Synthesis of a Pyridone-Based Phthalimide Fleximer and Its Characterization and Supramolecular Property Evaluation

In this study, a
novel pyridone-based phthalimide fleximer, that
is, ethyl 5-cyano-6-(3-(1,3-dioxoisoindolin-2-yl)­propoxy)-4-(3-methoxyphenyl)-2-methylnicotinate,
was synthesized, and its structure was established by the single-crystal
X-ray diffraction method. The supramolecular self-assembly of the
titled compound through noncovalent interactions was then investigated
thoroughly. The titled compound crystallized with two symmetry-independent
molecules (A and B, Z′
= 2). In agreement with experimental observations, our density functional
theory calculations also showed that the titled compound has a flexible
motif and can occur in various conformations, including molecules A and B. The investigation of the supramolecular
framework revealed that the molecules are notably bound by the nonclassical
C–H···O and C–H···N hydrogen
bonds and C–H···π interactions. Hirshfeld
surface analysis was carried out to quantify the various intermolecular
interactions. The dual anti-inflammatory activity of the tilted compound
was also explored by molecular docking in the active sites of 5-LOX
and COX-2 receptors, which revealed good binding affinities of −9.0
and −8.6 kcal/mol, respectively.