Photoactivatable Fluorogens by Intramolecular C–H Insertion of Perfluoroaryl Azide

Abstract

Molecules, capable of fluorescence turn-on by light, are highly sought-after in spatio-temporal labeling, surface patterning, monitoring cellular and molecular events, and high-resolution fluorescence imaging. In this work, we report a fluorescence turn-on system based on photoinitiated intramolecular C-H insertion of azide into the neighboring aromatic ring. The azide-masked fluorogens were efficiently synthesized via a cascade nucleophilic aromatic substitution of perfluoroaryl azides with carbazoles. The scaffold also allows for derivatization with biological ligands, as exemplified with D-mannose in this study. This photoinitiated intramolecular transformation led to high yields, high photo-conversion efficiency, and wellseparated wavelengths for photoactivation and fluorescence excitation. The mannose-derivatized structure enabled spatio-temporal activation and showed high contrast and signal amplification. Live cell imaging suggested that the mannose-tagged fluorogen was transported to the lysosomes.

Clickable Azide-Functionalized Bromo-Aryl-Aldehydes – Synthesis and Photophysical Characterization

“…This may be owing to the azide-moiety either as functional group or as part of the triazole heterocycle. Similar observations were already made on luminescent materials [73,74].…”

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

“…This may be owing to the azide moiety, either as a functional group or as part of the triazole heterocycle. Similar observations were already made for luminescent materials [74,75].…”

Azide-Masked and Trehalose-based Fluorescence Turn-On Probe for Mycobacteria

“…Tre-Cz was prepared by coupling the amine-derivatized trehalose V (Scheme S1) with the N-hydroxysuccinimide (NHS)-functionalized carbazole IV (Scheme S3). 17,33,[35][36][37][38] The reaction was carried out at room temperature in N,Ndimethylformamide (DMF), giving Tre-Cz in 60% yield (Scheme 2). Maltose (Mal), a disaccharide that consists of two glucose units like trehalose but has an a-1,4-glycosidic linkage instead of an a-1,1-glycosidic linkage in trehalose, was used as the control.…”

“…Photoactivation of the aryl azide generates the singlet nitrene, which reacts with the neighboring aryl ring through a C-H insertion reaction to form a fluorescent product P (Scheme 1). 17,33,34 We show that Tre-Cz was taken up by metabolically active mycobacteria, and the uptake was dependent on the LpqY-SugABC recycling transporter. Tre-Cz is highly specific to mycobacteria and was able to image mycobacteria in the presence of other Gram-positive and Gram-negative bacteria, as well as in sputum.…”