Bchm 675, Lecture 7
The Hydrophobic Effect
Transfer of Hydrocarbons to Water
Hydrophobicity
Heat capacity changes and changes and Nonpolar
Accessible Surface Area
Reading for the Molecular Interactions
Text: Chapter 3 (The presentation differs somewhat from my lecture
in the emphasis of the coverage
The Hydrophobic Effect
Reading
Books
1.  “The Hydrophobic Effect,” Charles Tanford (1973) John Wiley & Sons, Inc.
Research Papers
1.  Chothia, C. (1974) Nature, 248, 338-339
2.  Sturtevant, J. M. (1977) Proc. Natl. Acad. Sci., 74,
2236-2240.
3.  Spolar et al., (1989) Proc. Natl. Acad. Sci., 86, 8382-8385.
Water: the
structure even
in the liquid phase
is regular.
Unusual Properties of
water
More unusual properties of water
Clathrate
Model for solubilization of
hydrophobic molecules in water:
Think about this in terms
of entropy.
Mixing of two substances A and B
ΔGmixing = ΔH mixing −TΔSmixing
ΔH mixing = 2ΔH a−b − ΔH a−a − ΔH b−b
The probability of mixing depends on the relative values of
€ the enthalpies and entropies of mixing. Entropically mixing
is always favored and becomes more favorable with
temperature. The enthalpic contribution depends on the
relative strength of the A-A, B-B and A-B bonding. Examples
Thermodynamics
For standard mixing:
ΔGmixing = ΔH mixing −TΔSmixing
ΔH mixing = 2ΔH a−b − ΔH a−a − ΔH b−b
And the enthalpy is temperature-independent.
€
What about the hydrophobic effect?
What is the
structural basis of
the
thermodynamics of
the hydrophobic
effect? • Small enthalpy
change
• Large unfavorable
entropy change
•  Heat capacity
change
Consider a simple model
A central water
molecule
surrounded by four
water molecules.
6 possible ways to
H-bond with 4
nearest neighbors
Replace one water
molecule with a
hydrophobic
molecule that cannot
H-bond.
3 possible ways to H
-bond with 3 nearest
neighbors
Calculate the entropy loss on transferring a hydrophobic
solute into water.
o
− SHo 2O
ΔS o = Swithhydrophob
ΔS o = N A (k ln Wwithhydrophobe − k ln WH 2O )
3
ΔS o = N A k ln = N A k ln 0.5
6
TΔS o = RT ln 0.5
€
How can we relate the thermodynamics to the amount
of hydrophobic surface that is exposed or buried in a
process?
A simple model
for transfer of
a small hydrocarbon
from the pure state
to water.
The Gibbs free
energy of transfer
can be measured by measuring the
mole fraction of the hydrocarbon in
the hydrocarbon
and aqueous
phases.
Free energy of Transfer
Correlation
between the free energy of
transfer and the
change in the
solvent accessible
surface area.
Hydrophobicity
Scales
Many biological processes are characterized by large
Changes in the Heat Capacity
See Table 1 in Sturtevant, 1977
A process characterized
by a heat capacity change
does not have a temperature
independent enthalpy.
Spolar et al.
In these cases the temperature
Dependence of the equilibrium
constant is analyzed using the
following equation:
o
/ R )[(TH /T )− ln(TS /T )−1]
ln K A = (ΔC pobs
€
KA is the equilibrium association
constant
ΔCpo is the Heat capacity change at
constant pressure.
TS and TH reference temperatures
R is the gas constant.
Note that there are other forms of
this equation.
Heat Capacity
changes are
correlated with
the change in solvent accessible
nonpolar surface
area.