RELATIVE PARTITION-COEFFICIENTS FOR ORGANIC SOLUTES FROM FLUID SIMULATIONS

A procedure is noted for obtaining the difference in partition coefficients (log P) for two solutes between two solvents. Fluid simulations are required in which one solute is mutated to the other in both solvents, and the changes in free energies of solvation are computed. The method is illustrated for eight pairs of organic solutes partitioning between water and chloroform. Monte Carlo statistical mechanics simulations are used with statistical perturbation theory to calculate the requisite free energy changes. The results are compared with experimental log P data and relative free energies of hydration. For the present solute pairs, the differences in partition coefficients are dominated by the differences in hydration. Such computations are useful for providing estimates of the effects of substituent changes on partitioning behavior and for further testing of intermolecular potential functions. The paper also contains previously unreported potential function parameters for acetic acid, methyl acetate, acetone, and pyrimidine and a summary of thermodynamics results for the corresponding pure liquids. © 1990 American Chemical Society.