Activity coefficients in dilute aqueous solutions from free energy simulations

The free energy perturbation method with Monte Carlo simulations has been used to calculate relative solvation free energies and ratios of activity coefficients of organic solutes at infinite‐dilution in water at 25°C. Systems studied include hydrocarbons, chlorinated hydrocarbons, and alcohols. Analysis of the free energy simulations reveals that a major limitation of current methodologies is our inability to determine a priori the electron density distribution of a molecule in a condensed, polarizing medium. Moreover, currently employed simulation lengths may be inadequate for convergence of the averages in some aqueous systems. These problems do not, however, appear to be insurmountable. In contrast to group contribution methods, free energy simulations are still rather primitive to be applied in a routine fashion for the quantitative prediction of thermodynamic properties, but dramatic improvements in the technique are still to be made.