Predicting aqueous free energies of solvation as functions of temperature.

This work introduces a model, solvation model 6 with temperature dependence (SM6T), to predict the temperature dependence of aqueous free energies of solvation for compounds containing H, C, and O in the range 273-373 K. In particular, we extend solvation model 6 (SM6), which was previously developed (Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. J. Chem. Theory Comput. 2005, 1, 1133) for predicting aqueous free energies of solvation at 298 K, to predict the variation of the free energy of solvation relative to 298 K. Also, we describe the database of experimental aqueous free energies of solvation for compounds containing H, C, and O that was used to parametrize and test the new model. SM6T partitions the temperature dependence of the free energy of solvation into two components: the temperature dependence of the bulk electrostatic contribution to the free energy of solvation, which is computed using the generalized Born equation, and the temperature dependence of first-solvation-shell effects which is modeled using a parametrized solvent-exposed surface-area-dependent term. We found that SM6T predicts the temperature dependence of aqueous free energies of solvation with a mean unsigned error of 0.08 kcal/mol over our entire database, whereas using the experimental value at 298 K produces a mean unsigned error of 0.53 kcal/mol.