Solvation thermodynamics of neutral and charged solutes using the solvation‐layer interface condition continuum dielectric model

Abstract

AbstractWe demonstrate that the solvation‐layer interface condition (SLIC) continuum dielectric model for molecular electrostatics, combined with a simple solvent‐accessible‐surface‐area (SASA)‐proportional model for nonpolar solvent effects, accurately predicts solvation entropies of neutral and charged small molecules. The SLIC/SASA model has only seven fitting parameters in total and achieves this accuracy using a training set with only 20 compounds. Despite this simplicity, solvation free energies and entropies are nearly as accurate as those predicted by the more sophisticated Langevin dipoles solvation model. Surprisingly, the model automatically reproduces the negligible contribution of electrostatics to the solvation of hydrophobic compounds. Opportunities for improvement include nonpolar solvation, anion solvation entropies, and heat capacities. More molecular realism may be needed for these quantities. To enable a future, explicit‐solvent‐based assessment of the SLIC/SASA implicit‐solvent model, we predict solvation entropies for the Mobley test set, which are available as Supporting Information.