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Interpretation of the "Hydrophobic Effect"

A Molecular Interpretation of the "Hydrophobic Effect"

It's still hard to get a good molecular interpretation of the meaning of DCp. The diagram below helps to directly relate the two. The smaller, more compact native state, with buried Phe (F) side chains denatures to the more open D state with exposed F side chains. Since these are nonpolar, we can envision a "clathrate" or cage of ordered water around them. I've extrapolated the heat capacity curves for both the native and denatured state into region where T < Tm (even though there is very little denatured state in that region). Now the "caged" water around the exposed F in the D state is low energy due to the "ice-like" H bond network. More heat would be absorbed (as the temperature is increased) to break up that cage compared to the same amount of heat applied to the N state. Hence, Cp D > Cp N.

Is there a more quantitative description of the ordered water than a cage? Sharp et al investigated the "structure" of the caged water around nonpolar and polar molecules in a theoretical analysis supported by molecular dynamics (Monte Carlo) simulations. The average bond angles and lengths of water-water H bonds in the first hydration sphere around a nonpolar molecule like benzene decreased , but increased for polar ones such as potassium ions. The average changes noted arose from two types of H bonds compared to bulk water, those that were shorter and more linear, and those that were longer and more bent. They stated that "nonpolar groups do not so much increase the ordering of water as decrease the disordering".

Figure: Heat Capacity Changes: A Molecular Interpretation

 

19delCpClathrate.jpg

 

A recent review by Silverstein suggests that an immobile clathrate cage is not a good representation for water surrounding a hydrophobe. Although we like to envision molecular models that allows us to "explain" experimental thermodynamic findings, such models themselves should be subjected to rigorous experimentation. An alternative explanation hinges on water's small size (compared to other solvents), its tight packing and high density. Consider the density water compared to more nonpolar liquid solvents as seen the table below.

Table: Density of common solvents

Solvent Volume (Emin) (A3) (Spartan) Density (g/ml)
H2O 19.17 1.00
methanol CH3OH 40.66 0.791
ethanol CH3CH2OH 59.08 0.789
n-propanol CH3CH2CH2OH 75.35 0.804
n-butanol CH3CH2CH2CH2OH 95.68 0.810
hexane 124.8 0.654

Let's consider the density of water surrounding an exposed nonpolar. If we envision the surrounding water as a clathrate, we might assume it is "ice" like. So what are the physical properties of ice and water than might give us insight into the water surrounding a nonpolar molecule?

Ice, of course, has a lower density than liquid water. This can't be simply explained by the number of H bonds since experimental evidence shows that ice has an average of 4 H bonds per water molecule compared with liquid water, with an average of 2.4. Experimental data also shows that to accommodate water molecules into a rigid network of interacting waters with tetrahedral symmetry, the H-O-H bond angle increases to 106from 104.5. Liquid water molecules, with fewer packing constraints, can self organize to maximize packing and hence macroscopic density. Studies suggests that ten water molecules solvate a buried methyl group and infrared studies show that four of these have significant barriers to rotational diffusion, suggest they are effectively immobilized and hence "ice-like". Silverstein suggests then that the water surrounding a nonpolar group on solution should be consider in a dynamic sense with some immobilized (as in ice) and the remaining more fluid-like.