Korean researchers crack 50-year mystery of how light-activated molecules move

- KAIST and IBS track ultrafast structural changes in azobenzene using X-ray free-electron laser

- 'Molecular movie' reconstructed from split-second snapshots; findings published in Nature

From left in the back row: postdoctoral researcher Kim Jung-min, senior researcher Alekos Segalina, research fellow Ki Ho-seong and Professor Lee Hyo-chul. [Provided by KAIST]

Korean researchers have solved a nearly 50-year mystery surrounding azobenzene — a leading candidate for light-activated "molecular switches" capable of turning drug effects on and off or changing shape on demand — by capturing in precise detail how the molecule moves the instant it absorbs light.

KAIST announced Wednesday that a research team led by Professor Lee Hyo-chul of the Department of Chemistry, working with the Center for Advanced Reaction Dynamics at the Institute for Basic Science (IBS), had mapped the ultrafast structural transformation of azobenzene as it responds to light.

Azobenzene is a representative light-responsive molecule whose structure changes upon absorbing light. It consists of two benzene rings connected by two nitrogen atoms; when light strikes it, the relative positions of the two rings shift.

Because of this property, azobenzene has been studied as a key material in photopharmacology — where light controls drug activity — as well as in smart materials and miniature molecular machines.

The challenge was that the changes occurring immediately after light absorption happen so rapidly that directly observing the motion had proved nearly impossible. For roughly half a century, competing hypotheses had been proposed about whether the two benzene rings rotate broadly or whether the central nitrogen linkage moves instead.

The research team used the X-ray free-electron laser at the Pohang Accelerator Laboratory to track these fleeting movements. They fired a laser at azobenzene dissolved in methanol to trigger the reaction, then used ultrafast X-rays to measure structural changes over time.

Particularly challenging was isolating the faint signal from azobenzene amid the strong background noise generated by the surrounding solvent. The team stitched together structural snapshots captured at successive instants to reconstruct the molecule's motion as a kind of "molecular movie."

A schematic diagram of the research findings (AI-generated image). [Provided by KAIST]

As a result, the findings defied expectations: the two large benzene rings do not rotate broadly all at once. Instead, the carbon-nitrogen bonds twist first, and then the two sides of the central nitrogen linkage move in a coordinated, bicycle-pedal-like motion that reshapes the entire molecule.

This motion also offers a clue as to why azobenzene's reaction speed does not change significantly even when the viscosity of the surrounding solvent increases. Because the movement is concentrated around the molecule's center rather than involving full rotation of the large benzene rings, less space needs to be cleared through the surrounding liquid.

The findings do not immediately translate into better-performing drugs or materials based on azobenzene. However, by establishing at a structural level the precise pathway through which the molecule moves, the research could inform the design and validation of future light-responsive materials and molecular machines.

The study also demonstrated that ultrafast structural changes in organic molecules dissolved in solution — even those containing no heavy atoms — can be tracked using X-rays. The team plans to capture "molecular movies" of various other organic molecules by varying conditions such as solvent and light wavelength.

"This is a result that reveals the pathway by which azobenzene changes its shape after absorbing light," Lee said. "We expect it to contribute to understanding the operating principles of a wide range of light-responsive molecules."

The findings were published Wednesday in Nature (local time).

nbgkoo@heraldcorp.com