Ma Junchao, Yang Bing, Hu Xiaojie, Gao Yanzheng, Qin Chao
Institute of Organic Contaminant Control and Soil Remediation, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, 210095, PR China.
Institute of Organic Contaminant Control and Soil Remediation, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, 210095, PR China.
Environ Pollut. 2023 May 1;324:121342. doi: 10.1016/j.envpol.2023.121342. Epub 2023 Feb 22.
Benzophenone-type UV filters (BPs) are common in natural aquatic environments. They can cause endocrine disruption or other adverse effects once they enter the human body via the food chain or drinking water. The primary cause of BPs accumulation and toxicity is the transport of BPs into the human body. Functional group substitutions can have a significant impact on the interactions of BPs and transporters, resulting in a variety of impact effects. Therefore, we explored the interaction between human serum albumin (HSA, a typical transporter) and ten typical BPs [benzophenone (BP1), 2-hydroxybenzophenone (BP2), 4-hydroxybenzophenone (BP3), 2,2'-dihydroxybenzophenone (BP4), 2,4-dihydroxybenzophenone (BP5), 4,4'-dihydroxybenzophenone (BP6), 2,4,4'-trihydroxybenzophenone (BP7), 2,2',4,4'-tetrahydroxybenzophenone (BP8), 2-hydroxy-4-methoxybenzophenone (BP9), and 2,2'-dihydroxy-4-methoxybenzophenone (BP10)] to study the role of functional group substitutions in binding. The results showed that BPs could bind to HSA at site 2, with binding constants ranging from 2.01 × 10 to 4.57 × 10 L/mol. Compared to BP1, hydroxyl and methoxy substitutions enhanced the BPs-HSA binding. The combined effect of the number and site of hydroxyl substitution at BPs determined the binding strength between BPs and HSA. It was more accessible to bind HSA when BPs were substituted with para-hydroxyl (4-hydroxyl) groups than with ortho-hydroxyl (2-hydroxyl) groups. Moreover, the additional para-methoxy (4-methoxy) group increased the BP-HSA binding strength by approximately 47 times under the same hydroxyl substitution conditions. Theoretical calculations revealed that functional group substitutions increased the intermolecular binding force by increasing the negative electrostatic potential surface area of BPs, which significantly increased the electrostatic and dispersion forces between the BPs and HSA. This BPs-HSA binding decreased the α-helix of HSA and influenced the ratio of other secondary structures, including β-sheet, β-turn, and random coil of HSA. This study provides a theoretical and experimental foundation for understanding the human health risks associated with BPs.
二苯甲酮类紫外线过滤剂（BPs）在天然水生环境中很常见。一旦它们通过食物链或饮用水进入人体，就可能导致内分泌紊乱或其他不良影响。BPs积累和产生毒性的主要原因是其进入人体的过程。官能团取代会对BPs与转运蛋白的相互作用产生重大影响，从而产生多种影响效应。因此，我们探究了人血清白蛋白（HSA，一种典型的转运蛋白）与十种典型的BPs[二苯甲酮（BP1）、2-羟基二苯甲酮（BP2）、4-羟基二苯甲酮（BP3）、2,2'-二羟基二苯甲酮（BP4）、2,4-二羟基二苯甲酮（BP5）、4,4'-二羟基二苯甲酮（BP6）、2,4,4'-三羟基二苯甲酮（BP7）、2,2',4,4'-四羟基二苯甲酮（BP8）、2-羟基-4-甲氧基二苯甲酮（BP9）和2,2'-二羟基-4-甲氧基二苯甲酮（BP10）]之间的相互作用，以研究官能团取代在结合中的作用。结果表明，BPs可在位点2与人血清白蛋白结合，结合常数范围为2.01×10至4.57×10 L/mol。与BP1相比，羟基和甲氧基取代增强了BPs与HSA的结合。BPs上羟基取代的数量和位点的综合作用决定了BPs与HSA之间的结合强度。当BPs被对羟基（4-羟基）取代时，比被邻羟基（2-羟基）取代时更容易与人血清白蛋白结合。此外，在相同的羟基取代条件下，额外的对甲氧基（4-甲氧基）基团使BP与HSA的结合强度增加了约47倍。理论计算表明，官能团取代通过增加BPs的负静电势表面积来增加分子间结合力，这显著增加了BPs与HSA之间的静电和色散力。这种BPs与HSA的结合降低了HSA的α-螺旋结构，并影响了其他二级结构的比例，包括HSA的β-折叠、β-转角和无规卷曲。本研究为理解与BPs相关的人类健康风险提供了理论和实验基础。
