The mechanism of the nitrosation of α-amino acids: evidence for an intramolecular pathway

Abstract

The results of a kinetic study of the nitrosation of sarcosine, proline, cysteine, and the ethyl ester of sarcosine are reported. Under the conditions in which sarcosine and proline were studied, both first- and second-order terms were found for nitrite dependence. The experimental results are interpreted by a mechanism which involves NO⁺ and N₂O₃ as direct nitrosating agents, while the effect of acidity changes on the first-order term for nitrite shows that the N-nitroso compound is also formed in a parallel reaction in which a slow intramolecular rearrangement follows the attack of NO⁺ on the carboxylate group of the amino acid. This pathway is confirmed by the absence of such a parallel reaction in the nitrosation of the ethyl ester of sarcosine. The influence of acidity on the nitrosation of cysteine shows that S-nitrosation is brought about by the reaction of NO⁺ with both the N-protonated, HSCH₂–CH(NH₃)–CO₂H, and zwitterion, HSCH₂–CH([graphic omitted]H₃)–CO₂^–, forms of the amino acid. The values obtained for the bimolecular rate constants are compatible with diffusion control, the difference between the values for both forms of the amino acid being explicable in terms of charges of the reagents.