During the exit, we observe a sharp increase in the PMF, i.e., free energy for both substrate and product as they dissociate from the active site. The rise in PMF is mainly due to the force against the hydrophobic interactions (SI, Figure ) between substrate and cagesubstituents when substrate/product moves from 3 to 10-12Å from the reactive center, i.e., Fe=O for HM1. Interestingly, we observed that both t-butyl groups and the phenyl substitution of the cage act as doorways which can easily be shuttles from open to close conformation to allow the substrate entry and the product exit (Figure ). Interestingly, once substrate enters or product exists the cage, the two t-butyl groups and the phenyl groups, restore their previous orientations, indicating an important dynamics during the entry/exit of the substrate/product. As can be seen, the PMF becomes linear after the substrate/product dissociates the cage at 23 Å indicating no further force is applied. The total work (PMF) implies that the substrate can easily access the active oxidant inside the modeled cage, while the hydroxylated product can escape and leave the space. These findings shed light on the energetics and dynamics of the substrate/product dissociation process and have important implications for the design and optimization of supramolecular cages for catalytic applications.