No abstract

Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems . Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts . Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure . Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

Wholly synthetic molecules involving both mechanical bonds and a folded secondary structure are one of the most promising architectures for the design of functional molecular machines with unprecedented properties. Here, we report dynamic single-molecule force spectroscopy experiments that explore the energetic details of donor-acceptor oligorotaxane foldamers, a class of molecular switches. The mechanical breaking of the donor-acceptor interactions responsible for the folded structure shows a high constant rupture force over a broad range of loading rates, covering three orders of magnitude. In comparison with dynamic force spectroscopy performed during the past 20 y on various (bio)molecules, the near-equilibrium regime of oligorotaxanes persists at much higher loading rates, at which biomolecules have reached their kinetic regime, illustrating the very fast dynamics and remarkable rebinding capabilities of the intramolecular donor-acceptor interactions. We focused on one single interaction at a time and probed the stochastic rupture and rebinding paths. Using the Crooks fluctuation theorem, we measured the mechanical work produced during the breaking and rebinding to determine a freeenergy difference, ΔG, of 6 kcal·mol −1 between the two local conformations around a single bond.AFM | single-molecule force spectroscopy | molecular machines | foldamers | equilibrium dynamics B iological molecular machines are known to operate out of their thermodynamic equilibrium to carry out specific tasks such as cargo transport performed by single myosins (1), or cell movements driven by flagella rotary motions (2). The work performed by these natural molecular motors is related to their dynamics in solution, and to the force exerted by the molecule to drive the relevant process in one direction. The invention of synthetic routes to wholly artificial molecular machines with highly precise and controlled architectures has led to the production of amazing molecules able to perform mechanical tasks (3-7). Their integration into materials such as metal-organic frameworks (8) or polymer gels (9, 10) has been described recently. The resulting materials can experience a macroscopic change when each single machine is pulled out of its equilibrium state, as a result of an external stimulus, such as light irradiation or a change in solvent.Collecting information about the behavior of such molecules when driven out of their equilibrium is crucial for the design of more efficient molecular devices. Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) has emerged as a very elegant technique to probe inter-and intramolecular forces as well as mechanical processes (11-16). By trapping individual molecules between a mechanical probe and a substrate, it is possible to apply an external force to drive them out of the equilibrium and perform very precise and controlled operations in one direction. For 20 y, AFM-based SMFS was used to unravel the behavior of natural biomolecules under mechanical load and has led to a d...

Artificial molecular pumps (AMPs), inspired by the active cellular transport exhibited in biological systems, enable cargoes to undergo unidirectional motion, courtesy of molecular ratchet mechanisms in the presence of energy sources. Significant progress has been achieved, using alternatively radical interactions and Coulombic repulsive forces to create working AMPs. In an attempt to widen the range of these AMPs, we have explored the effect of molecular pumping on the photophysical properties of a collecting chain on a dumbbell incorporating a centrally located pyrene fluorophore and two terminal pumping cassettes. The AMP discussed here sequesters two tetracationic cyclophanes from the solution, generating a [3]­rotaxane in which the fluorescence of the dumbbell is quenched. The research reported in this Article demonstrates that the use of pumping cassettes allows us to generate the [3]­rotaxane in which the photophysical properties of fluorophores can be modified in a manner that cannot be achieved with a mixture of the dumbbell and ring components of the rotaxane on account of their weak binding in solution.