Visualizing Molecular Motion: A Breakthrough in Polypseudorotaxane

Aandrewasjyer · 2025-03-24T18:31:44+00:00

Polypseudorotaxanes, where α-cyclodextrin (α-CD) rings shuttle along a poly(ethylene glycol) (PEG) chain, hold great potential for molecular machines. However, their precise molecular dynamics have remained elusive. Researchers have now employed fast-scanning atomic force microscopy (FS-AFM) to directly observe α-CD rings moving along a PEG chain in real time. This advancement establishes FS-AFM as a powerful tool for studying supramolecular polymers and opens new possibilities for designing efficient molecular motors.

Imagine a microscopic locomotive moving autonomously along a track, propelled by its own structural changes. At the molecular level, this concept underpins the development of molecular motors—systems that could revolutionize advanced materials, targeted drug delivery, and nanoscale robotics.

Since the first synthetic molecular machine was created in 1994, researchers have drawn inspiration from nature’s molecular motors, driving rapid advancements in the field. These efforts culminated in the 2016 Nobel Prize in Chemistry for molecular machine design. Among the promising candidates for artificial molecular motors is polypseudorotaxane—a structure in which multiple α-CD rings self-assemble onto a PEG polymer chain in aqueous solutions and shuttle along its length. However, the exact mechanism behind this motion has remained unclear—until now.

A research team from the Japan Advanced Institute of Science and Technology (JAIST) has now visualized the dynamic movement of α-CD rings along a PEG chain for the first time. Led by Associate Professor Ken-ichi Shinohara, the team captured real-time images using FS-AFM, revealing localized structural changes that were previously undetectable. Their study, published in Macromolecules on March 4, 2025, introduces a novel approach to analyzing supramolecular polymers, which could pave the way for more advanced molecular machines.

"Although PEG@α-CD polypseudorotaxane is widely used, the structural changes that occur as α-CD rings shuttle along the polymer chain remain poorly understood. By revealing its structure at the solid-liquid interface, our study will contribute to the development of synthetic polymer motors driven by thermal fluctuations," explains Dr. Shinohara.

To prepare the polypseudorotaxane, the researchers mixed PEG100k with α-CD in an aqueous solution and allowed it to rest for over six hours, leading to the formation of a white solid. They then analyzed this structure using FS-AFM in a 15 millimolar potassium chloride aqueous solution. Unlike conventional optical microscopes, AFM scans surfaces using an ultra-sharp tip on a microscopic lever, capturing nanoscale details with high resolution.

Imaging the PEG100k chain alone revealed a highly flexible, dumbbell-shaped structure with globular formations at both ends, giving it spring-like properties. In its relaxed state, the chain appeared significantly shorter (averaging 48.1 nm) than its fully extended length of 790 nm. However, when α-CD rings were added, the structure became more rigid and elongated, averaging 499.6 nm in length, with end-cap formations preventing the rings from slipping off. Despite the increased rigidity, the chain retained its spring-like motion, allowing the α-CD rings to continue shuttling along its length.

"We observed that the polypseudorotaxane exhibited shrinking and extending motions driven by the shuttling of α-CD rings along the polymer chain. These movements were concentrated in the exposed, self-shrinking PEG segments, where repeated expansion and contraction occurred as the α-CD rings moved," explains Dr. Shinohara. Molecular dynamics simulations further confirmed these observations, replicating the shrinking and extending motions seen in the FS-AFM experiments.

While fully functional molecular machines remain a long-term goal, this study represents a significant step forward in understanding molecular motion in supramolecular systems. "FS-AFM is a promising technique for analyzing supramolecular materials, particularly when conventional spectroscopic methods are inadequate for structural analysis," notes Dr. Shinohara. These findings could ultimately lead to energy-efficient molecular motors that harness thermal energy at room temperature for controlled motion, bringing molecular machines one step closer to practical application.