Effect of phosphate on ferrihydrite transformation and the associated arsenic behavior mediated by sulfate-reducing bacterium.

Although PO43- is commonly found in association with iron (oxyhydr)oxide, the effect of PO43- on ferrihydrite reduction, mineralogical transformation, and associated As behavior in sulfate-reducing bacteria (SRB)-rich environments remains unclear. In this study, batch experiments, together with geochemical, mineralogical, and biological analyses, were conducted to elucidate these processes. The results showed that SRB can reduce ferrihydrite via direct and indirect processes, and PO43- promoted ferrihydrite reduction by supporting SRB growth at low and medium PO43- loadings. However, at high loadings, PO43- stabilized the ferrihydrite. PO43- shifted the transformation of ferrihydrite from magnetite and mackinawite to vivianite, which scavenges As effectively by incorporating As into its particle. In systems with 0.5 mM SO42-, PO43- exerted a weak effect on As mobilization. However, in systems with 10 mM SO42-, substantial amounts of As were released into the solution, and PO43- impacted As behavior strongly. Low PO43- loadings increased the mobilization of As because of the competitive adsorption of PO43- on mackinawite. Medium and high PO43- loadings were beneficial for As immobilization because of the substitution of mackinawite by vivianite. These findings have important implications for understanding the biogeochemistry of iron (oxyhydr)oxide and As behavior in SRB-containing sediments.

Carbon­sulfur coupling in a seasonally hypoxic, high-sulfate reservoir in SW China: Evidence from stable CS isotopes and sulfate-reducing bacteria.

Anthropogenic input of sulfate (SO42-) in reservoirs may enhance bacterial sulfate reduction (BSR) under seasonally hypoxic conditions in the water column. However, factors that control BSR and its coupling to organic carbon (OC) mineralization in seasonally hypoxic reservoirs remain unclear. The present study elucidates the coupling processes by analyzing the concentrations and isotopic composition of dissolved inorganic carbon (DIC) and sulfur (SO42-, sulfide) species, and the microbial community in water of the Aha reservoir, SW China, which has high SO42- concentration due to the inputs from acid mine drainage about twenty years ago. The water column at two sites in July and October revealed significant thermal stratification. In the hypoxic bottom water, the δ13C-DIC decreased while the δ34S-SO42- increased, implying organic carbon mineralization due to BSR. The magnitude of S isotope fractionation (Δ34S, obtained from δ34Ssulfate-δ34Ssulfide) during the process of BSR fell in the range of 3.4‰ to 27.0‰ in July and 21.6‰ to 31.8‰ in October, suggesting a change in the community of sulfate-reducing bacteria (SRB). The relatively low water column stability in October compared to that in July weakened the difference of water chemistry and ultimately affected the SRB diversity. The production of DIC (ΔDIC) scaled a strong positive relationship with the Δ34S in July (p < 0.01), indicating that high OC availability favored the survival of incomplete oxidizers of SRB. However, in October, Δ13C-DIC was correlated with the Δ34S in the bottom hypoxic water (p < 0.01), implying that newly degraded OC depleted in 13C could favor the dominance of complete oxidizers of SRB which caused greater S isotope fractionation. Moreover, the sulfide supplied by BSR might stimulate the reductive dissolution of Fe and Mn oxides (Fe(O)OH and MnO2). The present study helps to understand the coupling of C and S in seasonally hypoxic reservoirs characterized by high SO42- concentration.

Response to substrate limitation by a marine sulfate-reducing bacterium.

Sulfate-reducing microorganisms (SRM) in subsurface sediments live under constant substrate and energy limitation, yet little is known about how they adapt to this mode of life. We combined controlled chemostat cultivation and transcriptomics to examine how the marine sulfate reducer, Desulfobacterium autotrophicum, copes with substrate (sulfate or lactate) limitation. The half-saturation uptake constant (Km) for lactate was 1.2 µM, which is the first value reported for a marine SRM, while the Km for sulfate was 3 µM. The measured residual lactate concentration in our experiments matched values observed in situ in marine sediments, supporting a key role of SRM in the control of lactate concentrations. Lactate limitation resulted in complete lactate oxidation via the Wood-Ljungdahl pathway and differential overexpression of genes involved in uptake and metabolism of amino acids as an alternative carbon source. D. autotrophicum switched to incomplete lactate oxidation, rerouting carbon metabolism in response to sulfate limitation. The estimated free energy was significantly lower during sulfate limitation (-28 to -33 kJ mol-1 sulfate), suggesting that the observed metabolic switch is under thermodynamic control. Furthermore, we detected the upregulation of putative sulfate transporters involved in either high or low affinity uptake in response to low or high sulfate concentration.

