ACQ to AIE Switch of Rofecoxib Analogues via Positional Regulation of Donor–Acceptor and Their Fluorescent Behaviors

Abstract The conversion of aggregation‐caused quenching (ACQ) materials into aggregation‐induced emission (AIE) systems holds significant promise for expanding the library of AIEgens. In this study, we present two positional isomerization strategies to achieve ACQ‐to‐AIE photophysical switching based on a rofecoxib‐derived scaffold. The parent compound ROM , featuring a dimethylamino donor (D) and methanesulfonyl acceptor (A), exhibited typical ACQ behavior. Remarkably, relocating the D unit to generate M‐ROM or exchanging D‐A positions to form S‐ROM resulted in distinct AIE characteristics. Single‐crystal X‐ray analysis revealed that J‐aggregation modes and enhanced intermolecular interactions (C─H···π and C─H···O) in M‐ROM and S‐ROM restrict intramolecular motion, suppressing non‐radiative decay. All three compounds demonstrated solvatochromism and reversible acidochromism, with S‐ROM exhibiting ultrasensitive water detection in THF (LoD: 0.0106%) and rewritable security ink functionality via acid/base‐triggered emission switching. Furthermore, S‐ROM showed exceptional lipid droplet imaging specificity in live cells (Pearson's coefficient: 0.98), supported by low cytotoxicity. Taken together, this work not only synthesized two new AIE materials with multistimulus responsive ability, but also provides new perspective strategies for achieving ACQ to AIE conversion.