Theoretical studies on the pKa values of perfluoroalkyl carboxylic acids

Computational studies were conducted using the major levels of semiempirical, ab initio, density functional theory (DFT), and the CBS-Q//B3 method and various solvation models on a homologous series of straight chain perfluoroalkyl carboxylic acids (PFCAs) ranging in chain length from C~1~ (trifluoroacetic acid) to C~9~ (n-perfluorodecanoic acid) as well as the monomethyl branched C~7~ (n-perfluorooctanoic acid; n-PFOA) isomers. Regardless of perfluoroalkyl chain length and theoretical method employed, application of a computational thermodynamic cycle indicated no significant change in the estimated aqueous monomeric pK~a~ values between C~1~ and C~9~, all having a relatively constant pK~a~ of about 0 that is in agreement with earlier predictions and recent experimental evidence. Perfluoroalkyl chain helicity does not appear to result in increased monomeric PFCA pK~a~ values at chain lengths greater than 5. Increasing chain length does not substantially influence the structural or electronic character of the carboxylic acid head group. A MMFF94 conformational search yielded 2915 separate low- through high-energy conformers of n-PFOA. Ranking of these structures gave the 94 lowest MMFF94 energy conformations that were subjected to DFT investigations. Application of a thermodynamic cycle approach, coupled with aqueous and gas phase DFT calculations on the molecular and anionic forms for each of the conformers, gave conformationally averaged pK~a~ values for n-PFOA equal to the global minimum helical conformer pK~a~. The conformational populations under study occupy about 100 percent of the global n-PFOA conformational space, indicating no higher energy/low acidity conformations remain unexamined that could influence the predicted composite aqueous monomeric pK~a~ of zero for this compound.