Remarkably stable inclusion complexes with heptakis-[6-deoxy-6-(2-aminoethylsulfanyl)]-β-cyclodextrin

Abstract

Complexes of heptakis-[6-deoxy-6-(2-aminoethylsulfanyl)]-β-cyclodextrin (1) and a series of common cyclodextrin guests were studied by NMR, fluorescence spectroscopy, and ITC experiments. NMR conformational analysis shows that the thioethers of 1 are positioned over the hydrophobic cavity of the cyclodextrin, increasing potential hydrophobic interactions with guest molecules. The combination of the increased hydrophobic character, the electrostatic complementarity and a hypothesized conformational change in 1 lead to a complex with the dye 2,6-ANS (5) that is over 2000 times more stable than with the native β-cyclodextrin. One of the most stable host–guest complexes between a cyclodextrin and a small molecule measured to date was revealed between 1 and lithocholic acid (4) with an association constant of 5.5 × 10⁷ M⁻¹.