Dynamical Diffraction Analysis for 3D Electron Crystallography

项目摘要 衍射方法生成化合物的详细结构信息，推动了许多领域的发现。 横跨学术界和工业界。标准方法使用单晶体，其提供高度的 信息数据或纳米晶体粉末，其提供较少的信息。微晶电子衍射 （microED）具有单晶晶体学的所有数据丰富性优势，并适用于小晶体。 然而，用于microED数据采集和分析的方法尚未成熟到足以提供结果 其质量和可靠性可与X射线晶体学相媲美。挑战包括绝对配置 确定，有效的数据收集和衍射数据分析的存在下microED特定的 实验误差在SBIR第一阶段，我们将开发、实施和测试解决利手问题的方法 小分子晶体的测定，并将其与有效的方法相结合， 系统误差，以便能够合并来自多个晶体的数据集，实验定相和绝对定相 配置确定。在SBIR第二阶段，我们将扩展这些解决方案，并将其纳入一个易于使用的 使用，完成microED的晶体学包，并在广泛的范围内验证该方法 实验条件，定制解决方案的特点问题。 这些新方法将有利于所有类型的微电子衍射分析和结果（1）在绝对配置 测定所有类型的化合物，（2）扩大适用性，辐射敏感和其他难以- 处理晶体，和（3）模型和数据之间更好的一致性，这将增加对结果的信任， 特别是用于从头结构测定。这些好处对于这个迅速扩大的 因此，成功商业化的潜力很大。

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.