Department of Chemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, CEP 97105-900 Santa Maria, RS, Brazil.
Molecules. 2012 Oct 19;17(10):12287-96. doi: 10.3390/molecules171012287.
Diphenyl diselenide has shown interesting biological activities in various free-radical-induced damage models and can be considered as a potential candidate drug against oxidative stress. Apart from its anti-oxidant activity, this compound can oxidize various thiols. However there are no detailed studies in the literature about the thiol oxidase-like activity of this compound against biologically significant mono and di-thiols with respect to various pH conditions. Keeping in mind the scarcity of data in this area of organochalcogen chemistry, we report for the first time the kinetics of thiol oxidation by diphenyl diselenide, which was carried out in a commonly used phosphate buffer, not only at physiological pH, but also at a number of acidic values. The relative reactivities of the different thiols with diphenyl diselenide were independent of the pKa of the thiol group, such that at pH 7.4, cysteine and dithiothreitol were the most reactive, while 2,3-dimercapto-1-propanesulfonic acid and glutathione were weakly reactive and extremely low reactivity was observed with dimercaptosuccinic acid. Rate of oxidation was dependent on the pH of the incubation medium. The results obtained will help us in the design of rational strategies for the safe pharmacological use of diphenyl diselenide.
二苯二硒醚在各种自由基诱导损伤模型中表现出有趣的生物活性，可被视为一种潜在的抗氧化应激候选药物。除了抗氧化活性外，该化合物还可以氧化各种硫醇。然而，关于该化合物在不同 pH 条件下对具有生物学意义的单硫醇和二硫醇的硫醇氧化酶样活性，文献中尚无详细研究。考虑到有机硒化学这一领域数据的稀缺性，我们首次报道了二苯二硒醚对硫醇的氧化动力学，该动力学在常用的磷酸盐缓冲液中进行，不仅在生理 pH 值下，而且在许多酸性值下都进行了研究。不同硫醇与二苯二硒醚的相对反应性与硫醇基团的 pKa 无关，因此在 pH 7.4 时，半胱氨酸和二硫苏糖醇的反应性最强，而 2,3-二巯基-1-丙磺酸和谷胱甘肽的反应性较弱，二巯基丁二酸的反应性极低。氧化速率取决于孵育介质的 pH 值。所得结果将有助于我们设计合理的策略，以安全地进行二苯二硒醚的药理学应用。
