CALCULATIONS OF THE RELATIVE FREE-ENERGIES OF AQUEOUS SOLVATION OF SEVERAL FLUOROCARBONS - A TEST OF THE BOND POTENTIAL OF MEAN FORCE CORRECTION

The relative free energies of aqueous solvation of several fluorinated derivatives of methane were calculated using the free energy perturbation (FEP) method. The calculations in general duplicated the experimental free energies with relatively good accuracy, but the calculation of the bond potential of mean force (bond-PMF) contribution [D. A. Pearlman and P. A. Kollman, J. Chem. Phys. 94, 4532 (1991)] was necessary in order to get the most satisfactory agreement with experiment. In particular, it was necessary to use this contribution to obtain even qualitatively correct results for the relative free energies of hydration of methane and tetrafluoromethane. The reasons for this are discussed in terms of the accurate calculation of the effect of the size of the solute. In addition, it is noted that the bond-PMF contribution is important even for FEP calculations not involving large changes in size, such as the ethanol to ethane perturbation, if the length of a bond to a disappearing atom is changed during the perturbation. The relative free energy of aqueous solvation for ethanol and ethane was calculated to demonstrate that if the bond between the oxygen and the hydroxyl hydrogen being removed is ''shrunken'' during the perturbation without including the bond-PMF correction, the calculated free energy is too low by approximately 3 kcal/mol.