O→S Relay Deprotection: A General Approach to Controllable Donors of Reactive Sulfur Species.

Reactive sulfur species (RSS) are biologically important molecules. Among them, H2 S, hydrogen polysulfides (H2 Sn, n>1), persulfides (RSSH), and HSNO are believed to play regulatory roles in sulfur-related redox biology. However, these molecules are unstable and difficult to handle. Having access to their reliable and controllable precursors (or donors) is the prerequisite for the study of these sulfur species. Reported in this work is the preparation and evaluation of a series of O-silyl-mercaptan-based sulfur-containing molecules which undergo pH- or F- -mediated desilylation to release the corresponding H2 S, H2 Sn , RSSH, and HSNO in a controlled fashion. This O→S relay deprotection serves as a general strategy for the design of pH- or F- -triggered RSS donors. Moreover, we have demonstrated that the O-silyl groups in the donors could be changed into other protecting groups like esters. This work should allow the development of RSS donors with other activation mechanisms (such as esterase-activated donors).

Slow generation of hydrogen sulfide from sulfane sulfurs and NADH models.

Here we report the model studies of the reactions between NADH models (using HEH and BNAH) and sulfane sulfurs (using polysulfides). Such reactions could lead to the oxidation of NADH models and the production of hydrogen sulfide (H2S). Kinetics of the reaction between BNAH and elemental sulfur S8 were determined in ethanol and the second-order rate constant was found to be 0.074M-1min-1 (at 37°C) suggesting this is a slow process.

A General Strategy for Development of Near-Infrared Fluorescent Probes for Bioimaging.

Near-infrared (NIR) fluorescent dyes with favorable photophysical properties are highly useful for bioimaging, but such dyes are still rare. The development of a unique class of NIR dyes via modifying the rhodol scaffold with fused tetrahydroquinoxaline rings is described. These new dyes showed large Stokes shifts (>110 nm). Among them, WR3, WR4, WR5, and WR6 displayed high fluorescence quantum yields and excellent photostability in aqueous solutions. Moreover, their fluorescence properties were tunable by easy modifications on the phenolic hydroxy group. Based on WR6, two NIR fluorescent turn-on probes, WSP-NIR and SeSP-NIR, were devised for the detection of H2 S. The probe SeSP-NIR was applied in visualizing intracellular H2 S. These dyes are expected to be useful fluorophore scaffolds in the development of new NIR probes for bioimaging.

A Single Fluorescent Probe to Visualize Hydrogen Sulfide and Hydrogen Polysulfides with Different Fluorescence Signals.

Hydrogen sulfide (H2 S) and hydrogen polysulfides (H2 Sn , n>1) are endogenous regulators of many physiological processes. In order to better understand the symbiotic relationship and cellular cross-talk between H2 S and H2 Sn , it is highly desirable to develop single fluorescent probes which enable dual-channel discrimination between H2 S and H2 Sn . Herein, we report the rational design, synthesis, and evaluation of the first dual-detection fluorescent probe DDP-1 that can visualize H2 S and H2 Sn with different fluorescence signals. The probe showed high selectivity and sensitivity to H2 S and H2 Sn in aqueous media and in cells.

Benzothiazole Sulfinate: A Sulfinic Acid Transfer Reagent under Oxidation-Free Conditions.

Sulfinic acids are commonly encountered intermediates found in natural product synthesis and medicinal chemistry. However, because of high reactivity, instability, and harsh reaction conditions, they are difficult to synthesize. Herein we have developed an oxidation-free method to produce sulfinic acids and sulfinate salts using 2-sulfinyl benzothiazole (BTS). We have also demonstrated the synthetic usefulness by developing one-pot syntheses of sulfones and sulfonamides.

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders.

As an important endogenous gaseous signaling molecule, hydrogen sulfide (H2S) exerts various effects in the body. A variety of pathological changes, such as cancer, glycometabolic disorders, and diabetes, are associated with altered endogenous levels of H2S, especially decreased. Therefore, the supplement of H2S is of great significance for the treatment of diseases containing the above pathological changes. At present, many efforts have been made to increase the in vivo levels of H2S by administration of gaseous H2S, simple inorganic sulfide salts, sophisticated synthetic slow-releasing controllable H2S donors or materials, and using H2S stimulating agents. In this article, we reviewed the recent development of H2S releasing/stimulating reagents and their potential applications in two common pathological processes including cancer and glycometabolic disorders.

Benzothiazole Sulfinate: a Water-Soluble and Slow-Releasing Sulfur Dioxide Donor.

Sulfur dioxide (SO2) has long been considered a toxic environmental pollutant and byproduct of industrial processing. Recently it has become evident that SO2 may also have regulatory functions in mammalian pulmonary systems. However, the study of these effects has proven to be challenging due to the difficulty in administering SO2 in a reliable manner. In this work, we report the discovery of a new pH-dependent and water-soluble SO2 donor, benzothiazole sulfinate (BTS). We have found BTS to have slow and sustained SO2 release at physiological pH. Additionally, we have explored its vasorelaxation properties as compared to the authentic SO2 gas solutions. The slow release of BTS should make it a useful tool for the study of endogenously generated SO2.

9-Fluorenylmethyl (Fm) Disulfides: Biomimetic Precursors for Persulfides.

The development of a functional disulfide, FmSSPy-A (Fm = 9-fluorenylmethyl; Py = pyridinyl), is reported. It can effectively convert small molecule and protein thiols (-SH) to form -S-SFm adducts under mild conditions. This method allows for a H2S-free and biomimetic protocol to generate highly reactive persulfides (in their anionic forms). The high nucleophilicity of persulfides toward a number of thiol-blocking reagents is also demonstrated. The method holds promise for further understanding the chemical biology of persulfides and S-sulfhydration.

Persulfides: current knowledge and challenges in chemistry and chemical biology.

Recent studies conducted in hydrogen sulfide (H2S) signaling have revealed potential importance of persulfides (RSSH) in redox biology. The inherent instability of RSSH makes these species difficult to study and sometimes controversial results are reported. In this review article we summarize known knowledge about both small molecule persulfides and protein persulfides. Their fundamental physical and chemical properties such as preparation/formation and reactivity are discussed. The biological implications of persulfides and their detection methods are also discussed.