Deciphering the helicity switching mechanism: a case study of the rigid three-tiered stacked architecture

Abstract

Understanding the switching mechanism of helical molecular cages is critical in regulating their functions of asymmetric catalysis and enantioseparation. The helical inversion of a three-tiered stacked architecture was investigated by employing molecular dynamics simulations combined with free-energy calculations. A two-dimensional free-energy landscape characterizing the spinning processes of the top and bottom tiers around the z axis was determined using the extended adaptive biasing force method. The free-energy barrier in the least free-energy pathway was estimated to be 17.6 kcal mol⁻¹, in excellent agreement with experimental measurements. Further analysis revealed that the barrier was caused by geometric deformation, weakening of π–π stacking between aromatic rings, and the re-orientation of polarized amine moieties. The present contribution takes a step toward understanding the dynamic helicity-based functions related to asymmetric reactions and optical resolution.