Possible intermediates in the action of adriamycin—A pulse radiolysis study

Abstract

Over a wide range of pH, the semiquinone free radicals formed by reduction of adriamycin exist as a form which is strongly stabilised by internal hydrogen bonding and resonance. They protonate with pKa = 2.9. Below this pH they exhibit absorption maxima at 430 nm (Emax = 13,200 dm3 mol-1 cm-1) and approximately 720 nm (Emax = 4,200 dm3 mol-1 cm-1). Above pH 2.9 they have maxima at 480 nm (Emax = 14,600 dm3 mol-1 cm-1) and approximately 700 nm (Emax = 3,400 dm3 mol-1 cm-1). In acid and alkaline solution the radicals rapidly disappear by disproportionation, but within the approximate pH range 6 to 11 they appear to be relatively stable for at least 10-20 ms, existing in transient equilibrium with parent adriamycin and the full reduced form. Some rate constants for the formation and reactions of the semiquinone are given, including the reaction with oxygen to give O2.-. Fully reduced adriamycin has absorption maxima at 410 nm (Emax = 11,000 dm3 mol-1 cm-1) at pH 5 and 430 nm (Emax = 19,000 dm3 mol-1 cm-1) at pH 11. It undergoes decomposition within a few hundred ms. The intermediates from daunomycin would be expected to have properties similar to those from adriamycin.