Synthesis and characterization of coumarin-quinoline based NIR probes for viscosity: Mitochondria-Targeted probe with superior performance in autophagy and liver injury imaging.

BACKGROUND: Near-infrared (NIR) fluorescent probes with aggregation-induced emission (AIE) properties are highly desirable for biomedical imaging. Viscosity is a critical parameter reflecting microenvironment stability, and abnormal mitochondrial viscosity is linked to many diseases and cellular dysfunctions. Therefore, it is of important significance to develop new NIR fluorescent probes that can monitor the variations of mitochondrial viscosity accurately and in real time.

RESULTS: We developed three new NIR fluorescent probes (QI-1, QI-2, QI-3) based on a coumarin-quinoline structure with a donor-π-acceptor (D-π-A) design. These probes exhibit strong intramolecular charge transfer (ICT). Compared with the compounds QI-2 and QI-3, QI-1 showed outstanding performance, including excellent AIE behavior, a large Stokes shift, high quantum yield and high sensitivity to viscosity. Biological studies confirmed that QI-1 selectively localizes in mitochondria. This enables real-time monitoring of viscosity changes during cellular autophagy and in a mouse model of drug-induced (APAP) liver injury.

SIGNIFICANCE: This work presents a rational and effective design strategy for developing NIR fluorescent probes with AIE characteristics, specifically tailored for sensing microenvironmental viscosity. Probes based on this strategy allow for non-invasive, high-contrast visualization of pathophysiological processes across multiple biological scales, ranging from subcellular organelles to tissue microenvironments. This lays the foundation for advanced diagnostics and a deeper mechanistic understanding of mitochondrial dysfunction-related diseases.