Molecular Biology

COURCE CODE: BIOL 498

LECTURER: ANTON IRVING

CLASSES: Tu/Th
Chapter 3: The Importance of
Weak Chemical Interactions
Lecture 4
Characteristics of Chemical Bonds
The Concept of Free Energy
Weak Bonds in Biological Systems
Introduction

Our study will focus on proteins and nucleic

acids. These are made of amino acids and
nucleotides, respectively.

In both cases the constituents are joined by

covalent bonds to make polypeptides – proteins;
and polynucleotides – nucleic acids.

Covalent bonds are strong, stable bonds,

however, weak bonds also exist.
introduction

Weak bonds mediate the interaction

between enzymes and their substrates, and
between macromolecules.
Between proteins and DNA and RNA.
Between proteins and other proteins.
Between different parts of the individual
macromolecule, determining the shape of
those molecules and their biological function.
Introduction

A protein is a linear chain of covalently linked

amino acids, its shape and function are
determined by its stable three dimensional
structure.
This is determined by weak interactions
between amino acids, adjacent or other wise.
Similarly, it is the weak, non-covalent bonds
that hold the two chains of a DNA double
helix together.
Types of Weak Bonds

These bonds include:

van der Waals bonds
hydrophobic bonds
hydrogen bonds
and ionic bonds
Characteristics of chemical bonds

The strength of a bond is correlated with its

length.
The two atoms connected by a strong bond are
closer together than the same two atoms held
together by a weak bond.
e.g.
Two covalently bonded hydrogen atoms (H:H)
are 0.74 Å apart.
Hydrogen atoms held by van der Waal forces are
1.2 Å apart.
The maximum number of bonds that a given
atom can make is:
Fixed for covalent bonds.
More flexible for van der Waal bonds, as it is
limited by purely steric factors.
The formation of hydrogen bonds is subject
to greater restrictions.
The number of covalent bonds that an atom
can form is know as its valency.
The angle between two bonds originating from a
single atom is called the bond angle.

The angle between two covalent bonds is always

the same.
Carbon atom with 4 single covalent bonds: bond
angle = 1090

In contrast, the angle between weak bonds is

variable.
Bonds differ in their freedom of rotation.

Single covalent bonds permit free rotation of bound

atoms.
Double bonds and triple bonds are quite rigid.
Partial double bonds, such as the peptide bond are also
quite rigid.
The carbonyl (C=O) and imino (N=C) groups of the
peptide bond are rigid and lie in the same plane.
In contrast, much weaker ionic bonds have no
orientation restrictions.
ROTATION ABOUT THE C-C IN THE PLANAR SHAPE OF PEPTIDE
ETHANE BOND
Chemical Bonds are explained in
quantum mechanical terms

All chemical bonds, weak or as well as strong,

are based on electrostatic forces.

Quantum mechanics provided explanation

for covalent bonding by the sharing of
electrons and also for the formation of
weaker bonds.
Chemical bond formation involves a
change in the form of energy

The spontaneous formation of a bond between two

atoms involves the release of energy.
The stronger the bonds, the greater amount of
energy released upon its formation.

A + B → AB + energy

AB represents the bonded molecule.

The unit used to measure energy is the calorie.
One calorie is the amount of energy required to raise the temperature of 1g
of water 10C.
Heat energy can break chemical bonds.
As the temperature of a collection of molecules is
increased, the stability of their bonds decreases.

AB + energy → A + B

The amount of energy that must be added to

break a bond is exactly equal to the amount that
was released upon formation of the bond.
Equilibrium between bond making and
breaking

Every bond is thus a result of the combination

actions of bond-making and bond-breaking forces.
When in equilibrium it can be expressed as:

Keq =

Where Keq is the equilibrium constant, and concA

and concB and concAB are the concentrations of A,
B, and AB.
The Concept of Free Energy

Free Energy (∆G): Energy that has the ability

to work.
The second law of thermodynamics tells us
that a decrease in free energy (∆G is
negative) always occurs in spontaneous
reactions.
The free energy lost as equilibrium
approached or is either expressed as heat or
used to increase the amount of entropy.
Keq is exponentially related to ∆G

The stronger the bond the greater the

change in free energy (∆G) that accompanies
its formation.
∆G = -RT ln Keq or Keq = e -∆G/RT

Where R is the gas constant, T is the absolute

temperature.
In short ∆G values as low as 2 kcal/mole can
drive a bond forming reaction to completion.
Covalent bonds are very strong

The ∆G values during the formation of

covalent bonds (hydrogen or oxygen) are
very large and negative in sign, usually -50 to
-100 kcal/mole.
Weak bonds in biological systems

They are van der Walls bonds, hydrogen bonds,

hydrophobic bonds, ionic bonds.

Weak bonds have energies between 1 and 7 kcal/mole.

