Crown ether-tethered cyclodextrins: superiority of the secondary-hydroxy side modification in binding tryptophan

beta-Cyclodextrin (beta-CyD) derivatives bearing a benzo-X-crown-Y (X=15, 1 8 and Y=5, 6) moiety at the primary- or secondary-hydroxy side were synthes ized for molecular recognition toward tryptophan (Trp) in zwitterionic form . H-1 NMR titration experiments gave binding constants for a 1:1 host-guest complexation process, leading to the conclusions that the benzo-18-crown-6 moiety was superior to the benzo-15-crown-5 moiety in binding Trp and that the secondary-hydroxy side modification was preferable to the primary-hydr oxy side one for recognizing Trp. For the secondary-hydroxy side-modified b eta-CyDs, although the difference in the binding constants for D- and L-Trp were small, complexation-induced chemical shift changes and complexation-i nduced circular dichroism changes revealed that the hosts recognized the ch irality difference of Trp. The ammonium cation part of Trp was located at t he secondary-hydroxy side of the CyD cavity and is recognized by the benzo- 18-crown-6 moiety attached at the secondary-hydroxy side of CyD. This inter action between the ammonium cation and the benzo-18-crown-6 was confirmed b y 2D-ROESY. 2D-ROESY spectra also indicated that the benzo-18-crown-6-modif ied CyD accommodated the indole ring of Trp more shallowly in the CyD cavit y than the benzo-15-crown-5-modified CyD.