Correlation between calculated electronic properties and antibacterial activity of chiral amino acid schiff base copper(II) complexes

In this study, we investigated the antibacterial activity of 27 amino acid Schiff base copper(II) complexes and explored the relationships between molecular properties and antibacterial efficacy. Using density functional theory and protein-ligand docking calculations, we analyzed descriptors such as hydrophobicity, electronic energy (EE), polarizability, and topological polar surface area, alongside experimental and calculated LogP (logarithmic octanol-water partition coefficient) values. Antibacterial activity was evaluated against five bacterial strains, including Escherichia coli and Staphylococcus aureus. Active complexes were predominantly found within a narrow LogP range (1.0 to 2.0), and tended to show moderately high polarizability and EE values. Docking scores were generally higher for active compounds, though not strictly predictive of biological outcomes. Notably, tryptophan-containing complexes demonstrated potent activity despite falling outside typical electronic thresholds, which may be explained by favorable local interactions such as π–π stacking and CH–π interactions. Quantum chemical interaction energy calculations supported the energetic favorability of these local aromatic contacts. These results highlight the importance of combining global electronic descriptors with local binding interactions in evaluating biological activity. This integrated computational–experimental approach provides a valuable framework for rational design of bioactive metal complexes with improved antibacterial properties.