Free Energies of Solvation in Benzene and Hexafluorobenzene: Is Explicit Polarization Needed?

Free energies of solvation in liquid benzene and hexafluorobenzene
have been computed for 42 uncharged solutes. Monte Carlo statistical
mechanics was used with the free-energy perturbation theory and the
OPLS-AA force field. The results address the transferability of the
potential functions developed for pure liquids to mixed systems and
the potential importance of explicit polarization for neutral organic
molecules in aromatic solvents. Although the free-energy results cover
an 11 kcal/mol range, the average error in comparison with experimental
data points is only 0.4 kcal/mol. There is no systematic pattern to
the discrepancies, so the need to add explicit treatment of solute–solvent
polarization effects is not supported. This contrasts the situation
with cationic solutes as reflected in cation−π interactions.
Results for free energies of hydration are also provided for the 42
solutes in TIP4P water and give an average error of 0.49 kcal/mol.
Implications for modeling biomolecular systems with standard force
fields are considered. It is also interesting to note the overall
similar values for free energies of solvation in benzene and hexafluorobenzene
despite the reversal of polarity for the aromatic rings; the most
significant exception is the more favorable solvation of perfluoroalkanes
in the perfluoro solvent. Alternative accommodations of solutes in
the two solvents are illustrated.