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

Abstract

Acidity constants were calculated using the semiempirical PM6 pK _a 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 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 (C₂ through C₅). Increasing divergences are observed between calculated and experimental results by up to several pK _a units as the perfluoroalkyl chain length increases beyond C₅. 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.

Keywords:

• Perfluorinated compounds
• perfluorinated carboxylic acids
• physicochemical properties
• environmental partitioning
• acidity constants
• pK _a values
• computational methods

Acknowledgments

S.R. thanks the Natural Sciences and Engineering Research Council (NSERC) of Canada for financial support.

Notes

^a HG = PFCA homologue group.