Design and synthesis of fluorescent β-cyclodextrins for the enantioselective sensing of α-amino acids

Abstract

Fluorescent monofunctionalized β-cyclodextrins bearing a copper(II) binding side arm and a dansyl group (CD-NH-AA-CH2CH2NH-DNS) were designed as enantioselective sensors for unmodified α-amino acids. The side arm was derived from amino acid synthons (AA = L- and D-phenylalanine (1 and 2), L- and D-phenylglycine (3 and 4), L-proline (5), and L-cyclohexylglycine (6)) and was chosen in order to contain an amide, an amine, and a sulphonamide group. Enantioselectivity was evaluated by addition of copper(II) complexes of D- or L-valine and D- or L-proline. Chiral discrimination in the fluorescence response was observed in all cases, due to a ligand exchange process. The best conditions for these experiments were found to be the use of an excess (10: 1) of the copper complex. The cyclodextrin 4 containing a D-phenylglycine unit was found to be poorly enantioselective, as found for 2, suggesting that the best design can be obtained by using L-amino acids. All L-amino acid containing cyclodextrins showed good enantioselectivities, some of which were higher than those already reported for 1. Other analytes related to amino acids were studied using cyclodextrins 1 and 3. Enantiomers of α,α-disubstituted amino acids, N-methylamino acids, and amino acid amides were found to be discriminated, while β-phenylalanine and other molecules bearing a poor anchoring group at the α-carbon gave poor enantioselectivity. On the basis of the present data a model for the recognition process, based on the formation of ternary diastereomeric complexes, is proposed. © 2003 Wiley-Liss, Inc.