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

• Published in: Journal of inorganic biochemistry 2022-12, Vol.237, p.112015-112015, Article 112015
• Main Authors: Cavalcante, Cássia De Q.O., Garcia, Edgardo, da Mota, Tales H.A., de Oliveira, Diêgo M., Gatto, Claudia C.
• Format: Article
• Language: English
• Subjects: Anticancer activity; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Copper - chemistry; Crystal structure; Crystallography, X-Ray; Cu(II) complex; DFT; Dithiocarbazate; Halogens; Hirshfeld surface; Humans; Hydrogen Bonding; Ligands; Metals - chemistry
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2022.112015

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. Four new Cu(II) complexes with dithiocarbazates ligands were synthesized and analyzed and their biological activities were evaluated against the human glioma U251 cells. [Display omitted] •Four new Cu(II) complexes with dithiocarbazate ligands were synthesized.•The compounds were studied by X-ray crystallography and density functional theory.•The spectroscopic analyses and Hirshfeld surface were investigated.•The biological activity was evaluated in vitro against human glioma U251 cells.•The antitumor activity of the dithiocarbazate increased with the complexation.