光谱法与计算机模拟法研究六溴环十二烷与牛血清白蛋白的相互作用  

Study on Interaction Between Hexabromocyclododecane and Bovine Serum Albumin by Spectroscopy and Computer Simulation Methods

作　　者：庹浔 宋继敏 付豪 吕小兰 TUO Xun;SONG Ji-min;FU Hao;LV Xiao-lan(College of Chemistry,Nanchang University,Nanchang 330000,China;School of Pharmacy,Nanchang University,Nanchang 330000,China)

机构地区：[1]南昌大学化学学院,江西南昌330000 [2]南昌大学药学院,江西南昌330000

出　　处：《光谱学与光谱分析》2021年第5期1487-1492,共6页Spectroscopy and Spectral Analysis

基　　金：国家自然科学基金项目(31860153);江西省自然科学基金项目(20181BAB204003)资助。

摘　　要：六溴环十二烷(HBCD)是一种被人类广泛使用的溴系阻燃剂。近年来的研究表明HBCD已经广泛存在于环境中且对人类的健康具有较大威胁。目前还没有关于HBCD与牛血清白蛋白(BSA)之间相互作用机制的报道。该研究在模拟生理条件下,整合光谱学和计算机模拟研究等技术手段探究HBCD与BSA之间的相互作用,为揭示HBCD对人类的毒性作用机制提供新的视角和一些基础数据。荧光光谱法和紫外光谱法证明HBCD能够使BSA的内源荧光猝灭,猝灭机制为静态猝灭和非辐射能量转移。HBCD与BSA有1个结合位点,结合常数为2.7966×10^(4) L·mol^(-1)(288 K),2.1941×10^(4) L·mol^(-1)(293 K),1.1744×10^(4) L·mol^(-1)(298 K)。荧光光谱、紫外光谱、分子对接结果表明HBCD与BSA在结合位点Ⅰ处结合,结合距离为3.45 nm左右。根据热力学常数与结合常数之间的关系,计算得到ΔH=-61.749 kJ·mol^(-1),ΔS=^(-1)28.742 J·(mol·K)^(-1),两者之间的结合作用力为范德华力或氢键。三维荧光光谱实验、分子动力学模拟结果表明,HBCD不会对BSA的二级结构产生影响。Hexabromocyclododecane(HBCD)is widely used in industry as a kind of brominated flame retardant.However,more and more people pay close attention to the problem of HBCD contamination in the environment due to its potential risk to human health.There are no reports focuses on the transport mechanism of HBCD in the human body.Hence,multi-spectroscopy and computer simulation methods investigated the interaction mechanisms of HBCD and bovine serum albumin(BSA)-.The solution experiments confirmed that HBCD quenched BSA’s intrinsic fluorescence through the static quench mechanism and non-radiation energy transfer.The binding constants(Ka)between them were 2.7966×10^(4) L·mol^(-1)(288 K),2.1941×10^(4) L·mol^(-1)(293 K),and 1.1744×10^(4) L·mol^(-1)(298 K),respectively.The number of the binding site in the BSA-HBCD complex was approximately equal to 1.The thermodynamic constants were calculated to beΔH=-61.749 kJ·mol^(-1) andΔS=^(-1)28.742 J·(mol·K)^(-1),indicating that van der Waals or hydrogen bond play a key role in this binding process.The result of molecular docking and fluorescence spectrum indicated that the primary binding site for HBCD was located in the hydrophobic pocket of sub-domainⅡA of BSA,and the binding distance was about 3.45 nm.The secondary conformation of BSA did not affect by HBCD was observed in three-dimensional fluorescence spectra and MD simulations.This research provides a theoretical basis for further understanding of toxic effects of HBCD on human toxicity.

关 键 词：六溴环十二烷 多光谱法 计算机模拟 牛血清白蛋白 

分 类 号：TQ460.1[化学工程—制药化工]