CAREER: Developing Accurate Crystallography Without Diffraction

化学部的化学测量和成像项目将通过该奖项资助中佛罗里达大学的James Harper博士，以扩展理论方法的能力，以准确预测晶体结构。目前，许多化合物甚至整类化合物都不适合用传统的晶体学方法进行分析。该项目将晶格预测方法与实验核磁共振数据相结合，提供了能够解决目前难以解决的结构问题的新方法。这一结果将通过提高表征一系列新材料的能力来影响社会。例如，自1955年以来，已有近60种头孢菌素类抗生素被描述，但超过93%的结构从未被晶体学表征过。该项目的重点是表征关键的头孢菌素以及其他具有挑战性的材料。本项目旨在通过将实验固体核磁共振数据纳入预测过程，改进晶体结构的理论预测。核磁共振数据用于在预测过程之前识别单个高概率构象。由于许多晶格预测程序对刚性结构具有鲁棒性和准确性，但受到灵活性的挑战，因此核磁共振数据通过限制搜索的构象空间来改进预测。实验核磁共振测量主要集中在13C和15N的化学位移张量，因为这些数据为每个分子位置提供了三个可测量的参数。原子位置的不确定性通过分子动力学过程提供，最终创建适合存入晶体学数据库的结构。这项工作的更广泛的影响包括培训来自主要本科机构（华盛顿和杰斐逊学院）的学生参加每年为期三周的核磁共振课程，涉及6-8名学生，创建一系列描述核磁共振基本概念和更专业的张量测量方法的开放课程，并通过实验室参观和志愿教学荣誉徽章课程扩展到佛罗里达州中部的童子军社区。

With this award, the Chemical Measurements and Imaging Program of the Chemistry Division is funding Dr. James Harper of the University of Central Florida to extend the capability of theoretical methods to accurately predict crystal structures. Presently, many compounds and even entire classes of compounds are unsuitable for analysis by conventional crystallography methods. This project combines lattice prediction methods with experimental NMR data to provide new methodology capable of solving structural problems that are now intractable. This outcome will impact society by improving the ability to characterize a host of new materials. For example, nearly 60 cephalosporin antibiotics have been described since 1955, yet over 93% in the structures have never been characterized crystallographically. The project focuses on characterizing key cephalosporins as well as other challenging materials.This project focuses on improving the theoretical prediction of crystal structure by including experimental solid-state NMR data in the prediction process. The NMR data serve to identify a single high-probability conformation before the prediction process. Because many lattice prediction programs robustly and accurately treat rigid structures but are challenged by flexibility, the NMR data improves prediction by limiting the conformational space searched. The experimental NMR measurements focus primarily on 13C and 15N chemical shift tensors because such data provide three measurable parameters for each molecular position. Uncertainties in atomic positions are provided through a molecular dynamics process, to ultimately create structures suitable for deposit into crystallographic databases. The broader impact of this work includes training students from a primarily undergraduate institution (Washington and Jefferson College) in an annual three week NMR course involving 6-8 students, the creation of a series of Open Courseware lectures describing basic NMR concepts and the more specialized tensor measurement methods, and outreach into the scouting community of central Florida through lab tours and voluntary teaching of merit badge courses.