Monomeric copper(II) complexes with unsymmetrical salen environment: Synthesis, characterization and study of biological activities

Three new ONNO-donor tetradentate unsymmetrical salen ligands were synthesized by using o -phenyl diamine with substituted salicylaldehydes followed by a two-step reaction methodology. These three ligands by reaction with Cu(OAc)2.4H2O produced three new monomeric Cu(II) complexes, [CuII(L1 ?3)] (1-3). Elemental analysis, IR, UV-vis, NMR, and HR-ESI-MS techniques were used to analyze and characterize all the synthesized ligands and their corresponding metal complexes. Molecular structures of 1-3 were confirmed by the single-crystal-XRD analysis. Furthermore, the DNA binding ability of these complexes was checked through UV-vis, fluorescence spectroscopy, and also by circular dichroism studies. All the complexes were found to show an intercalation mode of binding with the Kb value in the range of 104-105 M-1. Finally, 1-3 was tested against two malignant (HeLa and A549) and non -cancerous (NIH-3T3) cell lines to check their in vitro antiproliferative activities. Among all, 1 is the most cytotoxic of the series having IC50 values of 5.7 +/- 0.9 and 6.0 +/- 0.3 mu M against HeLa and A549 cell lines, respectively. This result is also consistent with the DNA binding order. Furthermore, the apoptotic mode of cell death of all the complexes was also evaluated by DAPI, AO/EB, and Annexin V-FITC/PI double staining assays.