As recently shown via computational approaches, 43-50 the shuttling dynamics and mechanisms in such kinds of rotaxanes may be significantly determined by the influence of the environment (i.e., the solvent composition). It is thus interesting to characterize and compare the shuttling free-energy profiles for the system in different solvents. As test cases, we compared the dynamical behavior of system 1 as immersed in four different solvents. Given that the behavior of 1 is strongly controlled by the H-bonds between the macrocycle and the binding sites in the rotaxane, we chose to compare solvents having different β parameters (the hydrogen-bond acceptor ability): While ACN and in particular DMSO solvents may thus have considerable local effects on the dynamics of the shuttling, by forming H-bonds with the axle and thus competing with those of the macrocycle, DCM and CHCl 3 are "inert" in this sense, and may in principle contribute to the shuttling dynamics only via indirect eventual residual solvophobic effects. To explore in more detail the solvent impact and attain additional insight into the factors that regulate the equilibrium of the rotaxane, we also enriched our analysis through a breakdown of the free-energy profiles (∆G) into enthalpic (∆H) and entropic (-T∆S) contributions. To this end, we employed a validated approach recently proven useful for the study of the early nucleation stages in metal-organic frameworks for obtaining a deeper insight into the behavior of such rotaxane in different β solvents.