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

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
(ΔG⧧ < 8 kcal/mol, VT 1H NMR). Capsule 1 binds CH4, CH3Cl, CH2Cl2, CHCl3, and CCl4 with Ka < 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 ΔG⧧ = 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 (Ka =
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 fromP 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.