Spectroscopic Characterization, DFT Analysis, Molecular Docking and ADMET Evaluation 1-(4-Methylpiperazin-1-ylmethyl)-3-p-chlorobenzyl-4-(4-hydroxybenzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one

Abstract

In this study, 1-(4-metilpiperazin-1-il-metil)-3-p-klorobenzil-4-(4-hidroksibenzilidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-on (PCHT), a Mannich base derived from 1,2,4-triazole, was synthesized and its structural properties were investigated using both experimental and theoretical methods. The structure of the compound was experimentally characterized by FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopic techniques. Geometric optimization of the molecule was performed using Density Functional Theory (DFT) with B3LYP and B3PW91 functionals and the 6-31G(d,p) basis set. Theoretical vibrational frequencies and FT-IR, ¹H-NMR and ¹³C-NMR NMR isotropic chemical shift values were calculated via the GIAO method and compared with the experimental data. Furthermore, electronic parameters such as Mulliken atomic charges, HOMO–LUMO energy levels, energy gap (ΔEg), dipole moment, ionization potential, electron affinity, chemical hardness, chemical softness, and electronegativity were calculated. Molecular electrostatic potential (MEP) surface maps were generated to identify the reactive sites of the molecule, and nucleophilic and electrophilic regions were analyzed. In addition, Natural Bond Orbital (NBO) analysis was conducted to examine the electronic structure in more detail, evaluating donor–acceptor interactions and hyperconjugation effects. To investigate the biological activity potential, molecular docking studies were performed, and the binding energies and molecular interactions between the ligand and the target protein were examined. Lastly, the compound's pharmacokinetic properties were assessed using ADMET analysis, which highlighted the molecule's possible drug-like qualities by looking at factors like Lipinski's "rule of five," bioavailability, water solubility, gastrointestinal absorption, and blood-brain barrier permeability. 

Keywords

• 1,2,4-Triaole derivative
• Mannich base
• DFT calculations
• ADMET
• Molecular docking

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