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 C1(trifluoroacetic acid) to C9(n-perfluorodecanoic acid) as well as the monomethyl branched C7(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 pKa values between C1 and C9, all having a relatively constant pKa 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 pKa 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 pKa values for n-PFOA equal to the global minimum helical conformer pKa. The conformational populations under study occupy ∼100% of the global n-PFOA conformational space, indicating no higher energy/low acidity conformations remain unexamined that could influence the predicted composite aqueous monomeric pKa of zero for this compound.