Moving Past Quinone-Methides: Recent Advances Toward Minimizing Electrophilic Byproducts from COS/H2S Donors.

Hydrogen sulfide (H2S) is an important biomolecule that plays key signaling and protective roles in different physiological processes. With goals of advancing both the available research tools and the associated therapeutic potential of H2S, researchers have developed different methods to deliver H2S on demand in different biological contexts. A recent approach to develop such donors has been to design compounds that release carbonyl sulfide (COS), which is quickly converted to H2S in biological systems by the ubiquitous enzyme carbonic anhydrase (CA). Although highly diversifiable, many approaches using this general platform release quinone methides or related electrophiles after donor activation. Many such electrophiles are likely scavenged by water, but recent efforts have also expanded alternative approaches that minimize the formation of electrophilic byproducts generated after COS release. This mini-review focuses specifically on recent examples of COS-based H2S donors that do no generate quinone methide byproducts after donor activation.

Fungal Carbonyl Sulfide Hydrolase of Trichoderma harzianum Strain THIF08 and Its Relationship with Clade D ß-Carbonic Anhydrases.

Carbonyl sulfide (COS) is the most abundant and long-lived sulfur-containing gas in the atmosphere. Soil is the main sink of COS in the atmosphere and uptake is dominated by soil microorganisms; however, biochemical research has not yet been conducted on fungal COS degradation. COS hydrolase (COSase) was purified from Trichoderma harzianum strain THIF08, which degrades COS at concentrations higher than 10,000 parts per million by volume from atmospheric concentrations, and its gene cos (492 bp) was cloned. The recombinant protein purified from Escherichia coli expressing the cos gene converted COS to H2S. The deduced amino acid sequence of COSase (163 amino acids) was assigned to clade D in the phylogenetic tree of the ß-carbonic anhydrase (ß-CA) family, to which prokaryotic COSase and its structurally related enzymes belong. However, the COSase of strain THIF08 differed from the previously known prokaryotic COSase and its related enzymes due to its low reactivity to CO2 and inability to hydrolyze CS2. Sequence comparisons of the active site amino acids of clade D ß-CA family enzymes suggested that various Ascomycota, particularly Sordariomycetes and Eurotiomycetes, possess similar enzymes to the COSase of strain THIF08 with >80% identity. These fungal COSase were phylogenetically distant to prokaryotic clade D ß-CA family enzymes. These results suggest that various ascomycetes containing COSase contribute to the uptake of COS by soil.

Enumeration of Chemoorganotrophic Carbonyl Sulfide (COS)-degrading Microorganisms by the Most Probable Number Method.

Carbonyl sulfide (COS) is the most abundant sulfur compound in the atmosphere, and, thus, is important in the global sulfur cycle. Soil is a major sink of atmospheric COS and the numerical distribution of soil microorganisms that degrade COS is indispensable for estimating the COS-degrading potential of soil. However, difficulties are associated with counting COS-degrading microorganisms using culture-dependent approaches, such as the most probable number (MPN) method, because of the chemical hydrolysis of COS by water. We herein developed a two-step MPN method for COS-degrading microorganisms: the first step for chemoorganotrophic growth that supported a sufficient number of cells for COS degradation in the second step. Our new MPN analysis of various environmental samples revealed that the cell density of COS-degrading microorganisms in forest soils ranged between 106 and 108 MPN (g dry soil)-1, which was markedly higher than those in volcanic deposit and water samples, and strongly correlated with the rate of COS degradation in environmental samples. Numerically dominant COS degraders that were isolated from the MPN-positive culture were related to bacteria in the orders Bacillales and Actinomycetales. The present results provide numerical evidence for the ubiquity of COS-degrading microbes in natural environments.

