This is a research instrumentation proposal that requests funding for a Bruker X8 Prospector Ultra Single Crystal X-ray Diffractometer. The diffractometer will be integrated into the existing Chemistry Department Core X-ray Diffraction Facility, which is in turn is part of a larger Small Molecule Characterization Core. The instrument will be shared by a group of seven major users with NIH funding (Curran (PI), Brummond, Floreancig, Koide, Nelson, Wilcox, Wipf) and three minor users. It will be used primarily to solve the crystal structures of small and medium-sized organic molecules and biomolecules. The instrument will be operated by a full time Director of Crystallography with over two decades of experience, and will provide services to about 80 students and postdoctoral fellows on NIH-supported projects. The new diffractometer with a modern copper X-ray source will complement an aging but still useful diffractometer with conventional sealed tube Mo K? radiation. The new diffractometer will expedite the research of these groups by providing structures from smaller crystals (a critical current need), by providing rapid turn around time on synthetic intermediates, and by solving absolute configurations of samples without heavy atoms. This is a crucial support instrument for research in medicinal chemistry, diversity-oriented synthesis, library synthesis, synthetic methodology, catalysis development, sensor synthesis, natural products synthesis, and synthesis of peptides and oligosaccharides. Biomedical themes are replete and include drug discovery, biological probe discovery, new methods for drug synthesis, analysis of biological milieu, and understanding and imitation of important biomolecules. PUBLIC HEALTH RELEVANCE: This is a research instrumentation proposal that requests funding for a Bruker X8 Prospector Ultra Single Crystal X-ray Diffractometer. The instrument will be shared by a group of seven major users (all NIH funded) and three minor users primarily to solve the crystal structures of small and medium-sized organic molecules. This is a crucial support instrument for research in medicinal chemistry, diversity-oriented synthesis, library synthesis, synthetic methodology, sensor synthesis, natural products synthesis, and synthesis of peptides and oligosaccharides. Biomedical themes are replete and include drug discovery, biological probe discovery, new methods for drug synthesis, analysis of biological milieu, and understanding and imitation of important biomolecules.