Electron crystallography of Organic nanocrystals

This thesis focuses on the application of 3D electron diffraction (3D ED) in studying the crystal structures of natural products that may exist in nanocrystalline forms, as well as cocrystals synthesized via mechanochemistry. The 3D ED technique offers an alternative for crystal structure elucidation of submicron-sized crystalline samples that are unsuitable for the conventional single crystal X-ray diffraction (SCXRD) technique. The first part of the thesis introduces the fundamentals of 3D ED, including instrumentation, diffraction geometry in electron diffraction, data collection and data processing strategies. Sample preparation methods for either stable, beam or vacuum-sensitive samples are also discussed. Building on this foundation, the application of the technique in the round robin project was reported to establish the reproducibility of 3D ED. The results of 3D ED analysis by various laboratories demonstrated the reliability of the technique regardless of the instrument used in the analysis. 3D ED was then applied for the investigation of crystal structures of unreported phases of the natural product oxyresveratrol. Two new phases were found, including one anhydrate phase and a novel hydrate polymorph. Additionally, the crystal structures of three oxyresveratrol cocrystals synthesized using mechanochemistry were uncovered using 3D ED. To address the problem of beam sensitivity, which is a common challenge during data acquisition on organic samples, a novel method of data collection serial electron diffraction (SerialED), has been applied for the collection of diffraction data on a well-known active pharmaceutical ingredient, L-dopa. Preliminary results after the data analysis have been reported, showing a promising future for SerialED method of data collection.