An electroanalytical investigation on the redox properties of lacidipine supporting its anti-oxidant effect

The redox properties of lacidipine (PyH2), one of the most pharmacologically active N-unsubstituted 1,4-dihydropyridines, have been studied by cyclic voltammetry and controlled potential electrolysis in acetonitrile, an aprotic solvent that is, at best, a mimic of the lipofilic layer of biological membranes. PyH2 undergoes a two-electron oxidation process involving two consecutive one-electron releases, the latter requiring potentials much less positive than the former. The overall process occurs through a primary one-electron step accompanied by a fast proton release, with the formation of a neutral radical (PyH·), which undergoes a further and quite easier one-electron step, thus providing the main ultimate product (PyH+) consisting in the protonated form of the parent pyridine derivative. This appears relevant for the anti-oxidant effect since the radical intermediate is much more prone to be oxidized than to be reduced, thus preventing the propagation of the oxidative chain reaction. The mentioned release of protons in the primary electrode step causes the overall process to be complicated by a parassite side reaction involving the coupling between one of the electrode products (H+) and the starting species. The protonation of PyH2 subtracts part of the original species from the electrode process because the parent cationic species (PyH3+) is no longer electroactive. This parassite reaction occurs rather slowly in the timescale of electroanalytical measurements (the relevant kinetic constant has been estimated to be 6.4 l mol−1 s−1), thus markedly affecting the process only in the presence of relatively high PyH2 concentrations and progressively decreasing with the starting PyH2 concentration. All the products formed in the oxidation process (PyH+, H+ and PyH3+) have been identified by voltammetric evidences based on deep investigations on their cathodic behaviour. The advantageous anti-oxidant properties displayed by PyH2 with respect to those exhibited by phenolic anti-oxidants such as vitamin E are also discussed.