UCLA researchers in the Department of Chemistry and Biochemistry in collaboration with Caltech have developed a novel microcrystal electron diffraction (MicroED) system to unambiguously identify components of complex compound mixtures: delivering rapid, high-resolution atomic structures with minimal sample preparation or formal crystallization procedures.
BACKGROUND: Characterization of individual compounds within complex mixtures is a significant challenge in chemical and biological sciences, and the unambiguous identification of small molecules is one of the most important and challenging subjects. While there exists many solution-state characterization techniques like Nuclear Magnetic Resonance Spectroscopy (NMR), Liquid Chromatography tandem Mass Spectrometry (LC-MS), or Gas Chromatography tandem Mass Spectrometry (GC-MS), many of these methods have severe limitations (e.g., NMR-silent nuclei, or the method being destructive to the target sample). Instead, solid state analysis often conducted through crystallography remains an attractive method for identifying the underlying chemical structure of materials. Crystallography originated with studies made possible by X-rays, but severe limitations like sufficient crystal size (~ 0.1 mm3), often reduce the practicality of the technique. As an alternative, modern crystallographers make use of techniques like electron crystallography, that circumvents the need for large crystals. Unfortunately, electron crystallography techniques like microcrystal electron diffraction (MicroED) were developed for protein structures from frozen-hydrated crystals. This technique could be highly useful in the fields that produce low masses of product that are not amenable to the crystallization procedure needed for conventional X-ray crystallography.
INNOVATION: UCLA researchers in the Department of Chemistry and Biochemistry in collaboration with
Caltech have developed a novel electron cryo-microscopy (cryoEM) microcrystal electron diffraction (MicroED) system to unambiguously identify components of complex compound mixtures: delivering rapid,
high-resolution atomic structures with minimal sample preparation or formal crystallization procedures. From simple powders, with minimal sample preparation, high-quality MicroED data can be acquired from nanocrystals (~100 nm, ~10-15 g) resulting in atomic resolution (<1 Å) crystal structures in minutes. Moreover, the system is compatible with commercially available microscopes found in common research facilities. The researchers showed high practicality in adoption of the technique by applying its use in the determination of atomic resolution on samples that had not undergone formal crystallization and were isolated from simple purification techniques like flash chromatography. The proposed framework for atomic resolution determination is highly amenable to any research laboratory, and could be particularly helpful in fields like synthetic chemistry, natural product chemistry, and drug discovery.
POTENTIAL APPLICATIONS:
• Synthetic chemistry
• Nature product chemistry
• Drug discovery
ADVANTAGES:
• High efficiency
• Simple sample preparation
• Atomic resolution
• Compatible with commercial microscopes
DEVELOPMENT-TO-DATE:
Demonstrated with a variety of materials including small molecules, reactive organometallic species and other crude mixtures of natural or synthetic chemical compounds.
Related Papers
Jones, Christopher G., et al. "Characterization of reactive organometallic species via MicroED." ACS central science 5.9 (2019): 1507-1513.