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。
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.