Applied Chemical Engineering

Synthesis, Anti-Cancer Activity, and Molecular Docking of New Co(II), Ni(II) and Cu(II)Complexes with an Imidazole-Azo Ligand

Ali Abdulhussein

Department of Chemistry, Faculty of Science, University of Kufa, Najaf, Iraq

Israa N.Witwit

Department of Chemistry, Faculty of Science, University of Kufa, Najaf, Iraq

DOI: https://doi.org/10.59429/ace.v9i2.5986

Keywords: Azo-imidazole complexes; Nano-complexes; MCF-7 cytotoxicity; Molecular Docking; 5T92 Protein; Synergistic effect

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Abstract

Background: The development of metal-based therapeutics represents a significant advancement in medicinal inorganic chemistry. Here, the strategic synthesis and comprehensive characterization of a new imidazole-azo ligand, (E)-4-methyl-2-((4-phenoxyphenyl)diazinyl)imidazole (MPDI), are presented. Divalent transition metal complexes with Co(II), Ni(II), and Cu(II) were also investigated.

Methods: The compounds were characterized using 1HNMR, mass spectrometry, UV-Vis spectroscopy, and CHN analysis. Structural investigations, including molar conductivity and magnetic susceptibility measurements, confirmed a non-electrolytic octahedral geometry for all complexes. Scanning electron microscopy (SEM) revealed a significant morphological transformation from bulk microcrystalline ligands 5–20 μm to nano-sized, interconnected porous networks 100–250 nm in the  Ni(II)  complexes, attributed to the metal-template effect.

Results: Cytotoxicity was assessed against the MCF-7 breast cancer cell line using the MTT assay. Coordination resulted in a marked synergistic enhancement of bio-potency; the free ligand exhibited an IC50 of 1211.53 mu g/mL, while the Cu(II) complex demonstrated a 26.5-fold increase in efficacy with an IC50 of 45.70 \mu g/mL. Molecular docking simulations with the 5T92 protein (Estrogen Receptor Alpha) supported these results, revealing high binding affinities ranging from -15.26 to -17.24 kcal/mol. The Ni(II) complex showed the strongest theoretical affinity, stabilized by a unique π-cation interaction with ARG394.

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