Encapsulation of α-tocopherol in large-ring cyclodextrin containing 26 α-D-glucopyranose units: A molecular dynamics study

Abstract α-Tocopherol is the most biologically active form of vitamin E (VE) exhibiting various biological activities such as strong antioxidant activity, antitumor properties and antiaging effects. However, the low water solubility of α-tocopherol has limited its prospective use in food, cosmetic and pharmaceutical industry. One of the promising strategies to tackle such issue is the use of a supramolecular complex with cyclodextrins (CDs). In this study, the encapsulation of α-tocopherol with six different initial un-complexed states into the large-ring CD containing 26 α-D-glucopyranose units (CD26) was studied by means of 400-ns molecular dynamics (MD) simulations to investigate their host–guest association process and the preferential binding efficiency upon complexation at low concentration of α-tocopherol. The MD results show that α-tocopherol spontaneously interacted with CD26 within 20 ns and formed a stable inclusion complex during 150–400 ns. From all six independent simulations, the inclusion complexes can be divided into two groups, which were fully and partly encapsulated inside the cavity of CD26. The α-tocopherol of the first group was covered by 13–14 subunits of CD26, while α-tocopherol in another group was attached by 6–10 subunits of CD26. In addition, α-tocopherol was surrounded by one- or two-turn helix of one half-ring of CD26, leaving the rest of cavities for forming complexation with a larger number of α-tocopherol molecules. Therefore, CD26 can be used as a solubility and stability enhancer for α-tocopherol through inclusion complexation.