Reaction of Nitroxyl (HNO) with Hydrogen Sulfide and Hydropersulfides

Abstract

Nitroxyl (HNO) has gained a considerable amount of attention because of its promising pharmacological effects. The biochemical mechanisms of HNO activity are associated with the modification of regulatory thiol proteins. Recently, several studies have suggested that hydropersulfides (RSSH), presumed signaling products of hydrogen sulfide (H 2 S)-mediated thiol (RSH) modification, are additional potential targets of HNO. However, the interaction of HNO with reactive sulfur species beyond thiols remains relatively unexplored. Herein, we present characterization of HNO reactivity with H 2 S and RSSH. The reaction of H 2 S with HNO leads to the formation of hydrogen polysulfides and sulfur (S 8 ), suggesting a potential role in sulfane sulfur homeostasis. Furthermore, we show that hydropersulfides are more efficient traps for HNO than their thiol counterparts. The reaction of HNO with RSSH at varied stoichiometries has been examined with the observed production of various dialkylpolysulfides (RSS n SR) and other nitrogen-containing dialkylpolysulfide species (RSS−NH−S n R). We do not observe evidence of sulfenylsulfinamide (RS−S(O)−NH 2 ) formation, a pathway expected by analogy with the known reactivity of HNO with thiol.

C‐Nitrosothioformamide: A Donor Template for Dual Release of HNO and H2S

“…[9] Recently Toscano et al reported the first characterization of HNO/H 2 S interaction, indicating stoichiometry-dependent production of sulfane sulfurs -hydrogen polysulfides (H 2 S n ) or sulfur (S 8 ). [10] We wondered if the dual donors could also produce sulfane sulfurs. 3 b was incubated with a sulfane sulfur sensitive fluorescent probe, SSP4, [11] for 24 hours at 37 °C.…”

The Chemistry of HNO: Mechanisms and Reaction Kinetics

“…The stoichiometric analyses of such reaction should also take into account the possibility of the reaction between HNO and released NH 2 OH ( Reaction 23 ). The recent study of Zarenkiewicz et al (2021) on HNO reaction with H 2 S shows that this reaction leads to the formation of hydrogen polysulfides (H 2 S n ) or sulfur S 8 , depending on the relative concentrations of H 2 S and HNO. The reactivity of HNO towards selected inorganic scavengers is summarized in Scheme 2 and Table 1 .…”

“…As hydropersulfides have been detected in biological systems at high micromolar concentrations, they could be among important biological targets of azanone. The recent study of Zarenkiewicz et al (2021) on HNO reaction with hydropersulfides shows that RSSH are more potent traps for HNO, than RSH. They also reported that HNO reaction with small molecule RSSH leads to the formation of various RSS n SR and RSS-NH-S n R species ( Zarenkiewicz et al, 2021 ).…”

“…The recent study of Zarenkiewicz et al (2021) on HNO reaction with hydropersulfides shows that RSSH are more potent traps for HNO, than RSH. They also reported that HNO reaction with small molecule RSSH leads to the formation of various RSS n SR and RSS-NH-S n R species ( Zarenkiewicz et al, 2021 ).…”

Para-Substituted O-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources

“…In addition to dimerization, HNO reacts with thiols, generating a N-hydroxysulfenamide intermediate that can rearrange to a sulfinamide or further react with more thiol to yield a disulfide and hydroxylamine [10]. HNO similarly reacts with hydrogen sulfide (H 2 S), a second recognized gasotransmitter [1], to give short-chain hydrogen polysulfides (H 2 S n ) or S 8 depending on the relative concentrations of HNO and H 2 S [11]. Based on this chemistry, HNO can influence thiol-mediated biochemistry and potentially H 2 S-controlled reactions.…”