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Reactivity of Peroxynitrite with Melatonin as a Function of pH and CO 2 Content
Author(s) -
Peyrot Fabienne,
Martin MarieThérèse,
Migault Julie,
Ducrocq Claire
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200301)2003:1<172::aid-ejoc172>3.0.co;2-w
Subject(s) - chemistry , peroxynitrite , nitration , nitrosation , pyrrole , medicinal chemistry , adduct , hydrogen peroxide , aqueous solution , photochemistry , organic chemistry , superoxide , enzyme
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 CO 2 adduct ONOOCO 2 − . 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 · , H 2 O 2 , ...) 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 CO 2 content. At pH = 7.6 and in the presence of CO 2 , 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 CO 2 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 CO 2 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 CO 2 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)