In realistic conditions, the encapsulation/expulsion of guests as, e.g., 2 or 3 in/out the cavity of cage 1 may require crossing considerably high free energy barriers, which makes them rare events in the timescales accessible via classical atomistic MD simulations. As recently done for other host-guest and dynamic supramolecular systems, we thus reconstructed the thermodynamics and kinetics for the processes of encapsulation/expulsion of amide 2 in/out the cavity of cage 1 by means of a well-suited WT-MetaD 48 simulation protocol (complete computational details are available in the Supplementary Information). The extracted data are collected in Table and Figure .