Ultra-wideline 14N solid-state NMR as a method for differentiating polymorphs: glycine as a case study

Nitrogen-14 solid-state NMR (SSNMR) is utilized to differentiate three polymorphic forms and a hydrochloride (HCl) salt of the amino acid glycine. Frequency-swept Wideband, Uniform Rate, Smooth Truncated (WURST) pulses were used in conjunction with Carr-Purcell Meiboom-Gill refocusing, in the form of the WURST-CPMG pulse sequence, for all spectral acquisitions. The 14N quadrupolar interaction is shown to be very sensitive to variations in the local electric field gradients (EFGs) about the 14N nucleus; hence, differentiation of the samples is accomplished through determination of the quadrupolar parameters CQ and ηQ, which are obtained from analytical simulations of the 14N SSNMR powder patterns of stationary samples (i.e., static NMR spectra). Additionally, differentiation of the polymorphs is also possible via the measurement of 14N effective transverse relaxation time constants, Teff2(14N). Plane-wave density functional theory (DFT) calculations, which exploit the periodicity of crystal lattices, are utilized to confirm the experimentally determined quadrupolar parameters as well as to determine the orientation of the 14N EFG tensors in the molecular frames. Several signal-enhancement techniques are also discussed to help improve the sensitivity of the 14N SSNMR acquisition method, including the use of selective deuteration, the application of the BRoadband Adiabatic INversion Cross-Polarization (BRAIN-CP) technique, and the use of variable-temperature (VT) experiments. Finally, we examine several cases where 14N VT experiments employing Carr-Purcell-Meiboom-Gill (CPMG) refocusing are used to approximate the rotational energy barriers for RNH3+ groups