Investigating the molecular interactions of two long-chain PFASs with human serum albumin: Insights from...

Long-chain perfluoroalkyl substances (FPAS) are commonly detected in environmental and biological contexts. This study investigated the interactions of perfluoroundecanoic acid (PFUnDA) and perfluorotridecanoic acid (PFTrDA) with human serum albumin (HSA). Fluorescence quenching experiments demonstrated static quenching of HSA's intrinsic fluorescence by both PFUnDA and PFTrDA, resulting in the formation of stable HSA-PFAS complexes. At 298 K, PFUnDA exhibited a higher binding constant (5.50 × 10⁷ L/mol) than PFTrDA (1.01 × 10⁵ L/mol), indicating stronger binding affinity. Thermodynamic analysis indicated that hydrogen bonds and van der Waals forces were the predominant interactions in the binding processes. Molecular docking confirmed that both PFASs bind to the IIA subdomain of HSA, with PFUnDA exhibiting lower binding energy (-8.690 kcal/mol) than PFTrDA. Molecular dynamics simulations further supported these findings, with PFUnDA showing stronger binding energy (-13.894 kcal/mol) driven primarily by van der Waals forces and electrostatic interactions. Quantum chemical analysis reveals that the carbonyl groups in PFUnDA and PFTrDA exhibit significant molecular reactivity, indicating a propensity for more vigorous chemical interactions. This study not only reveals the potential biological activity of PFUnDA and PFTrDA, but also provides scientific basis for evaluating their biosafety and risks.