Experimental Determination of pKa for 10 PFAS, Mono-, Di-, and Trifluoroacetic Acid by 19F-NMR

Abstract

Accurate pK_a values of per- and polyfluoroalkyl substances (PFAS) are urgently needed to improve predictions of their environmental fate, bioaccumulation, and removal, yet reliable experimental data remain scarce. Here, we determined the pK_a values of 10 PFAS and three short-chain fluorinated acids (MFA: 2.58 ± 0.03; DFA: 1.22 ± 0.03, TFA: 0.03 ± 0.08) using ¹⁹F and ¹H NMR-based chemical shift perturbation. Results were compared to prior experimental values, OPERA predictions (CompTox), and our COSMO-RS calculations. Measured pK_a values include PFPrA (−0.18 to −0.54), PFOA (−0.27 ± 0.18), PFBS and PFOS (< −1.85), 6:2 FTS (<0.0), GenX (−0.20 ± 0.09), NFDHA (−0.32 ± 0.18), PFMPA (−0.26 ± 0.13), and 6:2 FTUCA (2.59 ± 0.11). Across C2, C3, and C8 homologues, PFCAs exhibit pK_a values of approximately −0.2 to −0.3. Telomerization markedly reduces acidity: 5:3 FTCA (pK_a = 4.05 ± 0.04) is >10⁴-fold less acidic than PFOA, with COSMO-RS predicting similar effects from PFOS to 6:2 FTS. The dominant acidifying influence arises from CF₂ groups at C1 and C2 near COOH or SO₃H. The unusually low pK_a values for TFA, PFOA, and GenX reflect our low-MeOH, sorption-resistant NMR method. COSMO-RS consistently outperformed OPERA, underscoring the need for experimental benchmarks to improve predictive models for emerging PFAS.