A Monte Carlo simulation study of the solvent effect on the relative free energies of solvation and the partition coefficients of organic solutes

Abstract

A study of Monte Carlo simulations (MCS) with statistical perturbation theory has been carried out to investigate the solvent effects on the relative free energies of solvation and the difference in partition coefficients (log P) for two solutes mutated to each other. It is proved that three or five MCS using doublewide sampling are necessary for obtaining results with enough precision and fluid simulations are required in which pyrazine is mutated to pyridine in several solvents. The computed results are compared with the previous published relative free energies of solvation and Δ log P data. For the present solute pairs, the solvent permittivity and the differences of solvation dominate the differences in the relative free energies of solvation and partition coefficients.