EFFECT OF FLUORINE SUBSTITUTION ON PHENOL ACIDITIES IN THE GAS-PHASE AND IN AQUEOUS-SOLUTION - A COMPUTATIONAL STUDY USING CONTINUUM SOLVATION MODELS

The effect of fluorine substitution on the gas and aqueous phase acidi ty of the monofluorophenols has been investigated with a combination o f computational techniques. The effects of aqueous solvation were incl uded using the SM2, SM3, and GB/SA continuum solvation models. These s olvation models produce calculated free energies of hydration that are in good agreement with the available experimental data and appear to be quite useful for the prediction of the solvent effects on the relat ive acidities of the fluorophenols with respect to phenol. A thorough analysis of the charge distribution in the gas and aqueous phases prov ides insight into the nature of the experimentally observed solvent at tenuation of substituent effects for these compounds. While fluorine s ubstitution increases the hydrophobicity of the phenols and phenoxides , the perturbation of ring charge density imparted by fluorine substit ution is quite similar in the gas and aqueous phases.