Encapsulation of menthol by cyclodextrins-comparison between experiments and molecular simulations

Cyclodextrins (CDs) are a traditional wall material for encapsulating flavor ingredients. Given the substantial structural differences among flavor ingredients, experimentally deriving the selection criteria for CDs suitable for these flavor substances is a time-consuming process. However, most existing literature relies on the embedding efficiency from practical experiments to evaluate the binding effect between flavor ingredients and CDs. This article used menthol as the research subject and investigated the binding effects of three different CDs through experiments and computer simulations. The experimental results revealed that β-CD exhibited the optimal encapsulation efficiency (EE, 36.54%) on menthol, subsequently, γ-CD showed a 33.35% EE value, whereas α-CD was unable to form an inclusion complex (IC) with menthol. Conformation changes, root mean square deviation (RMSD), radius of gyration (Rg), Radial distribution function (RDF), solvent accessible surface area (SASA), and hydrogen bonds, and binding free energy were analyzed through molecular dynamics simulation and compared with the experimental results. The results indicated that the IC formed between β-CD and menthol (menthol/β-CD-IC) is the most stable, with a binding free energy (ΔGbind) of −7.27 kcal/mol. The IC formed between α-CD and menthol (menthol/α-CD-IC) is the least stable one (ΔGbind = 2.59 kcal/mol). The results revealed a high degree of consistency between the experimental outcomes and those of molecular simulation, so molecular simulation can serve as a more efficient screening method, an alternative to practical experiments, to obtain the combination ability between host-guest molecules.