ENANTIOSELECTIVE BINDING OF TRYPTOPHAN BY ALPHA-CYCLODEXTRIN

H-1 and C-13 NMR studies of racemic and optically pure tryptophan binding with alpha-cyclodextrin are carried out to explain chiral recognition in this guest-host system. The changes in chemical shifts, coupling constants, and relaxation times for the R enantiomer are larger than for S upon binding, and differential changes of R vs S in the bound state are larger for the more tightly bound R enantiomer. An intermolecular NOE between guest and host places the indole ring near the secondary hydroxyl rim of the cyclodextrin for both enantiomers, suggesting similar modes of binding. Results extracted from molecular dynamics simulations are that both guests are highly localized on the interior of the host, the ammonium group of the zwitterionic tryptophan does not contribute to the recognition process, and the more tightly bound R enantiomer forms twice as many hydrogen bonds as its optical antipode, most of which are multiple-contact hydrogen bonds. Both R and S guests are found to use the same kinds of intermolecular interactions but to a greater or lesser extent. Armstrong's chiral recognition model has been slightly modified but generally remains intact.