Schubert, U.
S. (2004). Synthesis of 2,2´-Bipyridines: Versatile Building Blocks for Sexy
Architectures and Functional Nanomaterials. Eur. J. Org. Chem., 2, 235-254. (c)
Hissler, M.; Harriman, A.; Khatyr, A., and Ziessel, R. (1999). Intramolecular Triplet
Energy Transfer in Pyrene-Metal Polypyridine Dyads: A Strategy for Extending the
Triplet Lifetime of the Metal Complex. Chem. Eur. J., 5, 3366-3381. (d) Constable, E.
C. (1989). Homoleptic Complexes of 2,2'-Bipyridine. Advan. Inorg. Chem., 1989, 34,
1-63. (e) McWhinnie, W. R., and Miller, J. D. (1969). Chemistry of Complexes
Containing 2,2'-Bipyridyl, 1,10-Phenanthroline, or 2,2',6',2"-Terpyridyl as Ligands.
Advan. Inorg. Chem., Radiochem., 12, 135-215.
[11] Le Stang, S.; Paul, F., and Lapinte, C. (2000). Molecular Wires: Synthesis and
Properties of the New Mixed-Valence Complex [Cp*(dppe)Fe-C≡C-X-
C≡CFe(dppe)Cp*][PF6] (X = 2,5 -C4H2S) and Comparison of its Properties with those
of the Related All-Carbon-Bridged Complex (X = -C4-). Organometallics, 19, 1035-
1043.
[12] Wong, W. Y.; Lu, G. L.; Ng, K. F.; Choi, K. H., and Lin, Z. (2001). Synthesis,
Structures and Properties of Platinum(II) Complexes of Oligothiophene-Functionalized
Ferrocenylacetylene. J. Chem. Soc., Dalton Trans., 22, 3250-3260. (b) Viola, E.; Lo
Sterzo, C., and Trezzi, F. (1996). Formation of a Molybdenum-Iron Heterobimetallic
Bis(acetylide) Derivative of 2,5-Diethynylthiophene via Palladium-Catalyzed Metal-
Carbon Coupling. Organometallics, 15, 4352-4354.
[13] Lang, H.; Packheiser, R., and Walfort, B. (2006). Organometallic π-Tweezers, NCN
Pincers, and Ferrocenes as Molecular “Tinkertoys” in the Synthesis of
Multiheterometallic Transition-Metal Complexes. Organometallics, 25, 1836-1851.
[14] (a) Packheiser, R.; Walfort, B., and Lang, H. (2006). Heterobi- and Heterotrimetallic
Transition Metal Complexes with Carbon-Rich Bridging Units. Organometallics, 25,
4579-4587. (b) Al-Anber, M.; Stein, T., and . Lang, H. (2005). Organometallic π-
Tweezers Incorporating Pyrazine- and Pyridine-Based Bridging Units. Inorg. Chim.
Acta, 358, 50-56. (c) Bruce, M. I.; Zaitseva, N. N.; Skelton, B. W.; Somers, N., and
White, A. H. (2003). Crystal and Molecular Structures of Some Alkynyl-Group
9/Group 11 Complexes [M2m4(C2R)8(PPh3)2] (M = Rh, Ir; m = Cu, Ag; R = Ph, Fc
(Ir/Cu only)). Aust. J. Chem., 56, 509-516. (d) Lang, H.; Stein, T.; Back, S., and
Rheinwald, G. (2004). Titanocene-Based Group-11 Metal Ions; Solid-State Structure of
[(η5-C5H4SiMe3)2Ti(C≡CPh)2]2AgNO3. J. Organomet. Chem., 689, 2690-2696. (e) Al-
Anber, M.; Walfort, B.; Stein, T., and Lang, H. (2004). {[Ti](C≡CSiMe3)2}Ag(OClO3)
π-Tweezer Units Bridged by Pyrazine. Inorg. Chim. Acta, 357, 1675-1681. (f) Lang, H.;
Meichel, E.; Stein, Th.; Weber, C.; Kralik, J.; Rheinwald, G., and Pritzkow, H. (2002).
Stabilisierung niedervalenter Ni(CO)-Bausteine durch [Ti](C≡CR)2; Reaktionsverhalten

von {[Ti](C≡CR)2}Ni(CO) gegenüber Triphenylphosphan und Phosphiten. J.
Organomet. Chem., 664, 150-160. (g) Stein, T., and Lang, H. (2002). Monomere
Kupfer(I)-Alkyle mit β-Wasserstoffatomen und Kupfer(I)-Aryle mit kondensierten
Aromaten; die Festkörperstruktur von [(η5-C5H4SiMe3)2Ti(C≡CSiMe3)2]CunC4H9. J.
Organomet. Chem., 664, 142-149. (h) Stein, T.; Lang, H., and Holze, R.
(2002).Intramolecular Intermetallic Interactions in Bi- and Tetrametallic
Organometallic Complexes as Demonstrated with Cyclic Voltammetry, J. Electro.
Chem., 520, 163-167. (i) Back, S.; Stein, T.; Frosch, W.; Wu, I.-Y.; Kralik, J.; Büchner,
M.; Huttner, G.; Rheinwald, G., and Lang, H. (2001). Heterometallic Early–Late π-
Tweezer Complexes: Their Synthesis, Electrochemical Behaviour and the Solid-State
Structures of (η5- C5H4SiMe3)2Ti(C≡CPh)2 and [(η5-C5H4SiMe3)2Ti(C≡CPh)2]Pd(PPh3).
Inorg. Chim. Acta., 325, 94-102. (j) Frosch, W.; Back, S.; Müller, H.; Köhler, K.;
Driess, A.; Schiemenz, B.; Huttner, G., and Lang, H. (2001). Donor-funktionalisierte
Alkinyle von Titan(IV), Kupfer(I) und Silber(I); Festkörperstrukturen von
[Ti](C≡CCH2NMe2)2 und {[Ti](C≡CtBu)2}CuC≡CC≡CC2H5. J. Organomet. Chem.,
619, 99-109. (k) Lang, H.; Mansilla, N., and Rheinwald, G. (2001). First Example of
Zinc(II) Monomeric Species Stabilized by η2-Bonded Alkynes. Organometallics, 20,
1592-1596. (m) Frosch, W.; Back, S.; Rheinwald, G.; Köhler, K.; Zsolnai, L.; Huttner,
G., and Lang, H. (2000). Mono-, Di-, and Tricarboxylic Acids: Central Building Blocks
for the Formation of Multinuclear Transition Metal Complexes. Organometallics, 19,
5769-5779. (n) Lang, H.; George, D., and Rheinwald, G. (2000). Bis(alkynyl)
Transition Metal Complexes, R1C≡C-[M]-C≡CR2, as Organometallic Chelating
Ligands; Formation of μ,η1(2)- Alkynyl-Bridged Binuclear and Oligonuclear
Complexes. Coord. Chem. Rev., 206-207, 101-197, and references cited therein. (o)
Frosch, W.; Back, S.; Rheinwald, G.; Köhler, K.; Pritzkow, H., and Lang, H. (2000).
(η2-Alkyne)2CuMe as a Synthetic Tool in the Preparation of Numerous Inorganic and
Organic Copper(I) Species. Organometallics, 19, 4016-4024. (p) Rupp, R.; Huttner, G.;
Lang, H.; Heinze, K.; Büchner, M., and Robert, E. (2000). Synthesis and π-Tweezer
Properties of Tripod Cobalt-Bisalkynyl Compounds [CH3C(CH2PPh2)3Co(C≡CR)2] -
Application to the Oxidative Coupling of Alkynyl Groups. Eup. J. Inorg. Chem., 9,
1953-1959. (q) Frosch, W.; del Vilar, A., and Lang, H. (2000). Heterobimetallische
Komplexe von Titan(IV)-Quecksilber(II) und Platin(II)-Quecksilber(II). J. Organomet.
Chem., 602, 91-96. (r) Frosch, W.; Back, S.; Köhler, K., and Lang, H. (2000). Zur
Umsetzung von Bis(alkinyl)-Titanocenen mit Übergangsmetall-Verbindungen von
Cu(II), Pd(II), Pt(II), Fe(III) und Au(III). J. Organomet. Chem., 601, 226-232. (s) Back,
S.; Rheinwald, G., and Lang, H. (2000). Synthesis, Electrochemistry and Electronic
Spectra of Tetranuclear Bis(η2-alkynyl) Transition-Metal Complexes. The Molecular
Structure of [(η5-C5H4SiMe3)2Ti(C≡CFc)2]CuBr. J. Organomet. Chem., 601, 93-99. (t)
Lang, H.; Weinmann, S.; Wu, I. Y.; Stein, T.; Jacobi, A., and Huttner, G. (1999). (η5-
C5H4SiMe3)2Ti(C≡C–SiMe2–C≡CSiMe3)2: a Unique Entry to Monomeric and
Oligomeric Alkyne–Copper(I) and Alkyne–Silver(I) Halides. J. Organomet. Chem.,
575, 133-140. (u) Lang, H., and Rheinwald, G. (1999). Kupfer, Silber, Gold; fixiert in
metallorganischen π-Pinzetten. J. Prakt. Chem., 341, 1-19. (v) Back, S.; Pritzkow, H.,
and Lang, H. (1998). C2-Bridged Titanocene-Ferrocenyl Complexes: Synthesis,
Reaction Chemistry, and Electrochemical Behavior. Organometallics, 17, 41-44. (w)
Hayashi, Y.; Osawa, M.; Kobayashi, K.; Sato, T.; Sato, M., and Wakatsuki, Y. (1998).
The Reaction of Titanocene Bis(ferrocenylacetylide) and Bis(ruthenocenylacetylide)
with Silver Cation: Formation of Bis(Ti-Tweezers) Silver Complexes. J. Organomet.
Chem., 569, 169-175. (x) Back, S.; Rheinwald, G.; Zsolnai, L.; Huttner, G., and Lang
H. (1998). Synthesis, Reaction Chemistry and Electrochemical Behaviour of (η5-
C5H4SiMe3)2Hf(C≡CFc)2. J. Organomet. Chem., 563, 73-79. (y) Koehler, K.; Silverio,
S.; Hyla-Kryspin, I.; Gleiter, R.; Zsolnai, L.; Driess, A.; Huttner, G., and Lang, H.
(1997). Trigonal-Planar-Coordinated Organogold(I) Complexes Stabilized by
Organometallic 1,4-Diynes: Reaction Behavior, Structure, and Bonding.
Organometallics, 16, 4970-4979. (z) Lang, H., and Weinmann, M. (1996). Bis(alkynyl)
Titanocenes as Organometallic Chelating Ligands for the Stabilization of Monomeric
Organo Copper(I) Compounds. Synlett, 1, 1-10. (aa) Hayashi, Y.; Osawa, M.;
Kobayashi, K., and Wakatsuki, Y. (1996). Reductive Elimination by Remote Electron
Transfer Activation in C4-Bridged Titanocene-Ferrocenyl Complexes. Chem. Commun.,
1617-1618. (bb) Janssen, M. D.; Herres, M.; Zsolnai L.; Grove, D. M.; Spek, A. L., and
Lang, H. (1995). A Stable Bimetallic Copper(I) Titanium Acetylide. Organometallics,
14, 1098-1100. (cc) Janssen, M. D.; Smeets, W. J. J.; Spek, A. L.; Grove, D.M.; Lang,
H., and van Koten, G. (1995). Intramolecular Addition of Monomeric Arylcopper
Entities Across an Alkyne Grouping in a Complex of Type [(η5-C5H4SiMe3)2-
Ti(C≡CSiMe3)2]CuR; X-ray Structure of [(η5-C5H4SiMe3)2Ti(C≡CSiMe3)(μ-
C=C(SiMe3)(C6H3(CH2NMe2)2-2,6))Cu]. J. Organomet. Chem., 505, 123-126. (dd)
Janssen, M. D.; Herres, M.; Spek, A. L.; Grove, D. M.; Lang, H., and van Koten, G.
(1995). Monomeric Bis(η2-Alkyne) Complexes of (η1-Mesityl)Copper(I) and (η1-
mesityl)Silver(I) Obtained from a Bis(Alkynyl)Titanocene; X-ray Structure of [(η5-
C5H4SiMe3)2Ti(C≡CSiMe3)2]Cu(η1-Mes) (Mes = C6H2Me3-2,4,6). J. Chem. Soc.,
Chem. Commun., 925-926. (ee) Janssen, M. D.; Herres, M.; Zsolnai, L.; Spek, A. L.;
Grove, D. M.; Lang, H., and van Koten, G. (1996). Monomeric Bis(η2-
Alkyne)Copper(I) and -Silver(I) Halides, Pseudohalides, and Arenethiolates. Inorg.
Chem., 35, 2476-2483. (ff) Back, S.; Rheinwald, G., and Lang, H. (1999). Synthesis
and Electrochemistry of a Bis- η2-Coordinated Tetrametallic Transition-Metal
Complex. Crystal Structure of [(η5-C5H4SiMe3)2Ti(C≡CFc)2]Pd(PPh3). Organo-
metallics, 18, 4119-4122. (gg) Lang, H., and Leschke, M. (2002). From
Heterobimetallic Transition Metal Complexes to Linear Coordination Polymers Based
on cis- and trans-L2Pt(C≡CPh)2. Heteroat. Chem., 13, 521-533.
[15] (a) Gosiewska, S.; Martinez, S. H.; Lutz, M.; Spek, A. L.; van Koten, G., and Klein
Gebbink, R. J. M. (2006). Diastereopure Cationic NCN-Pincer Palladium Complexes
with Square Planar η4-N,C,N,O Coordination. Eup. J. Inorg. Chem., 22, 4600-4607. (b)
Köcher, S.; Lutz, M.; Spek, A. L.; Prasad, R.; van Klink, G. P.M.; van Koten, G., and
Lang, H. (2006). Heterobimetallic Fe–Pd and Fe–Pt NCN Pincer Complexes (NCN =
[C6H2(CH2NMe2)2-2,6]−). Inorg. Chim. Acta, 359, 4454-4462. (c) Szabo, K. J. (2006).
Palladium-Pincer-Complex-Catalyzed Transformations Involving Organometallic
Species. Synlett, 6, 811-824. (d) Slagt, M. Q.; van Zwieten, D. A.P.; 144 Heinrich Lang
and Alexander Jakob Moerkerk, A. J. C. M; Klein Gebbink, R. J. M., and van Koten, G.
(2004). NCN–Pincer Palladium Complexes with Multiple Anchoring Points for
Functional Groups. Coord. Chem. Rev., 248, 2275-2282. (e) van der Boom, M., and
Milstein, D. (2003). Cyclometalated Phosphine-Based Pincer Complexes: Mechanistic
Insight in Catalysis, Coordination, and Bond Activation. Chem. Rev., 103, 1759-1792.
(f) Singleton, J. T. (2003). The Uses of Pincer Complexes in Organic Synthesis.
Tetrahedron, 59, 1837-1857. (g) Martin, A., and van Koten, G. (2001). Platinum Group
Organometallics Based on „Pincer” Complexes: Sensors, Switches, and Catalysts.
Angew. Chem. Int. Ed., 40, 3750-3781. (h) Gossage, R.; van de Kuil, L. A., and van
Koten, G. (1998). Diaminoarylnickel(II) "Pincer" Complexes: Mechanistic
Considerations in the Kharasch Addition Reaction, Controlled Polymerization, and
Dendrimeric Transition Metal Catalysts. Acc. Chem. Res., 31, 423-431. (i) Rietveld, M.
H. P.; Grove, D. M., and van Koten, G. (1997). Recent Advances in the Organometallic
Chemistry of Aryldiamine Anions that Can Function as N,C,N'- and C,N,N'- Chelating
Terdentate "Pincer" Ligands: an Overview. New J. Chem., 21, 751-771.
[16] Sutcliffe, O. B., and Bryce, M. R. (2003). Planar Chiral 2-Ferrocenyloxazolines and
1,1′-Bis(oxazolinyl)ferrocenes: Syntheses and Applications in Asymmetric Catalysis.
Tetrahedron: Asymmetry, 14, 2297-2325. (b) Dai, L.-X.; Tu, T.; You, S.-L.; Deng, W.-
P., and Hou, X.-L. (2003). Asymmetric Catalysis with Chiral Ferrocene Ligands. Acc.
Chem. Res., 36, 659-667. (c) Herberhold, M. (2002). 1,1´-Ferrocenedi(amido) Chelate
Ligands in Titanium and Zirconium Complexes. Angew. Chem. Int. Ed., 41, 956-958.
(d) Colacot, T. J. (2001). Ferrocenyl Phosphine Complexes of the Platinum Metals in
Non-Chiral Catalysis. Platinum Metals Rev., 45, 22-30. (e) Bandoli, G., and Dolmella,
A. (2000). Ligating Ability of 1,1′-Bis(diphenylphosphino)ferrocene: a Structural
Survey (1994-1998). Coord. Chem. Rev., 209, 161-196. (f) Vogler, A., and Kunkely, H.
Photochemistry (2000). Induced by Metal-to-Ligand Charge Transfer Excitation.
Coord. Chem. Rev., 208, 321-329. (g) Thomas, J. M.; Maschmeyer, T.; Johnson, B. F.
G. (1999). Shephard, D. S. Constrained Chiral Catalysts. J. Mol. Catalysis A: Chemical,
141, 139-144. (h) Beyer, L.; Richter, R., and Seidelmann, O. (1999).
Ferrocensubstituierte 1,3-bidentate Liganden und ihre heteronuklearen
Übergangsmetallchelate. J. Prakt. Chem., 341, 704-726. (i) Fong, A. S.-W., and Hor, A.
T. S. (1998). Clusters and Aggregates of 1,1′-Bis(diphenylphosphino)ferrocene (dppf).
J. Cluster Sci., 9, 351-392.
[17] Haussler, M.; Sun, Q.; Xu, K.; Lam, J. W. Y.; Dong, H., and Tang, B. Z. (2005).
Hyperbranched Poly(ferrocenylene)s Containing Groups 14 and 15 Elements:
Syntheses, Optical and Thermal Properties, and Pyrolytic Transformations into
Nanostructured Magnetoceramics. J. Inorg. Organomet. Poly. Mat., 15, 67-81. (b)
Fery-Forgues, S., and Delavaux-Nicot, B. (2000). Ferrocene and Ferrocenyl Derivatives
in Luminescent Systems. J. Photochem. Photobio., 132, 137-159. (c) Yuan, Z.;
Collings, J.; Taylor, N. J.; Marder, T. B.; Jardin, C., and Halet, J.-F. (2000). Linear and
Nonlinear Optical Properties of Three-Coordinate Organoboron Compounds. J. Solid
State Chem., 154, 5-12. (d) Delville, M.-H. (1999). Organometallic Electron Reservoir
Sandwich Iron Complexes as Potential Agents for Redox and Electron Transfer Chain
Catalysis. Inorg. Chim. Acta, 291, 1-19. (e) Bethell, D.; Schiffrin, D. J., and Brust, M.
(1996). Method of Synthesizing Materials Having Controlled Electronic, Magnetic,
and/or Optical Properties. PCT Int. Appl., 56 pp. PIXXD2 WO 9607487 A1 19960314
Can 125:24123 AN 1996:365688. (f) Sokolov, V. I. (1995). Optically Active
Organometallic Compounds (a Personal Account from the Inside). J. Organomet.
Chem., 500, 299-306. (g) Astruc, D.; Desbois, M. -H.; Lacoste M., Moulines, F.;
Hamon, J. -R., and Varret, F. (1990). Iron Sandwiches as Molecular Reservoir

Materials: Design, Electronic Properties and Prospects. Polyhedron, 2727-2732.
[18] Special issue, “50th Anniversary of the Discovery of Ferrocene”. (2001). J. Organomet.
Chem., 637-639 (Adams, R. D., Ed.), and references cited therein.
[19] For example: (a) Rüffer, T.; Ohashi, M., Shima, A.; Mizomoto, H.; Kaneda, Y., and
Mashima, K. (2004). Unique Oxidative Metal-Metal Bond Formation of Linearly
Aligned Tetranuclear Rh-Mo-Mo-Rh Clusters. J. Am. Chem. Soc., 126, 12244-12245
and references cited therein. (b) Sterenberg, B. T.; Scoles, L., and Carty, A. J. (2002).
Synthesis, Structure, Bonding and Reactivity in Clusters of the Lower Phosphorus
Oxides. Coord. Chem. Rev., 231, 183-197. (c) Adams R. D., and Qu, B. (2001). Mixed
Metal Cluster Complexes Containing the Bis-Ferrocenylbutadiyne Ligand: Their
Structures and Electrochemical Responses. J. Organomet. Chem., 620, 303-307. (d)
Bruce, M. I.; Low, P. J.; Ke, M.; Kelly, B. D.; Skelton, B. W.; Smith, M. E.; White, A.
H., and Witton, N. B. (2001). Some Chemistry of Diynyl-Tungsten Complexes. Aust. J.
Chem., 54, 453-460. (e) Bruce, M. I., and Humphrey, M. G. (2000). Organo-Transition
Metal Cluster Compounds. Organomet. Chem., 28, 275-366. (f) Blenkiron, P.; Enright,
G. D., and Carty, A. J. (1997). Polycarbon Ligand Chemistry. Novel Behaviour of μ-
η1,η2__-Butadiynyls towards Metal Fragment Additions. Chem. Commun., 5, 483-484.
(g) Doherty, S.; Corrigan, J. F.; Carty, A. J., and Sappa, E. (1995). Homometallic and
Heterometallic Transition Metal Allenyl Complexes: Synthesis, Structure, and
Reactivity. Adv. Organomet. Chem., 37, 39-130. (h) Bantel, H.; Powell, A. K., and
Vahrenkamp, H. (1990). Alkyne-Bridged Tetranuclear Clusters by Expansion of
Trinuclear Clusters. Chem. Ber., 123, 677-684. (i) Huttner, G., and Knoll, K. (1987).
RP-Bridged Carbonyl Metal Clusters: Synthesis, Properties and Reactions. Angew.
Chem., 99, 765-783.
[20] (a) Taher, D., Walfort, B., and Lang, H. (2004). A New Approach to Novel
Homobimetallic Palladium Complexes. Inorg. Chem. Commun., 7, 1006-1009. (b)
Taher, D.; Walfort, B.; van Koten, G., and Lang, H. (2006). Thiol End-Capped One-
Dimensional Platinum and Palladium Complexes. Inorg. Chem. Commun., 9, 955-958.
(c) Lang, H.; Taher, D.; Walfort, B., and Pritzkow, H. (2006). Linear Homobimetallic
Palladium Complexes. J. Organomet. Chem., 691, 3834-3845. (d) Jung, D. R., and
Czanderna, A. W. (1994). Chemical and Physical Interactions at Metal/Self-Assembled
Organic Monolayer Interfaces. Crit. Rev. Solid State Mater. Sci., 19, 1-54. (e) Herdt, G.
C.; Jung, D. R., and Czanderna, A. W. (1995). Weak Interactions between Deposited
Metal Overlayers and Organic Functional Groups of Self-Assembled Monolayers.
Prog. Surf. Sci., 50, 103-129. (f) Tarlov, M. J. (1992). Silver Metalization of
Octadecanethiol Monolayers Self -Assembled on Gold. Langmuir, 8, 80-89. (g) Ohgi,
T.; Sheng, H. Y.; Dong, Z. C., and Nejoh, H. (1999). Observation of Au Deposited
Self-Assembled Monolayers of Octanethiol by Scanning Tunneling Microscopy. Surf.
Sci., 442, 277-282. (h) Ohgi, T.; Fujita, D.; Dong, Z. C., and Nejoh, H. (2001).
Scanning Tunneling Microscopy and X-Ray Photoelectron Spectroscopy of Silver
Deposited Octanethiol Self-Assembled Monolayers. Surf. Sci., 493, 453-459. (i) Fisher,
G. L.; Hooper, A. E.; Opila, R. L.; Allara, D. L., and Winograd, N. (2000). he 146
Heinrich Lang and Alexander Jakob Interaction of Vapor-Deposited al Atoms with
CO2H Groups at the Surface of a Self- Assembled Alkanethiolate Monolayer on Gold.
J. Phys. Chem. B, 104, 3267-3273. (j) Konstadinidis, K.; Zhang, P.; Opila, R. L., and
Allara, D. L. (1995). An In-Situ X-Ray Photoelectron Study of the Interaction between

Vapor-Deposited Ti Atoms and Functional Groups at the Surfaces of Self-Assembled
Monolayers. Surf. Sci., 338, 300- 312. (k) Hooper, A. E.; Fisher, G. L.; Konstadinidis,
K.; Jung, D.; Nguyen, H.; Opila, R. L.; Collins, R. W.; Winograd, N., and Allara, D. L.
(1999). Chemical Effects of Methyl and Methyl Ester Groups on the Nucleation and
Growth of Vapor-Deposited Aluminum Films. J. Am. Chem. Soc., 121, 8052-8064. (l)
Fisher, G. L.; Walker, A. V.; Hooper, A. E.; Tighe, T. B.; Bahnck, K. B.; Skriba, H. T.;
Reinard, M. D.; Haynie, B. C.; Opila, R. L.; Winograd, N., and Allara, D. L. (2002).
Bond Insertion, Complexation, and Penetration Pathways of Vapor-Deposited
Aluminum Atoms with HO- and CH3OTerminated Organic Monolayers. J. Am. Chem.
Soc., 124, 5528-5541. (m) Carlo, S. R.; Wagner, A. J., and Fairbrother, D. H. (2000).
Iron Metalization of Fluorinated Organic Films: A Combined X-ray Photoelectron
Spectroscopy and Atomic Force Microscopy Study. J. Phys. Chem. B, 104, 6633-6641.
(n) Nuzzo, R. G., and Allara, D. L. (1983). Adsorption of Bifunctional Organic
Disulfides on Gold Surfaces. J. Am. Chem. Soc., 105, 4481-4483. (o) Lehn, J. M.
(1995). Supramolecular Chemistry-Concepts and Perspectives. Weinheim, Germany:
VCH. (p) Mayor, M.; von Hänisch, C.; Weber, H. B.; Reichert, J., and Beckmann, D.
(2002). A trans-Platinum(II) Complex as a Single-Molecule Insulator. Angew. Chem.,
Int. Ed., 41, 1183-1186. (q) Mayor, M., and Weber, H. B. (2004). Statistical Analysis of
Single-Molecule Junctions. Angew. Chem., 43, 2942-2884. (r) van Ryswyk, H.; Moore,
E. E.; Joshi, N. S.; Zeni, R. J.; Eberspacher, A. T., and Collman, J. P. (2004). Surface-
Confined Metalloporphyrin Oligomers. Angew. Chem., 43, 5827-5830.
[21] (a) Creutz, C., and Taube, H. (1969). A Direct Approach to Measuring the Franck-
Condon Barrier to Electron Transfer between Metal Ions. J. Am. Chem. Soc., 91, 3988-
3989. (b) C. Creutz, C. (1983). Mixed Valence Complexes of d5-d6 Metal Centers.
Prog. Inorg. Chem., 30, 1-73. (c) Creutz, C.; Newton, M. D., and Sutin, N.
(1994).Metal-Ligand and Metal-Metal Coupling Elements. J. Photochem. Photobiol. A:
Chem.,82, 47-59.
[22] For further literature see: (a) Ward, M. D. (1995). Metal-Metal Interactions in Binuclear
Complexes Exhibiting Mixed Valency; Molecular Wires and Switches. Chem. Soc.
Rev., 24, 121-134. (b) Barlow, S., and O´ Hare, D. (1997). Metal-Metal Interactions in
Linked Metallocenes. Chem. Rev., 97, 637-669. (c) Whittall, I. R., McDonagh, A. M.,
Humphrey and M. G.; Samoc, M. (1998). Organometallic Complexes in Nonlinear
Optics II: Third-Order Nonlinearities and Optical Limiting Studies. Adv. Organomet.
Chem., 43, 349-405. (d) Astruc, D. (1997). From Organotransition-Metal Chemistry
Toward Molecular Electronics: Electronic Communication Between Ligand-Bridged
Metals. Acc. Chem. Res., 30, 383-391. (e) Skibar, W., Kopacka, H., Wurst, K.,
Salzmann, C., Ongania, K. H., de Biani, F. F., Zanello, P., and Bildstein, B. (2004).
α,ω-Diferrocenyl Cumulene Molecular Wires. Synthesis, Spectroscopy, Structure,
and Electrochemistry. Organometallics, 23, 1024-1041. (f) Chung, M. C.; Gu, X.;
Etzenhouser, R. A.; Spuches, A. M.; Rye, P. T.; Seetharaman, S. K.; Rose, D. J.,
Zubieta, J., and Sponsler, M. B. (2003). Intermetal Coupling in [(η5-C5R5)Fe(dppe)]2(μ-
CH=CHCH=CH) and in Their Dicationic and Monocationic Mixed-Valence Forms.
Organometallics, 22, 3485-3494. (g) Zheng, Q.; Hampel, F., and Gladysz, J. A. (2004).
Longitudinally Extended Molecular Wires Based upon PtC≡CC≡CC≡CC≡C Repeat
Units: Iterative Syntheses of Functionalized Linear PtC8Pt, PtC8PtC8Pt, and

