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

生命过程化学（CLP）项目的这一奖项支持乔治城大学的Timothy H. Warren教授对铜离子中一氧化氮（NO）及其生化亲族s -亚硝基硫醇（RSNO）和硝基（HNO）的生成和相互转化的基础研究。尽管NO和RSNOs在导致血管舒张等生理反应的生化信号通路中具有既定的重要性，但与一氧化氮生物学相关的这些分子的产生和相互转化的酶促途径尚未明确描述。合成建模方法将允许详细检查铜离子在与生物学中发现的富氮配位环境中促进的这些各种no衍生物之间的转化。铜位点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具体因素。在这项工作中探索的铜配合物的直接合成将允许那些合成经验非常有限的学生，或者根本没有合成经验的学生，比如一年级本科生（甚至高中）的学生，为这个项目做出贡献。该研究将为评估铜离子在天然前体如羟胺（H2NOH）和n -羟基胍中NO、RSNOs和HNO的生物形成和相互转化中的作用奠定坚实的基础。无血红素方法将阐明除铁以外的金属离子在一氧化氮及其分子亲戚的生物处理中所起的作用，这些分子亲戚参与了无数的生理事件。

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.