Infrequent WT-MetaD simulations provide also more detail into the kinetic characterization of blue-box movement between the two main metastable states, namely the dynamic binding with recognition sites (see scheme in Fig. ). For steric reasons, the NP site plane needs to assume a parallel configuration respect to the CBPQT 4+ bipiridyne plane in order to allow the threading of the macrocycle along the axle and the binding with the other recognition site. Provided the entropic nature of free-energy minima seen in Fig. , as said we can impute such a kinetic barrier of transition from one NP site to the other mostly to this constraint.