PtC8PtC8PtC8Pt Assemblies. Organometallics, 23, 5896-5899. (h) Chanda, N.; Sarkar,
B.; Fiedler, J.; Kaim, W., and Lahiri, C. K. (2003). Synthesis and Mixed Valence
Aspects of [{(L)ClRu}2(μ-tppz)]n+ incorporating 2,2´-Dipyridylamine (L) as Ancillary
and 2,3,5,6-Tetrakis(2-pyridyl)pyrazine (tppz) as Bridging Ligand. Dalton Trans., 18,
3550-3555. (i) Venkatesan, K.; Blacque, O., and Berke, H. (2006). Metallacumulenes
as Potential Electron Reservoir Devices. Organometallics, 25, 5190-5200. (j) Akita, M.;
Sakurai, A.; Chung, M.-C., and Moro-oka, Y. (2003). Cluster Compounds Containing a
Linear Carbon Chain Derived From Polyynediyl and Polyynyl Complexes, Fp*-
(C≡C)n-X [X = Fp*, H; Fp*=Fe(η5-C5Me5)(CO)2]. J. Organomet. Chem., 670, 2-10 and
references cited therein. (k) Nguyen, P.; Gomez-Elipe, P., and Manners, I. (1999).
Organometallic Polymers with Transition Metals in the Main Chain. Chem. Rev., 99,
1515-1548. (l) Paul, F., and Lapinte C. (1998). Organometallic Molecular Wires and
other Nanoscale-Sized Devices. An Approach Using the Organoiron (dppe)Cp*Fe
Building Block. Coord. Chem. Rev., 178-180, 431-509. (m) Sauvage, J. P.; Collin, J. P.;
Chambron, J. C.; Guillerez, S.; Coudret, C.; Balzani, V.; Barigelletti, F.; De Cola, L.,
and Flamigni, L. (1994). Ruthenium(II) and Osmium(II) Bis(terpyridine) Complexes in
Covalently-Linked Multicomponent Systems: Synthesis, Electrochemical Behavior,
Absorption Spectra, and Photochemical and Photophysical Properties. Chem. Rev., 94,
993-1019. (n) Low, P. J., and Bruce, M. I. (2001). Transition Metal Chemistry of 1,3-
Diynes, Polyynes, and Related Compounds. Adv. Organomet. Chem., 48, 71-286. (o)
Rigaut, S.; Massue, J.; Touchard, D.; Fillaut, J. L.; Golhen, S., and Dixneuf, P. H.
(2002). Unprecedented Coupling of Allenylidene and Diynyl Metal Complexes: A
Bimetallic Ruthenium System with a C7 Conjugated Bridge. Angew. Chem., Int. Ed.,
41(23), 4513-4517. (p) Schwab, P. F. H.; Levin, M. D., and Michl, J. (1999). Molecular
Rods. 1. Simple Axial Rods. Chem. Rev., 99, 1863-1933. (q) Weyland, T.; Costuas, K.;
Toupet, L.; Halet, J. F., and Lapinte, C. (2000). Organometallic Mixed-Valence
Systems. Two-Center and Three-Center Compounds with meta Connections around a
Central Phenylene Ring. Organometallics, 19, 4228-4239. (r) Ceccon, A.; Santi, S.;
Orian, L., and Bisello, A. (2004). Electronic Communication in Heterobinuclear
Organometallic Complexes through Unsaturated Hydrocarbon Bridges. Coord. Chem.
Rev., 248, 683-724. (s) Mantovani, N.; Brugnati, M.; Gonsalvi, L.; Grigiotti, E.; Laschi,
F.; Marvelli, L.; Peruzzini, M.; Reginato, G.; Rossi, R., and Zanello, P. (2005).
Synthesis, Characterization, and Electrochemical Behavior of Mono- and Bimetallic
Ruthenium and Rhenium Allenylidenes Bearing Multiconjugated Organic Spacers.
Organometallics, 24, 405-418. (t) Le Narvor, N., and Lapinte, C. (1993). First C4
Bridged Mixed-Valence Iron(II)–Iron(III) Complex Delocalized on the Infrared
TimeScale. J. Chem. Soc., Chem. Commun., 4, 357-359. (u) Dewhurst, R. D.; Hill, A.
F., and Willis, A. C. (2005). Stoichiometric and Catalytic Demercuration of
is(tricarbido) mercurials: The First Dimetallaoctatetraynes. Organometallics, 24, 3043-
3046. (v) Roue, S.; Lapinte, C., and Bataille, T. (2005). Organometallic Mixed-Valence
Systems. Electronic Coupling through an Alkyndiyl Bridge Incorporating Methylene
Groups. Organometallics, 23, 2558-2567. (w) Coat, F.; Paul, F.; Lapinte, C.; Toupet,
L.; Costuas, K., and Halet, J. F. (2003). Chemistry of the 1,3,5,7-Octatetraynediyl
Carbon Rod End-Capped by Two Electron-Rich (η5-C5Me5)(η2-dppe)Fe Groups. J.
Organomet. Chem., 683, 368-378. (x) Roue, S.; Le Stang, S.; Toupet, L., and Lapinte,
C. (2003). Magnetic Communication Between two [(η5-C5Me5)(η2-dppe)Fe(III)] Units

Mediated by the 2,5-Bis(ethynyl)thiophene Spacer. C. R. Chim., 6, 353-366. (y) Jiao,
H.; Costuas, K.; Gladysz, J. A.; Halet, J. F.; Guillemot, M.; Toupet, L.; Paul, F., and
Lapinte, C. (2003). Bonding and Electronic Structure in Consanguineous and Conjugal
Iron and Rhenium sp Carbon Chain Complexes [MC4M']n+: Computational Analyses of
the Effect of the Metal. J. Am. Chem. Soc., 125, 9511-9522. (z) Bruce, M. I.; Ellis, B.
G.; Skelton, B. W., and White, A. H. (2005). Further Reactions of some
Bis(vinylidene)diruthenium Complexes. J. Organomet. Chem., 690, 792-801. (aa)
Bruce, M. I.; Buntine, M. A.; Costuas, K.; Ellis, B. G.; Halet, J. F.; Low, P. J.; Skelton,
B. W., and White, A. H. (2004). Some Ruthenium Complexes Containing Cyanocarbon
Ligands: Syntheses, Structures and Extent of Electronic Communication in Binuclear
Systems. J. Organomet. Chem., 689, 3308-3326. (bb) Liu, S. H.; Xia, H.; Wan, K. L.;
Yeung, R. C. Y.; Hu, Q. Y., and Jia, G. (2003). Synthesis of [TpRu(CO)(PPh3)]2(μ-
CH=CH-CH=CH-C6H4-CH=CH-CH=CH) from Wittig Reactions. J. Organomet.
Chem., 683, 331-336. (cc) Cifuentes, M. P., and Humphrey, M. G. (2004). Alkynyl
Compounds and Nonlinear Optics. J. Organomet. Chem., 689, 3968-3981. (dd)
Novikova, L. N.; Peterleitner, M. G.; Sevumyan, K. A.; Semeikin, O. V.; Valyaev, D.
A.; Ustynyuk, N. A.; Khrustalev, V. N.; Kuleshova, L. N., and Antipin, M. Y. (2001).
Oxidative Dehydrodimerization of Manganese Phenylvinylidene Complex (η5-
C5H5)(CO)2Mn=C=C(H)Ph. X-ray Structure of Phenyl(trityl)vinylidene Complex (η5-
C5H5)(CO)2Mn=C=C(CPh3)Ph. J. Organomet. Chem., 631, 47-53. (ee) Vicente, J.;
Chicote, M. T.; Alvarez-Falcon, M. M., and Bautista, D. (2004). The First Metal
Complexes Derived from 3,5-Diethynylpyridine. X-ray Crystal Structure of
[(AuPTo3)2{μ-(C≡C)2Py}] (Py = Pyridine-3,5-diyl; To = p-Tolyl). Organometallics, 23,
5707-5712. (ff) Weyland, T.; Ledoux, I.; Brasselet, S.; Zyss, J., and Lapinte, C. (2000).
Nonlinear Optical Properties of Redox-Active Mono-, Bi-, and Trimetallic σ-Acetylide
Complexes Connected through a Phenyl Ring in the Cp*(dppe)Fe Series. An Example
of Electro-Switchable NLO Response. Organometallics, 19, 5235-5237. (gg) Yam, V.
W. W.; Tao, C. H.; Zhang, L.; Wong, K. M. C., and Cheung, K. K. (2001). Synthesis,
Structural Characterization, and Luminescence Properties of Branched Palladium(II)
and Platinum(II) Acetylide Complexes. Organometallics, 20, 453-459. (hh) Russo, M.
V.; LoSterzo, C.; Franceschini, P.; Biagini, G., and Furlani, A. (2001). Synthesis of
Highly Ethynylated Mono and Dinuclear Pt(II) Tethers Bearing the 4,4′-
Bis(ethynyl)biphenyl (debp) Unit as Central Core. J. Organomet. Chem., 619, 49-61.
(ii) Hoshino, Y. (2001). Molecular Design for Long-Range Electronic Communication
between Metals Polyyne and Ethynylated Aromatic Systems as Molecular Wires in
Binuclear Ruthenium β-Diketone Complexes. Platinum Met. Rev., 45, (1), 2-11. (jj)
Meyer, W. E.; Amoroso, A. J.; Horn, C. R.; Jaeger, M., and Gladysz, J. A. (2001).
Synthesis and Oxidation of Dirhenium C4, C6, and C8 Complexes of the Formula (η5-
C5Me5)Re(NO)(PR3)(C≡C)n(R3P)(ON)Re(η5-C5Me5) (R = 4-C6H4R', c-C6H11): In
Search of Dications and Radical Cations with Enhanced Stabilities. Organometallics,
20, 1115-1127. (kk) Doppiu, A.; Minghetti, G.; Cinellu, M. A.; Stoccoro, S.; Zucca, A.,
and Manassero, M. (2001). Unprecedented Behavior of 2,2':6',2' '-Terpyridine:
Dinuclear Platinum(II) Derivatives with a New N,C^C,N Bridging Ligand.
Organometallics, 20, 1148-1152. (ll) Matsuzaka, H.; Okimura, H.; Sato, Y.; Ishii, T.;
Yamashita, M.; Kondo, M.; Kitagawa, S., and Shiro, M.; Yamasaki, M. (2001).
Synthesis, Structure and Reactivities of the Dinuclear μ-η1:η6-Arylethynyl Ruthenium
Complexes [Cp(PR3)2Ru(μ-η1:η6-C≡CC6H4Me-p)RuCp*]·Cl (R = Ph, Me; Cp = η5-
C5H5, Cp* = η5-C5Me5). The Molecular Structure of [Cp(PPh3)2Ru(μ-η1:η6-
C≡CC6H4Me-p)RuCp*]·PF6. J. Organomet. Chem., 625, 133-139. (mm) Ara, I.;
Berenguer, J. R.; Eguizabal, E.; Fornies, J.; Gomez, J.; Lalinde, E., and Saez-Rocher, J.
M. (2000). Synthesis, Photophysical Properties, and Theoretical Studies of Hydride-
Alkynyl Platinum(II) Complexes. Molecular Structures of [trans-PtH(C≡CC5H4N-
2)(PPh3)2] and [Pt(η2-HC≡CCPh2OH)(PPh3)2]. Organometallics, 19, 4385-4397. (nn)
Hartmann, H.; Scheiring, T.; Fiedler, J., and Kaim, W. (2000). Structures and
Spectroelectrochemistry (UV–vis, IR, EPR) of Complexes [(OC)3ClRe]n(abpy), n = 1,
2; abpy = 2,2′-Azobispyridine. J. Organomet. Chem., 604, 267-272. (oo) Hartbaum, C.;
Mauz, E.; Roth, G.; Weissenbach, K., and Fischer, H. (1999). Bimetallic Complexes
with Conjugated C4, C6, C10, and C14 Bridges: Synthetic Routes to Alkynediyl-Bridged
Bis(carbene) Complexes. Organometallics, 18, 2619-2627. (pp) Peters, T. B.; Bohling,
J. C.; Arif, A. M., and Gladysz, J. A. (1999). C8 and C12 sp Carbon Chains That Span
Two Platinum Atoms: The First Structurally Characterized 1,3,5,7,9,11-Hexayne.
Organometallics, 18, 3261-3263. (qq) Xia, H. P.; Ng, W. S.; Ye, J. S.; Li, X. Y.; Wong,
W. T.; Lin, Z.; Yang, C., and Jia, G. (1999). Synthesis and Electrochemical Properties
of C5H-Bridged Bimetallic Iron, Ruthenium, and Osmium Complexes.
Organometallics, 18, 4552-4557. (rr) Kheradmandan, S.; Heinze, K.; Schmalle, H. W.,
and Berke, H. (1999). Electronic Communication in C4-Bridged Binuclear Complexes
with Paramagnetic Bisphosphane Manganese End Groups. Angew. Chem. Int. Ed., 38,
2270-2273. (ss) Sato, M.; Iwai, A., and Watanabe, M. (1999). Synthesis and Redox
Behavior of Ruthenium(II) 2,3,4,5-Tetramethylruthenocenylacetylide and Related
Complexes. Formation of μ-η6:η1-[(Cyclopentadienylidene)ethylidene]diruthenium
Complexes Containing a Strong Metal-Metal Interaction. Organometallics, 18, 3208-
3219. (tt) Sakurai, A.; Akita, M., and Moro-oka, Y. (1999). Synthesis and
Characterization of the Dodecahexaynediyldiiron Complex, Fp*-(C≡C)6-Fp* [Fp*
=Fe(η5-C5Me5)(CO)2], the Longest Structurally Characterized Polyynediyl Complex.
Organometallics, 18, 3241-3244. (uu) Glöckle, M., and Kaim, W. (1999). An
Exceedingly Stable Diiron(II,III) Complex Ion [(tz){Fe(CN)5}2]5- with
Comproportionation Constants between 108 (in H2O) and 1019 (in CH3CN). Angew.
Chem. Int. Ed., 38, 3072-3074. (vv) Coat, F.; Guillemot, M.; Paul, F., and Lapinte, C.
(1999). First Synthesis and Spectroscopic Characterization of Isolated Butatrienylidene
Complexes of Transition Metals. J. Organomet. Chem., 578, 76-84. (ww) Akita,
M.;Chung, M. C.; Sakurai, A.; Sugimoto, S.; Terada, M.; Tanaka, M., and Moro-oka,
Y. (1997). Synthesis and Structure Determination of the Linear Conjugated Polyynyl
and Polyynediyl Iron Complexes Fp*-(C≡C)n-X (X = H (n = 1, 2); X = Fp* (n = 1, 2,
4); Fp* = (η5-C5Me5)Fe(CO)2). Organometallics, 16, 4882-4888. (xx) Steenwinkel, P.;
Grove, D. M.; Veldman, N.; Spek, A. L., and van Koten, G. (1998). Ionic 4,4'-
Biphenylene-Bridged Bis-ruthenium Complexes [Ru2(4,4'-{C6H2(CH2NMe2)2-
2,6}2)(terpy)2]n+ (n = 2 and 4) and their Reversible Redox Interconversion: A Molecular
Switch. Organometallics, 17, 5647-5655.
[23] (a) Marcus, R. A., and Sutin, N. (1985). Electron Transfers in Chemistry and Biology.
Biochim. Biophys. Acta, 811, 233-322. (b) Hush, N. S. (1985). Distance Dependence of
Electron Transfer Rates. Coord. Chem. Rev., 64, 135-157. (c) Coe, B. J. (1999).
Molecular Materials Possessing Switchable Quadratic Nonlinear Optical Properties.
Chem. Eur. J., 5, 2464-2471. (d) Bruce, M. I.; de Montigny, F.; Jevric, M.; Lapinte, C.;
Skelton, B. W.; Smith, M. E., and White, A. H. (2004). Molecular Materials Possessing
Switchable Quadratic Nonlinear Optical Properties. J. Organomet. Chem., 689, 2860-
2871. (e) Weng, W.; Ramsden, J. A.; Arif, A. M., and Gladysz, J. A. (1993). A New
Form of Coordinated Carbon: An Unsupported C3 Chain Spanning Two Different
Transition Metals. J. Am. Chem. Soc., 115, 3824-3825. (f) Bullock, R. M.; Femke, F.R.,
and Szalda, D. J. (1990). Complexes Containing a C2 Bridge between an Electron-Rich
Metal and an Electron-Deficient Metal. An Agostic Interaction in a RuCH2CH2Zr
Moiety. J. Am. Chem. Soc., 112, 3244-3245. (g) Bürger, H., and Kluess, (1973). C.
Titan-Stickstoff-Verbindungen XVII. σ-(Ferrocenyl)-Titan-Dialkylamide. J.
Organomet. Chem., 56, 269-277. (h) Razuvaev, G. A.; Domrachev, G. A.; Sharutin, V.
V., and Suvorova, O. N. (1977). Ferrocenyl Derivatives of Dicyclopentadienyl-
Titanium, -Zirconium and -Hafnium. J. Organomet. Chem., 141, 313-317. (i) Zakharov,
L. N.; Struchkov, V. T., Sharutin, V. V., and Suvorova, O. N. (1979). Crystal Structure
of Diferrocenyltitanocene, C30H28Fe2Ti. Cryst. Struct. Commun., 8, 439-444. (j) Dias,
A. R.; Salema, M. S., and Simoes, J. A. M. (1982). Enthalpies of Formation of Bis(η5-
cyclopentadienyl)diphenyltitanium and Bis(η5-cyclopentadienyl) Diferrocenyltitanium.
Organometallics, 1, 971-973. (k) Wedler, M.; Roesky, H. W., and Edelmann, F. T.
(1988). Ferrocenyl Complexes of the Early Transition Metals - Synthesis and Structure.
Z. Naturforsch., B43, 1461-1467. (l) Lemke, F. R.; Szalda, D. J.; Bullock, R. M. (1991).
Ruthenium/Zirconium Complexes Containing C2 Bridges with Bond Orders of 3, 2, and
1. Synthesis and Structures of Cp(PMe3)2RuCHnCHnZrClCp2 (n = 0, 1, 2). J. Am. Chem.
Soc., 113, 8466-8477. (m) Gu, X., and Sponsler, M. B. (1998). Synthesis of Fe-C≡C-M
Complexes through Condensation of Fe-C≡C-H with M-H or M-NMe2.
Organometallics, 17, 5920-5923. (n) Mitani, M.; Hayakawa, M.; Yamada, T., and
Mukaiyama, T. (1996). Novel Zirconium-Iron Multinuclear Complex Catalysts for
Olefin Polymerizations. Bull. Chem. Soc. Jpn., 69, 2967-2976. (o) Qian, C.; Guo, J.;
Sun, J.; Chen, J.; Zheng, P. (1997). Heterobimetallic Complexes with
Phenylcyclopentadienyl Ligand: Syntheses and Structures of Tricarbonylchromium-
η6,η5-Phenylcyclopentadienyl-Transition Metal Complexes. Inorg. Chem., 36, 1286-
1295. (p) Weng, W.; Bartik, T., and Gladysz, J. A. (1994). On the Way to Coupling of
Single Metals to One-Dimensional Carbon Wires: Charge Transfer between Terminal
Rhenium and Manganese Centers in C5-Cumulene. Angew. Chem., Int. Ed. Engl., 33,
2199-2202. (q) Stepnicka, P.; Podlaka, J.; Horacek, M.; Hanus, V., and Mach, K.
(1999). A Directly Ring-to-Ring Linked Ferrocene–Pseudotitanocene Complex. J.
Organomet. Chem., 580, 210-213. (r) Wong, W. Y.; Ho, K. Y.; Ho, S. L., and Lin,
Z.(2003). Carbon-Rich Organometallic Materials Derived from 4-
Ethynylphenylferrocene. J. Organomet. Chem., 683, 341-353. (s) Yam, V. W. W.;
Wong, K. M. C.;Chong, S. H. F.; Lau, V. C. Y.; Lam, S. C. F.; Zhang, L., and Cheung,
K. K. (2003). Synthesis, Electrochemistry and Structural Characterization of
Luminescent Rhenium(I) Monoynyl Complexes and their Homo- and Hetero-Metallic
Binuclear Complexes. J. Organomet. Chem., 670, 205-220. (t) Launay, J. P. (2001).
LongDistance Intervalence Electron Transfer. Chem. Soc. Rev., 30, 386-397. (u)
Brunschwig, B. S., and Sutin, N. (1999). Energy Surfaces, Reorganization Energies,
and Coupling Elements in Electron Transfer. Coord. Chem. Rev., 187, 233-254. (v)
Wong, K. M. C.; Lam, S. C. F.; Ko, C. C.; Zhu, N.; Yam, V. W. W.; Roue, S.; Lapinte,
C.; Fathallah, S.; Costuas, K.; Kahlal, S., and Halet, J. F. (2003). Electroswitchable
Photoluminescence Activity: Synthesis, Spectroscopy, Electrochemistry, Photophysics,
and X-ray Crystal and Electronic Structures of [Re(bpy)(CO)3(C≡C-C6H4-C≡C)-
Fe(C5Me5)(dppe)][PF6]n (n = 0, 1). Inorg. Chem., 42, 7086-7097. (w) Paul, F.; Meyer,
W. E.; Toupet, L.; Jiao, H.; Gladysz, J. A., and Lapinte, C. (2000). A "Conjugal"
Consanguineous Family of Butadiynediyl-Derived Complexes: Synthesis and
Electronic Ground States of Neutral, Radical Cationic, and Dicationic Iron/Rhenium C4
Species. J. Am. Chem. Soc., 122, 9405-9414. (x) Wheatley, N., and Kalck, P. (1999).
Structure and Reactivity of Early-Late Heterobimetallic Complexes. Chem. Rev., 99,
3379-3419. (y) Guo, J. H., and Qian, C. T. (1996). Synthesis and Reactivity of
Heterobimetallic Complexes. Youji Huaxue, 16, 301-309. (z) Kuwabara, J.; Takeuchi,
D., and Osakada, K. (2004). Preparation and Properties of Cp2Zr(μ-
N=CAr2)2PdCl(Me), New Zr/Pd Heterobimetallic Complexes with Bridging
Alkylideneamido Ligands. Organometallics, 23, 5092-5095. (aa) Berenguer, J. R.;
Bernechea, M.; Fornie´s, J.; Garcia, A., and Lalinde, E. (2004). (p-Cymene)-
Ruthenium(II)(diphenylphosphino)alkyne Complexes: Preparation of (μ-Cl)(μ -
PPh2C≡CR)-Bridged Ru/Pt Heterobimetallic Complexes. Organometallics, 23, 4288-
4300. (bb) Gauthier, S.; Quebatte, L.; Scopelliti, R., and Severin, K. (2004). Syntheses
and Structures of Homo- and Heterobimetallic, Chloro-Bridged Complexes Containing
the RuCl3(AsPh3)n Fragment (n = 1, 2). Inorg. Chem. Commun., 7, 708-712. (cc)
Thurston, J. H.; Tang, C. G. Z.; Trahan, D. W., and Whitmire, K. H. (2004). Toward
Rational Control of Metal Stoichiometry in Heterobimetallic Coordination Complexes:
Synthesis and Characterization of Pb(Hsal)2(Cu(salen*))2, [Pb(NO3)(Cu(salen*))2]-
(NO3), Pb(OAc)2(Cu(salen*)), and [Pb(OAc)(Ni(salen*))2](OAc). Inorg. Chem., 43,
2708-2713. (dd) Yang, Y.; Abboud, K. A., and McElwee-White, L. (2003).
Heterobimetallic Complexes with dppm-Bridged Ru/Pd, Ru/Pt, Ru/Au and Ru/Cu
Centers. Dalton Trans., 22, 4288-4296. (ee) Berenguer, J. R.; Fornie s, J.; Lalinde, E.,
and Martinez, F. (1996). Reactions of (σ-Alkynyl)platinum Complexes with [Pd(η3-
C3H5)Cl]2. Synthesis of Bis(η2-alkyne)(η3-allyl)palladium(II) Complexes. Crystal and
Molecular Structure of [cis-(PPh3)2Pt(μ-η1:η2-C≡CtBu)2Pd(η3-C3H5)](ClO4).
Organometallics, 15, 4537-4546. (ff) Dennett, J. N. L.; Knox, S. A. R.; Anderson, K.
M.; Charmant, J. P. H., and Orpen, A. G. (2005). The Synthesis of [FeRu(CO)2(μ-
CO)2(η-C5H5)(η-C5Me5)] and Convenient Entries to its Organometallic Chemistry.
Dalton Trans., 1, 63-73. (gg) Friedrich, H. B.; Howie, R. A.; Laing, M., and Onani, M.
O. (2004). Transition Metal-Substituted Paraffins: Synthesis and Properties of some μ-
Saturated Heterobimetallic Complexes Containing Mo and W or Fe and the Crystal
Structures of [(η5-C5H5)(CO)3W(CH2)3Mo(CO)2(PPh3)(η5-C5H5)] and [(η5-
C5H5)(CO)2(PPh3)Mo(CH2)3Fe(CO)2(η5-C5H5)]. J. Organomet. Chem., 689, 181-193.
(hh) Li, Q. S.; Xu, F. B.; Cui, D. J.; Yu, K.; Zeng, X. S.; Leng, X. B.; Song, H. B., and
Zhang, Z. Z. (2003). Heterobimetallic Pt(II)–M(I) (M = Cu, Ag) Eight-Membered
Macrocyclic Complexes with Large-Bite P,N-Ligand Bridges. Dalton Trans., 8, 1551-
1557. (ii) Fornie s-Camer, J.; Claver, C.; Masdeu-Bulto, A. M., and Cardin, C. J.
(2002). New Half-Sandwich Heterobimetallic CpMPt (M = Rh, Ir) Dithiolato Bridged
Complexes. X-Ray Structure of [(PPh3)2Pt(μ-S(CH2)2S)RhCl(η5-C5H5)]BF4. J.
Organomet. Chem., 662, 188-191. (jj) Meichel, E.; Stein, T.; Kralik, J.; Rheinwald, G.,
and Lang, H. (2002). Synthese von [(η5-C5H5)2Ti(Cl)(C≡CSiMe3)]Ni(CO) und dessen
Reaktionsverhalten gegenüber Phosphiten: die Festkörperstruktur von (CO)2Ni-
[P(OC6H4CH3-2)3]2. J. Organomet. Chem., 649, 191-198. (kk) Le Gendre, P.; Picquet,
M.; Richard, P., and Moise, C. (2002). Ti–Ru Bimetallic Complexes: Catalysts for
Ring-Closing Metathesis. J. Organomet. Chem., 643-644, 231-236. (ll) Burgos, F.;
Chavez, I.; Manriquez, J. M.; Valderrama, M.; Lago, E.; Molins, E.; Delpech, F.;
Castel, A., and Rivie´re, P. (2001). A New Heterobimetallic Ru, Rh Complex with a
Dianionic Pentalene as Bridging Ligand. Synthesis, Crystal Structure, and Catalytic
Activity of [Cp*Ru(μ-η5,η3-C8H6)Rh(η4-COD)]. Organometallics, 20, 1287-1291.
(mm) Bruce, M. I.; De Montigny, F.; Jevric, M.; Lapinte, C.; Skelton, B. W.; Smith, M.
E., and White, A. H. (2004). Synthesis, Structures and some Reactions of
Ru(C≡CC≡CFc)(PP)Cp (PP = dppm, dppe) and Related Compounds. J. Organomet.
Chem., 689, 2860-2871. (nn) Bruce, M. I., and Low, P. J. (2004). Transition Metal
Complexes Containing All-Carbon Ligands. Adv. Organomet. Chem., 50, 179-444. (oo)
Antonova, A. B.; Bruce, M. I.; Ellis, B. G.; Gaudio, M.; Humphrey, P. A.; Je vric, M.;
Melino, G.; Nicholson, B. K.; Perkins, G. J.; Skelton, B. W.; Stapleton, B.; White, A.
H., and Zaitseva, N. N. (2004). A Novel Methodology for the Synthesis of Complexes
Containing Long Carbon Chains Linking Metal Centres: Molecular Structures of
{Ru(dppe)Cp*}2(μ-C14) and {Co3(μ-dppm)(CO)7}2(μ3:μ3-C16). Chem. Commun., 8,
960-961. (pp) Bruce, M. I.; Skelton, B. W.; White, A. H., and Zaitseva, N. N. (2003).
Preparation and Molecular Structures of some Complexes Containing C5 Chains. J.
Organomet. Chem., 683, 398-405. (qq) Low, P. J., and Bruce, M. I. (2001). Transition
Metal Chemistry of 1,3-Diynes, Poly-ynes, and Related Compounds. Adv. Organomet.
Chem., 48, 71-286. (rr) Bruce, M. I.; Ellis, B. G.; Gaudio, M.; Lapinte, C.; Melino, G.;
Paul, F.; Skelton, B. W.; Smith, M. E.; Toupet, L., and White, A. H. (2004).
Preparation, Structures and some Reactions of Novel Diynyl Complexes of Iron and
Ruthenium. Dalton Trans., 10, 1601-1609. (ss) Bruce, M. I.; Hall, B. C.; Low, P. J.;
Smith, M. E.; Skelton, B. W., and White, A. H. (2000). Heterometallic Complexes
Containing C4 Chains. X-Ray Structures of {Cp(OC)3W}C≡C-C≡C{Ir(CO)(PPh3)2-
(O2)} and cis-Pt{C≡CC≡C[W(CO)3Cp]}2(PEt3)2. Inorg. Chim. Acta, 300-302, 633-644.
(tt) Cheung, K. L.; Yip, S. K., and Yam, V. W. W. (2004). Synthesis, Characterization,
Electrochemistry and Luminescence Studies of Heterometallic Gold(I)–Rhenium(I)
Alkynyl Complexes. J. Organomet. Chem., 689, 4451-4462. (uu) Enders, M.; Kohl, G.,
and Pritzkow, H. (2002). Novel Heterobimetallic Compounds with Metal-Metal Bonds:
The Use of Quinolyl-Substituted Metallocenes as Tridentate Ligands. Organometallics,
21, 1111-1117. (vv) Dewhurst, R. D.; Hill, A. F., and Smith, M. K. (2004).
Heterobimetallic C3 Complexes through Silylpropargylidyne Desilylation. Angew.
Chem. Int. Ed., 43, 476-478. (ww) Pizzotti, M.; Ugo, R.; Roberto, D.; Bruni, S.;
Fantucci, P., and Rovizzi, C. (2002). Organometallic Counterparts of Push-Pull
Aromatic Chromophores for Nonlinear Optics: Push-Pull Heteronuclear Bimetallic
Complexes with Pyrazine and trans-1,2-Bis(4-pyridyl)ethylene as Linkers.
Organometallics, 21, 5830-5840. (xx) Zhang, L. Y.; Chen, J. L.; Shi, L. X., and Chen,
Z. N. (2002). Utilizing Diruthenium Components for the Design of Cyanide-Linked

