Experimental and Computational Investigation of Cu(II) and Zn(II) complexes: DFT, Docking, and Anti-Lung Cancer Studies.

Aims: This study aimed to synthesize and characterize a Schiff base ligand, (Z)-2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamide (1), and its copper(II) (2) and zinc(II) (3) complexes, as well as evaluate their binding interactions with the epidermal growth factor receptor (EGFR) and anticancer activity against the human lung cancer A549 cell line.

Materials & methods: The Schiff base ligand was synthesized by refluxing isatin and thiosemicarbazide for 3 hours. Complexes 2 and 3 were formed and characterized using elemental analysis, molar conductivity, IR, NMR, and UV-Visible spectroscopy. The geometry of complex 3 was determined via X-ray diffraction. Theoretical calculations were conducted using DFT with the hybrid GEN B3LYP method. Molecular docking was performed to assess binding energies with EGFR, and anticancer activity was evaluated against the A549 cell line.

Results: Characterization confirmed successful synthesis of the compounds. Zinc complexation led to notable spectral shifts, and X-ray diffraction revealed complex 3 adopted a distorted tetrahedral geometry. DFT analysis highlighted complex 2 with the lowest energy gap (0.331 eV). Docking results showed strong EGFR binding energies (-5.70, -5.54, and -7.30 kcal/mol). Complex 2 demonstrated the highest anticancer efficacy with a cell viability of 1.35% after 48 h.

Conclusions: Complex 2 exhibits significant anticancer potential and warrants further investigation as a therapeutic agent.