Integrated Experimental and Computational Investigation of a Pyridine Derivative Compound: X-ray, DFT, and Docking Studies

Abstract

In this study, a pyridinone-based compound was structurally characterized and computationally analyzed using integrated experimental and theoretical methods. The single-crystal X-ray diffraction (SC-XRD) results confirmed that the molecule adopts a non-planar conformation stabilized by strong N–H···O hydrogen bonds and weak π–π interactions. Density Functional Theory (DFT) calculations reveal a wide HOMO–LUMO energy gap (7.12 eV), indicative of high molecular stability and polar nature. Molecular docking simulations were carried out against Topoisomerase II (PDB ID: 3QX3) to investigate the binding affinity and interaction profile. The compound exhibited a moderate binding energy of –5.23 kcal/mol, dominated by van der Waals, hydrogen bonding, and π–π stacking interactions, suggesting a stable binding orientation within the enzyme’s active site. The combined results highlight the structural stability, electronic properties, and biointeraction potential of the synthesized ligand, supporting its relevance for future structure–activity relationship and anticancer studies.