Diffraction methods generate detailed structural information for chemical compounds, driving discoveries in manyfields across academia and industry. The standard approaches use either single crystals, which provide highlyinformative 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 resultswith quality and reliability comparable to X-ray crystallography. The challenges include absolute configurationdetermination, efficient data collection, and diffraction data analysis in the presence of microED-specificexperimental errors. In SBIR Phase I, we will develop, implement, and test methods that address handednessdetermination for small molecule crystals and combine them with effective approaches to greatly reducesystematic errors, to enable merging datasets from multiple crystals, experimental phasing and absoluteconfiguration 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 ofexperimental conditions, tailoring the solutions to characteristic problems.These new methods will benefit all types of microED analysis and result (1) in absolute configurationdetermination 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 expandingfield, so the potential for successful commercialization is high.
Public Health Relevance Statement: Project Narrative
Microcrystal electron diffraction (microED) can use micron and sub-micron crystals for structure determination,
which are much easier to produce than the large crystals needed for the standard approach by X-ray diffraction.
However, microED needs to be more robust and advanced to cover specific sub-problems of high interest, such
as absolute configuration determinations. We will develop approaches producing and analyzing microED data
to make the method widely used and applicable.
Project Terms: | <3-D><3D><3-Dimensional><3-D analysis><3-dimensional analysis><3D analysis>
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