Use of Dithiasuccinoyl-Caged Amines Enables COS/H2S Release Lacking Electrophilic Byproducts

The enzymatic conversion of carbonyl sulfide (COS) to hydrogen sulfide (H₂S) by carbonic anhydrase has been used to develop self-immolating thiocarbamates as COS-based H₂S donors to further elucidate the impact of reactive sulfur species in biology. The high modularity of this approach has provided a library of COS-based H₂S donors that can be activated by specific stimuli. A common limitation, however, is that many such donors result in the formation of an electrophilic quinone methide byproduct during donor activation. As a mild alternative, we demonstrate here that dithiasuccinoyl groups can function as COS/H₂S donor motifs, and that these groups release two equivalents of COS/H₂S and uncage an amine payload under physiologically relevant conditions. Additionally, we demonstrate that COS/H₂S release from this donor motif can be altered by electronic modulation and alkyl substitution. These insights are further supported by DFT investigations, which reveal that aryl and alkyl thiocarbamates release COS with significantly different activation energies.     

Colorimetric Carbonyl Sulfide (COS)/Hydrogen Sulfide (H2S) Donation from γ‐Ketothiocarbamate Donor Motifs

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. The p‐nitroaniline released upon donor activation provides an optical readout that correlates directly to COS/H₂S release, thus enabling colorimetric measurement of H₂S donation.     

Hydrogen Sulfide Donors Activated by Reactive Oxygen Species

Hydrogen sulfide (H₂S) exhibits promising protective effects in many (patho)physiological processes, as evidenced by recent reports using synthetic H₂S donors in different biological models. Herein, we report the design and evaluation of compounds denoted PeroxyTCM, which are the first class of reactive oxygen species (ROS)‐triggered H₂S donors. These donors are engineered to release carbonyl sulfide (COS) upon activation, which is quickly hydrolyzed to H₂S by the ubiquitous enzyme carbonic anhydrase (CA). The donors are stable in aqueous solution and do not release H₂S until triggered by ROS, such as hydrogen peroxide (H₂O₂), superoxide (O₂^?), and peroxynitrite (ONOO^?). We demonstrate ROS‐triggered H₂S donation in live cells and also demonstrate that PeroxyTCM‐1 provides protection against H₂O₂‐induced oxidative damage, suggesting potential future applications of PeroxyTCM and similar scaffolds in H₂S‐related therapies.     

Esterase‐Sensitive Prodrugs with Tunable Release Rates and Direct Generation of Hydrogen Sulfide

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, H₂S release rates can be tuned. Such prodrugs directly release hydrogen sulfide without the involvement of perthiol species, which are commonly encountered with existing H₂S 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 H₂S 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 H₂S prodrugs shows great potential as both research tools and therapeutic agents.     

A Persulfide Donor Responsive to Reactive Oxygen Species: Insights into Reactivity and Therapeutic Potential

Persulfides (RSSH) have been hypothesized as critical components in sulfur‐mediated redox cycles and as potential signaling compounds, similar to hydrogen sulfide (H₂S). Hindering the study of persulfides is a lack of persulfide‐donor compounds with selective triggers that release discrete persulfide species. Reported here is the synthesis and characterization of a ROS‐responsive (ROS=reactive oxygen species), self‐immolative persulfide donor. The donor, termed BDP‐NAC, showed selectivity towards H₂O₂ over other potential oxidative or nucleophilic triggers, resulting in the sustained release of the persulfide of N‐acetyl cysteine (NAC) over the course of 2 h, as measured by LCMS. Exposure of H9C2 cardiomyocytes to H₂O₂ revealed that BDP‐NAC mitigated the effects of a highly oxidative environment in a dose‐dependent manner over relevant controls and to a greater degree than common H₂S donors sodium sulfide (Na₂S) and GYY4137. BDP‐NAC also rescued cells more effectively than a non‐persulfide‐releasing control compound in concert with common H₂S donors and thiols.     

A Single-Component Dual Donor Enables Ultrasound-Triggered Co-release of Carbon Monoxide and Hydrogen Sulfide

The development of dual gasotransmitter donors can not only provide robust tools to investigate their subtle interplay under pathophysiological conditions but also optimize therapeutic efficacy. While conventional strategies are heavily dependent on multicomponent donors, we herein report an ultrasound-responsive water-soluble copolymer ( PSHF ) capable of releasing carbon monoxide (CO) and hydrogen sulfide (H₂S) based on single-component sulfur-substituted 3-hydroxyflavone (SHF) derivatives. Interestingly, sulfur substitution can not only greatly improve the ultrasound sensitivity but also enable the co-release of CO/H₂S under mild ultrasound irradiation. The co-release of CO/H₂S gasotransmitters exerts a bactericidal effect against Staphylococcus aureus and demonstrates anti-inflammatory activity in lipopolysaccharide-challenged macrophages. Moreover, the excellent tissue penetration of ultrasound irradiation enables the local release of CO/H₂S in the joints of septic arthritis rats, exhibiting superior therapeutic efficacy without the need for any antibiotics.     

