What the research is about
A spark flashes for only an instant before disappearing. In the molecular world, there are particles that behave in a similar way-appearing for a brief moment during a reaction and then immediately transforming into something else. These highly reactive particles are called radicals. Because radicals contain an unpaired electron, they react very easily and readily bond with other molecules.
One important reaction involving radicals is the isocyanide reaction, which has long been of interest in chemistry. Isocyanides are valuable starting materials used in synthesizing pharmaceuticals and other complex molecules. By the 1990s, chemists had shown that when an isocyanide accepts a radical, it forms an intermediate called an imidoyl radical, which then transforms into more complex structures. However, this intermediate is so short-lived that observing it directly had been nearly impossible.
This challenge, however, had already been partly overcome by Associate Professor Shigekazu Ito and his research team at Institute of Science Tokyo (Science Tokyo). In their earlier work, they used a different isocyanide compound and succeeded in detecting the imidoyl radical, which existed for only one microsecond (one millionth of a second). But there was a puzzle: Theory predicted that the imidoyl radical should vanish almost instantly and move on to the next structure. Yet experiments showed that it stayed around longer than expected.
To solve this mystery, the team set out to observe the molecular changes in even greater detail. By using muons-elementary particles that act as probes to reveal what is happening inside molecules-they succeeded in tracking reactions on the nanosecond (one billionth of a second) timescale.
Why this matters
The team's most significant achievement is that they experimentally confirmed, for the first time, the theoretical prediction that the imidoyl radical transforms within nanoseconds. Even more importantly, they directly observed the radical formed immediately afterward-the quinoxalinyl radical-a feat never before accomplished.
The quinoxalinyl radical contains an unpaired electron in a specific orbital, making it extremely reactive. Observing this species allowed the researchers to uncover details of the reaction pathway that had previously remained hidden.
The team also examined the radical both in solution and in crystal form, discovering that its behavior changes depending on the surrounding environment. This insight is valuable for designing new materials and for understanding how molecules interact within biological systems.
What's next
A deeper understanding of radical reactions could lead to more efficient design of pharmaceuticals and advanced functional materials. Because the radical identified in this study is known to react with components of DNA, the findings may also open new possibilities in life science and medical research.
Capturing such fleeting molecular moments-far too fast to see with the naked eye-provides essential clues for shaping the future of chemistry, biology, and materials science.
Comment from the researcher
When theory and experiment didn't match, we treated that mismatch as an opportunity. We rebuilt the study from the molecular design stage, and finally succeeded in observing a radical reaction that occurs in just nanoseconds. It felt as if one piece of a long-standing puzzle had finally clicked into place.
（Shigekazu Ito, Associate Professor, Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo）
