The potential impact of 6PPD and its oxidation product 6PPD-quinone on human health: A case study on their interaction with human serum albumin.

6PPD and its oxidation product, 6PPD-quinone have garnered widespread attention due to their adverse effects on aquatic ecosystems and human health, and are recognized as emerging pollutants. In this study, we investigated the interaction mechanism between 6PPD/6PPD-quinone and human serum albumin (HSA) through various experiments. Experimental findings reveal that the IC50 values of 6PPD-quinone and 6PPD against HEK293T cells were 11.78 and 40.04 μM, respectively. Additionally, the cytotoxicity of these compounds was regulated by HSA, displaying an inverse correlation with their binding affinity to HSA. Furthermore, 6PPD/6PPD-quinone can spontaneously insert into site I on HSA, forming a binary complex that induces changes in the secondary structure of HSA. However, their effects on the esterase-like activity of HSA exhibit a dichotomy. While 6PPD activates the esterase-like activity of HSA, 6PPD-quinone inhibits it. Molecular docking analyses reveal that both 6PPD and 6PPD-quinone interact with many amino acid residues on HSA, including TRP214, ARG222, ARG218, ALA291, PHE211. The π electrons on the benzene rings of 6PPD/6PPD-quinone play pivotal roles in maintaining the stability of complexes. Moreover, the stronger binding affinity observed between 6PPD and HSA compared to 6PPD-quinone, may be attributed to the larger negative surface potential of 6PPD.