A novel cadmium(II) complex of bipyridine derivative: synthesis, X-ray crystal structure, DNA-binding and antibacterial activities.

A mononuclear cadmium(II) complex of formula [Cd(5,5'-dmbipy)2(OAc)2]·2H2O (5,5'-dmbipy = 5,5'-dimethyl-2,2'-bipyridine and OAc = acetato ligand) has been synthesized and characterized by FT-IR, UV-Vis, 1H-NMR, elemental analysis and single-crystal X-ray structure analysis. The molecular structure of the complex shows a distorted tetragonal antiprism CdN4O4 coordination geometry around the cadmium atom, resulting in coordination by four nitrogen atoms from two 5,5'-dmbipy ligands and four oxygen atoms from two acetate anions. The interaction of this complex to FS-DNA (fish sperm DNA) has also been studied by electronic absorption, fluorescence and gel electrophoresis techniques. Binding constant (Kb), Stern-Volmer constant (Ksv), number of binding sites (n) and bimolecular quenching rate constant (kq) have been calculated from these spectroscopic data. These results have revealed that the metal complex can bind effectively to FS-DNA via groove binding. The calculated thermodynamic parameters (ΔH°, ΔS° and ΔG°) show that hydrogen bonding and van der Waals forces have an important function in the Cd(II) complex-DNA interaction. The antibacterial effects of the synthesized cadmium complex have also been examined in vitro against standard bacterial strains: one Gram-positive (Staphylococcus aureus, ATCC 25923) and one Gram-negative (Escherichia coli, ATCC 25922) bacteria, using disk diffusion and macro-dilution broth methods. The obtained results show that the Cd(II) complex exhibits a marked antibacterial activity which is significantly better than those observed for its free ligand and metal salt for both Gram-positive and Gram-negative bacteria. However, this metal complex is a more potent antibacterial agent against the Gram-positive than that of the Gram-negative bacteria.Communicated by Ramaswamy H. Sarma.

A novel binuclear hydrazone-based Cd(II) complex is a strong pro-apoptotic inducer with significant activity against 2D and 3D pancreatic cancer stem cells.

A novel binuclear Cd complex (1) with hydrazone-based ligand was prepared and characterized by spectroscopy and single crystal X-ray diffraction techniques. Complex 1 reveals a strong pro-apoptotic activity in both human, mammary adenocarcinoma cells (MCF-7) and pancreatic AsPC-1 cancer stem cells (CSCs). While apoptosis undergoes mostly caspase-independent, 1 stimulates the activation of intrinsic pathway with noteworthy down regulation of caspase-8 activity in respect to non-treated controls. Distribution of cells over mitotic division indicates that 1 caused DNA damage in both cell lines, which is confirmed in DNA interaction studies. Compared to 1, cisplatin (CDDP) does not achieve cell death in 2D cultured AsPC-1 cells, while induces different pattern of cell cycle changes and caspase activation in 2D cultured MCF-7 cells, implying that these two compounds do not share similar mechanism of action. Additionally, 1 acts as a powerful inducer of mitochondrial superoxide production with dissipated trans-membrane potential in the majority of the treated cells already after 6 h of incubation. On 3D tumors, 1 displays a superior activity against CSC model, and at 100 µM induces disintegration of spheroids within 2 days of incubation. Fluorescence spectroscopy, along with molecular docking show that compound 1 binds to the minor groove of DNA. Compound 1 binds to the human serum albumin (HSA) showing that the HSA can effectively transport and store 1 in the human body. Thus, our current study strongly supports further investigations on antitumor activity of 1 as a drug candidate for the treatment of highly resistant pancreatic cancer.