Effects of Ring Size and Polar Functional Groups on the Glutathione Peroxidase-Like Antioxidant Activity of Water-Soluble Cyclic Selenides
Effects of Ring Size and Polar Functional Groups on the Glutathione Peroxidase-Like Antioxidant Activity of Water-Soluble Cyclic Selenides
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DOI：
10.1021/acs.joc.5b00544
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发表时间：
2015-06-05
影响因子：
3.6
通讯作者：
Iwaoka, Michio
中科院分区：
文献类型：
--
作者：
Arai, Kenta;Kumakura, Fumio;Iwaoka, Michio
为了阐明环结构和取代基对脂肪族硒化物类谷胱甘肽过氧化物酶（GPx-）类抗氧化活性的影响，合成了一系列具有可变环大小和极性官能团的水溶性环硒化物，并在水中用H2O2和谷胱甘肽（GSH）进行nadph偶联实验，在甲醇中用H2O2和二硫苏糖醇（DTTred）进行核磁共振波谱分析。在水中发现了类gpx活性、硒化物氧化的二阶速率常数和水中计算的HOMO能级之间的强相关性。结果支持了氧化过程是催化循环速率决定步骤的结论。另一方面，在甲醇中观察到的活性没有得到这种相关性。确定最佳环尺寸为5个。取代基的类型（NH2 < OH < CO2H）和数量也能控制活性，而立体构型对水中活性的影响很小。然而，在甲醇中，活性等级不能用适用于水的简单场景来解释。
To elucidate the effects of ring structure and a substituent on the glutathione peroxidase- (GPx-) like antioxidant activities of aliphatic selenides, series of water-soluble cyclic selenides with variable ring size and polar functional groups were synthesized, and their antioxidant activities were evaluated by NADPH-coupled assay using H2O2 and glutathione (GSH) in water and also by NMR spectroscopy using H2O2 and dithiothreitol (DTTred) in methanol. Strong correlations were found among the GPx-like activity in water, the second-order rate constants for the oxidation of the selenides, and the HOMO energy levels calculated in water. The results support the conclusion that the oxidation process is the rate-determining step of the catalytic cycle. On the other hand, such correlations were not obtained for the activity observed in methanol. The optimal ring size was determined to be five. The type of substituent (NH2 < OH < CO2H) and the number can also control the activity, whereas the stereoconfiguration has only marginal effects on the activity in water. In methanol, however, the activity rank could not be explained by the simple scenarios applicable in water.