A Stimuli-Responsive Molecular Capsule with Switchable Dynamics, Chirality, and Encapsulation Characteristics

Abstract

In this study, we report the preparation, conformational dynamics, and recognition characteristics of novel molecular capsule 1 comprising a bowl-shaped framework conjugated to a tris(2-pyridylmethyl)amine (TPA) lid. With the assistance of experiment (¹H NMR spectroscopy) and theory (MM and DFT) we found that C₃ symmetric 1 is poorly preorganized with three pyridines at the rim adopting a propeller-like orientation and undergoing P-to- M (or vice versa) stereoisomerization (Δ G^⧧ < 8 kcal/mol, VT ¹H NMR). Capsule 1 binds CH₄, CH₃Cl, CH₂Cl₂, CHCl₃, and CCl₄ with K_a < 7 M^-1. Protonation of 1 with HCl, however, gives [1·H]-Cl, with the solid-state structure showing the TPA lid being "flattened" and the ⁺N-H---Cl hydrogen-bonded group residing outside. Importantly, the P-to- M stereoisomerization would for [1·H]-Cl occur with Δ G^⧧ = 11 kcal/mol (VT ¹H NMR). Less dynamic and more preorganized [1·H]-Cl binds CH₄, CH₃Cl, CH₂Cl₂, CHCl₃, and CCl₄ guests with a greater affinity ( K_a = 100-400 M^-1) than 1. The results of our studies suggest that the complexation of increasingly larger guests takes place in an induced-fit fashion, with [1·H]-Cl (a) elongating along its vertical axis and concurrently potentially (b) twisting pyridines from P into M (and vice versa) orientation. The addition of Et₃N to [1·H]-Cl⊂CH₂Cl₂ causes deprotonation of the capsule and the release of CH₂Cl₂ with the process being fully reversed after the addition of HCl. Allosteric capsule 1 with unique structural and dynamic characteristics is expected to, in the future, assist the construction of complex molecular machines and smart functional materials.