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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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Colorimetric Carbonyl Sulfide (COS)/Hydrogen Sulfide (H 2 S) Donation from γ‐Ketothiocarbamate Donor Motifs
Abstract Hydrogen sulfide (H2S) is a biologically active molecule that exhibits protective effects in a variety of physiological and pathological processes. Although several H2S‐related biological effects have been discovered by using H2S donors, knowing how much H2S has been released from donors under different conditions remains challenging. Now, a series of γ‐ketothiocarbamate (γ‐KetoTCM) compounds that provide the first examples of colorimetric H2S donors and enable direct quantification of H2S release, were reported. These compounds are activated through a pH‐dependent deprotonation/β‐elimination sequence to release carbonyl sulfide (COS), which is quickly converted into H2S by carbonic anhydrase. Thep‐nitroaniline released upon donor activation provides an optical readout that correlates directly to COS/H2S release, thus enabling colorimetric measurement of H2S donation.
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- PAR ID:
- 10074321
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 57
- Issue:
- 40
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 13101-13105
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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