Free Energies of Solvation with Surface, Volume, and Local Electrostatic Effects and Atomic Surface Tensions to Represent the First Solvation Shell.

Abstract

Building on the SVPE (surface and volume polarization for electrostatics) model for electrostatic contributions to the free energy of solvation with explicit consideration of both surface and volume polarization effects, on the SMx approach to including first-solvation-shell contributions, and on the linear relationship between the electric field and short-range electrostatic contributions found by Chipman, we have developed a new method for computing absolute aqueous solvation free energies by combining the SVPE method with semiempirical terms that account for effects beyond bulk electrostatics. The new method is called SMVLE, and the elements it contains are denoted by SVPE-CDSL where SVPE denotes accounting for bulk electrostatic interactions between solute and solvent with both surface and volume contributions, CDS denotes the inclusion of solvent cavitation, changes in dispersion energy, and possible changes in local solvent structure by a semiempirical term utilizing geometry-dependent atomic surface tensions as implemented in SMx models, and L represents the local electrostatic effect derived from the outward-directed normal electric field on the cavity surface. The semiempirical CDS and L terms together represent the deviation of short-range contributions to the free energy of solvation from those accounted for by the SVPE term based on the bulk solvent dielectric constant. A solute training set containing a broad range of molecules used previously in the development of SM6 is used here for SMVLE model calibration. The aqueous solvation free energies predicted by the parameterized SMVLE model correlate exceedingly well with experimental values. The square of the correlation coefficient is 0.9949 and the slope is 1.0079. Comparison of the final SMVLE model against the earlier SMx solvation model shows that the parameterized SMVLE model not only yields good accuracy for neutrals but also significantly increases the accuracy for ions, making it the best implicit solvation model to date for aqueous solvation free energies of ions. The semiempirical terms associated with the outward-directed electric field account in a physical way for the improvement in the predictive accuracy for ions. The SMVLE method greatly decreases the need to include explicit water molecules for accurate modeling of solvation free energies of ions.