Dynamical Diffraction Analysis for 3D Electron Crystallography

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Project Abstract Diffraction methods generate detailed structural information for chemical compounds, driving discoveries in many fields across academia and industry. The standard approaches use either single crystals, which provide highly informative data, or powders of nanocrystals, which provide less information. Microcrystal electron diffraction (microED) has all the data richness benefits of single crystal crystallography and works with small crystals. However, the methods for microED data acquisition and analysis are not yet mature enough to provide results with quality and reliability comparable to X-ray crystallography. The challenges include absolute configuration determination, efficient data collection, and diffraction data analysis in the presence of microED-specific experimental errors. In SBIR Phase I, we will develop, implement, and test methods that address handedness determination for small molecule crystals and combine them with effective approaches to greatly reduce systematic errors, to enable merging datasets from multiple crystals, experimental phasing and absolute configuration determination. In SBIR Phase II, we will expand and incorporate these solutions into an easy-to- use, complete crystallographic package for microED and also validate the approach in a broad range of experimental conditions, tailoring the solutions to characteristic problems. These new methods will benefit all types of microED analysis and result (1) in absolute configuration determination for all type of compounds, (2) expanded applicability to radiation-sensitive and other difficult-to- handle crystals, and (3) better agreement between the model and the data which will increase the trust in results, in particular for de novo structure determination. These benefits are of high significance for this quickly expanding field, so the potential for successful commercialization is high.