2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels

Cui, Qi; Shieh, Meg; Pan, Tony W.; Nishimura, Akiyuki; Matsunaga, Tetsuro; Kelly, Shane S.; Xu, Shi; Jung, Minkyung; Ogata, Seiryo; Morita, Masanobu; Yoshitake, Jun; Chen, Xiaoyan; Robinson, Jerome R.; Qian, Wei-Jun; Nishida, Motohiro; Akaike, Takaaki; Xian, Ming

doi:10.1038/s41467-024-46652-7

Title: 2H-Thiopyran-2-thione sulfine, a compound for converting H₂S to HSOH/H₂S₂ and increasing intracellular sulfane sulfur levels

Journal Article · 19 March 2024 · Nature Communications

DOI: https://doi.org/10.1038/s41467-024-46652-7 · OSTI ID:2417637

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Brown Univ., Providence, RI (United States)
National Institues of Natural Sciences, Okazaki (Japan). National Institute for Physiological Sciences (NIPS) and xploratory Research Center on Life and Living Systems (ExCELLS)
Tohoku Univ., Sendai (Japan)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
National Institues of Natural Sciences, Okazaki (Japan). National Institute for Physiological Sciences (NIPS) and xploratory Research Center on Life and Living Systems (ExCELLS); Kyushu Univ., Fukuoka (Japan)

Reactive sulfane sulfur species such as persulfides (RSSH) and H₂S₂ are important redox regulators and closely linked to H₂S 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 H₂S to HSOH, and then to H₂S₂ in the presence of excess H₂S. 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 H₂S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H₂S donors, the corresponding donors of H₂S₂ (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.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2417637

Report Number(s):: PNNL-SA--195718

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
HSOH
donors
hydrogen persulfide (H2S2)
hydrogen sulfide (H2S)
redox signaling

Title: 2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels

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Title: 2H-Thiopyran-2-thione sulfine, a compound for converting H₂S to HSOH/H₂S₂ and increasing intracellular sulfane sulfur levels