Tri- and Tetranuclear Organometallic Complexes with Multistep One-Electron Redox
Processes. Organometallics, 21, 5919-5925. (yy) Adams, C. J., and Raithby, P. R.
(1999). Novel Mixed-Metal–Alkynyl Complexes Stabilised by Di-Imine Ligands:
Synthesis, Characterisation and Electrochemistry of [(tBu2bipy)Pt(C≡CR)2M(SCN)] (R
= C6H4Me, SiMe3; M = Cu, Ag). J. Organomet. Chem., 578, 178-185. (zz) Thomas, K.
R. J.; Lin, J. T.; Lin, H. M.; Chang, C. P., and Chuen, C. H. (2001). Ruthenium and
Rhenium Complexes of Fluorene-Based Bipyridine Ligands: Synthesis, Spectra, and
Electrochemistry. Organometallics, 20, 557-563. (aaa) Prim, D.; Auffrant, A.; Plyta, Z.
F.; Tranchier, J. P.; Rose-Munch, F., and Rose, E. (2001). Bimetallic π-Conjugated
Complexes Modulated by a Carbonyl Spacer: Synthesis of Arenetricarbonylchromium–
Ferrocene Derivatives. J. Organomet. Chem., 624, 124-130. (bbb) Richardson, G. N.,
and Vahrenkamp, H. (2000). Cyanide Bridged Trinuclear Complexes with Fe-CN-
MCl2-NC-Fe Backbones (M = Ni, Cu, Zn). J. Organomet. Chem., 593-594, 44-48. (ccc)
Low, P. J.; Rousseau, R.; Lam, P.; Udachin, K. A.; Enright, G. D.; Tse, J. S.; Wayner,
D. D. M., and Carty, A. J. (1999). Polycarbon Ligand Chemistry: Electronic
Interactions between a Mononuclear Ruthenium Fragment and a Cobalt-Carbon Cluster
Core. Organometallics, 18, 3885- 3897. (ddd) Bruce, M. I.; Hall, B. C.; Low, P. J.;
Skelton, B. W., and White, A. H. (1999). Some Ruthenium Complexes Derived from
1,4-Diethynylbenzene: Molecular Structure of Ru{η3-C[=C(CN)2]C(C6H4C≡CH-
4)=C(CN)2}(PPh3)Cp. J. Organomet. Chem., 592, 74-83. (eee) Briel, O.; Fehn, A., and
Beck, W. (1999). Hydrocarbon Bridged Metal Complexes XLV. Dinuclear Polyene-
Bridged Fischer Carbene Complexes and a Star-Shaped Benzene-Bridged
Tris(ferrocenyldecapentaenyl) Compound. J. Organomet. Chem., 578, 247-251. (fff)
Colbert, M. C. B.; Lewis, J.; Long, N. J.; Raithby, P. R.; White, A. J. P., and Williams,
D. J. (1997). Synthetic, Structural, Electrochemical and Electronic Characterisation of
Heterobimetallic Bis(acetylide) Ferrocene Complexes. J. Chem. Soc., Dalton Trans.,
99-104. (ggg) Lin, J. T.; Wu, J. J.; Li, C. S.; Wen, Y. S., and Lin, K. J. (1996).
Conjugated Pyridines with an End-Capping Ferrocene. Organometallics, 15, 5028-
5034. (hhh) Le Stang, S. L.; Lenz, D.; Paul, F., and Lapinte, C. (1999). New Pyridyl-
Functionalized Organoiron Alkynyl Complexes. Easy Access to Polymetallic
Architectures Featuring an Electroactive Site by Simple Coordination Reactions. J.
Organomet. Chem., 572, 189-192. (iii) Stepnicka, P.; Gyepes, R., and Cisarova, I.
(1999). Synthesis and Structure of Titanocene Complexes with η2-Coordinated Internal
Ferrocenylacetylenes. Organometallics, 18, 627-633.
[24] (a) Laus, G.; Strasser, C. E.; Holzer, M.; Wurst, K.; Pürstinger, G.; Ongania, K.-H.;
Rauch, M.; Bonn, G., and Schottenberger, H. (2005). The (E)-2-
Ferrocenylethenylcobaltocenium Cation. A Missing Link in Heteronuclear
Bimetallocene-Based Donor-Acceptor Conjugate Chemistry Exhibiting Irregular
Solvatochromism. Organometallics, 24, 6085-6093 (b) Obendorf, D.; Reichart, E;
Rieker, C., and Schottenberger, H. (1994) Voltammetric Study of some Metallocene-
Substituted (η4-1,3-Cyclopentadiene-5-exo-yl) Cobalt Complexes; ([CpCo(η4-C5H5R)],
R = −C≡C-(η5−C5H4)FeCp; -(η5−C5H4)FeCp; -(η5C5H4)NiCp). Electrochimica Acta,
39, 2367-2375. (c) Wildschek, M.; Rieker, C.; Jaitner, P; Schottenberger, H., and
Schwarzhans, K. E. (1990). Ethynylcobaltocenium Compounds as Precursors for
Bridged, Heteronuclear Oligometallocenes: Preparation and Reactions of Ethynyl-
,trimethylsilylethynyl- and Ferrocenylethynylcobaltocenium Salts. J. Organomet.

Chem., 396, 355-361.
[25] Bartik, T.; Weng, W.; Ramsden, J. A.; Szafert, S.; Falloon, S. B.; Arif, A. M., and
Gladysz, J. A. (1998). New Forms of Coordinated Carbon: Wirelike Cumulenic C3 and
C5 sp Carbon Chains that Span Two Different Transition Metals and Mediate Charge
Transfer. J. Am. Chem. Soc., 120, 11071-11081.
[26] (a) Venkatesan, K.; Fox, T.; Schmalle, H. W., and Berke, H. (2005). Synthesis and
Characterization of Redox-Active C4-Bridged Rigid-Rod Complexes with Acetylide-
Substituted Manganese End Groups. Organometallics, 24, 2834-2847. (b) Venkatesan,
K.; Blacque, O.; Fox, T.; Alfonso, M.; Schmalle, H. W., and Berke, H. (2004).
Synthetic Access to Half-Sandwich Manganese C4 Cumulenic Complexes.
Organometallics, 23, 4646-4671. (c) Fernández, F. J.; Venkatesan, K.; Blacque, O.;
Alfonso, M.; Schmalle, H. W., and Berke, H. (2003). Generation and Coupling of
[Mn(dmpe)2(C≡CR)(C≡C)]. Radicals Producing Redox-Active C4-Bridged Rigid-Rod
Complexes. Chem. Eur. J., 9, 6192-6206. (d) Venkatesan, K.; Fox, T.; Schmalle, H. W.,
and Berke, H. (2005). New Access to Homodinuclear Half-Sandwich
Vinylidenemanganese Complexes. Eur. J. Inorg. Chem., 901-909. (e)Venkatesan, K.;
Blacque, O.;Fox, T.; Alfonso, M.; Schmalle, H. W.; Kheradmandan, S., and Berke, H.
(2005). μ-Carbon-Carbon Bonds of Dinuclear Manganese Half-Sandwich Complexes as
Electron Reservoirs. Organometallics, 24, 920-932.
[27] Kheradmandan, S.; Venkatesan, K.; Blacque, O.; Schmalle, H. W., and Berke, H.
(2004). Facile Access to Redox-Active C2-Bridged Complexes with Half-Sandwich
Manganese End Groups. Chem. Eur. J., 10, 4872-4885.
[28] (a) Herrmann, C.; Neugebauer, J.; Gladysz, J. A., and Reiher, M. (2005). Theoretical
Study on the Spin-State Energy Splittings and Local Spin in Cationic [Re]-Cn-[Re]
Complexes. Inorg. Chem., 44, 6174-6182. (b) Neugebauer, J., and Reiher, M. Mode
(2004). Tracking of Preselected Vibrations of One-Dimensional Molecular Wires. J.
Phys. Chem. A, 108, 2053-2061. (c) Horn, C. R., and Gladysz, J. A. (2003). Syntheses
of Dimetallamacrocycles by Intramolecular Oxidative Couplings of Dinuclear Bis(1,3-
butadiynyl) Complexes: A New Approach to Steric Shielding in (sp-Carbon
chain)dirhenium Complexes [(η5-C5Me5)Re(NO)(PR3)(C≡CC≡CC≡CC≡C)(R3P)(ON)-
Re(η5-C5Me5)]. Eur. J. Inorg. Chem., 2211-2218.
[29] Smith, M. E.; Cordiner, R. L.; Albesa-Jové, D.; Yufit, D. S.; Hartl, F.; Howard, J. A.
K., and Low, P. J. (2006). The Synthesis, Structure, and Electrochemical Properties of
Fe(C≡CC≡N)(dppe)Cp and Related Compounds. Can J. Chem., 84, 154-163. (b) Low,
P. L.; Roberts, R. L.; Cordiner, R. L., and Hartl, F. (2005). Electrochemical Studies of
Bi- and Polymetallic Complexes Featuring Acetylide Based Bridging Ligands. J. Solid
State Electrochem., 9, 717-731 (c) Cordiner, R. L. Corcoran, D.; Yufit, D. S.; Goeta, A.
E.; Howard, J. A. K., and Low, P. J. (2003). Cyanoacetylenes and Cyanoacetylides:
Versatile Ligands in Organometallic Chemistry. Dalton Trans., 3541-3549.
[30] LeVanda, C.; Cowan, D. O.; Leitch, C., and Bechgaard, K. (1974). Mixed-Valance
Diferrocenylacetylene Cation. J. Am. Chem. Soc., 96, 6788-6789.
[31] (a) Y. Masuda, Y., and Shimizu, C. (2006). Solvent Effect on Intramolecular Electron
Transfer Rates of Mixed-Valence Biferrocene Monocation Derivatives. J. Phys. Chem.,
110, 7019-7027. (b) Jiao, J.; Long, G. J.; Rebbouh, L.; Grandjean, F.; Beatty, A. M.,
and Fehlner, T. P. (2005). Properties of a Mixed-Valence (FeII)2(FeIII)2 Square Cell for
Utilization in the Quantum Cellular Automata Paradigm for Molecular Electronics. J.

Am. Chem. Soc., 127, 17819-17831. (c) Kramer, J. A., and Hendrickson, D. N. (1980).
Electron Transfer in Mixed-Valent Diferrocenylacetylene and [2.2]-Ferrocenophane-
1,13-diyne. Inorg. Chem., 19, 3330-3337. (d) Brady, M.; Weng, W.; Zhou, Y.; Seyler,
J. W.; Amoroso; A. J.; Arif, A. M. Böhme, M.; Frenking, G., and Gladysz, J. A. (1997).
Consanguineous Families of Coordinated Carbon: A ReC4Re Assembly That is Isolable
in Three Oxidation States, Including Crystallographically Characterized ReC≡CC≡CRe
and +Re=C=C=C=C=Re+ Adducts and a Radical Cation in which Charge is Delocalized
between Rhenium Termini. J. Am. Chem. Soc., 119, 775-788.
[32] (a) Mochida, T., and Yamazaki, S. (2002). Mono- and Diferrocenyl Complexes with
Electron-Accepting Moieties Formed by the Reaction of Ferrocenylalkynes with
Tetracyanoethylene. J. Chem. Soc., Dalton Trans., 3559-3564. (b) Levanda, C.
Bechgaard, K., and Cowan D. O. (1976). Mixed Valence Cations. Chemistry of n-
Bridged Analogues of Biferrocene and Biferrocenylene. J. Org. Chem., 41, 2700-2704.
(c) Adams, R. D.; Qu, B.; Smith, M. D., and Albright, T. A. (2002). Syntheses,
Structures, Bonding, and Redox Behavior of 1,4-Bis(ferrocenyl)butadiyne Coordinated
Osmium Clusters. Organometallics, 21, 2970-2978. (d) McAdam, C. J.; Brunton, J. J.;
Robinson, B. H., and Simpson, J. (1999). Ferrocenylethynylnaphthalenes and
Acenaphthylenes; Communication Between Ferrocenyl and Cluster Redox Centres. J.
Chem. Soc. Dalton Trans., 2487-2496. (e) Jutzi, P., and Kleinebekel, B. (1997).
Octamethylferrocenylethynyl Units as Peripheral Groups in Rigid, π-Conjugated
Molecular Architectures. J. Organomet. Chem., 545-546, 573. (f) Levanda, C.; Cowan,
D. O.; Leitch, C., and Bechgaard, K. (1974). Mixed-Valence Diferrocenylacetylene
Cation. J. Am. Chem. Soc., 96, 6788-6789. (g) McManis, G. E.; Gochev, A.; Nielson, R.
M., and Weaver, M. J. (1989). Solvent Effects on Intervalence Electron-Transfer
Energies for Biferrocene Cations: Comparisons with Molecular Models of Solvent
Reorganization. J. Phys. Chem., 93, 7733-7739. (h) Delgado-Pena, F.; Talham, D. R.,
and Cowan, D. O. (1983). Near-IR Spectroscopic Studies of Mixed-Valence Di-, Tri-,
and Tetraferrocene Derivatives. J. Organomet. Chem., 253, C43-C46. (i) Powers, M. J.
Meyer, T. J. (1978). Intervalence Transfer in Mixed-Valence Biferrocene Ions. J Am.
Chem. Soc., 100, 4393-4398.
[33] Schimanke, H., and Gleiter, R. (1998). Synthesis and Electrochemical Properties of
Butadiyne-Bridged Cyclopentadienylcobalt-Cyclobutadiene Complexes.
Organometallics, 17, 275-277.
[34] (a) Hore, L.-A.; John McAdam, C.; Kerr, J. L.; Duffy, N. W.; Robinson, B. H., and
Simpson, J. (2000). Communication between Co2(CO)4dppm Units via
Polyferrocenylalkyne Linkages. Organometallics, 19, 5039-5048. (b) Richardson, D.
E., and Taube, H. (1981). Determination of E20-E10 in Multistep Charge Transfer by
Stationary-Electrode Pulse and Cyclic Voltammetry: Application to Binuclear
Ruthenium Ammines. Inorg. Chem., 20, 1278-1285. (c) Cotton, F. A.; Donohue, J. P.,
and Murillo, C. A. (2003). Polyunsaturated Dicarboxylate Tethers Connecting
Dimolybdenum Redox and Chromophoric Centers: Syntheses, Structures, and
Electrochemistry. J. Am. Chem. Soc., 125, 5436-5450. (d) Berry, J. F.; Cotton, F. A.,
and Murillo, C. A. (2004). A Trinuclear EMAC-Type Molecular Wire with Redox-
Active Ferrocenylacetylide "Alligator Clips" Attached. Organometallics, 23, 2503-
2506. (e) Sheng, T.; Appelt, R.; Comte, V., and Vahrenkamp, H. (2003). Chain-Like
Tetra-, Penta- and Heptanuclear Cyanide-Bridged Complexes by Attachment of

Organometallic Cyanides to M2, M3 and M5 Units. Eur. J. Inorg. Chem., 3731-3737.
[35] Köcher, S. (2000). Mehrkernige Übergangsmetallkomplexe: Synthese,
Reaktionsverhalten und elektronische Eigenschaften. Diploma Thesis, TU Chemnitz.
[36] Hayashi, Y.; Osawa, M., and Wakatsuki, Y. (1997). Reductive Coupling Reaction
Induced by Remote-Site Oxidation in Titanocene Bis(metallocenylacetylide), where
Metallocenyl = Ferrocenyl or Ruthenocenyl: a Novel Route to Cn (n = 4, 6, and 8) Wire
with the Metallocenyl Groups at Both Terminals. J. Organomet. Chem., 542, 241-246.
[37] Wetzold, N. (2003). Sythese Lewis-Basen-stabilisierter Bis(alkinyl)-Platin-Komplexe
und deren Reaktionsverhalten. Diploma Thesis, TU Chemnitz.
[38] (a) Osella, D.; Milone, L.; Nervi, C., and Ravera, M. (1995). Electronic Interactions in
Organometallic Dimers. An Electrochemical Approach. J. Organomet. Chem., 488, 1-7.
(b) Osella, D.; Gobetto, R.; Nervi, C.; Ravera, M.; D’Amato, R., and Russo, M. V.
(1998). Synthesis and Characterisation of Bis(ferrocenylethynyl) Complexes of
Platinum (II) a Re-Investigation of their Electrochemical Behaviour. Inorg. Chem.
Commun., 1, 239-245. (c) Russo, M. V., and Furlani, A. (1994). Synthesis of some
Bis(triphenylphosphine)(ethynylferrocenyl) Platinum(II) Complexes; Molecular
Structure of [PtH(C≡C-C5H4FeC5H5)(PPh3)2]. J. Organomet. Chem., 469, 245-252.
[39] Müller, T. J. J., and Lindner, H. J. (1996). Palladium-Copper-Catalyzed Coupling of
Tricarbonylchromium-Complexed Phenylacetylene with Iodoarenes. A Facile Access to
Alkynyl-Bridged Cr(CO)3-Complexed Benzenes. Chem. Ber., 129, 607-613. (b) Müller,
T. J. J.; Ansorge, M., and Lindner, H. J. (1996). Synthesis and Substituent Interactions
of Tricarbonylchromium-Complexed (Arylalkynyl)benzenes. Novel Organometallic
Push-Pull Chromophores. Chem. Ber., 129, 1433-1440. (c) Müller, T. J. J. (1999).
Redox Active Alkenyl-Bridged Bi- and Trinuclear Arene–Cr(CO)3-Complexes by
Horner–Emmons–Wadsworth Olefinations. J. Organomet. Chem., 578, 95. (d) Müller,
T. J. J.; Netz, A.; Ansorge, M.; Schmälzlin, E.; Bräuchle, C., and Meerholz, K. (1999).
Syntheses and NLO Properties of Chromium Carbonyl Arene Complexes with
Conjugated Side Chains: The Amphoteric Nature of Chromium Carbonyl Complexation
in Push-Pull Chromophores. Organometallics, 18, 5066.
[40] Friedrich, D. (2006). Alkinyl-Übergangsmetallkomplexe: Synthese und
Reaktionverhalten. Diploma Thesis, TU Chemnitz.
[41] Sato, M., and Emiko, M. (1995). Unprecedented Promoting Effect of a Ferrocenyl
Group for the Oxidatively Induced Reductive Elimination in cis-Aryl(ferrocenyl
acetylide)platinum(II) Complexes. Organometallics, 14, 3157-3159.
[42] Kirchbauer, F. G.; Pellny, P.-M.; Sun, H.; Burlakov, V. V.; Arndt, P.; Baumann, W.;
Spannenberg, A., and Rosenthal, U. (2001). Synthesis and Reactions with Carbon
Dioxide of Mono(σ-alkynyl) Titanocene(III) Complexes Cp*2Ti(C≡CR) (R = Me, t-
Bu) and the Corresponding "Ate" Complexes [Cp*2Ti(C≡CR)2Li(THF)n] (R = SiMe3, t-
Bu, Ph). Organometallics, 20, 5289-5296.
[43] Erker, G.; Frömberg, W.; Benn, R.; Mynott, R.; Angermund, K., and Krüger, C. (1989).
π-Conjugation and Dynamic Behavior in Doubly Acetylide-Bridged Binuclear Group 4
Bent Metallocene Complexes. Organometallics, 8, 911-920
[44] Back, S.; Gossage, R. A.; Rheinwald, G.; Lang, H., and van Koten, G. (1999). Titanium
σ-Acetylides as Building Blocks for Heterobimetallic Transition Metal Complexes:
Synthesis and Redox Behaviour of π-Conjugated Organometallic Systems. J.

Organomet. Chem., 582, 126.
[45] Lang, H., and Stein, T. (2001). Bis(alkynyl)-Titanium and -Platinum Complexes in the
Synthesis of Oligo- and Polynuclear Early-Late and/or Late-Late Transition Metal
Species: An Overview. Abhath Al-Yarmouk: Basic Sci. Eng., 10, 155; Chem.
Abstr.(2001), 142, 38297.
[46] Lemket, F. R., and Bullock, R. M. (1992). Insertion and Beta-Hydride Elimination
Reactions of Ruthenium/Zirconium Complexes Containing C2 Bridges with Bond
Orders of 1, 2, and 3. Organometallics, 11, 4261-4267.
[47] Back, S.; Gossage, R. A.; Lutz, M.; del Rio, I.; Spek, A. L.; Lang, H., and van Koten,
G. (2000). Bis-ortho-chelated Diaminoaryl Platinum Compounds with _-Acetylene
Substituents. Investigations into Their Stability and Subsequent Construction of
Multimetallic Systems. The Crystal Structure of [(μ2-[(η2-NCN)Pt(η1-CO)C≡CSiMe3])
Co2(CO)6] (NCN = 2,6-Bis[(dimethylamino)methyl]phenyl). Organometallics, 19,
3296-3304.
[48] Packheiser, R. (2003). Multimetallische Übergangsmetallkomplexe mit π-konjungierten
organischen Bausteinen. Diploma Thesis, TU Chemnitz.
[49] Köcher, S. (2007). Ph.D. Thesis, TU Chemnitz.
[50] Köcher, S.; Walfort, B.; Lutz, M.; Spek, L. A.; Prasad, R.; van Koten, G., and Lang, H.
Submitted for publication in J. Organomet. Chem.
[51] Frosch, W.; Back, S.; del Río, I.; van Koten, G., and Lang, H. (1999). An Easy Entry to
Novel Early–Late Oligonuclear Transition Metal Complexes Containing π-Conjugated
Systems. Inorg. Chem. Commun., 2, 584-586.
[52] Back, S., and Lang, H. (2000). Heterometallic Assemblies with Bridging Cyano
Ligands. Organometallics, 19, 749-751.
[53] (a) Wilson, A. J. C. (1995). In International Tables of Crystallography; Kluwer
Academic: London, Vol. C. (b) Lang, H. Köhler, K., and Schiemenz B. (1995).
Lewisbasen Addukte monomerer bis(η2-alkin) AgIX-Verbindungen (X = BF4 oder
OSO2CF3). J. Organomet. Chem., 495, 135-140.
[54] Ara, I.; Berenguer, J. R.; Forniés, J.; Lalinde, E., and Moreno, M. T. (1996). Synthesis
and Characterization of Cationic Heteronuclear Complexes of Platinum(II) and Silver(I)
Bridged by Alkynyl Ligands. J. Organomet. Chem., 510, 63-70.
[55] del Villar, A.; Rheinwald, G., and Lang, H. Unpublished results.
[56] Lang, H., and del Villar, A. (2003). Heterobimetallic Platinum–Copper and Platinum–
Silver Transition Metal Complexes Based on cis-[Pt](C≡CPh)2: An Overview. J
Organomet.Chem., 670, 45-55.
[57] Lang, H.; del Villar, A.; Walfort, B., and Rheinwald, G. (2007) in press J. Organomet.
Chem.
[58] Wong, W.-Y.; Lu, G.-L., and Choi, K.-H. (2002). Synthesis, Characterization and
Structural Studies of New Heterometallic Alkynyl Complexes of Platinum and Group
11 Metals with Chelating Bis(diphenylphosphino)ferrocene Ligand. J. Organomet.
Chem., 659, 107-116.
[59] del Villar, A.; Rheinwald, G.; Walfort, B., and Lang, H. Unpublished.
[60] (a) Bassetti, M. Floris, B., and Illuminati G. (1985). Reaction of Ethynylferrocene with
Mercuric Acetate. Organometallics, 4, 617-623. (b) Cook, D. J.; Hill, A. F., and
Wilson, D. J. (1998). Convenient Synthesis of Alkynyl Aryl Seleno- and Telluro Ethers.
J. Chem. Soc. Dalton Trans., 7, 1171-1173. (c) Dewhurst, R. D.; Hill, A. F., and Smith,
M. K. (2006). Hazards Associated with Bis(alkynyl)mercurials. Organometallics, 25,
2388-2389.
[61] Wetzold, N. (2007). Bis(alkinyl)-Komplexe und Ferrocene als modulare Bausteine für
den Aufbau mehrkerniger Übergangsmetallkomplexe. PhD Thesis, TU Chemnitz.
[62] Köcher, S., and Lang, H. (2001). 4-Ethinyl-benzonitrile-ferrocenes Bridged by a
Pd(PPh3)2 Unit; the Solid-State Structure of (η5-C5H5)Fe(η5-C5H4C≡CC6H4C≡N-1,4). J.
Organomet. Chem., 637-639, 198-203.
[63] Köcher, S.; Walfort, B.; van Klink, G. P. M.; van Koten, G., and Lang, H. (2006).
Trimetallic FePd2 and FePt2 4-Ferrocenyl-NCN Pincer Complexes. J. Organomet.
Chem., 691, 3955-3961.
[64] Packheiser, R. (2007). PhD Thesis, TU Chemnitz.
[65] (a) Ohs, A. C.; Rheingold, A. L.; Shaw, M. J., and Nataro, C. (2004). Electrochemistry
of Group VI Metal Carbonyl Compounds Containing 1,1'-Bis(diphenylphosphino)-
ferrocene. Organometallics, 23, 4655-4660. (b) Koo, L. K.; Phang, L. T.; Hor, T. S. A.,
and Lee, H. K. (1991). High-Performance Liquid Chromatographic Separation of Metal
Carbonyl Complexes Substituted with Bridging and Chelating 1,1'-
Bis(diphenylphosphino) ferrocene. J. Liquid Chromatography, 14, 2079-2087. (c)
Chan, H. S. O.; Hor, T. S. A.; Phang, L. T., and Tan, K. L. (1991). XVI. X-ray
Photoelectron Spectroscopic Differentiation of Chemically Distinct Phosphorus
Environments in Unidentate Complexes of 1,1′-Bis(diphenylphosphino)ferrocene. J.
Organomet. Chem., 407, 353-357. (d) Hor, T. S. A.; Phang, L.-T.; Liu, L.-K., and Wen,
Y. S. (1991). Substituted Metal Carbonyls XV. Crystal and Molecular Structures of
Two Isomorphous Singly Diphosphine-Bridged Complexes (OC)5M(μ-
dppf)M(CO)5·CH2Cl2(M = Cr, Mo; dppf = (Ph2PC5H4)2Fe). J. Organomet. Chem., 397,
29-39. (e) Hor, T. S. A., and Phang, L.-T. (1989). Substituted Metal Carbonyls XI. 1,1′-
Bis(diphenylphosphino)ferrocene — a Bridging, Chelating and Unidentate Ligand in
the Synthesis of M2(CO)10(μ-P-P), M(CO)4(η2-P-P) and M(CO)5(η1-P-P) (where M =
Cr, Mo, W and P-P = Fe(C5H4PPh2)2). J. Organomet. Chem., 373, 319-324. (f) Estevan,
F.; Lahuerta, P.; Latorre, J.; Sanchez, A., and Sieiro, C. (1987). Electrochemical Study
of Dinuclear Ruthenium(II)-Arene Compounds: Electrogeneration of Ru(II)-Ru(I)
Species. Polyhedron, 6, 473-478. (g) Houlton, A.; Roberts, R. M. G., and Silver, J.
(1991). Studies on Gold(I) Complexes of 1,1′-Bis(diphenylphosphino)ferrocene. J.
Organomet. Chem., 418, 269-275. (h) Mai, J.-F., and Yamamoto, Y. (1998).
Preparations and Structures of (η6-Arene)ruthenium(II) Complexes Bearing 1,1′-
Bis(diphenylphosphinomethyl)ferrocene or 1,1′-Bis(diphenylphosphino)ferrocene. J.
Organomet. Chem., 560, 223-232. (i) Delgado, E.; Hernandez, E.; Mansilla, N.;
Moreno, M. T., and Sabat, M. (1999). Co-ordinative Ability of the New Compounds
[Ti(η5-C5H4R)2(C≡CBut)2] (R = PPh2, Ph2P=O or Ph2P=S) as Precursors in the
Synthesis of Heterodi- and Heterotri-Nuclear Species. Crystal Structure of [ClCu(μ-
η5:σ P-C5H4PPh2)2Ti(μ-η2-C≡CtBu)2CuCl] J. Chem. Soc., Dalton Trans., 4, 533-538.
(j) Ara, I.; Berenguer, J. R.; Fornie´s, J., and Lalinde, E. (1997). Synthesis,
Characterisation and NMR Study of Paramagnetic Heteropolynuclear Anionic Pt-Co
Species. Crystal Structures of [NBu4]2[cis-Pt(C6F5)2(C≡CSiMe3)2CoCl3)2·0.5(CH3)2CO
and NBu4]2[Pt(C≡CtBu)42]·1.5(CH3)2CO. Inorg. Chim. Acta, 264, 199-210.
[66] Charmant, J. P. H.; Gomez, J.; Orpen, A. G.; Falvello, L. R.; Fornie´s, J.; Rueda, A.;
Gomez, J.; Lalinde, E., and Moreno, M. T. (1999). Synthesis, Structural
Characterisation and Luminescence Studies of the First Alkynyl Stabilised Platinum–
Cadmium Complexes. Chem. Commun., 20, 2045-2046.
[67] Zhang, D.; McConville, D. B.; Tessier, C. A., and Youngs, W. J. (1997). Synthesis and
Crystallographic Characterization of the Planar Tetraethynylplatinum Complex
(NBu4)2[Pt(OBET)2] and its Double-Tweezer Mercury Dichloride Complex
(NBu4)2[Pt(OBET)2](HgCl2)2. Organometallics, 16, 824-825.
[68] Zhu, Y.; Olivier Clot, O.; Wolf, M. O., and Yap, G. P. A. (1998). Effect of Ancillary
Ligands on Ru(II) on Electronic Delocalization in Ruthenium(II) Bisferrocenylacetylide
Complexes. J. Am. Chem. Soc., 120, 1812-1821.
[69] (a) Lebreton, C.; Touchard, D.; Pichon, L. L.; Daridor, A.; Toupet, L., and Dixneuf, P.
H. (1998). Mono- and Bis-Alkynyl Ruthenium(II) Complexes Containing the
Ferrocenyl Moiety; Crystal Structure of trans-[Ru(C≡CC5H4FeC5H5)2(Ph2PCH2CH2-
PPh2)2] and Electrochemical Studies. Inorg. Chim. Acta, 272, 188-196. (b) Jones, N. D.,
and Wolf, M. O. (1997). Synthesis of a Ferrocenyl-Capped Ruthenium(II) Bis-
(acetylide) Complex: A Model for Organometallic Molecular Wires. Organometallics,
16, 1352-1354.
[70] (a) Vives, G.; Carella, A.; Sistach, S.; Launay, J.-P., and Rapenne, G. (2006). Synthesis
of Triester-Functionalized Molecular Motors Incorporating Bis-Acetylide trans-
Platinum Insulating Fragments. New J. Chem., 30, 1429-1438. (b) D'Amato, R.;
Furlani, A.; Colapietro, M.;, G. Portalone, G.; Casalboni, M.; Falconieri, M., and
Russo, M. V. (2001). Synthesis, Characterisation and Optical Properties of Symmetrical
and Unsymmetrical Pt(II) and Pd(II) Bis-Acetylides. Crystal Structure of trans-
[Pt(PPh3)2(C≡C–C6H5)(C≡C–C6H4NO2)]. J. Organomet. Chem., 627, 13-22. (c) Osella,
D.; Gambino, O.; Nervi, C.; Ravera, M.; Russo, M. V., and Infante, G. (1994). Electron
Transfer in trans-[Pt(PPh3)2(C≡CFc)2] and Related Compounds. Inorg. Chim. Acta,225,
35-40.
[71] Jakob, A., and Lang, H. Unpublished.
[72] (a) Ferrocene/ferrocenium redox couple: Gritzner, G., and Kuta, J. (1984).
Recommendations on Reporting Electrode Potentials in Nonaqueous Solvents. Pure
Appl. Chem., 56, 461. (b) Strehlow, H.; Knoche, W.; Schneider, H. (1973). A
Conversion of Given Electrode Potentials to the Standard Normal Hydrogen Electrode
is Possible. Ber. Bunsen-Ges. Phys. Chem., 77, 760-717.
[73] Al-Anber, M.; Vatsadze, S.; Holze, R.; Thiel, W. R., and Lang, H. (2005). π-
Conjugated N-heterocyclic Compounds: Correlation of Computational and
ElectroChemical Data. J. Chem. Soc., Dalton Trans., 3632. (b) Vatsadze, S.; Al-Anber,
M.; Thiel, W. R.; Lang, H., and Holze, R. (2005). Electrochemical Studies and
Semiempirical Calculations on p-Conjugated Dienones and Heterocyclic Nitrogen
Containing Donor Ligand Molecules. J. Solid State Electrochem., 9, 764.
[74] For example: (a) Puddephatt, R. J. (1987). In Comprehensive Coordination Chemistry;
G. Wilkinson, R. D. Gillard, J. A. McCleverty (Eds.); (Vol. 5, p 861) Oxford, U.K.:
Pergamon. (b) Grohmann, A.; Schmidbaur, H. (1995). In Comprehensive
Organometallic Chemistry II; E. W. Abel, F. G. A. Stone, G. Wilkinson, (Eds.); (Vol.
3, p 1). Oxford, U.K.: Pergamon. (c) Jia, G.; Puddephatt, R. J.; Scott, J. D., and Vittal,
J. J. (1993). Organometallic Polymers with Gold(I) Centers Bridged by Diphosphines
and Diacetylides. Organometallics, 12, 3565-3574. (d) Mingos, D. M. P.; Yau, J.;
Menzer,S., and Williams, D. J. (1995). A Gold(I) [2]-Catene. Angew. Chem., Int. Ed.
Engl., 34, 1894-1895. (e) Puddephatt, R. J. (1998). Precious Metal Polymers: Platinum
or Gold Atoms in the Backbone. Chem. Commun., 1055-1062. (f) Irwin, M. J.; Jia, G.;
Payne, N. C., and Puddephatt, R. J. (1996). Rigid-Rod Polymers and Model
Compounds with Gold(I) Centers Bridged by Diisocyanides and Diacetylides.
Organometallics, 15, 51-57. (g) Irwin, M. J.; Vittal, J. J., and Puddephatt, R. J. (1997).
Luminescent Gold(I) Acetylides: From Model Compounds to Polymers.
Organometallics, 16, 3541-3547. (h) Yam, V. W. W.; Choi, S. W. K., and Cheung, K.
K. (1996). Synthesis and Design of Novel Tetranuclear and Dinuclear Gold(I)
Phosphine Acetylide Complexes. First X-ray Crystal Structures of a Tetranuclear
([Au4(tppb)(C≡CPh)4]) and a Related Dinuclear ([Au2(dppb)(C≡CPh)2]) Complex.
Organometallics, 15, 1734-1739. (i) Irwin, M. J.; Manojlovic-Muir, L.; Muir, K. W.;
Puddephatt, R. J., and Yufit, D. S. (1997). Trigold Triacetylides: Polymerization
through Gold···Gold Bonding or Bridging ligands. Chem. Commun., 219-220. (j) Lang,
H.; Köcher, S.; Back, S.; Rheinwald, G., and van Koten, G. (2001). Synthesis and
Coordination Chemistry of Gold(I) Acetylides. The Solid-State Structure of {[η2-
(Ph3P)AuC≡CFc]Cu(μ-Cl)}2. Organometallics, 20, 1968-1972. (k) Back, S.; Gossage,
R. A.; Lang, H., and van Koten, G. (2000). Mixed Metal Acetylides: The Pt(II) Aryl
Acetylide"[PtC6H2(CH2NMe2)2-2,6-(C≡C)-4]"as a Connective Fragment Eur. J. Inorg.
Chem., 1457-1464. (l) Yam, V. W. W. (2002). Molecular Design of Transition Metal
Alkynyl Complexes as Building Blocks for Luminescent Metal-Based Materials:
Structural and Photophysical Aspects. Acc. Chem. Res., 35, 555-563. (m) Whittall, I.
R.; Humphrey, M. G.; Houbrechts, S.; Persoons, A., and Hockless, D. C. R. (1996).
Organometallic Complexes for Nonlinear Optics. 8. Syntheses and Molecular Quadratic
Hyperpolarizabilities of Systematically Varied (Triphenylphosphine)gold σ-
Arylacetylides: X-ray Crystal Structures of Au(C≡CR)-(PPh3) (R = 4-C6H4NO2, 4,4'-
C6H4C6H4NO2). Organometallics, 15, 5738-5745. (n) Naulty, R. H.; Cifuentes, M. P.;
Humphrey, M. G.; Houbrechts, S.; Boutton, C.; Persoons, A.; Heath, G. A.; Hockless,
D. C. R.; Luther-Davies, B., and Samoc, M. (1997). Syntheses and Quadratic
Hyperpolarizabilities of some (Pyridylalkynyl)metal Complexes: Crystal Structures of
[Ni{2-(C≡C)C5H3NNO2-5}(PPh3)(η5-C5H5)], [Au{2-(C≡C)C5H3NNO2-5}(PPh3)] and
[Au{2-(C≡C)C5H4N}(PPh3)] . J. Chem. Soc., Dalton Trans., 4167-4174. (o) Whittall, I.
R.; Humphrey, M. G.; Samoc, M.; Luther-Davies, B., and Hockless, D. C. R. (1997).
Organometallic Complexes for Non-Linear Optics XII Syntheses and Second-Order
Susceptibilities of (Neomenthyldiphenylphosphine) Gold σ-Arylacetylides: X-ray
Crystal Structures of Au(C≡CPh) (nmdpp) and Au((E)-4,4′-
C≡CC6H4CH=CHC6H4NO2)(nmdpp). J. Organomet. Chem., 544, 189-196. (p) Whittall,
I. R.; Humphrey, M. G.; Samoc, M., and Luther-Davies, B. (1997). Molecular Cubic
Hyperpolarizabilities of Systematically Varied (Triphenylphosphane)-Gold-σ-
Arylalkynyl Complexes. Angew. Chem., Int. Ed. Engl., 36, 370-371. (q) Yamamoto, Y.;
Shiotsuka, M., and Onaka, S. (2004). Luminescent Rhenium(I)–Gold(I) Hetero
Organometallics Linked by Ethynylphenanthrolines. J. Organomet. Chem., 689, 2905-
2911. (r) Ferrer, M.; Rodriguez, L.; Rossell, O.; Lima, J. C.; Gomez-Sal, P., and Martin,
A. (2004). Unexpected Alkyne Transfer between Gold and Rhenium Atoms and its
Application to the Synthesis of Alkynyl Rhenium(I) Compounds. Organometallics, 23,

