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

By Christopher G. Jones, M. Martynowycz, Johan Hattne, Tyler J Fulton, B. Stoltz, José A. Rodríguez, H. Nelson, Tamir Gonen. 2018

328 citations recorded by the source corpus.

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.

Subfields: Radiation, Structural Biology, Surfaces, Coatings and Films

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The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Structural Biology

1. Bridget O. Carragher
2. Anchi Cheng
3. Clinton S. Potter
4. Sjors H. W. Scheres

In Surfaces, Coatings and Films

1. Bridget O. Carragher
2. Anchi Cheng
3. Clinton S. Potter

Citations in the corpus

• Leginon: New features and applications (2020, methodology): “The method has been developed over several years for protein crystals(19) but recently gained attention when it was demonstrated that the method could also be applied to small organic crystals, to produce data at sub-Angstrom resolution which can be phased using ab initio methods.(20,21) This applic”
• Artificial Intelligence For Natural Product Drug Discovery (2023, background): “Recently, the microcrystal electron diffraction (MicroED) technique, which has the potential to accelerate structure elucidation by allowing analysis of submicron-sized crystals of chemical compounds, was added to this arsenal 39,40 .”