Probing Intermolecular Interactions in Chiral Chromatography with NMR Spectroscopy

Abstract

NMR spectroscopy was used to probe the intermolecular interactions in chiral chromatography. Three chiral sypathiometric analytes were studied; ephedrine, norephedrine, and pseudoephedrine along with a chiral surfactant; N-dodecocycarbonylvaline (DDCV). One dimensional diffusion experiments were performed to determine the complex with the greatest binding constant. Two dimensional ROESY experiments were collected to determine the intermolecular and intramolecular interactions of the analyte:surfactant mixtures and to generate binding maps. Experimental results determined that ephedrine exhibited stronger binding to the micelles than the pseudoephedrine. The norephedrine:DDCV association constants spanned a wider range than ephedrine or pseudoephedrine. The two-dimensional ROESY data suggested that one strong H-bond between the analyte and the micelle produced a lower energy complex than two weak H-bond and/or two competing H-bonds between the –OH and the –NH donor sites on the analyte. The two-dimensional ROESY data also suggested that once the analyte is H-bonded to the micelle, the analyte remained near the micelle surface within the chiral pocket, with the aromatic ring pointing towards the hydrocarbon chain, rather than interacting with the hydrophobic core of the micelle.