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

Abstract

AbstractRegio‐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.