The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination
Abstract
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 (~100 nm, ~10–15 g) resulting in atomic resolution (<1 Å) crystal structures in minutes.
- Authors:
-
[1];
- The Warren and Katharine Schlinger Laboratory of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States
- Publication Date:
- Research Org.:
- Univ. of California, Los Angeles, CA (United States); California Institute of Technology (CalTech), Pasadena, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF); National Inst. of Health (NIH) (United States)
- OSTI Identifier:
- 1480568
- Alternate Identifier(s):
- OSTI ID: 1508759
- Grant/Contract Number:
- FC02-02ER63421; DGE-1650604; R01GM080269; R35GM128867; R35 GM128936
- Resource Type:
- Published Article
- Journal Name:
- ACS Central Science
- Additional Journal Information:
- Journal Name: ACS Central Science Journal Volume: 4 Journal Issue: 11; Journal ID: ISSN 2374-7943
- Publisher:
- American Chemical Society
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Jones, Christopher G., Martynowycz, Michael W., Hattne, Johan, Fulton, Tyler J., Stoltz, Brian M., Rodriguez, Jose A., Nelson, Hosea M., and Gonen, Tamir. The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination. United States: N. p., 2018.
Web. doi:10.1021/acscentsci.8b00760.
Jones, Christopher G., Martynowycz, Michael W., Hattne, Johan, Fulton, Tyler J., Stoltz, Brian M., Rodriguez, Jose A., Nelson, Hosea M., & Gonen, Tamir. The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination. United States. https://doi.org/10.1021/acscentsci.8b00760
Jones, Christopher G., Martynowycz, Michael W., Hattne, Johan, Fulton, Tyler J., Stoltz, Brian M., Rodriguez, Jose A., Nelson, Hosea M., and Gonen, Tamir. Fri .
"The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination". United States. https://doi.org/10.1021/acscentsci.8b00760.
@article{osti_1480568,
title = {The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination},
author = {Jones, Christopher G. and Martynowycz, Michael W. and Hattne, Johan and Fulton, Tyler J. and Stoltz, Brian M. and Rodriguez, Jose A. and Nelson, Hosea M. and Gonen, Tamir},
abstractNote = {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 (~100 nm, ~10–15 g) resulting in atomic resolution (<1 Å) crystal structures in minutes.},
doi = {10.1021/acscentsci.8b00760},
journal = {ACS Central Science},
number = 11,
volume = 4,
place = {United States},
year = {Fri Nov 02 00:00:00 EDT 2018},
month = {Fri Nov 02 00:00:00 EDT 2018}
}
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https://doi.org/10.1021/acscentsci.8b00760
https://doi.org/10.1021/acscentsci.8b00760
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Cited by: 204 works
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Figures / Tables:
Figure 1: Process of applying MicroED to small molecule structural analysis. Here commercial progesterone (1) was analyzed, and an atomic resolution structure was determined at 1 Å resolution. Grid holes are 1 μm in diameter.
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Works referencing / citing this record:
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