Harnessing Intramolecular Rotation To Enhance Two‐photon Imaging of Aβ Plaques through Minimizing Background Fluorescence. Issue 17 (20th March 2019)

• Record Type: Journal Article
• Authors: Shin, Jinwoo; Verwilst, Peter; Choi, Hayoung; Kang, Sangrim; Han, Jiyou; Kim, Na Hee; Choi, Jin Gyu; Oh, Myung Sook; Hwang, Ji Sun; Kim, Dokyoung; Mook‐Jung, Inhee; Kim, Jong Seung
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 17(2019)
• Page Start: 5648
• Page End: 5652
• Publication Date: 2019-03-20
• Subjects: Alzheimer's disease -- fluorescent probes -- imaging agents -- molecular rotation -- two-photon probes; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201900549
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The aggregation of amyloid beta (Aβ) proteins in senile plaques is a critical event during the development of Alzheimer's disease, and the postmortem detection of Aβ‐rich proteinaceous deposits through fluorescent staining remains one of the most robust diagnostic tools. In animal models, fluorescence imaging can be employed to follow the progression of the disease, and among the different imaging methods, two‐photon microscopy (TPM) has emerged as one of the most powerful. To date, several near‐infrared‐emissive two‐photon dyes with a high affinity for Aβ fibrils have been developed, but there has often been a tradeoff between excellent two‐photon cross‐sections and large fluorescence signal‐to‐background ratios. In the current work, we introduced a twisted intramolecular charge state (TICT)‐based de‐excitation pathway, which results in a remarkable fluorescence increase of around 167‐fold in the presence of Aβ fibrils, while maintaining an excellent two‐photon cross section, thereby enabling high‐contrast ex vivo and in vivo TPM imaging. Overall, the results suggest that adopting TICT de‐excitation in two‐photon fluorophores may represent a general method to overcome the tradeoff between probe brightness and signal‐to‐background ratio. Abstract : Do the twist : A twisted intramolecular charge state (TICT)‐based de‐excitation pathway was introduced in an Aβ dye. This gave a 167‐fold fluorescence increase in the presence of Aβ fibrils, while maintaining an excellent two‐photon cross‐section, thereby enabling high‐contrast two‐photon microscopy (TPM) imaging. TICT de‐excitation in two‐photon fluorophores may represent a general method to overcome the tradeoff between brightness and signal‐to‐background ratio.