CHROMATOGRAPHIC AND H-1-NMR SUPPORT FOR A PROPOSED CHIRAL RECOGNITIONMODEL

Liquid chromatography and H-1 NMR spectroscopy were used in an investi gation of a chiral recognition rationale which was previously advanced to account for the resolution of naproxen (NAP-COOH) enantiomers on b rush-type chiral stationary phases, CSP-1 and CSP-2, identical except for tether length. CSP-1 has recently been commercialized as the Whelk -O 1. This chiral stationary phase (CSP), basically an immobilized ena ntiomer of robenzoyl)-4-amino-1,2,3,4-tetrahydrophenanthrene, was desi gned to have a cleft in which one enantiomer is preferentially bound. The cleft consists of pi-acidic and pi-basic aromatic systems held mor e or less perpendicular to each other. Aromatic substituents in the an alyte were expected to be held in this cleft by simultaneous face-to-f ace and face-to-edge pi-pi interactions. To ascertain whether analytes are truely bound in this cleft, NMR studies of mixtures of several na proxen-like analytes and chiral solvating agent 3, a soluble version o f the selector used in CSP-1, were undertaken. Additional motivation f or the study came from the observation that the enantiomers of NAP-COO H and NAP-COOMe elute in a different order than do the enantiomers of NAP-CONHMe, and NAP-CON(Me)(2). This difference in the elution order o f the amide derivatives with respect to the esters and free acid was n ot totally unexpected, for the chiral recognition hypothesis used in t he design of the chiral selector allowed for such an eventuality. It w as known from reciprocal chromatographic studies that the enantiomers of soluble analogs of the Whelk-O 1 CSP show different elution orders on naproxen-derived amide CSPs than they do on naproxen-derived ester CSPs. These data aided in formulation of the initial chiral recognitio n rationale. Evidence for the occurance of the specific molecular inte ractions suggested by this rational is provided by the presently descr ibed H-1 NMR study of the enantioselective complexation of the enantio mers of NAP-COOH, NAP-COOMe, NAP-CONHMe, and NAP-CON(Me)(2) by a singl e enantiomer of a soluble analog of the Whelk-O 1 CSP.