MCB 250 - Lecture 2

Some Chemical
Fundamentals
Chemical Fundamentals: Chemical Bonds
• Strong Bonds
– Covalent bonds
– Cis/trans isomerism
– Resonance and aromaticity, UV absorbance
– Stereoisomerism (D,L)
• Weak Bonds
– Ionic bonds
– Hydrogen bonds
– Van der Waals interactions
– Hydrophobic “bonds”
 Absorption of Light
An absorption spectrum

Absorbance
Wavelength
•  Electrons move in “quantized” orbitals.
•  Light of the appropriate energy
can kick electrons into a higher energy orbital.
•  The “absorption spectrum” provides
information about molecular structure.
•  All molecules absorb radiation.
•  Aromatics and compounds with conjugated double
bonds absorb light in the UV or visible range.
 β - carotene

•  More conjugated double bonds means that light

of lower energy will be absorbed.
•  β-carotene absorbs in the visible blue range
(~450 nm) and is, therefore, intensely colored
red-orange.
•  The bases of DNA and RNA absorb light at 260
nm, while the aromatic amino acid tryptophan
absorbs light at 280 nm.
Stereoisomerism
Nineteen of the 20 amino acids can exist as distinct
L- or D- stereoisomers. Life evolved to use only
L-amino acids in proteins.
 Why only one stereoisomer in biological systems?
Most biological interactions depend on precise
interactions between chiral molecules. Only one form
will fit, the other won’t.

This one fits. This one doesn’t.

 High Energy Bonds
“High Energy”
Phosphoanhydride
Bond

Condensation
Reaction Phosphate Transfer

“High Energy”
Phosphoester Bond

ΔG ~ -7 kcal/mol

This does not refer to bonds that are “strong”, but rather those that release
significant energy when hydrolyzed. ATP hydrolysis is a perfect example.
Weak Chemical Interactions Important In
Biology

•  Hydrogen bonds
•  Ionic bonds
•  van der Waals interactions
•  Hydrophobic interactions
Water is a polar molecule: it has a dipole
moment as a result of unequal sharing of
electrons.
Hydrogen Bonds
Account for the
Properties of
Water, which
forms a Lattice
Structure
 Clicker Question
Despite its lattice structure, water can flow
because ...
A.  hydrogen bonds break and re-form rapidly.
B.  many water molecules have no hydrogen
bonds.
C.  hydrogen ions can move between
molecules.
D.  hydrogen bonds are too weak to affect
movements.
E.  None of the above.
 Biology Happens in Water

•  H2O is a polar solvent.

•  H2O is a protic solvent: it makes hydrogen
bonds. It is both a H-bond donor and an H-
bond acceptor.
•  These two properties make the interactions
that underlie biological processes possible.
 Hydrogen Bonds

Two Water Two Parts of

Molecules One Large
Molecule

Strength of the Hydrogen Bond is Affected by Orientation

Straight is Better
 Hydrogen Bonds
•  Hydrogen covalently bonded to
electronegative elements (O and N in
biological systems), the H-bond donor, can
interact with another electronegative element
(O or N), the H-bond acceptor.
•  H-bonds are directional: stronger interaction if
linear (see next slide).
•  Not all H-bonds are equally strong but
generally ΔG approximately 3-7 kcal/mole.
 C

C O H N
Example: hydrogen bond
between two peptide
N backbones.

Orientation Matters

Stronger

Weaker

All things being equal, they’ll

line up to maximize (straighten)
the hydrogen bond
Ionic Bonds = Electrostatic Interactions

Opposite Charges Attract

CH2-CH2-CH2-CH2-NH3+
- OOC-CH
2

Lysine Aspartate

ΔG approximately 5 kcal/mole in water but stronger

interactions are possible inside protein molecules.
These interactions are not directional.
Note also that like charges repel.
 van der Waals Forces
•  The electron clouds of all molecules attract each
other very weakly. (The attraction is weaker than
ionic or H-bonds).
•  The effect is very dependent on the distance
between the two molecules (1/r6) but if the
molecules are too close the electron clouds repel.
•  Individual van der Waals interactions are weak
but the sum of a number of van der Waals
interactions can result in a significant force.
•  van der Walls forces are therefore most
significant when two large surfaces fit together.
BAW.2.34(

van(der(Waals(Forces(

REPULSION
radius (r)

ATTRACTION
maximal bond
energy

Bond( strength( is( maximized( at( a( par<cular( distance,( when( the(

par<cipa<ng(electrons(overlap(to(a(specific(degree.(
van der Waals Forces in Protein
Structure
 Stacking of Aromatic Rings

