Hydrophobic hydration: a free energy perturbation study

Abstract

Differences in free energy of hydration between molecules within a class of chemical compounds, such as normal alkanes, tetraalkylmethanes, alkyl- and tetraalkylammonium ions, amines and aromatic compounds, have been calculated by a coordinate coupled free energy perturbation method. The calculated free energy differences agree reasonably well with the experimental values. The patterns of variation of free energy change with coupling parameter {lambda} are found to differ for different classes of compounds. These results are interpreted in terms of the differing hydration processes of these molecules. Hydrophobic hydration of hydrocarbons and ammonium ions bearing large hydrocarbon groups seems to result from tightly bound water structure around the solute. In contrast, the water structure around amines and aromatic compounds bearing polar functional groups is dictated by the directional hydrogen bonding of the polar group with water. The direction of the free energy change seems to be dictated by solute-solvent interaction energy, which has major contribution to free energy change for alkyl-substituted ammonium ions.