Copper(II) complexes with new fluoroquinolones: Synthesis, structure, spectroscopic and theoretical study, DNA damage, cytotoxicity and antiviral activity

• X-ray structure reveals a distorted square pyramidal coordination of copper(II).
• DNA cleavage activity is enhanced by the copper(II) ion and H2O2.
• Experimental UV–vis and IR data are analyzed with the help of DFT calculations.
• DFT geometry optimizations are compared with molecular dynamics simulations.
• Cytotoxic effects and antiviral activity against MHV-68 have been investigated.

Copper(II) complexes with fluoroquinolones in the presence of the nitrogen donor heterocyclic ligands 1,10-phenanthroline have been considered in detail. The phenanthroline moiety was introduced into the ligand environment with the aim to determine whether the nuclease activity is feasible. All suitable X-ray structures of the complexes under study reveal a distorted square pyramidal coordination geometry for Cu(II) atom. The conformational and spectroscopic (FT-IR and UV–visible) behavior has been analyzed and has been interpreted with respect to B3LYP/6-311G* calculations including molecular dynamics. The ability of the complexes to cleave DNA was studied by agarose gel electrophoresis with plasmid DNA pBSK+. The results have confirmed that the complexes under study behave as the chemical nucleases. Nuclease like activity in the absence of hydrogen peroxide allows us to deduce an interaction of the complexes with the DNA resulting in the conversion of supercoiled circular DNA to the nicked form. The DNA cleavage activity enhanced by the presence of hydrogen peroxide demonstrates the participation of reactive oxygen species, such as superoxide radical anions and hydroxyl radicals which presence was confirmed independently using the standard radical scavenging agents. It has been suggested that the radical formation through the Fenton/Haber–Weiss reaction is mediated by the redox cycling mechanisms with the participation of cupric/cuprous ions. Cytotoxic activity was evaluated as the 50% cytotoxic concentration (CC50). The potential effects of tested compounds on replication of murine gammaherpesvirus 68 (MHV-68) under in vitro conditions were also evaluated. However, no antiviral activity against MHV-68 was observed.

Synthesis, structure and spectroscopic characterization of copper(II) complexes with new fluoroquinolone ligands and 1,10-phenanthroline are reported. Obtained X-ray structures and UV–vis/IR spectra are critically confronted with theoretical calculations at the B3LYP level of theory including QM/MM simulations. DNA damage, cytotoxicity and antiviral activity are investigated.Figure optionsDownload as PowerPoint slide