Rational Design and Facile Synthesis of a Highly Tunable Quinoline-Based Fluorescent Small-Molecule Scaffold for Live Cell Imaging

Journal of the American Chemical Society
Joomyung V JunDavid M Chenoweth

Abstract

Small-molecule fluorescent probes are powerful tools for chemical biology; however, despite the large number of probes available, there is still a need for a simple fluorogenic scaffold, which allows for the rational design of molecules with predictable photophysical properties and is amenable to concise synthesis for high-throughput screening. Here, we introduce a highly modular quinoline-based probe containing three strategic domains that can be easily engineered and optimized for various applications. Such domains are allotted for (1) compound polarization, (2) tuning of photophysical properties, and (3) structural diversity. We successfully synthesized our probes in two steps from commercially available starting materials in overall yields of up to 95%. Facile probe synthesis was permitted by regioselective palladium-catalyzed cross-coupling, which enables combinatorial development of structurally diverse quinoline-based fluorophores. We have further applied our probes to live-cell imaging, utilizing their unique two-stage fluorescence response to intracellular pH. These studies provide a full demonstration of our strategy in rational design and stream-lined probe discovery to reveal the diverse potential of quinoline-based...Continue Reading

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Citations

Nov 28, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Maria StrianeseClaudio Pellecchia
Jan 10, 2020·Chembiochem : a European Journal of Chemical Biology·Pankaj E HandeSantosh J Gharpure
Jul 22, 2020·Organic & Biomolecular Chemistry·Joomyung V JunE James Petersson
Jul 1, 2020·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Giovanny Carvalho Dos SantosJohannes Gierschner
Dec 8, 2020·Chemical Society Reviews·Liqian GaoShao Q Yao
Jun 1, 2021·ACS Medicinal Chemistry Letters·René MaltaisDonald Poirier
Jun 2, 2021·Chembiochem : a European Journal of Chemical Biology·Sachin B WaghAlexander Kornienko
Nov 13, 2019·ACS Synthetic Biology·Michael Patrick Torrens-SpenceJing-Ke Weng
Dec 29, 2020·The Journal of Organic Chemistry·Savio CardozaVibha Tandon
Dec 7, 2019·ACS Central Science·Krysten A JonesBryan C Dickinson
Sep 14, 2021·Journal of the American Chemical Society·Elizabeth M SantosBabak Borhan
Oct 26, 2021·Chembiochem : a European Journal of Chemical Biology·Pankaj E HandeSantosh J Gharpure

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