5096-5099. (s) Lu, X. X.; Li, C. K.; Cheng, E. C. C.; Zhu, N., and Yam, V. W. W.
(2004). Syntheses, Structural Characterization, and Host-Guest Chemistry of
Ethynylcrown Ether Containing Polynuclear Gold(I) Complexes. Inorg. Chem., 43,
2225-2227.
[75] (a) Bruce, M. I.; Cole, M. L.; Gaudio, M.; Skelton, B. W., and White, A. H. (2006).
Some Complexes Containing Carbon Chains End-Capped by M(CO)2Tp′ [M = Mo, W;
Tp′ = HB(pz)3, HB(dmpz)3] Groups. J. Organomet. Chem., 691, 4601-4614. (b) Fillaut,
J. L.; Dua, N. N.; Geneste, F.; Toupet, L., and Sinbandhit, S. (2006). Nitrile Ligands for
Controlled Synthesis of Alkynyl-Ruthenium based homo and Hetero Bimetallic
Systems. J. Organomet. Chem., 691, 5010-5018. (c) Onitsuka, K.; Ohara, N.; Takei, F.,
and Takahashi, S. (2006). Synthesis and Redox Properties of Trinuclear Ruthenium–
Acetylide Complexes with Tri(ethynylphenyl)amine Bridge. Dalton Trans., 3693-3698.
(d) Sato, M.; Kubota, Y.; Kawata, Y.; Fujihara, T.; Unoura, K., and Oyama, A. (2006).
Synthesis and Some Properties of Binuclear Ruthenocenes Bridged by Oligoynes:
Formation of Bis(cyclopentadienylidene)cumulene Diruthenium Complexes in the
Two-Electron Oxidation. Chem. Eup. J., 12, 2282-2292. (e) Paul, F.; Ellis, B. G.;
Bruce, M. I.; Toupet, L.; Roisnel, T.; Costuas, K.; Halet, J. F., and Lapinte, C. (2006).
Bonding and Substituent Effects in Electron-Rich Mononuclear Ruthenium σ-
Arylacetylides of the Formula [(η2-dppe)(η5-C5Me5)Ru(C≡C)-1,4-(C6H4)X][PF6]n (n
=0, 1; X = NO2, CN, F, H, OMe, NH2). Organometallics, 25, 649-665. (f) Kuo, C.-K.;
Chang, J.-C.; Yeh, C.-Y.; Lee, G.-H.; Wang, C. C., and Peng, S. M. (2005). Synthesis,
Structures, Magnetism and Electrochemical Properties of Triruthenium–Acetylide
Complexes. Dalton Trans., 3696-3701. (g) Xu, G.-L.; Crutchley, R. J.; DeRosa, M. C.;
Pan, Q.-J.; Zhang, H.-X.; Wang, X., and Ren, T. (2005). Strong Electronic Couplings
between Ferrocenyl Centers Mediated by Bis-Ethynyl/Butadiynyl Diruthenium Bridges.
J. Am. Chem. Soc., 127, 13354-13363. (h) Hu, Q. Y.; Lu, W. X.; Tang, H. D.; Sung, H.
H. Y.; Wen, T. B.; Williams, I. D.; Wong, G. K. L.; Lin, Z., and Jia, G. (2005).
Synthesis and Photophysical Properties of Trimetallic Acetylide Complexes with a
1,3,5-Triazine Core. Organometallics, 24, 3966-3973. (i) Wilton-Ely, J. D. E. T.;
Honarkhah, S. J.; Wang, M.; Tocher D. A., and Slawin, A. M. Z. (2005). σ-Organyl
Complexes of Ruthenium and Osmium Supported by a Mixed-Donor Ligand. Dalton
Trans., 1930-1939.
[76] Ara, I.; Berenguer, J. R.; Eguizabal, E.; Fornies, J., and Lalinde, E. (2001). Formation
of an Unsymmetrical Pt-Ir Tetraalkynyl Complex and Investigation into Subsequent
Construction of Multimetallic Systems. Organometallics, 20, 2686-2696.
[77] Wu, I. Y.; Lin, J. T.; Luo, J.; Sun, S. S.; Li, C. S.; Lin, K. J.; Tsai, C.; Hsu, C. C., and
Lin, J. L. (1997). Syntheses and Reactivity of Ruthenium σ-Pyridylacetylides.
[78] (a) Vicente, J.; Chicote, M.-T.; Alvarez-Falcón, M. M., and Jones, P. G. (2005).
Platinum(II) and Mixed Platinum(II)/Gold(I) σ-Alkynyl Complexes. The First Anionic
σ-Alkynyl Metal Polymers. Organometallics, 24, 2764-2772. (b) Chin, C. S.; Kim,
M.; Won, G.; Jung, H., and Lee, H. (2003). Diastereocontrolled Synthesis of cis-Olefins
by Selective C–C Bond Formation Between Alkyl and Alkynyl Groups Coordinated to
„Ir(CH=CHPPh3)(CO)(PPh3)2“. Dalton Trans., 2325-2328. (c) Albinati, A.; Leoni, P.;
Marchetti, L., and Rizzato, S. (2003). Assembling Metal Clusters with Covalent
Linkers: Synthesis and Structure of a Quasi-Planar Pt18 Dendrimer Containing Five
Clusters Connected by σ-Alkynyl Spacers. Angew. Chem. Int. Ed., 42, 5990-5993. (d)
Chin, C. S.; Kim, M.; Lee, H.; Noh, S., and Ok, K. M. (2002). Regio- and
Stereoselective C-C Bond Formation between Alkynes: Synthesis of Linear Dienynes
from Alkynes. Organometallics, 21, 4785-4793. (e) Bruce, M. I.; Davy, J.; Hall, B. C.;
van Galen, Y.; Skelton, B. W., and White, A. H. (2002). Some Platinum(II) Complexes
Derived from Aromatic Alkynes. Appl. Organomet. Chem., 16, 559-568.
[79] Weyland, T.; Lapinte, C.; Frapper, G.; Calhorda, M. J.; Halet, J.-F., and Toupet, L.
(1997). Bi- and Trimetallic σ-Acetylide Complexes Connected Through a Phenyl Ring
in the Fe(Cp*)(dppe) Series. Organometallics, 16, 2024-2031.
[80] (a) Cifuentes, M. P.; Powell, C. E.; Morrall, J. P.; McDonagh, A. M.; Lucas, N. T.;
Humphrey, M. G.; Samoc, M.; Houbrechts, S.; Asselberghs, I.; Clays, K.; Persoons, A.,
and Isoshima, T. (2006). Electrochemical, Spectroelectrochemical, and Molecular
Quadratic and Cubic Nonlinear Optical Properties of Alkynylruthenium Dendrimers. J.
Am. Chem. Soc.; 128, 10819-10832. (b) McDonagh, A. M.; Powell, C. E.; Morrall, J.
P.; Cifuentes, M. P., and Humphrey, M. G. (2003). Convergent Synthesis of
Alkynylbis(bidentate phosphine)ruthenium Dendrimers. Organometallics, 22, 1402-
1413. (c) Long, N. J.; Martin, A. J.; White, A. J. P.; Williams, D. J.; Fontani, M.;
Laschi, F., and Zanello, P. (2000). Synthesis and Characterisation of Unsymmetrical
Metal (RuII, OsII) and Ferrocenyl Complexes of 1,3,5-Triethynylbenzene. J. Chem.
Soc., Dalton Trans., 3387-3392.
[81] (a) Hearshaw, M. A., and Moss, J. R. (1999). Organometallic and Related Metal-
Containing Dendrimers. Chem. Commun. 1-8. (b) Stoddart, F. J., and Welton, T.
(1999). Metal-Containing Dendritic Polymers. Polyhedron, 18, 3575-3591. (c)
Cuadrado, I.; Morań, M.; Casado, C. M.; Alonso, B., and Losada, J. (1999).
Organometallic Dendrimers with Transition Metals. Coord. Chem. Rev., 193-5, 395-
445. (d) Astruc, D.; Blais, J.-C.; Cloutet, E.; Djakovitch, L.; Rigaut, S.; Ruiz, J.; Sartor,
V., and Vale´rio, C. (2000). The First Organometallic Dendrimers: Design and Redox
Functions. In F. Vögtle, (Ed.), Topics in Current Chemistry (Vol. 210, p 229-259).
Berlin, Germany: Springer. (e) Juris, A.; Venturi, M.; Ceroni, P.; Balzani, V.;
Campagna, S., and Serroni, S. (2001). Dendrimers Based on Electroactive Metal
Complexes. A Review of Recent Advances. Collect. Czech. Chem. Commun., 66, 1-32.
(f) van Manen, H.-J.; van Veggel, F. C. J. M.; Reinhoudt, D. N. (2001). Non-Covalent
Synthesis of Metallodendrimers. In F. Vögtle and C. A. Schalley, (Eds.) Topics in
Current Chemistry; (Vol. 217, p 121-161). Berlin, Germany: Springer. (g) Kreiter, R.;
Kleij, A. W.; Klein Gebbink, R. J. M.; van Koten, G. (2001). Dendritic Catalysts. In F.
Vögtle, and C. A. Schalley, (Eds.) Topics in Current Chemistry (Vol. 217, p 163-199).
Berlin, Germany: Springer. (h) Astruc, D. (2003). Organometallic Chemistry at the
Nanoscale. Dendrimers for Redox Processes and Catalysis. Pure Appl. Chem., 75,
461481. (i) Sengupta, S. (2003). A Ferrocene Dendrimer Based on a
Cyclotriphosphazene core. Tetrahedron Lett., 44, 7281-7284. (j) Poniatowska, E., and
Salamonćzyk, G. M. (2003). Phosphite Dendrimers and their Organometallic
Derivatives. Tetrahedron Lett., 44, 4315-4317. (k) Angurell, I.; Muller, G.; Rocamora,
M.; Rossell, O., and Seco, M. (2003). Synthesis and Catalytic Properties of Neutral and
Cationic Rhodium- and Iridium-Containing Carbosilane Dendrimers. Dalton Trans., 3

1194-1200. (l) Angurell, I.; Muller, G.; Rocamora, M.; Rossell, O., and Seco, M.
(2004). Single and Double Metallic Layer-Containing Ruthenium Dendrimers.
Synthesis and Catalytic Properties. Dalton Trans., 2450-2457. (n) Astruc, D. (2004).
Organoiron Activation Combined with Electron- and Proton Transfer: Implications in
Biology, Organic Synthesis, Catalysis and Nanosciences. J. Organomet. Chem., 689,
4332-4344. (o) Busetto, L.; Cassani, M. C.; van Leeuwen, P. W. N. M.; Mazzoni, R.
(2004). Synthesis of New Poly(propylenimine) Dendrimers DAB-dendr-
[NH(O)COCH2CH2OC(O)C5H4Rh(NBD)]n {n = 4, 8, 16, 32, 64} Functionalized with
Alkoxycarbonylcyclopentadienyl Complexes of Rhodium(I). Dalton Trans., 2767-
2770. (p) Onitsuka, K.; Fujimoto, M.; Kitajima, H.; Ohshiro, N.; Takei, F., and
Takahashi, S. (2004). Convergent Synthesis of Platinum-Acetylide Dendrimers. Chem.
Eur. J., 10, 6433-6446. (q) Caminade, A.-M., and Majoral, J.-P. (2005). Phosphorus
Dendrimers Possessing Metallic Groups in their Internal Structure (Core or Branches):
Syntheses and Properties. Coord. Chem. Rev., 249, 1917-1926. (r) Turrin, C.-O.;
Donnadieu, B.; Caminade, A.-M., and Majoral, J.-P. (2005). Organometallic
Derivatives at the Core of Phosphorus-Containing Dendrimers. Z. Anorg. Allg. Chem.,
631, 2881-2887. (s) Angurell, I.; Rossell, O.; Seco, M., and Ruiz, E. (2005).
Dendrimers Containing Two Metallic Layers. Chloride Migration from Peripheral
Gold, Palladium, or Rhodium Metals to Internal Ruthenium Atoms. Organometallics,
24, 6365-6373. (t) Ornelas, C.; Vertlib, V.; Rodrigues, J., and Rissanen, K. (2006).
Ruthenium Metallodendrimers Based on Nitrile-Functionalized Poly(alkylidene
imine)s. Eur. J. Inorg. Chem., 1, 47-50.
[82] Mongin, O.; Papamicaël, C.; Hoyler, H., and Gossauer, A. (1998). Modular Synthesis
of Benzene-Centered Porphyrin Trimers and a Dendritic Porphyrin Hexamer. J. Org.
Chem., 63, 5568-5580.
[83] Chong, S. H-F.; Lam, S. C.-F.; Yam, V. W.-W.; Zhu, N., and Cheung, K.-K. (2004).
Luminescent Heterometallic Branched Alkynyl Complexes of Rhenium(I)-
Palladium(II): Potential Building Blocks for Heterometallic Metallodendrimers.
[84] Jakob, A. (2007). PhD Thesis, TU Chemnitz.
[85] Baumgartner, T.; Fiege, M.; Pontzen, F., and Arteaga-Müller, R. (2006). Redox-Active,
Multinuclear (Ferrocenylethynyl)phosphanes and Their Palladium and Platinum
Complexes. Organometallics, 25, 5657-5664.
[86] Milde, B. (2007). Diploma Thesis, TU Chemnitz.
[87] Stein, T. (2001). Bi- und oligonukleare Komplexe basierend auf Metallorganischen π-
Pinzetten. PhD Thesis, TU Chemnitz.
[88] Köcher, S.; van Klink, G. P. M.; van Koten, G., and Lang, H. (2006). Biferrocene NCN
Pincer Metal-d8 Complexes: Synthesis, Reaction Chemistry and Cyclovoltammetric
Studies. J. Organomet. Chem., 691, 3319-3324.
[89] (a) Horikoshi, R.; Mochida, T.; Torigoe, R., and Yamamoto, Y. (2002). Preparation and
Electrochemical Properties of Polynuclear Organometallic Complexes Derived from
Ferrocene-Containing Bidentate Ligands. Eur. J. Inorg. Chem., 3197-3203. (b) Lohan,
M. (2005). Biferrocene in der metallorganischen Synthese. Diploma Thesis, TU
Chemnitz.
[90] Lohan, M. PhD Thesis, TU Chemnitz.
[91] Dong, T.-Y.; Lin, M.; Chiang, M. Y.-N., and Wu, J.-Y. (2004). Development of
Polynuclear Molecular Wires Containing Ruthenium(II) Terpyridine Complexes.
[92] Packheiser, R.; Walfort, B., and Lang, H. (2007). Synthesis and Characterization of a
Heterometallic Fe-Au-Ti-Cu Transition Metall Complex. Jord. J. Chem., in press.
[93] Kühnert, J. (2008). PhD Thesis, TU Chemnitz.
[94] Frosch, W.; Back, S., and Lang, H. (1999). 1,1'-Ferrocenyldicarboxylic Acid as Starting
Material for the Formation of Trimetallic Ti(IV)-Fe(II)-Cu(I) and Pentametallic
Ti2(IV)-Fe(II)-Cu2(I) Complexes. Organometallics, 18, 5725-5728.
[95] Stein, T., and Lang, H. (2001). A Cross-Shaped Ag5Ti4 Molecule Based on a
[Ag(C≡N)4]3– Core. Chem. Commun., 1502-1503.
[96] Al-Anber, M. (2003). Organic and/or Inorganic π-Conjugated Units in the Synthesis of
Multinuclear Transition Metal Complexes. PhD Thesis, TU Chemnitz.
[97] Al-Anber, M.; Taher, D.; Walfort, B., and Lang, H. (2007). Novel Heterotetrametallic
Fe-Au-Ti-Cu Transition Metal Complexes. Jordan J. Chem., 1, 121-127 .
[98] (a) Müller, T. E.; Green, J. C.; Mingos, D. M. P.; McPartlin, C. M.; Whittingham, C.;
Williams, D. J., and Woodroffe, T. M. (1998). Complexes of Gold(I) and Platinum(II)
with Polyaromatic Phosphine Ligands. J. Organomet. Chem., 551, 313-330. (b) Müller,
T. E.; Choi, S. W.-K.; Mingos, D. M. P.; Murphy, D.; Williams, D. J., and Yam, V. W.-
W. (1994). Synthesis, Structural Characterization and Photophysical Properties of
Ethyne-Gold(I) Complexes. J. Organomet. Chem., 484, 209-224.
[99] Garrison, J. C.; Panzner, M. J.; Custer, P. D.; Reddy, D. V.; Rinaldi, P. L.; Tessier, C.
A., and Youngs, W. J. (2006). Synthesis and Characterization of a Trigonal
Bipyramidal Supramolecular Cage Based upon Rhodium and Platinum Metal Centers.
Chem. Commun., 4644-4646.
[100] Vives, G.; Carella, A.; Launay, J.-P., and Rapenne, G. (2006). A Star-Shaped
Ruthenium Complex with Five Ferrocenyl-Terminated Arms Bridged by trans-
Platinum Fragments. Chem. Commun., 2283-2285.
[101] Packheiser, R., and Lang, H. (2007). A First Mixed Heteropentametallic Transition
Metall Complex: Synthesis and Charcterisation. Inorg. Chem. Commun., 10, 580-582.
Chapter 12
REACTIVITY OF UNSTABLE CHEMICALS

*
IN THE PRESENCE OF TRANSITION METALS
Mieko Kumasaki
National Institute of Occupational Safety and Health, Tokyo, Japan
ABSTRACT
Some hazardous materials show characteristic features in their reaction with
transition metals; they are unstabilized, and sometimes decompose when in contact with
transition metals. Their chemical structure indicates that they have a high tendency to
interact with transition metals since they include electronegative atoms. Transition metal
atoms attract lone pairs of electronegative atoms. This tendency leads to the formation of
a complex of transition metals and the molecules. However, some complexes, especially
those with unstable molecules, can dissociate immediately along with decomposition of
unstable chemicals, or they can be unstabilized by heat, friction and other stimulation
because bond strength is affected and weakened by electronic condition change through
complex formation. The effect sometimes results in a reaction beyond control and
explosion. This article provides an overview of current research on the reactivity of
transition metals and unstable chemicals, and the decomposition behavior of unstable
chemicals interacting with metals. The subject is related through three viewpoints: the
stability change caused by the interactions, the reaction features from the viewpoint of
heat release, and the interaction features of oxygen and nitrogen with Fe3+.
1. INTRODUCTION
Hazardous materials are those materials which represent characteristic features or have
potential to pose damages: physical damages by explosion and runaway reaction, or
biological damage such as mutation or acute toxicity [1,2]. The damages impact basic
*
A version of this chapter also appears in Research Progress in Materials Science, edited by William Olsson and
Filip Lindberg, published by Nova Science Publishers, Inc. It was submitted for appropriate modifications in
an effort to encourage wider dissemination of research.
454 Mieko Kumasaki
reliance on chemical industries even though they have provided demanded chemicals, and
contributed to an affluent society.
The physical damage, in particular, can produce widespread as well as long-term
consequences. It sometimes triggers biological damage, also. In terms of wide-spread
consequence, the chemical plant explosion occurring in 1991 in Japan is taken for example.
The explosion killed and injured personnel working inside the premises, even far from the
explosion center. The deadly fragments flew about 100m to break through iron bars on the
window. Other fragments flew more than 250m to crash through a ceiling. As for a long-term
consequence, destruction of facility allowed chemicals on site to spill into rivers, ocean, soil,
and air. The chemicals can remain long term in the environment and may cause a biological
impact. For this reason, knowledge of the reactivity of hazardous materials is essential to
retain them under control, and to prevent any disaster for the sustainable development of
modern society.
One of the characteristic reactions of some hazardous materials is found in their reaction
with transition metals [1]. Considering the chemical structures of hazardous materials, most
of them include electronegative atoms, especially for unstable and reactive molecules.
Electronegative atoms can easily interact with transition metals by donating lone pairs to
vacant atomic orbit of transition metals. The interaction results in the formation of a complex:
species of a central metal atom or ion surrounded by a set of ligands [3]. A complex consists
of coordination linkage whose bond electrons are donated by ligands. Various kinds of
complexes are found in nature such as hemoglobin, Vitamin B12, and so on. These
complexes are stabile to serve in a body or natural environment when ligands are stable
enough.
On the contrary, complex formation has an intensified impact on unstable molecules as
ligands. Transition metals provide perturbation to the electronic condition of a molecule, and
this can change molecular form and bond strength. Strength of bond affects molecular
stability since chemicals generally start decomposition with a break in weak bonds. Therefore
unstable molecules can change bond strength and be unstabilized through complex formation.
Furthermore, some complexes dissociate immediately after complex formation, along
with rearrangement within ligands or decomposition of ligands. While this kind of function is
utilized as catalysts to generate valuable chemicals [4], it sometimes leads a reaction beyond
control (runaway reaction) and explosion. Unstable chemicals as ligands decompose easily,
and have the potential to lead to explosion because of their fragility.
This article provides an overview of current research on the interaction between transition
metals and unstable chemicals. It can be divided into three parts: the stability change caused
by interactions, the reaction features from the viewpoint of heat release, and the interaction
features of oxygen and nitrogen with Fe3+.
The first part describes cases where the kind of interaction changes sensitivity to heat,
friction, electronic spark, and mechanical impact. Tetrazole and triazole (azoles) are subjected
to investigation. The chemicals are utilized in pyrotechnic devices as energetic materials: that
means they are categorized in reactive materials. By formation of complexes, they change
sensitivity as well as energy release behavior.
The second part focuses on heat release behavior of hydrogen peroxide (H2O2), hydrazine
(NH2NH2), and hydroxylamine (NH2OH) which are the simplest molecules containing
electronegative atoms. Simple chemical structure enables us to eliminate structural hindrance
to metal-electronegative atom interaction which frequently occurs in a large molecule.
Reactivity of Unstable Chemicals in the Presence of Transition Metals 455
Additionally, tracking heat release behavior provides information about reactions since heat
generation directly corresponds to the enthalpy difference between reactant and stable
products. The results can provide some insight into reactivity difference between nitrogen and
oxygen, as well as their individual reactivity.
Contrary to the second part, the third part relates the reaction between NH2OH and Fe3+
affected by steric hindrance. This part focuses on the reaction of substituted NH2OH by the
methyl group. The Steric hindrance by the methyl group can restrict the reaction center in
NH2OH. This part also relates the protected iron ion by ligands, acidity of solutions, and
charge distribution on NH2OH by way of ab initio molecular orbital calculation.
2. THE STABILITY CHANGE CAUSED BY INTERACTIONS:

THE STABILITY CHANGE OF TETRAZOLE AND TRIAZOLE THROUGH
THE INTERACTION WITH TRANSITION METAL [5]
This section provides an overview of the effect of the interaction on the sensitivity to
azoles by way of synthesized azole-metal complexes. Azoles are energetic materials which
are frequently used as an ingredient of pyrotechnic devices. In the field of energetic materials,
azole complexes with transition metals, however, had less attraction compared to a mixture of
azoles and transition metal compounds. For instance, transition metal oxides have been added
to propellants and other energetic devices so as to enhance reactivity by releasing oxygen
[7,8]. Some oxides achieved better heat conduction and promotion of the electron-transfer
process as well as improvement of burning rate.
In that sense, the evaluation of azole-metal complexes started originally from the attempt
to enhance the reactivity of azoles by means of effective interaction between azoles and
transition metal as catalysts [5]. Since the distance between transition metal and azole
becomes shorter in complex, the interaction was expected to be stronger. Through the
experiments and analysis, the interaction has been recognized as perturbation on azole’s
stability.
This section describes the evaluation of 1H-tetrazole-metal complex and 1H-1,2,4-
triazole-metal complex in terms of sensitivity (Figure 1). 1H-tetrazole (abbreviated as 1HT)
and 1H-1,2,4-triazole (abbreviated as 1HTRI) are basic azoles which can easily coordinate to
transition metals through nitrogen atoms. Previous studies reported that azoles exist as
bidentate ligands in many azole-metal complexes [8, 9]. Many transition metals are able to
form complexes with azoles. This section is concerned only with complexes including copper,
apart from other reports which have assessed their sensitivity and reactivity [10-13].
Figure 1. The chemical structures of 1H-tetrazole(a) and 1H-1,2,4-triazole(b).

