Rational construction and evaluation of a dual-functional near-infrared fluorescent probe for the imaging of Amyloid- and mitochondrial viscosity

Alzheimer's disease is a fatal, incurable, chronic neurodegenerative disease. Diagnosis in its early and even preclinical stages will be beneficial for its prevention and treatment. In the accepted pathological theory, abnormal accumulation of A beta protein and abnormal mitochondrial function, including changes in mitochondrial viscosity, is closely related to Alzheimer's disease. To date, rare fluorescent probes have been reported that can simultaneously image A beta plaques and mitochondrial viscosity. Therefore, the development of a dual-functional fluorescent probe for real-time fluorescence imaging of A beta plaques and mitochondrial viscosity is crucial to discover a novel approach and strategy for the treatment of Alzheimer's disease, and to understand the pathological process and crosstalk between different biomarkers of Alzheimer's disease. Herein, we rationally designed and synthesized a series of fluorescent probes QM-SF-1 similar to 5 with dimethylamino-quinolinium as the skeleton and thiophene as the 7C bridge to connect the groups with different electron-push/pull capacities. Among them, QMSF-2 exhibited excellent properties such as large Stokes shift (168 nm), near-infrared emission (689 nm), and high selectivity and sensitivity (limit of detection was 1.07 liM) to A beta aggregate and mitochondrial viscosity changes, indicating its promising prospects as a dual-functional imaging tool in the pathological study of Alzheimer's disease.