Association of structural modifications with bioactivity in three new copper(II) complexes of Schiff base ligands derived from 5-chlorosalicylaldehyde and amino acids

Three novel structurally associated copper(II) complexes [Cu-II(SalCl-Gly)(H2O)(2)] (1), [Cu-II(SalCl-Ala)(H2O)] (2) and [Cu-II(SalCl-Gly)(bipy)] center dot 0.5H(2)O (3) (SalCl-Gly = 5-chloro-2-hydroxybenzylidene-glycine, SalCl-Ala = 5-chloro-2-hydroxybenzylidene-alanine, bipy = 2,2'-bipyridine) have been synthesized and characterized by X-ray crystallography, elemental analysis, IR and fluorescence spectroscopy. Single-crystal diffraction reveals that complex 1 is an infinite 1D zigzag chain in which SalCl-Gly serves as both a chelating and a bridging ligand, while complexes 2 and 3 are mononuclear. Cu(II) ions in complexes 1-3 exhibit distorted quasi-hexacoordinated octahedral, tetracoordinated square planar, and pentacoordinated square pyramid geometry, respectively. Their interactions with calf thymus DNA (CT-DNA) have been investigated by viscosity measurements and fluorescence spectroscopy. The apparent binding constant (K-app) values for 1-3 are 1.02 x 10(5), 0.98 x 10(5) and 1.57 x 10(5) M-1, respectively. All complexes displayed efficient oxidative cleavage of supercoiled DNA in the presence of H2O2. Complex 2, whose ligand can be regarded as a methyl-modification of SalCl-Gly of 1, showed a reduced DNA cleavage activity and a little-changed DNA-binding ability compared with 1. While attaching a 2,2'-bipyridine group to 1, the resulting complex 3 was conferred an enhanced intercalation into DNA. Moreover, cytotoxicity studies of three complexes against HepG-2 (human liver hepatocellular carcinoma) and NCI-H460 (human large-cell lung carcinoma) cells indicated that, thereto, complex 3 possessed the highest inhibition on viability of tested cells. (C) 2015 Published by Elsevier Inc.