Given the high propensity to guest encapsulation (P in (cage) ⇠1), in this specific case the reaction acceleration in the system is found to be little dependent on the guest encap-sulation/expulsion equilibrium. On the other hand, the reactivity turns out to be rather controlled by the fact the guest is more favored to assume reactive conformations inside the cage cavity (compared to the case when this is free in solution). This is in full agreement with the available experimental evidences on these systems. Finally, it is worth noting that while the summations in Equation and Equation 4 run in principle over all possible values of ! (have different reactivities -see Figure ), the data of Figure clearly show that, due to the intrinsically high isomerization barrier, the relative probability for observing twisted (an extremely reactive) 2 conformers (e.g., ⇡/2, ⇡/4, etc.) is very low. These are distorted, very unstable conformers, with a survival lifetime which tend to 0, and for which the product ! • P conf ! ⇠ 0. The unique conformers with survival life and P conf ! 6 = 0 are 2 cis (! = 0) and 2 trans (! = ⇡). The latter, however, is substantially non-reactive (Figure : ⇡ ⇠ 0), so that also in this case ⇡ • P conf ⇡ ⇠ 0. Based on these observations, in our case the reactivity of the system seems thus to be largely related to (i) how much over-stabilized is the reactive 2 cis conformer and (ii) how accessible is the amide to the co-reactant solvent molecules in such conformation in the cage cavity vs. in solution.