Enantiodifferentiation by Complexation with β-Cyclodextrin: Experimental (NMR) and Theoretical (MD, FEP) Studies

Diastereomeric complexes between β-CyD and both enantiomers of mandelic acid, hexahydromandelic acid, and 1-cyclohexylethylamine were studied by NMR spectroscopy. Their inclusion complexes were studied by molecular dynamics (MD) calculations. Induced chemical shifts gave association constants of about 102–103 M−1. Computed geometries for the inclusion complexes are in agreement with those deduced experimentally by NOE experiments. MD (free energy perturbation) calculations correctly predict the most stable diastereomer when enantiomers are individually complexed with β-CyD.