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Hydrogen sulfide (H2S) is an endogenous signaling molecule that greatly influences several important (patho)physiological processes related to cardiovascular health and disease, including vasodilation, angiogenesis, inflammation, and cellular redox homeostasis. Consequently, H2S supplementation is an emerging area of interest, especially for the treatment of cardiovascular-related diseases. To fully unlock the medicinal properties of hydrogen sulfide, however, the development and refinement of H2S releasing compounds (or donors) are required to augment its bioavailability and to better mimic its natural enzymatic production. Categorizing donors by the biological stimulus that triggers their H2S release, this review highlights the fundamental chemistry and releasing mechanisms of a range of H2S donors that have exhibited promising protective effects in models of myocardial ischemia-reperfusion (MI/R) injury and cancer chemotherapy-induced cardiotoxicity, specifically. Thus, in addition to serving as important investigative tools that further advance our knowledge and understanding of H2S chemical biology, the compounds highlighted in this review have the potential to serve as vital therapeutic agents for the treatment (or prevention) of various cardiomyopathies.
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This content will become publicly available on August 1, 2026
Self-Reporting H2S Donors: Integrating H2S Release with Real-Time Fluorescence Detection
Hydrogen sulfide (H2S), once regarded solely as a highly toxic gas, is now recognized as a crucial signaling molecule in plants, bacteria, and mammals. In humans, H2S signaling plays a role in numerous physiological and pathological processes, including vasodilation, neuromodulation, and cytoprotection. To exploit its biological functions and therapeutic potential, a wide range of H2S-releasing compounds, known as H2S donors, have been developed. These donors are designed to release H2S under physiological conditions in a controlled manner. Among them, self-reporting H2S donors are seen as a particularly innovative class, combining therapeutic delivery with real-time fluorescence-based detection. This dual functionality enables spatiotemporal monitoring of H2S release in biological environments, eliminating the need for additional sensors or probes that could disrupt cellular homeostasis. This review summarizes recent advancements in self-reporting H2S donor systems, organizing them based on their activation triggers, such as specific bioanalytes, enzymes, or external stimuli like light. The discussion covers their design strategies, performance in biological applications, and therapeutic potential. Key challenges are also highlighted, including the need for precise control of H2S release kinetics, accurate signal quantification, and improved biocompatibility. With continued refinement, self-reporting H2S donors offer great promise for creating multifunctional platforms that seamlessly integrate diagnostic imaging with therapeutic H2S delivery.
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- Award ID(s):
- 2143826
- PAR ID:
- 10649094
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Chemistry
- Volume:
- 7
- Issue:
- 4
- ISSN:
- 2624-8549
- Page Range / eLocation ID:
- 116
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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