Synthesis, characterization, and in silico evaluation of novel Schiff base (E)-N'-(2-hydroxybenzylidene)-2-((4-methylbenzyl)oxy)benzohydrazide: DFT, NLO properties, molecular dynamic simulation, pharmacokinetic analysis, and molecular docking studies for the development of an antitubercular drug

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health concern, necessitating the development of new and effective therapeutic agents. In this study, a novel Schiff base, (E)-N'-(2-hydroxybenzylidene)-2-((4-methylbenzyl)oxy)benzohydrazide (HL), was synthesized via condensation reaction and characterized using FTIR, UV–Vis, ¹H NMR, mass spectrometry, and single-crystal X-ray diffraction, supported by DFT calculations. Hirshfeld surface analysis revealed dominant H⋯H interactions (49.2%) along with significant π–π stacking contributions, indicating a stable crystal packing environment. The HOMO–LUMO energy gap (4.092 eV) suggests appreciable chemical reactivity, while the Gibbs free energy (ΔG = −1185.555 kcal/mol) indicates favorable binding potential with biological targets. MEP and NPA analyses identified carbonyl and hydroxyl oxygen atoms as key electrophilic sites. NCI-RDG analysis confirmed stabilization through hydrogen bonding and van der Waals interactions. The NLO analysis of HL shows a significantly enhanced first hyperpolarizability (βₜₒₜ = 137 × 10⁻³¹ esu), about 17.56 times higher than that of urea and comparable to para-nitroaniline, indicating strong second-order NLO activity. Increased polarizability, dipole moment, and anisotropy across solvents further confirm efficient intramolecular charge transfer and highlight its potential for advanced photonic applications. PASS prediction suggested antitubercular activity, supported by molecular docking studies showing stronger binding affinity toward InhA (PDB IDs: 2IDZ and 4TRN) compared to isoniazid. Molecular dynamics simulations confirmed stable protein–ligand interactions, while ADMET analysis indicated favorable pharmacokinetic properties. Overall, HL demonstrates promising dual functionality as a potential antitubercular agent and nonlinear optical material for future biomedical and optoelectronic applications.