Abstract：
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 (Ka) was 2.575 × 104 L/mol, 4.701 × 104 L/mol, 5.684 × 104 L/mol and 9.482 × 104 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 (ΔG0) 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 (ΔH0) and thermodynamic entropy change (ΔS0) 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.
摘要：
有机磷酸酯阻燃剂（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。磷酸三甲苯酯(TCPs),一组芳基OPFR，表现出神经毒性和内分泌干扰毒性。然而,TCPs与人血清白蛋白(HSA)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），选择磷酸三对甲苯酯（TpCP）来探索HSA和TCP之间的潜在相互作用。荧光光谱的结果表明，随着TpCP浓度的增加，观察到HSA的荧光强度降低和蓝移。结合常数(Ka)为2.575×104L/mol,4.701×104L/mol,在293K时5.684×104L/mol和9.482×104L/mol，298K,303K,和310K，分别。HSA和TpCP之间的荧光过程涉及静态和动态猝灭机制的混合。HSA-TpCP系统的gibbs自由能（ΔG0）在293K时为-24.452，-25.907，27.363和29.401kJ/mol，298K,303K,和310K，分别,提示HSA-TpCP反应是自发的。HSA-TpCP体系的焓变(ΔH0)和热力学熵变(ΔS0)分别为291.08J/Kmol和60.83kJ/mol,分别,表明疏水力是HSA-TpCP复合物的主要驱动力。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能与HSA自发形成稳定的复合物,与荧光实验结果一致。这项研究为人类OFPR的运输和分布提供了新的见解。
