Discovering Monoterpene Catalysis Inside Nanocapsules with Multiscale Modeling and Experiments.

Area of Science:

• Computational chemistry
• Supramolecular chemistry
• Chemical engineering

Background:

• Large-scale natural product synthesis, like terpenes, is challenging.
• Nanocapsules offer a promising platform for controlled chemical synthesis.
• Achieving enzyme-like control within nanoreactors remains an unmet goal.

Purpose of the Study:

• To develop a multiscale simulation approach for understanding nanoreactor chemistry.
• To model and explain the formation of monoterpenes within a specific nanocapsule.
• To investigate the factors influencing product distribution and identify pathways for novel product formation.

Main Methods:

• Hybrid quantum mechanics/molecular mechanics (QM/MM) simulations.
• High-temperature Langevin molecular dynamics.
• Multiscale nanoreactor simulation protocol.
• Experimental verification of simulation-derived hypotheses.

Main Results:

• Modeled the tail-to-head formation of monoterpenes in a resorcin[4]arene capsule.
• Provided rationale for observed kinetics and product distribution, explaining the absence of camphene.
• Successfully proposed and experimentally verified a method to synthesize camphene by feeding the capsule with pinene.

Conclusions:

• The developed multiscale simulation approach elucidates complex nanoreactor chemistry.
• Resorcin[4]arene nanocapsules can direct dynamic reaction cascades.
• π-cation interactions within the capsule play a crucial role in controlling chemical transformations.