Theoretical study of enantiodifferentiation in solid state cyclodextrins

A molecular mechanics investigation of R‐ vs. S‐phenylethanol, R‐ vs. S‐mandelic acid, R‐ vs. S‐flurbiprofen, and R‐ vs. S‐fenoprofen in their cyclodextrin crystal environments was undertaken. It was found that the dominant force responsible for guesthost complexation is the short‐range London force; the enantiodiscriminating forces tend to be very small and are generally, but not always, dominated by long‐range electrostatic contributions. Derivatized cyclodextrins are generally more enantiodiscriminating than native cyclodextrins, perhaps due to exterior rather than interior guest‐host binding.