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.在基于杯芳烃（calixarene）的轮烷（rotaxane）中，大环（macrocycle）的柔性可被调控以实现特定功能。本文所研究的轮烷由杯[6]芳烃大环穿于轴上构成，其在穿梭运动过程中会发生大环的锥-锥翻转（cone-to-cone inversion）。为了详细阐明该翻转路径的原子尺度图景，以及翻转对穿梭速率的影响，我们绘制了描述这两种运动的自由能面（free-energy landscape）。研究发现，杯[6]芳烃大环的锥-锥翻转由有利的静电相互作用（electrostatic interactions）驱动，并在两个相同结合位点之间的穿梭过程中，通过苯甲醚（anisole）单元逐一翻转得以完成。位于轴中部、对应于能垒（energetic barrier）的大环结构采取1,2,3-交替构象（1,2,3-alternate conformation），该构象可降低中心连接臂的空间位阻（steric hindrance），从而降低穿梭所需的自由能垒。因此可以得出结论：杯芳烃单元的翻转加速了轮烷中大环的穿梭运动。本文所揭示的穿梭与翻转耦合过程的完整认知，有助于探索利用杯芳烃柔性调控分子机器（molecular machines）运动特性的替代方案。