Photostable AIE luminogens for specific mitochondrial imaging and its method of manufacturing thereof

Patent metadata

Field	Value
Publication number	US-9315465-B2
Application number	US-201414164591-A
Country	US
Kind code	B2
Filing date	Jan 27, 2014
Priority date	Jan 29, 2013
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

AIE (aggregation-induced emission)-active TPE derivatives, TPE-TPP, TPE-MitoR and TPE-IQ are contemplated. These specific TPE derivatives are useful as fluorescent agents for mitochondrial imaging and as apoptosis inducers. Possessing high specificity to mitochondria, superior photostability and appreciable tolerance to microenvironment change, TPE derivatives are well-suited imaging agents for mitochondrial targeting and morphological change tracking. Because of their synthetic flexibility, TPE derivatives can be further modified as dual-functional probes for an array of applications such as sensing of ROS, metal ions, or pH change in mitochondria.

First claim

We claim:

1. A luminogen having aggregation-induced emission properties comprising a triphenylphosphonium-functionalized, benzothiazolium-functionalized, or isoquinoline-functionalized TPE derivative, wherein the TPE derivative comprises a backbone structure of a formula:

or a salt thereof, wherein R and R′ are each independently selected from the group consisting of

2. A method of imaging mitochondria in cells comprising:
contacting one or more live cells with a luminogen having aggregation-induced emission properties comprising a triphenylphosphonium-functionalized, benzothiazolium-functionalized, or isoquinoline-functionalized TPE derivative, wherein the TPE derivative comprises a backbone structure of a formula:

or a salt thereof, wherein R and R′ are each independently selected from the group consisting of

and imaging any mitochondrial activities.

3. The method of claim 2 , wherein the TPE derivative enters mitochondria through electrophoretic force and lipophilic interaction, activating fluorescence of the TPE derivative.

4. The method of claim 2 , wherein the living cells are living mammalian cells.

5. The method of claim 4 , wherein the triphenylphosphonium-functionalized, benzothiazolium-functionalized, or isoquinoline-functionalized TPE Derivative is incubated with the living mammalian cells.

6. The method of claim 5 , wherein fluorescence images are visualized by a fluorescence microscope and confocal microscope in the presence of the triphenylphosphonium-functionalized, benzothiazolium-functionalized, or isoquinoline-functionalized TPE Derivative with the living mammalian cells.

7. A method for in vivo monitoring of cell apoptosis comprising injecting a subject with the luminogen of claim 1 and detecting fluorescence, wherein the triphenylphosphonium-functionalized, benzothiazolium-functionalized, or isoquinoline-functionalized TPE Derivative is used as an apoptosis inducer.

Assignees

• Univ Hong Kong Science & Techn

Inventors

• Tang Benzhong
• Hong Yuning
• Chen Sijie
• Leung Wai Tung
• Zhao Engui
• Deng Haiqin

Classifications

• C07F9/5449

  Polyphosphonium compounds · CPC title

• C07D209/08

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• A61K49/0023

  Di-or triarylmethane dye (xanthene dyes A61K49/0041) · CPC title

• C07D217/04 Primary

  with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom · CPC title

• G01N33/52

  Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper {and including single- and multilayer analytical elements (immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72)} · CPC title