Structure elucidation is fundamental to understanding the chemical and physical properties of a material. Three-dimensional electron diffraction (3D ED) has shown great power for structure determination of nanometer- or submicrometer-sized crystals that are either too small or too complex for X-ray diffraction. 3D ED can be applied to a wide range of crystalline materials from inorganic materials, small organic molecules, to macromolecules. In this thesis, continuous rotation electron diffraction (cRED), also known as micro-crystal electron diffraction (MicroED) in macromolecular crystallography, has been applied for the determination of interesting novel crystal structures. New methods and protocols have been developed to push the current limitations of crystal structure determination by 3D ED.

The structure of silicate zeolite PST-24 is highly disordered. A combination of cRED with high-resolution transmission electron microscopy (HRTEM) revealed its unique channel system with varying dimensionality from 2D to 3D. The aluminum metal-organic framework CAU-23 nanocrystals form aggregates and are very beam sensitive. Its structure, as determined by cRED, is built by twisted helical Al-O chains connected by TDC^2- linkers, forming a chiral structure with square channels. The unique structure of CAU-23 provides high stability and high water adsorption capacity, making it an ideal material for ultra-low temperature adsorption driven chillers.

A simple pressure-assisted specimen preparation method, denoted Preassis, has been developed to overcome the challenges in the application of MicroED on biological samples with high viscosity and low crystal concentration. It has been successfully applied for the specimen preparation of several bio-molecular crystals including a novel R2lox metalloenzyme, which was crucial for its structure determination. Furthermore, an investigation of the influence of radiation damage on lysozyme crystals was performed to improve the data quality and final structural model. Finally, the crystal structure of acetylated amyloid-β fragment Ac-Aβ_16-20, related to Alzheimer’s disease, has been studied. The crystal has an active optical wave-guiding property with an excitation wavenumber of 488 nm due to its unique packing of Ac-KLVFF β–sheets.