Covalent Organic Pillars: Programmable Nanotubular Cavitands

Conspectus For more than half a century, the construction of molecular host compounds has emerged as a central theme in supramolecular chemistry, driven by the promise of controlling molecular recognition, transport, and reactivity. While a wide variety of macrocyclic hosts have been developed, achieving deep-cavity cavitands with confined inner spaces extending over several nanometers has remained challenging. This limitation has hindered systematic investigations of how confinement governs molecular behavior within the so-called “inner phase”, as originally articulated by Cram. Motivated by these challenges, our laboratory has pursued the design and synthesis of a family of covalent organic pillars (COPs)─single-molecule nanotubular architectures assembled through dynamic covalent imine condensation of aldehyde-functionalized paracyclophane building blocks with diamine linkers. In this Account, we summarize our efforts to establish COPs as a versatile class of open-ended nanotubular cavitands, offering highly preorganized one-dimensional cavities with lengths exceeding 2 nm that encapsulate guests with complementary size and surface properties. By adopting an isoreticular design strategy, we demonstrate that systematic variation of linker structure and length enables the construction of a series of COPs with precisely tunable cavity length, sidewall composition, and effective channel width. This modularity provides a rare opportunity to correlate host geometry with recognition behavior in a quantitative and predictive manner. Beyond host–guest chemistry, we show that COPs also provide a powerful platform for exploring dynamic stereochemical phenomena during self-assembly from inherently chiral yet stereolabile macrocyclic building blocks. Whereas COPs constructed from rigid diamine spacers undergo exclusive narcissistic chiral self-sorting, yielding pairs of enantiomeric nanotubular structures, incorporation of flexible aliphatic diamine spacers leads to pronounced odd–even effects in chiral self-sorting, giving either racemic mixtures of chiral COPs or achiral meso-COPs, depending on linker parity. This conformational flexibility further endows COPs with adaptive host–guest recognition behavior, enabling cooperative accommodation of guests through a balance of host deformation and guest distortion. A distinctive feature of our work is that the molecular structures of essentially all COPs and their key host–guest complexes are elucidated by single-crystal X-ray crystallography, providing a rigorous structural foundation that remains rare for deep-cavity molecular hosts. Overall, our studies establish COPs as a precision design paradigm for nanotubular cavitands that bridge the gap between discrete macrocycles and extended porous frameworks, thereby opening a new regime of molecular control in supramolecular chemistry.