Understanding the Dynamics of Mechanically Interlocked Molecular Systems via Metadynamics Simulations

Mechanically interlocked molecules, such as rotaxanes and catenanes, display complex internal dynamics and reciprocal motions that are central to their use as artificial molecular machines. Revealing how these motions occur, the key interactions, and the rate-limiting steps determining their kinetics is essential for understanding and designing functional systems. However, due to scale-, space-, and time-resolution limits, this is typically not easy to access via experimental techniques. In this Personal Account, we discuss representative examples from our recent work using classical molecular dynamics and metadynamics simulations to investigate the key mechanisms, the thermodynamics, and kinetics of the internal dynamics of rotaxanes and catenanes. This allows access to the dynamics of mechanically interlocked systems at atomistic resolution, disentangling bound, unbound, and intermediate states and the dynamical interconversion between them, and providing information on kinetic barriers and characteristic timescales. Such atomistic-scale simulations provide results that are reliable and in very good agreement with the available experimental measurements. Overall, this account illustrates the value of molecular simulations as a predictive and complementary tool for understanding mechanically interlocked molecules in motion.