Enhanced β-Amyloid Aggregation in Living Cells Imaged with Quinolinium-Based Spontaneous Blinking Fluorophores

Abstract

Abnormal accumulation of intracellular and extracellular β-amyloid (Aβ) aggregates is closely related to the pathogenesis of Alzheimer's disease (AD). In this work, we use quinolinium derivatives with electron-rich aniline substituents as the skeletons to develop a set of spontaneous blinking fluorophores by the formation of long-lived radicals. These probes can target Aβ 1−40 aggregates and exhibit strong deep-red emission upon binding to Aβ 1−40 aggregates. More importantly, at the singlemolecule level, these probes display spontaneous blinking, low duty cycle, and high photon output, which are suitable for the nanoscopic imaging of Aβ aggregates in living cells. The assembly process of the Aβ aggregates was then tracked with nanoscopic imaging. The elongation rate on the cell membrane was noticeably fast over that in the solution. This work provides a feasible strategy for the design of spontaneous blinking fluorophores for Aβ aggregates.

Synthesis, Photophysical Properties, Theoretical Studies, and Living Cancer Cell Imaging Applications of New 7-(Diethylamino)quinolone Chalcones

“…In all dyes, the emission displayed a fluorescence quenching with a red shift upon increasing amounts of water ( f W ) attributed to the influence of the TICT effect. In the TICT state, an N,N -diethylamino donor undergoes a torsional motion of around 90° when exposed to light, creating a chemically active species that does not emit light. − Molecules exhibiting TICT characteristics are consistently identified by their substantial molecular dipoles and a distinct uneven distribution of electrons in emission-related frontier molecular orbitals. These characteristics are confirmed by theoretical calculation results.…”