Electrochemical and spectroelectrochemical behavior of the main photodegradation product of nifedipine: the nitrosopyridine derivative.
OBJECTIVE
To characterize the electrochemical behavior of the photodegradation product of nifedipine, i.e., 2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridine-carboxylic acid dimethyl ester (NPD) in different electrolytic media. We also evaluated the interaction between free radicals generated from NPD and xeno/endobiotics.


METHODS
Tast polarography, differential pulse polarography, and cyclic voltammetry were used for the characterization. Controlled potential electrolysis and ultraviolet-visible spectroscopy were used to generate and to detect the nitroso radical anion.


RESULTS
In protic media, the NPD derivative gave a reversible well-defined peak either on Hg or glassy carbon electrodes in a reaction involving two electrons and two protons to give the hydroxylamine derivative. In mixed aqueous-organic media (pH 9) and in aprotic media, nitroso radical anion was isolated and characterized, exhibiting second-order dimerization rate constant (k2) values of 11,300 +/- 210 [Ms](-1) and 8,820 +/- 78 [Ms](-1), respectively. Reactivity of the nitroso radical anion with relevant pharmacologic targets revealed a significant interaction with the tested endo/xenobiotics (cysteamine, GSH, N-acetylcysteine, and adenine).


CONCLUSIONS
Both in mixed and aprotic media, NPD generated free-radical species, the nitroso radical anion. Taking into account their respective interaction rate constants, the following tentative rank order of reactivity can be established as follows: cysteamine > N-acetylcysteine > GSH > adenine.
Núñez-Vergara
L J
LJ
Laboratory of Bioelectrochemistry, Faculty of Chemical & Pharmaceutical Sciences, University of Chile, Santiago. lnunezv@ciq.uchile.cl
Bollo
S
S
Fuentealba
J
J
Sturm
J C
JC
Squella
J A
JA
D004563:Electrochemistry; D004572:Electrolysis / Q000379:methods; D009543:Nifedipine / Q000737:chemistry* / Q000378:metabolism; D009603:Nitroso Compounds / Q000737:chemistry* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism
D009603:Nitroso Compounds; D011725:Pyridines; D009543:Nifedipine