pH-Controlled Hydrogen Sulfide Release for Myocardial Ischemia-Reperfusion Injury

Kang, Jianming; Li, Zhen; Organ, Chelsea L.; Park, Chung‐Min; Liu, Jinbao; Pacheco, Armando; Wang, Difei; Lefer, David J.; Xian, Ming

doi:10.1021/jacs.6b01373

Cited by 227 publications

(188 citation statements)

References 38 publications

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“…While this very slow H 2 S release is not necessarily a problem, it would be ideal to also have access to faster release donors, so that researchers would have more options. With this idea in mind, Kang et al (2016) reported a series of phosphonamidothioate-based donors (e.g., JK donors), which showed enhanced H 2 S releasing capabilities.…”

Section: Ph-dependent Phosphonamidothioate-based Donors (Jk Donors)mentioning

confidence: 99%

Phosphonothioate-Based Hydrogen Sulfide Releasing Reagents: Chemistry and Biological Applications

2017

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Hydrogen sulfide (H2S) is a newly recognized gasotransmitter. Studies have demonstrated that the production of endogenous H2S and the exogenous administration of H2S can regulate many physiological and/or pathological processes. Therefore, H2S releasing agents (also known as H2S donors) are important research tools in advancing our understanding of the biology and clinical potential of H2S. Among currently available donors, GYY4137 is probably the most well-known and has been used in many studies in the past 10 years. Recently, a number of GYY4137 derivatives (e.g., phosphonothioate-based compounds) have been developed as H2S donors. In this review, we summarize the development and application of these donors, which include Lawesson’s reagent, substituted phosphorodithioates, cyclic phosphorane analogs, and pH-controlled phosphonamidothioates (JK donors). These donors have advantages such as good water-solubility, slow and controllable H2S release capability, and a variety of reported biological activities. However, it should be noted that the detailed H2S release profiles and byproducts under real biological systems are still unclear for many of these donors. Only after we figure out these unknowns we will see better applications of these donors in H2S research and therapy.

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Section: Ph-dependent Phosphonamidothioate-based Donors (Jk Donors)mentioning

confidence: 99%

Phosphonothioate-Based Hydrogen Sulfide Releasing Reagents: Chemistry and Biological Applications

2017

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“…38–40 Building on the need for mechanistically-understood systems, different controllable H 2 S donors have been designed and evaluated. 21–23,25 Such donors are typically activated by specific triggers, such as cellular thiols, 41–47 light, 48–49 esterase, 50 nitroreductase, 51 or pH, 52–53 to release H 2 S (Figure 1). In addition to their small-molecule counterparts, H 2 S-releasing biomaterials, including H 2 S releasing polymers, peptides, and microfibers, are also emerging as an important class of donor materials with modifiable macromolecular properties.…”

Section: Introductionmentioning

confidence: 99%

Kinetic Insights into Hydrogen Sulfide Delivery from Caged-Carbonyl Sulfide Isomeric Donor Platforms

2017

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Hydrogen sulfide (H2S) is a biologically-important small gaseous molecule that exhibits promising protective effects against a variety of physiological and pathological processes. To investigate the expanding roles of H2S in biology, researchers often use H2S donors to mimic enzymatic H2S synthesis or to provide increased H2S levels under specific circumstances. Aligned with the need for new broad and easily-modifiable platforms for H2S donation, we report here the preparation and H2S release kinetics from a series of isomeric caged-carbonyl sulfide (COS) compounds, including thiocarbamates, thiocarbonates, and dithiocarbonates, all of which release COS that is quickly converted to H2S by the ubiquitous enzyme carbonic anhydrase. Each donor is designed to release COS/H2S after the activation of a trigger by activation by hydrogen peroxide (H2O2). In addition to providing a broad palette of new, H2O2-responsive donor motifs, we also demonstrate the H2O2 dose-dependent COS/H2S release from each donor core, establish that release profiles can be modified by structural modifications, and compare COS/H2S release rates and efficiencies from isomeric core structures. Supporting our experimental investigations, we also provide computational insights into the potential energy surfaces for COS/H2S release from each platform. In addition, we also report initial investigations into dithiocarbamate cores, which release H2S directly upon H2O2-mediated activation. As a whole, the insights on COS/H2S release gained from these investigations provide a foundation for the expansion of the emerging area of responsive COS/H2S donors systems.

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“…Changes in endogenous H 2 S levels have been claimed to impact on a diverse range of physiological processes, including neuronal function, blood pressure, angiogenesis, oxygen sensing, inflammation, and mitochondrial energy production (4–16), and exposure to H 2 S can induce a suspended animation-like state in mice (17), but not in larger animals (18, 19). …”

Section: Introductionmentioning

confidence: 99%

Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA

Arndt

Baeza-Garza

Logan

et al. 2017

Journal of Biological Chemistry

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Hydrogen sulfide (H2S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H2S source and sink, and many of the biological effects of H2S relate to its interactions with mitochondria. However, the significance of mitochondrial H2S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo. Although a number of fluorescent H2S probes have been developed these are best suited to cells in culture and cannot be used in vivo. To address this unmet need we have developed a mitochondria-targeted H2S probe, MitoA, which can be used to assess relative changes in mitochondrial H2S levels in vivo. MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo. There, the aryl azido group reacts with H2S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H2S in vivo. Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H2S levels in vivo. As a proof of principle we used MitoA to show that H2S levels increase in vivo during myocardial ischemia.

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pH-Controlled Hydrogen Sulfide Release for Myocardial Ischemia-Reperfusion Injury

Cited by 227 publications

References 38 publications

Phosphonothioate-Based Hydrogen Sulfide Releasing Reagents: Chemistry and Biological Applications

Phosphonothioate-Based Hydrogen Sulfide Releasing Reagents: Chemistry and Biological Applications

Kinetic Insights into Hydrogen Sulfide Delivery from Caged-Carbonyl Sulfide Isomeric Donor Platforms

Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA

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