Neighboring molecules steer where radicals sit and how far they roam

Chemists at Pohang University of Science and Technology (POSTECH) and KAIST have directly captured the fleeting first encounters between radicals and the molecules that surround them, and the results show that a radical’s behavior depends strikingly on its neighbors. Using time-resolved X-ray solution scattering, the team recorded these interactions on a timescale of 100 picoseconds—one ten-billionth of a second—and found that the structure of a neighboring molecule changes both where a radical resides and the range over which it moves. The study, led by Professor Kyung Hwan Kim of POSTECH’s Department of Chemistry in collaboration with Professor Seung Jun Hwang’s team at KAIST, was published in the Journal of the American Chemical Society.

Radicals are molecules or fragments with unpaired electrons, which makes them extraordinarily reactive. That reactivity is useful: radicals readily form new bonds, and chemists exploit them to build complex molecules. But it also makes them hard to control. In solution, a radical will latch onto nearby molecules almost indiscriminately, and the outcomes of such reactions—whether a drug candidate or a functional material is made efficiently and cleanly—depend heavily on where the radical ultimately attaches. The research team describes these restless species as a chemical world’s impatient molecules, unable to stay still even for a moment.

The importance of controlling this behavior comes down to selectivity. Where a single atom attaches to a molecule can make a substantial difference to a drug’s effectiveness or a material’s performance, much as the placement of a single LEGO brick changes what gets built. Researchers have long known that changing the environment around a catalyst can alter reaction outcomes, but the encounters between radicals and their neighbors are so brief that no one had been able to observe directly how those neighbors influence where a radical sits or in which directions it moves. The new work addresses exactly that gap.

The team focused on what they call the first contact: the moment when a radical and a neighboring molecule stay close to one another just before a bond forms. To watch it, they used time-resolved X-ray solution scattering, or TR-XSS, a technique that captures molecular motion as a series of snapshots separated by extremely short intervals. Much as a high-speed camera records a bullet in flight frame by frame, TR-XSS records fleeting molecular moments in successive images, allowing researchers to reconstruct structures that exist for only fractions of a nanosecond.

The experiments were carried out at a synchrotron facility of the High Energy Accelerator Research Organization (KEK) in Japan. The researchers prepared separate solutions of molecular iodine in two solvents, benzene and mesitylene. Laser pulses split the iodine molecules to generate iodine radicals, and X-ray pulses probed the solutions after precisely controlled time delays. The measurements showed that contact complexes—arrangements in which radicals come into close contact with neighboring molecules—had already formed just 100 picoseconds after the laser pulse.

What happened next depended entirely on the solvent. In benzene, whose molecules consist of a simple hexagonal ring, the iodine radical occupied positions near the ring’s edge and moved rapidly around its perimeter, as if riding a carousel. In mesitylene, which carries three small methyl groups attached to the benzene ring, the radical instead favored a direction without a side branch and moved only within a narrow range. The researchers liken benzene to open seating, where any seat is available, and mesitylene to assigned seating, where each seat is fixed. A small structural difference in the neighboring molecule changed not only the radical’s preferred position but also the paths it could take.

Professor Kim emphasized the methodological advance behind the result. The significance of the study, he said, is that the team 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. He added that extending the work to reactants used in practical synthesis should help researchers design molecular environments that guide desired reactions.

The findings offer a new perspective on radical reactions, one 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 molecular environment, chemists could in principle steer radicals toward desired sites so that only the intended reactions take place. The authors suggest this lays groundwork for synthetic strategies aimed at more precise production of effective new drugs and high-performance materials, though the current study examined iodine radicals in two aromatic solvents rather than the reactants of practical synthesis.

The research was supported by National Research Foundation of Korea programs funded by the Ministry of Science and ICT, the Basic Science Research Institute Fund, and the Samsung Science and Technology Foundation.

Subject of Research: Direct observation of radical–arene contact complexes and how neighboring molecular structure shapes radical position and motion

Article Title: “The same radical—so why the difference?” Neighboring molecules change its paths

Article References: “The same radical—so why the difference?” Neighboring molecules change its paths. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: radicals, time-resolved X-ray solution scattering, selectivity, iodine, benzene, mesitylene, contact complexes, POSTECH, KAIST, chemical reactions, solvent effects, JACS