Omnisol: Fast Prediction of Free Energies of Solvation and Partition Coefficients

Abstract

The SM5.0R model for predicting solvation energies using only geometry-dependent atomic surface tensions was developed previously for aqueous solution. Here we extend it to organic solvents. The method is based on gas-phase geometries and exposed atomic surface areas; electrostatics are treated only implicitly so a wave function or charge model is not required (which speeds up the calculations by about 2 orders of magnitude). The SM5.0R model has been parametrized for solvation free energies of solutes containing H, C, N, O, F, S, Cl, Br, and I. The training set for organic solvents consists of 227 neutral solutes in 90 organic solvents for a total of 1836 data points. The method achieves a mean unsigned error of about 0.4 kcal/mol when applied using gas-phase geometries calculated at either the Hartree−Fock level with a heteroatom-polarized valence-double-ζ basis set (HF/MIDI!) or when applied using semiempirical molecular orbital gas-phase geometries. In related work reported here, the parametrization for predicting aqueous solvation free energies is also extended to include organic solutes containing iodine. This extension is based on eight solutes and yields a mean unsigned error of 0.25 kcal/mol. The resulting SM5.0R model for solvation energies in aqueous and organic solvents can therefore be used to predict partition coefficients (including log P for octanol/water) for any solute containing H, C, N, O, F, S, Cl, Br, and/or I.