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

Chiral recognition of a-amino acid derivatives by charged beta-cyclodextrins has been studied by means of H-1 NMR spectroscopy. Protonated heptakis(6-amino-6-deoxy)-beta-cyclodextrin (per-NH3+-beta-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 beta-cyclodextrin (mono-NH3+-beta-CD) also recognizes the chirality of the amino acids while native cyclodextrins such as alpha- and beta-cyclodextrins do not. The K values for the per-NH3+-beta-CD-guest anion complexes are much larger than those for the mono-NH3+-beta-CD complexes. The large K value of the per-NH3+-beta-CD-(S)-AcTrp complex is ascribed to a large positive Delta S 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 alpha-amino acid methyl esters in the cationic forms and heptakis[6-(2-thioglycolic acid)-6-deoxy]-beta-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.