Crystal structure and supramolecular features of N-(thiazole-2-yl) benzamide benzoate: A combined experimental and theoretical study

A novel thiazole-based co-crystal, N-(thiazol-2-yl) benzamide benzoate[TBB], was synthesized and characterized using single-crystal X-ray diffraction. Crystal structure analysis revealed that the compound crystallizes in the monoclinic crystal system with space group P2 1 /n and exhibits a nearly planar molecular geometry with a dihedral angle of 9.66°. The crystal packing is stabilized through N–H···O, O–H···N, and C–H···O hydrogen bonds together with π···π stacking and dispersive intermolecular interactions. Hirshfeld surface analysis identified H···H contacts as the dominant contribution to crystal packing (38%), followed by H···C/C···H (11.3%) and H···O/O···H (5.9%) interactions, indicating the significant role of van der Waals forces in crystal stabilization. Energy framework calculations showed that dispersion energy (−156.43 kJ mol⁻¹) is the major stabilizing component, resulting in a total interaction energy of −146 kJ mol⁻¹ . DFT calculations performed at the B3LYP/6–311 + + G (d, p) level reproduced the experimental geometry and yielded a HOMO–LUMO energy gap of 4.624 eV, suggesting good kinetic stability and moderate chemical reactivity. QTAIM and NCI analyses confirmed the coexistence of hydrogen bonding, π···π stacking, van der Waals interactions, and steric effects governing the supramolecular assembly. NBO analysis revealed significant donor–acceptor charge transfer interactions with stabilization energies up to 57.62 kcal mol⁻¹ , demonstrating efficient electron delocalization within the molecular framework. Molecular docking studies against the aspirin-acetylated cyclooxygenase-2 protein (PDB ID: 5F19) exhibited a favorable binding affinity of −7.6 kcal mol⁻¹ , indicating promising molecular recognition behavior. The combined experimental and theoretical results highlight the importance of intermolecular interactions in controlling crystal stability and electronic properties, suggesting potential applications in pharmaceutical co-crystal engineering, supramolecular chemistry, molecular recognition, and functional molecular materials.