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 formation of the corresponding peroxyl radicals were investigated by both steady-state and pulse radiolysis. The steady-state MMC-radiolysis by OH-attack followed at both absorption bands showed different yields: at 218 nm G_i (-MMC) = 3.0 and at 364 nm G_i (-MMC) = 3.9, indicating the formation of various not yet identified products, among which ammonia was determined, G(NH₃) = 0.81. By means of pulse radiolysis it was established a total κ (OH + MMC) = (5.8 ± 0.2) × 10⁹ dm³ mol^?1 s^?1. The transient absorption spectrum from the one-electron oxidized MMC showed absorption maxima at 295 nm (ε = 9950 dm³ mol^?1 cm^t-1), 410 nm (ε = 1450 dm³ mol^?1 cm^?1) and 505 nm ( ε = 5420 dm³ mol^?1 cm^?1). At 280–320 and 505 nm and above they exhibit in the first 150 μs a first order decay, κ₁ = (0.85 ± 0.1) × 10³ s^?1, and followed upto ms time range, by a second order decay, 2κ = (1.3 ± 0.3) × 10⁸ dm³ mol^-1 s^?1. Around 410 nm the kinetics are rather mixed and could not be resolved.

The steady-state MMC-radiolysis in the presence of oxygen featured a proportionality towards the absorbed dose for both MMC-absorption bands, resulting in a G_i (-MMC) = 1.5. Among several products ammonia-yield was determined G(NH₃) = 0.52. The formation of MMC-peroxyl radicals was studied by pulse radiolysis, likewise in neutral aqueous solution, but saturated with a gas mixture of 80% N₂O and 20% O₂. The maxima of the observed transient spectrum are slightly shifted compared to that of the one-electron oxidized MMC-species, namely: 290 nm (ε = 10100 dm³ mol^?1 cm^?1), 410 nm (ε = 2900 dm³ mol^?1 cm^?1) and 520 nm (ε = 5500 dm³ mol^?1 cm^?1). The O₂-addition to the MMC-one-electron oxidized transients was found to be at 290 to 410 nm gk(MMC·OH + O₂) = 5 × 10⁷ dm³ mol^?1 s^?1, around 480 nm κ = 1.6 × 10⁸ dm³ mol^?1 s^?1 and at 510 nm and above, κ = 3 × 10⁸ dm³ mol^?1 s^?1. The decay kinetics of the MMC-peroxyl radicals were also found to be different at the various absorption bands, but predominantly of first order; at 290–420 nm κ₁ = 1.5 × 10³ s^?1 and at 500 nm and above, κ = 7.0 × 10³ s^?1.

The presented results are of interest for the radiation behaviour of MMC as well as for its application as an antitumor drug in the combined radiation-chemotherapy of patients.