304854-99-7Relevant articles and documents
Reactivity of peroxynitrite with melatonin as a function of pH and CO2 content
Peyrot, Fabienne,Martin, Marie-Therese,Migault, Julie,Ducrocq, Claire
, p. 172 - 181 (2003)
Peroxynitrite is known to be a strong oxidant and a nitrating agent of aromatic phenolic or heterocyclic rings, depending on its form in aqueous solutions: the anion ONOO-, its conjugate acid ONOOH, or its CO2 adduct ONOOCO2-. Various reactions have been observed with melatonin (1), a tryptophan derivative, in phosphate-buffered solutions. Melatonin (1) is recognized as a scavenger of several strong oxidants (HO', H2O2,...) accounting for its biological and pharmacological effects. Here we describe two oxidation routes that give rise to indol-2-ones 2 (probably via a 2,3-epoxyindole) and kynuramines 6 (by cleavage of the pyrrole ring), attributable to reactions of ONOOH and ONOO-, respectively, according to the effects of pH and CO2 content. At pH = 7.6 and in the presence of CO2, an important conversion is the cyclization of the lateral amide function, giving 3-substituted pyrroloindoles 4. At neutral pH, therefore, all routes coexist, with a balance between indol-2-ones 2 and pyrroloindoles 4 on the one side and kynuramines 6 on the other, depending on the CO2 content. Furthermore, under specific conditions substitutions of the hydrogen atom on the pyrrole nitrogen atom, affording the 1-nitro-(5) and the unstable 1-nitrosomelatonin (7), are among the major transformations: formation of the nitrosation product, together with that of kynuramines 6, rises sharply when the pH of the medium increases, confirming the implication of ONOO-in their synthesis; conversely, both reaction yields decrease with increasing CO2 content, to favor 1-nitromelatonin (5). Finally, nitration by aromatic substitution occurring essentially on C-4 becomes important at acidic pH, and also at pH = 7.6 over a narrow range of CO2 concentrations. Most of the reactions are typical of the indole moiety, suggesting that melatonin (1) is a model of potential use for investigation of tryptophan chemistry with peroxynitrite. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
