Harnessing Intramolecular Rotation To Enhance Two-photon Imaging of Aβ Plaques through Minimizing Background Fluorescence

Jinwoo Shin, Peter Verwilst, Hayoung Choi, Sangrim Kang, Jiyou Han, Na Hee Kim, Jin Gyu Choi, Myung Sook Oh, Ji Sun Hwang, Dokyoung Kim, Inhee Mook-Jung, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)5648-5652
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number17
Publication statusPublished - 2019 Apr 16


  • Alzheimer's disease
  • fluorescent probes
  • imaging agents
  • molecular rotation
  • two-photon probes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)


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