Electronic structure and spectroscopic behavior of methisazone using DFT TDDFT and NBO analysis

Abstract

A detailed quantum-chemical investigation of methisazone (MSZ) has been performed using Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT) to elucidate its structural, electronic, and spectroscopic properties. The molecular geometry was optimized at the B3LYP/6-31G level in the gas phase, and the absence of imaginary frequencies confirmed the stability of the optimized structure. The calculated geometrical parameters indicate a conjugated molecular framework with significant π-electron delocalization, which promotes efficient electronic communication between the carbonyl, hydrazine, thiocarboxamide, and aromatic fragments. Frontier molecular orbital analysis reveals a moderate HOMO–LUMO energy gap, demonstrating a balanced combination of molecular stability and intramolecular charge-transfer capability. The molecular electrostatic potential surface identifies electron-rich regions primarily around the oxygen and sulfur atoms, revealing the non-uniform electronic polarization responsible for the predicted reactivity of the molecule. Natural Bond Orbital (NBO) analysis further confirms that donor–acceptor interactions within the conjugated framework are responsible for the observed electron delocalization. The TD-DFT-simulated UV–Visible spectrum shows dominant π → π* and n → π* transitions, which originate from the calculated frontier orbital distribution and support the proposed charge-transfer mechanism. Vibrational frequency calculations provide infrared and Raman spectra, while Raman depolarization analysis highlights pronounced polarizability anisotropy. Comparison of the calculated IR vibrational frequencies with the available experimental spectrum demonstrates good agreement for the characteristic functional-group vibrations, providing additional validation of the optimized molecular structure. The isotropic magnetic shielding distribution, obtained using the GIAO method, together with the calculated 13 C NMR shielding pattern, provides independent spectroscopic evidence for the predicted electronic environment within the conjugated framework. Overall, the combined DFT and TD-DFT analyses establish a consistent relationship between the optimized electronic structure, intramolecular electron delocalization, and the spectroscopic behaviour of methisazone, providing a reliable theoretical framework for interpreting its electronic and spectroscopic properties.