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

2-Nitronaphtho[2,3-b]thiophen-4,9-quinone (1) is biologically active. The r educible groups have conjugate interaction. Electrochemical experiments (cy clic voltammetry and electrolysis) were performed in order to verify possib le intramolecular electron transfer or secondary redox systems and to gain insight into the redox behaviour to help in the understanding of its trypan ocidal 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, th e two first related to quinone reduction and the third one relative to a ca talytic process. After cathodic reduction, at potentials close to the third electron uptake, protons from adventitious water or ammonium quaternary sa lts can be reduced. Hydrogen formation, with the regeneration of the quinon e dianion could be the cause of its catalytic nature. This effect is more p ronounced with TEAP. Macroscale electrolyses reinforce the findings. This r eaction call be hampered by addition of electrophiles to the medium. Simula ted curves fit the experimental ones well. The fourth wave, present at fast scan rates, where the catalysis is not effective, is related to further re duction of the nitro radical anion to the hydroxylamino derivative. At the time scale of cyclic voltammetry, no intramolecular electron transfer was o bserved. The biological activity of 1 is, possibly, related to the very ele ctrophilic quinone group, generating reactive radical oxygen species throug h redox cycling. (C) 1999 Elsevier Science S.A. All rights reserved.