Dicopper Complexes of -Cresol-2,6-bis(amide-tether-dpa) (X = MeO and Cl): Selective ROS Generation and Cytotoxicity Enhancement Controlled by Electronic and Hydrophobic Effects of the MeO and Cl Groups.

Two new -cresol-2,6-bis(amide-tether-dpa) ligands (HL, X = MeO and Cl) and their dicopper complexes [Cu(μ-1,1-OAc)(μ-1,3-OAc)(L)]Y (Y = PF , OAc ) and [Cu(μ-1,3-OAc)(L)]Y (Y = ClO , OAc ) were synthesized. The electronic and hydrophobic effects of the MeO and Cl groups were examined compared with nonsubstituted complex [Cu(μ-1,1-OAc)(μ-1,3-OAc)(L)] (). The electronic effects were found in crystal structures, spectroscopic characterization, and redox potentials of these complexes.

Roles of DNA Target in Cancer Cell-Selective Cytotoxicity by Dicopper Complexes with DNA Target/Ligand Conjugates.

The DNA target/ligand conjugates (HL, X = P and M, = 1-3) were synthesized where various lengths of -CONH(CHCHO)CHCHNHCO- linkers with a 9-phenanthrenyl (P) or methyl (M) terminal as DNA targets replace the methyl group of 2,6-di(amide-tether cyclen)-cresol ligand (HL). DNA binding, DNA cleavage, cellular uptake, and cytotoxicity of [Cu(μ-OH)(L)](ClO) () are examined and compared with those of [Cu(μ-OH)(L)](ClO) () to clarify roles of DNA targets. Upon reaction of with HO, μ-1,1-OH complexes are formed for DNA cleavage.