Department of Chemistry, Brown University, Providence, RI, 02912, USA.
Division of Cardiocirculatory Signaling, National Institute for Physiological Sciences (NIPS) and Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, 444-8787, Japan.
Nat Commun. 2024 Mar 19;15(1):2453. doi: 10.1038/s41467-024-46652-7.
Reactive sulfane sulfur species such as persulfides (RSSH) and HS are important redox regulators and closely linked to HS signaling. However, the study of these species is still challenging due to their instability, high reactivity, and the lack of suitable donors to produce them. Herein we report a unique compound, 2H-thiopyran-2-thione sulfine (TTS), which can specifically convert HS to HSOH, and then to HS in the presence of excess HS. Meanwhile, the reaction product 2H-thiopyran-2-thione (TT) can be oxidized to reform TTS by biological oxidants. The reaction mechanism of TTS is studied experimentally and computationally. TTS can be conjugated to proteins to achieve specific delivery, and the combination of TTS and HS leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established HS donors, the corresponding donors of HS (or its equivalents) are obtained. Cell-based studies reveal that TTS can effectively increase intracellular sulfane sulfur levels and compensate for certain aspects of sulfide:quinone oxidoreductase (SQR) deficiency. These properties make TTS a conceptually new strategy for the design of donors of reactive sulfane sulfur species.
活性硫物种，如过硫物（RSSH）和 HS，是重要的氧化还原调节剂，与 HS 信号密切相关。然而，由于这些物质的不稳定性、高反应活性以及缺乏合适的供体来产生它们，因此对这些物质的研究仍然具有挑战性。在这里，我们报告了一种独特的化合物 2H-噻喃-2-硫酮亚磺酰（TTS），它可以特异性地将 HS 转化为 HSOH，然后在过量 HS 的存在下转化为 HS。同时，反应产物 2H-噻喃-2-硫酮（TT）可以被生物氧化剂氧化，重新形成 TTS。TTS 的反应机制通过实验和计算进行了研究。TTS 可以与蛋白质结合，实现特异性递送，并且 TTS 和 HS 的结合导致蛋白质高度有效地发生过硫化。当 TTS 与已建立的 HS 供体联合使用时，可以得到相应的 HS 供体（或其等价物）。基于细胞的研究表明，TTS 可以有效地增加细胞内硫烷硫水平，并补偿亚硫酸氢盐：醌氧化还原酶（SQR）缺乏的某些方面。这些特性使 TTS 成为设计活性硫烷硫物种供体的一种新概念策略。
