Manganese Porphyrin-Based SOD Mimetics Produce Polysulfides from Hydrogen Sulfide

Manganese-centered porphyrins (MnPs), MnTE-2-PyP5+ (MnTE), MnTnHex-2-PyP5+ (MnTnHex), and MnTnBuOE-2-PyP5+ (MnTnBuOE) have received considerable attention because of their ability to serve as superoxide dismutase (SOD) mimetics thereby producing hydrogen peroxide (H2O2), and oxidants of ascorbate and simple aminothiols or protein thiols. MnTE-2-PyP5+ and MnTnBuOE-2-PyP5+ are now in five Phase II clinical trials warranting further exploration of their rich redox-based biology. Previously, we reported that SOD is also a sulfide oxidase catalyzing the oxidation of hydrogen sulfide (H2S) to hydrogen persulfide (H2S2) and longer-chain polysulfides (H2Sn, n = 3–7). We hypothesized that MnPs may have similar actions on sulfide metabolism. H2S and polysulfides were monitored in fluorimetric assays with 7-azido-4-methylcoumarin (AzMC) and 3′,6′-di(O-thiosalicyl)fluorescein (SSP4), respectively, and specific polysulfides were further identified by mass spectrometry. MnPs concentration-dependently consumed H2S and produced H2S2 and subsequently longer-chain polysulfides. This reaction appeared to be O2-dependent. MnP absorbance spectra exhibited wavelength shifts in the Soret and Q bands characteristic of sulfide-mediated reduction of Mn. Taken together, our results suggest that MnPs can become efficacious activators of a variety of cytoprotective processes by acting as sulfide oxidation catalysts generating per/polysulfides.

Real-time monitoring of a photoactivated hydrogen persulfide donor for biological entities

A visible light responsive H2S2 donor based on the ESIPT mechanism with real-time monitoring ability using a non-invasive fluorescence technique.

Computational insight into hydrogen persulfide and a new additive model for chemical and biological simulations

From high-level quantum chemistry calculations of H2S2molecular complexes to the development of a hydrogen persulfide model for chemical and biological simulations.