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

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.