A Reductant-Resistant and Metal-Free Fluorescent Probe for Nitroxyl Applicable to Living Cells

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• 作者：Kodai Kawai ; Naoya Ieda ; Kazuyuki Aizawa ; Takayoshi Suzuki ; Naoki Miyata ; Hidehiko Nakagawa
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：August 28, 2013
• 年：2013
• 卷：135
• 期：34
• 页码：12690-12696
• 全文大小：421K
• 年卷期：v.135,no.34(August 28, 2013)
• ISSN：1520-5126

文摘

Nitroxyl (HNO) is a one-electron reduced and protonated derivative of nitric oxide (NO) and has characteristic biological and pharmacological effects distinct from those of NO. However, studies of its biosynthesis and activities are restricted by the lack of versatile HNO detection methods applicable to living cells. Here, we report the first metal-free and reductant-resistant HNO imaging probe available for use in living cells, P-Rhod. It consists of a rhodol derivative moiety as the fluorophore, linked via an ester moiety to a diphenylphosphinobenzoyl group, which forms an aza-ylide upon reaction with HNO. Intramolecular attack of the aza-ylide on the ester carbonyl group releases a fluorescent rhodol derivative. P-Rhod showed high selectivity for HNO in the presence of various biologically relevant reductants, such as glutathione and ascorbate, in comparison with previous HNO probes. We show that P-Rhod can detect not only HNO enzymatically generated in the horseradish peroxidase-hydroxylamine system in vitro but also intracellular HNO release from Angeli鈥檚 salt in living cells. These results suggest that P-Rhod is suitable for detection of HNO in living cells.