Structural Design, Anticancer Evaluation, and Molecular Docking of Newly Synthesized Ni(II) Complexes with ONS-Donor Dithiocarbazate Ligands.

The current article reports the investigation of three new Ni(II) complexes with ONS-donor dithiocarbazate ligands: [Ni(L1)PPh3] (1), [Ni(L2)PPh3] (2), and [Ni(L2)Py] (3). Single-crystal X-ray analyses revealed mononuclear complexes with a distorted square planar geometry and the metal centers coordinated with a doubly deprotonated dithiocarbazate ligand and coligand pyridine or triphenylphosphine. The non-covalent interactions were investigated by the Hirshfeld surface and the results revealed that the strongest interactions were π⋅⋅⋅π stacking interactions and non-classical hydrogen bonds C-H···H and C-H···N. Physicochemical and spectroscopic methods indicate the same structures in the solid state and solution. The toxicity effects of the free ligands and Ni(II) complexes were tested on the human breast cancer cell line MCF-7 and non-malignant breast epithelial cell line MCF-10A. The half-maximal inhibitory concentration (IC50) values, indicating that the compounds were potent in inhibiting cell growth, were obtained for both cell lines at three distinct time points. While inhibitory effects were evident in both malignant and non-malignant cells, all three complexes demonstrated lower IC50 values for malignant breast cell lines than their non-malignant counterparts, suggesting a stronger impact on cancerous cell lines. Furthermore, molecular docking studies were performed showing the complex (2) as a promising candidate for further therapeutic exploration.

Dithiocarbazate ligands and their Ni(II) complexes with potential biological activity: Structural, antitumor and molecular docking study.

In the search for new metal complexes with antitumor potential, two dithiocarbazate ligands derived from 1,1,1-trifluoro-2,4-pentanedione (H2L1) and (H2L2) and four Ni(II) complexes, [Ni(L1)PPh3] (1), [Ni(L1)Py] (2), [Ni(L2)PPh3] (3), and [Ni(L2)Py] (4), were successfully synthesized and investigated by physical-chemistry and spectroscopic methods. The crystal structure of the H2L1 and the Ni(II) complexes has been elucidated by single-crystal X-ray diffraction. The obtained structure from H2L1 confirms the cyclization reaction and formation of the pyrazoline derivative. The results showed square planar geometry to the metal centers, in which dithiocarbazates coordinated by the ONS donor system and a triphenylphosphine or pyridine molecule complete the coordination sphere. Hirshfeld surface analysis by d norm function was investigated and showed π-π stacking interactions upon the molecular packing of H2L1 and non-classical hydrogen bonds for all compounds. Fingerprint plots showed the main interactions attributed to H⋅H C⋅H, O⋅H, Br⋅H, and F⋅H, with contacts contributing between 1.9% and 38.2%. The mass spectrometry data indicated the presence of molecular ions [M + H]+ and characteristic fragmentations of the compounds, which indicated the same behavior of the compounds in solution and solid state. Molecular docking simulations were studied to evaluate the properties and interactions of the free dithiocarbazates and their Ni(II) complexes with selected proteins and DNA. These results were supported by in vitro cytotoxicity assays against four cancer cell lines, showing that the synthesized metal complexes display promising biological activity.

Comparative investigation of Cu(II) complexes with dithiocarbazate: Structural design, theoretical calculation, and in vitro antitumor activity.

The present work reports the synthesis and investigation by semi-empirical Density Functional Theory (DFT), physical chemistry, and spectroscopic methods of two dithiocarbazates, 2-acetylpyridine-S-p-bromobenzyl-dithiocarbazate (HL1) and 2-acetylpyridine-S-p-nitrobenzyl-dithiocarbazate (HL2) and their Cu(II) complexes, [Cu(L1)Cl] (1), [Cu(L1)Br] (2), [Cu(L2)Cl] (3) and [Cu(L2)Br] (4). Single crystal X-ray analyzes showed distorted square planar geometry to the metal centers, which tridentate ligands coordinated by the NNS system and an additional halogen (Cl- or Br-) to complete the coordination sphere. Mass spectrometry data indicated the presence of [Cu(L1)(DMF)]+ and [Cu(L2)(DMF)]+, due to the exchanging of chloride/bromide ions and characteristic fragmentations of the compounds. The DFT composite method B97-3c was employed to optimize the geometries of ligands and complexes and IR spectra were calculated revealing good agreement with experimental data. Hydrogen bonds and π⋅⋅⋅π stacking interactions upon the molecular packing were investigated by Hirshfeld surface and fingerprint plots with the main interactions attributed to the H⋅⋅⋅H contacts. The biological activity of the dithiocarbazates and their Cu(II) complexes were evaluated in vitro against the human glioma U251 cells. Results revealed that the free dithiocarbazates present great in vitro antitumor activity that is increased after the complexation with copper. The measurement of cytotoxicity of the compounds showed biological activity in a low range of concentration, which indicates high efficiency as potential drugs.