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

ACS Omega. 2022 Jul 7;7(28):24485-24497. doi: 10.1021/acsomega.2c02095. eCollection 2022 Jul 19.

Abstract

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.