Chiral recognition of α-amino acids by charged cyclodextrins through cooperative effects of Coulomb interaction and inclusion

Abstract

Chiral recognition of α-amino acid derivatives by charged β-cyclodextrins has been studied by means of ¹H NMR spectroscopy. Protonated heptakis(6-amino-6-deoxy)-β-cyclodextrin (per-NH₃⁺-β-CD) forms complexes with the (S)-enantiomers of N-acetylated Trp, Phe, Leu and Val in their anionic forms more preferentially than the (R)-enantiomers, though the difference in the binding constants (K) between the enantiomers is small. Inclusion of the guest into the host cavity and intermolecular Coulomb interactions participate cooperatively in complexation. Monoaminated β-cyclodextrin (mono-NH₃⁺-β-CD) also recognizes the chirality of the amino acids while native cyclodextrins such as α- and β-cyclodextrins do not. The K values for the per-NH₃⁺-β-CD–guest anion complexes are much larger than those for the mono-NH₃⁺-β-CD complexes.

The large K value of the per-NH₃⁺-β-CD–(S)-AcTrp complex is ascribed to a large positive ΔS value which might be due to extended dehydration of both host and guest during complexation. The enantioselective complexation was also found in the system composed of the α-amino acid methyl esters in the cationic forms and heptakis[6-(2-thioglycolic acid)-6-deoxy]-β-cyclodextrin in the anionic form where the (R)-enantiomers were preferable guests. The present study demonstrates the advantage of Coulomb interactions as an attractive force in recognition of central chirality in host–guest chemistry.