Cyclopentadiene dimerization in cucurbiturils: Origin of catalysis, dynamics and solvent effect

Cucurbit[7]uril (CB7) was recently identified as an efficient supramolecular catalyst for the challenging cyclopentadiene (CPD) dimerization. However, it remains unclear how host-guest interactions and solvent modulate the reaction mechanism and dynamics, especially the key factors controlling the catalytic effect of cucurbiturils. Herein, we computationally investigated the reaction profiles and dynamics of CPD dimerization confined in CB7 and CB8 in the gas phase and the implicit water environment. Our results revealed that water changes the alignment of the CPD molecular plane from the preferred parallel orientation in the gas phase to a perpendicular orientation towards the principal axis of CB7 during the reaction. We emphasized the importance of the host having a comparable or enhanced affinity with the guest in the transition state compared to that in the reactant complex in order to achieve excellent catalysis. Our detailed analysis demonstrated that for CPD dimerization in CB7, the largest contribution (similar to 65 %) to catalysis is the formation of a thermodynamically stable reactant complex, with the remaining contribution mainly from transition state entropic stabilization. The inferior performance of CB8 can be largely explained by electronic destabilization of the transition state owing to the reduced host-guest interactions in the transition state. Born-Oppenheimer trajectory simulations revealed that CB7 stabilizes the entropic intermediate with an increasing ratio of dynamically stepwise trajectories. This study will enrich our understanding of how reactions obtain enhancement and occur in a confined environment.