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

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