Chiral Self‐Sorting of Flexible Covalent Organic Pillars for Adaptive Molecular Recognition

Flexible covalent organic pillars (flex-COP-n) are introduced as a family of dual-open-ended nanotubular hosts constructed via dynamic imine condensation between pillararene-derived macrocyclic building blocks and conformationally mobile ─(CH₂)_n─ aliphatic linkers. These discrete molecular containers feature well-defined tubular channels capable of adaptive host-guest interactions. The self-assembly process exhibits a pronounced odd-even effect, yielding either enantiomeric or meso duplexes through distinct chiral self-sorting pathways. Host-guest interactions between flex-COP-4 and a series of α,ω-dibromoalkanes were systematically investigated using NMR spectroscopy and single-crystal X-ray crystallography. The resulting inclusion complexes span a continuum of binding modes-from relaxed encapsulation to strained, overpacked assemblies-governed by geometric complementarity and mutual host-guest deformation. These findings highlight the role of conformational flexibility in modulating molecular recognition under nanoscale confinement and establish flex-COP-n as a dynamic platform for mimicking adaptive features of biological receptors.