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

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.

Non‐Covalent Interactions in the Self‐Assembly of Dihydropyridone Supramolecules and In Vitro Anti‐Cancer Assessment in Human Lung Adenocarcinoma Cell Line (A549)

“…The 4H-pyrans (10 mmol) and excess formic acid (20 mL) refluxed at 115 °C for 3-4 h. After the reaction, the formic acid was reduced under a rotary evaporator, and the residue obtained was recrystallized in methanol to obtain pure products (1)(2)(3)(4). This alternative method is more straightforward, convenient, and favorable than method A.…”

“…In structural chemistry and crystallography, non-covalent interactions which are weaker than covalent bonds or an electrostatic interaction (i. e., ionic bond) play a significant role in holding up the molecules to form a crystal. [1][2][3] Besides their importance in stabilizing the crystallographic structures, noncovalent interactions also govern the molecular recognition properties of the molecules within the biological systems. [4,5] These weak interactions are important in the formation of inclusion complexes, and also provides self-assembly features.…”