Redox reactions of sanazole (AK-2123) in aqueous solutions: a pulse radiolysis study.

The redox chemistry of sanazole, an efficient hypoxic cell radiosensitizer, generally referred to as AK-2123, was studied by pulse radiolysis with eaq-, CO2-., 2-propanol radicals and CH2OH radicals. AK-2123 reacts with eaq-, CO2-. and 2-propanol radicals at almost diffusion-controlled rates, producing a nitro radical anion (lambda max = 290 nm) within a few microseconds. The decay kinetics of the radical anion was independent of the pH. The radical anion reacts with oxygen with a rate constant of 3.4 x 10(6) dm3 mol-1 s-1. An electron-transfer reaction was observed from the thymine radical anion to AK-2123. From redox equilibria with methyl viologen, the one-electron reduction potential of AK-2123 in aqueous solution, determined by pulse radiolysis, was estimated to be -0.33 +/- 0.02 V vs. NHE. Depletion of intracellular nonprotein thiols did not mitigate the radiosensitizing affect of the hypoxic radiosensitizer, AK-2123.