HNO, NO, and RSNO Formation and Reactivity at Non-Heme Sites

HNO、NO 和 RSNO 在非血红素位点的形成和反应性

• 批准号: 0957606
• 负责人: Timothy Warren
• 金额: $ 43.25万
• 依托单位: Georgetown University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0957606&HistoricalAwards=false
• 关键词: HNO; NO; RSNO; Formation; Reactivity

This award in the Chemistry of Life Processes (CLP) program supports work by Professor Timothy H. Warren at Georgetown University to carry out fundamental studies on the generation and interconversion of nitric oxide (NO) and its biochemical relatives S-nitrosothiols (RSNO) and nitroxyl (HNO) at copper ions. Despite the established importance of NO and RSNOs in biochemical signaling pathways leading to physiological responses such as vasodilation along with a rapidly growing interest in HNO, enzymatic pathways for the generation and interconversion of these molecules connected to the biology of nitric oxide are not clearly delineated. A synthetic modeling approach will allow for the detailed examination of transformations among these various NO-derivatives promoted by copper ions in nitrogen-rich coordination environments related to those found in biology. Variation of the copper site along with mechanistic and spectroscopic study will reveal specific factors that promote or inhibit these processes. The straightforward synthesis of copper complexes explored in this work will allow students with very limited synthetic experience, or none at all, such as first year undergraduate (or even high school) students, to contribute to the project.This study will lay a firm foundation upon which to assess the role of copper ions in the biological formation and interconversion of NO, RSNOs, and HNO from naturally occurring precursors such as hydroxylamine (H2NOH) and N-hydroxyguanidines. The heme-free approach will illuminate roles that metal ions other than iron play in the biological processing of nitric oxide and its molecular relatives which are involved in a myriad of physiological events.

生命过程化学(CLP)项目的这一奖项支持乔治敦大学的Timothy H.Warren教授开展基础研究，研究一氧化氮(NO)及其生化近亲S-亚硝硫醇(RSNO)和氮氧基(HNO)在铜离子上的生成和相互转化。尽管NO和RSNO在导致血管扩张等生理反应的生化信号通路中的重要性已经得到证实，而且人们对HNO的兴趣也迅速增长，但这些与一氧化氮生物学相关的分子的产生和相互转化的酶途径尚未被清楚地描绘出来。合成建模方法将允许详细检查在富氮配位环境中由铜离子促进的这些不同NO-衍生物之间的转化，这些转化与生物学中发现的相关。铜位置的变化以及机理和光谱研究将揭示促进或抑制这些过程的特定因素。这项工作中探索的铜络合物的直接合成将允许合成经验非常有限的学生或根本没有合成经验的学生为该项目做出贡献。这项研究将为评估铜离子在生物形成和转化NO、RSNO和HNO过程中的作用奠定坚实的基础。这种无血红素的方法将阐明铁以外的金属离子在一氧化氮及其分子相关物质的生物过程中所起的作用，这些物质参与了无数的生理事件。