Unraveling the Dynamic Molecular Motions of a Twin‐Cavity Cage with Slow Configurational but Rapid Conformational Interconversions

Featuring diverse structural motions/changes, dynamic molecular systems hold promise for executing complex tasks. However, their structural complexity presents formidable challenge in elucidating their kinetics, especially when multiple structural motions are intercorrelated. We herein introduce a twin-cavity cage that features interconvertible C3- and C1-configurations, each configuration exhibiting interchangeable P- and M-conformations. This molecule is therefore composed of four interconnected chiral species (P)-C3, (M)-C3, (P)-C1, (M)-C1. We showcase an effective methodology to decouple these sophisticated structural changes into two kinetically distinct pathways. Utilizing time-dependent 1H NMR spectroscopy at various temperatures, which disregards the transition between mirror-image conformations, we first determine the rate constant (kc) for C3- to C1-configuration interconversion; while time-dependent circular dichroism spectroscopy at different temperatures quantifies the observed rate constant (kobs) of ensemble of all structural changes. As kobs >> kc, it allows us to decouple the overall molecular motions into a slow configurational transformation and rapid conformational interconversions, the latter further dissected into two independent conformational interchanges, namely (P)-C3 ⇄ (M)-C3 and (P)-C1 ⇄ (M)-C1. This work therefore sheds light on comprehensive kinetic study of complex molecular dynamics, offering valuable insights for the rational design of smart dynamic materials for applications of sensing, separation, catalysis, molecular machinery, etc.