Project Summary/Abstract The University of Utah Departments of Biochemistry and Chemistry are proposing to acquire a new Rigaku XtalLab Synergy-DW single crystal X-ray diffractometer (scXRD) equipped with a high brilliance, dual wavelength (Cu and Mo Kα) micro-focus rotating anode X-ray source; hybrid photon counting detector with an ultra-wide dynamic range; X-ray beam optics optimized for dual wavelength with fully adjustable divergence slit controls; 4-circle Kappa goniometer; and a modern electronically controlled cabinet with sample lighting, high-resolution crystal video imaging, and ergonomic accessibility to crystal mounting and recovery. The requested system will replace aging instrumentation in both of these departments that are routinely utilized by a large number of NIH- funded investigators, but where the entire system or key components no longer have vendor support and are experiencing increasing maintenance challenges. Further, the shared X-ray instrumentation upgrade needs within these two departments has provided the impetus for developing a new University of Utah X-ray Crystallography Core Facility, where the proposed scXRD system would serve as the centerpiece. Thus, the overall goal of this proposal is to update and replace aging scXRD instrumentation, while simultaneously ensuring continued NIH funded investigator accessibility to in-house state-of-the-art X-ray resources, as well as reducing redundancy by consolidating instrumentation and core facility resources. In particular, the proposed dual Cu and Mo Kα wavelength rotating anode X-ray source will afford structure/function analyses for diverse chemical and biological processes including novel chemical compounds for therapeutic development, transition- metal mediated small molecule activation, supra molecular chemistry via self-assembly, cellular oxidation of nucleic acids, transcriptional regulation, cell division and proliferation, and viral replication. Pairing of this X-ray source with vendor specific optics assembly and extremely sensitive hybrid photon counting detector with small pixel size will greatly enhance research capabilities in multiple profound ways. Specifically, for groups focused on characterization of small molecules, the proposed scXRD features will afford analysis of small weakly diffracting crystals and determination of absolute stereochemical configuration, capabilities not currently available. Analogously, for characterization of macromolecular systems, features of this high-performance instrumentation, including the capacity to vary beam divergence, will afford acquisition of high-quality data sets from small crystals, including those with large unit cells. In addition, the ability of the requested system to collect sulfur-SAD data will facilitate determination of novel structures without the preparation of heavy atom derivatives or the incorporation of selenomethione, which can be problematic for many especially valuable targets. In short, acqui...