NMR studies of hindered rotations in drugs. Use of achiral and chiral lanthanide shift reagents with mecloqualone, an axially chiral drug of abuse. Rigorous definition of spin systems.

The axially chiral sedative/hypnotic drug of abuse, mecloqualone, (1) under bar, has been studied in cDCl(3) by H-1 NMR at 60 and 300 MHz with the added achiral lanthanide shift reagent (LSR), tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium(III), (2) under bar, and the chiral LSR, tris[3(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium-(III), (3) under bar. Rigorous distinctions between the two (CH)(4) spin systems of (1) under bar with added (2) under bar or (3) under bar were achieved by two-dimensional homonuclear chemical shift correlation spectroscopy, COSY. Substantial <(upfield)under bar> ("anomalous") shifts were observed for several nuclei of (1) under bar with each LSR. Use of the chiral (3) under bar elicited enantiomeric shift differences with baseline separations for several nuclei that should permit direct determinations of enantiomeric excess. COSY spectra allow determination of the relative sense of magnetic nonequivalence of selected nuclei of (1) under bar with (3) under bar.