Synthesis, DNA binding and anticancer properties of new Cu(II) and Zn(II) complexes of a Schiff base ligand containing a triphenylphosphonium as a lipophilic cation

Abstract

A new quinoline-Schiff base ligand (LTPP) containing the lipophilic triphenylphosphonium cation and its complexes [Cu(LTPP)Cl]Cl and [Zn(LTPP)Cl]Cl were synthesized and characterized. The structures of the ligand and metal complexes were characterized by FTIR, elemental analysis, NMR (for ligand), UV–Vis absorption and fluorescence spectroscopies. DNA binding interactions of the ligand and its metal complexes were investigated by UV–vis absorption and fluorescence spectroscopies as well as viscosity measurements. The DNA binding affinity (Kb) for the ligand and complexes [Cu(LTPP)Cl]Cl and [Zn(LTPP)Cl]Cl) obtained from absorption spectra were found as 4.33, 4.66 and 6.01 (×105 M−1), respectively. The ligand and its Cu(II) complex showed similar propensities to interact with DNA, yet the DNA binding affinity of the Zn(II) complex was relatively higher than free ligand and its Cu(II) complex. Docking studies were conducted in order to further investigate the DNA binding interactions. The ligand and its complexes were screened for their cytotoxic properties towards malignant mesothelioma (H2452) and healthy human umbilical vein endothelial (HUVEC) cells. The Cu(II) and Zn(II) complexes that were loaded into the cells (H2452) confirm their intracellular uptake by fluorescence-based cell imaging. Complex [Zn(LTPP)Cl]Cl emitted fluorescent light even after entering the cell suggesting that the compound can be used for cell tracking purposes. In order to find out whether the compounds we synthesized had the potency to enter human cells, we measured the florescent light emission of H2452 cells treated with the products at their IC50 concentration for 24 h. In vitro antioxidant properties of the ligand and its metal complexes were also studied.