Stacking interactions – van der Waals

Overlapping p-bonds stabilize interaction of stacked
aromatics. Very important in stabilizing DNA structure.
Hydrophobic Interactions
•  Hydrophobic – water hating
•  Hydrophilic – water loving
–  Have dipole moments and can form
hydrogen bonds
•  Molecules without a dipole moment
do not interact well with H2O
•  These hydrophobic molecules are
excluded by H2O
•  “Oil and water
don’t mix”
 Fatty Acids are Examples of
Hydrophobic Biomolecules

O
CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 C
H 3C CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 OH

Stearic Acid – C18

Phosphatidylcholine – a Lipid
Choline Amphipathic
Molecules
Phosphate have BOTH
Hydrophobic
and
Glycerol Hydrophilic
Regions
Fatty Acid
Hydrophobic interactions drive the formation
of lipid bilayers in biological membranes.
 Hydrophobic interactions stabilize the folded structures of
proteins and are important for interactions between protein
molecules.

End
view
Side
view

Note that the forces that hold this 4-

helix bundle together involve
hydrophobic interactions between
hydrophobic amino acid side chains.

PNAS 103:8060, 2006.

The sum of all of
these weak
interactions allow
and define specific
interactions
between biological
molecules.
 Importance of Weak Interactions in
Biology
•  Many interactions in biology are dynamic:
molecules come together and then come apart,
e.g., enzyme and substrate.
•  If the interactions were too strong, interacting
molecules would be too stable and wouldn’t
come apart.
Many Biological Molecules are Charged
•  5 of the 20 amino acids found in proteins have
side chains that are charged at neutral pH.
•  The phosphate residues in the sugar-phosphate
backbone of DNA and RNA are charged at
neutral pH.
•  Phospholipids are charged at neutral pH.
•  Biological molecules frequently interact via
electrostatic (charge-charge) forces.
•  The charge of biological molecules depends on
the pH of their environment.
pH: a measure of H+ concentration
Keq [H+][OH-]
H2O H+ + OH- Keq =
[H2O]

Keq [H2O] = Kw = [H+][OH-] = 1.0 x 10-14

In pure water: [H+] = [OH-] = 1.0 x 10-7

Degree of acidity or basicity of an aqueous solution is determined

by measuring the [H+]

pH = -log[H+]
pH Scale
 Weak Acids and Bases in Biology
A Carboxylic Acid Group – Weak Acid

OH Ka O- O
C C + H+ = C + H+
O O O
Weak acid Conjugate base

An Amino Group – Weak Base

H H
N+ H
Ka
N + H+
H H
Conjugate acid Weak base
 Ionization of Weak Acids
Ka [H+][A-]
HA H+ + A- Ka =
[HA]

[A -]
[HA] pH = pKa + log
[H+] = Ka [HA]
[A-]
Henderson-Hasselbach Equation

[A -] -]
-
When [HA] = [A ] then [A
[HA] = 1 and log [HA] = 0

So when pH = pKa, [A-] = [HA]. When the pH is one unit above the pKa
[A-]/[HA] = 10, and when pH is one unit below the pKa [A-]/[HA] = 0.1
 pKa
O H
C N
% Deprotonated O H

50

OH H
C N+ H
O H

1 pH 14
[H+] pKa pKa [H+]
Ka
HA H+ + A-
 Weak Acids and Bases in Biology

Charge
Group Example pKa pH 2 pH 7 pH 12
Carboxylate Aspartate 3.9 0 - -
Amino Lysine 10.5 + + 0

The pKa is affected by the local environment. The pKa of an amino

acid side chain in the interior of a protein may differ from the pKa of
the same side chain on the surface of a protein.
The charge of a protein or peptide at neutral pH
is determined by the number of glutamic acid,
aspartic acid, lysine and arginine residues.

Glu, Asp (pKa approx. 4)

Essentially 100% negatively charged at neutral pH.

Lys (pKa approx. 10.5), Arg (pKa approx. 12).

Essentially 100% positively charged at neutral pH.
 Ionic Bonds in Proteins are
Affected by pH
pH Lysine Attraction?
Aspartate

<2 CH2-CH2-CH2-CH2-NH3+ HOOC-CH2 No

7 CH2-CH2-CH2-CH2-NH3+ - OOC-CH
2 Yes

>12 CH2-CH2-CH2-CH2-NH2 - OOC-CH No

2