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 reveal 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 photo-induced 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.