456 Mieko Kumasaki
2.1. Synthesis
On of the sample was prepared by mixing aqueous solutions of 1HT and

Cu(NO3)2･3H2O. Pale blue precipitate immediately generated. The precipitate was
subsequently washed with water, methanol, ether, and dried under reduced pressure. Their
molecular formula were determined to be [Cu(CN4H)2]H2O (abbreviated 1HTCu) based on an
elemental analysis. One proton was liberated from 1HT since the parent molecule has a pKa
value of about 4.8, which is similar to that of acetic acid [14]. All attempts to dissolve the
complexes in common solvents failed because of poor solubility.
The other complex of 1HTRI was synthesized in the aqueous solution as well as one of
1HT. Purple precipitate was determined as [Cu(C2N3H3)2](NO3)2 (abbreviated 1HTRICu)
based on elemental analysis. All attempts to dissolve the complexes in common solvents
failed because of poor solubility, either. The poor solubility precluded recrystalization.
2.2. Sensitivity Tests to Friction, Mechanical Impact, and Electronic Spark
The drop Hammer Test is a popular method of assessing the sensitivity of explosives to
mechanical impact [15]. There exist a few kinds of the tests for mechanical impact developed
at Swiss Chemicals Industry, Bundesanstalt für Materialforschung und prüfung (Federal
Institute for Materials Research and Testing in English, BAM), the U.S. Bureau of Mines, and
Japan Industrial Standards (JIS). In this study, experiments carried out in the manner of JIS.
The test sample is sandwiched between two cylinders and placed on anvil in a tester so that
5kg of a dropping hammer free-fall onto it. The experimental results provide sensitivity to
mechanical impact as a function of energies calculated from dropping heights.
Based on the up-and-down method, the 50% explosion height and the corresponding
energy were determined as is presented in Table 1 [16]. For the complexes, the test was
carried out 6 times with a hammer height setting of 50cm. Both complexes did not explode in
this test and were categorized as grade 8 according to JIS. The test revealed that complex is
more stable to mechanical impact than azoles. Although this test is strongly influenced by
physical properties such as grain size and humidity, the interaction between azole and
transition metal appear to stabilize azole to mechanical impact.
Friction sensitivity test was carried out in accordance with JIS K 4810 by using of BAM
friction test apparatus [17]. Substance is spread onto a porcelain plate, and the ceramic place
is dragged under weighed porcelain stick. Sensitivity of substance to friction is evaluated
from an amount of load at which one explosion occurs at least out of 6 trials. The load is
utilized as indexes for 1/6 explosion point.
From the friction sensitivity test, the 1/6 explosion point was equal to be 25.2kgf for 1HT
and 24.2-25.2kgf for 1HTRI. On the other hand, 1HTCu and 1HTRI did not explode at the
highest load of 36.0kgf. Therefore, they are too insensitive to measure using the BAM friction
sensitivity test. These results are summarized in Table 2.
This test is strongly influenced by physical properties such as grain size and humidity as
well as drop hammer test. However, the azole-metal complexes can be considered to be more
stable to friction than azoles.
Table 1. Summary of the results of Drop Hammer Test
Samples H50[cm] E50[J]

1HT 12 5.9
1HTRI 3.4 1.7
1HTCu >50 >24.5
1HTRICu >50 >24.5
Table 2. Summary of the results of BAM friction sensitivity test
Samples M1/6[kgf]
1HT 25.2
1HTRI 24.2-25.2
1HTCu >36.0
1HTRICu >36.0
Meanwhile, they showed different tendency of the sensitivity to electronic spark from
other stimulation. Sensitivity to electronic spark was evaluated according to Electrostatic
Sensitivity Test in Japan Explosives Society Standard (IV) [18]. The sample was sandwiched
between two electrodes connected to condensers and the electrical spark applied by discharge.
The sensitivity was estimated by the 50% explosion point using an up-and-down method.
The results of the electric spark ignition are shown in Table 3. The test revealed that the
complexes were sensitive compared to the pure azoles. The sensitivity of 1HTCu was close to
the mixture of Al and KClO4 (logE50 is -0.76) which is utilized as spark source in fireworks
[19, 20]. As for 1HTRICu, the sensitivity was close to the mixture of B and KClO3 which is
utilized as igniter for propellants and airbag inflator (0.06).
Sakata reported that the sodium and potassium salts of 1HT were more insensitive to
impact, friction and electric spark than 1HT [21]. The copper complex showed the same trend
except for the sensitivity to static electricity.
2.3. Thermal Analysis for Sensitivity to Heat
Sealed Cell-Differential Scanning Calorimetry (SC-DSC) was used for surveying

behavior under heating conditions. In the analysis, the calorimeter heats sample and reference
under the programmed temperature control. The heat release or absorption data as a function
of temperature enable to estimate sensitivity of the sample to heat. The sample weight for the
investigation was about 1.0mg. The heating rate was 10K/min.
Table 3. Summary of the results of sensitivity test to static electricity
Samples LogE50 E50[mJ]

1HT 0.52 3.29
1HTRI 0.04 1.10
1HTCu -0.88 0.13
1HTRICu -0.08 0.84
458 Mieko Kumasaki
Figures 2 and 3 show the SC-DSC charts of the azoles, azole-metal complexes and
tetrazole-metal nitrate mixtures. Horizontal axis indicates temperature. Upward peaks indicate
heat release (exothermic) while downwards do heat absorption (endothermic). The
exothermic peaks of the complex stretched sharply compared with the pure azole and azole-
metal nitrate mixture. The 1HT in complexes decompose faster than as pure azole. These
results confirmed that an azole definitely interacts with a metal and coordination to the metal
effects on the decomposition velocity.
Figure 2.
Figure 3.
In figures 2 and 3, the azoles exhibit endothermic behavior corresponding to melting

below their decomposition temperatures at which heat release starts. For the complexes,
however, the endothermic peaks disappeared. This disappearance is considered to be due to a
change in their electronic properties. Neutral molecules link together via a Van der Waals
force in the pure azole crystal. In 1HTCu, however, tetrazole negatively charged because of
proton liberation. In this way, 1HT molecules and copper link via a Coulombic force in the
complex solid because copper positively charged. Contrary to 1HT in complex, 1HTRI can be
considered to slightly charge positively in complex because 1HTRI donate electrons to metal
to form coordination linkage. The electron-donation also generates Coulombic force. Since
the Coulombic force is stronger than the Van der Waals force, 1HTCu and 1HTRICu as ionic
crystal are difficult to melt compared molecular crystals of 1HT and 1HTRI.
The values of TDSC and QDSC are summarized in Table 4. TDSC is an onset temperature of
exothermic peak which indicates the temperature explosion or decomposition starts. QDSC is
the heat of reaction per unit mass calculated based on peak integral. Since there are heavy
copper atoms (and nitrate anion for 1HTRICu) in the complex, the QDSC of the complexes
should decrease. As for 1HTCu, the heat of reaction per unit mass was naturally smaller than
1HT. However, the heat of reaction per azole molecule calculated based on the elemental
analysis results is almost the same as 1HT, but larger than the potassium and sodium salts.
Meanwhile, QDSC of 1HTRICu was larger than that of the 1H-1,2,4-triazole. This is
considered to be due to fragmentation easily progresses in 1HTRICu. Williams et al. reported
that triazoles are able to form polymers [22]. As a result of complex formation, a high
reactivity achieved fragmentation during decomposition and a more exothermic reaction
along with generation of small stable molecules.
As for TDSC, the thermal stability of 1HTCu was higher compared to 1HT. In the study on
substituted tetrazoles, Ohno concluded that tetrazoles were thermally stabilized by electron
donating substituents because of an increase of aromaticity [23]. In 1HTCu, the tetrazole
valence was –1 and the electronic state of triazole ring is similar to one in the tetrazole with
electron-donating groups which make tetrazole ring slightly anionic.
Figure 4 indicates the optimized structures of the anionic and neutral 1H-tetrazoles by
using a molecular orbital calculation at the HF/6-31G* level of theory with GAUSSIAN94
[24]. In the optimized structures, the uniformity of the bond lengths and an increase in the
aromaticity were found in the anionic 1H-tetrazole. The calculation results indicate the
anionic character of 1H-tetrazole influences the thermal stabilities. Furthermore, the N1-C5
and N3-N4 bonds are shorter in the anionic state than in the neutral state. Considering that the
decomposition of 1H-tetrazole starts from breaking these bonds under the stated condition
[25], it can be said that the anionic state is more stable than the neutral state.
For 1HTRICu, the triazole ring has a slight cationic character due to electron donation.
The cationic state of the molecule was optimized and is shown in Figure 5. In this calculation,
triazole valence was +1 so as to simulate slightly charged condition. Consequently, the
standard deviation of the average bond length became greater in the cationic state than in the
neutral state. This might indicate a decrease in aromaticity. That can explain the stability of
1HTRI decreased.
460 Mieko Kumasaki
Figure 4. Optimized structures of neutral and negatively charged 1HT.
Figure 5. Optimized structures of Neutral and positively charged 1HTRI.
The concept of aromaticity can explain well the change in thermal stability for copper
complex. However, some complex of 1HT and 1HTRI behave differently. For instance,
complex of nickel and 1HTRI exhibited the similar thermal stability to 1HTRI [10]. To reveal
principle for stability of the complexes, analysis will be required for structural information
and coordination manner.
Table 4. Summary of the results under the heating condition
Sample TDSC[oC] QDSC[J/g] QDSC[kJ/mol] QDSC[kJ/azole]

1HT 204 4257 298
1HTCu 264 2516 552 276
1HTNa[21] 324 1700 157
1HTK[21] 311 1620 175
1HTRI 342 1506 104
1HTRICu 312 1987 647 324
3. THE REACTION FEATURES FROM THE VIEWPOINT OF HEAT

RELEASE: THE REACTION BETWEEN TRANSITION METAL AND
SIMPLE MOLECULES WITH ELECTRONEGATIVE ATOMS [26-29]
In chemical structures of reactive hazardous materials, nitrogen and oxygen atoms appear
most frequently. Both of them have a capability to interact with transition metals by donating
electrons used in coordination bond formation. Their affinity for transition metals must be one
of the subjects of research to reveal the nature of the reactivity.
Starting research from simpler molecule is common line of reasoning for research on
chemistry. This section describes the research on three chemicals with simple molecular
structures: hydrazine (NH2NH2), hydroxylamine (NH2OH), and hydrogen peroxide(H2O2).
They have similar chemical structure composed of two electronegative atoms and hydrogen
atoms. All of them exhibit high solubility into water. Furthermore, they have triggered several
explosion accidents due to high reactivity. As for NH2NH2, it is easy to understand to explode
since this compound is utilized in a rocket propellant ingredient. NH2OH and its salts are
widely available commercially and frequently used industrially in chemical synthesis and the
manufacturing of semiconductors. NH2OH, however, killed five people in the state of
Pennsylvania in the U.S.A. in 1999, and four people in Japan, in 2000. The accidents
occurred by H2O2 is too numerous to enumerate. The numerous number of the accident of
H2O2 reflects its utility in chemical industry, as environmentally-friendly breaching agent and
bactericide.
Besides, similar properties are found in some regards: redox behavior. They are available
as both of reducing agent and oxidizing agent.
In general, H2O2, NH2OH and NH2NH2 act as reducing agent in acidic solutions and as
oxidizing agents in neutral or alkaline media. Based on the potential of half-reactions, H2O2
serves as oxidizing agent, NH2NH2 does as reducing agent, and NH2OH is considered as the
intermediate compound. However, by varying the conditions, H2O2 has a capacity as reducing
agent in contact with stronger oxidizers [30, 31]
In acid solution:
2H2OJH2O2 + 2H+ +2e- E=1.77V as oxidizer (1)
H2O2JO2 + 2H+ +2e- E=0.68 as reducer (2)
N2H5+ J N2 + 5H+ + 4e- E=-1.16 as reducer [31] (3)
NH4+ +H2O J HONH3+ +2H+ + 2e- E=1.35 as oxidizer (4)
HONH3+ J 0.5N2 + 2H+ + H2O + e- E=-1.87 as reducer (5)
2HONH3+ J N2O + 6H+ + H2O + 4e- E=-0.05 as reducer (6)
2HONH3+ J H2N2O2 + 6H+ + 4e- E=-0.44 as reducer (7)

462 Mieko Kumasaki
In basic solution:
3OH- J HO2- + H2O + 2e- E=0.87 as oxidizer (8)
N2H4+4OH- J N2+4H2O+4e- E=-1.16 as reducer [31] (9)
2NH2OH + 2OH- J N2+ 4H2O + 2e- E=-3.04 as reducer (10)
2NH2OH + 4OH- J N2O + 5H2O + 4e- E=-1.05 as reducer (11)
2NH2OH + 6OH- J N2O22- + 6H2O + 4e- E=-0.73 as reducer (12)
Meanwhile, transition metal generally works as oxidizer. They can have several oxidation
states and transition easily from higher oxidation state to lower oxidation state companied
with oxidizing neighboring reducer.
Furthermore, some transition metals are able to reverse the direction of the transition, and
be oxidized under some conditions. For example, Fe2+ is easily oxidized into Fe3+ in a basic
solution. This kind of metal functions as catalysts through the process of exchange electrons
between metal and substrates as is shown below. In the process, the metal can supply chain
reaction carrier such as radicals and lead hazardous materials to react and decompose even in
a small amount existence. In particular, it can trigger a severe accident if a substance behaves
as both of oxidizer and reducer.
P (oxidizer) + Mn+ J P･ + M(n+1)+
R･ (reducer) + M(n+1)+ J R + Mn+
Through this section, the difference in reactivity of three compounds is observed in terms
of heat release behavior.
3.1. An Experimental Apparatus for Tracking Heat Release Behavior:

SuperCRC
Figure 6 shows the schematic view of the Super-CRC. Super-CRC is one of the reaction
calorimeters. Among several reaction calorimeters on the market, Super-CRC is characterized
by small-scaled (16ml at a maximum), differential system and built-in magnetic stirrer.
In this study, all experiments were carried out in an isothermal mode. A glass vial
containing 1ml of substrates (aqueous solution of H2O2, NH2OH and NH2NH2) was placed in
the heat sink. An amount of 1ml of water was used as a reference. After the baseline got
stabilized, 0.1g of the metal aqueous solutions(prepared to give 0.2mmol/g) were injected
respectively to vials at once through Teflon tubes instead of needle so as to prevent metal
contamination and completely dose a small amount of solutions. Since the Super-CRC is a
differential calorimeter, the temperature difference between substrates and iron solution can
be canceled as long as the same amount of solution is injected into both reactors. Therefore
the heat flow curve is supposed to be independent of the differences. The data collection
carried out under the continuous stirring. A heat-flow datum point was obtained every 3
seconds during the course of the reaction. The limitation of a maximum of 15,000 data points
defined the maximum test duration as 12.5 hours.
If the reactions were complete within 12.5h, the measurements were stopped after the
heat flow curves reached their baseline levels. When the chemicals slowly reacted and
continuously generated heat, the measurement continued until the maximum test duration.
Three trials were carried out for each sample, and average values of the peak and overall heat
of the reaction were calculated.
Figure 6. Schematic view of the Super-CRC.

464 Mieko Kumasaki
3.2. Reactivity of H2O2 and NH2NH2 with Fe3+
Figures 7, 8, and 9 show the reaction at 35oC with three Fe3+ compounds, Fe(NO3)3,
Fe2(SO4)3 and FeCl3. The concentration of H2O2 and NH2NH2 is 30wt.%. The mixing with
Fe3+ aqueous solution showed moderate heat release for NH2NH2 and completed to give dark
precipitate regardless of the different anions. It remained unconfirmed whether any reduced
iron species generated such as oxides of Fe2+, complex like [Fe(NH2NH2)2Cl2]･2H2O,
[Fe(NH2NH2)2SO4]･H2O, [Fe(NH2NH2)2(NO3)2]･H2O reported in previous study [32], and so
forth. The precipitation, however, appeared Fe(OH)3 due to the basicity of the NH2NH2
aqueous solution. Even under the reductive condition due to NH2NH2, it is possible that Fe
persist in Fe(OH)3 since basic condition lets reduction of Fe3+ more difficult rather than acidic
one [33].
Meanwhile, the reactivity of H2O2 exhibited quite different feature. H2O2 released heat
immediately after injection and gives transparent solution without precipitation. Considering
the concentration of H2O2 (8.8x10-3mol in a vial) and Fe(III)(2x10-5mol), Fe(III) species
works as catalyst for H2O2.
Figure 7. Heat release behavior in the reaction of H202 (circle) and NH2NH2 (square) with FeCI3.
inset: the behavior of NH2NH2.
Figure 8. Heat release behavior in the reaction of H202 (circle) and NH2NH2 (square) with Fe(NO3)3.
Figure 9. Heat release behavior in the reaction of H202(cicrle) and NH2NH (square) with Fe2(SO4)3/
466 Mieko Kumasaki
The mechanism of the reaction between Fe(III) and H2O2 has not been focused
intensively in spite of numerous researches on the reaction H2O2 and Fe(II) referred as the
“Fenton reaction” [34, 35]. Among the research on Fe(III), Kremer mentioned the reaction of
Fe3+ associated with oxidation of Fe2+ in a report. The idea that Fe2+ ions participate in the
Fe3+ ion reaction, however, has not been proved [36] while the main process of the reaction
considered as the fission of the O-O bond within complex with Fe3+ ion.
3.3. Reactivity of NH2OH with Transition Metals
NH2OH is intermediate compounds of H2O2 and NH2NH2. It has capability to oxidize or

reduce depending on counterpart compounds. Reactivity with various kind of transition metal
is overviewed both in basic and acidic conditions by way of calorimetric measurements
[26,27].
An aqueous solution of NH2OH (abbreviated as HA, basic solution), NH2OH･HCl
(abbreviated as HACl, acidic solution), were used, and carefully prepared to give 2mol/l
(about 6.4w.t.%). Solutions of the transition metals were prepared to give 0.2mmol/g of
solutions by dissolving Fe(NH4)(SO4)2･12H2O(Fe3+), Cr(NH4)(SO4)2･12H2O(Cr3+),
K2Cr2O7(Cr6+), KMnO7(Mn7+), Co(NH4)2(SO4)2･6H2O(Co2+), [Co(NH4)6]Cl3(Co3+), and
Cu(NH4)2(SO4)･6H2O(Cu2+).
UV-Vis absorption spectra were collected before and after the reactions in order to follow
the redox reaction from the aspect of the valence of metals. In case of precipitation, fine
precipitate leads Tyndall phenomenon and light scattering. That inhibited collection of UV-
Vis absorption spectra.
3.3.1. Reactivity of NH2OH with Fe3+

Figure 10 shows a view of the exothermic behavior of HA and HACl caused by Fe3+. The
average overall heat of the reaction was 3.39J for HACl, and one for HA was more than
237.82J. The reaction did not allow to calculate exact overall heat of the reaction since the
reaction released heat to the maximum test duration. HA was consumed during the reaction
despite the HA/Fe3+ molar ratio of 100/1. Therefore, Fe3+ was supposed to act as a catalyst in
the decomposition of HA.
After the injection of Fe3+, HA released heat immediately. In the reaction mixture, red-
blown precipitate considered as Fe(OH)3 and the evolution of gas was observed. The gas was
recognized as NH3 from its odor and the results of a previous study [37]. The following
reaction schemes have been suggested in previous studies under basic condition [30]:
NH2OH J 1/3NH3 + 1/3N2 + H2O
In contrast, the reaction of HACl was complete within one hour. The addition of free Fe3+
to HACl provided a colorless mixture and no precipitation. The disappearance of the orange
color in the Fe3+ meant that HACl had turned Fe3+ into Fe2+. No further reaction due to Fe2+
was supposed to occur in an acidic condition.
Figure 10. Heat release behavior in the reaction of HA (white triangle) and HACI (black circle) with
Fe(Nh4)(SO4).
Figure 11. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with Cr3+.
468 Mieko Kumasaki
3.3.2. Reactions with Cr3+ and Cr6+

Cr6+ has the highest oxidation state of any chromium, and is a strong oxidizing reagent.
On the other hand, Cr3+ has a lower oxidation state and is less oxidizing. The redox behavior
of HA can be investigated by comparing these two oxidative states of chromium.
The heat flow profiles of the reactions with Cr3+ are shown in Figure 11. No heat release
was observed for HACl in the reaction with Cr3+. The UV - Vis spectra exhibited no
absorption change, either. The mixture suggested that Cr3+ existed as [Cr(H2O)6]3+ and no
redox reaction occurred by the reductive HACl. Meanwhile HA exothermically reacted with
Cr3+. The reaction produced a sage-green precipitate, and the precipitation changed color to
violet in a few hours. The green sage precipitation was Cr(OH)3, which is generated from
Cr3+ in an alkaline solution. However, the generation mechanism of the violet precipitate has
not been currently understood. The precipitation suggested Cr3+ is enough to stable to HA
species, in other words, HA worked as neither oxidizing nor reducing agent for Cr3+ despite
acidity of solution.
Figure 12 shows the exothermic behavior caused by Cr6+. In contact with CrO42-, HACl
bubbles and the yellow CrO42- changed to a champagne color; the reactions of HACl
completed within 30 minutes. The UV-Vis absorptions of CrO42- disappeared (at 257 and
351nm), and new peaks suggesting the presence of [Cr(H2O)6]3+ appeared at 562nm.
Figure 12. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with Mn7+.
As far as the reaction with Cr6+, the acidic HACl exhibited a higher reactivity than HA.
These results can be explained by the well-known fact that the oxidative ability of Cr6+ is
higher in an acidic solution than it is in a basic solution. The HA continuously generated heat
for more than the maximum test duration, and a violet precipitate was obtained in HA. The
origin of the continuous heat generation was unclear, however, transition among several
oxidation states of chromium along with HA redox reaction or catalytic ability of surface of
the precipitates would be plausible as what was behind.
3.3.3. Reactions with Mn7+

Figure 13 shows the heat flow curves of HA and HACl caused by MnO4-. During the
mixing, Mn7+ exhibited a strongly oxidizing character as well as Cr6+. When the MnO4-
solutions were injected into the substrates, bubble evolved, and the deep violet color of MnO4-
immediately disappeared. HA gradually produced a white precipitate. The precipitate was
considered to be Mn(OH)2.
HACl completed the reaction within 30 minutes, whereas HA continuously generated
heat for longer than the maximum test durations. The UV-Vis absorptions of manganese in
HACl were too weak to identify any products. However, [Mn(H2O)6]2+ was plausible because
of its weak UV-Vis absorption and its lowest redox potential among the manganese ions.
Figure 13. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with MN7+.
470 Mieko Kumasaki
Figure 14. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with Co2+.
3.3.4. Reactions with Co3+ and Co2+

Both of Co3+ and Co2+ are intermediate oxidation states of cobalt. They can act as either
an oxidizer or a reducing agent, depending on the circumstances. The heat flow curves of the
substrates caused by Co2+ are shown in Figure 14. The UV-Vis spectra showed no absorption
change in HACl. No heat release was observed in the mixing, either. From these results, it can
be deduced that no redox reaction occurred in the substance. However, Co2+ continuously
generated heat with HA and produced a brown precipitate.
In the reaction of HACl and Co3+, neither peak in the heat flow curve nor evidence of a
redox reaction was observed. The orange color of [Co(NH3)6]3+ remained in HACl and UV-
Vis spectra indicate the existence of the species. Upon mixing with HA, no reaction seemed
to occur at the beginning of the monitoring. However, the heat flow curve started to gradually
rise following the injection, and it exhibited a peak about 10 hours later (Figure 15). After the
induction period, the mixture provided a brown precipitate although it exhibited no change in
color during the early hours.
3.3.5. Reactions with Cu2+

Copper has three major oxidation states: Cu2+, Cu+, and Cu0. Since Cu2+ is the highest
oxidation state, Cu2+ is considered liable to undergo reduction despite its low oxidation
number.
Figure 15. Heat release behavior in the reaction of HA (triangle) with Co3+.
The heat flow curve caused by Cu2+ is shown in Figure 16. The blue color of
[Cu(H2O)6]2+, which originated from Cu(NH4)2(SO4) was too visually faint to be determine
whether the reactions occurred in HACl. UV-Vis spectroscopy doesn’t cover the range in
which the absorption peaks of [Cu(H2O)6]2+ appear [38]. As another plausible product,
[Cu(NH3)4]2+, which has an absorption peak is at 590nm, was not detected, whereas the
APTAC experiments showed the complex from 50%HA and copper [37]. In order to generate
[Cu(NH3)4]2+, ammonia-rich conditions are required and the mild condition in this experiment
did not allow this complex to be generated. In HA, a yellow green film was observed on the
liquid surface, which changed to brown. The appearance of a brown precipitate suggested that
Cu2O formed.
Apart from the spectroscopic results, calorimetric experiments showed the exothermic
behavior of HA and HACl. Both substrates continuously generated a heat flow. The
maximum heat flow of HA was not high; however, a continuous release of heat resulted in a
high overall heat of the reaction.
3.3.6. Comparing Reactivity among the Three Chemicals

H2O2, NH2NH2, and NH2OH consist of two electronegative atoms and hydrogen atoms.
Despite the similar chemical structure, they exhibited different behavior in contact with Fe3+.
H2O2 and NH2OH exhibited high reactivity compared to NH2NH2. Fe3+ reacted as a catalyst
in H2O2 and NH2OH while NH2NH2 released small heat along with precipitation. As for
precipitation, NH2OH also generate precipitation. NH2OH, however, continuously released
heat by the reaction on surface of precipitated gel, considered as Fe(OH)3.
472 Mieko Kumasaki
Figure 16. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with Cu2+.
Table 5 summarize the result of the reaction of NH2OH and transition metals. All mixture
of NH2OH generate precipitate because of its basicity while its acidic chloride salt prevented
precipitation and showed moderate redox reactions in contact with high oxidative metals.
NH2OH seems to maximize the reactivity under the basic condition while hydrogen peroxide
works in acidic condition.
The chemicals structures and reactivity implies that oxygen serves important roll in terms
of heat releasing reactions. In the reactions, transition metals works catalytic. On the other
hand, NH2NH2 has a tendency to work as ligand to remain in complex while the others
decompose immediately after the contact with metals.
Table 5. Summary of the reactivity of HA and HACl
Metal HA HACl
Fe3+ Precipitation Fe3+ JFe2+
Cr3+ Precipitation No reaction
Cr6+ Precipitation Cr6+ JCr3+
Mn7+ Precipitation Mn7+ JMn2+
Co2+ Precipitation No reaction
Co3+ Precipitation No reaction
Cu2+ Precipitation Not distinguishable
4. THE INTERACTION FEATURES OF OXYGEN AND NITROGEN WITH

FE3+: THE REACTION BETWEEN FE3+ AND SUBSTITUTED NH2OH
This section relates some investigation to deepen understanding of the nature of reactivity
of NH2OH by using of structural change. The investigation can be divided into two parts:
steric hindrance on Fe3+, and steric hindrance on NH2OH. Steric hindrance on Fe3+ also
contributes to hydrophilicity. The previous section related the manner that precipitation
decelerated the heat release of NH2OH. Aqueous solution of NH2OH is basic and easy to
precipitate metal hydroxide. By using suitable ligands for Fe3+, precipitation can be prevented
and observed an interaction. Two complexes of iron are focused in this article: [Fe(CN)6]3-
and Fe(EDTA)-.
Additionally, intended steric crowding for NH2OH enables to restrict reaction center. For
example, NH2OH is expected to reaction with metal on oxygen if methyl group attaches on
nitrogen atom. By using of steric hindrance, the affinity of oxygen or nitrogen to transition
metal was able to be investigated. At the same time, the acidic condition was controlled by
using NaOH since the acidity has influence on the reactivity of NH2OH shown in the previous
section.
4.1. Exothermic Behavior Caused by Coordinated Fe3+
CN- is known as a ligand which strongly coordinates to metals. In the complex, six CN-
species occupy coordination sites around Fe3+. The donating atom is C, and Fe3+, C, and N
atoms form a line in the six directions [39] (Figure 17). EDTA is the common chelating
reagent that exists in the complex as EDTA4- and is associated with the liberation of four H+.
The complex with Fe3+ has the highest stability of all EDTA complexes, excluding that with
V3+. The previous X-ray study of Fe(EDTA)- revealed that Fe was surrounded by six
donating atoms of EDTA and an O atom of H2O which could easily substitute with substrate
[40]; the geometry about Fe3+ is pentagonal bipyramidal (Figure 18).
Figure 17. The Structure of [Fe(CN)6]3-.

