CAREER: Developing accurate crystallography without diffraction

有了这个奖项，化学部的化学测量和成像计划正在资助中央佛罗里达大学的詹姆斯哈珀博士，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，甚至整个类别的化合物是不适合通过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NMR数据相结合，以提供能够解决现在难以解决的结构问题的新方法。 这一成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，已经描述了近60种头孢菌素抗生素，但超过93%的结构从未被晶体学表征。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。该项目的重点是通过在预测过程中包括实验固态NMR数据来改进晶体结构的理论预测。 NMR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稳健且准确地处理刚性结构，但受到灵活性的挑战，因此NMR数据通过限制搜索的构象空间来改进预测。 实验NMR测量主要集中在13 C和15 N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。 通过分子动力学过程提供原子位置的不对称性，以最终产生适合于存款到晶体学数据库中的结构。 这项工作的更广泛的影响，包括培训学生从一个主要的本科院校（华盛顿和杰斐逊学院）在每年三个星期的NMR课程涉及6-8名学生，创建一系列的开放式课程讲座，描述基本的NMR概念和更专业的张量测量方法，并推广到中央佛罗里达通过实验室图尔斯和志愿教学的优秀徽章课程的童子军社区。

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.