Design and Synthesis of 2-Pyridone Based Flexible Dimers and Their Conformational Study through X-ray Diffraction and Density Functional Theory: Perspective of Cyclooxygenase-2 Inhibition

Abstract

This paper describes the results of X-ray crystallography of 4-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (1) and its propylene bridged dimers 2 and 3. Influence of inter- and intramolecular interactions on the conformation of propylene linker have been studied through single crystal X-ray crystallography and density functional theory studies. Hirshfeld surface analysis has been employed for the study of intermolecular interactions. However, differential scanning calorimetry analysis of compounds 2 and 3, and thermogravimetric analysis of compound 3 has been performed to determine the thermal stability. Along with molecular packing and thermal analysis, molecular docking has also been performed in the catalytic site of cyclooxygenase-2 to identify the potential anti-inflammatory activity of dimer 2 and 3. The above results suggest that the supramolecular aggregate structures which are formed in solution are of lowest energy. However, cyclooxygenase-2 active site prefers the higher energy conformers.