474 Mieko Kumasaki
Figure 18.
Figure 19. Heat release behavior in the reaction of HA and Fe(CN)63-.
Figures 19 and 20 show the expanded views of the exothermic behavior caused by
Fe(CN)63- and Fe(EDTA)- . NH2OH notably reacted with both Fe3+ species. The heat flow of
NH2OH provided by Fe(EDTA)- rose slowly, compared with that of free Fe3+ from
Fe(NH4)(SO4). However, the maximum height of the curve was 489mW, which was larger
than that of free Fe3+. Overall heat of reaction was 421.93J. The gas, including NH3, also
evolved. The heat release caused by Fe(EDTA)- ended within 100 minutes. The difference to
free Fe3+ in the heat of the reaction was due to the EDTA4- that dissolved Fe3+/Fe2+ species in
basic NH2OH and leads free contact with NH2OH homogeneously in solution, whereas Fe3+
precipitated as the reaction proceeded and decreased the effective area for the reaction with
NH2OH. Fe(CN)63- also triggered an exothermic reaction of NH2OH, however, the maximum
heat of reaction(99.11mW) and overall heat of reaction(6.26J) were low compared with that
of the other Fe3+ species. In the reaction mixture, Fe(CN)64- was supposed to exist because the
yellow color of Fe(CN)63- disappeared and [Fe(CN)6]3-/ [Fe(CN)6]4- remain stable under high
pH condition. CN- ligand dissolve the Fe3+/Fe2+ species even in basic conditions, and also
prevent precipitation as well as EDTA4-. In case of CN, no catalytic function appeared.
Considering the stability, the redox reaction of [Fe(CN)6]3- can be described with outer
sphere mechanism. The mechanism is an electron transfer in outer complex contact without
ligand substitution, or with faster electron transfer than ligand substitution. The reaction
manner implies [Fe(CN)6]3- has no site to contact directly with NH2OH. Six CN- occupy
coordinate sites of Fe and prevent further intrusion of ligands onto inner sphere of Fe.
Meanwhile, Fe(EDTA)- keep a coordination site open so as to interact with HA as shown in
Figure 20. Not only electric effect but also steric effect has influence on the reaction with
NH2OH
4.2. Exothermic Behavior of Substituted Hydroxylamine
NH2OH includes oxygen and nitrogen atoms both of which can interact with transition
metals. The chemical structure attracts the researchers’ interests and raises questions on how
it interacts with metals and how the initiation process starts.
Using steric hindrance is one of the ways to gain information about the reactivity. The
steric crowding of ligands is expected to decrease associative process with metals. In case of
blocking of position on nitrogen atom in NH2OH, a metal ion should prefer the interaction on
oxygen atom, and vice versa. The difference in reactivity can imply the affinity of oxygen and
nitrogen atoms to a metal atom. This section also reports reactivity depending on the acidic
condition since acidity of aqueous solution appeared to have an effect on the reactivity in
previous section.
For the experiment, chemicals were chosen so as to include one or two adequate space-
filling substituent groups: N-Methylhydroxylamine hydrochloride, NH(CH3)OH HCl
(abbreviated as NHACl indicating methyl group attaching to a nitrogen atom), O-
Methylhydroxylamine hydrochloride, NH2OCH3･HCl (OHACl), N,N-
Dimethylhydroxylamine hydrochloride, N(CH3)2OH･HCl (NNHACl), N,O -
Dimethylhydroxylamine hydrochloride NH(CH3)OCH3･HCl (NOHACl). Corresponding
basic substances were prepared by adding equivalent NaOH aqueous solution. They were
NH(CH3)OH (NHA), NH2OCH3 (OHA), N(CH3)2OH (NNHA), NH(CH3)OCH3 (NOHA).
Aqueous solutions of substituted NH2OH were carefully prepared to give 2mol/l.
The heat release behavior at mixing with iron species is obtained with SuperCRC, and
summarized in Table 6. 2x10-3mol of substituted NH2OH and 2x10-5mol of Fe3+ species were
mixed. The result of NH2OH is added to the summary for reference. All the substituted
chemicals exhibited lower reactivity than NH2OH. As a whole, acidic condition and steric
hindrance on oxygen decelerate the interaction with metal. This phenomena is notable in the
interaction with Fe(EDTA)-.
476 Mieko Kumasaki
Figure 20. Heat release behavior in the reaction of HA and Fe (EDTA)-.
Ab inito calculation provides some insight from the viewpoint of electronic structure on
this matter. Figures 21 and 22 show the optimized structure of NHA and NNHA by ab initio
molecular orbital calculations using density functional theory (DFT) in conjunction with
B3LYP approach with Gaussian03 [41]. The 6-31G+(d,p) basis set was used. For acidic
condition, the calculation indicated molecules protonated on nitrogen are more stable rather
than on oxyegn.
Figure 21. Optimized stable structure of NHA(A), and NNHA(b) under basic condition.
Figure 22. Optimized stable structure of protonated NHA(A), and NNHA(b) under acidic condition.
Mulliken charge analysis showed the difference on charge distribution in basic and acidic
condition (Figure 23). Mulliken population analysis allocates charge onto atoms, and provides
information about charge distribution in a molecule. The diameter of circles is proportional to
amount of calculated charge. In basic condition, more charge lie on oxygen rather than
nitrogen. On the contrary, optimized structures in basic condition shows more charge on
nitrogen rather than oxygen. This result is consistent with the experimental result that
substituted HA reacts more in basic condition with Fe3+ since Fe3+ prefers electrons in order
to form coordination linkage.
Figure 23. Charge distribution calculated by Muliken population analysis; (a)NHA, (b) protonated
NHA, (c) NNHA, and (d) protonated NNHA.
478 Mieko Kumasaki
Figure 24. Optimized structure of Fe(NH2OH): (a) interacting through 0, (b) interacting through N.
The molecular orbital calculation also provided some insight of the interaction manner
between Fe3+ and NH2OH. Using Hartree Fock approach and 3-21G basis set, the optimized
structures were calculated simulating the interaction (Figure 24). For Fe3+, only high-spin
states were considered. Frequency calculations were performed to classify each stationary
point. The structure was calculated assuming hydrated Fe3+ with six H2O molecles. One of the
H2O surrounding Fe3+ is substituted with NH2OH. Based on the calculation results,
interaction through the oxygen atom caused extend the N-O bond in NH2OH; the length of N-
O is 1.4692A, and 1.4899A in the complex. The coordination bond between Fe3+ and the
oxygen atom is 2.0733A. In the optimized structure simulating interaction through the
nitrogen, however, 2.2185A is the most stable distance between Fe3+ and the nitrogen atom.
Based on the N-O distance in the complex (1.4704A), N-Fe3+ interaction may be difficult to
represent the linkage formation.
Table 6. Summary of overall heat of reaction
Under acidic condition

HACl NHACl OHACl NNHACl NOHACl
3+
Fe 3.39 4.53 0.26 0.28 0.20
3-
[Fe(CN)6] 2.96 0.36 2.50 1.15 0.03
Fe(EDTA)- 2.02 0.74 1.01 0.07 0.18
Under basic condition
HA NHAOH OHAOH NNHAOH NIHAOH
3+
Fe >238 20.6 0.71 1.70 2.45
3-
[Fe(CN)6] 99.1 5.29 0.05 2.29 4.30
Fe(EDTA)- 489 165 0.22 133 3.47
CONCLUSION
The nature of hazardous materials is their unstability, in other words, high reactivity. A
molecule with high reactivity can interact with neighboring molecules and change their
structure and itself. Hence, some hazardous materials have been utilized widely in chemical
reaction in chemical and other industries. Some highly reactive materials, however,
decompose by themselves if trigged by a slight stimulus such as heat, friction, impact, and so
on. The decomposition generates sometimes stable gas molecules; the enthalpy difference
between an unstable reactant and stable products turns into heat. Stable gas products expand
by heat, and causes destruction. Alternatively, the heat ignites flammable gas product and
causes fire. In order to prevent disasters caused by hazardous materials, knowledge of the
reactivity is inevitably required so as to manage them safely and maximize their useful
properties.
This article overviewed current research on hazardous materials interacting with
transition metals. The first part focused on sensitivity of a complex synthesized from copper
and azole. The complex was stable enough to evaluate the change in sensitivity by complex
formation. The interaction with transition metal has an influence on the sensitivity of azoles,
especially to heat. Following this part, reaction behaviors of three simple unstable chemical,
H2O2, NH2NH2, NH2OH were observed by way of mixing experiments. Despite their similar
chemical structures, the three chemicals exhibited different properties respectively. Acidic
H2O2 shows high reactivity in contact with Fe3+, while basic NH2NH2 released heat
moderately, along with precipitation. Intermediate NH2OH demonstrated changed behavior
depending on acidity. The acidic solution showed easy-to-understand redox reaction with
high oxidated metals, while the basic solution generated precipitation and released heat
continuously with some metals. The results proved the idea that oxygen plays a key role in
the reaction. Based on the idea, the last section related the reaction manner of Fe3+ and
NH2OH by using of steric hindrance. The experimental result and ab initio molecular orbital
calculation supported the idea.
In the field of hazardous materials, most of the studies are case studies, or derivatives
from accidents. In this way, researchers tend to focus on a quantitative study on released
power, or resulting damage. There have been quite a few studies with this inductive approach.
The research related in this article is trials to overview the properties of hazardous materials
by way of chemical structure, and require further development. There are various kinds of
questions remaining regarding the principle of hazardous materials’ properties. Further
intensive research is expected to clarify the subject and contribute to safe handling of
hazardous materials.
REFERENCES
[1] Urben, P.G.; Pitt, M.J.; Battle, L.A.; Ed; Bretherick’s Handbook of Reactive Chemical
Hazards, fifth edition; Butterworth Heinemann: Oxford, 1995.
[2] Recommendations of the Transportation of Dangerous Goods, Twelfth revised edition,
United Nations, 2001.
480 Mieko Kumasaki
[3] Shriver, D.F.; Atkins,P.W.; Langford,C.H. Inorganic Chemistry, second edition;

Oxford University Press: Oxford, 1994; Chapter 6.
[4] Martell,A.E.; Calvin, M.; Chemistry of Metal Chelate Compounds; Prentice-Hall:
NewYork, 1952; p380.
[5] Kumasaki, M.; Miyasaka, R.; Kiuchi, H.; Wada, Y.; Arai, M.; Tamura, M., J. Japan
Explosives Soc. 2001, Vol.62, 109-116.
[6] Krishnan, S.; Swami,R.D. J. Propul. Power 1998, Vol. 14, 295-300.
[7] Kishore, K.; Sunitha,M.R. AIAAJ 1979, Vol. 17, 1119-1123.
[8] Moore, D.S.; Robinson, S.D. Adv. Inorg. Chem. 1998, Vol.32, 171-239.
[9] Haasnoot, J.G.Coord. Chem. Rev. 2000, Vol.200-202, 131-185.
[10] Kowhakul,W.; Miyasaka,R.; Kumasaki,M.; Wada,Y.; Arai,M.; Tamura,M. J. Japan
[11] Kowhakul, W.; Kumasaki,M.; Wada,Y.; .Arai,M; Tamura,M. Sci. Tech. Energetic
Materials 2005, Vol.66, 229-232.
[12] Kowhakul,W.; Kumasaki, M.; Arai, M. Sci. Tech. Energetic Materials 2005, Vol.66
425-430.
[13] Kowhakul, W.; Kumasaki, M.; Wada, Y.; Arai, M.; Tamura, M. Sci. Tech. Energetic
Materials 2006, Vol.67, 87-90.
[14] Mihina, J.S.; Herbst, R.M. J. Org. Chem. 1950, Vol.15, 1082.
[15] Yoshida, T; Safety of Reactive Chemicals, Industrial Safety Series volume 1; Elsevier,
1987,250-265.
[16] Dixon, W.J.; Masseg, F.J. Introduction to Statistical Analysis, second Edition, 1957,
McGraw Hill , 318.
[17] Japan Explosives Society, Japan Explosives Society Standard (IV) Sensitivity test
method, 1996, 65-68.
[18] Japan Explosives Society, Japan Explosives Society Standard (IV) Sensitivity test
method, 1996, 76-80.
[19] Yoshida,T.; Ding, D. Safety technique of chemical substances 1996, Tokyo Progress
System , 108.
[20] Aochi, T.; Miyake, A.; Ogawa, T.; Matsunaga, T.; Nakagawa, Y.; Iida, M. J. Japan
Explosives. Soc. 1997, Vol.58, 202-210.
[21] Sakata, K.; Materials of SG society for the study, third meeting at Tokyo, 1992.
[22] Williams,J.K.; Palopoli,S.F.; Brill, T.B. Combust. Flame 1994, Vol.98, 197.
[23] Ohno, Y.; Akutsu, Y.; Arai, M.; Tamura, M.; Matsunaga, M. J. Japan Explosives Soc.
1999, Vol. 60, 110-117.
[24] Frish, M.J.; Trucks, G.W. Schlegel, H.B.; Gill, P.M.W.; Johnson, B.G; Robb, M.A.;
Cheeseman, J.R.; Keith, T.; Petersson, G.A.; Montgomery, J.A.; Taghavachari, K.; Al-
Laham, M.A.; Zakrzewski, V.G.; Ortiz, J.V.; Foresman, J.B.; Cislowski, J., Stefanov,
B.B.; Nanayakkara, A.; Challacombe, M.; Peng, C.Y.; Ayala, P.Y.; Chen, W.; Wong,
M.W.; Andres, J.L.; Replogle, E.S.; Gomperts, R.; Martin; R.L.; Fox, D.J.; Binkley,
J.S.; Defrees, D.J.; Baker, J.; Stewart, J.P., Head-Gordon, M.; Gonzalez, C.; Pople, J.A.
Gaussian 94, Revision D.3. Gaussian, Inc., Pittsburgh, 1995.
[25] Kawaguchi, S.; Kumasaki, M.; Wada, Y.; Akutsu, Y.; Arai, M.; Tamura, M. J. Japan
[26] Kumasaki,M.; Fujimoto, Y.; Ando, T. J. Loss Prev. Ind. 2003, Vol.16, 507-512.
[27] Kumasaki, M.; J. Haz. Mat. 2004, Vol.115, 57-62.
[28] Kowhakul, W.; Kumasaki, M.; Arai, M.; Tamura, M.; J. Loss Prev. Ind. 2006, Vol.19,
452-458.
[29] Kumasaki, M.; J. Loss Prev. Ind. 2006, Vol. 19, 307-311.
[30] Bailar, JR J.C.; Emeleus, H.J.; Nyholm, R; Trotman-Dickenson, A.F. Comprehensive
Inorganic Chemistry, Volume 2, Pergamon Press, 1973, 272-273.
[31] Schmidt, E. W. Hydrazine and Its Derivatives, Preparation, Properties, Applications,
second edition, Volume 1, John Wiley & Sons, 2001, 498.
[32] Aliev, R. Y.; Kuliev, A.D.; Klyuchnikov, N.G.;Ingibitory Korroz. Met., Moscow 1974,
86, 135-138.
[33] Bailar, JR J.C.; Emeleus, H.J.; Nyholm, R; Trotman-Dickenson, A.F. Comprehensive
Inorganic Chemistry, Volume 3, Pergamon Press, 1973, 1006.
[34] Fenton,H.J.H. J.Chem.Soc. 1894, 65, 899-910.
[35] Wardman, P.; Candeias, L.P. Radiaton Research 1996, 145, 523-531.
[36] Kremer, M.L. Trans. Faraday Soc.1963, 59, 2535-2542.
[37] Cisneros, L.O.; Rogers, W. J.; Mannan, M. S. J. Hazard. Mat. 2002, A95, 13-25.
[38] The Chemical Society of Japan, Handbook of Chemistry: Pure Chemistry II. Third
edition, 1993, Maruzen: Tokyo.
[39] Wilkinson, Sir G. FRS, Comprehensive Coordination Chemistry, The Synthesis,
Reactions, Properties and Applications of Coordination Compounds, Volume4 Middle
Transition Elements, Pergamon Books, 1987, 220-221.
[40] Hoard,J. L.; Lind,M.; Silverton, J. V. J. Am. Chem. Soc. 1961, 83, 2770-2771.
[41] Frisch, M. J.; Trucks, G. W.; Schlegel,H. B.; Scuseria,G. E.; Robb, M. A.;
Cheeseman,J. R;. Montgomery, Jr.,; Vreven,J. A. T.; Kudin,K. N.; Burant,J. C.;
Millam, J. M;. Iyengar,S. S.; Tomasi,J.; Barone,V.; Mennucci,B.; Cossi,M.;
Scalmani,G..; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota,
K.; Fukuda, R.; Hasegawa, J.; Ishida,M.; Nakajima, T.; Honda, Y.; Kitao,O.; Nakai,H.;
Klene,M.; Li,X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G..; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J.
V.; Cui, Q. A.; Baboul, G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin,R. L.; Fox, D. J.; Keith, T.; Al-
Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe,M.; Gill,P. M. W.; Johnson,
B.; Chen, W.; Wong, M.W.; Gonzalez, C.; Pople, J.A. Gaussian 03, Revision D.01,
Gaussian, Inc., Wallingford CT, 2004.
INDEX
aluminium, 332, 334, 338, 339, 345, 350

A ambient air, 18, 19
amine, 164, 176, 181, 182, 268, 285, 286, 305, 308,
absorption spectra, 193, 196, 464
309, 310, 332, 400, 408, 446
absorption spectroscopy, 175
amines, 163, 164, 176, 300, 303, 305, 307, 308, 310
abstraction, 28, 33
ammonia, 12, 34, 35, 284, 304, 469
acetic acid, 4, 121, 257, 398, 454
ammonium, 180, 326, 332, 406
acetone, 254, 391, 404
amygdala, 24, 52
acetonitrile, 181, 409, 419
amyloid beta, 23, 53, 54, 55, 57
acetylcholine, 32
amyloid deposits, 52
acidity, 261, 342, 453, 466, 471, 473, 477
amyloidosis, 25
acidosis, 57
amyotrophic lateral sclerosis, 44, 361, 363
activation energy, 118
anemia, 267, 270
active compound, vii, 2, 15, 297, 302
angiogenesis, 11, 44, 270
active oxygen, 274
anhydrase, 2, 13, 273, 291, 352
active site, 6, 10, 14, 31, 36, 158, 165, 194, 195, 220,
annealing, 97, 105, 118, 120, 122, 123, 124, 125,
221, 250, 262, 263, 273, 275, 280, 283, 353, 370
126, 127, 128, 129, 130, 132, 133, 136, 142, 143,
active transport, 12
144, 145, 146, 148, 149, 152, 153, 154, 155, 335
acylation, 194
anorexia, 270, 273
adaptations, 315
antagonism, 268
adenosine triphosphate, 265
antiarthritis, 2
adjustment, 185, 318
anticancer drug, 45, 285, 292, 293
adsorption, 299, 305, 318, 319
anticonvulsant, 266
aerosols, 12
antigen, 274
aetiology, 7
anti-inflammatory drugs, 266, 269
aggregation, 23, 25, 26, 27, 28, 29, 31, 39, 53, 54,
antioxidant, 7, 11, 22, 24, 29, 36, 58, 264, 265, 266,
55, 56, 59, 61, 89, 280, 361, 362
268, 269, 274, 281, 282, 340, 359, 364, 368
aggregation process, 30
antitumor, 2, 11, 274, 277, 292, 293
alanine, 174
apoptosis, 21, 50, 271, 360, 362, 363, 364
albumin, 8, 10, 12
aqueous solutions, 192, 370, 454, 460
alcohols, 196, 259, 298, 304, 306, 307, 308, 310
aqueous suspension, 335
aldehydes, 15, 164, 168, 306, 308, 310, 355
aromatic compounds, 304
alkaline earth metals, 176
aromatic hydrocarbons, 301, 306, 307, 308, 309, 310
alkaline media, 459
aromatic rings, 245, 247, 301
alkane, 181
arsenic, 1, 4, 5, 6, 19, 46, 331
alkenes, 300, 304, 306, 307
ascorbic acid, 20, 29, 58, 60, 182, 290, 356
alopecia, 13
asparagines, 10
alpha-tocopherol, 50
aspartate, 13, 55, 271, 272
alters, 32, 34, 65
aspartic acid, 26, 281
484 Index
astrocytes, 10, 12, 44, 55 boric acid, 190, 269

