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Hydrogen sulfide (H 2 S) is an important cellular signaling molecule that exhibits promising protective effects. Although a number of triggerable H 2 S donors have been developed, spatiotemporal feedback from H 2 S release in biological systems remains a key challenge in H 2 S donor development. Herein we report the synthesis, evaluation, and application of caged sulfenyl thiocarbonates as new fluorescent H 2 S donors. These molecules rely on thiol cleavage of sulfenyl thiocarbonates to release carbonyl sulfide (COS), which is quickly converted to H 2 S by carbonic anhydrase (CA). This approach is a new strategy in H 2 S release and does not release electrophilic byproducts common from COS-based H 2 S releasing motifs. Importantly, the release of COS/H 2 S is accompanied by the release of a fluorescent reporter, which enables the real-time tracking of H 2 S by fluorescence spectroscopy or microscopy. Dependent on the choice of fluorophore, either one or two equivalents of H 2 S can be released, thus allowing for the dynamic range of the fluorescent donors to be tuned. We demonstrate that the fluorescence response correlates directly with quantified H 2 S release and also demonstrate the live-cell compatibility of these donors. Furthermore, these fluorescent donors exhibit anti-inflammatory effects in RAW 264.7 cells, indicating their potential application as new H 2 S-releasing therapeutics. Taken together, sulfenyl thiocarbonates provide a new platform for H 2 S donation and readily enable fluorescent tracking of H 2 S delivery in complex environments.
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This content will become publicly available on October 30, 2026
Cysteine-activated hydrogen selenide (H 2 Se) delivery from isoselenocyanates
Hydrogen selenide (H2Se) is an emerging bioregulator and precursor to essential selenium-containing biomolecules. We show that aryl isoselenocyanates (ISeC-R) release H2Se upon activation by cysteine, and that electronic substitution can modulate release profiles. We also demonstrate applications to live cell imaging, expanding available tools for investigating H2Se chemical biology.
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- Award ID(s):
- 2004150
- PAR ID:
- 10651378
- Publisher / Repository:
- Chemical Communications
- Date Published:
- Journal Name:
- Chemical Communications
- Volume:
- 61
- Issue:
- 94
- ISSN:
- 1359-7345
- Page Range / eLocation ID:
- 18685 to 18688
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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