Scientists at the US Department of Energy’s (DOE) Brookhaven National Laboratory have helped measure how unpaired electrons in atoms at one end of a molecule can cause chemical reactivity on the opposite side of the molecule. As described in an article recently published in the Journal of the American Chemical Societythis work, in collaboration with Princeton University, shows how molecules containing these so-called free radicals could be used in an entirely new class of reactions.
“Most reactions involving free radicals take place at the site of the unpaired electron,” explained Brookhaven Lab chemist Matthew Bird, one of the paper’s co-corresponding authors. The Princeton team had become adept at using free radicals for a range of synthetic applications, such as polymer recycling. But they wondered if free radicals could influence the reactivity of other parts of the molecule as well, pulling electrons away from those more distant places.
“Our measurements show that these radicals can exert powerful ‘electron-withdrawing’ effects that make other parts of the molecule more reactive,” Bird said.
The Princeton team demonstrated how this long-distance pull can overcome energy barriers and bring together otherwise unreactive molecules, potentially leading to a new approach to the synthesis of organic molecules.
The research drew on the combined resources of a Princeton-led DOE Energy Frontiers Research Center (EFRC) focused on bio-inspired light-escalation chemistry (BioLEC). The collaboration brings together leading synthetic chemists with groups with advanced spectroscopic techniques for studying reactions. Its funding was recently renewed for another four years.
Robert Knowles, who led Princeton’s role in this research, said: “This project is an example of how the combined expertise of BioLEC has enabled the team to quantify an important physical property of these radical species, which in turn allowed us to design the resulting synthesis methodology. “
The main contribution of the Brookhaven team is a technique called pulsed radiolysis – available only at Brookhaven and one other site in the United States.
“We use the Laser Electron Accelerator Facility (LEAF) – part of the Accelerator Center for Energy Research (ACER) in Brookhaven’s Chemistry Division – to generate intense pulses of high-energy electrons,” Bird explained. “These pulses allow us to add or subtract electrons from molecules to create reactive species that might be difficult to make using other techniques, including short-lived reaction intermediates. With this technique, we we can intervene in part of a reaction and monitor what is happening.”
For the current study, the team used pulsed radiolysis to generate molecules with oxygen-centered radicals, then measured the effects of “electron withdrawal” on the other side of the molecule. They measured the attraction of electrons by tracking how well oxygen on the opposite side attracts protons, the positively charged ions moving in solution. The stronger the attraction of the radical, the more acidic the solution must be for the protons to bind to the molecule, Bird explained.
The Brookhaven scientists discovered that the acidity had to be high to allow the capture of protons, which meant that the oxygen radical was a very strong electron-withdrawing group. This was good news for the Princeton team. They then demonstrated that it was possible to exploit the “electron-withdrawing” effect of oxygen radicals by making generally inert parts of 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 towards the radical to make the ‘far’ side more reactive,” Bird explained.
These discoveries have enabled a new substitution reaction on phenol-based raw materials to make more complex phenolic products.
“This is a great example of how our pulse radiolysis technique can be applied to cutting-edge scientific problems,” Bird said. “We were delighted to welcome an excellent graduate student, Nick Shin, from the Knowles group for this collaboration. We look forward to further collaborative projects in this second phase of BioLEC and to seeing what new problems we can explore using pulsed radiolysis.
Brookhaven Lab’s role in this work and the EFRC at Princeton were funded by the DOE Office of Science (BES). Princeton received additional funding for the synthesis work from the National Institutes of Health.