Structure and in vitro and in silico biological activity of zinc(II) complexes with 3,5–dichloro–salicylaldehyde

Five Zn(II) complexes with 3,5–dichloro–salicylaldehyde (3,5–diCl–saloH) in the absence or presence of N,N′–donor co–ligands (2,2′–bipyridine, 1,10–phenanthroline, 2,9–dimethyl–1,10–phenanthroline, or 2,2′–bipyridylamine) were synthesized and formulated as [Zn(3,5–diCl–salo)2(CH3OH)2] (1) and [Zn(3,5–diCl–salo)2(N,N′–donor)] (2–5), respectively, and characterized by diverse techniques. The crystal structures of four complexes were determined by single–crystal X–ray crystallography. The ability of the compounds to scavenge 1,1–diphenyl–picrylhydrazyl and 2,2′–azinobis(3–ethylbenzothiazoline–6–sulfonic acid) radicals and to reduce H2O2 was investigated. In addition, their antimicrobial profile against two Gram–positive and two Gram–negative bacterial strains were investigated. The affinity of the complexes for calf–thymus DNA was examined by diverse techniques, and the DNA–binding constants of the complexes were determined. The cleavage ability of the complexes towards supercoiled circular pBR322 plasmid DNA was examined by agarose gel electrophoretic experiments. The binding of the complexes with bovine and human serum albumins was investigated in order to determine the corresponding binding constants and the binding subdomain. In order to explain the described in vitro activity of the compounds and possibly establish a rational approach in the mechanism of action, molecular docking studies were adopted on the crystal structure of E. coli and S. aureus DNA–gyrase, 5–lipoxygenase, and 5–lipoxygenase–activating protein. Five zinc(II) complexes of 3,5–dichloro–salicylaldehyde ligands and α–diimine co-ligands were synthesized and structurally characterized. In vitro and in silico evaluation of the biological properties showed that complexes may intercalate to calf-thymus DNA, cleave plasmid DNA, bind tightly to albumins and bear promising antioxidant and antimicrobial potency. [Display omitted] •Synthesis and characterization of zinc(II) complexes of 3,5-dichlorosalicylaldehyde•The complexes present moderate antioxidant and antibacterial properties•The complexes may bind to DNA via intercalation and cleave plasmid DNA•The complexes bind to serum albumins reversibly, the binding site is determined•In vitro findings were in agreement with in silico molecular docking results