Molecular structural heterogeneity of bisphenols governs their serum albumin binding

Xingchen Zhao, Penghui Li, Shanjun Song*, Huiyu Wang, Lining Zhao, Wansong Zong, Haiyan Zhang, Guangbo Qu, Ligang Hu, Zongwei Cai*, Guibin Jiang

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

12 Citations (Scopus)


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 × 103 M−1), BPF (1.05 × 104 M−1), and BPS (7.89 × 103 M−1) determined via equilibrium dialysis shows moderate binding ability with multiple binding sites. The HSA-water partition coefficients (log KHW > 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 × 1014 M−1 s−1) » BPS (4.08 × 1012 M−1 s−1) > BPAF (1.20 × 1012 M−1 s−1) > BPF (3.06 × 1011 M−1 s−1) ≈ BPA (4.47 × 1011 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 Km and Vmax except for BPS (increased Km and Vmax) 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.

Original languageEnglish
Article number146499
JournalScience of the Total Environment
Early online date27 Mar 2021
Publication statusPublished - 10 Aug 2021

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

User-Defined Keywords

  • Bisphenols
  • Blood
  • Molecular docking
  • Protein conformation
  • Structural heterogeneity


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