Theoretical Studies on DNA-Cleavage Mechanism of Copper(II) Complexes: Probing Generation of Reactive Oxygen Species

Theoretical studies on DNA-cleavage properties of [Cu­(bba)­(diimine)] 1–4 have been carried out using density functional theory (DFT) and docking methods. The optimized structures of Cu­(II) complexes were docked into DNA, glutathiones (GSH), and ascorbic acids (VC) so that the corresponding docking models were obtained. To explore DNA-cleavage properties of Cu­(II) complexes, the docking models of complexes with GSH and VC were further optimized using DFT method, while the docking models of complexes with DNA were optimized using QM/MM method because DNA is a supramolecular system. The rate constants ket between complexes and DNA, GSH, and VC, oxidation–reduction potentials of complexes, and binding energies of complexes with GSH and VC were computed. The DNA-cleavage abilities of Cu­(II) complexes in the presence VC, GSH, and H2O2 were explored and the experimental results could be reasonably explained. Finally, the DNA-cleavage mechanism of Cu­(II) complexes was described in detail, which would contribute to future design of novel anticancer Cu­(II) complexes.