atherosclerosis, 267, 270, 276 bounds, 362
atmosphere, 30, 45, 120, 191 brain, 6, 9, 10, 12, 13, 22, 24, 25, 26, 29, 30, 31, 32,
atomic force, 30 33, 34, 35, 36, 37, 38, 40, 42, 43, 44, 46, 52, 55,
atrophy, 23, 24, 29 56, 58, 60, 269, 270, 350, 358, 360, 362, 364,
autosomal recessive, 9, 15, 21 365, 367, 368
brain damage, 350
brain functions, 364
B brain stem, 37
brain structure, 38
bacteria, 16, 18, 21, 280, 284, 340 brass, 349
band gap, 65, 206
breakdown, 85, 101, 348
barium, 328
breast cancer, 11, 19, 44, 45, 48
basal ganglia, 13, 40, 60 breathing, 268
base catalysis, 256 building blocks, 381, 382, 390, 391, 394, 398, 405,
base pair, 18
409, 412, 414, 420, 422
basic research, 365
bulimia nervosa, 273
basicity, 231, 301, 302, 303, 462, 470 bulk materials, 64
batteries, 19
benefits, 137, 353
benzene, 165, 193, 276, 301, 305, 381, 382, 388, C
405, 406, 413
beryllium, 19 Ca2+, 2, 3, 4, 278, 315, 316, 367
beta-carotene, 50 cadmium, 5, 7, 8, 11, 18, 19, 22, 42, 253, 262, 304,
binding energy, 151, 371 376 305, 308, 310, 348
bioavailability, 32, 57, 271 calcination temperature, 335
biochemical processes, 18 calcium, 1, 2, 9, 14, 25, 65, 269, 277, 278, 279, 289,
biochemistry, viii, 6, 46, 56, 291, 365 346, 350
biological markers, 291 calorimetric measurements, 464
biological processes, viii, 220, 354 cancer, 11, 19, 21, 22, 48, 49, 50, 267, 269, 270, 276,
biological roles, 271 293, 341, 346, 350, 354, 361, 365
biological samples, 318 cancer cells, 22, 267, 270, 341
biological systems, vii, 8, 14, 39, 46, 173, 220, 264, capillary, 9, 305, 308, 371
277, 278, 279, 348, 353, 357, 363 carbides, 139, 142, 143, 144, 146
biologically active compounds, 301 carbohydrate, 3, 264, 288, 353
biomaterials, 319 carbohydrate metabolism, 3, 353
biomedical applications, vii, 292, 293 carbohydrates, 262, 268
biomolecules, 10, 220, 264, 316, 348, 354 carbon, 2, 20, 120, 122, 123, 125, 126, 127, 128,
biosynthesis, 16, 270 129, 130, 131, 132, 133, 135, 140, 194, 251, 271,
biotechnology, 350 305, 349, 350, 355, 381, 384, 385, 386, 387, 388,
blood, 7, 8, 10, 12, 13, 17, 23, 43, 45, 47, 51, 267, 390, 391, 405, 412, 413, 421, 422
269, 270, 274, 276, 277, 347, 352, 358, 366 carbon atoms, 140, 387
blood vessels, 267, 270 carbon dioxide, 271, 350
blood-brain barrier, 7, 12, 43, 45 carbon monoxide, 305
bonding, vii, 6, 25, 173, 183, 230, 256, 258, 259, carbonyl groups, 285, 286, 359
262, 285, 286, 299, 303, 304, 311, 347, 349, 350, carboxyl, 181, 182, 183, 262, 264, 317
390, 398 carboxylic acid, 183, 194, 253, 286, 343
bonds, 184, 223, 246, 247, 248, 249, 267, 272, 276, carcinogen, 19, 340, 341, 342, 363
285, 286, 308, 315, 316, 318, 333, 386, 388, 452, carcinogenesis, 21, 22, 44, 47, 48, 49, 277, 340, 341,
457 363, 366
bone, 12, 13, 269, 274, 277, 279, 290, 352 carcinogenicity, 19, 22, 48, 50, 289, 339, 340, 341
bone form, 277 cardiovascular disease, 17, 47, 264, 268, 270, 289
bone marrow, 290 cardiovascular system, 266, 269
bone mass, 13
Index 485
catalysis, vii, 6, 14, 29, 52, 163, 164, 173, 195, 200, chromatography, 167, 297, 298, 299, 300, 301, 302,
220, 255, 264, 282, 291, 314, 347, 348, 355, 367, 303, 304, 305, 306, 308, 309, 310, 311, 312, 313,
405 314, 315, 316, 319, 320, 323, 324, 341
catalyst, vii, 7, 271, 272, 344, 350, 356, 369, 370, chromium supplementation, 17, 47
371, 374, 375, 376, 378, 405, 462, 464, 469 chromosome, 9, 20, 340, 341, 345, 346
catalytic activity, viii, 157, 158, 174, 262, 272, 350 chronic diseases, 289
catalytic properties, 30, 55, 157, 158, 273, 333, 349, cleavage, 23, 30, 41, 49, 180, 263, 356, 388
383 clinical application, 365
catecholamines, 36, 58, 59 closed shell zinc element, 2
cation, 11, 40, 200, 223, 283, 303, 333, 338, 344, clusters, 10, 31, 37, 108, 110, 118, 119, 137, 140,
397 159, 177, 292, 384
C-C, 386, 389, 390, 391, 393, 399, 405, 417, 422, C-N, 391, 404
436, 441, 447 CNS, 10, 60
CCA, 331 CO2, 2
cell biology, 261, 288 coatings, 327, 331, 332, 333
cell culture, 31, 340 cobalamines, 16
cell cycle, 21, 341, 368 cobalt, 1, 3, 4, 5, 6, 8, 16, 39, 48, 182, 183, 187, 194,
cell death, 21, 25, 29, 34, 36, 55, 61, 278, 279, 291, 196, 283, 304, 312, 334, 344, 349, 351, 359, 365,
294, 341, 360, 362, 363 370, 375, 376, 378, 387, 427, 438, 468
cell division, 3, 285 coenzyme, 16, 194
cell line, 271, 276, 279, 294 cognitive function, 32, 52, 271
cell membranes, 25, 265, 274 cognitive impairment, 24, 52
cell surface, 31, 262, 359 coke formation, 370
cellular immunity, 274 collagen, 10, 265, 269
central nervous system, 12, 288, 360, 361 colon cancer, 21
ceramic, vii, 334, 335, 336, 337, 339, 351, 407, 454 color, 325, 327, 328, 331, 332, 333, 335, 337, 338,
cerebellum, 362 464, 466, 467, 468, 469, 473
cerebrospinal fluid, 24, 30, 52, 55 colorectal cancer, 21, 50, 286, 354
ceruloplasmin, 7, 9, 24, 31, 52, 264, 268, 269, 290 combustion, 18, 19, 350
charge density, 39 composites, 63, 64, 65, 66, 84, 87, 88, 89, 90, 91, 92,
chelates, 42, 188, 189, 193, 266, 304, 308, 309, 310, 93, 95, 96, 97, 99, 101, 103, 105, 106, 344
311, 312, 316, 319 composition, 66, 120, 122, 124, 128, 129, 133, 135,
chemical industry, 459 136, 137, 138, 141, 142, 145, 153, 155, 156, 158,
chemical interaction, 117 159, 263, 326, 327, 328, 329, 332, 335, 336, 338,
chemical properties, 22, 173, 176, 184, 261, 297, 348 339, 345, 369, 370, 377, 398, 420, 421
chemical reactions, 348 compression, 119, 126, 153
chemical reactivity, 354 condensation, 57, 164, 167, 172, 174, 176, 183, 186,
chemical structures, 452, 453, 459, 477 195, 200, 206, 417
chemiluminescence, 357, 359, 366 conductance, 176, 186, 193, 205
chemisorption, 305 conduction, 151, 156, 157, 453
chemotherapy, viii conductivity, 196, 206, 349
chitin, 320 conductors, vii, 347, 349
chlorination, 344 configuration, 2, 14, 172, 177, 185, 190, 196, 203,
chlorine, 1, 173 308, 348, 351, 407
chloroform, 406 connective tissue, 265, 269, 352
chlorophyll, 2, 3, 342, 346 construction, 136, 137, 332, 335, 349, 384
CHO cells, 340, 341 consumption, 12, 17, 30, 33, 330
cholesterol, 264, 267, 276 control group, 19
choline, 365, 366 COOH, 164, 181, 186, 206, 224
chondrocyte, 294 copolymerization, viii
choroid, 9 coronary heart disease, 266, 267
chromatid, 341, 346 correlation, 21, 24, 39, 220, 230, 241, 244, 250, 342
chromatographic technique, 298, 316 correlation analysis, 250
486 Index
correlations, 57, 220, 221, 233, 244, 252, 255 dendritic simplification, 25, 53
corrosion, 137, 327, 329, 331, 332 dendritic spine loss, 25
cortex, 42, 367 density functional theory, 474
cortical neurons, 28, 31, 56 deoxyribose, 36
cotton, 330 dephosphorylation, 224
coupling constants, 247 depolarization, 294
covalent bond, 221, 262, 264, 283, 298, 299, 315 deregulation, 22, 24, 52, 362
covalent bonding, 315 derivatives, 25, 58, 168, 192, 193, 206, 221, 222,
covering, 165, 326, 330 233, 260, 263, 286, 289, 293, 298, 305, 310, 311,
critical value, 121 312, 326, 381, 400, 477
crystal structure, 117, 161, 182, 183, 184, 186, 206, desorption, 298
219, 239, 240, 245, 246, 247, 248, 249, 251, 252, destruction, 33, 118, 121, 271, 274, 276, 452, 477
253, 254, 255, 256, 258, 259, 275, 293, 334, 335, detection, 29, 311, 391
344 detoxification, 265, 353
crystalline, 106, 155, 159, 165, 187, 253, 332, 339 deviation, 338
crystallization, 86 diabetes, 17, 264, 266, 276, 277, 278, 289, 293, 367
crystals, 63, 65, 333, 335, 338, 339, 457 diagnostic markers, 52
CSF, 24, 30, 43 dialysis, 290
culture, 25, 29, 32, 37, 341 diamines, 163, 165, 185, 189, 195
culture medium, 29, 341 diarrhea, 13, 354
cyanide, 393, 416 dielectric constant, 84
cycles, viii, 30 dielectrics, 63, 65, 66, 107, 108
cycling, 6, 10, 17, 27, 29, 36, 348, 354, 355 dienes, 303
cyclopentadiene, 418 diet, 13, 15, 17, 18, 47, 265, 270
cysteine, 8, 10, 18, 20, 36, 59, 265, 271, 274, 276, dietary intake, 16, 18, 264
277, 280, 292, 294, 341 dietary supplementation, 17
cytochrome, 3, 6, 10, 30, 36, 56, 58, 195, 268, 270, diffraction, 53, 67, 87, 99, 143, 146, 155
352, 356, 361 diffuse reflectance, 338, 339
cytochromes, 6, 8, 16, 38, 352 diffusion, 12, 100, 118, 119, 124, 136, 159
cytokines, 274 diffusion process, 136
cytoplasm, 4, 7, 10, 275 dihydroxyphenylalanine, 36
cytotoxic agents, 274 dimethylsulfoxide, 410
cytotoxicity, 20, 27, 37, 54, 276, 293, 340, 360 diodes, 350
dipeptides, 258
discrimination, 311
D disease progression, 361
diseases, 2, 15, 19, 22, 262, 266, 267, 268, 269, 271,
decomposition, 20, 146, 150, 155, 200, 219, 278,
277, 361, 362
279, 282, 311, 332, 339, 348, 353, 356, 372, 411,
disequilibrium, 131, 136
451, 452, 456, 457, 464, 477 dislocation, 118, 120, 122, 124, 125, 126, 127, 129,
decomposition temperature, 457 130, 131, 133, 134, 135, 136, 137, 138, 139, 140,
defects, 13, 85, 93, 106, 117, 118, 119, 121, 124,
141, 158, 160
126, 129, 133, 134, 135, 137, 141, 155, 160, 161,
disorder, 9, 12, 13, 23, 33, 38, 159, 161, 270
273 dispersion, 108, 283, 376
deficiencies, 17, 274 displacement, 6, 118, 135, 158, 159, 161, 189, 247,
deficiency, 2, 9, 12, 13, 15, 16, 32, 43, 46, 57, 266,
284
267, 268, 269, 270, 271, 273, 290, 292, 361, 364,
distortions, 117, 118, 119, 126, 130, 131, 133, 140,
365 147, 148, 152, 156, 159
deficit, 298 distribution, 4, 9, 58, 85, 86, 93, 123, 124, 125, 155,
deformation, 120, 122, 333
277, 317, 333, 344, 366, 370, 453, 475
degenerate, 67, 96
diversity, 220
degradation, 8, 15, 24, 224, 225, 255 DMF, 172, 180, 196
dehydrate, 253
dementia, 32, 56, 58, 60, 367
Index 487
DNA, 9, 10, 13, 14, 18, 19, 20, 21, 22, 23, 28, 29, electronic structure, 65, 220, 301, 474
34, 40, 42, 48, 49, 50, 57, 58, 61, 263, 264, 265, electrons, vii, 6, 14, 38, 40, 110, 120, 151, 152, 156,
275, 281, 283, 284, 285, 286, 287, 288, 292, 340, 157, 161, 187, 228, 243, 247, 262, 270, 271, 298,
341, 345, 346, 354, 355, 363, 364, 367, 368 299, 300, 301, 302, 303, 304, 347, 349, 350, 351,
DNA damage, 20, 22, 40, 42, 48, 49, 61, 341, 346, 353, 354, 387, 393, 452, 457, 459, 460, 475
363, 367 electroplating, 19
DNA repair, 19, 21, 22, 48, 341, 363, 368 elementary particle, 119
DNA strand breaks, 22 elongation, 136, 141
donors, 299, 300, 301, 302, 316, 382 elucidation, 150, 263
dopamine, 10, 33, 34, 35, 36, 37, 38, 40, 41, 57, 58, emission, 52, 189, 330, 357, 358, 359
59, 61, 361, 367 enantiomers, 297, 298, 310, 314, 315, 320
dopaminergic, 33, 34, 37, 38, 39, 41, 59, 60, 61, 361 encapsulation, 164, 282
dopants, 335 endothelial cells, 9
doping, 118, 136 endothermic, 456, 457
dose-response relationship, 21 energetic materials, 452, 453
double bonds, 257, 301 energy, vii, 5, 12, 13, 26, 63, 66, 67, 68, 69, 70, 71,
Drosophila, 29, 32, 55 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 85,
drug delivery, viii, 45 86, 87, 91, 92, 95, 96, 98, 100, 101, 102, 103,
drug design, 26 104, 105, 106, 107, 117, 119, 136, 151, 157, 158,
drugs, 2, 33, 58, 261, 263, 266, 269, 273, 274, 275, 159, 167, 187, 229, 265, 270, 271, 299, 300, 302,
278, 284, 293 330, 335, 362, 367, 382, 386, 410, 452, 454
drying, 369, 370, 372, 374, 376, 377 environmental impact, 58
DSC, 455, 456 Environmental Protection Agency (EPA), 48, 289,
ductility, 347, 349 345
duodenum, 8 enzymatic activity, 272
durability, 332 epidemiology, 340
dusts, 11, 12, 18, 19, 44 epilepsy, 266, 269, 362
dwarfism, 273 EPR, 26, 28, 30, 39, 61, 174, 181, 251, 359, 434
dyes, 19, 330 equilibrium, 118, 121, 130, 135, 136, 145, 149, 155,
dysmenorrhea, 274 156, 159, 160, 168, 171, 172, 175, 277, 278, 280,
dystrophic neuritis, 23 288, 303
erythrocytes, 8, 17
ESI, 420, 421
E ESR, 20, 21, 167, 172, 186, 197, 387
ESR spectra, 167, 197
elastin, 10, 265
ester, 257, 307, 311
electric field, 66, 284 estrogen, 14, 270
electrical conductivity, 206, 349
ethanol, 176, 254
electrical properties, 349
ethers, 300, 303, 304, 306, 307, 308, 309, 310
electrical resistance, 149, 151 ethylene, 298, 302, 308, 309, 316, 437
electricity, vii, 25, 347, 349, 455 ethylene glycol, 302
electrochemical behavior, 381, 409
etiology, 58, 267
electrochemistry, 408
evacuation, 121, 153
electrodes, 284, 386, 455 evidence, 2, 17, 19, 21, 22, 23, 25, 33, 49, 54, 85,
electroluminescence, 382 155, 255, 266, 269, 270, 277, 341, 357, 360, 362,
electrolysis, 325
364, 468
electrolyte, 205, 325, 389, 401, 403
evolution, 157, 464
electromagnetic, 64, 84, 91 excitation, 64, 89, 92, 102, 106
electromigration, 314 exciton, 342
electron diffraction, 140, 141, 145, 146
excretion, 9, 11, 12, 15
electron microscopy, 60, 136, 143
exothermic peaks, 456
electron pairs, 299, 300 experimental condition, 93, 107
electron paramagnetic resonance, 60, 258
Electron Paramagnetic Resonance, 39
488 Index
exposure, 5, 7, 11, 12, 15, 19, 20, 21, 33, 38, 41, 48, gene expression, 14, 31, 48, 290, 350
49, 61, 86, 130, 133, 142, 148, 150, 267, 340, genes, 22, 29, 46, 51
341, 342, 345, 350, 363, 402, 412 genetic defect, 15
genetic disease, 21
genetic information, 13
F genetic predisposition, 22
genomic instability, 22, 341
facilitators, 6 genomic stability, 43
factories, 346 geometry, 6, 26, 27, 39, 54, 64, 164, 166, 171, 185,
failure to thrive, 9 190, 228, 230, 231, 237, 239, 243, 251, 271, 272,
ferric ion, 22 282, 283, 300, 301, 394, 402, 405, 471
ferric state, 267 Germany, 63, 110, 322, 381, 423, 431, 447
ferritin, 7, 8, 21, 29, 31, 37, 38, 51, 60, 264, 352, 356 gestation, 12
ferromagnetism, 229, 232, 258 GG sequence, 285
ferrous ion, 12, 38 Gibbs energy, 338
fertilizers, 3, 4 glasses, 63, 65, 85, 86, 88, 89, 90, 91, 93, 95, 107
fibers, 27 glia, 35
fibrillation, 39, 61 glial cells, 24
fibroblasts, 56, 340 gluconeogenesis, 12
fibrosis, 23 glucose, 17, 264, 270, 276, 293, 353, 366
field theory, 364 glue, 265
financial, 110, 208, 422 glutamate, 271, 362
financial support, 110, 422 glutamine, 12
first generation, 387 glutathione, 2, 5, 6, 11, 17, 18, 19, 20, 22, 29, 34, 36,
first transition series, 2, 6 38, 40, 48, 49, 55, 58, 60, 265, 275, 284, 340,
flow curves, 461, 467, 468 341, 348, 354, 360, 361, 364
fluctuations, 85, 155, 159 glycerol, 121
fluorescence, 21, 189, 261, 283, 342, 346 glycol, 298, 302, 303
fluorine, 1, 4, 6 glycosaminoglycans, 12
formula, 120, 160, 194, 196, 219, 225, 228, 234, gold and platinum complexes, 2
235, 330, 333, 334, 336, 338, 339, 454 gold compound, 274, 276, 292
foundations, 331 gold nanoparticles, 63, 66, 97, 103, 104, 106, 107
four-wave mixing, 96 grain boundaries, 130, 138, 142, 143, 144, 145, 146,
fragments, 39, 143, 155, 281, 282, 283, 285, 381, 153
382, 384, 386, 387, 389, 390, 392, 394, 406, 412, grain size, 122, 454
418, 421, 452 growth factor, 31
free energy, 18, 151, 159 growth hormone, 3
free GSH, 40 growth rate, 125
free radicals, 11, 21, 22, 33, 34, 35, 36, 37, 38, 43, guanine, 49, 265, 284, 285
50, 268, 339, 348, 353, 354, 363, 364
friction, 451, 452, 454, 455, 477
frontal cortex, 361, 362, 364 H
fruits, 12, 13
FTIR, 333 Hamiltonian, 187, 229
functionalization, 262 haptoglobin, 8
fusion, 108 hazardous materials, 451, 452, 459, 460, 477
hazardous waste, 20
H-bonding, 206, 285, 286
G health problems, 350
heart disease, 267, 276
gadolinium, 177, 196 heat capacity, 106
gallium, 97 heat release, 451, 452, 455, 456, 457, 460, 462, 466,
gastrointestinal tract, 7, 9, 12 468, 471, 472, 473
gel, 175, 298, 315, 319, 469 heat transfer, 93, 106
Index 489
heating rate, 455 hydrolysis, 192, 193, 195, 253, 255, 263, 285, 286,
heavy metals, 34, 261, 327 288
heme, 8, 38, 43 hydrolytic stability, 262
hemochromatosis, 50, 51, 354 hydroperoxides, 39, 282, 348, 353, 355, 356, 359,
hemoglobin, 6, 8, 279, 280, 341, 352, 452 363
hepatocarcinogenesis, 363, 365 hydrophilicity, 471
hepatocellular carcinoma, 11, 21, 44 hydroxide, 14, 291, 335, 336, 338, 471
hepatocytes, 9, 21 hydroxyl, 7, 10, 20, 21, 22, 29, 30, 31, 34, 35, 37, 38,
hepatotoxicity, 342, 348, 363 39, 49, 55, 56, 61, 188, 264, 268, 273, 298, 317,
heterogeneity, 155, 319 340, 348, 354, 355, 366
heterogeneous catalysis, vii hypothesis, 27, 38, 53, 151, 152, 266, 355, 359, 364
hexane, 305
hippocampus, 24, 32, 38, 51, 52, 361, 362, 364
histidine, 10, 25, 26, 27, 28, 30, 31, 54, 55, 271, 272, I
279, 281
histogram, 125, 135 immobilization, 175, 283, 298, 315, 317
histone, 19, 48 immune function, 13, 270, 354
history, 278 immune response, 269, 274, 291
homeostasis, 9, 13, 30, 34, 43, 45, 56, 57, 278, 279, immune system, 271
288, 350, 362, 364, 366, 368 impact strength, 148, 149
homogeneity, 305 impaired immune function, 264
homogeneous catalyst, 167 implantation of silver ions, 100
homolytic, 355 impregnation, 369, 370, 371, 373, 375, 376, 377
hormones, 3, 265, 271, 277 improvements, 335
host, 22, 84, 92, 93, 106 impurities, 127, 130, 134, 135, 136, 139, 140, 337
human, 1, 2, 4, 5, 8, 9, 12, 14, 15, 17, 18, 19, 20, 21, in transition, 7, 349
22, 30, 33, 36, 37, 38, 39, 42, 43, 44, 47, 48, 49, in vitro, 21, 25, 29, 31, 33, 49, 58, 59, 60, 208, 268,
50, 52, 55, 56, 59, 60, 61, 262, 265, 276, 277, 270, 277, 282, 285, 292, 293, 341, 346, 354, 355,
290, 291, 292, 294, 331, 340, 341, 345, 346, 350, 364
352, 353, 354, 356, 361, 363, 364, 365, 367 In vitro precipitation, 25
human aliments, 2 in vivo, 7, 10, 12, 28, 29, 31, 37, 61, 261, 270, 271,
human body, 4, 5, 9, 265, 350, 352, 361 277, 278, 285, 289, 292, 293, 342, 355, 357, 359
human brain, 36, 37, 38, 59, 354 incubation period, 30, 134, 135, 141, 158
human exposure, 345 Iindium, 67
human genome, 14 individuals, 12, 21, 38
human health, 5, 6, 42, 47, 364 inducer, 27, 363
hydrazine, 183, 452, 459 induction, 22, 120, 292, 362, 363, 468
hydrides, 45 infarction, 267
hydrocarbons, 301, 303, 304, 305, 308, 309, 310 infection, 269, 270
hydrogen, 2, 6, 16, 21, 25, 29, 33, 34, 48, 49, 50, 53, inflammation, 20, 23, 25, 33, 49, 266, 268, 269, 270,
55, 183, 184, 188, 220, 221, 223, 234, 245, 246, 273, 274, 276, 290
247, 248, 249, 255, 256, 257, 258, 259, 260, 262, inflammatory responses, 21, 341, 350
264, 268, 270, 286, 300, 301, 302, 311, 348, 350, influenza virus, 289, 346
352, 354, 355, 357, 371, 376, 402, 452, 459, 469, infrared spectroscopy, 59
470 inherited disorder, 46
hydrogen abstraction, 355, 357 inhibition, 19, 22, 26, 30, 56, 58, 59, 263, 274, 282,
hydrogen atoms, 402, 459, 469 283, 362, 363, 367
hydrogen bonds, 220, 221, 234, 245, 246, 247, 248, inhibitor, 30, 32, 58, 271, 291, 331
249, 260, 300, 302 inhomogeneity, 124
hydrogen peroxide, 6, 21, 29, 34, 48, 49, 50, 53, 55, initial state, 128, 129, 130, 131, 133, 134, 142, 149
262, 264, 268, 348, 352, 354, 355, 452, 459, 470 initiation, 33, 268, 353, 355, 357, 473
hydrogenase, 18 inorganic micronutrients, 2
hydrogenation, 165, 350, 373, 374 insertion, viii, 10, 336, 337
insulin, 17, 28, 47, 264, 277, 278, 279, 289, 293
490 Index
insulin resistance, 17, 47

insulin sensitivity, 17, 264, 289 L
insulin signaling, 17
lactic acid, 270
integrated circuits, 350
lactoferrin, 294, 352
integrated optics, 64
landfills, 20
integrity, 13, 159, 268, 340, 364
lanthanide, 186, 191, 196
interference, 22, 354, 363
laser radiation, 86, 87, 89, 90, 92, 93, 95, 97, 98,
intermolecular interactions, 245, 300
100, 101, 102, 106, 107, 108
internalization, 8, 341
lasers, 84
interstitial atom, 118, 121, 122, 123, 124, 131, 134,
lateral sclerosis, 368
135, 139, 140, 156, 159
lattice parameters, 142, 147, 148, 338
intestinal tract, 9
lattices, 283
intestine, 7, 9, 15, 42
LDL, 267
intoxication, 56, 278, 279, 354, 368
LEA, 61
iodine, 1, 4, 6, 46, 352
leaching, 331
ion implantation, vii, 63, 64, 65, 66, 67, 84, 85, 86,
lead, 2, 5, 6, 8, 11, 18, 19, 20, 22, 25, 26, 28, 30, 34,
87, 92, 95, 96, 97, 99, 100, 101, 102, 103, 104,
36, 38, 60, 63, 107, 118, 151, 164, 165, 230, 246,
105, 111
262, 263, 272, 284, 325, 327, 328, 329, 335, 336,
ion transport, 29, 42
339, 340, 341, 346, 350, 355, 360, 362, 452, 460
ion-exchange, 338
lean body mass, 17
ionizing radiation, 267
learning, 288
IR spectra, 164
lecithin, 267
iridium, 404, 405
lesions, 13, 20, 51, 269, 284, 340, 341
iron transport, 268
leukemia, 50, 267
irradiation, 89, 93, 95, 101, 103, 117, 118, 119, 120,
liberation, 34, 192, 457, 471
121, 122, 124, 126, 127, 129, 130, 131, 132, 133,
lipid metabolism, 264, 288, 353
134, 135, 136, 137, 138, 139, 140, 141, 155, 156,
lipid oxidation, 39
157, 158, 159, 160, 161
lipid peroxidation, 7, 19, 21, 22, 23, 29, 55, 268, 278,
IR-spectra, 97
279, 282, 348, 354, 355, 356, 357, 358, 359, 360,
ischemia, 362
361, 362, 363, 364, 366
isobutane, 302
lipoproteins, 266, 268
isolation, 298, 311, 315, 318, 319, 320
liposomes, 357, 358, 359
isoleucine, 174, 311
liquid chromatography, 315
isomers, 219, 220, 228, 301, 302, 303, 305, 308, 309,
liquid phase, 282, 297, 299
314
liquids, vii, viii, 17, 116, 311
isotope, 15, 420
lithium, 65
liver, 8, 9, 12, 13, 21, 23, 38, 41, 50, 269, 339, 342,
J 354, 357, 358, 362, 363, 365, 367
liver cancer, 21
jejunum, 8 liver damage, 339, 342, 354
joints, 267, 276 liver disease, 12, 13
localization, 51
locus, 37
K lung cancer, 19, 21, 48, 342, 363
Luo, 49, 367, 446
K+, 3, 4 lymphocytes, 49, 341
ketones, 300, 303, 304, 306, 307, 308, 310, 312
kidney(s), 10, 12, 342, 366
kinetics, 26, 46, 135, 143, 146, 261, 268, 300, 302
Index 491
metabolizing, 280, 340

M metal complexes, vii, viii, 163, 164, 165, 167, 168,
169, 174, 176, 195, 197, 202, 206, 254, 256, 258,
macromolecules, 245, 272, 283, 294, 318, 339, 348,
259, 261, 263, 297, 298, 299, 301, 304, 305, 314,
354, 363
320, 383, 384, 390, 399, 405, 406, 422, 453, 454,
macronutrients, 1, 2
456
magnesium, 1, 2, 14, 253, 304, 327, 334
metal extraction, 175
magnetic field, 172, 349, 353
metal nanoparticles, vii, 63, 64, 65, 67, 107, 111
magnetic materials, 220, 221
metal oxides, 304, 333, 334, 337, 350, 453
magnetic moment, 166, 167, 173, 184, 186, 189,
metal phase (MNPs), 63, 64, 65, 66, 83, 84, 85, 87,
193, 194, 197, 205
88, 89, 90, 91, 92, 93, 95, 97, 100, 101, 102, 103,
magnetic properties, 177, 187, 220, 221, 227, 230,
104, 106, 107, 110
234, 240, 243, 249, 250, 252, 253, 254, 255, 256,
metal salts, 168, 171, 172, 202, 206, 251, 415
257, 258, 259, 383, 422
metal-based photodynamically active compounds, 2
magnetic resonance imaging, 13
metal-free conditions, 17
magnetism, 163, 195, 220, 250, 251, 252, 257
metallo- therapeutics, 2
magnitude, 93, 95, 107, 135, 136, 137, 141, 200,
metalloenzymes, 10, 12, 13, 165, 194, 195, 221, 262,
220, 229, 230, 231, 232, 234, 236, 237, 238, 241,
263, 271, 291
243, 244, 247, 349
metallo-therapy, 2
major histocompatibility complex, 274
metallurgy, 345, 347, 348
mammalian cells, 7, 21, 346, 348, 356, 360
metal-organic complexes, 2, 38
mammals, 11, 16, 43, 45, 47, 347, 352
metal-oxide-semiconductor, 65
manganese, 1, 4, 5, 8, 11, 12, 14, 24, 33, 39, 40, 45,
metastasis, 267
46, 61, 182, 252, 253, 291, 292, 304, 305, 312,
methanol, 168, 200, 260, 344, 406, 454
325, 334, 335, 336, 337, 350, 364, 467
methodology, viii, 413
mass spectrometry, 167, 176
methyl group, 172, 197, 453, 471, 473
matrix, 32, 66, 84, 93, 95, 100, 106, 117, 122, 123,
methyl groups, 172, 197
124, 126, 127, 128, 129, 130, 140, 143, 145, 146,
methylcobalamin (MeCbl), 16
147, 148, 152, 155, 156, 158, 159, 161, 317, 318
Mexico, 364
matrixes, 67
Mg2+, 2, 4
matter, iv, 37, 115, 261, 474
MHC, 274
MCP, 342
mice, 19, 21, 31, 32, 48, 50, 57, 289, 291, 346
MCP-1, 342
microelectronics, 64, 65
mechanical properties, 25, 118, 136, 137
micronutrients, 2, 3, 352
mechanical stress, 117
microorganisms, 1, 16
mechanical testing, 120, 140
microphotographs, 140
media, 63, 64, 89, 97
microscope, 121, 335
medicine, viii, 60, 261, 266, 288, 289, 292, 295, 299,
microscopy, 26, 30, 51
320
microsomes, 348, 354
melanin, 10, 37, 59, 60, 265
microstructure, 118, 121, 143, 155
mellitus, 367
midbrain, 33
melting, vii, 108, 120, 131, 347, 349, 350, 457
migration, 118, 180, 314
membrane permeability, 341
milligrams, 12
membranes, 35, 319, 348, 354
mineralization, 12, 279
Mendeleev, 294
miniaturization, 64
mental state, 24
mitochondria, 8, 10, 12, 30, 37, 41, 59, 61, 348, 352,
mercury, 5, 7, 11, 13, 19, 262, 303, 305, 348, 398,
354, 360, 361, 362, 365, 367
444
mitogen, 363
metabolic disturbances, 361
mitosis, 285, 340
metabolic pathways, 353
mitotic index, 20
metabolism, 3, 8, 9, 12, 13, 14, 15, 16, 23, 32, 33,
mixing, 67, 118, 119, 155, 156, 157, 158, 159, 160,
34, 35, 36, 42, 43, 261, 262, 277, 281, 288, 341,
161, 338, 374, 454, 462, 467, 468, 473, 477
348, 361, 365
MMP, 32
metabolites, 6, 37, 58, 340
492 Index
MMP-3, 32 Nd, 84, 85, 97, 196

