Dicopper(II) Complexes of -Cresol-2,6-Bis(dpa) Amide-Tether Ligands: Large Enhancement of Oxidative DNA Cleavage, Cytotoxicity, and Mechanistic Insight by Intracellular Visualization.

Dicopper complexes of a new -cresol-2,6-bis(dpa) amide-tether ligand (HL1), Cu(μ-OH)(μ-1,3-OAc)(L1) () and [Cu(μ-1,1-OAc)(μ-1,3-OAc)(L1)]X (X = ClO (), OAc ()) were synthesized and structurally characterized. rapidly cleaves supercoiled plasmid DNA by activating HO at neutral pH to a linear DNA and shows remarkable cytotoxicity in comparison with related complexes. As is more cytotoxic than HL1, the dicopper core is kept in the cell. A boron dipyrromethene (Bodipy)-modified complex of the -cresol-2,6-bis(dpa) amide-tether ligand having a Bodipy pendant (HL2), Cu(μ-OAc)(L2) (), was synthesized to visualize intracellular behavior, suggesting that attacks the nucleolus and mitochondria. A comet assay clearly shows that does not cleave nuclear DNA. The apoptotic cell death is evidenced from flow cytometry.