Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
J Am Chem Soc. 2011 Aug 3;133(30):11675-85. doi: 10.1021/ja203652z. Epub 2011 Jul 11.
Recent studies distinguish the biological and pharmacological effects of nitroxyl (HNO) from its oxidized/deprotonated product nitric oxide (·NO), but the lack of HNO detection methods limits the understanding its in vivo mechanisms and the identification of endogenous sources. We previously demonstrated that reaction of HNO with triarylphosphines provides aza-ylides and HNO-derived amides, which may serve as stable HNO biomarkers. We now report a kinetic analysis for the trapping of HNO by phosphines, ligations of enzyme-generated HNO, and compatibility studies illustrating the selectivity of phosphines for HNO over other physiologically relevant nitrogen oxides. Quantification of HNO using phosphines is demonstrated using an HPLC-based assay and ligations of phosphine carbamates generate HNO-derived ureas. These results further demonstrate the potential of phosphine probes for reliable biological detection and quantification of HNO.
最近的研究将亚硝酰自由基（HNO）的生物学和药理学效应与其氧化/去质子化产物一氧化氮（·NO）区分开来，但缺乏 HNO 检测方法限制了对其体内机制的理解和内源性来源的识别。我们之前证明，HNO 与三芳基膦的反应提供了氮杂酰基和 HNO 衍生的酰胺，它们可以作为稳定的 HNO 生物标志物。我们现在报告了一种动力学分析，用于研究膦对 HNO 的捕获、酶生成的 HNO 的连接以及相容牲研究，这些研究说明了膦对 HNO 的选择性高于其他生理相关的氮氧化物。使用基于 HPLC 的测定法和膦氨基甲酸酯的连接来定量 HNO，生成 HNO 衍生的脲。这些结果进一步证明了膦探针在可靠的生物检测和 HNO 定量方面的潜力。
