Single Crystal X-ray Diffractometer with Microfocus Rotating Anode Source (Cu)

项目概要/摘要 该提案要求支持购置一台新的X射线衍射仪， 约翰霍普金斯大学（JHU）化学系。请求的仪器是理学仪器 XtaLAB Synergy-R系统配备高通量旋转阳极X射线源和混合光子 计数探测器。该仪器将大大提高基础研究的能力， 提案中确定的19个主要和次要用户，涉及化学、生物物理学、 材料科学、化学和生物分子工程。取得了重大 X射线衍射仪技术的进步，因为先前收购（2012年）的电流 衍射仪安置在化学在JHU，这些进步允许一个重大的飞跃， 具有挑战性的晶体材料的表征。这样的材料是：（i）不 结晶良好和/或仅以非常小的晶体尺寸（例如10-40 μm）生长，（ii）高值 化学靶分子（例如，中间物种，新型金属有机骨架，超分子 组件），其由于差的长程有序而具有有限的衍射能力，和/或包含大的 量的溶剂包合物，和（iii）具有相对长的晶胞尺寸（> 150 μ m）的蛋白质。这些 材料将是非常困难的，或不可能的，以目前的仪器表征， JHU。拟议的仪器将改变NIH资助的主要用户Goldberg，Karlin， 和Garcia-Bosch通过提供化合物的分子结构，所述化合物是亚稳定的并且只能是 在非常小尺寸的晶体中分离和/或弱衍射;以及主要用户Huang的 表征金属蛋白的催化功能。结构上的主客体相互作用 在骨架材料（例如金属有机和共价有机骨架（MOFs，COFs））中， 主要用户Thoi的研究，但这些晶体的脆性，多孔性和小尺寸的单晶 框架通常使结构表征成为不可能。理学XtaLAB Synergy- R衍射仪应能克服这些障碍，并能检查主客体关系， 单晶到单晶的转变，以及MOF/COF中化学机制的快照 材料.建议的衍射仪的功率也将允许主要用户加西亚-莫雷诺检查 蛋白质的结构-能量关系，特别是pH敏感性。此类研究 在癌症生物学中很重要，因为癌性实体瘤的标志之一是pH失调， 而获得的基本结构知识可以用来提高 蛋白质疗法总的来说，获得拟议的仪器将大大加强研究 主要和次要用户提供的能力，以获得详细的结构信息， 分子和大的生物分子，这将是不可能的，以目前的仪器表征。

Project Summary / Abstract This proposal requests support for the acquisition of a new X-ray diffractometer to be housed in the Chemistry Department at Johns Hopkins University (JHU). The requested instrument is a Rigaku XtaLAB Synergy-R system equipped with a high-flux rotating anode X-ray source and a Hybrid Photon Counting detector. This instrument will dramatically advance the capabilities in fundamental research of 19 Major and Minor Users identified in the proposal, involving investigators from chemistry, biophysics, materials science, and chemical and biomolecular engineering. There have been significant advancements in X-ray diffractometer technology since the prior acquisition (2012) of the current diffractometer housed in Chemistry at JHU, and these advances allow for a major leap forward in the characterization of challenging crystalline materials. Such materials are: (i) compounds that do not crystallize well and/or grow with only very small crystal dimensions (e.g. 10-40 µm), (ii) high value chemical target molecules (e.g., intermediate species, novel metal-organic frameworks, supramolecular assemblies) that have limiting diffraction power due to poor long-range order, and/or contain large amounts of solvent inclusion, and (iii) proteins with relatively long unit cell dimensions (> 150 Å). These materials would be extremely difficult, or impossible, to characterize with the current instrumentation at JHU. The proposed instrument will transform the NIH-funded research of Major Users Goldberg, Karlin, and Garcia-Bosch by providing molecular structures of compounds that are meta-stable and can only be isolated in crystals of very small dimensions and/or are weakly diffracting; and of Major User Huang by characterizing metalloproteins for catalytic functions. The delineation of structural, host-guest interactions in framework materials (e.g. metal-organic and covalent organic frameworks (MOFs, COFs)) is critical to the research of Major User Thoi, but the fragility, porosity, and small size of single crystals of these frameworks often makes structural characterization impossible. The proposed Rigaku XtaLAB Synergy- R diffractometer should overcome these barriers and enable the examination of host-guest relationships, single-crystal-to-single-crystal transformations, and snapshots of chemical mechanism in MOF/COF materials. The power of the proposed diffractometer will also allow Major User García-Moreno to examine structure-energy relationships in proteins, especially with regards to pH sensitivity. Such studies are important in cancer biology, as one of the hallmarks of cancerous solid tumors is dysregulation of pH, and the fundamental structural knowledge to be gained can be harnessed to increase the specificity of protein therapeutics. Overall, the acquisition of the proposed instrument will greatly enhance the research of Major and Minor users by providing the ability to obtain detailed structural information on small molecules and large biomolecules that would be impossible to characterize with current instrumentation.