Pushing the limits of NMR crystallography: a study on three forms of glycylglycine.

NMR crystallography (NMRX), which integrates solid-state NMR (SSNMR) spectroscopy, X-ray diffraction (XRD), and density functional theory (DFT) calculations, provides deeper insight into crystal structures than any of these methods individually. With the goal of pushing the limits of NMRX, we have characterized three solid forms of the dipeptide glycylglycine, including a free base, a hydrochloride salt, and an unusual hemihydrochloride salt-the latter form is synthesized and characterized by single-crystal XRD here for the first time. SSNMR data include 2D 1H-1H DQ-SQ BABA spectra that are used to measure 1H chemical shifts and provide assignments through homonuclear dipolar correlations, slow-spinning 1H-13C and 1H-15N CP/MAS spectra to determine the 13C and 15N chemical shift tensors, ultra-wideline 14N WURST-CPMG spectra to measure the 14N electric field gradient (EFG) tensors, 1D 35Cl spectra to determine the 35Cl EFG and chemical shift tensors, and 2D 35Cl → 1H D-RINEPT spectra to determine heteronuclear dipolar correlations between the chloride ions and nearby protons. Together with state-of-the-art DFT calculations, these parameters are related directly to molecular- and crystal-level structure and intermolecular hydrogen bonding. Modern DFT approaches using double-hybrid functionals are critical for predicting subtle differences in 13C and 15N chemical shift tensors between the three solid forms. By highlighting the current capabilities of NMRX, it is hoped that these results will open new avenues for the exploration of a plethora of materials and biosolids.