Complex Movements in Rotaxanes: Shuttling Coupled with Conformational Transition of Cyclodextrins

In cyclodextrin (CD)-based rotaxanes, the shuttling rate of the macrocycle along the thread, is crucial, to characterize their function-as molecular machines. In general, the composition of the thread and the environment are considered to be important. factors affecting the. nature,of the movement. Yet, the role of ancillary motions on the shuttling rate remains unclear. In the present Contribution, two rotaxanes having the same components, yet significantly different shuttling rates between two stable states in an aqueous environment, have been-investigated at the atomic level using numerical simulations. These two rotaxanes consist of an axle with two stations linked by a 2-thethylpyridipium group and an alpha-CD sliding-on the axle and assuming two different orientations. We found that a number of cyclodextrin glucopyranose units (GLUs) isomenzed during shuttling, which we anticipate to affect the shuttling rate. The two-dimensional free-energy landscapes characterizing the isomerization of the,GLUs and, the shuttling along the thread were mapped and revealed that the energetic barriers hampering spontaneous transition between the two stations significantly differ for the two rotaxanes. Structural analysis shows that this difference Mainly,arises from steric hindrances caused by the methyl substituent of-the pyridinium group,, which-leads to a different number of the GLUs experiencing conformational change,during shuttling. Moreover, the thermodynamic stability of the complex is found to, be distinct between the two rotaxanes. This discrepancy may be ascribed to the dipole moment of the complex, which is sensitive to the orientation of CD. It can be concluded that shuttling in the,rotaxanes is not only highly coupled with isomerization of GLUs but also affected by thermodynamic stability, resulting in a:shuttling, rate sensitive to the orientation of the CD. The present results help understand the complex molecular motionin CD-based Molecular shuttles, and are expected to Serve-in the design of molecular filters for selectively screening mblecules with a specific orientation.