Synthesis, X-ray, molecular electronic property investigation, and molecular docking analysis of two imino Schiff...

In this study, we report the first synthesis and comprehensive characterization of two positional isomers of iodo-substituted imino Schiff bases, Im1 was synthesized using 2-iodoaniline, whereas Im2 was obtained from 4-iodoaniline. Compound Im1 represents a new derivative, while Im2 is fully characterized crystallographically for the first time. The structures were confirmed by FT-IR, UV-Vis, ¹H and ¹³C NMR spectroscopy, and single-crystal X-ray diffraction, which revealed that Im2 crystallizes in the monoclinic space group P2₁/c. Hirshfeld surface and fingerprint analyses provided insights into key intermolecular interactions governing crystal stability. Among the two compounds, Im2 exhibited the highest antibacterial activity, forming an 11.00 ± 0.00 mm inhibition zone against Klebsiella pneumonia, whereas Im1 demonstrated the strongest inhibition (11.67 ± 0.47 mm) against Escherichia coli. DFT calculations (B3LYP/LANL2DZ) and molecular docking with the FimH receptor (PDB ID: 8BVD) revealed electronic and structural features influencing binding affinity (-3.737 to -4.266 kcal/mol). ADME-T predictions indicated favorable drug-likeness, suggesting these Schiff bases as promising scaffolds for further optimization toward antibacterial development. This novel comparative analysis of the two imines revealed the pronounced influence of ortho and para-iodine substitution on biological activity and inhibitory potency, demonstrating a clear structure-activity relationship (SAR) governing their antibacterial performance. In the future, Im1 and Im2, when combined with other bioactive scaffolds, may serve as promising candidates for enhanced therapeutic and biological applications.