Solvent isotope effect on thermodynamics of hydration

Partial molar heat capacities of five linear alcohols (methanol, ethanol, n-propanol, n-butanol, n-pentanol) and five N-substituted amides (n-propionamide, N-methylformamide, N-methylacetamide, N-methylpropionamide, N-ethylacetamide) in aqueous D(2)O solution have been measured at 25 degrees C. The heat capacities of transfer of these compounds from H(2)O to D(2)O were calculated using previously reported (Makhatadze et al., Biophys. Chem. 64 (1997) 93) values of partial heat capacities of alcohols and amides in aqueous H(2)O solutions. It is shown that the sign and magnitude of the heat capacity change upon transfer from H(2)O to D(2)O depends on the relative amount of polar and non-polar solvent accessible surface areas of solute. Analysis shows that transfer of non-polar surface from H(2)O to D(2)O is accompanied by a positive heat capacity change. In contrast, transfer of polar surface from H(2)O to D(2)O occurs with negative heat capacity change. Estimates show that the solvent isotope effect on the heat capacity changes upon protein unfolding can be predicted using the changes of the polar and non-polar surface area changes upon protein unfolding and the transfer data of model compounds. Analysis of the thermodynamic functions of transfer of non-polar compounds from H(2)O to D(2)O shows puzzling behavior which contradicts current definitions of the hydrophobic effect.