Molecular insight on the binding of halogenated organic phosphate esters to human serum albumin and its effect on cytotoxicity of halogenated organic phosphate esters

Zihang Zhang; Lulu Dai; Kaiyu Yang; Jiaqing Luo; Yue Zhang; Pei Ding; Jianwen Tian; Xun Tuo; Baozhu Chi

doi:10.1016/j.ijbiomac.2024.132383

Molecular insight on the binding of halogenated organic phosphate esters to human serum albumin and its effect on cytotoxicity of halogenated organic phosphate esters

Int J Biol Macromol. 2024 May 15;270(Pt 2):132383. doi: 10.1016/j.ijbiomac.2024.132383. Online ahead of print.

Authors

Zihang Zhang¹, Lulu Dai¹, Kaiyu Yang², Jiaqing Luo¹, Yue Zhang², Pei Ding², Jianwen Tian¹, Xun Tuo³, Baozhu Chi⁴

Affiliations

¹ School of Chemistry and Chemical Engineering, Nanchang University, Nanchang 330031, Jiangxi, China.
² School of Pharmacy, Nanchang University, Nanchang 330031, Jiangxi, China.
³ School of Chemistry and Chemical Engineering, Nanchang University, Nanchang 330031, Jiangxi, China. Electronic address: tuoxun@ncu.edu.cn.
⁴ School of Chemistry and Chemical Engineering, Nanchang University, Nanchang 330031, Jiangxi, China. Electronic address: chibaozhu@ncu.edu.cn.

PMID: 38754667
DOI: 10.1016/j.ijbiomac.2024.132383

Abstract

Halogenated Organic Phosphate Esters (OPEs) are commonly found in plasticizers and flame retardants. However, they are one kind of persistent contaminants that can pose a significant threat to human health and ecosystem as new environmental estrogen. In this study, two representative halogenated OPEs, tris(1,3-dichloro-2-propyl) phosphate (TDCP) and tris(2,3-dibromopropyl) phosphate (TDBP), were selected as experimental subjects to investigate their interaction with human serum albumin (HSA). Despite having similar structures, the two ligands exhibited contrasting effects on enzyme activity of HSA, TDCP inhibiting enzyme activity and TDBP activating it. Furthermore, both TDCP and TDBP could bind to HSA at site I, interacted with Arg222 and other residues, and made the conformation of HSA unfolded. Thermodynamic parameters indicated the main driving forces between TDBP and HSA were hydrogen bonding and van der Waals forces, while TDCP was mainly hydrophobic force. Molecular simulations found that more hydrogen bonds of HSA-TDBP formed during the binding process, and the larger charge area of TDBP than TDCP could partially account for the differences observed in their binding abilities to HSA. Notably, the cytotoxicity of TDBP/TDCP was inversely proportional to their binding ability to HSA, implying a new method for determining the cytotoxicity of halogenated OPEs in vitro.

Keywords: Computer simulation; Cytotoxicity; Esterase activity; Halogenated OPEs; Human serum albumin.