A Novel Bidentate Schiff Base and Its Cu(II)/Cd(II) Complexes: Synthesis, Bioactivity, and Computational Modeling

Objective: This study aimed to synthesize a novel bidentate Schiff base ligand and its copper (II) and cadmium (II) complexes and comprehensively evaluate their structural properties and biological potential. Methodology: The ligand (HPN) was synthesized by condensing (E)-2-(p-tolylimino)propanal with (4-nitrophenyl)hydrazine. Its metal complexes were characterized through elemental analysis, FT-IR, UV-Vis, and mass spectrometry, molar conductivity, and thermogravimetric analysis. Density Functional Theory (DFT) calculations investigated their electronic structures and properties. The biological activities were assessed via antimicrobial assays against bacterial and fungal pathogens and cytotoxicity screening against MCF-7 breast cancer cells. Molecular docking simulations were performed to predict interactions with key microbial and cancer-related protein targets. Main Findings: The analytical and spectroscopic data confirmed the formation of stable, distorted octahedral complexes. Theoretical calculations indicated that coordination to the metal center enhanced the system's stability and modulated its reactivity. Biological evaluation demonstrated that the Cd (II) complex possessed superior activity, exhibiting significant antimicrobial effects against all tested strains and potent anticancer activity with an IC50 value of 14 μg/mL. Molecular docking revealed that the Cd(II) complex had a markedly stronger binding affinity than the free ligand, demonstrating superior interactions with key therapeutic targets. This was most notably observed with carbonic anhydrase IX (CAIX, PDB: 6NLV) at -15.1 kcal/mol and Streptococcus mutans glucansucrase (PDB: 3AIC) at an exceptional -27.0 kcal/mol, highlighting its potential for targeted anticancer and antimicrobial applications. Conclusion: The Cd (II) complex is a highly promising compound, showing enhanced bioactivity supported by strong theoretical binding predictions. This multidisciplinary approach provides a strong foundation for developing novel metallotherapeutic agents with dual antimicrobial and anticancer applications.