Synthesis, Stability, and Kinetics of Hydrogen Sulfide Release of Dithiophosphates
Ontology highlight
ABSTRACT:
SUBMITTER: Brown E
PROVIDER: S-EPMC8569798 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Hydrogen sulfide (H2S) is an important biological signaling agent that exerts action on numerous (patho)physiological processes. Once generated, H2S can be oxidized to generate reductant-labile sulfane sulfur pools, which include hydrodisulfides/persulfides. Despite the importance of hydrodisulfides in H2S storage and signaling, little is known about the physical properties or chemical reactivity of these compounds. We report here the synthesis, isolation, and characterization (NMR, IR, Raman, HRMS, X-ray) of a small-molecule hydrodisulfide and highlight its reactivity with reductants, nucleophiles, electrophiles, acids, and bases. Our experimental results establish that hydrodisulfides release H2S upon reduction and that deprotonation results in disproportionation to the parent thiol and S(0), thus providing a mechanism for transsulfuration in the sulfane sulfur pool.
| S-EPMC4120993 | biostudies-literature
Project description:"Caged" gem-dithiol derivatives that release H2S upon light stimulation have been developed. This new class of H2S donors was proven, by various spectroscopic methods, to generate H2S in an aqueous/organic medium as well as in cell culture.
| S-EPMC3701299 | biostudies-literature
Project description:Hydrogen sulfide (H2S) is an important signaling molecule that provides protective activities in a variety of physiological and pathological processes. Among the different types of H2S donor compounds, thioamides have attracted attention due to prior conjugation to nonsteroidal anti-inflammatory drugs (NSAIDs) to access H2S-NSAID hybrids with significantly reduced toxicity, but the mechanism of H2S release from thioamides remains unclear. Herein, we reported the synthesis and evaluation of a class of thioamide-derived sulfenyl thiocarbamates (SulfenylTCMs) that function as a new class of H2S donors. These compounds are efficiently activated by cellular thiols to release carbonyl sulfide (COS), which is quickly converted to H2S by carbonic anhydrase (CA). In addition, through mechanistic investigations, we establish that COS-independent H2S release pathways are also operative. In contrast to the parent thioamide-based donors, the SulfenylTCMs exhibit excellent H2S releasing efficiencies of up to 90% and operate through mechanistically well-defined pathways. In addition, we demonstrate that the sulfenyl thiocarbamate group is readily attached to common NSAIDs, such as naproxen, to generate YZ-597 as an efficient H2S-NSAID hybrid, which we demonstrate releases H2S in cellular environments. Taken together, this new class of H2S donor motifs provides an important platform for new donor development.
| S-EPMC7023849 | biostudies-literature
Project description:Recent efforts have expanded the development of small molecule donors that release the important biological signaling molecule hydrogen sulfide (H2S). Previous work on 1,2,4-thiadiazolidin-3,5-diones (TDZNs) reported that these compounds release H2S directly, albeit inefficiently. However, TDZNs showed promising efficacy in H2S-mediated relaxation in ex vivo aortic ring relaxation models. Here, we show that TDZNs release carbonyl sulfide (COS) efficiently, which can be converted to H2S by the enzyme carbonic anhydrase (CA) rather than releasing H2S directly as previously reported.
| S-EPMC9893878 | biostudies-literature
Project description:A series of O-aryl- and alkyl-substituted phosphorodithioates were designed and synthesized as hydrogen sulfide (H2S) donors. H2S releasing capability of these compounds was evaluated using fluorescence methods. O-aryl substituted donors showed slow and sustained H2S release while O-alkylated compounds showed very weak H2S releasing capability. We also evaluated donors' protective effects against hydrogen peroxide (H2O2)-induced oxidative damage in myocytes and donors' toxicity toward B16BL6 mouse melanoma cells.
