Spectroscopic investigation of the reaction of metallo-protoporphyrins with hydrogen sulfide.

Hydrogen sulfide (H2S) is the most recently discovered gasotransmitter molecule joining nitric oxide and carbon monoxide. In addition to being biologically important gases, these gasotransmitters also provide distinct modes of reactivity with biomimetic metal complexes. The majority of previous investigations on the reactivity of H2S with bioinorganic models have focused on Fe-based porphyrin systems, whereas investigations with other metals remains underinvestigated. To address this gap, we report here an examination of the reactions of H2S, HS-, and S8 with MgII, CuII, CoII, ZnII, CrII, SnIV, and MnII/III protoporphyrins.

A Synthetic Supramolecular Receptor for the Hydrosulfide Anion.

Hydrogen sulfide (H2 S) 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 H2 S 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.

A practical guide to working with H2S at the interface of chemistry and biology.

Hydrogen sulfide (H2S) is the most recently accepted endogenously produced gasotransmitter and is now implicated in a variety of physiological functions. In this tutorial review, our goal is to provide researchers new to the field of H2S chemical biology with practical considerations, pitfalls, and best practices to enable smooth entry into investigations focused on biological H2S. We present practical handling and safety considerations for working with this reactive biomolecule, and cover basic roles of H2S biogenesis and action. Experimental methods for modulating H2S levels, including enzymatic knockout, RNA silencing, enzymatic inhibition, and use of small molecule H2S donors are highlighted. Complementing H2S modulation techniques, we also highlight current strategies for H2S detection and quantification.

Stabilization of a Zn(ii) hydrosulfido complex utilizing a hydrogen-bond accepting ligand.

Hydrogen sulfide (H2S) has gained recent attention as an important biological analyte that interacts with bioinorganic targets. Despite this importance, stable H2S or HS(-) adducts of bioinorganic metal complexes remain rare due to the redox activity of sulfide and its propensity to form insoluble metal sulfides. We report here reversible coordination of HS(-) to Zn(didpa)Cl2, which is enabled by an intramolecular hydrogen bond between the zinc hydrosulfido product and the pendant tertiary amine of the didpa ligand.

Spectroscopic investigations into the binding of hydrogen sulfide to synthetic picket-fence porphyrins.

The reversible binding of hydrogen sulfide (H2S) to hemeprotein sites has been attributed to several factors, likely working in concert, including the protected binding pocket environment, proximal hydrogen bond interactions, and iron ligation environment. To investigate the importance of a sterically-constrained, protected environment on sulfide reactivity with heme centers, we report here the reactivity of H2S and HS(-) with the picket-fence porphyrin system. Our results indicate that the picket-fence porphyrin does not bind H2S in the ferric or ferrous state. By contrast, reaction of the ferric scaffold with HS(-) results in reduction to the ferrous species, followed by ligation of one equivalent of HS(-), as evidenced by UV-vis, NMR spectroscopy and mass spectrometry studies. Measurement of the HS(-) binding affinities in the picket-fence or tetraphenyl porphyrin systems revealed identical binding. Taken together, these results suggest that the protected, sterically-constrained binding pocket alone is not the primary contributor for stabilization of ferric H2S/HS(-) species in model systems, but that other interactions, such as hydrogen bonding, must play a critical role in facilitation of reversible interactions in ferric hemes.

NBu4SH provides a convenient source of HS(-) soluble in organic solution for H2S and anion-binding research.

Hydrogen sulfide (H2S) has gained significant interest within the scientific community due to its expanding roles in different (patho)physiological processes. Despite this importance, the chemical mechanisms by which H2S exerts its action remain under-scrutinized. Biomimetic investigations in organic solution offer the potential to clarify these mechanisms and to delineate the differential reactivity between H2S and HS(-). However, such studies are hampered by the lack of readily-available sources of HS(-) that are soluble in organic solution. Here we present a simple method for preparing analytically pure tetrabutylammonium hydrosulfide (NBu4SH), which we anticipate will be of significant utility to researchers in the H2S and anion-binding communities.

Chemically reversible reactions of hydrogen sulfide with metal phthalocyanines.

Hydrogen sulfide (H2S) is an important signaling molecule that exerts action on various bioinorganic targets. Despite this importance, few studies have investigated the differential reactivity of the physiologically relevant H2S and HS(-) protonation states with metal complexes. Here we report the distinct reactivity of H2S and HS(-) with zinc(II) and cobalt(II) phthalocyanine (Pc) complexes and highlight the chemical reversibility and cyclability of each metal. ZnPc reacts with HS(-), but not H2S, to generate [ZnPc-SH](-), which can be converted back to ZnPc by protonation. CoPc reacts with HS(-), but not H2S, to form [Co(I)Pc](-), which can be reoxidized to CoPc by air. Taken together, these results demonstrate the chemically reversible reaction of HS(-) with metal phthalocyanine complexes and highlight the importance of H2S protonation state in understanding the reactivity profile of H2S with biologically relevant metal scaffolds.