Supramolecular Materials Based on Methylene-Linked Water-Soluble Macrocyclic Calixpyridinium and Pillarpyridinium

Abstract

While transitioning supramolecular materials into aqueous environments is critical for biological and environmental applications, designing macrocyclic hosts that are simultaneously easy to synthesize, intrinsically water-soluble, and dynamically responsive remains a formidable challenge. Intrinsically water-soluble macrocycles constructed from bipyridinium or pyridinium cations linked via π-electron-conjugated groups are highly representative hosts, where a major limitation of the pioneering “Blue Box” is its susceptibility to irreversible structural decomposition in alkaline media, severely restricting its application scope. To overcome this fundamental limitation, extensive systematic exploration over the past decade has been dedicated to a unique class of non-π-electron-conjugated methylene-linked pyridinium macrocycles: calixpyridinium and pillarpyridinium. Both of these intrinsically water-soluble macrocycles are accessible via a simple one-step synthesis. Furthermore, calixpyridinium uniquely exhibits an extraordinary response to alkaline conditions without any skeletal decomposition.

This Account chronicles our decade-long systematic efforts to translate these simple molecular building blocks into sophisticated, multiresponsive supramolecular materials. We begin by establishing the foundational rulebook governing host–guest binding. Crucially, beyond conventional factors such as the guest’s geometry, charge number, and size, we highlight our significant discovery that the π-electron-conjugated degree of the guest acts as a pivotal influencing factor, which broadened traditional guest selection criteria and vastly expanded the scope of viable guests for designing calixpyridinium-based supramolecular materials.

While these noncovalent host–guest interactions enabled the construction of various supramolecular assemblies, the true watershed moment in our research was the discovery of an extraordinary, nondestructive structural transformation: under alkaline conditions or irradiation with 254 nm UV light, the acidic methylene of calixpyridinium undergoes a site-specific deprotonation. The deprotonation process triggers a cascade of profound changes. Specifically, the generated carbanions conjugate with adjacent pyridinium cations to yield unsaturated double bonds, not only enhancing the skeleton’s photoactivity but also facilitating the dynamic regulation of supramolecular morphologies. Moreover, the ability of the deprotonated skeleton to act as a dynamic proton acceptor makes it an exceptional building block for engineering biomimetic, far-from-equilibrium dissipative pathways. Furthermore, the resulting decrease in positive charge predictably weakens the host’s affinity toward anionic guests, which can be harnessed to develop smart nanocarriers for on-demand drug delivery. Finally, the transition from a colorless, nonfluorescent state to a highly π-electron-conjugated, brightly colored, and fluorescent state provides dual visual signals, facilitating the construction of visual supramolecular sensors and intelligent optical materials. By systematically harnessing these transformations, we drastically elevated the overall performance of calixpyridinium-based supramolecular materials. This unique deprotonation-driven design strategy serves as the central blueprint for our material innovations. Ultimately, it is anticipated that the principles and strategies outlined herein will provide a valuable conceptual framework for researchers aiming to engineer advanced functional materials via basic molecular building blocks.