Oak Ridge National Laboratory Supercomputers


image: The asymmetric nucleus of the catalyst molecule (colored atoms in the center) and a molecule placed on the catalyst (gray).
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Credit: Dmytro Bykov, ORNL

In October, a scientist whose research was supported by modeling and simulation efforts on supercomputers at the US Department of Energy’s (DOE) Oak Ridge National Laboratory (ORNL) shared the 2021 Nobel Prize in Chemistry .

The award-winning duo, Benjamin List of Max-Planck-Institut für Kohlenforschung and David MacMillan of Princeton University, have developed a new, highly selective way of constructing chiral molecules, molecules that mirror each other. others. This was achieved through asymmetric organocatalysis, a process in which an organic molecule serves as a catalyst that results in chemical transformation into a desired product.

Typically, the synthesis of catalysts is tedious experimental work. This requires careful planning and a working hypothesis of the reaction mechanism to refine the activity of the catalyst. However, the process is much more complex in real life than it is on paper as the details of the reaction mechanism are not known.

The team led by List at the Max-Planck-Institut needed a computer modeling of the phenomenon to augment their ongoing physical experiments in the laboratory. This is where the Oak Ridge Leadership Computing Facility (OLCF) and Dmytro Bykov, a computer scientist at ORNL, came in. Bykov used the 200 petaflop Summit, OCLF’s flagship supercomputer, to simulate the team’s new catalysts turning molecules into specific end products. The modeling helped the team determine if the new catalysts would be effective.

“With Summit, I could build a molecule, optimize it, and converge to a stable conformation,” Bykov said. “Then I could take a molecule that the team had in its reaction, put it in that catalyst, and see how it broke through that barrier in my simulation. “

The team specifically studied the role of catalysts in the conversion of inert molecules called olefins. Olefins are among the most abundant chemical compounds in nature and are generally obtained from crude oil. They are of interest in biochemistry because they are ideal for use as precursors of drug compounds and other chemicals.

Catalysts work by lowering the energy barriers of a chemical transformation and thereby directing a molecule to particular products. However, the products can be chiral, which means that they share the same composition and similar structure but are reversed left or right of each other. Catalysts can force molecules to adopt a left or right conformation, and these different positions can have completely different effects, for example in a human body.

“In a pairing, the molecule on the left can be a drug, and the right molecule can even be a poison in some extreme examples,” Bykov said. “For this reason, it is important to synthesize them in a specific direction. “

Without the right catalysts, scientists could end up with a mix of left and right molecules that could have deleterious effects. Organocatalysis offers a way around this problem.

“The team had theorized the most promising catalysis candidates, but needed details of the reaction mechanisms that are difficult to determine in the laboratory,” Bykov said. “For example, computer modeling can find structures of transition states, reaction barriers and alternative pathways and ultimately shed light on the nature of substrate activation.”

Bykov’s simulations gave the team a way to figure out how to stress a molecule in a specific way to bring it closer to the desired product.

“In one experiment, the initial assumption may not work, and you may end up with something that you think should be responsive, but it doesn’t,” said Bykov. “Computer modeling can help guide experimental efforts so that we can synthesize these new and important organic catalysts in a more predictive and rational way.”

The OLCF is a user facility of the DOE Office of Science located at ORNL.

Associated publication: Nobuya Tsuji, Jennifer L. Kennemur, Thomas Buyck, Sunggi Lee, Sébastien Prévost, Philip SJ Kaib, Dmytro Bykov, Christophe Farès and Benjamin List, “Activation of Olefins via Asymmetric Brønsted Acid Catalysis” Science 359, no. 6383 (2018): 1501–05, doi: 10.1126 / science.aaq0445.


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