Development of Photoactivated Fluorescent N-Hydroxyoxindoles and Their Application for Cell-Selective Imaging

Details

• Alternative Title:
  Chemistry
• Personal Author:
  Lai, Jinping ; Yu, An ; Yang, Letao ; Zhang, Yixiao ; Shah, Birju P. ; Lee, Ki Bum
• Description:
  Photoactivatable fluorophores are essential tools for studying the dynamic molecular interactions within important biological systems with high spatiotemporal resolution. However, currently developed photoactivatable fluorophores based on conventional dyes have several limitations including reduced photoactivation efficiency, cytotoxicity, large molecular size, and complicated organic synthesis. To overcome these challenges, we herein report a class of photoactivatable fluorescent N-hydroxyoxindoles formed through the intramolecular photocyclization of substituted o-nitrophenyl ethanol (ONPE). These oxindole fluorophores afford excellent photoactivation efficiency with ultra-high fluorescence enhancement (up to 800-fold) and are small in size. Furthermore, the oxindole derivatives show exceptional biocompatibility by generating water as the only photolytic side product. Moreover, structure-activity relationship analysis clearly revealed the strong correlation between the fluorescent properties and the substituent groups, which can serve as a guideline for the further development of ONPE-based fluorescent probes with desired photophysical and biological properties. As a proof-of-concept, we demonstrated the capability of a new substituted ONPE that has an uncaging wavelength of 365-405 nm and an excitation/emission at 515 and 620 nm, for the selective imaging of a cancer cell line (Hela cells) and a human neural stem cell line (hNSCs).
• Subjects:
  Fluorescent Dyes HeLa Cells Humans Indoles Molecular Dynamics Simulation Oxindoles Photochemical Processes Photolysis Structure-Activity Relationship
• Keywords:
  Cage Compounds Dyes/Pigments Fluorescence Imaging Fluorescent Probes Oxindole
• Source:
  Chemistry. 22(18):6361-6367
• Pubmed ID:
  27004772
• Pubmed Central ID:
  PMC5808866
• Document Type:
  Journal Article
• Funding:
  DP2 OD006462/OD/NIH HHSUnited States/ ; R21 NS085569/NS/NINDS NIH HHSUnited States/ ; 1DP20D006462-01/DP/NCCDPHP CDC HHSUnited States/ ; 1R21NS085569-01/NS/NINDS NIH HHSUnited States/
• Volume:
  22
• Issue:
  18
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:9dff01eee440af67801cdf7f9f25e8eeacff2a2b917a12be528d1f961ef326fa
• Download URL:
  https://stacks.cdc.gov/view/cdc/51677/cdc_51677_DS1.pdf
• File Type:
  [PDF - 834.77 KB ]