Structure-Dependent Complexation of Fe3+ by Anthracyclines. 1. The Importance of Pendent Hydroxyl Functionality

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• 作者：Krzysztof Nawara ; John L. McCracken ; Pawe艂 Krysi艅ski ; G. J. Blanchard
• 刊名：The Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：June 13, 2013
• 年：2013
• 卷：117
• 期：23
• 页码：6859-6867
• 全文大小：505K
• 年卷期：v.117,no.23(June 13, 2013)
• ISSN：1520-5207

文摘

We have investigated the stability of doxorubicin and daunorubicin complexes with Fe³⁺ in aqueous solution. Doxorubicin and daunorubicin are anthracycline chemotherapeutic agents that differ structurally by the presence of a hydroxymethylketone functionality in doxorubicin versus a methyl ketone moiety in daunorubicin. We demonstrate that the presence of the hydroxyl group in doxorubicin enhances its 1:1 complexation with Fe³⁺ relative to that seen for daunorubicin. We utilize UV鈥搗isible absorbance, circular dichroism, fluorescence and EPR spectroscopies, molecular dynamics, and semiempirical calculations to understand how the presence of an additional hydroxyl group affects the interactions of anthracyclines with Fe³⁺. Our data indicate that the binding mode of iron in the complex is different for doxorubicin and daunorubicin.