The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination

Tech ID: 30373 / UC Case 2019-360-0


UCLA researchers in the Department of Chemistry and Biochemistry have developed a novel use of the cryogenic electron microscopy (CryoEM) method electron micro-diffraction (MicroED) to provide routine and unambiguous structural determination of small organic molecules.


Nuclear magnetic resonance (NMR) spectroscopy has been a mainstay in chemistry and the most predominant method employed in both routine synthetic chemistry experiments and in advanced structural elucidation of complex small molecules. Single crystal X-ray diffraction produces unequivocal structural information about the position, orientation, connectivity, and placement of individual atoms and bonds within a given molecule. However, the use of X-ray diffraction is largely limited by the difficulty to produce high quality crystals amenable for X-ray diffraction. For this reason, X-ray diffraction has not been routinely used by most practicing organic chemists, despite that the structural data provided is superior to any other methods.


Researchers at UCLA have developed a cryogenic electron microscopy (CryoEM)-based electron micro-diffraction (MicroED) method to address the need for fast and reliable structure determination in organic chemistry. They have demonstrated that with minimal sample preparation and experiment time, simple powders and amorphous materials could be directly used in MicroED studies, rapidly leading to high quality molecular structures at atomic resolution (<1 Angstrom).


  • Small molecule structure determination at atomic resolution


  • Faster and simper preparation to acquire crystals 
  • High quality atomic resolution structures of complex, small molecules

State Of Development

The described method has been experimentally validated.

Related Materials

  • Jones, C.G., Martynowycz, M.W., Hattne, J., Fulton, T.J., Stoltz, B.M., Rodriguez, J.A., Nelson, H.M. and Gonen, T., 2018. The cryoEM method MicroED as a powerful tool for small molecule structure determination. ACS central science, 4(11), pp.1587-1592.


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  • Nelson, Hosea

Other Information


Cryogenic electron microscopy, CryoEM, electron micro-diffraction, MicroED, structure determination, small molecule

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