An Inhospitable Cryptand: The Importance of Conformational Freedom in Host‐Guest Complexation

Abstract

Two new cryptands were synthesized from bis(5‐bromomethyl‐1,3‐phenylene)‐32‐crown‐10 (4). The third arms, containing 19 or 21 atoms, were installed via Williamson ether syntheses with bisphenols containing 2,6‐disubstituted pyridines. 2,6‐Diaminopyridine was converted into the bis(p‐hydroxybenzoyl) derivative 3 for the first cryptand (5) and 2,6‐dicarboxypyridine was converted into the bis(p‐hydroxybenzylamide) 9 for the second cryptand (10). Cryptand 5 did not complex viologen derivatives 11–13 to an extent detectable by 1H NMR. We attribute the lack of complexation between viologen derivatives and 5 to its lack of conformational flexibility that prevents π‐stacking, a necessary component for complexation of viologens. In contrast longer and more flexible cryptand 10 did complex dimethyl paraquat (11) with Ka = 1.6 (±0.2) × 103 m–1 in acetone at 23 °C, probably by π‐stacking with the p‐oxybenzyl moieties of the host, made available by its enhanced flexibility.

Crown‐Ether‐Based Cryptands with Rarely Strong Affinities for Binding Neutral Organic Molecules

“…According to the previous studies of multi crown-etherbased cryptands, spatial size is crucial for binding affinities. [6,18,[20][21] Spatial size affects the spatial fitting and the distances and angles that govern the strength of the noncovalent interactions between the host and guest. [21] Moreover, additional and optimized non-covalent interactions, including π-π stacking and H-bond interactions between the host and guest, are vital for increasing cryptands' binding affinity.…”

“…[6,18,[20][21] Spatial size affects the spatial fitting and the distances and angles that govern the strength of the noncovalent interactions between the host and guest. [21] Moreover, additional and optimized non-covalent interactions, including π-π stacking and H-bond interactions between the host and guest, are vital for increasing cryptands' binding affinity. As shown in Figure 1, cryptand H1 and H2, reported by Huang's group, were both designed with the potential to offer π-π stacking and H-bond interactions with guest molecules.…”

“…According to the previous studies of multi crown‐ether‐based cryptands, spatial size is crucial for binding affinities [6,18,20–21] . Spatial size affects the spatial fitting and the distances and angles that govern the strength of the non‐covalent interactions between the host and guest [21] .…”