Hydrogen Sulfide: Novel Endogenous and Exogenous Modulator of Oxidative Stress in Retinal Degeneration Diseases

Oxidative stress (OS) damage can cause significant injury to cells, which is related to the occurrence and development of many diseases. This pathological process is considered to be the first step to trigger the death of outer retinal neurons, which is related to the pathology of retinal degenerative diseases. Hydrogen sulfide (H₂S) has recently received widespread attention as a physiological signal molecule and gas neuromodulator and plays an important role in regulating OS in eyes. In this article, we reviewed the OS responses and regulatory mechanisms of H₂S and its donors as endogenous and exogenous regulators in retinal degenerative diseases. Understanding the relevant mechanisms will help to identify the therapeutic potential of H₂S in retinal degenerative diseases.     

A Synthetic Supramolecular Receptor for the Hydrosulfide Anion

Hydrogen sulfide (H₂S) has emerged as a crucial biomolecule in physiology and cellular signaling. Key challenges associated with developing new chemical tools for understanding the biological roles of H₂S include developing platforms that enable reversible binding of this important biomolecule. The first synthetic small molecule receptor for the hydrosulfide anion, HS^?, using only reversible, hydrogen‐bonding interactions in a series of bis(ethynylaniline) derivatives, is reported. Binding constants of up to 90 300±8700 m ^?1 were obtained in MeCN. The fundamental science of reversible sulfide binding, in this case featuring a key CH???S hydrogen bond, will expand the possibility for discovery of sulfide protein targets and molecular recognition agents.     

Biocompatible metal–organic frameworks for the storage and therapeutic delivery of hydrogen sulfide

Hydrogen sulfide (H₂S) is an endogenous gasotransmitter with potential therapeutic value for treating a range of disorders, such as ischemia-reperfusion injury resulting from a myocardial infarction or stroke. However, the medicinal delivery of H₂S is hindered by its corrosive and toxic nature. In addition, small molecule H₂S donors often generate other reactive and sulfur-containing species upon H₂S release, leading to unwanted side effects. Here, we demonstrate that H₂S release from biocompatible porous solids, namely metal–organic frameworks (MOFs), is a promising alternative strategy for H₂S delivery under physiologically relevant conditions. In particular, through gas adsorption measurements and density functional theory calculations we establish that H₂S binds strongly and reversibly within the tetrahedral pockets of the fumaric acid-derived framework MOF-801 and the mesaconic acid-derived framework Zr-mes, as well as the new itaconic acid-derived framework CORN-MOF-2. These features make all three frameworks among the best materials identified to date for the capture, storage, and delivery of H₂S. In addition, these frameworks are non-toxic to HeLa cells and capable of releasing H₂S under aqueous conditions, as confirmed by fluorescence assays. Last, a cellular ischemia-reperfusion injury model using H9c2 rat cardiomyoblast cells corroborates that H₂S-loaded MOF-801 is capable of mitigating hypoxia-reoxygenation injury, likely due to the release of H₂S. Overall, our findings suggest that H₂S-loaded MOFs represent a new family of easily-handled solid sources of H₂S that merit further investigation as therapeutic agents. In addition, our findings add Zr-mes and CORN-MOF-2 to the growing lexicon of biocompatible MOFs suitable for drug delivery.

Metal–organic frameworks enable the delivery of hydrogen sulfide (H₂S), an endogenous gasotransmitter with potential therapeutic value for treating disorders such as ischemia-reperfusion injury.     

