title: Structure-dependent complexation of Fe3+ by anthracyclines. 1. The importance of pendent hydroxyl functionality.
abstract: We have investigated the stability of doxorubicin and daunorubicin complexes with Fe(3+) 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 Fe(3+) relative to that seen for daunorubicin. We utilize UV-visible 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 Fe(3+). Our data indicate that the binding mode of iron in the complex is different for doxorubicin and daunorubicin.
authors.affiliation: Department of Chemistry, University of Warsaw, Pasteura 1, Warsaw 02-093, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Nawara
authors.forename: John L
authors.initials: JL
authors.lastname: McCracken
authors.forename: Paweł
authors.initials: P
authors.lastname: Krysiński
authors.forename: G J
authors.initials: GJ
authors.lastname: Blanchard
mesh_terms: D018943:Anthracyclines / Q000737:chemistry*; D002942:Circular Dichroism; D003630:Daunorubicin / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D013056:Spectrophotometry, Ultraviolet; D014867:Water / Q000737:chemistry
chemical_list: D018943:Anthracyclines; D005290:Ferric Compounds; D007477:Ions; D014867:Water; D004317:Doxorubicin; D003630:Daunorubicin