A rare dihydroxo copper(ii) complex with ciprofloxacin; a combined experimental and ONIOM computational study of the interaction of the complex with DNA and BSA

Abstract

A rare mononuclear Cu(II) complex, trans-[Cu(cip)₂(OH)₂]·2CH₃OH·6H₂O, where cip^+/− is a zwitterionic form (⁺H₂N–⋯–COO⁻) of ciprofloxacin, has been synthesized and characterized by spectroscopic methods and X-ray crystallography. In vitro studies (UV-Vis spectroscopy, emission titration, voltammetric techniques, and gel electrophoresis) show that the complex interacts with calf-thymus DNA (CT-DNA) via an intercalative binding mode. The microenvironment and the secondary structure of BSA are changed in the presence of the complex. Also, our Own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) method, based on the hybridization of QM/MM methodology, was carried out to investigate the interaction of the complex with DNA and BSA. The calculated electronic interaction energy of the complex with DNA in the gas phase and water is −64.358 and −56.685 kcal mol⁻¹, respectively. The calculated interaction of the complex with BSA is −54.231 kcal mol⁻¹. The theoretical data confirm the experimental results with respect to the mechanism of binding and binding constants. Finally, the calculations indicate that the QM/MM is a more precise method than the docking method for determination of the electronic interaction energies because of two reasons: (I) it considers the complex quantum mechanically in calculations, and (II) it accounts for the polarization of the wave function of the complex by the charge distribution of the molecular mechanical part (DNA and BSA).