Solvation thermodynamics revisited

Most chemical and biochemical reactions occur in solution; however, many details of the thermodynamics of solvation are not well understood, especially with regard to the role of energy and entropy in the solvation process. Currently, a prevailing view in the field is that the solvation free energy is fully determined by solute-solvent interactions acting through both energetic and entropic contributions. This rests on the claim, presented by Yu and Karplus [J. Chem. Phys. 89, 2366 (1988)], that the solvent-solvent energetic and entropic contributions to the solvation free energy exactly cancel. Here, we show that this result is not correct but rather arises from an erroneous assignment of the solvent-solvent and solute-solvent entropic contributions. Namely, we demonstrate that the solvent-solvent and solute-solvent energetic contributions to the free energy, which have an unambiguous assignment, are not compatible with the Yu-Karplus decomposition of the solvation entropy. This indicates that, contrary to a now commonly held view, rearrangements of the solvent upon introduction of a solute may contribute both energetically and entropically to the solvation free energy.