Computational approaches may underestimate pKa values of longer-chain perfluorinated carboxylic acids: Implications for assessing environmental and biological effects

Acidity constants were calculated using the semiempirical PM6 pKa estimation method for all C2 through C9 perfluoroalkyl carboxylate (PFCA) congeners and the straight-chain C10 through C13 isomers. According to the PM6 estimates, the linear congeners within each PFCA homologue group have the highest pKa values by up to 6 units depending on the degree of branching in the perfluoroalkyl chain. In general, the higher the degree of branching in the perfluoroalkyl chain within a homologue group, the lower the estimated pKa value. When the branching is closest to the terminal carboxylate group, the effect on the calculated pKa is greatest. Although the PM6 calculated pKa values agree well with previously reported estimates for selected linear PFCA congeners using the SPARC and COSMOtherm approaches, all computational approaches only show good agreement with reported experimental values for short chain PFCAs (C2 through C5). Increasing divergences are observed between calculated and experimental results by up to several pKa units as the perfluoroalkyl chain length increases beyond C5. The findings demonstrate a need for additional experimental pKa measurements for an expanded set of both linear and branched PFCA congeners to confirm previous experimental reports that are potentially in error, and upon which to calibrate existing computational methods and environmental, toxicological, and waste treatment method models.