Journal of Inclusion Phenomena and Macrocyclic Chemistry
44 (1-4): 107-110, December 2002
Copyright © 2002 Kluwer Academic Publishers
All rights reserved
Inclusion Complexation of a Seleno-Organic Antioxidant, Ebselen, with Cyclodextrins in Aqueous Solution
Yukihiko Nagase, Norio Suzuki, Hitoshi Yamauchi, Sunyong Kim, Koki Wada, Hidetosh Arima, Fumitoshi Hirayama, Kaneto Uekama
Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
Abstract
The interaction of ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, a novel neuroprotective agent, with cyclodextrins (CyDs) in aqueous solution was studied by the solubility method and spectroscopic methods. The ability of sulfobutyl ether β-CyD (SBE7-β-CyD, average degree of substitution= 6.2) to solubilize ebselen was greater, and its stability constant (> 2000 M-1) was significantly higher than those (< 1000 M-1) of other CyD complexes employed. The stability constant of the complexes rose as hydrophobicity of the substituents of CyDs increased, whereas it was negligibly affected by change in ionic strength of the medium, indicating a significant contribution of hydrophobic interaction in the complexation. SBE7-β-CyD gave positive and negative CD bands at around 320 and 350 nm, respectively, indicating that the guest is embedded in the asymmetric locus of the CyD cavity. 1H-NMR spectroscopic studies suggested that the mono-substituted benzene ring of ebselen is preferably included in the cavity of SBE7-β-CyD. The results indicate that SBE7-β-CyD is useful as a solubilizing agent for ebselen.

Keywords
cyclodextrin, ebselen, inclusion complex, solubility, solubilization, sulfobutyl ether β-cyclodextrin