Prediction of solvation free energies from computed properties of solute molecular surfaces

We have shown that the solvation energies of a group of 12 solutes in 7 dif ferent solvents can be presented analytically in terms of quantities comput ed at the density functional B3P86/6-31+G** level for the isolated solute m olecules. These quantities include the molecular surface;area and several p roperties of the electrostatic potential on the surface, e.g., the most pos itive and negative values, the average deviation of the potential, the posi tive and negative portions of the surface, and their average potentials. Ov erall, the average absolute deviation of the predicted from the experimenta l solvation free energies is 0.25 kcal/mol; the poorest results are obtaine d for the solute butanone, for which the average absolute deviation is 0.63 kcal/mol. The forms of the relationships reflect the natures of the solute -solvent interactions; for the solvents with low dielectric constants, thes e are primarily global, involving extended portions of the molecular surfac es, whereas for the more polar solvents, site-specific interactions also pl ay key roles. (C) 2000 John Wiley & Sons, Inc.