Design, synthesis, and characterization of metal-based N-heterocyclic carbene complexes for potential pharmaceutical...

A series of imidazolium-derived N-heterocyclic carbene (NHC) ligands (L1-L3), their selenium adducts (C1-C3) and corresponding silver-NHC complexes (C4-C6) were synthesized and characterized, and their electronic properties and biological potentials were investigated. The imidazolium salts were prepared by N-alkylation of 1-phenethyl-1H-imidazole and converted to selenium adducts via treatment with elemental selenium and to Ag-NHC complexes using Ag₂O. Structures were characterized by FT-IR, ¹H/¹³C NMR and computational methods. DFT calculations provided frontier orbital energies and global descriptors, showing increased HOMO-LUMO gaps on metal coordination and trends consistent with enhanced stability of Ag complexes. Molecular docking of the selenium adducts against human AKR1C2 (PDB: 4XO6) indicated modest binding (ΔG ≈ -5.3 kcal·mol^-1) compared with 5-fluorouracil (-6.8 kcal·mol^-1). Biological screening against MCF-7 cancer cells found higher antiproliferative activity for Ag complexes (IC₅₀ ≈ 13.7 μg·mL^-1) than for selenium adducts or salts. The Ag-NHCs also exhibited potent antibacterial activity (MICs ≈ 5-6 μM against E. coli and S. aureus), whereas selenium adduct C2 showed the strongest antioxidant (DPPH) activity (IC₅₀ ≈ 4.9-5.5 μg·mL^-1).