Predicting Salt Effects on the Binding of PFAS to Protein

Per- and polyfluoroalkyl substances (PFAS) are known to bind to specific proteins, leading to their accumulation in specific organs/tissues, ultimately resulting in adverse health effects. Salts strongly impact PFAS and protein behaviors in the environment and biota, but the impact of salt on PFAS/protein interaction has not been assessed. In this study, we investigated the impact of salt on anionic PFAS (including PFBA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFBS, PFHxS, PFOS, and GenX) and bovine serum albumin (BSA) interactions. PFAS/BSA binding affinity was found to depend on PFAS chain length and headgroup, salt composition, ionic strength, and solution pH. PFAS/BSA interactions weakened with increasing ionic strength and decreasing cation valency. The molecular structure of PFAS did not affect how the ionic strength influenced binding affinities. However, the binding affinity exhibits pH dependence, with salt effects becoming more pronounced as the pH decreased. Thermodynamic analysis indicated a hydrophobic-dominant interaction between PFAS and BSA. Additionally, we developed a model to predict binding affinity under varying salt conditions, suggesting that different PFAS associate with wastewater to differing extents, strongly influenced by salt content. This model can be used to predict PFAS environmental fate and toxicity.