Introduction

On Life and Chemistry…..

• “Living things are composed of lifeless

molecules” (Albert Lehninger)

• “Chemistry is the logic of biological

phenomena” (Garrett and Grisham)
 Distinctive Properties of Living Systems

• Organisms are complicated and highly

organized
• Biological structures serve functional
purposes
• Living systems are actively engaged in
energy transformations
• Living systems have a remarkable
capacity for self-replication

A Biomolecular Hierarchy

Simple Molecules are the Units for Building

Complex Structures

• Metabolites and Macromolecules

• Organelles
• Membranes
• The Unit of Life is the Cell
Molecular organization
in the cell is a hierarchy.

Chemistry 40 (Summer 2007)

Properties of Biomolecules Reflect Their Fitness to

the Living Condition

• Macromolecules and Their Building Blocks

Have a “Sense” or Directionality
• Macromolecules are Informational
• Biomolecules Have Characteristic Three-
Dimensional Architecture
• Weak Forces Maintain Biological Structure
and Determine Biomolecular Interactions
 Chemistry 40 (Summer 2007)

The sequence of monomeric units in a biological polymer has the potential to contain
information if the diversity and order of the units are not overly simple or repetitive. Nucleic
acids and proteins are information-rich molecules; polysaccharides are not.

IN008

Chemistry 40 (Summer 2007)

 Properties of Biomolecules Reflect Their Fitness to
the Living Condition

• van der Waals: 0.4-4.0 kJ/mole

• Hydrogen bonds: 12-30 kJ/mole
• Ionic bonds: 20 kJ/mole
• Hydrophobic interactions: <40 kJ/mole

Chemistry 40 (Summer 2007)

 Organization and Structure of Cells

• Prokaryotic cells
– A single (plasma) membrane
– no nucleus or organelles
• Eukaryotic cells
– much larger in size than prokaryotes
– 103-104 times larger!
– Nucleus plus many organelles
– ER, Golgi, mitochondria, etc.

Methods for Separating and Purifying

Biomolecules

• Salt fractionation • Electrophoresis –

(precipitation of paper, high voltage,
proteins with agarose, cellulose
ammonium sulfate) acetate, starch gel,
• Chromatography – polyacrylamide gel,
paper, ion-exchange, SDS-PAGE
affinity, thin-layer, • Ultracentrifugation
gas-liquid, high
pressure liquid, gel
filtration
 Methods for Determining Biomolecular
Structures

• Elemental analysis • X-ray crystallography

• UV-VIS, IR, NMR
spectroscopy
• Acid/base hydrolysis
• Enzymatic
degradation
• MS
• Specific sequencing
methods

Preparations for Studying Biochemical

Processes

• Whole animal • Subfractionation of

(transgenic and with organelles
gene knockout) • Purified metabolites
• Isolated perfused and enzymes
organ • Isolated genes (PCR
• Tissue slice and site-directed
• Whole cells mutagenesis)
• Homogenate
• Isolated cell
organelles
 Major Causes of Diseases

All of the causes listed act by influencing the various

biochemical mechanisms in the cell or in the body.
• Physical agents –
mechanical trauma,
extremes of T,
sudden changes in
atmospheric P,
radiation, electric
shock
• Chemical agents,
including drugs:
certain toxic
compounds,
therapeutic drugs,
etc.
• Biologic agents:
viruses, bacteria,
fungi, higher forms of
parasites

Major Causes of Diseases

• Oxygen lack: loss of • Immunologic

blood supply, reactions –
depletion of the anaphylaxis,
oxygen carrying autoimmune disease
capacity of the blood, • Nutritional imbalances
poisoning of the – deficiencies,
oxidative enzymes excesses
• Genetic disorders – • Endocrine imbalances
congenital, molecular – hormonal
deficiencies,
excesses
 Water

What Are the Properties of Water?

• High b.p., m.p., heat of vaporization,

surface tension
• Bent structure makes it polar
• Non-tetrahedral bond angles
• H-bond donor and acceptor
• Potential to form four H-bonds per water
 The Solvent Properties of Water Derive from Its
Polar Nature

• Ions are always hydrated in water and carry

around a "hydration shell"
• Water forms H-bonds with polar solutes
• Hydrophobic interactions - a "secret of life"

Hydration shells
surrounding ions in
solution. Water
molecules orient so
that the electrical
charge on the ion is
sequestered by the
water dipole. For
positive ions (cations),
the partially negative
oxygen atom of H2O is
toward the ion in
solution. Negatively
charged ions (anions)
attract the partially
positive hydrogen
atoms of water in
creating their hydration Chemistry 40 (Summer 2007)
shells.
 Hydrophobic Interactions

• A nonpolar solute "organizes" water

• The H-bond network of water reorganizes to
accommodate the nonpolar solute
• This is an increase in "order" of water
• This is a decrease in ENTROPY

Formation of a clathrate structure by water molecules

surrounding a hydrophobicChemistry
solute. 40 (Summer 2007)
 Acid-base Equilibria

The pH Scale

• A convenient means of writing small

concentrations:
• pH = -log10 [H+]
• If [H+] = 1 x 10 -7 M
• Then pH = 7

Dissociation of Weak Electrolytes

Consider a weak acid, HA

• The acid dissociation constant is given by:

• HA → H+ + A-
• Ka = [ H + ] [ A - ]
____________________

[HA]
 The Henderson-Hasselbalch Equation

For any acid HA, the relationship

between the pKa, the concentrations
existing at equilibrium and the
solution pH is given by:
• pH = pKa + log10 [A¯ ]
[HA]

Consider the Dissociation of Acetic Acid

Assume 0.1 eq base has been added to a

fully protonated solution of acetic acid
The Henderson-Hasselbalch equation can be
used to calculate the pH of the solution:

With 0.1 eq OH¯ added:

•pH = pKa + log10 [0.1]

[0.9]
•pH = 4.76 + (-0.95)
•pH = 3.81
 Consider the Dissociation of Acetic Acid

• Another case....
• What happens if exactly 0.5 eq of base is
added to a solution of the fully protonated
acetic acid?
• With 0.5 eq OH¯ added:
• pH = pKa + log10 [0.5]
[0.5]
• pH = 4.76 + 0
• pH = 4.76 = pKa

Consider the Dissociation of Acetic Acid

A final case to consider....

What is the pH if 0.9 eq of base is added to a
solution of the fully protonated acid?
With 0.9 eq OH¯ added:

pH = pKa + log10 [0.9]

[0.1]
pH = 4.76 + 0.95
pH = 5.71
The titration curve
for phosphoric
acid. The
chemical formulas
show the
prevailing ionic
species present at
various pH values.
Phosphoric acid
(H3PO4) has three
titratable
hydrogens and
therefore three
midpoints are
seen: at pH 2.15
(pK1), pH 7.20
(pK2), and pH 12.4
(pK3).

Chemistry 40 (Summer 2007)

What Are Buffers, and What Do They Do?

• Buffers are solutions that resist changes in

pH as acid and base are added
• Most buffers consist of a weak acid and its
conjugate base
• Buffers can only be used reliably within a
pH unit of their pKa