Intramolecular Thiol‐ and Selenol‐Assisted Delivery of Hydrogen Sulfide
Intramolecular Thiol‐ and Selenol‐Assisted Delivery of Hydrogen Sulfide
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分子内硫醇和硒醇辅助硫化氢的传递
DOI：
10.1002/anie.202210754
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Lukesh, III, John C.
中科院分区：
文献类型：
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作者：
Hu, Qiwei;Suarez, S. Israel;Hankins, Rynne A.;Lukesh, III, John C.
芳基硫胺经常被用来评估硫化氢（H2S）的化学生物学和药理学。然而，这类供体的硫化氢释放效率极低，相关的机制研究也被忽略。因此，需要毫摩尔浓度的芳基硫酰胺来释放微量的H2S，并且通过一个未知的机制途径，这使得对其使用产生的任何生物活性的解释变得模糊。在这里，我们报告了H2S释放从这类有价值的供体可以通过分子内亲核辅助显着增强。具体来说，我们证明了二硫化物和二硫化物连接的硫酰胺都对生物相关浓度的谷胱甘肽有反应，并通过分子内环化释放两摩尔当量的H2S，这大大提高了它们在缓冲液和活的人类细胞中的硫化物递送速度和效率。
Arylthioamides have been frequently employed to assess the chemical biology and pharmacology of hydrogen sulfide (H2S). From this class of donors, however, extremely low H2S releasing efficiencies have been reported and proper mechanistic studies have been omitted. Consequently, millimolar concentrations of arylthioamides are required to liberate just trace amounts of H2S, and via an unidentified mechanistic pathway, which obfuscates the interpretation of any biological activity that stems from their use. Herein, we report that H2S release from this valuable class of donors can be markedly enhanced through intramolecular nucleophilic assistance. Specifically, we demonstrate that both disulfide‐ and diselenide‐linked thioamides are responsive to biologically relevant concentrations of glutathione and release two molar equivalents of H2S via an intramolecular cyclization that significantly augments their rate and efficiency of sulfide delivery in both buffer and live human cells.