Van der Walls bonds have energies of 1-2 kcal/mole.
Slightly greater than the kinetic energy of heat
motion which is 0.6 kcal/mole.
The energy of hydrogen and ionic bonds range
between 3-7 kcal/mole.
The distinction between polar and
nonpolar molecules

All forms of weak interactions are based on

attractions between electric charges.
Atoms that have a tendency to gain electrons are
called electronegative.
Atoms that have a tendency to give up electrons
are called electropositive.
Molecules (such as water) that have a dipole
moment are called polar molecules.
Dipole moment is a combination of separated
positive and negative charges.
Van der Waals Forces

Van der Waals bonds arises from a

nonspecific attractive force originating when
two atoms come close to each other.
It is due to the nearness (distance) of
molecules.
It operates between all types of molecules.
Nonpolar as well as polar.
There is also a van der Waal repulsive force,
which comes into play at short distance.
The repulsion is due to the overlap of the outer
negative electron shell of the atoms involved.
This distance is the van der Waals radius.
The strongest type of van der Waals contact arise
when a molecule contains a cavity exactly
complementary in shape to a protruding group of
another molecule, as in the case of an antigen
antibody reaction.
The binding energy can be as great as 20-30
kcal/mole.
Hydrogen Bonds

A hydrogen bond is formed between a donor

hydrogen atom with some positive charge
and a negative charged acceptor atom.
e.g. hydrogen atom of the amino group (-
NH2) attracted by the negatively charged
keto oxygen (-C=O) atom.
Hydrogen-bonded atoms may have a unit
charge (NH3+ or COO-).
Hydrogen Bonds

The most import biological hydrogen bonds

involve hydrogen atoms covalently bound to
oxygen atoms (O-H) or nitrogen atoms (N-H).
The negative acceptor atoms are usually
nitrogen or oxygen.
Hydrogen bond energies range between 3
and 7 kcal/mole.
Hydrogen bonds are weaker than covalent
bonds but stronger than van der Wall bonds.
Hydrogen Bonds

Hydrogen bonds, unlike van der Waals

bonds, are highly directional.
In the stronger hydrogen bonds, the
hydrogen atoms point directly at the
acceptor atom.
If they point more than 30 0 away, the bond
energy is much less.
Hydrogen bonds are much more specific than
van der Waals bonds.
Hydrogen Bonds
Approximate Bond Lengths of Biologically Important Hydrogen Bonds

Bond Approximate H Bond Length (Å)

O-H……..O 2.70 ± 0.10
O-H……..O- 2.63 ± 0.10
O-H……..N 2.88 ± 0.13
N-H……..O 3.04 ± 0.13
N+-H…….O 2.93 ± 0.10
N-H……..N 3.10 ± 0.13
Some Ionic bonds are Hydrogen Bonds

The electrostatic forces acting between

oppositely charged groups (COO- and NH3+) are
called ionic bonds. Their average bond energy in
an aqueous solution is about 5 kcal/mole.
In many cases, either an inorganic cation like
Na+, K+, or Mg2+ or anion Cl- or So42- neutralizes
the charge of ionized organic molecules.
However, they do not assist in determining the
shapes of organic molecules.
Weak Interactions Demand
Complementary Molecular Surfaces

Weak binding forces are effective only when

the interacting surfaces are close.
This closeness is only possible when the
molecules surfaces have complementary
structures. This is termed a lock-and-key
relationship.
There are many molecules with the necessary
symmetry to permit self-interaction.
Water is a prime example of this.
Water Molecules Form Hydrogen
Bonds

Water molecules rarely ionize to form H+ and

OH- ions.
They exist as polar H-O-H molecules with
both hydrogen and oxygen atoms forming
strong hydrogen bonds.
The hydrogen bonds are directed
tetrahedrally. The oxygen atom can bind to
two hydrogen atoms, and each hydrogen
atom (2) can bind to one adjacent oxygen.
Weak Bonds between Molecules in
Aqueous Solutions

Most molecules in aqueous solution will form

secondary bonds to other molecules.
Due to steric differences, a molecule will tend
to move until it is next to a molecule with
which it can form the strongest possible
bond.
Interactive energies as low as 2-3 kcal/mole
are sufficient to allow for strong secondary
bonds.
Organic Molecules that tend to form
Hydrogen Bonds are water soluble
The energy of hydrogen bonds is much
greater than that of van der Waals bond, thus
atoms will form hydrogen bonds I preference
to van der Waals bonds.
In a mixture of water and benzene, water
molecules form hydrogen bonds amongst
themselves, while benzene (non-polar)
molecules separate and form van der Waals
bonds.
Polar molecules such as glucose and
pyruvate, which contain a large number of
groups that form hydrogen bonds (=O or
OH), are soluble in water.
They interchange their hydrogen bonds with
the hydrogen bonds of water.
However, water-water hydrogen bonds are
thermodynamically preferred resulting in
limited solubility of polar organic molecules.
Hydrophobic Bonds stabilize
Macromolecules

The strong tendency of water to exclude

nonpolar groups is referred to as hydrophobic
bonding.

Hydrophobic bonds are important in

stabilization of proteins, complexes of
proteins with other molecules, and in the
partition of proteins into membranes.
Weak bonds attach enzymes to
substrates

Weak bonds are the basis by which enzyme

and their substrates initially combine.
Enzymes have notable affinity for their own
substrate.
The ∆G for enzyme-substrate reactions is
between 5 and 10 kcal/mole.
∆G is not exceptionally high, and the enzyme-
substrate complex can be made and broken
apart rapidly. This explains why enzymes can
function quickly. Not possible in stronger bond.
Weak Bonds Mediate most Protein-DNA
and Protein-Protein Interactions

Interaction between proteins and DNA, and

between proteins and proteins, lie at the
heart of how cells detect and respond to
signals, express genes, replicate, repair , and
recombine their DNA.