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Absorption spectra of the superoxide ion have been studied in dimethylformamide (DMF) and acetonitrile (AN). It was found that the superoxide ion existed in equilibrium with an ion pair in AN ( K , = 20M-', BQN+ is the cation) and as "free" (solvated) ion in DMF. The addition of DMF caused the destruction of an ion pair in AN. The addition of the proton donors HX (water or ethanol) to the 0, solutions in DMF and AN caused the formation of new ion pairs (BQN+O&HX. The equilibrium constants of these ion pairs were determined in DMF and AN.

The interaction of superoxide ion with adriamycin has been studied in aprotic and protic solutions by the use of electronic absorption and n.m.r. spectroscopy. It was found that superoxide ion reacted with adriamycin by one-electron transfer in both aprotic and protic media (in the latter case against the reduction potential) due to irreversible transformation of the adriamycin semiquinone via dimerisation and deglycosation. The one-electron mechanism was confirmed by electrochemical reduction of adriamycin and by its reduction with NaBH,, benzosemiquinone, and ascorbate. In both aprotic and protic media one-electron reduction of adriamycin by superoxide ion was favoured over deprotonation. The possible application of this mechanism to the reaction of 02-* with other anthraquinones was also considered.Free-radical reactions of adriamycin (AdrH,) and other anthracycline (AnthH,) antibiotics have been much studied in connection with the suggestion that both the anti-cancer effects 3*4 and the cardiotoxicity ' of these antibiotics may be accounted for by the generation of oxygen and semiquinone free radicals. It has been shown4-* that the incubation of anthracycline antibiotics with microsomes and mitochondria leads to a sharp increase in superoxide production, which was explained by the one-electron oxidation of antibiotic semiquinones by molecular oxygen [equation (l)].AnthH,-* + 0, AnthH, + 02-' (1)Chemical studies are not in full agreement with this proposal. Thus, although pulse-radiolysis studies 9,10 show that in aqueous solution equilibrium (1) must indeed be shifted to the right ( K , cu. lo3),'' we have previously found that in aprotic media (DMF) superoxide ion reacts with adriamycin practically irreversibly. We assumed that the reaction proceeds oiu a oneelectron transfer mechanism to form the adriamycin semiquinone which at the next stage forms a dimeric or oligomeric diamagnetic complex. Recently, our conclusion was questioned.I2'l3 The authors of these papers argued that 02-' reacts with anthracycline antibiotics oia the deprotonation reaction (2) and not oiu the one-electron transfer ( -1). 02-' +We re-investigated the interaction of superoxide ion with adriamycin in aprotic media (acetonitrile) and extended the study to water-acetonitrile solutions with a water content up to 900;. Acetonitrile was chosen as the aprotic solvent instead of dimethylformamide because in this solvent 02-* has a strongly marked maximum at 249 nm.I4

The interaction of superoxide ion and ascorbate anion with anthracycline antibiotics (adriamycin and aclacinimycin A) as well as with their Fe3+ complexes has been studied in aprotic and protic media. It was found that both superoxide and ascorbate reduce anthracyclines to deoxyaglycons via a one-electron transfer mechanism under all conditions studied. The reaction of ascorbate anion with adriamycin and aclacinomycin A in aqueous solution proceeded only in the presence of Fe3+ ions; it is supposed that an active catalytic species was Fe3+ adriamycin. It is also supposed that the reduction of anthracycline antibiotics by O2-. and ascorbate in cells may increase their anticancer effect.