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

A study of Monte Carlo simulations (MCS) with statistical perturbation theo ry has been carried out to investigate the solvent effects on the relative free energies of solvation and the difference in partition coefficients (lo g 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 eno ugh precision and fluid simulations are required in which pyrazine is mutat ed to pyridine in several solvents. The computed results are compared with the previous published relative free energies of solvation and Delta log P data. For the present solute pairs, the solvent permittivity and the differ ences of solvation dominate the differences in the relative foe energies of solvation and partition coefficients. (C) 2000 Elsevier Science B.V. All r ights reserved.