Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China.
Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China.
Chemosphere. 2021 Oct;280:130627. doi: 10.1016/j.chemosphere.2021.130627. Epub 2021 Apr 30.
Serious harmful effects have been reported for thiophenols, which are widely used industrial materials. To date, little information is available on whether such chemicals can elicit endocrine-related detrimental effects. Herein the potential binding affinity and underlying mechanism of action between human transthyretin (hTTR) and seven halogenated-thiophenols were examined experimentally and computationally. Experimental results indicated that the halogenated-thiophenols, except for pentafluorothiophenol, were powerful hTTR binders. The differentiated hTTR binding affinity of halogenated-thiophenols and halogenated-phenols were observed. The hTTR binding affinity of mono- and di-halo-thiophenols was higher than that of corresponding phenols; while the opposite relationship was observed for tri- and penta-halo-thiophenols and phenols. Our results also confirmed that the binding interactions were influenced by the degree of ligand dissociation. Molecular modeling results implied that the dominant noncovalent interactions in the molecular recognition processes between hTTR and halogenated-thiophenols were ionic pair, hydrogen bonds and hydrophobic interactions. Finally, a model with acceptable predictive ability was developed, which can be used to computationally predict the potential hTTR binding affinity of other halogenated-thiophenols and phenols. Taken together, our results highlighted that more research is needed to determine their potential endocrine-related harmful effects and appropriate management actions should be taken to promote their sustainable use.
噻吩酚类物质被广泛用作工业材料，已有报道称其具有严重的有害影响。迄今为止，关于此类化学物质是否会引发与内分泌相关的有害影响的信息很少。在此，通过实验和计算研究了人甲状腺素运载蛋白（hTTR）与七种卤代噻吩之间的潜在结合亲和力和作用机制。实验结果表明，除了五氟噻吩酚外，卤代噻吩酚都是强有力的 hTTR 结合物。观察到卤代噻吩酚和卤代苯酚之间存在不同的 hTTR 结合亲和力。单卤代和二卤代噻吩的 hTTR 结合亲和力高于相应的苯酚；而对于三卤代和五卤代噻吩和苯酚，则观察到相反的关系。我们的结果还证实，结合相互作用受配体离解程度的影响。分子建模结果表明，在 hTTR 与卤代噻吩之间的分子识别过程中，主要的非共价相互作用是离子对、氢键和疏水相互作用。最后，开发了一个具有可接受预测能力的模型，可用于计算预测其他卤代噻吩和苯酚的潜在 hTTR 结合亲和力。总之，我们的研究结果强调，需要进一步研究它们潜在的与内分泌相关的有害影响，并应采取适当的管理措施以促进其可持续利用。
