3D electron diffraction: a single crystal method for nanocrystalline pharmaceutical compounds

3D electron diffraction can provide 3D single crystal electron diffraction data on crystal grains of few hundreds nanometers. The data collection is performed by tilting the crystal around the goniometric axis and recording a pattern every 1°. Due to the peculiar diffraction geometry where the patterns are usually far from highly symmetrical zone axis orientations, the dynamical scattering is significantly reduced and the integrated diffracted intensities can be successfully used as kinematical in ab-initio structure solution attempts. By combining this data collection method with a new generation of single electron detectors designed for diffraction, which are at the same time, extremely fast and very sensitive, it is possible to reduce the total collection time to less than one minute. The experiments can be carried out in low illumination with electron doses of the order of 0.01 el s-1 Å-2 [1]. With such experimental set up it is possible to analyze sample that in standard illumination conditions are amorphized after few seconds of exposure. Pharmaceutical are the perfect target of this methodology. Example of structure solutions of several pharmaceutical compound crystallized in nanometric grains will be provided. Among them the structure solution of a polymorph of metaxalone stands out.