Oxygen isotope effects during microbial sulfate reduction: applications to sediment cell abundances.

The majority of anaerobic biogeochemical cycling occurs within marine sediments. To understand these processes, quantifying the distribution of active cells and gross metabolic activity is essential. We present an isotope model rooted in thermodynamics to draw quantitative links between cell-specific sulfate reduction rates and active sedimentary cell abundances. This model is calibrated using data from a series of continuous culture experiments with two strains of sulfate reducing bacteria (freshwater bacterium Desulfovibrio vulgaris strain Hildenborough, and marine bacterium Desulfovibrio alaskensis strain G-20) grown on lactate across a range of metabolic rates and ambient sulfate concentrations. We use a combination of experimental sulfate oxygen isotope data and nonlinear regression fitting tools to solve for unknown kinetic, step-specific oxygen isotope effects. This approach enables identification of key isotopic reactions within the metabolic pathway, and defines a new, calibrated framework for understanding oxygen isotope variability in sulfate. This approach is then combined with porewater sulfate/sulfide concentration data and diagenetic modeling to reproduce measured 18O/16O in porewater sulfate. From here, we infer cell-specific sulfate reduction rates and predict abundance of active cells of sulfate reducing bacteria, the result of which is consistent with direct biological measurements.

Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions.

The recent discovery of hydropersulfides (RSSH) in mammalian systems suggests their potential roles in cell signaling. However, the exploration of RSSH biological significance is challenging due to their instability under physiological conditions. Herein, we report the preparation, RSSH-releasing properties, and cytoprotective nature of alkylamine-substituted perthiocarbamates. Triggered by a base-sensitive, self-immolative moiety, these precursors show efficient RSSH release and also demonstrate the ability to generate carbonyl sulfide (COS) in the presence of thiols. Using this dually reactive alkylamine-substituted perthiocarbamate platform, the generation of both RSSH and COS is tunable with respect to half-life, pH, and availability of thiols. Importantly, these precursors exhibit cytoprotective effects against hydrogen peroxide-mediated toxicity in H9c2 cells and cardioprotective effects against myocardial ischemic/reperfusion injury, indicating their potential application as new RSSH- and/or COS-releasing therapeutics.

Carbonyl Sulfide (COS) Donor Induced Protein Persulfidation Protects against Oxidative Stress.

The emergence of hydrogen sulfide (H2 S) as an important signalling molecule in redox biology with therapeutic potential has triggered interest in generating this molecule within cells. One strategy that has been proposed is to use carbonyl sulfide (COS) as a surrogate for hydrogen sulfide. Small molecules that generate COS have been shown to produce hydrogen sulfide in the presence of carbonic anhydrase, a widely prevalent enzyme. However, other studies have indicated that COS may have biological effects which are distinct from H2 S. Thus, it would be useful to develop tools to compare (and contrast) effects of COS and H2 S. Here we report enzyme-activated COS donors that are capable of inducing protein persulfidation, which is symptomatic of generation of hydrogen sulfide. The COS donors are also capable of mitigating stress induced by elevated reactive oxygen species. Together, our data suggests that the effects of COS parallel that of hydrogen sulfide, laying the foundation for further development of these donors as possible therapeutic agents.

Cyclic Sulfenyl Thiocarbamates Release Carbonyl Sulfide and Hydrogen Sulfide Independently in Thiol-Promoted Pathways.

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.

Development and Application of Carbonyl Sulfide-Based Donors for H2S Delivery.

