DFT calculations and docking simulation study of (E)-4-fluoro-N'-(diphenyl-dimethylpiperidinylidene) benzhydrazide

• The compound (E)-4-fluoro-Nˊ-(3,3-dimethyl-2,6-diphenylpiperidine-4-ylidene)benzohydrazide (1z) have been synthesized. • Single crystal X-ray diffraction analysis reveals the stereochemistry of the C=N bond and chair conformation of the piperidin-4-one ring. • DFT calculations were performed to computationally evaluate its chemical reactivity. • Molecular docking studies of the compound (1z) were conducted with 2NSD protein. A novel and synthetically valuable piperidine-4-one derivative, (E)-4-fluoro-N′-(diphenyl-dimethylpiperidinylidene) benzhydrazide (1z), was synthesized via a straightforward and efficient procedure. The chemical entity was thoroughly characterized using FT-IR and NMR spectroscopy, along with single-crystal X-ray diffraction (SCXRD). Density functional theory ( DFT/B3LYP/6-31G (d,p)) calculations were employed to investigate the optimized molecular geometry, Mulliken charge distribution, molecular electrostatic potential (MEP), and frontier molecular orbital (SOMO–LUMO) energies, which showed good agreement with the experimental findings. Structural analysis confirmed the chair conformation of the piperidine-4-one core and established the orientation of the hydrazone moiety. Intermolecular interactions were further examined through Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing the dominant contributions of hydrogen bonding and van der Waals interactions. In silico molecular docking studies against the Mycobacterium tuberculosis InhA enzyme demonstrated favorable binding interactions, with Glide scores ranging from −5.63 to −6.47 kcal/mol, suggesting the potential of the synthesized compound as a promising antitubercular lead for further biological evaluation.