Illinois research team accelerates imaging techniques for capturing small molecules' structures
Pinshane Huang, far left, joins, Priti Kharel, second from left, Justin Bae and Patrick Carmichael, far right, at the Materials Research Laboratory. Pictured on the tablet is Blanka Janicek. Credit: Heather Coit/The Grainger College of Engineering

A University of Illinois research effort led by Pinshane Huang is making it easier to see small molecule structures clearly. Their discovery has the potential to improve everyday life applications.

The Department of Materials Science and Engineering associate professor has collaborated with two other people to prove the methodology for a project.

There are additional co- authors, including graduate student Sang hyun Bae. Their research was published in a journal.

The team's efforts expose the molecule's atomic structure allows researchers to understand how it reacts, learn its chemical processes and see how to synthesise its chemical compounds.

The structure of a molecule is so important. We made it possible to see that structure directly.

The structure of a small molecule is important. The example of thalidomide given by Kharel shows how important it is.

Thalidomide was prescribed to pregnant women in the 1960's to treat morning sickness, but it was later found to cause birth defects and even death.

Why did it go wrong? The drug caused devastating effects to the fetus when it was used to treat morning sickness.

The research effort that began with sheer curiosity has been encouraged by the need for proactive science.

It's important to accurately determine the structures of the molecule.

Nuclear magnetic resonance or X-ray Diffraction are used to determine the structure of the molecule. Scientists don't have a good understanding of a molecule's makeup because of incorrect structures produced by indirect methods. Direct image methods could be used to eliminate the ambiguity around small molecule structures.

The last decade has seen significant improvements in the use of electron microscopes.

I wanted to know what was keeping them from doing the same thing for small Molecules. The man said, "Huh?" You might be able to figure out how to synthesise a natural compound if we could do that. "Like a great disease-fighter, this could turn out to be really important."

The challenge is that their structures are hard to detect because they are so small.

The students decided to use existing large molecule methodology as a starting point for developing techniques to make small molecule structures appear.

Small Molecules are easily overwhelmed by their surroundings. The team came up with a plan to keep the small molecule's structures intact instead of using ice.

Illinois research team accelerates imaging techniques for capturing small molecules' structures
Pinshane Huang and her researchers discovered how to view structures in molecules, which opens a whole new realm of scientific possibilities. Credit: Heather Coit/The Grainger College of Engineering

How can you make a molecule behave in a certain way? Graphene can be used by using it.

Graphene is a single layer of carbon atoms that form a honeycomb lattice.

The Illinois researchers had to manage more than stabilizing the small molecule's environment. The team had to limit the number of elections it used to illuminate the molecule to less than one million.

The researchers use low doses of electrons to make the molecule move.

The molecule doesn't like to be bombarded by higher-energy elections, but we need to do that to be able to see the structure, and Graphene helps diminish some of that charge away from the molecule so that we can actually get a nice picture.

The molecule were almost invisible in the picture.

When a low-dose image is taken, it looks like nothing at all.

To see the spatial frequencies of the atomic structures, the trick was to use a Fourier transform.

We took hundreds of thousands of images and added them together to create a clear image.

The team was able to create images of the atoms without damaging their integrity.

"Month after month, week after week, our resolution got better," he said. One day, my students came in and showed me the individual carbon atoms. They have gained a lot of knowledge about how to design an experiment and how to get data out of it.

This discovery is paving the way for many more discoveries.

There are a lot of small molecule that have been left out in the cold. We want to shine a light on how we get there. How do we make something that is so difficult for us? The man said, "Huh?" It will not be one day, that's the hope.

The first step is turning that dream into reality.

The way we solve the structure of a small molecule will be one day. The molecule will be thrown into the electron microscope and taken a picture.

The Illinois team was inspired by that dream.

"That is potentially life-changing, and we have made it exist," he said. We haven't made it easy, but this will change a lot of science.

More information: Priti Kharel et al, Atomic-Resolution Imaging of Small Organic Molecules on Graphene, Nano Letters (2022). DOI: 10.1021/acs.nanolett.2c00213 Journal information: Nano Letters