Enantiorecognition of a new chiral selector, β-cyclodextrin perphenylcarbamate, as studied by NMR spectroscopy and molecular energy calculation

Abstract

The mechanism of enantioselective binding of chiral atenolol (AT) by β-cyclodextrin perphenylcarbamate (PhCD) has been studied by NMR spectroscopy and by molecular modelling techniques including conformational and free energy of binding calculations for the AT–PhCD complexes. Among the various models tested, the (R)-enantiomer was found from the calculations to bind with the PhCD with its asymmetric carbon moiety inside the toroid of cyclodextrin, while its aromatic ring is outside the toroidal cavity at the secondary hydroxy group side; in contrast, the (S) counterpart preferred to locate its aromatic ring inside the toroid, while retaining the asymmetric carbon moiety outside the cavity at the primary hydroxy group side. The differential changes in 1H NMR chemical shifts and linewidths between the enantiomers of AT, caused as a result of interaction with PhCD, clearly reflected the difference in the binding mode suggested from the present molecular modelling calculations. It was concluded that although the binding affinity of (S)-AT is weaker than that of (R)-AT, the mobility of the (S)-enantiomer is lowered more than the (R) counterpart as a result of the interaction with PhCD.