P74: The reaction between H2S and 8-nitro-cGMP: Substitution or reduction?

Abstract

Amongst the molecular reactions of H2S accounting for its role as gaseous transmitter is the reaction between hydrogen sulfide and electrophiles. The reaction between H2S and 8-NO2-guanosine 3 ′ , 5 ′ -cyclic monophosphate (8-NO2-cGMP) leading to the thiol derivative 8-SH-cGMP by “sulfhydration” was proposed to take place in cells, but the chemical reaction is in fact sluggish and requires the catalysts cysteine and transition metals or metalloproteins (Nishida et al., Nat. Chem. Biol. 8 (2012) 714–724). In this work, we show that the direct reaction between H2S and 8-NO2-guanosine (8-NO2-Gua, used as a model of 8-NO2-cGMP) or 8-NO2-cGMP does not lead to the substitution of the nitro group by HS−, but to a redox reaction yielding the radical [8-NO2-Gua]·-. Because of futile redox cycling with dioxygen, the reaction does not proceed further. However, under hypoxic conditions the reaction between H2S and 8-NO2-cGMP goes to completion and yields the amino derivative 8-NH2-cGMP, a reaction which may be relevant to the first step in the cellular recycling of 8-NO2-cGMP into cGMP.