Electrochemical and EPR characterization of 1,4-dihydropyridines. Reactivity towards alkyl radicals.
This work reports the electrochemical oxidation of a series of three synthesized 4-substituted-1,4-dihydropyridine derivatives in different electrolytic media. Also, an EPR characterization of intermediates and the reactivity of derivatives towards ABAP-derived alkyl radicals are reported. Dynamic, differential pulse and cyclic voltammetry studies on a glassy carbon electrode showed an irreversible single-peak due to the oxidation of the 1,4-dihydropyridine (1,4-DHP) ring via 2-electrons to the corresponding pyridine derivative. Levich plots were linear in different media, indicating that the oxidation process is diffusion-controlled. Calculated diffusion coefficients did not exhibit significant differences between the derivatives in the same medium. The oxidation mechanism follows the general pathway (electron, H+, electron, H+) with formation of an unstable pyridinium radical. One-electron oxidation intermediate was confirmed with controlled potential electrolysis (CPE) and EPR experiments. On applying N-tert-butyl-alpha-phenylnitrone (PBN) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as the spin trap, these unstable radical intermediates from the oxidation of 1,4-DHP derivatives were intercepted. The final product of the CPE, i.e. pyridine derivative, was identified by GC-MS technique. Direct reactivity of the synthesized compounds towards alkyl radicals was demonstrated by UV-Vis. spectroscopy and GC-MS technique. Results indicate that these derivatives significantly react with the radicals, even compared with a well-known antioxidant drug such as nisoldipine.
Núñez-Vergara
Luis J
LJ
Laboratory of Bioelectrochemistry, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, PO Box 233, Santiago, Chile. lnunezv@ciq.uchile.cl
López-Alarcón
C
C
Navarrete-Encina
P A
PA
Atria
A M
AM
Camargo
C
C
Squella
J A
JA
D004095:Dihydropyridines / Q000138:chemical synthesis / Q000737:chemistry*; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D013053:Spectrophotometry; D013113:Spin Labels
D004095:Dihydropyridines; D005609:Free Radicals; D013113:Spin Labels