Molecular structure, DFT computations, and docking studies of an imidazo[1,2-a]pyridine derivative containing 1,2,3-triazole and 4-bromophenyl moieties.

Herein, we report theoretical investigations of the imidazo[1,2-a]pyridine derivative IPD (systematic name 2-(1-(4-bromophenyl)-5-methyl-1H-1,2,3-triazol-4-yl)imidazo[1,2-a]pyridine), and compare the computational outcome with experimental data available from X-ray crystallography studies and spectroscopic analysis. Density functional theory (DFT) was employed as a computational chemistry approach to optimize the geometry and investigate the electronic properties, molecular descriptors, and frontier molecular orbital features of the investigated compound. The DFT-optimized molecular geometry showed good agreement with the experimental structure determined by single-crystal X-ray diffraction (RMSD = 0.2074 Å). The electrostatic potential map of the IPD molecule revealed potential sites for electrophilic attack at the nitrogen in the imidazole ring and at the nitrogen atoms within the 1,2,3-triazole moiety. Additional calculations, however, indicated a higher proton affinity (246.44 kcal/mol) at the aforementioned nitrogen atom in the imidazo[1,2-a]pyridine ring system, suggesting it is the most likely site of protonation. Molecular docking simulations were conducted to investigate the inclusion of the title compound into β-cyclodextrin and to explore the interactions of the IPD molecule with the epidermal growth factor receptor tyrosine kinase (EGFR-TK) as part of an in silico anticancer study. The electronic structures of the docked complexes were further explored using the DFT method, revealing that the intermolecular interactions between the IPD ligand and the receptors also involved a coupling of frontier molecular orbitals.