Development of a shape‐controlled H2S delivery system using epoxide‐functional nanoparticles

Hydrogen sulfide (H₂S), an endogenous modulator of signaling processes, has potential as a therapeutic drug or in combination drug therapies. Due to its broad biological impacts and malodorous nature, there is considerable interest in vehicles capable of delivering H₂S in a controlled manner. Herein, we report postpolymerization modification of polymers incorporating glycidyl methacrylate (GMA) units to form thiol‐triggered macromolecular H₂S donors. By combining this approach with polymerization‐induced self‐assembly, this methodology allows the facile preparation of polymeric nanoparticulate donors with either spherical or worm‐like morphology. The thiol‐reactive epoxide functional groups in poly(GMA) were chemically transformed into acyl‐protected perthiol groups using a three‐step procedure throughout which both morphologies remained intact. The H₂S releasing properties were subsequently studied, with both spherical and worm‐like nanoparticulate donors shown to successfully release H₂S in the presence of the model thiol, l ‐cysteine. In addition, the donor polymers were shown to effectively increase H₂S inside cells, upon exposure to biologically relevant endogenous thiol levels. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1982–1993     

A Novel QCM-based Biosensor for Detection of Microorganisms Producing Hydrogen Sulfide

Abstract

A novel piezoelectric quartz crystal microbalance (QCM) device with gas permeable membrane is proposed for the detection of microorganisms producing hydrogen sulfide (H₂S). The detection theory is based on the adsorption of hydrogen sulfide onto the silver electrode of the piezoelectric crystal sensor, which causes a dramatic decrease in the resonant frequency of QCM. A 100 Hz frequency shift is chosen as the criteria value to judge the presence of microorganisms producing H₂S. Factors affecting detection were investigated. Desiccant is of great practical importance in sensor response. This new biosensor can be a potential candidate for detecting bacteria which produce hydrogen sulfide.     

Reactions of Group V Metal Atoms with Hydrogen Sulfide:Argon Matrix Infrared Spectra and Theoretical Calculations

The reaction of laser-ablated vanadium, niobium and tantalum atoms with hydrogen sulfide has been investigated using matrix isolation FTIR and theoretical calculations. The metal atoms inserted into the H-S bond of H₂S to form the HMSH molecules (M=V, Nb, Ta), which rearranged to H₂MS molecules on annealing for Nb and Ta. The HMSH molecule can also further react with another H₂S to form the H₂M(SH)₂ molecules. These new molecules were identified on the basis of the D₂S and H₂³⁴S isotopic substitutions. DFT (B3LYP and BPW91) theoretical calculations are used to predict energies, geometries, and vibrational frequencies for these novel metal dihydrido complexes and molecules. Reaction mechanism for formation of group V dihydrido complex was investigated by DFT internal reaction coordinate calculations. The dissociation of HVSH gave VS+H₂ on broad band irradiation and reverse reaction happened on annealing. Based on B3LYP calculation releasing hydrogen from HVSH is endothermic only by 13.5 kcal/mol with lower energy barrier of 16.9 kcal/mol.     

Novel fluorescent probe based on dicoumarin for detection of hydrogen sulfide in real samples

A novel dicoumarin-derived hydrogen sulfide (H₂S) selective fluorescent “turn-on” probe 3-(2,4-dinitrobenzenesulfonate)-dicoumarin (DC-HS) created by covalent bonding between the 2,4-dinitrobenzenesulfonyl (DNBS) and the 3-hydroxy-dicoumarin (DC-OH) units. Upon the addition of H₂S, the probe DC-HS solution's fluorescence significantly increased, and its appearance is changed from practically colorless to brilliant yellow. Probe DC-HS also showed significant fluorescence amplification that was quantitatively detectable in the concentration range of 0–1.5 μM and had a low detection limit or limit of detection of 0.2 nM. Moreover, with a high recovery rate and excellent accuracy, the developed fluorescent molecule was used successfully for the analysis of H₂S in red wine samples.     

Decomposition of Gaseous Sulfide Compounds in Air by Pulsed Corona Discharge

The effectiveness of applying a pulsed corona discharge to the destruction of olfactory pollution in air was investigated. This paper presents a comparative study of the decomposition of three representative sulfide compounds in diluted concentrations: hydrogen sulfide (H₂S), dimethyl sulfide (DMS), and ethanethiol (C₂H₅SH), which could be completely removed when a sufficient but reasonable energy density was deposited in the gas. DMS showed the lowest energy cost (around 30 eV/molecules); C₂H₅SH and H₂S had an EC of respectively 45 eV and 115 eV. The efficiency of the non-thermal plasma process increased with decreasing the initial concentration of sulfide compounds, while the energy yield remained almost unchanged. SO₂ was the only identified byproduct of H₂S decomposition, but the sulfur balance suggests the formation of undetected SO₃. The byproducts analyzed during the degradation of DMS and C₂H₅SH enabled to propose a reaction mechanism, starting with radical attack and breaking of C–S bonds.     

