Similarly to what we have seen in ACN solvent, the free-energy profile computed in CHCl 3 solvent (β = 0.10, Fig. , top: black curve) also shows two minima close to the recognition sites (at |d| ∼ 1.5 -2 nm from the axle center). Also in this case the ∆H profile (Fig. , top: red) exhibits a global minimum in the configuration with the macrocycle clamped around the benzimidazolium terminal groups (d ∼ ±2.1 nm). However, in CHCl 3 the ∆H difference between the macrocycle bound vs. unbound/shuttling states is found higher than in ACN solvent (∼ 10 kcal mol -1 ). In Fig. (bottom) it is interesting to note that when the green HBs drop to 0 due to macrocycle unbinding from the terminal stations, in this case, no HBs involving the CHCl 3 solvent molecules are possible, and the pink HBs curve remains equal to 0 everywhere (see also snapshot in Fig. ). In terms of the whole system (solute plus solvent), this makes the shuttling states less favorable than in ACN solvent in this case and consequently, the bound ones are more stable in CHCl As additional tests, very similar results to those in CHCl 3 are obtained when studying the system in DCM, which has β = 0.10 (as CHCl 3 -see Figs. ). On the contrary, the freeenergy profile obtained for the same rotaxane in DMSO solvent (β = 0.76, even higher than that of ACN) suggests a behavior closer to that in ACN, and even more pronounced. As it can be observed from Fig. (top panel), while showing a similar FES shape (e.g., position of the black curve minima), the ∆G between the unbound and bound states is reduced to ∼ 9.5 kcal mol -1 ) in this case (and the free-energy barrier computed via infrequent WT-MetaD is reduced to ∆G ‡ ∼ 16.5 ± 0.3 kcal mol -1 : see SI and Figs. and). These results fit with a faster shuttling kinetics of the macrocycle between the unbound and bound states.