Development of Redox-Switchable Resorcin[4]arene Cavitands

CONSPECTUS: Within the framework of miniaturization of electromechanical devices, the development of a redox-switchable molecular gripper as a tool for nanorobotics is appealing both from an academic and from a practical perspective. Such a tool should be able to controllably grab a molecular cargo, translocate it over considerable distances and time scales, and release it. Resorcin[4]arene cavitands seem to be an ideal platform for the development of molecular grippers due to their ability to adopt two spatially well-defined conformations: an expanded kite and a contracted vase. Furthermore, they possess legs for functionalization and attachment to metal surfaces. While changes in temperature, pH, and metal-ion concentration were known to induce conformational switching, redox-switchable cavitands remained a challenge. In this Account, we describe our efforts toward the development of a new class of resorcin[4]arene cavitands that are redox-switchable. First, we introduced the naphthoquinone moiety as a redox-active wall component and showed that cavitands containing four quinone walls strongly prefer the open kite conformation in both the quinone and hydroquinone redox states, while cavitands that contain two quinone and two quinoxaline walls can adopt both the vase and the kite conformations depending on solvent but not on redox state. Next, in order to introduce a driving force for the conformational switching process in diquinone cavitands, we designed cavitands with hydrogen bond acceptor groups on the quinoxaline walls. These acceptors were sought to establish hydrogen bonds with the hydroquinone groups in the reduced redox state, thereby stabilizing the vase form. Oxidation to the quinone state would remove these interactions, switching the cavitand back to the kite form. Cavitands equipped with different hydrogen bond acceptor groups were synthesized and evaluated. We found that carboxamide moieties are best suited to assist redox-induced switching of conformational and binding properties. With the goal of further increasing association constants and reducing guest-exchange rates via steric congestion, we exchanged the naphthoquinone with the triptycene-quinone moiety. The congesting influence of the triptycene-quinone moiety on the binding properties was quantified both in the presence and in the absence of additional hydrogen bond interactions that stabilize the vase form. X-ray crystallographic studies provided insights into the solid-state structures of the cavitands in different solvents and redox states. A significant enhancement of association constants and reduction in guest release rates was observed in the reduced redox state compared with the top-open system, yielding redox-switchable cavitand baskets. These studies represent a step towards the development of redox-switchable molecular grippers on metal surfaces. Future challenges will consist in the development of cavitands that will no longer rely on an external proton source for the switching process, allowing redox-switching to be performed in purely aprotic media. Finally, suitable leg functionalization would enable the grippers to be interfaced with metal surfaces.