Journal
ACS CENTRAL SCIENCE
Volume 4, Issue 11, Pages 1587-1592Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acscentsci.8b00760
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Funding
- National Science Foundation [DGE-1650604]
- NIH-NIGMS [R35 GM128936, R01GM080269, R35GM128867]
- DOE [DE-FC02-02ER63421]
- Packard Foundation
- Sloan Foundation
- Pew Charitable Trusts
- Howard Hughes Medical Institute
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In the many scientific endeavors that are driven by organic chemistry, unambiguous identification of small molecules is of paramount importance. Over the past 50 years, NMR and other powerful spectroscopic techniques have been developed to address this challenge. While almost all of these techniques rely on inference of connectivity, the unambiguous determination of a small molecule's structure requires X-ray and/or neutron diffraction studies. In practice, however, X-ray crystallography is rarely applied in routine organic chemistry due to intrinsic limitations of both the analytes and the technique. Here we report the use of the electron cryo-microscopy (cryoEM) method microcrystal electron diffraction (MicroED) to provide routine and unambiguous structural determination of small organic molecules. From simple powders, with minimal sample preparation, we could collect high-quality MicroED data from nanocrystals (similar to 100 nm, similar to 10(-15) g) resulting in atomic resolution (<1 angstrom) crystal structures in minutes.
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