Integrated Experimental and Computational Investigation of Fluorinated Benzoylthiourea Derivatives: Structural Characterization, Hirshfeld Surface Analysis, Antioxidant Activity, and MAO–B Inhibitory Potential for Parkinson’s Disease

Abstract Three novel fluorinated benzoylthiourea derivatives, namely FBTU1–FBTU3, were successfully synthesized in 79–86% yields and fully characterized using spectroscopic techniques including FT–IR, 1H, 13C and 19F NMR, UV–Vis spectroscopy, elemental analysis, and single–crystal X–ray diffraction (SCXRD). All three compounds crystallize in the monoclinic system (P21/c for FBTU1 and FBTU3; P21/n for FBTU2) with Z = 4. The crystallographic analysis revealed well–defined molecular geometries stabilized by intramolecular and intermolecular interactions. Hirshfeld surface and energy framework analyses indicate that the crystal packing is primarily governed by centrosymmetric N–H···S hydrogen bonds (D···A = 3.432–3.483 Å), together with supporting π···π stacking and C–H···π interactions. The calculated total lattice energies were −211.9, −220.6, and −216.7 kJ/mol for FBTU1–FBTU3, respectively. The density functional theory (DFT) calculations were performed, and the results showed good agreement with the experimental structural parameters. Frontier molecular orbital analysis indicated significant electronic delocalization across the benzoylthiourea framework, influenced by the position of the fluorine substituent. The compounds showed moderate DPPH radical-scavenging activity. In addition, ADMET prediction studies indicated favorable pharmacokinetic profiles, including acceptable absorption characteristics and overall drug–likeness behavior, suggesting their potential suitability for further biological evaluation. Molecular docking studies against monoamine oxidase–B (MAO–B, PDB ID: 1GOS) identified FBTU1 as the compound with the most favorable calculated binding energy (ΔG = −8.12 kcal/mol, Ki = 1.13 μM).