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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 = ΔHmixing −TΔSmixing

ΔHmixing = 2ΔHa−b − ΔHa−a − ΔHb−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 = ΔHmixing −TΔSmixing

ΔHmixing = 2ΔHa−b − ΔHa−a − ΔHb−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 Replace one water molecule molecule with a surrounded by four hydrophobic water molecules. molecule that cannot 6 possible ways to H-bond. H-bond with 4 3 possible ways to H nearest neighbors -bond with 3 nearest neighbors Calculate the entropy loss on transferring a hydrophobic solute into water.

So So So Δ = withhydrophob − H2O So N (k lnW k lnW ) Δ = A withhydrophobe − H2O 3 ΔSo = N k ln = N k ln 0.5 A 6 A TΔSo = RT ln 0.5

How can we relate the thermodynamics to the amount of hydrophobic surface that is exposed or buried in a process?

The Gibbs free A simple model energy of transfer for transfer of can be measured by a small hydrocarbon measuring the from the pure state fraction of the to water. hydrocarbon in the hydrocarbon and aqueous phases. Correlation between the free energy of transfer and the change in the accessible Transfer of Free energy 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 is analyzed using the following equation: o ln KA = (ΔC pobs / R)[(TH /T )− ln(TS /T )−1]

KA is the equilibrium association constant € o ΔCp is the Heat capacity change at constant .

TS and TH reference temperatures R is the . Note that there are other forms of this equation. Heat Capacity changes are correlated with the change in solvent accessible nonpolar surface area.