4-(4-ethylphenyl)-3-(p-tolyl)-1,2,4-thiadiazol-5(4H)-one: Synthesis, X-ray, Hirshfeld surface, Fukui function, spectroscopic analysis, solvent effects of electronic properties, topological assessment, ADME and molecular docking studies

Eşme A., Kara Y. S., Tekin N.

Journal of Molecular Structure, cilt.1381, ss.147761-147777, 2026 (Hakemli Dergi)

Özet

A new thiadiazole-containing compound, 4-(4-ethylphenyl)-3-(p-tolyl)-1,2,4-thiadiazol-5(4H)-one (EPTT) was synthesized. An experimental and theoretical comprehensive spectroscopic and quantum chemical investigation has been conducted on EPTT utilizing the DFT B3LYP/6–311+G(d,p) approach. The synthesized EPTT compound underwent comprehensive characterization through spectroscopic techniques, including X-ray, UV-visible, and FT-IR spectroscopy. The C2‒H21⋅⋅ N2 and C17‒H172⋅⋅ S1 intermolecular interactions were stabilized the crystal packing. HS analysis was employed to quantify the various interactions, revealing that the H⋅⋅⋅H interaction comprised the largest share of the total HS at 41.6%. A comprehensive approach combining experimental spectroscopy with detailed DFT calculations has been employed to accurately identify the structure of the synthesized compound. The mapping of Molecular Electrostatic Potential (MEP) was conducted utilizing gas and solvent environments, including water, ethanol, chloroform, and toluene, to gain a deeper insight into the electronic charge distributions. Concurrently, topological analyses, such as the Electron Localization Function (ELF), Localized Orbital Locator (LOL), Reduced Density Gradient (RDG), were employed to offer a comprehensive characterization of noncovalent interactions. The ADME properties of the newly synthesized molecule were investigated in detail, utilizing the smile code. The synthesized compound exhibited significant binding energies (-7.48 kcal/mol, -7.09 kcal/mol) against AChE (PDB code: 1C2O, 4EY7) receptor proteins, suggesting potential drug for the treatment of Alzheimer’s disease (AD)