Coordination behavior of cocaine toward d-block metal ions: Synthesis, spectral analysis, density functional theory (DFT) studies, and chemotherapeutic activity

Abstract

The exploration of novel bioactive metallopharmaceuticals for the treatment of diseases such as microbial infections or cancer, with a focus on reducing side effects and drug resistance, is a prominent area of investigation within the field of medicinal inorganic chemistry. In this study, a new series of binary cocaine (COC) metal complexes with some d-block metal ions were synthesized and structurally characterized. Except for Co(II) and Ni(II) complexes, which had a 1:2 metal-to-ligand stoichiometric ratio, all of the produced complexes were found to have a 1:1 metal-to-ligand stoichiometry. The Fe(III) and Cd(II) complexes were further analysed through theoretical density functional theory (DFT) calculations to investigate their geometry optimization and electronic transitions. The anticancer activity of the complexes was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The Co(II) complex demonstrated potential cytotoxic effects against the hepatoblastoma (HepG-2) and Michigan Cancer Foundation-7 (MCF-7) cell lines, with IC50 values of 9.78 µM and 10.36 µM, respectively. Moreover, it exhibited good safety on human normal cells. Additional research was conducted on the Co(II) complex to explore its impact on cellular concentrations of the human p21 and p27 tumor suppressor nuclear proteins, as well as its effects on apoptosis, metastasis, and oxidative stress in the MCF-7 cancer cell line. The findings revealed that the Co(II) complex showed promising antiproliferative and antimetastatic properties while maintaining a high level of safety and tolerability on normal cells. The antimicrobial activity of the complexes was also investigated, with both the Cr(III) and Ni(II) complexes exhibiting antibacterial activity comparable to the standard gentamicin against Escherichia coli. Additionally, the Fe(III) and Cd(II) complexes demonstrated inhibitory effects on Salmonella typhimurium equivalent to that of gentamicin.