New Model for Calculation of Solvation Free Energies:  Correction of Self-Consistent Reaction Field Continuum Dielectric Theory for Short-Range Hydrogen-Bonding Effects

Abstract

We present self-consistent reaction field (SCRF) calculations, utilizing correlated ab initio quantum mechanics, of aqueous solvation free energies for a large data base of molecular solutes. We identify a subset of chemical functional groups for which there are systematic deviations in the comparison of theory and experiment; furthermore, for one case which has been extensively investigated, methylated amines, similar deviations appear in explicit solvent free energy perturbation calculations employing several commonly used molecular mechanics potential functions. By carrying out high-level ab initio quantum chemical calculations of hydrogen-bonding energies of the solutes to a water molecule, we arrive at a coherent explanation of the disagreements between theory and experiment, namely, that hydrogen-bonding energies are in some cases poorly correlated with classical electrostatic interaction energies. We show that the deviation in hydrogen-bonding energies of a solute from a reference molecule (for which there is good agreement between the SCRF calculations and experiment) is an excellent predictor of the errors made for that solute in the SCRF calculations. A new SCRF model is developed in which short-range empirical corrections, based upon solvent accessibility, are made for these chemical functional groups; this reduces the mean error of the calculated solvation free energies for the entire data base by a factor of ∼2, to 0.37 kcal/mol. These results have significant implications for the accuracy of explicit solvent potential functions as well as dielectric continuum models. Finally, we also identify cases where the observed discrepancies in solvation free energies cannot be explained by pair hydrogen-bonding results and suggest problems here that may be specific to dielectric continuum theory.

Oxygen Atom Transfer and Oxidative Water Incorporation in Cuboidal Mn3MOn Complexes Based on Synthetic, Isotopic Labeling, and Computational Studies

“…[4]. We included solvation effects using the Poisson-Boltzmann continuum (PBF) approximation [6] for dimethylformamide (DMF; =36.7…”

Mechanism of Oxidative Shuttling for [2]Rotaxane in a Stoddart−Heath Molecular Switch: Density Functional Theory Study with Continuum-Solvation Model

“…At the final geometry, the solvation energy in AN (dielectric constant 35.69, density 0.7857 g/cm 3 at 20°C, 43 probe radius 2.18 Å) is also calculated in B3LYP/ 6-31G** (since the solvation energy is not very sensitive to the choice of basis set 42 ) using the Poisson-Boltzmann continuum-solvation model. 44,45 The following atomic radii are used (in Å): 42 H 1.15, C 1.9, N 1.6, O 1.6, F 1.682, P 2.074, and S 1.7 (which has been changed from 1.9 to reproduce the experimental reduction potentials of TTF). All calculations are done using Jaguar v5.5.…”

DFT Study on the Catalytic Reactivity of a Functional Model Complex for Intradiol-Cleaving Dioxygenases

“…Corrections of 3-4 kcal/mol were calculated for these long-range dispersion interactions. To reproduce the polarization effects of the solvent used in the experiments, the selfconsistent reaction field (SCRF) method implemented in Jaguar 5.5 was employed [27,28]. The solvent was modeled as a macroscopic continuum with a dielectric constant of 36.6 (corresponding to acetonitrile), and the solute was placed in a cavity contained in this continuous medium.…”