3D ELECTRON DIFFRACTION ON NANOCRYSTALLINE MATERIALS: FROM HIGH PRESSURE SYNTHESIS TO MACROMOLECULES

3D electron diffraction (3D ED) is now a technique able to deliver single crystal electron diffraction data collected on nanocrystalline domains, which are suitable for crystal structure solution. The data collection consists of a sequence of patterns recorded either in step or continuously while the sample is rotated around the goniometer axis of the transmission electron microscope. Thanks to the peculiar diffraction geometry the electron diffraction intensities are quasi kinematical and can be used as a reliable approximation of the square modulus of the structure factor in ab-initio structure solution methods. The availability of parallel electron beams of few hundreds nanometers determines the minimum size of the diffracting domains, stating that it is possible to isolate a single crystal of this size inside a matrix or to diffract on ordered nanometric domains surrounded by disordered or amorphous areas. Obtaining 3D diffraction on crystals that are at least four order of magnitude smaller than those observable with x-ray diffraction opens the possibility of solving all crystallographic problems where the growth of large crystals is an issue.

Recently the appearance of a new generation of single electron detectors that are radiation hard and therefore can stand diffraction signals, has pushed 3D ED one step forward into the crystallography of very beam sensitive materials. Specific low dose protocols of data collections have been developed that ,with a total dose of 1 el/Å^-2, allow a complete 3D data collection in half a minute. It has been possible to collect data on and to solve metallorganic framework that in standard illumination condition are amorphized after few seconds. For the first time the crystal structure of pharmaceutical compounds have been solved with electron diffraction data and in some cases the samples resisted to the beam without the need to work under cryo condition. Finally 3D ED has been effective in determining the crystal structure of peptides, known proteins structures and also the crystal structure of a new lysozyme polymorph.

The actual development of the technique will be described and several examples of structures solved by 3D ED in material science, experimental petrology, metalorganic chemistry, pharmaceutical chemistry and macromolecular crystallography will be presented.