Screening and inclusion of luteolin for <i>β</i> -cyclodextrin: molecular simulations and experiments

In this study, we first established a guest small molecule screening mechanism by molecular simulation and then screened lignans from ten polyphenolic compounds to identify the most suitable guest molecule for encapsulation with β-cyclodextrin (β-CD). Subsequently, the subject–guest interactions and encapsulation mechanisms of lignans with β-CD, 2-hydroxypropyl-cyclodextrin, and 2,6-dimethyl-cyclodextrin (DM-β-CD) were investigated using a combination of molecular simulation and experimental methods, respectively. Molecular simulations were performed to calculate the microstructural parameters, including solubility parameters, binding energies, and mean square displacements. The simulation results demonstrated that DM-β-CD exhibited the strongest interaction with luteolin and formed the most stable inclusion complex. The inclusion complexes of luteolin with the three cyclodextrins were prepared by the freeze-drying method, and the formation of the inclusion complexes was demonstrated using infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and ultraviolet-visible spectroscopy. Phase solubility studies confirmed the formation of 1:1 stoichiometric inclusion complexes of lignans with cyclodextrins. Furthermore, 2,2-diphenyl-1-pyridine hydrazine free radical scavenging experiments demonstrated that the inclusion complexes exhibited enhanced antioxidant capacity. In light of these findings, it can be concluded that among the three cyclodextrins, DM-β-CD was optimally encapsulated with luteolin.