Diazine <i>Endo</i> ‐Functionalized Tetraphenylethylene‐Based Cyclo[6]arenes for Molecular Recognition in Both Solution and Aggregate States

ABSTRACT Merging tetraphenylethylene (TPE) into cyclic skeletons endows fluorescent sensing capabilities for pillar[6]arenes aggregates, but results in losing their host–guest recognition function in dilute solutions. Inspired by natural enzymes, here we describe a series of TPE‐based cyclo[6]arenes (termed TPz , TDz , and TTz ) with endo ‐functionalized cavities containing inward‐directed diazine motifs (pyrazine, pyridazine, and phthalazine) that act as hydrogen‐bond acceptor sites. Combining electrostatic potential analysis and host–guest binding studies reveals that subtle variations in these diazine motifs substantially affect charge distribution and hydrogen‐bond interactions within the internal microenvironment. These differences translate into disparate host–guest affinities, with TTz exhibiting the optimal performance. Unlike TPz , which recognizes guests only in aggregate states, 1,2‐diazine‐modified TDz and TTz possess dual‐state recognition functionality. They enable size‐selective binding for cationic guests in dilute solutions and sensitive fluorescence detection of nitrophenol pollutants in aggregate states through a photoinduced electron transfer‐driven static quenching mechanism. This study underscores the potential of 1,2‐diazine motifs as transformative hydrogen‐bond acceptors for biomimetic host models with emergent properties.