Combined ab initio/DFT and Monte Carlo calculation of relative standard chemical potentials in solution.

A method has been proposed for pure theoretical estimation of relative standard chemical potentials (1 mol/dm(3) standard state) and related K(c) equilibrium constants for tautomers/conformers dissolved in some solvents. The relative internal free energy could be obtained by means of in-solution ab initio/DFT methods. Using the free energy perturbation method for the transformation of the involved species, the solvation contribution to the relative standard chemical potential can be determined by considering 1 M solution models. Comparison of the ΔG(solv)/MC value calculated for the 1 M solution with those obtained for the system at other concentrations helps explore the ratio of the activity coefficients in nonstandard states. The method has been applied for the study of the tautomeric pair of formaldoxime and nitrosomethane with large structural differences. It was pointed out that the ΔG(solv)/MC values for the 1 and 0.11 M solutions differ by up to 0.2 kcal/mol, when atomic charges are derived on the basis of the in-solution IEF-PCM/B3LYP/aug-cc-pvtz molecular electrostatic potential. On the basis of calculated free energy differences, the ratio of the CH(3)NO and CH(2)NOH activity coefficients in 0.11 molar aqueous and dichloromethane solutions were predicted as of 1.4 and 0.8, respectively. The 0.11 M model is hypothetical by assuming that only one of the tautomers exists in the solution box. As an extension of the method, a procedure has been outlined where contributions to the change of the solvation free energy by terms related to relative activity coefficients might be assessed at physically relevant concentrations for the equilibrated tautomers.