Evaluation of transnitrosating ability of N-nitrosoguanidines to alkyl thiols and thiol amino acids

Abstract

The transfer of the nitroso group from 1-nitroso-1-methyl-3-tolylsulfonylguanidine (NOTSG) and 1-nitroso-1-methyl-3-benzoylguanidine (NOBMG) to some thiols, including the amino acid cysteine, was studied in a pH range between 7 and 12.The measured apparent bimolecular rate constant of transnitrosation (ktrapp) revealed a bell-shaped pH dependence that clearly indicates that both nitrosoguanidines react through the corresponding neutral form, and the nucleophiles in the thiolate anion form to give the corresponding S-nitrosothiol. Regarding cysteine, the existence of three macroscopic acidity constants influenced the kinetic behavior of the transnitrosation reaction. Transnitrosation rates (ktr) of the two possible nucleophilic species were obtained and it was found that NOBMG has lower thiol transnitrosation capacity due to the lower electron-withdrawing effect of benzoyl group and to the possible stabilization of the anionic structure as a consequence of the establishment of the intramolecular hydrogen bond. The ktr values of the studied nucleophiles were calculated and a Brønsted-type plot was established giving unexpected negatives βnuc(βnuc(NOBMG)=−0,17 and βnuc(NOTSG)=−0,11). The atypical βnuc values were attributed to the need for previous desolvation of the nucleophile.