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

Abstract

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.