An insight into non-covalent interactions in binary, ternary and quaternary copper (II) complexes: Synthesis, X-ray structure, DFT calculations, antimicrobial activity and molecular docking studies

Abstract

Levofloxacin is a synthetic antibacterial agent that effectively inhibits DNA replication and is commonly used for the treatment of genitourinary, respiratory, and gastrointestinal tract infections. Metallodrugs interact with DNA, RNA, proteins, receptors, and lipids, making them unique and more effective as chemotherapy agents than their parent drugs. On this basis, herein four copper(II) complexes assembled from antibacterial levofloxacin ligand were synthesized and characterized using different analytical and spectroscopic measurements. X- ray perceived the formation of a ternary dimer and a ternary monomer complexes both in distorted square pyramidal geometry, with the existence of levofloxacin in a zwitterionic form. The other two complexes were verified, as binary and quaternary complexes having distorted octahedral geometry. Structure elucidation of these complexes was also explored by density functional theory methods and optimized geometrical parameters. Ternary dimer complex demonstrated higher stability than the ternary monomer complex. Natural bond orbital (NBO) analysis and molecular electrostatic potential (MESP)were investigated. Electronic absorption spectra of the optimized structure were performed using the time-dependent density functional theory (TD-DFT)/CAM-B3LYP method with LANL2DZ basis set in the gas phase. Binary copper complex exhibited significant antimicrobial activity and ternary monomer complex was more potent than ternary dimer complex. Interestingly levofloxacin and ternary copper complexes were completely devoid of antifungal activity, whereas octahedral binary and quaternary copper complexes displayed antifungal activity. In-silico molecular docking studies were accomplished with 3T88 (E-Coli) and 2GNP (S. pneumonia) receptors. Results proved powerful interaction at the docked site through the formation of hydrogen bond and van der wall interactions.