Key result
The methoxy group and pendent daunosamine functionality sterically interact to destabilize anthracycline-iron(III) complex formation in aqueous solution.
The methoxy and daunosamine moieties play important steric roles in the formation and stability of anthracycline-iron(III) complexes, which may have implications for understanding their pharmacological and toxicological properties.
May inform anthracycline design to reduce iron-related toxicity; leaves open in vivo and clinical translation.
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.
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Nawara et al. (2013) studied this question. Methoxy and daunosamine sugar moieties in anthracyclines was evaluated on Stability of anthracycline complexes with Fe(3+) in aqueous solution. The methoxy group and pendent daunosamine functionality sterically interact to destabilize anthracycline-iron(III) complex formation in aqueous solution.
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