Free radical formation from anthracycline antitumour agents and model systems--I. Model naphthoquinones and anthraquinones.

Abstract

Several naphthoquinones and anthraquinones were chosen as simple models of the anthracycline drugs and their semiquinone radical anions were generated by various methods. With the exception of 1,4-naphthoquinone, all of the quinones studied gave radicals that were highly reactive with oxygen, but which, in its absence, were stable over a limited pH range. The radicals were studied using electron spin resonance (ESR) spectroscopy and an examination was made of the effect on the distribution of the unpaired electron, of introducing various groups into the conjugated ring system. Hydroxyl groups capable of participating in strong intramolecular hydrogen bonding with neighbouring carbonyl groups had a marked influence on electron distribution and reduced the effects of intermolecular hydrogen bonding of the radicals with solvent molecules.