Posted by Achieving unidirectional molecular motion remains a formidable challenge, primarily due to the randomizing influence of Brownian motion. In biological systems, this obstacle is overcome through chemically fueled ratcheting mechanisms that drive biomolecular motors—an elegant strategy that has inspired chemists to develop artificial molecular systems with comparable directional control.
In a recent study [1], Enxu Liu and co-workers lead by the highly recognized organic, biological and supramolecular glycochemist Matthieu Sollogoub at Sorbonne University, CNRS present a system in which a selectively functionalized cyclodextrin, threaded onto an axle comprising three distinct segments, exhibits unidirectional motion. The cyclodextrin’s distinctive three-dimensional architecture allows for precise rim-selective functionalization and regioselective deprotection of temporary stoppers along the rotaxane axle.
Crucially, the cyclodextrin in this system is capable of actively opening molecular gates in a single direction. This forward motion is reinforced by a subsequent gate-closing reaction, which is kinetically favored once the cyclodextrin has passed the gate—an effect attributed to its conical geometry. Together, these features establish a synergistic, double-gated, one-way ratcheting mechanism made possible by the unique structure of the cyclodextrin.
The functionalization with tertiary amines on the primary rim of the CD threaded on an axle enables mechanospecific deprotection of Fmoc groups on an amine located on the axle in front of it. It has been shown that this axle-amine can be reprotected with a Fmoc group more rapidly when the CD has moved over it, i.e., when it then presents its larger rim to the amine. The combination of kinetic biases enable the unidirectional movement of the CD along the axle when fueled with a Fmoc-protecting reagent. A key feature of this system is the intramolecular mechanospecific gate-opening reaction made possible by the rim-differentiated CD. In this process, the macrocycle effectively ‘‘opens its own way,’’ with the ‘‘gate’’ closing faster behind it. This constitutes a novel one-way ratchet mechanism, operating irreversibly and driven by chemical fuel. Overall, the mechanospecific reaction enhances directionality and thus the potential energy stored in the system, which would translate to higher efficiency of a motor in a cyclic system and enable long-distance translational motion.
At the end of the paper the authors acknowledge the support of CycloLab, Hungary.
[1] Enxu Liu, Dania Daou, Bernold Hasenknopf, Guillaume Vives, Matthieu Sollogoub,
Not going back: Unidirectional movement by intramolecular one-way ratcheting of functionalized cyclodextrin, Chem, 2025, 102623, https://doi.org/10.1016/j.chempr.2025.102623.