Universal Quantum Mechanical Model for Solvation Free Energies Based on Gas-Phase Geometries

Abstract

We present a new solvation model for predicting free energies of transfer of organic solutes from the gas phase to aqueous and organic solvents. The model is based on class II charges, gas-phase geometries, a generalized Born approximation to the polarization free energy, and SM5-type atomic surface tensions. The initial parametrization of the new model was developed to utilize the MNDO/d Hamiltonian, and we also present parameters for the MNDO, AM1, and PM3 Hamiltonians. These parametrizations are based on reasonably accurate gas-phase geometries for 43 ions and 260 neutral solute molecules composed of H, C, N, O, F, S, Cl, Br, and I and containing a wide variety of functional groups. For aqueous solutions, the parametrization is based on data for 248 of the neutrals and all of the ions. For organic solvents, it is based on 1836 experimental data points for 227 of the neutral solutes in 90 organic solvents. The parametrization based on the MNDO/d Hamiltonian is called SM5.2R/MNDO/d, and it yields a mean unsigned error of 3.8 kcal/mol for the free energy of hydration of ions and a mean unsigned error of 0.38 kcal/mol for the free energy of solvation of neutral solutes. Gas-phase geometries for all solute molecules were calculated at the Hartree−Fock level with a heteroatom-polarized valence-double-ζ basis set (HF/MIDI!), and we confirmed that the average errors increase only about 0.1 kcal/mol if we use the MNDO/d geometries.