Effects of the Ligand Structure of Cu(II) Complexes on Oxidative DNA Cleavage

Cu complexes were synthesized by substituting the hydrogen of the amine group of basic ligand 2,2′-dipicoylamine (dpca) (complex 2) with CH₃CO (complex 1), phenyl (complex 3), and methyl (complex 4), respectively, and their DNA cleavage activity was investigated using linear dichroism (LD) and electrophoresis. The DNA cleavage efficiencies of Cu complexes 3 and 4 with phenyl and methyl, which are electron-donating functional groups, turned out to be the highest, and LD magnitudes rapidly decreased at 260 nm. In particular, Cu complex 3 showed a rapid LD magnitude reduction to 63% of the total for 90 min, and to 50% of the total at 12 min. DNA cleavage efficiencies were high in the order of phenyl > methyl > HCH₃CO, and the highest DNA cleavage efficiency was observed in the presence of electron-donating groups. The electrophoresis results are also consistent with the changes in LD spectra over time. The Cu complexes (1–4) were found to cleave DNA through oxidative pathways, and the major reaction oxygen species involved in DNA cleavage were the superoxide radical (·O₂⁻), singlet oxygen (¹O₂), and hydroxyl radical (·OH).