Solid-state NMR meets electron diffraction: determination of crystalline polymorphs of small organic microcrystalline samples

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.