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.