Solution structure of iron(III)-anthracycline complexes.
The interaction of Fe(3+) with the anthracycline anticancer drug idarubicin (Ida) was studied by absorption, CD, Mössbauer, and EPR spectroscopy. The formation of two major Fe(3+)-Ida complexes, labeled I and II, was observed. In complex I, Fe(3+) ion was bound to anthracycline at the {C(12)=O; C(11)-O(-)} coordination site. In complex II, two Fe(3+) ions were bound at sites {C(5)=O; C(6)-O(-)} and {C(12)=O; C(11)-O(-)}, respectively. Complex I was an equimolar monomeric species with a 1:1 Fe(3+):Ida stoichiometry (beta(1) = 4.8 x 10(11) M(-1)), whereas in complex II the anthracycline ligand was bridging two metal ions, alternatively bound to both anthracycline ring chelating sites with the assumption that the ratio of Fe(3+):Ida in complex II was 2:1 (beta(2) = 5.3 x 10(24) M(-2)). Alternatively, complex II may be oligomeric with Fe(3+):Ida = 1:1 and with each Fe(3+) bridging two Ida molecules. Our findings could be important in understanding the biological effects of the anthracycline-ferric complexes. Thus, providing information about the nature of the Fe(3+)-Ida system, we suggest that the formal 1:3 Fe(3+):anthracycline complexes, reported in the previous literature, could be a mixture of species I, II, and free ligand.
Fiallo
M M
MM
Chimie Bioinorganique, LPBC, ESA 7033, Université Paris Nord, 74, rue Marcel Cachin, 93017 Bobigny Cedex, France. fiallo@smbh.univ-paris13.fr
Drechsel
H
H
Garnier-Suillerot
A
A
Matzanke
B F
BF
Kozlowski
H
H
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D004126:Dimethylformamide; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D015255:Idarubicin / Q000737:chemistry* / Q000494:pharmacology; D007501:Iron / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D020014:K562 Cells; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D015204:Spectroscopy, Mossbauer; D014867:Water
D000970:Antineoplastic Agents; D007502:Iron Chelating Agents; D009942:Organometallic Compounds; D012996:Solutions; D014867:Water; D004126:Dimethylformamide; D007501:Iron; D015255:Idarubicin