Catalysis by Hydrogen Carbonate and Silicate Anions of the Oxidation of Diethyl Sulfide with Hydrogen Peroxide in Aqueous and Aqueous–Alcoholic Media

The kinetics of the oxidation of diethyl sulfide (Et₂S) with hydrogen peroxide, catalyzed by hydrogen carbonate and silicate anions, agree with the assumption that peroxymonocarbonate (HCO^– ₄) and peroxymonosilicate (HSiO^– ₄) anions are formed as intermediates. The rate of reaction of Et₂S with HCO^– ₄ is about 100 times as fast as with H₂O₂. Transfer to aqueous–alcoholic solutions leads to an increase in the solubility of Et₂S while retaining the catalytic effects.     

Microbial oxidation of mixtures of methylmercaptan and hydrogen sulfide

Refinery spent-sulfidic caustic, containing only inorganic sulfides, has previously been shown to be amenable to biotreatment withThiobacillus denitrificans strain F with complete oxidation of sulfides to sulfate. However, many spent caustics contain mercaptans that cannot be metabolized by this strict autotroph. An aerobic enrichment culture was developed from mixedThiobacilli and activated sludge that was capable of simultaneous oxidation of inorganic sulfide and mercaptans using hydrogen sulfide (H₂S) and methylmercaptan (MeSH) gas feeds used to simulate the inorganic and organic sulfur of a spent-sulfidic caustic. The enrichment culture was also capable of biotreatment of an actual mercaptancontaining, spent-sulfidic caustic but at lower rates than predicted by operation on MeSH and H₂S fed to the culture in the gas phase, indicating that the caustic contained other inhibitory components.     

Gallium-containing sulfide binary and ternary materials by atomic layer deposition: precursor reactivities and growth fine chemistries

Gallium sulfide (Ga_xS) and copper gallium sulfide (Cu_xGa_yS_z) were synthetized by atomic layer deposition (ALD), using copper acetylacetonate Cu(acac)₂, hexakis(dimethylamino)digallium [Ga(NMe₂)₃]₂ and hydrogen sulfide (H₂S). Thanks to the compatibility of the Cu_xS and Ga_xS ALD windows, a supercycle strategy that combines single growth cycles of the two binary compounds was used to generate the ternary material. A wide range of compositions and properties can be obtained from Ga-rich to Cu-rich via copper gallium sulfide thin films. Structural, morphological, and optoelectronic characterizations were performed on all films. Surface and in-depth chemical compositions were determined by X-ray photoelectron spectroscopy profiling, allowing a better understanding of the chemical reactions involved during the growth process. In the case of Ga_xS films, other Ga precursors have been tested. Our experimental observations, combined with reported ones and density functional theory calculation results have highlighted the specific reactivity of alkylamido precursor in ALD chemistry. Compositional studies revealed a significant O content which origin is discussed and represents an important challenge to address in ALD of sulfide materials in general.     

Design and characterization of 3-azidothalidomide as a selective hydrogen sulfide probe

Hydrogen sulfide (H₂S) has been recently recognized as an important signaling molecule in biological systems. Herein, we report the development of a fluorescence turn-on probe based on the structure of pomalidomide, a FDA approved drug for the treatment of multiple myeloma. Various characterizations demonstrated high selectivity and sensitivity of this probe toward H₂S. Furthermore, the application of this probe to detect H₂S in living cells was confirmed by flow cytometry and fluorescence imaging studies.     

Chemisorption of hydrogen sulfide on lead sulfide

The hydrogen sulfide chemisorption on lead sulfide at 22–100°C is studied by static testing in a vacuum and by pulsed chromatography. It is established that H₂S is sorbed in reversible and irreversible forms and that the process is accompanied by the sample charging. Irreversibly sorbed hydrogen sulfide is removed by heating the sample in a vacuum or in an inert-gas stream at temperatures exceeding the adsorption temperature by 30–50°C.     

ZnO Nanocluster as a Potential Catalyst for Dissociation of H2S Molecule

Adsorption of hydrogen sulfide (H₂S) on the external and internal surface of Zn₁₂O₁₂ nanocluster was studied by using density functional calculations. The results indicate that the H₂S molecule is physically adsorbed or chemically dissociated by the nanocluster. It was found that the H₂S molecule can dissociate into –H and–SH fragments, suggesting that the nanocluster might be a potential catalyst for dissociation of the H₂S molecule. Also, dissociation of H₂S to S species in internal surface of the Zn₁₂O₁₂ nanocluster is energetically impossible. The HOMO–LUMO energy gap of H₂S dissociation configuration is changed about 27.68 %, indicating that the electronic properties of the nanocluster by dissociation process have strongly changed.