NitroxylFluor: A Thiol-Based Fluorescent Probe for Live-Cell Imaging of Nitroxyl

Nicholas W. Pino, Jerome Davis, Zhengxin Yu, Jefferson Chan

Research output: Contribution to journalArticle

Abstract

Detection of nitroxyl (HNO), the transient one-electron reduced form of nitric oxide, is a significant challenge owing to its high reactivity with biological thiols (with rate constants as high as 109 M-1 s-1). To address this, we report a new thiol-based HNO-responsive trigger that can compete against reactive thiols for HNO. This process forms a common N-hydroxysulfenamide intermediate that cyclizes to release a masked fluorophore leading to fluorescence enhancement. To ensure that the cyclization step is rapid, our design capitalizes on two established physical organic phenomena; the alpha-effect and the Thorpe-Ingold effect. Using this new trigger, we developed NitroxylFluor, a selective HNO-responsive fluorescent probe. Treatment of NitroxylFluor with an HNO donor results in a 16-fold turn-on. This probe also exhibits excellent selectivity over various reactive nitrogen, oxygen, and sulfur species and efficacy in the presence of thiols (e.g., glutathione in mM concentrations). Lastly, we successfully performed live cell imaging of HNO using NitroxylFluor.

Original languageEnglish (US)
Pages (from-to)18476-18479
Number of pages4
JournalJournal of the American Chemical Society
Volume139
Issue number51
DOIs
StatePublished - Dec 27 2017

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'NitroxylFluor: A Thiol-Based Fluorescent Probe for Live-Cell Imaging of Nitroxyl'. Together they form a unique fingerprint.

  • Cite this