In addition to nitric oxide and carbon monoxide, hydrogen sulfide (H2S) has been recently recognized as an important biological signaling molecule with implications in a wide variety of processes, including vasodilation, cytoprotection, and neuromodulation. In parallel to the growing number of reports highlighting the biological impact of H2S, interest in developing H2S donors as both research tools and potential therapeutics has led to the growth of different H2S-releasing strategies. Many H2S investigations in model systems use direct inhalation of H2S gas or aqueous solutions of NaSH or Na2S; however, such systems do not mimic endogenous H2S production. This stark contrast drives the need to develop better sources of caged H2S. To address these limitations, different small organosulfur donor compounds have been prepared that release H2S in the presence of specific activators or triggers. Such compounds, however, often lack suitable  control compounds, which limits the use of these compounds in probing the effects of H2S directly. To address these needs, our group has pioneered the development of carbonyl sulfide (COS) releasing compounds as a new class of H2S donor motifs. Inspired by a commonly used carbamate prodrug scaffold, our approach utilizes self-immolative thiocarbamates to access controlled release of COS, which is rapidly converted to H2S by the ubiquitous enzyme carbonic anhydrase (CA). In addition, this design enables access to key control compounds that release CO2/H2O rather than COS/H2S, which enables delineation of the effects of COS/H2S from the organic donor byproducts. In this Account, we highlight a library of first-generation COS/H2S donors based on self-immolative thiocarbamates developed in our lab and also highlight challenges related to H2S donor development. We showcase the release of COS in the presence of specific triggers and activators, including biological thiols and bio-orthogonal reactants for targeted applications. We also demonstrate the design and development of a series of H2O2/reactive oxygen species (ROS)-triggered donors and show that such compounds can be activated by endogenous levels of ROS production. Utilizing approaches in bio-orthogonal activation, we establish that donors functionalized with an o-nitrobenzyl photocage can enable access to light-activated donors. Similar to endogenous production by cysteine catabolism, we also prepared a cysteine-selective COS donor activated by a Strongin ligation mechanism. In efforts to help delineate potential differences in the chemical biology of COS and H2S, we also report a simple esterase-activated donor, which demonstrated fast COS-releasing kinetics and inhibition of mitochondrial respiration in BEAS-2B cells. Additional investigations revealed that COS release rates and cytotoxicity correlated directly within this series of compounds with different ester motifs. In more recent and applied applications of this H2S donation strategy, we also highlight the development of donors that generate either a colorimetric or fluorescent optical response upon COS release. Overall, the work described in this Account outlines the development and initial application of a new class of H2S donors, which we anticipate will help to advance our understanding of the rapidly emerging chemical biology of H2S and COS.

Skin permeation of oxides of nitrogen and sulfur from short-term exposure scenarios relevant to hazardous material incidents.

Permeation of oxides of nitrogen and sulfur gases through skin and the consequences of dermal exposure are still poorly understood. We measured the penetration profile of three common industrial gases through skin, for short-term exposures relevant to HAZMAT scenarios. Time variations of gas concentration, clothing effects, temperature and humidity on epidermal absorption and penetration were assessed. Fabric off-gassing profiles were also investigated. The results show oxides of nitrogen (NO and NO2) at airborne concentrations up to lethal inhalation levels (e.g. 3000 ppm) have little skin penetration ability. Skin absorption and reservoir effects were noted. Skin exposed to SO2 (3000 ppm/30 min) shows negligible skin absorption or penetration. Fabric on skin marginally increased SO2 absorption and subsequent ventilation did not reduce the absorbed fraction. Increased temperature and humidity had limited additional effect on skin penetration. Importantly, clothing demonstrated sink properties, especially for SO2. Short-term skin exposure relevant to accidents will not significantly contribute to body burden. The greatest concern will likely be off-gassing of chemical-laden fabric for asthma suffers. The risk-based management approach is to avoid potential secondary inhalation from fabric off-gassing by removal of outer layer of bulky clothing. Decontamination and moving into an area of enhanced ventilation may also be advised.

Influences of light and humidity on carbonyl sulfide-based estimates of photosynthesis.

Understanding climate controls on gross primary productivity (GPP) is crucial for accurate projections of the future land carbon cycle. Major uncertainties exist due to the challenge in separating GPP and respiration from observations of the carbon dioxide (CO2) flux. Carbonyl sulfide (COS) has a dominant vegetative sink, and plant COS uptake is used to infer GPP through the leaf relative uptake (LRU) ratio of COS to CO2 fluxes. However, little is known about variations of LRU under changing environmental conditions and in different phenological stages. We present COS and CO2 fluxes and LRU of Scots pine branches measured in a boreal forest in Finland during the spring recovery and summer. We find that the diurnal dynamics of COS uptake is mainly controlled by stomatal conductance, but the leaf internal conductance could significantly limit the COS uptake during the daytime and early in the season. LRU varies with light due to the differential light responses of COS and CO2 uptake, and with vapor pressure deficit (VPD) in the peak growing season, indicating a humidity-induced stomatal control. Our COS-based GPP estimates show that it is essential to incorporate the variability of LRU with environmental variables for accurate estimation of GPP on ecosystem, regional, and global scales.

