Modulation of AIE\nand Intramolecular Charge Transfer\nof a Pyrene-Based Probe for Discriminatory Detection and Imaging of\nOligomers and Amyloid Fibrils

Oligomers and amyloid fibrils formed at different stages\nof protein\naggregation are important biomarkers for a variety of neurodegenerative\ndiseases including Alzheimer’s and Parkinson’s diseases.\nThe development of probes for the sensitive detection of oligomeric\nspecies is important for early stage diagnosis of amyloidogenic diseases.\nMany small molecular dyes have been developed to probe the dynamic\ngrowth of amyloid fibrils. However, there is a lack of discriminatory\ndetection strategies to monitor the dynamics of both oligomers and\namyloid fibrils based on the differential modulation of the photophysical\nproperties of a single dye. Here we report a pyrene-based intramolecular\ncharge transfer (ICT) dye with large Stokes shifted red-emitting aggregation\ninduced emission (AIE) for monitoring the dynamic populations of both\noligomers and fibrils during the aggregation of hen egg white lysozyme\n(HEWL) protein. At the early stage of protein aggregation, the accumulation\nof HEWL oligomers results in a rapid and substantial increase in the\nred AIE intensity at 660 nm. Later, as the oligomers transform into\nmature fibrils, the dye exhibits a distinct photophysical change.\nBinding of the dye to HEWL fibrils strongly suppresses the red AIE\nand enhances ICT emission. This is evidenced by a gradual decrease\nin the AIE intensity (∼660 nm) and an increase in LE (∼490\nnm) and ICT (∼540 nm) emission intensities during the later\nstages of protein aggregation. Thus, the dye provides simultaneous\nmeasurements of the population dynamics of both HEWL oligomers and\nfibrils during protein aggregation based on the discriminatory modulation\nof AIE and ICT of the dye. The dye also enables imaging of both HEWL\noligomers and fibrils simultaneously using different emission channels\nin super-resolution confocal fluorescence microscopy.