Theoretical study of the formation of inclusion complexes with some terpenes using different solvating models

Essential oil molecules have various nutritional and medical uses. However, their applications are limited by their low polarity and high volatility. Inclusion complexes provide a way to overcome these limitations. Cyclodextrins are cyclic oligosaccharides composed of macrocyclic rings of glucose units linked by α-1,4 glycosidic bonds, which are used to prepare inclusion complexes with essential oils. Experiments on the formation of inclusion complexes show that essential oil molecules can bind to cyclodextrins in various ways. Electronic structure calculations help to understand why some essential oil molecules bind more effectively than others in the formation of inclusion complexes with cyclodextrins.

Our study employed theoretical calculations to investigate the interaction between beta-cyclodextrin and six essential oil molecules. The selected essential oil molecules were carvacrol, carvone, eugenol, limonene, p-cymene, and thymol. Molecular docking between the essential oil molecules and cyclodextrin resulted in both complexed structures and non-complexed structures, with some molecules positioned outside the cyclodextrin cavity. The interaction energies, calculated using the AutoDock Vina program, indicated that the complexed essential oil molecules exhibit the lowest energy. Electronic structure calculations were performed using the Gaussian16 program to analyze the structures obtained from the docking process. DFT calculations employing the ωB97XD functional to describe the inclusion complex and PM7 to describe the solvent model in the ONIOM approach revealed that molecules containing hydroxyl groups form hydrogen bonds with cyclodextrin, resulting in more stable structures compared to those lacking this functional group. Additionally, the use of explicit solvent facilitates the inclusion of essential oil molecules by altering the deformation energies of cyclodextrin. These theoretical results explain the advantage of using solvents in the preparation of experimental inclusion complexes.