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

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.