Controlled assembly of rotaxane translational isomers using dual molecular pumps

Introduction

Conformational isomerism is a foundational concept^{1, 2–3} in classical stereochemistry. Even so-called pure compounds are often a dynamic equilibrium of numerous conformations with different chemistries and reactivities⁴. Many biochemical processes depend on precise changes in the conformations of nucleic acids and proteins, resulting in highly stereospecific chemical outcomes⁵. For example, finely tuned conformational adaptations play a key role in defining the catalytic activity of enzymes^6,7.

Drawing inspiration from the machine-like behavior of some of these naturally occurring macromolecules, scientists began to contemplate⁸ the design of wholly synthetic systems through which relative molecular motion could be controlled externally. In the simplest of cases e.g., molecular switches, external stimuli can be used to orchestrate changes in the configuration or conformation of molecules^{9, 10, 11, 12, 13, 14, 15–16}. Structurally, many of these switches are based on mechanically interlocked molecules (MIMs), e.g., bistable catenanes^{17, 18, 19–20} and rotaxanes^{21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31–32}. In these switches, the relative positioning of the interlocked components—referred to as coconformations³³—can be controlled. An early³⁴, and still popular^31,32,35,36 approach to the design of these switches is the controlled relative translation of interlocked rings (and dumbbells in the case of rotaxanes) to encircle different recognition sites driven by a panoply of noncovalent interactions. In these switches, the superstructures corresponding to the threaded rings encircling each recognition site represent a subcategory of co-conformational isomers called translational isomers^{37, 38–39}.

The isolation of catenane translational isomers has been reported³⁹ several times in the literature. In 1981, Schill and colleagues³⁷ described the preparation of [3]catenanes consisting of a large ring containing two bulky aromatic units mechanically interlocked with a pair of identical smaller rings. The bulky aromatic units acted as covalent templates for the cyclization of the smaller rings during catenane formation; these sterically bulky components were large enough, however, to prevent ring translation in the final MIMs, resulting in two distinct regions for ring occupancy. The resulting [3]catenanes can exist as three possible translational isomers. One of these translational isomers, in which a single smaller ring occupies each region, was separated chromatographically from a mixture of the two...