Two-Dimensional High-Speed CP/MAS NMR Spectroscopy of Polymorphs. 1. Uniformly 13C-Labeled Aspartame

Three forms of crystalline aspartame have been observed: two hemihydrate polymorphs and a dihemihydrate. The 13C CP/MAS NMR spectra of two of the forms of aspartame showed that certain carbons have up to three resonances due to different conformations/arrangements of molecules in the asymmetric unit cell. Techniques for assigning resonances based upon the number of attached protons or J couplings were not effective because the multiple resonances arise from the same carbon in the molecule. We used two-dimensional exchange experiments on uniformly 13C-labeled aspartame to assign the spectra of aspartame. Experiments performed with typical MAS rates (7 kHz) and 1H decoupling powers (63 kHz) of uniformly 13C-labeled aspartame were uninformative because 1H−13C and 13C−13C dipolar couplings significantly broadened these resonances. Increasing the spinning rate to 28 kHz and the 1H decoupling power to 263 kHz increased the resolution sufficiently to observe crystallographically inequivalent sites. Two-dimensional radio frequency driven dipolar recoupling (RFDR) and exchange experiments using very high spinning speed and decoupling power gave complimentary assignment information for short (1−2 bond) and long (>3 bonds) range interactions in the two polymorphic forms. For one form of aspartame, peaks were assigned to aspartame molecules in three inequivalent crystalline environments.