CHIRAL MOLECULAR RECOGNITION IN A TRIPEPTIDE BENZYLVIOLOGEN CYCLOPHANE HOST

A cationic chiral cyclophane was synthesized and studied as a host for chiral and racemic pi-donor molecules. The cyclophane host has a rigi d binding cavity flanked by (S)-(valine-leucine-alanine) and N,N'-dibe nzyl-4,4'-bipyridinium subunits, which allow for hydrogen-bonding and pi-stacking interactions with included aromatic guest molecules. H-1 N MR binding titrations were performed with several different pharmaceut ically interesting guest molecules including beta-blockers, NSAIDs, an d amino acids and amino acid derivatives. The host-guest complexation constants were generally small for neutral and cationic guests (0-39 M -1 at 20 degrees C in water/acetone mixtures). However, a (R)/(S) enan tioselectivity ratio of 13 +/- 5 was found for DOPA, a strongly, pi-do nating cationic guest. Two-dimensional NOESY H-1 NMR spectra confirm t hat (R)-DOPA binds inside the cavity of the host and that there is no measurable interaction of the cavity with (S)-DOPA under the same cond itions.