Pyrazolo[3,4-b](dihydro)quinoline-5-ones: Single-crystal exploration, Hirshfeld surface analysis, and DFT calculation

Abstract

Structural studies of five pyrazolo[3,4-b]-4,9-dihydroquinoline-5-one and pyrazolo[3,4-b]quinoline-5-one derivatives were performed by analyzing their single crystal structures. X-ray crystallographic analysis of two pyrazolo[3,4-b]-4,9-dihydroquinoline-5-ones successfully addressed the challenges raised regarding the occurrence of possible tautomeric forms for structures without substitution on the N1-atom of the pyrazole ring. Furthermore, DFT computational studies confirmed and strengthened these results by comparison of the total energy content of both tautomeric forms. Results of both studies revealed the definitive presence of more stable N2-H pyrazole ring in these structures. Single crystal structure studies and Hirshfeld surfaces analysis clearly demonstrated the occurrence of the intermolecular interactions (hydrogen bonding and π-π stacking), which are essential for investigation of the crystal stability and cohesion. DFT computational studies on the optimized structures of the target molecules by comparing characteristic bond lengths, NBO atomic charges, and molecular electrostatic potential (MEP) mapping indicated the change in the electron density and its effect on establishment of intermolecular interactions. The energies of frontier molecular orbitals (FMOs) also lead to understanding the global reactivity descriptors (GRDs) in each molecule. © 2025