Copper(II) complexes of bidentate mixed ligands as artificial nucleases: Synthesis, crystal structure, characterization and evaluation of biological properties

Abstract

Mixed ligand transition metal complexes play a significant role in biological processes by interacting with small molecules and activating the enzymes for nuclease activity. Four mixed ligand copper(II) complexes [Cu(5-nsal)(bipy)(ClO4)] (1), [Cu(2-hnap)(bipy) (ClO4)] (2), [Cu(5-nsal)(biim)(ClO4)] (3) and [Cu(2-hnap)(biim)(ClO4)] (4) (bipy = 2,2′-bipyridyl, biim = 2,2′-bi-1H-imidazole, 5-nsal = 5-nitrosalicylaldehyde and 2-hnap = 2-hydroxynaphthaldehyde) were successfully synthesized and physico-chemically characterized. The X-ray quality single crystals of copper(II) complexes 1 and 2 showed that the copper atom was penta-coordinated with square-pyramidal geometry. The physicochemical characterizations of the copper(II) complexes also confirmed the formation of anticipated structures. The redox potentials of the complexes assessed by cyclic voltammetry showed a quasi-reversible redox behavior consistent with Cu(II)/Cu(I) reduction in the cathodic region. The results of ctDNA binding studies using absorption, fluorescence and circular dichroism spectra exposed that the synthesized complexes interact via intercalation mode. The molecular docking studies (in silico) showed that complexes interact via major grooves which supported the results obtained from in vitro DNA binding studies. The nuclease activity of the complexes showed a moderate cleave of the supercoiled plasmid pBR322 DNA in presence of reducing agent (MPA) via hydroxy radical formation. All the copper (II) complexes exhibited a significant antimicrobial activity against two gram-positive, two gram-negative bacterial stains and two fungal species.