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

Acidity constants were calculated using the semiempirical PM6 pK(a) estimation method for all C(2) through C(9) perfluoroalkyl carboxylate (PFCA) congeners and the straight-chain C(10) through C(13) isomers. According to the PM6 estimates, the linear congeners within each PFCA homologue group have the highest pK(a) 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 pK(a) value. When the branching is closest to the terminal carboxylate group, the effect on the calculated pK(a) is greatest. Although the PM6 calculated pK(a) 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 (C(2) through C(5)). Increasing divergences are observed between calculated and experimental results by up to several pK(a) units as the perfluoroalkyl chain length increases beyond C(5). The findings demonstrate a need for additional experimental pK(a) 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.