Understanding the mechanisms underlying chemical reactions is fundamental to many areas of science, from drug discovery to climate research. When chemists combine molecules to form new products, they are often unsure of the details of short-lived molecules that exist during this transition.
But this unseen interplay of atoms governs the why and how of chemical reactions. Harnessing computer simulations to unravel these molecular intricacies promises to advance both knowledge and technology.
Now, researchers at the Chemistry Department and Pritzker School of Molecular Engineering (PME) at the University of Chicago have developed a computational approach to accurately describe these states for many chemical reactions.
“The Holy Grail of our field is to be able to completely predict products of a chemical reaction given a set of conditions, but that task is so complex that you need to understand every detail of a reaction to be accurate,” said Daniel King, graduate student and first co-author of the new work. “I think our new approach moves the field much closer to being able to do this.”
A New Tool
When carrying out a reaction that turns chemical A into chemical B, chemists have a pretty good idea of what the transition state looks like at a chemical level—generally a mixture of A and B. But describing the behavior of the electrons in these states—their “electronic structure”—is much more difficult.
Traditionally, the electrons in these systems have been calculated using density functional theory (DFT), a framework to describe the behavior of electrons in a system. However, DFT simplifies transition states, assuming just one configuration of electrons when there are likely many.
“It can be very hard to get a complete description of transition states using DFT,” said Jacob Wardzala, a graduate student and co-first author of the work.
The new approach developed by King, Wardzala, and coworkers solves this problem by describing the many ways in which electrons can be arranged when forming and breaking bonds, allowing these states to be characterized much more accurately.
“Quantum chemistry has witnessed remarkable strides over the past sixty years. However, accurately and affordably describing various chemical reactions, encompassing radical species and transition states, has remained a formidable challenge. Our novel method marks a significant leap forward in addressing this complexity. Its implementation promises to streamline and automate computations of chemical reactions. We have enjoyed working on this project in collaboration with Lawal Ogunfowora and Brett Savoie at Purdue University,” says senior author Laura Gagliardi, the Richard and Kathy Leventhal Professor of Chemistry and Molecular Engineering.
While these methods have been used in the past to describe reactions in an academic context, the new approach makes them scalable and robust for climate and industrial applications. So far, this new approach has been applied only to organic reactions, but the researchers plan to move toward using it to describe complex transition metal-based reactions critical to industrial synthesis.
The new tool is available publicly in a package called PySCF.
Citation: “Organic Reactivity Made Easy and Accurate with Automated Multireference Calculations,” Wardzala et al., ACS Central Science, March 27, 2024. DOI: 10.1021/acscentsci.3c01559
Funding: This work was supported by the National Science Foundation and the Office of Naval Research.