Near-Infrared Fluorescent Probes with Rotatable Polyacetylene Chains for the Detection of Amyloid-β Plaques

The plaques of accumulated β-amyloid (Aβ) in the parenchymal brain are accepted as an important biomarker for the early diagnosis of Alzheimer's disease (AD). Many near-infrared (NIR) probes, which were based on the D−π–A structure and bridged by conjugated double bonds, had been reported and displayed a high affinity to Aβ plaques. Considering the isomerization caused by the polyethylene chain, however, the conjugated polyacetylene chain is a better choice for developing new NIR Aβ probes. Hence, in this report, a new series of NIR probes with naphthyl or phenyl rings and different numbers of conjugated triple bonds were designed, synthesized, and evaluated as NIR probes for Aβ plaques. Upon interaction with Aβ aggregates, these probes displayed a significant increase in fluorescence intensity (45- to 360-fold) and a high to moderate affinity (6.05–56.62 nM). Among them, probe 22b displayed excellent fluorescent properties with a 183-fold increase in fluorescence intensity and an emission maximum at 650 nm after incubated with Aβ aggregates. Furthermore, 22b had a high affinity to Aβ aggregates (Kd = 12.96 nM) and could efficiently detect the Aβ plaques in brain sections from both transgenic mice and AD patients in vitro. In summary, this work may lead to a new direction in the development of novel NIR probes for the detection of Aβ plaques.