Discovering Monoterpene Catalysis Inside Nanocapsules with Multiscale Modeling and Experiments

Large-scale
production of natural products, such as terpenes, presents
a significant scientific and technological challenge. One promising
approach to tackle this problem is chemical synthesis inside nanocapsules,
although enzyme-like control of such chemistry has not yet been achieved.
In order to better understand the complex chemistry inside nanocapsules,
we design a multiscale nanoreactor simulation approach. The nanoreactor
simulation protocol consists of hybrid quantum mechanics–molecular
mechanics-based high temperature Langevin molecular dynamics simulations.
Using this approach we model the tail-to-head formation of monoterpenes
inside a resorcin[4]­arene-based capsule (capsule I). We provide a rationale for the experimentally observed
kinetics of monoterpene product formation and product distribution
using capsule I, and we explain why
additional stable monoterpenes, like camphene, are not observed. On
the basis of the in-capsule I simulations,
and mechanistic insights, we propose that feeding the capsule with
pinene can yield camphene, and this proposal is verified experimentally.
This suggests that the capsule may direct the dynamic reaction cascades
by virtue of π-cation interactions.