New Faster and Simpler Way to Map Out the Structure of Small Molecules

Scientists from two California universities have achieved a breakthrough in finding an easier method for understanding the structure of small molecules.

The task in organic chemistry is to constantly devise ways to observe interconnected tiny structures that serve as the building blocks for practically everything around us, and it can be useful for everything from to improving water purification systems to mapping out the smallest components of delicate structures like orchids

Now, there is a breakthrough study from researchers from Caltech and UCLA which offers a fresh and innovative approach to quickly and efficiently assessing the structure and nature of small molecules. The method shaves hours--and potentially days--off the normal process: they have evolved a method that can be carried out in as short as 30 minutes. 

To achieve the startling results, the researchers used a technique called micro-electron diffraction (MicroED), which involves 3D diffraction of microscopic crystals with the help of an electronic microscope. For collecting data, continuously rotating nanocrystals have electrons hurled at them.

Below is a video that illustrates the process:

Caltech Chemistry Professor Brian Stoltz, who was also co-author on the study, explained how the strength of the method is that it doesn't rely on the quality or preparation time of the samples.  "We took the lowest-brow samples you can get and obtained the highest-quality structures in barely any time," adding, optimistically, "When I first saw the results, my jaw hit the floor." 

Expanding the Capabilities of MicroED

Tamir Gonen, UCLA Biological Chemistry and Physiology Professor, and study co-author, participated in an earlier study from two years before which outlined the details of the cryo-electron microscopy (CryoEM) method of MicroED. Where his research fell short, however, was in using the technique mostly on crystallized proteins, but thanks to the partnership with the other scientists, new research options were explored.

New Faster and Simpler Way to Map Out the Structure of Small Molecules

After this, it became clear that the team "didn't have to grow crystals, and that's around the time that [we] started to realize that we could apply this method to a whole new class of molecules with wide-reaching implications for all types of chemistry," explains Hosea Nelson, UCLA Assistant Professor of Chemistry and Biochemistry, who also took part in the study. 


Results Beyond the Scientists' Expectations

Stoltz was unrestrained in describing the enormous impact of the surprising outcome: "This is like science fiction. I didn't think this would happen in my lifetime—that you could see structures from powders." This study is a good example of what happens when scientists, operating on a hunch, decided to revisit existing methods and theories. In this case, their instincts really paid off.


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Chemists everywhere--both now and in the future--stand to benefit from this simple, straightforward and highly effective approach. Robert Grubbs, Caltech Chemistry Professor, sums it up best:

"The last big break in structure determination before this was nuclear magnetic resonance spectroscopy, which was introduced by Jack Roberts at Caltech in the late '60s."

Details about the study appear in a paper, titled "The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination", which was published November 8th in the ACS Central Science journal. 

Via: Caltech