An Asymmetric Mechanism in a Symmetric Molecular Machine.

The design of molecular architectures exhibiting functional motions is a promising area for disruptive technological development. Toward this goal, rotaxanes and catenanes, which undergo relative motions of their subunits in response to external stimuli, are prime candidates. Here, we report on the computational analysis of the contraction/extension of a bistable [c2]daisy chain rotaxane. Using free-energy calculations and transition path optimizations, we explore the free-energy landscape governing the functional motions of a prototypical molecular machine with atomic resolution. The calculations reveal a sequential mechanism in which the asynchronous gliding of each ring is preferred over the concerted movement. Analysis of the underlying free-energy surface indicates that the formation of partially rearranged intermediates entails crossing of much smaller barriers. Our findings illustrate an important design principle for molecular machines, namely that efficient exploitation of thermal fluctuations may be realized by breaking down the large-scale functional motions into smaller steps.