Purpose. To study the reactivity of C4‐substituted 1,4‐dihydropyri‐ dines (1,4‐DHP), with either secondary or tertiary nitrogen in the dihydropyridine ring, toward SIN‐1‐derived peroxynitrite in aqueous media at pH 7.4.
Methods. Reactivity was followed by changes in the absorptivity of the UV‐Vis bands corresponding to 1,4‐DHP. Gas Chromatography/Mass Spectrometer (GC‐MS) and Electron Paramagnetic Resonance (EPR) spin trap techniques were used to characterize the final product and the intermediates of the reaction, respectively.
Results. 1,4‐DHPs significantly reacted toward peroxynitrite at varied rates, according to the calculated kinetic rate constants. By EPR spectroscopy, a carbon‐centered radical from the 1,4‐DHP was intercepted with N‐tert‐butylamine‐α‐phenylnitrone (PBN), as the intermediate for the reaction with peroxynitrite. Likewise, the oxidized derivative (i.e., the pyridine) was identified as the final product of the reaction by GC‐MS. By using the technique of deuterium kinetic isotope effect, the participation of the hydrogen of the 1‐position on the 1,4‐DHP ring was shown not to be the rate‐limiting step of the reaction.
Conclusions. The direct participation of the 1,4‐DHP derivatives in the quenching of SIN‐1‐derived peroxynitrite has been demonstrated. Kinetic rate constant of tested 1,4‐DHP toward peroxynitrite showed a direct relationship with the oxidation peak potential values; that is, compounds reacting faster were more easily oxidized.
