Scientists at the US Department of Energy’s Brookhaven National Laboratory helped measure how unpaired electrons in atoms at one end of a molecule can drive a chemical reaction on the opposite side of the molecule. As shown in a recently published paper in Journal of the American Chemical SocietyThis work, in collaboration with Princeton University, shows how molecules containing these so-called free radicals can be used in a whole new class of reactions.
“Most reactions involving free radicals occur in the unpaired electron site,” explained Matthew Beard, a chemist at Brookhaven Lab, one of the paper’s co-authors. The Princeton team has become experts at using free radicals for a range of synthetic applications, such as polymer recycling. But they wondered if free radicals might affect the reaction in other parts of the molecule as well, by pulling electrons away from those more distant sites.
“Our measurements show that these radical radicals can exert strong ‘electron withdrawal’ effects that make other parts of the molecule more reactive,” Beard said.
The Princeton University team has shown how such long-distance drag can overcome energy barriers and aggregate non-reactive molecules, which could lead to a new approach for the synthesis of organic molecules.
The research drew on the shared resources of the Princeton-led Department of Energy’s (DOE) Frontier Energy Research Center focused on light-inspired biochemistry (BioLEC). This collaboration brings together pioneers in synthetic chemistry with groups that have advanced spectroscopy techniques to study reactions. Its financing was recently renewed for another four years.
Robert Knowles, who led the Princeton role on this research, said, “This project is an example of how BioLEC’s combined expertise enabled the team to identify an important physical property of these extremophiles, which in turn allowed us to design the resulting synthetic methodology.”
The main contribution of the Brookhaven team is a technology called pulse radiolysis – which is only available at Brookhaven and one other location in the US
“We are using the Laser Electron Accelerator Facility (LEAF) — part of the Accelerator Center for Energy Research (ACER) in the Brookhaven Department of Chemistry — to generate intense, high-energy electron pulses,” Beard explained. “These pulses allow us to add or subtract electrons from molecules to make reactive species that would otherwise be difficult to make using other techniques, including short-lived reaction intermediates. With this technique, we can go into one part of the reaction and observe what happens.”
For the current study, the team used pulsed radiolysis to generate molecules with oxygen-focused radicals, and then measured the effects of “electron withdrawal” on the other side of the molecule. They measured electron withdrawal by tracking how much oxygen on the other side attracts protons, the positively charged ions that roll around in solution. Baird explained that the greater the attractive force of the radical, the more acidic the solution had to be in order for the protons to bind to the molecule.
The Brookhaven scientists found that the acidity had to be high to enable proton capture, which meant that the oxygen radical was a very strong electron-withdrawing group. That was good news for the Princeton team. They then showed that it was possible to exploit the “electron withdrawal” effect of oxygen radicals by making parts of generally inert molecules more chemically reactive.
“The oxygen radical induces a transient ‘polarity reversal’ within the molecule – causing electrons that normally want to stay on that far side to move toward the radical to make the ‘far’ side more reactive,” Beard explained.
These results enabled a novel alternative reaction on phenol-based starting materials to make more complex phenolic products.
“This is a great example of how our method of pulsed radiolysis can be applied to cutting-edge scientific problems,” said Baird. “We were delighted to host an excellent graduate student, Nick Shin, from Knowles Group for this collaboration. We look forward to more collaborative projects on this Phase 2 BioLEC and to see what new problems we can explore with pulsed radiolysis.”
Brookhaven Lab’s role in this work and EFRC at Princeton were funded by the Department of Energy’s (BES) Office of Science. Princeton received additional funding for the synthesis work from the National Institutes of Health.