Crosstalk among Thiol, Nitrite, and Dichalcogenides in Nitric Oxide Signaling: Insights into the Role of Noncovalent Interactions

Although nitrite-to-nitric oxide (NO) transformation from the interactions between a thiol and nitrite at classical transition-metal sites is well known in the context of understanding the enzymatic reduction of nitrite, insights into the nonenzymatic routes affording NO gas and factors affecting such pathways are poorly understood. This study illustrates a biologically relevant crosstalk among nitrite, thiol, and organic dichalcogenides with -SeS- and -SeSe- moieties, resulting in a facile protonation of nitrite to provide transient nitrous acid (HNO₂). The overall transformation of nitrite to NO and nitrate is proposed to occur through the disproportionation of metastable HNO₂. Though direct interaction between nitrite and thiol is inefficient for the intermolecular proton transfer, multinuclear (¹H/⁷⁷Se) NMR studies depict that the weak noncovalent interactions (e.g., σ-hole and H-bonding) dictate the efficiency of the thiol-nitrite crosstalk in the presence of organic dichalcogenides. Thus, this work not only reveals that the organoselenium compounds are capable of influencing nonenzymatic NO_x-dependent signaling processes in the presence of a thiol but also illustrates the potential role of NO_x^- anions in regulating the reactivity of organochalcogen moieties in the biological milieu.