Molecular structural heterogeneity of bisphenols governs their serum albumin binding

Abstract

Bisphenol A (BPA) and its analogs (bisphenol F, BPF; bisphenol AF, BPAF; bisphenol S, BPS; and tetrabromobisphenol A, TBBPA) are transported by blood and bind estrogen receptors of target organs or cells. They were confirmed to bind human serum albumin (HSA) in blood, and the binding constants of BPA (5.14 × 10 3 M −1 ), BPF (1.05 × 10 4 M −1 ), and BPS (7.89 × 10 3 M −1 ) determined via equilibrium dialysis shows moderate binding ability with multiple binding sites. The HSA-water partition coefficients (log K HW > 3) are greater than their octanol-water distribution coefficients, and may follow the order: TBBPA > BPAF > BPA (3.75) > BPF (3.61) > BPS (3.27). Functional groups and substitutions of bisphenols (BPs) determine the fluorescence quenching of Trp214 in HSA. The effects follow: TBBPA (4.41 × 10 14 M −1 s −1 ) » BPS (4.08 × 10 12 M −1 s −1 ) > BPAF (1.20 × 10 12 M −1 s −1 ) > BPF (3.06 × 10 11 M −1 s −1 ) ≈ BPA (4.47 × 10 11 M −1 s −1 ), which is in line with the molecular docking results. In this process, the enzymatic characteristics of HSA were changed simultaneously, as evidenced by decreased K m and V max except for BPS (increased K m and V max ) and increased catalytic efficiency, which may improve the hydrolysis of other drugs. However, the native conformation of the protein underwent locally adaptive changes due to the reversible binding. Overall, these data provide a mechanistic explanation for the transport of BPs in human blood, which may affect their retention and toxicity. • BPs in serum can be transported by serum albumin (SA). • BPs affiliate SA more than octanol, ranking as TBBPA > BPAF > BPA > BPF > BPS • SA undergoes locally adaptive structural changes regardless of their binding sites.