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

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 fluorescent compounds.

• Publication year

  2018

• Venue

  Journal of the American Chemical Society

• Publication date

  2018-07-20

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1021/jacs.8b03738PMID 30028130PMCID PMC7484945
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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