Glutathione peroxidase-like antioxidant activity of diaryl diselenides: A mechanistic study
Glutathione peroxidase-like antioxidant activity of diaryl diselenides: A mechanistic study
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DOI：
10.1021/ja994467p
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发表时间：
2001-02-07
影响因子：
15
通讯作者：
Butcher, RJ
中科院分区：
文献类型：
--
作者：
Mugesh, G;Panda, A;Butcher, RJ
介绍了几种分子内配位氨基的二芳基二硒醚的合成、结构和巯基过氧化物酶样抗氧化活性。对映体纯的R-（+）-和S-（-）-N，N-二甲基（1-二茂铁基乙基）胺衍生的二硒醚显示出优异的过氧化物酶活性。为了研究各种有机硒中间体的机械作用，已进行了详细的原位表征的中间体通过Se-77 MMR光谱。虽然大多数的二硒醚发挥其过氧化物酶活性通过硒醇，硒酸，和硒基硫化物中间体，二硒醚的相对活性的差异是由于分子内硒的不同程度。. .N交互。二硒醚具有较强的Se。. .N相互作用被发现是无活性的，由于它们的硒基硫化物衍生物的能力，以增强反向GPx循环（RSeSR + H2 O2 = RSeOH）。在这些情况下，硫醇的亲核攻击优先发生在硒而不是硫上，这通过终止正向反应减少了硒醇的形成。另一方面，具有弱Se . . .N相互作用被发现是更活跃的，由于硒基硫化物衍生物与硫醇的快速反应，以产生二苯基二硫化物和预期的硒醇（RSeSR + PhSH = PhSSPh + RSeH）。发现未取代的二芳基二硒醚活性较低，这是由于这些二硒醚与硫醇和过氧化氢的反应缓慢以及中间体的不稳定性。18和19的催化循环非常类似于天然酶谷胱甘肽过氧化物酶催化氢过氧化物还原的机制。
The synthesis, structure, and thiol peroxidase-like antioxidant activities of several diaryl diselenides having intramolecularly coordinating amino groups are described. The diselenides derived from enantiomerically pure R-(+)- and S-(-)-N,N-dimethyl(1-ferrocernylethyl)amine show excellent peroxidase activity. To investigate the mechanistic role of various organoselenium intermediates, a detailed in situ characterization of the intermediates has been carried out by Se-77 MMR spectroscopy. While most of the diselenides exert their peroxidase activity via selenol, selenenic acid, and selenenyl sulfide intermediates, the differences in the relative activities of the diselenides are due to the varying degree of intramolecular Se . . .N interaction. The diselenides having strong Se . . .N interactions are found to be inactive due to the ability of their selenenyl sulfide derivatives to enhance the reverse GPx cycle (RSeSR + H2O2 = RSeOH). In these cases, the nucleophilic attack of thiol takes place preferentially at selenium rather than sulfur and this reduces the formation of selenol by terminating the forward reaction. On the other hand, the diselenides having weak Se . . .N interactions are found to be more active due to the fast reaction of the selenenyl sulfide derivatives with thiol to produce diphenyl disulfide and the expected selenol (RSeSR + PhSH = PhSSPh + RSeH). The unsubstituted diaryl diselenides are found to be less active due to the slow reactions of these diselenides with thiol and hydrogen peroxide and also due to the instability of the intermediates. The catalytic cycles of 18 and 19 strongly resemble the mechanism by which the natural enzyme, glutathione peroxidase, catalyzes the reduction of hydroperoxides.