Chemical reactions have their own “impatient molecules.” Unable to stay still even for a moment, they latch onto other molecules indiscriminately. Researchers have now found that even these molecules change where they “sit” and how far they roam depending on who their neighbors are. The findings are expected to help scientists make better medicines and materials by directing reactions only to the desired sites.
A research team led by Professor Kyung Hwan Kim of the Department of Chemistry at Pohang University of Science and Technology, in collaboration with Professor Seung Jun Hwang’s team in the Department of Chemistry at KAIST, captured the first encounters between radicals and neighboring molecules on a timescale of one ten-billionth of a second, or 100 picoseconds. The team found that the structure of the neighboring molecule changes where a radical resides and the range over which it moves. The study was published in the Journal of the American Chemical Society ( JACS ), a prestigious journal in chemistry.
Where a single atom attaches can make a substantial difference to a drug’s effectiveness or a material’s performance, much as where a LEGO brick is placed changes what gets built. This is why “selectivity”—directing reactions to the desired sites—is important in developing new drugs and functional materials. Radicals are molecules with unpaired electrons. They are useful for forming new bonds, but their high reactivity makes them difficult to control. Researchers have known that changing the environment around a catalyst can alter reaction outcomes. Yet these encounters were too fleeting to observe how neighboring molecules influence where radicals reside and in which directions they move.
The team focused on the “first contact,” when a radical and a neighboring molecule briefly stay close to one another just before a bond forms. They used time-resolved X-ray solution scattering (TR-XSS), a technique that captures molecular motion in a series of snapshots separated by extremely short intervals. Much as a high-speed camera captures a bullet in flight frame by frame, the technique records fleeting molecular moments in successive snapshots.
At a synchrotron facility of the High Energy Accelerator Research Organization (KEK) in Japan, the team prepared separate solutions of molecular iodine in benzene and mesitylene. Laser pulses split the iodine molecules to generate radicals, and X-rays probed the solutions after controlled time delays. The measurements showed that “contact complexes,” in which radicals come into close contact with neighboring molecules, had already formed just 100 picoseconds later.
The radicals behaved very differently in the two solvents. In benzene, which has a hexagonal ring, the radical occupied positions near the ring’s edge and rapidly moved around its perimeter, as if riding a carousel. In mesitylene, where three small side branches called “methyl groups” are attached to the benzene ring, the radical instead favored a direction without a side branch and moved only within a narrow range. Benzene was like “open seating,” where any seat is available, while mesitylene was like “assigned seating,” where each seat is fixed. A small difference in the neighboring molecule’s structure changed not only the radical’s preferred position but also the “paths” it could take.
The study presents a perspective on radical reactions that considers not only how stably a radical is held, but also where it resides and in which directions it moves. By carefully designing the surrounding environment, researchers can guide radicals to desired sites so that only the intended reactions take place. The findings are expected to lay the groundwork for synthetic strategies that enable more precise production of effective new drugs and high-performance materials.
“The significance of this study is that we moved beyond inferring reaction processes from their final products to directly identifying the structure of a short-lived contact state between a radical and a neighboring molecule,” said Professor Kim. “We expect that extending this work to reactants used in practical synthesis will help us design molecular environments that guide desired reactions.”
This research was supported by National Research Foundation of Korea (NRF) research programs funded by the Ministry of Science and ICT (MSIT), the Basic Science Research Institute Fund, and the Samsung Science and Technology Foundation.
JACS
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