Gent 2001

Cyclodextrins
An Overview

Matthias Arensktter
Florence Folmer
Chris Llewellyn
Aurlie Pardo
Frank Reinecke
Grazia Trebbi

Cyclodextrins - An Overview
1. Introduction
2. Microbial Production
3. Purification And
Fractionation
4. Properties
5. Applications

Introduction
Cyclodextrins (CDs) are torus shaped cyclic
oligomers consisting of 6 (),7 () or 8 (-CD)
glucose units with -1,4-linkages with a
hydrophobic cavity Oand a hydrophilic exterior
CH2OH
O

OH

CH OH
O 2
HO

HO

O
OH
O

OH

CH2OH

OH

OH

HO

O
HO
O

OH
OH
CH2OH O

HO

CH2OH
O

CH2OH

Introduction
History:
1891 Discovery, Villiers
1903 Descriptions of properties, Shardinger
1939 Tilden and Hudson were able to show that
the conversion of starch to CD was due to the
action of an enzyme, CD Glycosyl-Transferase
(CGTase), which was secreted into the culture
medium.

Introduction
1957 Complexation ability of CDs widely
accepted; Cramer, French
1981 First International Symposium on
CDs, Szejtli
1987 Total synthesis, Ogawa
1994 Total synthesis of
cyclo[D-Glcp(1->4)]5

Introduction
Today CDs are only synthesized either by
fermentation or enzymatically.
Many CGTases from different
microorganisms are known, cloned,
sequenced, characterized and used for
production of CDs.

Introduction
Applications:
Because of their unique properties CDs allow
packaging on a molecular level of various
molecules which is applied in pharmaceutics,
food and flavours etc...
Used in chromatographic columns CDs can
separate stereoisomers.
Derivatives of CDs can even be used to mimic
enzymes.

Cyclodextrins - An Overview
1. Introduction
2. Microbial Production
3. Purification And
Fractionation
4. Properties
5. Applications

Microbial Production
CGTases are produced by many different
bacterial species of the genus Bacillus but
also by Flavobacterium sp., Klebsiella
pneumoniae and Micrococcus sp.
Genes have been cloned and recombinantly
expressed in Escherichia coli and other
organisms, including for example Solanum
tuberosum (Potato).

Microbial Production
The CGTase acts on linear starch and
transfers a part of the chain (F) to its own
non-reducing end (A) as indicated in this
model:
E

A
C

starch

E
D

CGTase

F
A

-CD

Cyclodextrins - An Overview
1. Introduction
2. Microbial Production
3. Purification And
Fractionation
4. Properties
5. Applications

Purification and Fractionation

Enzymatic synthesized CDs are selectively
precipitated by organic solvents.

-CD
-CD
-CD

precipitating agent
1-decanol
toluene
cyclohexadec-8-en-1-ol

yield (%)
40
50-60
40-50

Cyclodextrins - An Overview
1. Introduction
2. Microbial Production
3. Purification And
Fractionation
4. Properties
5. Applications

Properties
Important Properties:
CDs have hydrophobic cavities of different sizes enabling
the complexation of hydrophic guest molecules.
These complexes represent a solution for insolubility.
They have neither a reducing nor a non-reducing end-group.

Properties
Stability:
CDs are not decomposed by hot aqueous alkali and rather resistant
to acid hydrolysis.
CDs are resistant to -amylases (except microbial enzymes) and
they are completely resistant to yeast-fermentation and
amylases.

Properties

Properties
Molecular weight
Glucose monomers
Internal cavity diameter
(angstroms)
Water solubility
(g/100mL: 25 deg. C)
Melting range (deg. C)
Water of crystallization
Water molecules in cavity
Cavity volume (ml/mol)
Price (US$/g pharma-grade)

972
6
4.7-5.3

1135
7
6.06.6

1297
8
7.58.3

14.2

1.85

23.2

255-260
10.2
6
174
1.0

255-265
13-15
11
262
0.025

240-245
8-18
17
472
0.8

Cyclodextrins - An Overview
1. Introduction
2. Microbial Production
3. Purification And
Fractionation
4. Properties
5. Applications

Applications
Pharmaceutical industry:
Treatment of inflammation or throat infection (with iodine)
Coronary dilatation (with nitroglycerin)
Anti-ulcerate (with benexate)
Vectors for vitamins or hormones
Reduction of side-effects and increase in efficiency of anti-cancer drugs

Applications
Solid
Complex

Pharmaceutical
Dissolution
(k )
industry:

Cyclodextrin
Competing
Agent

(kc)
Dissolved
Complex

(ki)

Adsorption
(ka)
Drug
Competing AgentCycloddextrin Complex

Biomembrane
Systemic Circulation
Drug

Applications
Cosmetics & Hygiene:
Long-lasting perfume release
Deodoriser (with peppermint oil, i.e.)
Removal of dryness wrinkles (with seaweed compounds, Vitamin A & E)
Anti-cellulitis compound
Shampoo industry
Teeth cleaning, anti-plaque compound
Antibacterial in refrigerators

Applications
Food industry:
Emulsion stabiliser
Taste-masking
Long-lasting flavouring
Removal of cholesterol from milk, butter, eggs, a.o.

Applications
Paint industry:
Increase in compatibility of paint ingredients
Increase in stability of the paint
Increase in the range of colours and in the quality of dyes

Applications
Environmental protection:
Reduction in oxidiser requirements in paper production
Environmentally friendly oil-spill clean-up
Treatment of tree-wounds (with auxin)
Mobilisation of toxins without leaving toxic residues behind
(innovative technique)

Applications
Environmental protection:
Removal or detoxification of waste material, esp.
aromatic pollutants
Use in agriculture to increase the stability and the
efficiency of herbicides, insecticides, repellents,

Applications
Chemical and biochemical applications:
Reaction catalyst in adhesives
Use in chromatography (separation of stereoisomers)
Increase in speed of diagnostic test reaction

Applications
Chemical and biochemical applications:
Enzyme mimicry

S
N

+ N
La
O
O O O
P
O
O

Dimer of -cyclodextrin linked on primary side by a metal-binding-group as catalyst of hydrolysis of a phosphate diester

O2N

NO2

Summary
When Cyclodextrins were discovered they were just a chemical
curiosity but today a lot of applications are known.
Due to intensive studies and advances in production procedures prices
continue to decrease making CDs attractive for many applications.
To date more than 3300 European Patents are registered indicating
great industrial interest.

Group Members
Matthias Arensktter, Westflische WilhelmsUniversitt Mnster, Germany
Florence Folmer, University of Wales Bangor, UK
Chris Llewellyn, University of Wales Swansea,
UK
Aurlie Pardo, Institue Nationale Polytechnique de
Toulouse, France
Frank Reinecke , Westflische WilhelmsUniversitt Mnster, Germany
Grazia Trebbi, Universita di Bologna, Italy