Improving the Accuracy of PCM-UAHF and PCM-UAKS Calculations Using Optimized Electrostatic Scaling Factors

Abstract

The optimal electrostatic scaling factor (ESF) for the calculation of solvation Gibbs free energies with the polarizable continuum model (PCM) was determined via extensive benchmarking against 1719 experimental solvation Gibbs free energies and transfer free energies taken from the MNSol-v2012 database, as well as 45 aqueous pKa values covering nine solute types (amines, thiols, carbon acid cations, pyridines, alcohols, anilines, carboxylic acids, carbon acid neutrals, phenols) and 20 pKa values in acetonitrile covering four solute types (phenols, carbon acids, carboxylic acids, pyridines). Optimal values for the ESF in a range of solvents are reported. For example, in water, the optimal ESF value is 1.2 and this does not vary with solute charge, radius type, or method. For acetonitrile, we recommend 1.1 for neutrals, 1.0 and 1.1 respectively for cations with UAHF and UAKS radii types, 1.3 for anions for IEFPCM-UAHF, and 1.4 for other anions. At the same time, we show that ESF optimization does not address all errors in PCM, and is thus not a substitute for the appropriate use of explicit solvent molecules, nor for the use of isodesmic methods to enhance systematic error cancellation. For a representative subset of the data we show that the errors in PCM are somewhat larger than in SMD and somewhat smaller than in COSMO-RS, although the latter has not benefited from cavity scaling. Show more