ONE-ELECTRON OXIDATION OF MITOMYCIN-C AND ITS CORRESPONDING PEROXYL RADICALS - A STEADY-STATE AND PULSE-RADIOLYSIS STUDY

The one-electron oxidation of Mitomycin C (MMC) as well as the formati on of the corresponding peroxyl radicals were investigated by both ste ady-state and pulse radiolysis. The steady-state MMC-radiolysis by OH- attack followed at both absorption bands showed different yields: at 2 18 nm G(i) (-MMC) = 3.0 and at 364 nm G(i) (-MMC) = 3.9, indicating th e formation of various not yet identified products, among which ammoni a was determined, G(NH3) = 0.81. By means of pulse radiolysis it was e stablished a total k (OH + MMC) = (5.8 +/- 0.2) x 10(9) dm(3) mol(-1) s(-1). The transient absorption spectrum from the one-electron oxidize d MMC showed absorption maxima at 295 nm (epsilon = 9950 dm(3) mol(-1) cm(-1)), 410 nm (epsilon = 1450 dm(3) mol(-1) cm(-1)) and 505 nm (eps ilon = 5420 dm(3) mol(-1) cm(-1)). At 280-320 and 505 nm and above the y exhibit in the first 150 mu s a first order decay, k(1) = (0.85 +/- 0.1) x 10(3) s(-1), and followed upto ms time range, by a second order decay, 2k = (1.3 +/- 0.3) x 10(8) dm(3) mol(-1) s(-1). Around 410 nm the kinetics are rather mixed and could not be resolved. The steady-st ate MMC-radiolysis in the presence of oxygen featured a proportionalit y towards the absorbed dose for both MMC-absorption bands, resulting i n a G(i) (-MMC) = 1.5. Among several products ammonia-yield was determ ined G(NH3) = 0.52. The formation of MMC-peroxyl radicals was studied by pulse radiolysis, likewise in neutral aqueous solution, but saturat ed with a gas mixture of 80% N2O and 20% O-2. The maxima of the observ ed transient spectrum are slightly shifted compared to that of the one -electron oxidized MMC-species, namely: 290 nm (epsilon = 10100 dm(3) mol(-1) cm(-1)), 410 nm (epsilon = 2900 dm(3) mol(-1) cm(-1)) and 520 nm (epsilon = 5500 dm(3) mol(-1) cm(-1)). The O-2-addition to the MMC- one-electron oxidized transients was found to be at 290 to 420 nm k(MM C.OH + O-2) = 5 x 10(7) dm(3) mol(-1) s(-1), around 480 nm k = 1.6 x 1 0(8) dm(3) mol(-1) s(-1) and at 510 nm and above, k = 3 x 10(8) dm(3) mol(-1) s(-1). The decay kinetics of the MMC-peroxyl radicals were als o found to be different at the various absorption bands, but predomina ntly of first order; at 290-420 nm k(1) = 1.5 x 10(3) s(-1) and at 500 nm and above, k(1) = 7.0 x 10(3) s(-1). The presented results are of interest for the radiation behaviour of MMC as well as for its applica tion as an antitumor drug in the combined radiation-chemotherapy of pa tients. (C) 1997 Elsevier Science Ltd.