| S-EPMC3789624 | biostudies-literature
Project description:Ammonium tetrathiomolybdate (TTM) was found to be a slow hydrogen sulfide (H2S) releasing agent. Its H2S generation capability in aqueous solutions was confirmed by UV-vis and fluorescence assays. TTM also showed H2S-like cytoprotective effects in hydrogen peroxide (H2O2)-induced oxidative damage in HaCaT cells.
| S-EPMC4775341 | biostudies-literature
Project description:Hydrogen sulfide (H2S) is one of the important biological mediators involved in physiological and pathological processes in mammals. Recently developed H2S donors show promising effects against several pathological processes in preclinical and early clinical studies. For example, H2S donors have been found to be effective in the prevention of gastrointestinal ulcers during anti-inflammatory treatment. Notably, there are well-established medicines used for the treatment of a variety of diseases, whose chemical structure contains sulfur moieties and may release H2S. Hence, the therapeutic effect of these drugs may be partly the result of the release of H2S occurring during drug metabolism and/or the effect of these drugs on the production of endogenous hydrogen sulfide. In this work, we review data regarding sulfur drugs commonly used in clinical practice that can support the hypothesis about H2S-dependent pharmacotherapeutic effects of these drugs.
| S-EPMC7072623 | biostudies-literature
Project description:Heterosubstituted disulfides are an understudied class of molecules that have been used in biological studies, but they have not been investigated for their ability to release hydrogen sulfide (H2S). The synthesis of two sets of chemicals with the diaminodisulfide (NSSN) and dialkoxydisulfide (OSSO) functional groups was reported. These chemicals were synthesized from commercially available sulfur monochloride or a simple disulfur transfer reagent. Both the diaminodisulfide and dialkoxydisulfide functional groups were found to have rapid rates of H2S release in the presence of excess thiol. The release of H2S was complete with 10 min, and the only byproducts were conversion of the thiols into disulfides and the amines or alcohols originally used in the synthesis of the diaminodisulfide or dialkoxydisulfide functional groups. These results will allow the design of H2S releasing chemicals that also release natural, biocompatible alcohols or amines. Chemicals with the diaminodisulfide and dialkoxydisulfide functional groups may find applications in medicine where a controlled, burst release of H2S is needed.
| S-EPMC8280695 | biostudies-literature
Project description:We conducted a detailed kinetic study of the reaction of the vitamin B12 analog diaquacobinamide ((H2O)2Cbi(III)) with hydrogen sulfide in water from pH 3 to 11. The reaction proceeds in three steps: (i) formation of three different complexes between cobinamide and hydrogen sulfide, viz. (HO-)(HS-)Cbi(III), (H2O)(HS-)Cbi(III), and (HS-)2Cbi(III); (ii) inner-sphere electron transfer (ISET) in the two complexes with one coordinated HS- to form the reduced cobinamide complex [(H)S]Cbi(II); and (iii) addition of a second molecule of hydrogen sulfide to the reduced cobinamide. ISET does not proceed in the (HS-)2Cbi(III) complex. The final products of the reaction between cobinamide and hydrogen sulfide were found to be independent of pH, with the main product being a complex of cobinamide(II) with the anion-radical SSH2-.
| S-EPMC4286256 | biostudies-literature
Project description:Prodrugs that release hydrogen sulfide upon esterase-mediated cleavage of an ester group followed by lactonization are described herein. By modifying the ester group and thus its susceptibility to esterase, and structural features critical to the lactonization rate, H2 S release rates can be tuned. Such prodrugs directly release hydrogen sulfide without the involvement of perthiol species, which are commonly encountered with existing H2 S donors. Additionally, such prodrugs can easily be conjugated to another non-steroidal anti-inflammatory agent, leading to easy synthesis of hybrid prodrugs. As a biological validation of the H2 S prodrugs, the anti-inflammatory effects of one such prodrug were examined by studying its ability to inhibit LPS-induced TNF-α production in RAW 264.7 cells. This type of H2 S prodrugs shows great potential as both research tools and therapeutic agents.
| S-EPMC4902284 | biostudies-literature