Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, 646000, China.
Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, 646000, China; People's Hospital of Chongqing Hechuan, Chongqing, 401519, China.
Chem Biol Interact. 2024 Sep 1;400:111144. doi: 10.1016/j.cbi.2024.111144. Epub 2024 Jul 24.
Organophosphate flame retardants (OPFRs) pose the significant risks to the environment and human health and have become a serious public health issue. Tricresyl phosphates (TCPs), a group of aryl OPFRs, exhibit neurotoxicity and endocrine disrupting toxicity. However, the binding mechanisms between TCPs and human serum albumin (HSA) remain unknown. In this study, through fluorescence and ultraviolet-visible (UV-vis) absorption spectroscopy, molecular docking and molecular dynamics (MD), tri-para-cresyl phosphate (TpCP) was selected to explore potential interactions between HSA and TCPs. The results of the fluorescence spectroscopy demonstrated that a decrease in the fluorescence intensity of HSA and a blue shift were observed with the increasing concentrations of TpCP. The binding constant (K) was 2.575 × 10 L/mol, 4.701 × 10 L/mol, 5.684 × 10 L/mol and 9.482 × 10 L/mol at 293 K, 298 K, 303 K, and 310 K, respectively. The fluorescence process between HSA and TpCP involved a mix of static and dynamic quenching mechanism. The gibbs free energy (ΔG) of HSA-TpCP system was -24.452 kJ/mol, -25.907 kJ/mol, -27.363 kJ/mol, and - 29.401 kJ/mol at 293 K, 298 K, 303 K, and 310 K, respectively, suggesting that the HSA-TpCP reaction was spontaneous. The enthalpy change (ΔH) and thermodynamic entropy change (ΔS) of the HSA-TpCP system were 60.83 kJ/mol and 291.08 J/(mol·>k), respectively, indicating that hydrophobic force was the major driving force in the HSA-TpCP complex. Furthermore, multispectral analysis also revealed that TpCP could alter the microenvironment of tryptophan residue and the secondary structure of HSA and bind with the active site I of HSA. Molecular docking and MD simulations confirmed that TpCP could spontaneously form a stable complex with HSA, which was consistent with the fluorescence experimental results. This study provides novel insights into the mechanisms of underlying the transportation and distribution of OPFRs in humans.
有机磷阻燃剂 (OPFRs) 对环境和人类健康构成重大风险，已成为严重的公共卫生问题。磷酸三邻甲苯酯 (TCPs) 是一组芳基 OPFRs，具有神经毒性和内分泌干扰毒性。然而，TCPs 与人体血清白蛋白 (HSA) 之间的结合机制尚不清楚。在这项研究中，通过荧光和紫外-可见 (UV-vis) 吸收光谱、分子对接和分子动力学 (MD)，选择三邻-对-甲苯基磷酸酯 (TpCP) 来探索 HSA 与 TCPs 之间的潜在相互作用。荧光光谱研究结果表明，随着 TpCP 浓度的增加，HSA 的荧光强度降低，蓝移。在 293 K、298 K、303 K 和 310 K 时，结合常数 (K) 分别为 2.575×10 L/mol、4.701×10 L/mol、5.684×10 L/mol 和 9.482×10 L/mol。HSA 与 TpCP 之间的荧光过程涉及静态和动态猝灭机制的混合。HSA-TpCP 体系的吉布斯自由能 (ΔG) 分别为 -24.452 kJ/mol、-25.907 kJ/mol、-27.363 kJ/mol 和-29.401 kJ/mol，表明 HSA-TpCP 反应是自发的。HSA-TpCP 体系的焓变 (ΔH) 和热力学熵变 (ΔS) 分别为 60.83 kJ/mol 和 291.08 J/(mol·K)，表明疏水力是 HSA-TpCP 配合物的主要驱动力。此外，多光谱分析还表明，TpCP 可以改变色氨酸残基的微环境和 HSA 的二级结构，并与 HSA 的活性位点 I 结合。分子对接和 MD 模拟证实，TpCP 可以与 HSA 自发形成稳定的配合物，这与荧光实验结果一致。这项研究为 OPFRs 在人体内的运输和分布机制提供了新的见解。
