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.

Comparison of some dispersion-corrected and traditional functionals as applied to peptides and conformations of cyclohexane derivatives

“…20 Both B3LYP and X3LYP predict results that are reasonably close to the several experimental values for polyalanine, [23][24][25] polyglutamic acid, 26 and polylysine, 27 and some previous predictive 28 theoretical values 20 available. While the experimental values refer to aqueous solution, we note that SM5.2 29 estimates of the differences in free energies of solvation for the α-helix and polyproline II structure of polyalanine are quite small. 21 We have recently reported a more complete analysis of the aqueous solvation of polyalanine α-helices.…”

Semi‐Synthetic Ecdysteroids as Gene‐Switch Actuators: Synthesis, Structure–Activity Relationships, and Prospective ADME Properties

“…Aqueous solubility of the ecdysteroid O-alkyl ether analogues were determined using the AMSOL method and software. [84] Log D measurements: log D was measured by Absorption Systems, Inc. PoA and 20E were measured at 100 mm in equal volumes of pH 7.4 buffer and water-saturated 1-octanol in a 1.5 mL shake flask system in duplicate using testosterone standard. Each shake flask was agitated for 60 min at room temperature, then allowed to stand for 1 hour at room temperature.…”

Electrostatic component of solvation: Comparison of SCRF continuum models

“…The SMx models (x ϭ 1-5.42) [17][18][19][21][22][23][24][25]52,53 do not compute the solute-solvent polarization directly from solution of the Poisson equation, as in the MPE and MST methods, but instead from the GB formula, 5,[12][13][14][15][16][17][18][19][20] which may be considered to be an approximation to the solution of the Poisson equation. In fact, it is a multicenter generalization of the one-center Born 54 equation for monatomic ions.…”