Crystallographic, Hirshfeld Surface, and DFT Analyses of a Fluorine-Bromine Schiff Base: Insights into Structural Features and MAO-A Binding Potential

Abstract

In this study, a fluorine-bromine-substituted Schiff base compound, (E)-2-(((2-bromophenyl)imino)methyl)-6fluorophenol (BFSB), was synthesized and structurally investigated using both experimental and theoretical approaches. The crystal structure, determined by single-crystal X-ray diffraction, revealed an orthorhombic system featuring a stabilizing intramolecular O-H & sdot;& sdot;& sdot;N hydrogen bond, complemented by halogen and dispersion interactions, as demonstrated through Hirshfeld surface and energy framework analyses. Computational studies employing Density Functional Theory (DFT) provided a reliable match with experimental geometry and offered insight into the molecule's electronic structure and reactivity. Additionally, ADMET evaluations predicted favorable drug likeness and ease of synthesis despite some pharmacokinetic limitations. Molecular docking simulations were conducted against a range of protein targets to explore potential biological interactions, among which MAO-A showed the strongest affinity. Overall, the results underscore the relevance of combining crystallographic data with computational modeling to characterize multifunctional small molecules.