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

项目摘要/摘要 这项提议要求支助购置一台新的X射线衍射仪，安装在 约翰霍普金斯大学(JHU)化学系。请求的乐器是Rigaku 配备高通量旋转阳极X射线源和混合光子的XtaLAB Synergy-R系统 计数检测器。这台仪器将极大地提高在基础研究方面的能力 提案中确定的19个主要用户和次要用户，涉及来自化学、生物物理、 材料科学、化学和生物分子工程。已经有了重大的 自上一次(2012)收购Current以来，X射线衍射仪技术的进步 衍射仪被安置在JHU的化学中，这些进步允许在 具有挑战性的晶体材料的表征。这类材料是：(I)不 结晶良好和/或仅用非常小的晶体尺寸(例如10-40微米)生长，(Ii)高价值 化学目标分子(如中间体、新型金属有机骨架、超分子 组件)，其由于较差的长程有序而具有有限的衍射率，和/或包含大量 溶剂包裹量；和(Iii)具有相对较长单位晶胞尺寸的蛋白质(&gt；150？)。这些 材料将非常困难，或不可能用目前的仪器来表征 JHU。拟议的仪器将改变NIH资助的主要用户Goldberg，Karlin， 和Garcia-Bosch，通过提供亚稳定的化合物的分子结构 隔离在尺寸很小和/或衍射很弱的晶体中；主要用户黄通过 表征金属蛋白的催化功能。描述结构性的主-客互动 在骨架材料中(例如，金属-有机和共价有机骨架(MOF、COF))对 主要用户THOI的研究，但这些单晶的脆性、多孔性和小尺寸 框架通常使结构表征变得不可能。建议的Rigaku XtaLab协同- R衍射仪应克服这些障碍，并能够检查主-客关系， MOF/COF中单晶到单晶的转变和化学机制的快照 材料。拟议的衍射仪的能力还将允许主要用户加西亚-莫雷诺检查 蛋白质中的结构-能量关系，特别是在pH敏感性方面。这类研究是 在癌症生物学中很重要，因为癌症实体肿瘤的标志之一是pH调节失调， 而要获得的基本结构知识可以被利用来增加 蛋白质疗法。总体而言，收购拟议的仪器将极大地加强研究 通过提供获取有关小用户的详细结构信息的能力，来管理主要用户和次要用户 分子和大的生物分子，用目前的仪器是不可能表征的。

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.