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

β-Cyclodextrin (β-CyD) derivatives bearing a benzo-X-crown-Y (X = 15, 18 and Y = 5, 6) moiety at the primary- or secondary-hydroxy side were synthesized for molecular recognition toward tryptophan (Trp) in zwitterionic form. 1H 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-hydroxy side one for recognizing Trp. For the secondary-hydroxy side-modified β-CyDs, although the difference in the binding constants for D- and L-Trp were small, complexation-induced chemical shift changes and complexation-induced circular dichroism changes revealed that the hosts recognized the chirality difference of Trp. The ammonium cation part of Trp was located at the 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 interaction between the ammonium cation and the benzo-18-crown-6 was confirmed by 2D-ROESY. 2D-ROESY spectra also indicated that the benzo-18-crown-6-modified CyD accommodated the indole ring of Trp more shallowly in the CyD cavity than the benzo-15-crown-5-modified CyD.