NMR Crystallographic Approach to Study the Variation of the Dynamics of Quinine and Its Quasienantiomer Quinidine

Abstract

The structure and dynamics of quinine and its quasienantiomer quinidine were studied at the atomic resolution by measuring the chemical shift anisotropy (CSA) tensor and site-specific spin-lattice relaxation time. For quinine, there are three crystallographically independent molecules "a", "b", and "c"in an asymmetric unit since its 13C CP-MAS SSNMR spectrum features three distinct resonance peaks for certain carbon nuclei. The 13C assignments are fulfilled by DFT calculations. The experimental 13C isotropic chemical shifts well match the calculated values. These variations of isotropic chemical shift for three independent molecules are also observed by two-dimensional 13C-1H heteronuclear correlation spectroscopy (HETCOR) of quinine. The spin-lattice relaxation time, and the principal components of CSA parameters are also varied substantially for certain carbon nuclei of "a", "b", and "c"molecules. For quinidine, its 13C CP-MAS SSNMR spectrum is remarkably different from that of quinine despite, their almost identical solution NMR spectra. Furthermore, the remarkable change in the structure and dynamics of quasienantiomers are also observed including the steric effect of the substituent vinyl group, the variation of helical motifs, and the variation of the strength of the intermolecular hydrogen bonds. The variation of the structure and dynamics of quasienantiomers are thoroughly studied by solid-state NMR measurements. These types of studies will enrich the field of NMR crystallography. © 2022 American Chemical Society.