Nitroso Group Transfer in S-Nitrosocysteine:  Evidence of a New Decomposition Pathway for Nitrosothiols

Abstract

The rate of S-nitrosocysteine decomposition in a pH range between 0.7 < pH < 13 exhibits first- and second-order dependence on total cysteine concentration. The second-order term is only observed for pH values between 6.9 < pH < 12. Both first- and second-order terms show a complex dependence on the acidity of the medium. They increase with increasing pH, reaching a maximum value around pH = 8 and then decrease with further increase in pH. An analysis of the reaction products reveals the absence of nitrite ion and ammonia. No evidence of catalysis by copper ions is observed. These results suggest the existence of a new decomposition pathway for S-nitrosocysteine, which proceeds via an intramolecular nitroso group transfer producing a primary N-nitrosamine that decomposes rapidly to give the corresponding diazonium salt. The nitroso group transfer reaction occurs intermolecularly for the decomposition pathway exhibiting a quadratic dependence on cysteine concentration. Both nitroso group transfer pathways are subject to acid catalysis by cysteine. Kinetic results indicate that the extent of S...NO bond cleavage in the transition state is ahead of protonation of the AH...S sulfur atom. The results obtained show the existence of a new decomposition pathway for the S-nitrosocysteine where NO is not released, and hence, it has a significant biological impact due to the potential use of nitrosothiols as NO donors.

S-Nitroso-N-acetylcysteine Generates Less Carcinogenic N-Nitrosamines in Meat Products than Nitrite

“…In the current study, our aim was to determine the differences in nitrosamine formation in red meat and in red meat in the stomach between nitrite, Cys-SNO, and NAC-SNO as possible meat-curing agents. We show RSNO containing primary amines can efficiently deliver reactive nitrogen species to secondary amines to generate carcinogenic N-NA by the S- to N-transnitrosation-decomposition pathway of RSNO . These results suggest that a primary amine in RSNO molecules has a major influence on nitrosamine formation.…”

“…The reaction is facilitated by the presence of additional l -Cys that acts as a binucleophile. In this regard, Adam et al demonstrated a linear dependence of the reaction rate constant k obs to decomposition of Cys-SNO in the presence of elevated concentrations of free cysteine. This amino acid facilitated the S- to N-transnitrosation of Cys-SNO, forming reactive nitrogen species, carbon center radicals, and releasing nitrogen.…”

Enol Nitrosation Revisited: Determining Reactivity of Ambident Nucleophiles

“…Typical examples are the O-NOǞN-NO migrations observed in the nitrosation of amides and ureas, [14] amino acids [15] in acidic media, and hydroxylamines; [16] the C-NOǞN-NO migrations found in the nitrosation of indoles [17] in acidic media; and the N-NOǞC-NO migrations observed in the Fischer-Hepp rearrangement. [18] Also, S-NOǞN-NO migrations are common when studying nitrosation of cysteine in acidic [19] and basic or neutral [20] media, thioureas [21] and thioproline or thiomorpholine. [22] Scheme 4.…”

Enzymatically degradable nitric oxide releasing S-nitrosated dextran thiomers for biomedical applications

“…It is widely reported that S-nitrosothiols are stabilized under acidic conditions. [60][61][62] (see Fig. S4 in ESI † for a detailed explanation.)…”