A combination of solid-state NMR (ssNMR) and electron diffraction (ED) has been used to determine the crystalline polymorphs in small-organic microcrystalline molecules. Although 13C cross-polarization magic angle spinning (CPMAS) is a widely used method for determining crystalline polymorphs, even in a mixture, it sometimes fails if the molecular conformations are similar. On the other hand, ED can, in principle, differentiate crystalline forms with different lattice parameters, even when they have very similar molecular conformations. However, its application is usually limited to inorganic molecules only. This is because the ED measurements of organic molecules are very challenging due to degradation of the sample by electron irradiation. We overcame these difficulties by the use of 1H double-quantum/single-quantum correlation experiments at very fast magic angle spinning, together with ED observations under mild electron irradiation. The experiments were demonstrated on L-histidine samples in L-histidine·HCl·H2O, orthorhombic L-histidine and monoclinic L-histidine.
Keywords: NMR crystallography; crystalline polymorphs; electron diffraction; solid-state NMR; transmission electron microscopy.