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

alpha-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 alpha-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 alpha-tocopherol with six different initial uncomplexed states into the large-ring CD containing 26 alpha-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 alpha-tocopherol. The MD results show that alpha-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 alpha-tocopherol of the first group was covered by 13-14 subunits of CD26, while alpha-tocopherol in another group was attached by 6-10 subunits of CD26. In addition, alpha-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 alpha-tocopherol molecules. Therefore, CD26 can be used as a solubility and stability enhancer for alpha-tocopherol through inclusion complexation. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

By using molecular dynamics simulations, this study investigated the encapsulation of alpha-tocopherol with CD26, a supramolecular complex, and found that alpha-tocopherol spontaneously interacts with CD26 within 20 ns and forms a stable inclusion complex during 150-400 ns. The results showed that there were two groups of inclusion complexes, fully and partly encapsulated, which can enhance the solubility and stability of alpha-tocopherol.