1H and 13C NMR and molecular dynamics study of chiral recognition of camphor enantiomers by α-cyclodextrin

H-1 and C-13 NMR spectra of the complexes of camphor enantiomers with alpha-cyclodextrin in D2O manifest splittings due to chiral recognition. The complexes were found to be of 1:2 guest-to-host stoichiometry. Free energies of the complex formation obtained from H-1 NMR titration data are equal to -7.95 +/- 0.09 kcal mol(-1) for the complex with (1S,4S)- and -7.61 +/- 0.06 kcal mol(-1) for that with (1R,4R)-enantiomer. Thus, the free energy difference between the complexes is equal to 0.34 +/- 0.11 kcal mol(-1), with the complex involving the (1S,4S)-camphor more stable. A strong positive cooperativity of the guests binding has been found. In agreement with experimental results, molecular dynamics simulations yielded greater stability of the complex with (1S,4S)-camphor. However, they reproduced only qualitatively the experimental trend since the corresponding difference in average energies obtained from molecular dynamic simulations carried out in a water solution is equal to 5 kcal/mol with the CVFF force field.