Cathodic reduction of 2-nitronaphthothiophen-4,9-quinone: evidence of catalysis by proton donors and its simulation

Abstract

Abstract 2-Nitronaphtho[2,3- b ]thiophen-4,9-quinone (1) is biologically active. The reducible groups have conjugate interaction. Electrochemical experiments (cyclic voltammetry and electrolysis) were performed in order to verify possible intramolecular electron transfer or secondary redox systems and to gain insight into the redox behaviour to help in the understanding of its trypanocidal mechanism of action. Cyclic voltammograms of 1 at the Hg electrode, in DMF+TBAP or DMF+TEAP showed the presence of at least three waves, the two first related to quinone reduction and the third one relative to a catalytic process. After cathodic reduction, at potentials close to the third electron uptake, protons from adventitious water or ammonium quaternary salts can be reduced. Hydrogen formation, with the regeneration of the quinone dianion could be the cause of its catalytic nature. This effect is more pronounced with TEAP. Macroscale electrolyses reinforce the findings. This reaction can be hampered by addition of electrophiles to the medium. Simulated curves fit the experimental ones well. The fourth wave, present at fast scan rates, where the catalysis is not effective, is related to further reduction of the nitro radical anion to the hydroxylamino derivative. At the time scale of cyclic voltammetry, no intramolecular electron transfer was observed. The biological activity of 1 is, possibly, related to the very electrophilic quinone group, generating reactive radical oxygen species through redox cycling.