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首页> 外文期刊>Chemistry: A European journal >Halogen-Bonding Interactions of Polybrominated Diphenyl Ethers and Thyroid Hormone Derivatives: A Potential Mechanism for the Inhibition of Iodothyronine Deiodinase
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Halogen-Bonding Interactions of Polybrominated Diphenyl Ethers and Thyroid Hormone Derivatives: A Potential Mechanism for the Inhibition of Iodothyronine Deiodinase

机译：聚溴二苯基醚和甲状腺激素衍生物的卤素键合相互作用：抑制碘氢萘醌脱碘酶的潜在机制

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摘要

Polybrominated diphenyl ethers (PBDEs) increase flame resistance in consumer goods, but these compounds and their hydroxylated derivatives (OH-BDEs) impair normal thyroid function. Halogen bonding (XB) of PBDEs to an active site selenocysteine may prevent iodothyronine deiodinase( Dio)-catalyzed activation/deactivation of thyroid hormone (TH) derivatives. In this study, we compare the strength of the XB interactions of TH derivatives, iodinebased contrast agents and PBDEs/OH-BDEs with a methylselenolate model of the Dio active site using density functional theory calculations. The strength of the XB interaction depends upon the acceptor halide, the position of the halide, the number of ring substituents, and the proximity of hydroxyl groups to the XB site. The weaker Se···Br interactions relative to Se···I interactions are consistent with a model of competitive inhibition that blocks binding of THs at elevated PBDE/OH-BDE concentrations. XB interactions were generally more favorable at ortho and meta positions and in substrates with more electron-withdrawing substituents. PBDEs/ OH-BDEs that mimic the binding behavior of THs, that is, containing ortho and meta bromides and adjacent hydroxyl groups, may be the most effective inhibitors. Highly-brominated PBDEs/OH-BDEs have comparable interaction energies to THs and may undergo debromination. These results may also suggest that XB strength must exceed a threshold value in order for PBDEs/OH-BDEs to undergo nucleophilic attack by Dio.
机译：聚溴二苯醚（PBDE）增加消费品的阻燃性，但这些化合物及其羟基化衍生物（OH-BDES）损害正常的甲状腺功能。将PBDES的卤素键合（XB）硒细胞体可以防止碘滴鼻丁胺酶（DIO） - 催化/去激活甲状腺激素（TH）衍生物。在这项研究中，我们使用密度函数理论计算比较DIO活性部位的甲基硒醇醚模型的XB XB相互作用的强度。 XB相互作用的强度取决于受体卤化物，卤化物的位置，环取代基的数量和羟基对XB位点的邻近。相对于SE··I相互作用的较弱的SE·····相互作用与竞争性抑制模型一致，其阻断在升高的PBDE / OH-BDE浓度下的TH的结合。 XB相互作用通常更有利于邻和元位和具有更多的吸电子取代基的底物中。用于模拟THs的结合行为的PBDES / OH-BDE，即含有Ortho和Meta溴和相邻的羟基，可以是最有效的抑制剂。高溴化的PBDES / OH-BDES对THS具有可比的相互作用能量，并且可能发生脱溴。这些结果还可以表明XB强度必须超过阈值，以便PBDES / OH-BDE经历DIO进行亲核攻击。

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