Experimental pKa Values of Substituted and Unsubstituted Perfluoroalkyl Sulfonamides Via 19F NMR.

Perfluoroalkyl sulfonamides (FASAs) are a class of per- and polyfluoroalkyl substances (PFAS) found throughout the environment in water, soil, and biota. Sorption behavior, bioaccumulation, and environmental longevity of ionogenic molecules like FASAs is governed by the acid dissociation constant (pKa). However, limited experimental pKa values are available for FASAs, with most values computationally modeled with unknown accuracy. In this research 19F Nuclear Magnetic Resonance (NMR) spectroscopy was used to experimentally determine the pKa of perfluorobutane sulfonamide (FBSA) (6.22 ± 0.06), N-methyl (Me) FBSA (7.46 ± 0.03), perfluorohexane sulfonamide (FHxSA) (6.22 ± 0.04), perfluorooctane sulfonamide (FOSA) (6.4 ± 0.3), Me-FOSA (7.7 ± 0.3), and N-ethyl FOSA (8.0 ± 0.3). The pKa of low aqueous solubility FASAs (FOSA, MeFOSA, and EtFOSA) were determined using acetonitrile (ACN):aqueous buffer mixtures and an aggregated mathematical approach developed to simultaneously fit the data for 40, 50, and 60% ACN. Fluorinated carbon number did not significantly impact pKa. Methyl substitution of nitrogen (MeFBSA) increased the pKa by 1.24 log units for C4 and 1.3 log units for C8 FASAs. Ethyl substitution increased the pKa by 1.6 log units (FOSA vs EtFOSA). Experimentally measured values were compared to four different prediction models. Our internally corrected DFT model gave the best agreement with experimental values while Chemicalize gave pKa values up to 4 log units lower than experimental values.