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

• Published in: The journal of physical chemistry. B 2013-06, Vol.117 (23), p.6868-6873
• Main Authors: Nawara, Krzysztof, Beeckman, Hillary, Krysiński, Paweł, Blanchard, G. J
• Format: Article
• Language: English
• Subjects: Anthracyclines - chemistry; Chemistry; Coordination Complexes - chemistry; Exact sciences and technology; Ferric Compounds - chemistry; General and physical chemistry; Hexosamines - chemistry; Idarubicin - chemistry; Ions - chemistry; Kinetics; Molecular Dynamics Simulation; Theory of reactions, general kinetics; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Thermodynamics; Water
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp4023508

We have investigated the effects of the methoxy and daunosamine sugar moieties on the stability of anthracycline complexes with Fe3+ 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.