model system, 60, 221 necrosis, 360, 365
modelling, 286 neocortex, 23
models, 7, 31, 51, 220, 221, 292, 367 nerve, 31, 33, 34, 57, 352
modern science, 63 nerve growth factor, 31, 57
modern society, 452 nervous system, 288
modifications, 19, 97, 315 neuritis, 23, 39
moisture, 197 neuroblastoma, 58
molar ratios, 337, 338, 339 neurodegeneration, 9, 30, 31, 51, 53, 59, 60, 268,
molar volume, 338 288, 354, 362, 365, 367
molecular mass, 25 neurodegenerative diseases, 7, 23, 24, 53, 58, 288,
molecular oxygen, 39, 262, 282, 339, 361 364, 367
molecular structure, 199, 224, 227, 228, 247, 248, neurodegenerative disorders, 2, 55, 56, 57, 271, 288,
251, 253, 256, 257, 258, 459 361, 366
molecular weight, 8, 10, 20, 186, 205, 221, 262, 268 neurofibrillary tangles, 23, 24, 52, 361, 362
molybdenum, 1, 2, 3, 4, 5, 9, 14, 15, 17, 46, 47, 120, neurologic symptom, 13
132, 133, 171, 270, 325, 327, 352, 370, 376 neurological disease, 60
monoclonal antibody, 50 neuronal cells, 23, 41
monomers, viii, 25, 27 neurons, 10, 23, 25, 29, 31, 32, 33, 35, 37, 38, 39,
mononucleotides, 285 44, 55, 59, 361, 362, 364
morphology, 26, 31, 118, 135, 333 neuropathy, 290
mortality, 48, 50, 346 neuropsychological tests, 24
motif, 10, 14, 183, 401, 407 neurotoxicity, 27, 29, 31, 40, 45, 53, 54, 57, 61, 348,
multiple factors, 33 360, 361, 363
multiplication, 22 neurotransmission, 288
muscle mass, 277 neurotransmitter, 33, 34, 38, 268, 362
muscles, 277, 278 neurotransmitters, 39, 367
mutant, 10, 28, 31, 32 neurotrophic factors, 31
mutation, 363, 451 neutral, 27, 28, 170, 172, 180, 223, 251, 263, 300,
mutations, 9, 22 359, 382, 384, 387, 401, 457, 458, 459
myelodysplasia, 267 neutrons, 120, 122, 129, 133, 136, 137, 138, 139,
myocardial infarction, 267 140, 141, 158
myoglobin, 6, 8, 280, 352 NH2, 39, 309, 446
nickel, 1, 4, 5, 6, 11, 18, 19, 27, 46, 47, 48, 49, 119,
120, 131, 135, 137, 138, 141, 142, 143, 145, 146,
N 147, 151, 152, 153, 154, 155, 157, 158, 159, 160,
161, 183, 194, 252, 253, 303, 305, 308, 312, 319,
Na+, 4, 305
333, 334, 339, 344, 348, 366, 458
Na2SO4, 304
nicotine, 32
NaCl, 35, 304 nicotinic acid, 264
NAD, 352, 354 nigrostriatal, 33, 38
NADH, 16, 18, 49, 354, 361
niobium, 120, 121, 122, 123, 126, 127, 128, 129,
nanomaterials, 64, 110, 119, 407
130, 132, 133, 135
nanoparticles, 65, 84, 85, 86, 88, 89, 90, 92, 93, 95, niobium carbonitrides, 120, 121, 122, 123, 126, 128,
99, 100, 101, 102, 106, 107, 108, 110, 114, 119, 129, 130, 132, 133
350
NIR, 386
nanostructured materials, 63, 111, 405
nitrates, 4, 332, 339, 377
nanostructures, 102, 162 nitric oxide, 366, 367
nanotechnology, viii, 64, 111 nitric oxide synthase, 367
NAS, 45
nitrogen, 2, 3, 6, 14, 27, 28, 39, 120, 122, 123, 125,
National Research Council, 45
126, 127, 128, 129, 130, 131, 132, 133, 135, 164,
NATO, 250 172, 180, 181, 191, 196, 197, 219, 223, 257, 258,
nausea, 354
NCS, 220, 254
Index 493
271, 279, 303, 304, 305, 316, 408, 451, 452, 453, oxalate, 19, 48, 286
459, 471, 473, 474, 475, 476 oxidation, 3, 6, 14, 15, 16, 18, 19, 20, 22, 25, 27, 28,
nitrogen fixation, 3 29, 33, 34, 35, 36, 37, 40, 41, 54, 58, 59, 109,
nitrogenase, 3, 15 164, 165, 174, 200, 202, 220, 262, 265, 274, 276,
NMR, 39, 45, 54, 172, 174, 176, 186, 189, 190, 193, 277, 278, 281, 282, 283, 327, 342, 347, 353, 354,
205, 277, 278, 285, 417, 421, 443 355, 358, 361, 363, 386, 388, 389, 390, 400, 410,
N-N, 184 418, 460,뫰464, 466, 467, 468
nonlinear optical response, 64, 66
oxidative damage, 29, 45, 52, 264, 348, 350, 354,
nonlinear optics, 63, 116
359, 360, 361, 362, 364, 365, 367, 368
non-steroidal anti-inflammatory drugs, 266
oxidative destruction, 282
nucleation, 103, 118, 124, 130, 140, 145, 147, 150,
oxidative reaction, 27
159
oxidative stress, 2, 5, 10, 22, 25, 29, 32, 33, 34, 35,
nuclei, 33, 159
36, 37, 38, 40, 41, 42, 51, 55, 57, 58, 59, 61, 278,
nucleic acid, 3, 8, 13, 19, 48, 49, 262, 268, 285, 361
279, 290, 348, 350, 354, 359, 360, 361, 362, 363,
nucleophiles, 316
365, 366, 367, 368
nucleotide sequence, 283
oxide nanoparticles, 364
nucleus, 8, 265, 340, 352
oxygen consumption, 33, 279, 362
nutrient(s), 2, 3, 4, 12, 16, 20, 47, 264, 277, 364
oxygen consumption rate, 33
nutrition, 12, 13, 43, 47, 50, 365
oxyhemoglobin, 280
nutritional status, 290
P
O
palladium, 258, 303, 350, 391, 398, 406, 407, 436
occlusion, 221
pallor, 37
olefins, viii, 302, 303, 304, 305, 306, 309
pancreas, 12
oleic acid, 282
pathogenesis, 24, 29, 30, 35, 55, 58
oligodendrocytes, 9
pathology, 51, 291, 359, 365
oligomeric structures, 394, 406
pathophysiology, 23
oligomerization, 25, 27
pathways, 31, 34, 46, 58, 59, 250, 263, 279, 285,
oligomers, 25, 26, 30, 55, 57, 278, 279, 362
294, 355, 360
operations, 18, 330
PCT, 429
optical limiters, 84, 89, 107
peptidase, 3
optical parameters, 88, 97, 107
peptide(s), 18, 23, 25, 26, 27, 28, 29, 30, 53, 54, 55,
optical properties, vii, 63, 64, 65, 66, 84, 89, 90, 93,
56, 57, 262, 264, 265, 268, 274, 276, 292, 297,
96, 102, 104, 107, 111, 115, 206
298, 299, 320, 361, 367
optoelectronics, 63
perchlorate, 251, 255, 257, 258
ores, 326, 351
Periodic Table, 348, 351, 352
organ, viii, 16, 169, 194, 269, 302, 304, 357, 359,
peripheral neuropathy, 264
382, 383, 384, 385, 386, 388, 390, 392, 393, 394,
permeability, 61, 362
397, 400, 401, 403, 405, 406, 408, 411, 412, 414,
pernicious anemia, 16
415, 416, 419, 420
perovskite oxide, 200
organic compounds, 194, 266, 297, 299, 300, 303,
peroxidation, 48, 266, 280, 282, 355, 356, 357, 359,
304, 305, 308, 309, 315
360, 362, 363
organic matter, 332
peroxide, 22, 29, 34, 56, 348, 355, 356
organic solvents, 339
petroleum, 174, 278, 320
organism, 262, 271
pH, 8, 13, 18, 27, 28, 34, 39, 57, 172, 180, 181, 185,
organometallics, viii, 2
263, 264, 276, 277, 278, 279, 281, 284, 285, 298,
organs, 269, 354, 358, 359, 363, 365
315, 318, 341, 359, 473
orthogonality, 200, 232, 234
pharmaceutics, 281
oscillation, 155, 157
pharmacology, 278, 279
osmium, 406
phase decomposition, 143, 144
osteoporosis, 267
phase diagram, 118, 142, 145, 150
overlap, 177, 200, 229, 231, 232, 244, 245, 303
494 Index
phase transformation, 143 polymer synthesis, viii

phase transitions, 146 polymerase, 352
phenol, 281, 282 polymeric chains, 225, 227, 234
phenolic compounds, 18 polymerization, viii, 257
phenotype, 10, 15, 272 polymers, 37, 66, 275, 305, 313, 330, 381, 399, 457
phenoxyl radicals, 281, 283 polynuclear complexes, 195, 220, 235, 257
Philadelphia, 43 polypeptide, 23
phosphate, 22, 49, 195, 265, 277, 278, 370 polypeptides, 263
phosphates, 19, 48, 316, 353, 377 polyphenols, 353
phosphoenolpyruvate, 12 polystyrene, 173
phospholipids, 19, 48, 264, 348, 355, 356, 359, 360 polyunsaturated fat, 33
phosphorous, 1, 2, 316, 370, 375 polyunsaturated fatty acids, 33
phosphorus, 9, 193, 369, 370, 371, 372, 373, 374, population, 11, 21, 38, 51, 52, 54, 340, 475
375, 376 porosity, 135, 140, 317
phosphorylation, 32, 57, 259, 264, 268, 361, 363 porphyrins, 416
photonics, 64, 111 positrons, 155, 156
photons, 89, 92, 95, 155, 359 potassium, 1, 276, 326, 328, 336, 341, 349, 418, 455,
photosynthesis, 3 457
physical characteristics, 160, 161 power lines, 349
physical mechanisms, 157 power plants, 119
physical properties, 148, 152, 311, 386, 404, 454 precipitation, 24, 25, 28, 34, 143, 144, 145, 146, 150,
physicochemical characteristics, 281 153, 327, 335, 372, 462, 464, 466, 469, 470, 471,
physicochemical properties, 49, 350 473, 477
physics, 119, 220 premature breast fed infants, 13
physiology, 291, 353 premature infant, 12
PI3K, 32 preparation, iv, 4, 64, 177, 181, 187, 202, 332, 333,
pigmentation, 349 335, 369, 370, 375, 382, 383, 386, 390, 397, 399,
pituitary gland, 52 406, 408, 414, 420, 422
placebo, 32 principles, 43, 98, 116, 263, 303, 313, 314, 318, 364
plant growth, 42 prions, 269
plants, 1, 2, 3, 5, 11, 12, 18, 20, 47, 342 probability, 39, 140, 156, 402, 414
plaque, 26, 29, 54 probe, 67, 278, 279
plasma membrane, 9, 348, 354 professionals, 47
plasticity, 39, 60, 220, 228, 230, 251 progesterone, 292
plastics, 327, 334, 335 progressive neurodegenerative disorder, 23
platinum, 2, 274, 276, 283, 284, 285, 286, 287, 303, project, 33
350, 354, 386, 389, 390, 391, 397, 400, 404, 405, proliferation, 22, 270, 332, 360, 363
406, 407, 408, 411, 417, 418, 424, 426, 429, 430, promoter, 21, 268
433, 436, 441, 442, 444, 445, 446, 448, 449 propagation, 87, 107, 244, 245, 353, 355, 359
point defects, 86, 117, 118, 126, 127, 130, 131, 132, propane, 251
133, 135, 137, 140, 141, 155, 156, 157, 158, 159, propylene, 309
160 protease inhibitors, 283
point mutation, 22 protective coating, 332
poison, 125 protective role, 37, 38
polarity, 300, 304 protein folding, 291
polarizability, 5, 316 protein kinase C, 13, 61
polarization, 66, 84, 272 protein kinases, 17, 363
pollutants, 8, 298 protein misfolding, 53
polyamine, 283, 309 protein oxidation, 23, 273, 361, 364
polyamines, 163, 165 proteinase, 3
polydimethylsiloxane, 304 proteins, 2, 6, 7, 9, 13, 14, 18, 19, 23, 24, 29, 31, 36,
polymer, viii, 37, 173, 174, 183, 251, 254, 298, 302, 38, 43, 48, 51, 60, 250, 262, 264, 265, 268, 269,
304, 315, 337, 339 270, 271, 272, 273, 274, 275, 278, 279, 291, 297,
Index 495
299, 315, 316, 318, 319, 320, 330, 347, 352, 353, reagents, 308
354, 355, 357, 360, 364, 365, 367 reasoning, 459
proteolysis, 271 receptors, 11, 14, 29, 31, 42, 50, 56, 262, 288
proteomics, 320 recognition, 64, 195, 292, 314
protons, 172, 263 recombination, 117, 118, 126, 127, 129, 130, 131,
psychiatric disorders, 23 132, 133, 134, 135, 137, 140, 141, 155, 156, 157,
publishing, 42 158, 159, 160
pumps, 353 recovery, 49, 267, 298, 311
purification, 123, 126, 291, 318, 319, 320 recrystallization, 120, 122, 123, 124, 125, 126, 127,
purines, 15 128, 129, 130, 132, 133, 136
purity, 133, 298, 310 recycling, 9, 174, 175, 350
red blood cells, 13, 24, 341
redistribution, 104, 151, 362
Q redox groups, 399
refractive index, 64, 66, 91, 106, 107, 108
quantum well, 65
refractive indices, 64
quantum yields, 261
regenerate, 30
quinolinic acid, 225 regeneration, 318
quinone(s), 34, 35, 36, 37, 58 relaxation process, 261
relaxation processes, 261
R relevance, 55, 59, 61, 220, 278, 279, 366
repair, 18, 19, 22, 49, 265, 266, 267, 268, 284, 340,
racemization, 311 341
radiation, 85, 88, 89, 91, 93, 94, 95, 97, 98, 99, 106, replication, 21, 291, 341
107, 110, 117, 118, 119, 120, 121, 122, 124, 126, requirements, 3, 42, 137, 187, 286, 335
127, 128, 129, 132, 135, 136, 137, 140, 141, 142, researchers, 27, 28, 37, 174, 205, 208, 268, 270, 276,
152, 155, 157, 158, 159, 160, 161, 267, 289, 337, 473, 477
346, 371 residues, 2, 10, 23, 26, 27, 30, 31, 36, 55, 274, 281,
radiation damage, 119, 120, 126, 128, 132, 135, 136, 282, 286, 292
140, 141, 157, 160 resins, 334
radiation therapy, 267 resistance, 11, 43, 64, 117, 118, 119, 135, 137, 150,
radical formation, 29, 49, 61, 270, 355, 356 152, 155, 157, 158, 159, 160, 161, 285, 330, 331,
radical reactions, 50, 268, 288, 353, 366 332, 334, 341
radicals, 10, 20, 22, 29, 30, 34, 35, 37, 38, 41, 42, 49, resolution, 311, 314
55, 56, 249, 264, 267, 268, 274, 348, 354, 355, respiration, 270, 347, 352, 361, 367
356, 357, 364, 365, 460 response, 19, 38, 49, 64, 91, 107, 172, 268, 281, 340,
radius, 87, 93, 97, 99, 107, 132, 157, 280, 301, 333, 341, 367, 386, 389, 399
351 restrictions, 39, 327
random media, 64, 110 restructuring, 146
raw materials, 327, 335, 337 retardation, 270, 273
reaction center, 6, 342, 453, 471 reticulum, 278, 279
reaction mechanism, viii, 11, 355, 398 reusability, 174
reaction medium, 172, 353 rhenium, 406, 418
reaction rate, 350, 360 rheumatoid arthritis, 274
reaction temperature, 327 rhodium, 253, 254, 304, 312, 313, 350, 404, 417
reaction time, 335, 394 rings, 25, 26, 120, 121, 227, 240, 247, 405
reactive groups, 22, 193, 299, 382 risk, 15, 17, 19, 21, 22, 23, 24, 38, 46, 48, 50, 59, 60,
reactive oxygen, 11, 21, 22, 24, 28, 29, 34, 36, 39, 264, 266, 268, 350, 366
44, 50, 281, 339, 354, 355, 359, 360, 362, 363, risk factors, 60, 264, 366
367 RNA, 11, 13, 28, 270, 281, 352, 354
reactivity, vii, viii, 6, 14, 22, 176, 250, 261, 264, rodents, 340
271, 285, 288, 316, 344, 353, 364, 451, 452, 453, ROOH, 355, 356, 357
457, 459, 460, 462, 466, 469, 470, 471, 473, 477
496 Index
room temperature, 122, 149, 167, 172, 187, 191, 197, silver, 63, 65, 84, 88, 89, 90, 95, 97, 99, 100, 101,
333, 336, 393, 409 102, 104, 106, 107, 302, 303, 305, 348, 386, 390,
roots, 13 393, 394, 397, 401, 403, 408, 411, 412, 416
rural areas, 38 sinusitis, 270
ruthenium, 390, 403, 404, 410, 418, 434, 443, 447 SiO2, 67, 69, 70, 71, 72, 73, 74, 77, 78, 79, 80, 81,
rutile, 338 82, 83, 85, 86, 87, 88, 89, 90, 91, 92, 93, 95, 96,
100, 107, 108, 109, 110, 328, 329
skeleton, 12, 23, 251, 387
S skin, 13, 21, 265, 267, 269, 273, 339, 342
small intestine, 10, 273
salicylates, 269 SO42-, 3
salts, 4, 21, 172, 184, 196, 219, 224, 225, 256, 268, society, 452, 478
274, 277, 304, 305, 330, 339, 349, 394, 417, 455, sodium, 1, 34, 49, 65, 121, 276, 326, 327, 331, 335,
457, 459 336, 349, 406, 455, 457
sapphire, 97, 106 solar cells, 350
saturated fat, 350 solid matrix, 104
saturation, 21, 66, 95, 110, 133, 156 solid solutions, 155, 333, 338, 339, 345
scandium, 347, 351 solid state, 163, 168, 172, 183, 197, 334, 335, 394,
scattering, 89 398, 402, 404, 405, 411, 413, 421
scavengers, 10 solid tumors, 267
Schiff base ligands, 163, 164, 165, 166, 185, 189, solubility, 14, 123, 124, 136, 261, 262, 265, 280,
193, 196 328, 340, 341, 454, 459
science, viii, 34, 64, 111, 119, 157, 220 solvation, 26, 263
secondary radiation, 117, 118, 129, 134, 137, 141, solvent molecules, 196
160, 161 solvents, viii, 183, 193, 398, 454
secretion, 32, 57 sorption, 315
segregation, 135, 137 spatial learning, 57
selectivity, 164, 175, 262, 263, 285, 293, 304, 305, speciation, 42, 278, 279
315, 317, 373, 374, 375, 376 specific adsorption, 317
selenium, 1, 4, 5, 6, 24, 352, 366 specific surface, 350
self-assembly, 26, 183 specifications, 327, 328
self-organization, 117, 119, 161 spectroscopic techniques, 39
semiconductor, 64, 65, 66, 67, 89, 97, 349 spectroscopy, viii, 28, 29, 30, 39, 54, 60, 61, 67, 110,
semiconductors, 347, 349, 459 176, 189, 251, 252, 254, 257, 258, 277, 278, 285,
sensitivity, 17, 107, 340, 342, 452, 453, 454, 455, 421, 469
477 spin, 21, 29, 39, 166, 167, 173, 184, 187, 195, 196,
sensors, 262 197, 198, 202, 203, 229, 234, 239, 243, 245, 251,
septum, 342 261, 280, 281, 353, 359, 476
serotonin, 33, 37 spine, 25, 53
serum, 8, 12, 17, 21, 24, 47, 52, 57, 268, 270, 289, spleen, 38
315, 319 stability, 85, 117, 119, 137, 161, 261, 262, 272, 281,
serum ferritin, 21 283, 300, 301, 302, 303, 316, 318, 330, 336, 337,
shape, 101, 104, 121, 155, 220, 283 338, 339, 382, 383, 451, 452, 453, 457, 458, 471,
showing, 31, 35, 65, 140, 299, 300, 400, 405 473
sickle cell, 270 stabilization, 131, 158, 258, 271, 272, 278, 279, 286,
side chain, 26, 28, 197, 236, 259, 271, 272, 319 335, 382, 390
side effects, 276 stabilizers, 262, 353
sideroblastic anemia, 290 stable complexes, 308, 330
signal transduction, 13, 29, 270, 363 standard deviation, 457
signaling pathway, 22, 341 steel, 120, 122, 123, 124, 125, 126, 127, 129, 130,
silica, 66, 175, 298, 302, 304, 305, 308, 309, 315, 133, 134, 135, 136, 141, 332, 349
347 stimulus, 477
silicon, 1, 4, 5, 6, 46, 65, 130, 327, 350 stoichiometry, 26, 54, 200, 224, 344, 394, 416
Index 497
stomach, 269, 342 techniques, vii, 63, 64, 297, 298, 299, 313, 314, 318,
storage, 6, 7, 8, 264, 291, 352, 354, 360, 362, 382 320
stress, 10, 27, 29, 37, 40, 41, 51, 58, 271, 278, 279, tellurium, 366
300, 305, 350, 359, 361, 362, 363, 365, 366 temperature dependence, 26
stretching, 177, 349 temporal lobe, 24, 29
striatum, 33, 34, 61 tension, 119, 126, 138, 139, 140
stromal cells, 292 teratogen, 363
strong interaction, 244, 303 ternary oxides, 333
strontium, 328, 329 terpenes, 303
structural changes, 149, 150, 281, 302 testing, 120, 140, 141, 276, 331, 332
structural characteristics, 27 testosterone, 14
structural transformations, 61, 149, 159 tetrahydrofuran, 397, 401, 403, 404, 409, 419, 421
substitution, 118, 130, 133, 135, 176, 283, 301, 302, textiles, 327, 331
333, 334, 338, 344, 405, 408, 473 TFE, 28
substitution reaction, 176 therapeutic benefits, 31
substrate, 63, 90, 93, 94, 95, 97, 99, 262, 263, 273, therapeutic interventions, 261, 288
282, 283, 353, 471 therapeutics, 2, 295
substrates, 18, 93, 194, 196, 263, 460, 467, 468, 469 therapy, 2, 12, 28, 32, 44, 51, 262, 267, 270, 276,
sulfate, 276, 277, 326, 327, 329 283
sulfonamides, 273 thermal aging, 158
sulfur, 2, 5, 14, 15, 174, 271, 275, 280, 316, 330, thermal analysis, 176
352, 356, 370, 376, 391 thermal decomposition, 200
sulphur, 1, 2, 11, 16, 28, 168, 171, 173, 197, 257, thermal energy, 157
280, 307, 356 thermal resistance, 304, 305
Sun, 45, 54, 253, 320, 324, 378, 429, 435, 441, 446 thermal stability, 312, 457, 458
supplementation, 17, 24, 30, 47, 273 thermal treatment, 104
surface area, 63 thermogravimetric analysis, 194
surface energy, 157 thermomechanical treatments, 121, 135
surface layer, 121 thymine, 284, 285
surface properties, 97 thymus, 49, 291
surface structure, 357 thyroid, 267, 271, 291
survival rate, 267 time resolution, 342
susceptibility, 18, 33, 64, 66, 84, 93, 94, 95, 99, 107, tin, 67, 193, 254, 330, 349
108, 132, 177, 183, 187, 258, 266, 268 tissue, 9, 11, 19, 22, 23, 25, 29, 32, 33, 34, 37, 44,
sustainable development, 452 45, 48, 50, 266, 267, 274, 276, 341, 342, 348,
swelling, 41, 119, 126, 127, 138, 157, 318, 342 352, 353, 354
symmetry, 164, 181, 220, 229, 230, 239, 242, 243 titanium, 138, 139, 160, 193, 337, 349, 389, 393,
synapse, 362 411, 416, 418
synergistic effect, 117, 283 toluene, 407
synthesis, vii, viii, 3, 59, 63, 64, 65, 66, 111, 163, tones, 332
164, 167, 173, 175, 176, 193, 195, 196, 200, 201, topology, 233, 234, 243
219, 221, 255, 259, 261, 263, 265, 268, 269, 270, total cholesterol, 264
276, 311, 330, 340, 344, 382, 383, 384, 390, 391, toxic effect, 12, 269, 278, 342, 353, 355, 359, 361
398, 399, 400, 405, 407, 409, 413, 414, 415, 418, toxic metals, 7, 363
419, 420, 421, 459 toxicity, 6, 9, 12, 15, 17, 18, 21, 26, 27, 28, 29, 31,
synthetic polymers, 330 32, 36, 37, 40, 42, 44, 45, 46, 53, 54, 55, 56, 58,
60, 261, 262, 265, 266, 268, 276, 277, 278, 279,
285, 288, 289, 290, 294, 339, 340, 348, 350, 353,
T 354, 355, 357, 358, 359, 360, 361, 362, 363, 364,
365, 451
T cell, 292
toxicology, 48, 278, 279
target, 10, 23, 262, 265, 278, 279, 281, 285, 286, 318 toxin, 33
target organs, 23, 265
trace elements, 1, 4, 5, 44, 47, 52, 290, 352, 353, 364
tau, 23, 27, 32, 57, 362
498 Index
trafficking, 295 vanadium, 1, 2, 4, 5, 6, 17, 18, 19, 41, 46, 47, 48, 49,
transactions, 345 160, 166, 200, 203, 276, 277, 278, 279, 293, 294,
transcription factors, 13, 14, 270, 291, 360, 365 304, 325, 334, 348
transferrin, 2, 8, 11, 12, 17, 21, 45, 50, 264, 267, vapor, 325
281, 352, 361 vascular dementia, 367
transistor, 65 vascular diseases, 366
transition elements, vii, 2, 34, 158, 189, 351 velocity, 93, 359, 456
transition metal ions, viii, 168, 176, 187, 195, 197, versatility, 165, 349
262, 291, 299, 348, 354, 355, 357, 363, 364 vibration, 344
transmittance spectra, 85, 95 vitamin A, 46
transport, 6, 7, 8, 10, 12, 23, 38, 43, 44, 45, 46, 220, vitamin B1, 3, 16, 194, 353
264, 265, 267, 268, 269, 275, 284, 286, 342, 347, vitamin B12, 3, 16, 194, 353
352, 360, 362, 365, 366, 387 vitamin B3, 264
transportation, 25 vitamin C, 9, 38, 268
transversion mutation, 22 vitamin D, 14
treatment, 2, 11, 13, 26, 32, 60, 122, 128, 131, 168, vitamin K, 46
187, 262, 266, 267, 268, 269, 270, 273, 274, 277, vitamins, 47
278, 293, 326, 331, 333, 340, 342, 354, 358, 361, VOCl3, 169
374, 393, 394, 397, 400, 404, 406, 408, 411, 413, volatility, 305, 308
416 vomiting, 354
tricarboxylic acid, 414 VSD, 67, 73, 81
triggers, 362, 367, 452
triglycerides, 264
triphenylphosphine, 276, 441 W
tryptophan, 38
tumor cells, 21, 269 waste, 339
tumor development, 11, 44 wastewater, 339, 345
tumor growth, 21, 50, 267 water vapor, 350
tungsten, 47, 325, 349 wave vector, 87
turnover, 8, 34, 58, 271 wavelengths, 84
type 2 diabetes, 17, 47 weak interaction, 241, 299
tyrosine, 28, 38, 258, 259 weakness, 267
weight gain, 264
weight loss, 264
U weight ratio, 330, 337
welding, 49
ulcer, 266, 269, 339 WHO, 46, 47
ultrafast time response, 64 wires, 102, 349
urea, 12 wood, 327, 331
uric acid, 15 wool, 330
urine, 15, 17, 47 workers, 19, 21, 48, 50, 165, 171, 173, 176, 187,
uterus, 274 189, 311, 342, 346
uti, 50 workforce, 19
UV, 42, 63, 86, 166, 174, 176, 186, 189, 193, 196, World Health Organization, 47
205, 332, 335, 339, 434, 464, 466, 467, 468, 469 worldwide, 23, 33, 286
wound healing, 266, 273
V
X
valence, 151, 182, 301, 338, 382, 384, 387, 392, 393,
457, 464 X-ray analysis, 223
valine, 311, 312 X-ray diffraction (XRD), 333, 335, 338, 339, 397
X-ray photoelectron spectroscopy (XPS), 338, 369,
370, 371, 376, 377, 378
Index 499
zinc, 1, 2, 4, 5, 7, 8, 9, 13, 14, 17, 19, 23, 27, 29, 31,

Y 32, 34, 37, 42, 43, 44, 46, 48, 50, 51, 52, 53, 54,
56, 57, 180, 181, 183, 253, 267, 268, 269, 270,
yeast, 11, 45
271, 272, 273, 274, 289, 290, 291, 292, 305, 308,
yield, 22, 28, 84, 176, 199, 282, 335, 342, 357, 398,
310, 315, 327, 328, 329, 332, 336, 337, 340, 343,
404, 406, 408, 409, 410, 418, 419
345, 348, 366
zinc deficiency disorder, 13
Z zinc oxide, 337
zirconium, 193, 390
zeolites, 305 ZnO, 75, 76, 329, 336, 337, 350
zwitterions, 223

Transition Metals Characteristics Properties and Uses PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Transition Metals Characteristics Properties and Uses PDF

Uploaded by

Copyright:

Available Formats

CHEMICAL ENGINEERING METHODS AND TECHNOLOGY

CHARACTERISTICS, PROPERTIES AND USES

Additional books in this series can be found on Nova’s website

Additional E-books in this series can be found on Nova’s website

MATERIALS SCIENCE AND TECHNOLOGIES

Additional books in this series can be found on Nova’s website

Additional E-books in this series can be found on Nova’s website

CHARACTERISTICS, PROPERTIES AND USES

AJAY KUMAR MISHRA

Nova Science Publishers, Inc.

NOTICE TO THE READER

Library of Congress Cataloging-in-Publication Data

Published by Nova Science Publishers, Inc. † New York

Chapter 10 Hydrodesulfurization of Dibenzothiophene over Various

ROLE OF REACTIVITY OF TRANSITION

Mohamed Fikry Ragai Fouda1, Omar Mohamed Abdel-Salam2

TRANSITION METALS AND PLANTS

Table 1. Functions of several micronutrients in higher plants

Micronutrients Functions in higher plants

CHEMICAL ELEMENTS IN LIFE

Table 2. The concentration of selected elements in the human body [6,7]

Element Concentration in body Concentration in

NUTRITIONALLY ESSENTIAL AND NON-ESSENTIAL METALS

Table 3. Nutritionally essential and non-essential elements

Nutritionally essential Elements with possible Elements with no known

THE BIOLOGICAL VALUES OF IRON, COPPER, MANGANESE,

involved in both metal-catalyzed (“auto”) oxidations and reactions leading to hydroxy1

Fe2++ H2O2 →Fe3+ +•OH +OH-

Net : O2-+H2O2 + Fe salt catalyst →O2+•OH+OH-

Vanadium, a dietary micronutrient, is yet to be established as an essential part of the

Nickel is widely distributed in the environment. Natural sources of atmospheric nickel

TRANSITION METALS AND HUMAN DISEASE

vanadium(III) trioxide, vanadium(IV) tetraoxide, or vanadium(V) pentoxide (V(2)O(3),

V(ΙV)+ H2O2→ V(V) +•OH+OH-

Cr(ΙΙ)+ H2O2→ Cr(ΙΙΙ) +•OH+OH-

Cr(V)+ H2O2→ Cr(VΙ) +•OH+OH-

dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints,

Role of Transition Elements in Some Neurodegenerative Diseases

TRANSITION METALS AND ALZHEIMER'S DISEASE

Amyloid Beta Protein (Aβ) Deposition in the Brain is a Hallmark of

The analysis of the assembly pathway of Aβ in vitro and biochemical characterization of

Monomeric Aβ + metal ions → Dimers → Oligomers→Protofibrills→Amyloid

The N-terminal region of Aβ can access different metal-ion-coordination environments

TRANSITION METALS, Aβ AND OXIDATIVE STRESS

METAL BRAIN LOWERING IN ALZHEIMER'S DISEASE

A recent placebo-controlled trial in 36 patients with Alzheimer’s disease showed that

TRANSITION METALS AND PARKINSONS'S DISEASE

Dopamine [2-(3,4-dihydroxyphenyl)-ethylamine] is a neurotransmitter that plays an

Figure 3. Dopamine and Dopaminochrome.

Normally, GSSG is efficiently reduced by glutathione reductase. The ratio of oxidized to

NaOCl + H2O2 → 1O2 + NaCl + H2O

Fiigure 5. Metaboolism of DA leaads to the formaation of several cytotoxic moleecules, includingg

Brain metaabolism generaates excess H2O2, not only via

and generate substantial H2O2 in the brain [288].

Oxidation of dopamine to an o-quinone and its subsequent product, aminochrome (2,3-

Neuromelanin (NM) is a dark pigment polymer belonging to the family of melanins.

THE ROLE OF IRON

Fe accumulation in the SNc of patients with Parkinson's disease is particularly important

ROLE OF OTHER TRANSITION METALS

binding mode at pH 7.4 involved coordination of His50 and its g and A

Figure 7. Oxidative DNA damage induced by dopamine oxidation [332].

Dopamine oxidation by Mn is a potential mechanism for Mn-induced oxidative stress,

Figure 8. Manganese induced dopamine oxidation [334].