System performance and microbial community in ethanol-fed anaerobic reactors acclimated with different organic carbon to sulfate ratios.

Sulfate influences the organics removal and methanogenic performance during anaerobic wastewater treatment. System performance, microbial community and metabolic pathways in ethanol-fed anaerobic reactors were investigated under different COD/SO42- ratios (2, 1 and 0.67) and control without sulfate addition. The sulfate removal percentages declined (99%, 60% and 49%) with decreasing COD/SO42- ratios, and methanogenesis was completely inhibited. Acetate accumulated to 903-734 mg/L, though propionate was constantly lower than 30 mg/L. Without sulfate, acetate and propionate did not accumulate, despite the extended time for propionate degradation. Incomplete oxidizing sulfate reducing bacteria (Desulfobulbus and Desulfomicrobium) and hydrolysis-acidification genera (Treponema and Bacteroidales) predominated but could not degrade acetate. Desulfobulbus was the key genus for propionate degradation through the pyruvate & propanoate metabolism pathway. Pseudomonas and Desulfobulbus, possessing genes encoding Type IV pili and cytochrome c6 OmcF, respectively, potentially participated in the direct interspecies electron transfer in sulfate-rich conditions.

Soil exchange rates of COS and CO18O differ with the diversity of microbial communities and their carbonic anhydrase enzymes.

Differentiating the contributions of photosynthesis and respiration to the global carbon cycle is critical for improving predictive climate models. Carbonic anhydrase (CA) activity in leaves is responsible for the largest biosphere-atmosphere trace gas fluxes of carbonyl sulfide (COS) and the oxygen-18 isotopologue of carbon dioxide (CO18O) that both reflect gross photosynthetic rates. However, CA activity also occurs in soils and will be a source of uncertainty in the use of COS and CO18O as carbon cycle tracers until process-based constraints are improved. In this study, we measured COS and CO18O exchange rates and estimated the corresponding CA activity in soils from a range of biomes and land use types. Soil CA activity was not uniform for COS and CO2, and patterns of divergence were related to microbial community composition and CA gene expression patterns. In some cases, the same microbial taxa and CA classes catalyzed both COS and CO2 reactions in soil, but in other cases the specificity towards the two substrates differed markedly. CA activity for COS was related to fungal taxa and ß-D-CA expression, whereas CA activity for CO2 was related to algal and bacterial taxa and α-CA expression. This study integrates gas exchange measurements, enzyme activity models, and characterization of soil taxonomic and genetic diversity to build connections between CA activity and the soil microbiome. Importantly, our results identify kinetic parameters to represent soil CA activity during application of COS and CO18O as carbon cycle tracers.

Colorimetric Carbonyl Sulfide (COS)/Hydrogen Sulfide (H2 S) Donation from γ-Ketothiocarbamate Donor Motifs.

Hydrogen sulfide (H2 S) is a biologically active molecule that exhibits protective effects in a variety of physiological and pathological processes. Although several H2 S-related biological effects have been discovered by using H2 S donors, knowing how much H2 S 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 H2 S donors and enable direct quantification of H2 S release, were reported. These compounds are activated through a pH-dependent deprotonation/ß-elimination sequence to release carbonyl sulfide (COS), which is quickly converted into H2 S by carbonic anhydrase. The p-nitroaniline released upon donor activation provides an optical readout that correlates directly to COS/H2 S release, thus enabling colorimetric measurement of H2 S donation.

Assessing canopy performance using carbonyl sulfide measurements.

