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

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, with 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 approach 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 (k_c) for the C₃- to C₁-configuration interconversion, while time-dependent circular dichroism spectroscopy at different temperatures quantifies the observed rate constant (k_obs) of the ensemble of all the structural changes. As k_obs $$ k_c, it allows us to decouple the overall molecular motions into a slow configurational transformation and rapid conformational interconversions, with the latter further dissected into two independent conformational interchanges, namely (P)-C₃ $$ (M)-C₃ and (P)-C₁ $$ (M)-C₁. This work, therefore, sheds light on the 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.