Issue 18, 2023

Monitoring amyloid aggregation via a twisted intramolecular charge transfer (TICT)-based fluorescent sensor array

Abstract

Imaging amyloid-beta (Aβ) aggregation is critical for understanding the pathology and aiding the pre-symptomatic intervention of Alzheimer's disease (AD). Amyloid aggregation consists of multiple phases with increasing viscosities and demands probes with broad dynamic ranges and gradient sensitivities for continuous monitoring. Yet, existing probes designed based on the twisted intramolecular charge transfer (TICT) mechanism mainly focused on donor engineering, limiting the sensitivities and/or dynamic ranges of these fluorophores to a narrow window. Herein, using quantum chemical calculations, we investigated multiple factors affecting the TICT process of fluorophores. It includes the conjugation length, the net charge of the fluorophore scaffold, the donor strength, and the geometric pre-twisting. We have established an integrative framework for tuning TICT tendencies. Based on this framework, a platter of hemicyanines with varied sensitivities and dynamic ranges is synthesized, forming a sensor array and enabling the observation of various stages of Aβ aggregations. This approach will significantly facilitate the development of TICT-based fluorescent probes with tailored environmental sensitivities for numerous applications.

Graphical abstract: Monitoring amyloid aggregation via a twisted intramolecular charge transfer (TICT)-based fluorescent sensor array

Supplementary files

Article information

Article type
Edge Article
Submitted
06 Dec 2022
Accepted
05 Apr 2023
First published
05 Apr 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 4786-4795

Monitoring amyloid aggregation via a twisted intramolecular charge transfer (TICT)-based fluorescent sensor array

C. Wang, W. Jiang, D. Tan, L. Huang, J. Li, Q. Qiao, P. Yadav, X. Liu and Z. Xu, Chem. Sci., 2023, 14, 4786 DOI: 10.1039/D2SC06710B

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