BONDING IN BIOMOLECULES

 Reversible molecular interactions are very

important in life.

 Weak, non-covalent forces play roles in:

Faithful replication of DNA,
The folding of proteins into intricate three-
dimensional forms,
The specific recognition of Substrates by
Enzymes and antigens by Antibodies,
The detection of signal molecules.
 There are bonds both between
biomolecules and within biomolecules.

 These are Intermolecular bonds and

Intramolecular bonds

 Types of bonds:
Covalent bond
Non-covalent bond
 Indeed, all biological structures and
processes depend on interplay of non-
covalent interactions as well as covalent
ones.
 Covalent bond is not important in daily
to daily movements of biomolecules as
it is a strong bond.

 It is difficult to build and to break.

 It is mostly found as an intramolecular

bond:

bond between C-C, C-H, N-H, C=O,

etc
 Non-covalent bonds are important bonds in
biological systems.

 They are easy to break and to build

without using much energy.

 They are affected by presence of water.

 These includes:
– Ionic bonds,
– Hydrogen bonds,
– Hydrophobic interactions and
– Van der Waals bonds

 These bonds/interactions differ in

geometry, strength and specificity.

 They are profoundly affected in different

ways by the presence of water.
 IONIC BOND
 This is a bond between oppositely charged
molecules.

 Negatively charged molecule forms a bond

with a positively charged molecule.

 This bond is a strong bond when not placed in

water but it is very weak when in water.

 Biological systems exists in water, hence it is

known as a weak bond.
 A charged group on a Substrate can attract an
oppositely charged group on an Enzyme.

 The Force (F) of ionic interaction is given by

Coulomb’s law:

F = q1q2
r 2D
 Whereby:
– q1 and q2 are the charges of two groups,
– r is the distance between them and
– D is the dielectric constant of the medium.

• Biological systems exists in water, hence it is known

as a weak bond.
 The attraction is strongest in a vacuum,
where D=1

 And is the weakest in a medium such as

water, where D= 80.

 This kind of attraction is also called

electrostatic bond, salt linkage,
salt bridge or ion pair.

 The distance between oppositely charged

atoms in an optimal electrostatic
attraction is about 2.8A
Dielectric constants of some solvents at 20 oC

Substance Dielectric constant

Hexane 1.9
Benzene 2.3
Diethyl ether 4.3
Chloroform 5.1
Acetone 21.4
Ethanol 24
Methanol 33
Water 80
Hydrogen cyanide 116
 HYDROGEN BOND
 This is a bond formed when hydrogen atom
is shared by two other atoms.

 It is formed between uncharged molecules

as well as charged ones.

 In hydrogen bond, a hydrogen atom is

shared by two other atoms.

 The atom to which hydrogen is more tightly

bound is known as a hydrogen donor while
the other one is hydrogen acceptor.
 The acceptor has partial negative charge
that attracts the hydrogen atom.

 In biological systems the donor is usually

Oxygen or Nitrogen atoms that has
covalently attached Hydrogen atoms.

 The acceptor is either Oxygen or

Nitrogen that has not-covalently
attached to Hydrogen atoms.

 The bond energies range from about 3 to

7 kcal/mol. [12.6 to 29.4 kJ/mol]
 Hydrogen bonds are stronger than van der
Waals bonds but much weaker than covalent
bonds.

 The length of hydrogen bond is intermediate

between that of covalent and a van der
Waals bond.

 An important feature of hydrogen bond is

that they are highly directional.

 The strongest Hydrogen bonds are those in

which the donor, hydrogen and acceptor
atoms are colinear.
 Typical Hydrogen bond lengths

Bond Length (A)

O-H --- O 2.70
O-H --- O- 2.63
O-H --- N 2.88
N-H --- O 3.04
N+-H --- O 2.93
N-H --- N 3.10
 Hydrogen bond is very important in
biological systems.

The alpha helix, a reccuring motif in

proteins, is stablized by hydrogen bonds
between amine [-NH] and carboxyl
[-C=O] groups.

The DNA double helix, which is held

together by hydrogen bonds between
bases on opposite strands.
HYDROPHOBIC INTERACTION
 It occurs when non-polar molecules or
groups are placed together in water.

 They tend to cluster together.

