2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels
Qi Cui, Meg Shieh, Tony W. Pan, Akiyuki Nishimura, Tetsuro Matsunaga, Shane S. Kelly, Shi Xu, Minkyung Jung, Seiryo Ogata, Masanobu Morita, Jun Yoshitake, X. M. Chen, Jerome R. Robinson, Weijun Qian, Motohiro Nishida, Takaaki Akaike, Ming Xian
Abstract
Abstract Reactive sulfane sulfur species such as persulfides (RSSH) and H 2 S 2 are important redox regulators and closely linked to H 2 S 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 H 2 S to HSOH, and then to H 2 S 2 in the presence of excess H 2 S. 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 H 2 S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H 2 S donors, the corresponding donors of H 2 S 2 (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.