Synthesis and structural characterization of ternary Cu (II) complexes of glycine with 2,2′-bipyridine and 2,2′-dipyridylamine. The DNA-binding studies and biological activity

In this study two new complexes [Cu(bpy)(Gly)Cl]·2H2O (1) and [Cu(dpa)(Gly)Cl]·2H2O (2) (bpy = 2,2′-bipyridine; dpa = 2,2′-dipyridylamine, Gly = glycine) have been synthesized and characterized by elemental analysis, IR, TGA, UV–vis and magnetic susceptibility measurements. The binding properties of the complexes with CT-DNA were investigated by electronic absorption spectra. The intrinsic binding constants (Kb) calculated from UV–vis absorption studies were 1.84 × 103 M−1 and 3.1 × 103 M−1 for complexes 1 and 2 respectively. Thermal denaturation has been systematically studied by spectrophotometric method and the calculated ΔTm was nearly 5 °C for each complex. All the results suggest that the interaction modes between the complexes and CT-DNA were electrostatic and/or groove binding. The redox behavior of the two complexes was investigated by cyclic voltammetry. Both complexes, in presence and absence of CT-DNA show a quasi-reversible wave corresponding to CuII/CuI redox couple. The change in E1/2, ΔE and Ipc/Ipa ascertain the interaction of complexes 1 and 2 with CT-DNA. Further insight into the binding of complexes with CT-DNA has been made by gel electrophoresis, where the binding of complexes is confirmed through decreasing the mobility and intensity of DNA bands. In addition, the antitumor activity of the complexes was tested on two cancer cell lines; the breast cancer (MCF7) and the human hepatocellular carcinoma (HEPG2), as well as one normal cell line; the human normal melanocytes (HFB4). The results showed that complex 1 was more potent antitumor agent than complex 2. The in-vitro antimicrobial activity of the two complexes was carried out using the disc diffusion method against different species of pathogenic bacteria and fungi. The activity data showed that complex 2 was more active in inhibiting the growth of the tested organisms.

[Cu(bpy)(Gly)Cl]·2H2O (1) and [Cu(dpa)(Gly)Cl]·2H2O (2) have been synthesized and characterized by physico-chemical analysis. The binding of complexes with CT-DNA has been studied by UV–vis spectroscopy and electrochemical techniques, as well as gel electrophoresis, revealing their strong binding ability. The calculated binding strength (Kb) of the two complexes to CT-DNA was found to be of lower magnitude than that of the classical intercalator EB (ethidium bromide) (Kb = 1.23(±0.07) × 105 M−1) suggesting an electrostatic and/or groove binding mode. This is also confirmed by the small change in thermal denaturation temperature of DNA (ΔTm) after binding of both complexes. Redox couple of the copper complexes was assigned as quasi-reversible from their cyclic voltammetric data. On testing the antitumor activity of the two complexes on some cancer cell lines and on normal human melanocytes cell line, the cytotoxicity of complex 2 was found to be much higher than that of complex 1. Complex 1 could be considered a specific target for DNA cancer cells due to its slight effect on human normal cells. The two complexes were tested for their antimicrobial activity.Figure optionsDownload as PowerPoint slideHighlights
► Two new complexes [Cu(bpy)(Gly)Cl]·2H2O and [Cu(dpa)(Gly)Cl]·2H2O were synthesized and characterized.
► The binding of these complexes with CT-DNA was studied by UV–vis spectroscopy, electrochemical technique and gel electrophoresis revealing strong binding ability.
► In addition, the two complexes exhibited antitumor and antimicrobial activities.