Multispectral Analysis and Molecular Simulation of the Interactions Between Perfluorodecanoic Acid/Perfluorosebacic Acid and Human Serum Albumin

Per- and polyfluoroalkyl substances (PFASs) have raised significant environmental and health concerns due to their persistence and toxicity. The study employed a comprehensive analytical approach to clarify the interaction mechanisms between perfluorodecanoic acid (PFDA) and perfluorosebacic acid (PFSEA) with human serum albumin (HSA). The results indicated that PFDA/PFSEA quench HSA's intrinsic fluorescence through static quenching. At 298 K, PFDA demonstrated a more pronounced effect, with a higher binding constant of 9.14 × 10 5 mol/L, surpassing PFSEA's constant of 7.65 × 10 4 mol/L. Thermodynamic analysis revealed that hydrogen bonding was the predominant force in the HSA-PFDA/PFSEA interaction, and the binding processes were exothermic and spontaneous. Quantum chemical structure analysis underscored the heightened reactivity at the carbonyl groups of PFDA and PFSEA. Molecular docking and competitive binding experiments confirmed that PFDA/PFSEA bind to HSA's IIA subdomain, inducing alterations in HSA's secondary structure and amino acid residue's microenvironment. The HSA-PFDA complex exhibited a lower binding free energy (−15.91 kcal/mol) than the HSA-PFSEA complex (−11.06 kcal/mol), indicating a stronger binding affinity. This study elucidated the interactions of PFDA and PFSEA with biological macromolecules, revealing their bioactivity and informing their biosafety and environmental risk assessment.