Integrated spectroscopic and computational data on 2-phenylacetophenone: structural, electronic, and binding insights into acetylcholinesterase for Alzheimer’s disease therapy

The molecular and pharmacological potential of 2-phenylacetophenone was examined using DFT-based B3LYP/6-311++G(d,p) computations along with integrated spectroscopic and molecular docking analyses. The compound’s optimized geometry and vibrational modes were validated using FT–IR and FT–Raman spectra, while UV–Vis transitions were calculated via TD–DFT and matched with experimental data. The chemical environments of 1H and 1³C nuclei were assessed using GIAO-based NMR calculations. Mulliken Population Analysis (MPA) and Natural Population Analysis (NPA) were performed to evaluate the charge distribution within the molecule, revealing significant electron-rich and electron-deficient regions. Frontier molecular orbital (FMO) analysis, electrostatic potential (ESP) mapping, and Hirshfeld surface analysis revealed electronic characteristics and reactive regions. Topological parameters (ELF, LOL, RDG) confirmed electron delocalization and non-covalent interactions. NBO analysis indicated strong donor–acceptor interactions, with a maximum stabilization energy of 22.14 kJ/mol. Global reactivity descriptors suggested promising bioactivity. Drug-likeness evaluation satisfied Lipinski’s rule, and molecular docking showed effective binding to neurodegenerative targets (AChE: 2H9Y and MAO-B: 4F1T), supporting its therapeutic potential against Alzheimer’s and Parkinson’s diseases.