Characterization of vitamin E succinate inclusion complexes with cyclodextrins: unraveling structure, properties, and mechanism via experimental and molecular modeling study

Novel VES/substituted β-CD inclusion complexes were successfully prepared. • Substituent effects and stoichiometric transitions co-govern binding modes. • The dimethyl-β-cyclodextrin proves most effective for carrying the VES. • DM-β-CD tail-to-tail dimers form dynamic hydrogen bonds in 1:2 complexes. • Encapsulation highly enhances VES water solubility and antioxidant activity. This study aimed to enhance the aqueous solubility and stability of vitamin E succinate (VES) through cyclodextrin encapsulation. Inclusion complexes of VES with β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and dimethyl-β-cyclodextrin (DM-β-CD) were prepared via freeze-drying. Structural analyses confirmed successful encapsulation. Phase solubility studies revealed 1:1 complexes for β-CD and HP-β-CD, while a more stable 1:2 complex formed with DM-β-CD. The VES/DM-β-CD complex showed a 108-fold solubility increase and significantly improved antioxidant activity, with DPPH and ABTS radical scavenging activities increased by 61.6% and 59.6%, respectively. Molecular simulations of various dimer orientation indicated that DM-β-CD dimers achieved the most complete encapsulation and highest binding affinity, particularly in the tail-to-tail (TT) conformation, which is driven by enhanced van der Waals interactions and dynamic hydrogen bonds. DM-β-CD is concluded to be the most effective carrier for optimizing VES delivery and functional performance. Download: Download high-res image (363KB) Download: Download full-size image