Electrochemical oxidation of 4-methyl-1,4-dihydropyridines in protic and aptrotic media - Spin trapping studies

This work reports the electrochemical oxidation of a new series of 4-methyl -1,4-dihydropyridine derivatives with platelet activation factor antagonist ic activity. Differential pulse and cyclic voltammetry studies on a glassy carbon electrode showed an irreversible single peak due to the oxidation of the dihydropyridine ring via two electron. Rotating disk electrode studies show a linear dependence between the current and the rotating rate, indica ting that the oxidation process is diffusion-controlled. Calculated diffusi on coefficients did not exhibit significant differences between the derivat ives. Voltammetric apparent pK(a) values for the protonation-deprotonation equilibrium of the N-heterocyclic nitrogen are compared with 4-phenyl subst ituted 4-aryl-1,4-dihydropyridine (1,4-DHP) derivatives. Based on voltammet ric experiments on glassy carbon electrodes, it is seen that the potential peak values are directly related to the electron density on the dihydropyri dine ring, wherein C-5 substituent with electron-withdrawing character prod uces the most oxidizable 1,4-DHP derivative. The oxidation mechanism follow s the general pathway: electron, H+, electron, H+, with formation of an uns table cation radical in the first step. A one-electron oxidation intermedia te was confirmed with controlled potential electrolysis and electron spin r esonance experiments. On applying N-benzilydene-t-butylamine-N-oxide as the spin trap, the unstable radical intermediates from the oxidation of 4-meth yl-1,4-dihydropyridine derivatives were intercepted. Comparison of the elec tron spin resonance spectra of the nitroxide spin adducts revealed no signi ficant differences in the splitting constants of the radicals. (C) 1999 The Electrochemical Society. S0013-4651(98)05-089-7. All rights reserved.