Bright NIR‐II AIEgens Enabled by Hydrogen‐Bond‐Assisted Conformational Locking for In Vivo Ischemia Imaging

ABSTRACT Early and highly sensitive detection of ischemia‐reperfusion injury (IRI) remains a major challenge in clinical diagnosis. In this context, the second near‐infrared (NIR‐II) fluorescence imaging has been recognized as a powerful approach with the benefits of deep tissue penetration and high contrast. However, developing NIR‐II fluorophores that simultaneously exhibit large absorption coefficients and high brightness remains challenging. Herein, we propose a stepwise intramolecular locking strategy that integrates covalent and hydrogen‐bond locks to construct highly bright NIR‐II aggregation‐induced emission luminogens (AIEgens) without the need for extension of π ‐fused frameworks. As a result, PTN‐4TPA was synthesized through stepwise rigidification of the molecular framework, wherein intramolecular hydrogen bonds enforce a planar donor–acceptor conformation, enhance charge transfer, and promote J‐type aggregation. These combined effects lead to a high molar extinction coefficient and enhanced brightness in the aggregated state. PTN‐4TPA nanoparticles (NPs) exhibit a 2.18‐fold brightness enhancement compared to the non‐hydrogen‐bonded analogue. Furthermore, the NPs enable deep‐tissue NIR‐II fluorescence imaging and sensitive visualization of thrombus formation in acute hindlimb and mesenteric thrombus models, achieving signal‐to‐background ratios up to 4.34. These results suggest that hydrogen‐bond locking provides an effective strategy to achieve high molar extinction coefficient and enhanced brightness of NIR‐II fluorophores.