However, the situation is surprisingly switched in the tightly packed 2•3 ⇢ 1 systems (Figure ). In highly confined conditions, the amide of 2 cis is found more exposed to the solvent within cage 1 compared to that of 2 trans (red vs. blue solid curves). This suggests that, while on the one hand the cis conformer of 2 is more tightly packed within the cage, the equilibrium configuration of 2 cis in the 2 • 3 ⇢ 1 complex may allow, at the same time, for an increased propensity to react. We explore at a deeper level the difference in terms of reactivity of the trans vs. cis conformers of 2 in the next section.