Carbonyl sulfide (COS) is a tracer of ecosystem photosynthesis that can advance carbon cycle research from leaf to global scales; however, a range of newly reported caveats related to sink/source strength of various ecosystem components hinder its application. Using comprehensive eddy-covariance and chamber measurements, we systematically measure ecosystem contributions from leaf, stem, soil, and litter and were able to close the ecosystem COS budget. The relative contributions of nonphotosynthetic components to the overall canopy-scale flux are relatively small (~4% during peak activity season) and can be independently estimated based on their responses to temperature and humidity. Converting COS to photosynthetic CO2 fluxes based on the leaf relative uptake of COS/CO2 , faces challenges due to observed daily and seasonal changes. Yet, this ratio converges around a constant value (~1.6), and the variations, dominated by light intensity, were found unimportant on a flux-weighted daily time-scale, indicating a mean ratio of daytime gross-to-net primary productivity of ~2 in our ecosystem. The seasonal changes in the leaf relative uptake ratio may indicate a reduction in mesophyll conductance in winter, and COS-derived canopy conductance permitted canopy temperature estimate consistent with radiative skin temperature. These results support the feasibility of using COS as a powerful and much-needed means of assessing ecosystem function and its response to change.

Emerging Roles of Carbonyl Sulfide in Chemical Biology: Sulfide Transporter or Gasotransmitter?

SIGNIFICANCE: Carbonyl sulfide (COS) is the most prevalent sulfur-containing gas in the Earth's atmosphere, and it plays important roles in the global sulfur cycle. COS has been implicated in origin of life peptide ligation, is the primary energy source for certain bacteria, and has been detected in mammalian systems. Despite this long and intertwined history with terrestrial biology, limited attention has focused on potential roles of COS as a biological mediator. Recent Advances: Although bacterial COS production is well documented, definitive sources of mammalian COS production have not been confirmed. Enzymatic COS consumption in mammals, however, is well documented and occurs primarily by carbonic anhydrase (CA)-mediated conversion to hydrogen sulfide (H2S). COS has been detected in ex vivo mammalian tissue culture, as well as in exhaled breath as a potential biomarker for different disease pathologies, including cystic fibrosis and organ rejection. Recently, chemical tools for COS delivery have emerged and are poised to advance future investigations into the role of COS in different biological contexts. CRITICAL ISSUES: Possible roles of COS as an important biomolecule, gasotransmitter, or sulfide transport intermediate remain to be determined. Key advances in both biological and chemical tools for COS research are needed to further investigate these questions. FUTURE DIRECTIONS: Further evaluation of the biological roles of COS and disentangling the chemical biology of COS from that of H2S are needed to further elucidate these interactions. Chemical tools for COS delivery and modulation may provide a first avenue of investigative tools to answer many of these questions. Antioxid. Redox Signal. 28, 1516-1532.

Multiple role of 3-mercaptopyruvate sulfurtransferase: antioxidative function, H2 S and polysulfide production and possible SOx production.

Rat 3-mercaptopyruvate sulfurtransferase (MPST) is a 32 808 Da simple protein. Cys247 is a catalytic site, and Cys154 and Cys263 are on the enzyme surface. MPST is found in all tissues, particularly in the kidneys, although the localization of its activity differs in each tissue. In this review, four functions of MPST are reviewed: (i) antioxidative function: Cys247 is redox-sensitive and serves as a redox-sensing switch. It is oxidized to cysteine sulfenate, which has a low redox potential, upon which the enzyme is inactivated. Then, reduced thioredoxin (Trx) with a reducing system (Trx reductase and NADPH) reduces the sulfenate to restore activity; meanwhile, Cys154 and Cys263 form an intermolecular disulfide bond, which serves as another redox-sensing switch. Consequently, Trx specifically cleaves the intermolecular disulfide bond by converting it from the inactive form (dimer) to the active form (monomer). (ii) Hydrogen sulfide and polysulfide production: hydrogen sulfide is produced via reduction of the persulfurated sulfur-acceptor substrate by reduced Trx or Trx with a reducing system; as an alternative process, stable polysulfurated or persulfurated Cys247 as a reaction intermediate is reduced by Trx with a reducing system to release hydrogen sulfide and polysulfides. (iii) Possible sulfur oxide production: sulfur oxides (SO, SO2 and SO3 ) can be produced in the redox cycle of sulfane sulfur formed at the catalytic site Cys247 (Cys-SO- , Cys-SO2- and Cys-SO3- ) as reaction intermediates and released by reduced Trx or Trx with a reducing system. (iv) Possible anxiolytic-like effects: MPST-knockout mice exhibited anxiolytic-like effects.

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

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 donor systems.