 These associations are called hydrophobic

(non polar) attractions.

 In figurative sense, water tend to squeeze

non polar molecules together.
 Hydrophobic interactions is a major
driving force in the:
– folding of macromolecules,
– binding of substrates to enzymes and
– formation of membranes that define the
boundaries of cells and their internal
compartments.

 Nonpolar solute molecules are driven

together in water not primarily because
they have a high affinity for each other
but because water bonds strongly to
itself.
 VAN DER WAALS FORCE
 It is a non-specific attractive force that
come into play when any two atoms are 3
to 4 A apart.

 Though it is weaker and less-specific than

the ionic bonds, van der Waals bonds are
not less important in biological systems.

 The basis of van der Waals bond is that

the distribution of electronic charge
around an atom changes with time.
 At any instant, the charge distribution is
not perfectly symmetric.

 This transient asymmetry in the

electronic charge around an atom
encourages a similar asymmetry in the
electron distribution around its
neighboring atoms.

 The resulting attraction between a pair of

atoms increases as they come closer, until
they are separated by the van der Waals
contact distance.
Energy of van der Waals interaction as function of
the distance between two atoms
 At a shorter distance, very strong
repulsive forces become dominant
because the outer electron clouds overlap.

 The contact distance between an Oxygen

and Carbon is 3.4A, which is obtained by
adding 1.4 and 2.0A, the contact radii of
Oxygen and Carbon atoms.
Van der Waals radii of atoms (A)

Atom Radius (A)

C 2.0
H 1.2
O 1.4
N 1.5
S 1.85
P 1.9
 The van der Waals bond energy of a pair
is about 1 kcal/mol [4.2 kJ/mol].

 It is considerably weaker than a hydrogen

bond or electrostatic bond.

 A single van der Waals bond counts for

very little because its strength is only a
little more than the average thermal
energy of molecules at room temperature
[0.6 kcal/mol].
 Furthermore, the van der Waals force
fades rapidly when the distance between
a pair of atoms becomes even 1A greater
than their contact distance.

 It becomes significant only when

numerous atoms in one of a pair of
molecules can simultaneously come close
to many atoms of the other molecule.

 This can happen only if the shapes of the

molecules match.
 Therefore, effective van der Waals
interactions depend on steric
complementarity.

 Failure to form this complementarity is

called steric hindrance

 Steric = Shape
 Though there is virtually no specificity in
a single van der Waals interaction,

 specificity arises when there is an

opportunity to make a large number of van
der Waals bonds simultaneously.

 Repulsions between atoms closer than the

van der waals contact distance are
important as attractions for establishing
specificity.
 BIOLOGICAL
IMPORTANCE OF WATER
 Water profoundly influences all molecular
interactions in biological systems.

 Water offers the aqueous media in the

cytosol and extracellular.

 The two properties of water that are

especially important in this regard are:
– Water is electrically a polar molecule
– Water is highly cohesive
 The polarity and hydrogen-bonding
capability of water make it a highly
interacting molecule.

 Water is an excellent solvent for polar

molecules.

 The reason is that water greatly weakens

electrostatic forces and hydrogen
bonding between polar molecules by
competing for their attractions.
 Therefore water solvates the polar
molecules and hence weakens ionic and
hydrogen bonds.

 Therefore, a strong hydrogen bond

between a C=O and an NH group of a
protein forms only if water is excluded.

 Water diminishes the strength of

electrostatic attraction by a factor of
80, the dielectric constant of water,
compared to same interaction in a vacuum.
 Water has an unusually high dielectric
constant because of its polarity and
capacity to form oriented solvent shells
around ions.

 These oriented solvent shells produce

electric fields of their own, which oppose
the fields produced by the ions.

 Consequently, electrostatic attractions

between ions are markedly weakened by
the presence of water.
 The existence of life on earth depends
critically on the capacity of water to
dissolve a remarkable array of polar
molecules that serve as:
fuels,
building blocks,
catalyst and
information carriers.

 High concentrations of these polar

molecules can coexist in water, where
they are free to diffuse and find each
other.
 However, the excellence of water as a
solvent poses a problem, for it also
weakens interactions between polar
molecules.

 Biological systems have solved this

problem by creating water-free
microenvironments where polar
interactions have maximal strength and
specificity.