Iron-DNA complex (Fe-DNA)

Iron complexes associated with DNA represent a critical interface in medicinal chemistry and pathology, where transition metal ions facilitate oxidative transformations of the genetic material. In a therapeutic context, the most prominent example is the glycopeptide antibiotic Bleomycin, which coordinates with ferrous iron [Fe(II)] and oxygen to form an activated complex that binds to the minor groove of DNA (Hecht, S. M., 2000, J. Nat. Prod.). This complex induces site-specific double-strand breaks through the abstraction of hydrogen atoms from the C4' position of the deoxyribose sugar, leading to cell death in neoplastic tissues (Burger, R. M., 1998, Chem. Rev.). Beyond exogenous drugs, endogenous iron-sulfur [4Fe-4S] clusters are increasingly recognized as essential components of DNA metabolism enzymes, including polymerases and helicases, where they may serve as redox switches or structural stabilizers (Fuss, J. O., et al., 2015, Biochim. Biophys. Acta). However, unregulated iron-DNA interactions are a major source of genomic instability, as free iron can catalyze the Fenton reaction to produce hydroxyl radicals that cause widespread oxidative DNA damage (Henle, E. S., & Linn, S., 1997, J. Biol. Chem.). Consequently, targeting these complexes or the pathways that regulate iron-DNA interactions is a key strategy in both oncology and the treatment of iron-overload disorders. The study of these complexes also extends to neurodegenerative diseases, where iron accumulation in the brain is linked to DNA damage and neuronal loss (Zecca, L., et al., 2004, Nat. Rev. Neurosci.).

Other names

DNA-iron adductsFerric-DNA complexBleomycin-iron-DNA complexIron-coordinated DNAFe-DNA adduct

Formation of a ternary drug-iron-DNA complex that facilitates the reduction of molecular oxygen to reactive oxygen species, leading to site-specific oxidative cleavage of the DNA backbone (Hecht, S. M., 2000, J. Nat. Prod.).