Intermolecular Assembly of Dual Hydrogen Bonding Regio-Isomers Generates High-Performance AIE Probes

Regio-isomers are utilized to design innovative AIE luminogens (AIEgens) by regulating molecular aggregation behavior. However, relevant examples are limited, and the underlying mechanism is not fully understood. Herein, a regio-isomer strategy is used to develop AIEgens by precisely regulating the intermolecular interactions in the solid state. Among the regio-isomers it is investigated, ortho- isomer (DCM-O3-O7) exhibits enhanced AIE-activity than the para- isomer (DCM-P6), and the size of the ortho- substituents is crucial for the AIE performance. The underlying mechanism of the strategy is revealed using DFT calculations and single-crystal analysis. Dual hydrogen bonds (C─H∙∙∙π and C─H∙∙∙N) are generated between the molecules, which contributes to form dimers, tetramers, and 1D supramolecular structures in the crystal. By restricting intramolecular motion and attenuating π–π interactions, solid-state fluorescence is significantly enhanced. This strategy's effectiveness is validated using other donor–acceptor fluorophores, with DCM-O6 and its analogues serving as efficient probes for bioimaging applications. Notably, DCM-OM, which bears a morpholinyl instead of piperidinyl group, displayed strong lysosome-targeting ability and photostability; DCM-OP, incorporated by the hydrophilic quaternary ammonium group, exhibited wash-free imaging and cell membrane-targeting capabilities; and DCM-O6 nanoparticles enabled high-fidelity in vivo tumor imaging. Therefore, this strategy affords a general method for designing bright AIEgens.