Structure-Dependent Complexation of Fe3+ by Anthracyclines. 2. The Roles of Methoxy and Daunosamine Functionalities

Abstract

We have investigated the effects of the methoxy and daunosamine sugar moieties on the stability of anthracycline complexes with Fe(3+) in aqueous solution. Idarubicin and daunorubicin are structurally very similar, differing only by the presence of the methoxy substituent at the 4-position. We demonstrate that the methoxy group interacts sterically with the proximal quinone oxygen atom and this interaction affects the stability of the anthracycline-iron(III) complex. A similar steric effect is seen for the pendent daunosamine moiety. Free daunosamine in solution does not show any significant interactions with iron(III), whereas the pendent daunosamine functionality destabilizes anthracycline-iron(III) complex formation. This body of information illustrates the important role of methoxy and daunosamine moieties in anthracycline-iron(III) complex formation and stability.