Synthesis, X-Ray, Spectroscopic Characterization, Hirshfeld Surface Analysis, Molecular Docking, and DFT Calculations of a New Series of 3-Hydrazono and 3-Phenylhydrazono Isatin Derivatives

Abstract

Two novel N-alkylated isatin derivatives (2–3) were synthesized under phase-transfer catalysis conditions. Their condensation with hydrazine hydrate and phenylhydrazine in refluxing ethanol as solvent generates two series of isatin derivatives (3-hydrazono and 3-phenylhydrazono) (4–7). The structures synthesized are elucidated using UV/Vis, FTIR, ¹³C-NMR, ¹H-NMR, and single crystal X-ray diffraction techniques of 2, 3, and 5. The experimental data were compared with the predicted ones obtained at the B3LYP/6-31G(d,p) level of theory. Relatively, good agreements were found between the calculated and experimental results. The intermolecular contacts in 2, 3, and 5 were investigated through the Hirshfeld surface analysis. The expected inhibitory efficiency of 2, 3, and 5 against cyclooxygenase-2 (COX-2) are investigated by their molecular docking into the binding site of COX-2, which revealed that 2 might have strong inhibition efficacy against COX-2 compared to 3.

Keywords:

• Isatin
• X-ray
• Hirshfeld surface
• molecular docking
• DFT

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research and JTM thanks Tulane University for support of the Tulane Crystallography Laboratory.

Disclosure statement

No potential conflict of interest was reported by the authors.