Solvation Free Energies Estimated from Macroscopic Continuum Theory: An Accuracy Assessment

The solvation thermodynamics of a set of small organic molecules is studied using a simple continuum model. Transfer from vapor or cyclohexane to water is decomposed into three steps: first the atomic partial charges of the solute are removed, then it is transferred into aqueous solution, and then its partial charges are restored. The electrostatic steps are treated using continuum electrostatics; the hydrophobic transfer step is treated using atomic «solvation parameters» or «surface tensions». Vapor-to-water transfer free energies of 35 neutral compounds were estimated, including analogues of 17 amino acid side chains. Variants of the model were tested, using from one to three atom types, each with its own surface tension