ABSTRACT'H NMR (600 MHz) measurements of chemical shift changes were made in acidified (DCI) CD30D/D20 1:9 v/v equimolar solutions of (S)-and (R,S)-6-methoxy-amethyl-2-naphthaleneacetic acid (naproxen) in the presence of l-(3-aminopropyl)-(5R, 8S, lOR)-terguride (AMP-TER). The most significant bonding interactions concurring to the formation of diastereoisomer complexes are seen as chemical shifts in proximity to the positively charged nitrogen N(6)-CH3 and of H(12), H(13), H(14) protons of the ergoline skeleton, both the adducts having an electrostatic term and different I T-stabilizing interactions. Chemical shift data exclude any contribution of the aminopropyl chain to the chiral recognition mechanism. These findings provide an experimental basis for the enantiodiscriminative process accounting for the observed chromatographic resolutions of arylcarboxylic acids on chiral stationary phases derived from AMP-TER. o 1994 wiley-Liss, Inc.KEY WORDS: diastereoisomer complexes, nuclear magnetic resonance spectroscopy, ergot alkaloid derivatives, haproxen enantiomers Two enantiomeric species can only be recognized and discriminated in the presence of a chiral resolving agent. Therefore, resolution of optical isomers by liquid chromatography necessarily requires a chiral selector, commonly bonded to an achiral matrix, to be involved in reversible interactions with the enantiomers, and competing with them in the formation of labile diastereoisomeric complexes. The stability difference between these complexes affects the degree of chiral discrimination. Therefore, models of chiral recognition accounting for observed enantioseparations are of great value, because they may be used to improve the synthesis of chiral stationary phases (CSPs), select suitable CSPs for the resolution of given racemates, or relate absolute configurations of resolved enantiomers to their elution order. Chiral recognition studies also allow the determination of the role of the achiral support in the enantiodiscriminative process.Nuclear magnetic resonance (NMR) spectroscopy has proved to be a powerful tool in the studies of such diastereoisomeric adducts. Shah et aL3 reported a NMR study of the association complexes of the enantiomers of 2,2,2-trifluoro-l-(g-antryl)-ethanol with butoxycarbonyl-(R)-valine. Prkle and Pochapsky4 confirmed through NMR measurements the chiral recognition model based on the Dalgleish three point con~e p t ,~ for selective retention of (3-DNB-leucine amide on a CSP derived from naphthylalanhe. Recently, we reported the separation of the enantiomers of the structurally analogous compounds, terguride and lisuride,7 and of a series of carboxylic acids' on a CSP derived from 1-(3-aminopropyl)-(5R,8S, lOR)-terguride (AMP-TER). Good enantioselectivity was shown by the above CSP toward underivatized 2-arylpropionic acids used as nonsteroidal antiinflammatory drugs (the selectivity factor for naproxen was a = 1.06)' indicating the high degree of chiral recognition and highly specific attractive interactions between the selecto...