Tumbling of Anisole Units in Calixarene Promotes Its Shuttling in Rotaxanes

In a calixarene-based
rotaxane, the flexibility of the macrocycle
is expected to be regulated, to achieve specific functions. Here,
a rotaxane composed of a calix[6]­arene wheel threaded onto an axle
shows a cone-to-cone inversion of the macrocycle during shuttling.
To provide a detailed atomistic picture of the inversion pathway and
the effect of the inversion on the shuttling rate, the free-energy
landscape describing these two movements is mapped. We find that the
cone-to-cone inversion of the calix[6]­arene wheel is driven by favorable
electrostatic interactions, and is accomplished by tumbling of the
anisole units one by one in the course of shuttling between two identical
stations. The structure of the macrocycle located at the middle of
the axle, corresponding to the energetic barrier, adopts 1,2,3-alternate
conformation, reducing the steric hindrance of the central linker
and thus lowering the free-energy barrier for shuttling. It can be,
therefore, concluded that the tumbling of calixarene units accelerates
the shuttling of the macrocycle in rotaxanes. The full understanding
of the coupled shuttling and inversion processes provided herein helps
in seeking an alternative approach to regulate the nature of motion
in molecular machines utilizing the flexibility of calixarenes.