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

生命过程化学（CLP）计划中的这一奖项支持了蒂莫西·H. Warren博士在乔治敦大学进行了一氧化氮（NO）及其生化亲属S-亚硝基硫醇（RSNO）和硝酰基（HNO）在铜离子上的生成和相互转化的基础研究。 尽管NO和RSNO在导致生理反应如血管舒张沿着对HNO的兴趣迅速增长的生物化学信号传导途径中的重要性已经确立，但是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途径还没有被清楚地描述。 一个合成的建模方法将允许这些不同的NO-衍生物之间的转换，促进铜离子在富氮的协调环境中发现的生物学的详细检查。 铜位点的变化沿着机械和光谱研究将揭示促进或抑制这些过程的特定因素。 在这项工作中探索的铜络合物的直接合成将允许非常有限的合成经验的学生，或者根本没有，例如一年级的本科生。本研究将为评价铜离子在NO，RSNOs，和HNO从天然存在的前体如羟胺（H2 NOH）和N-羟基胍。 血红素自由的方法将照亮的作用，金属离子而不是铁在生物加工的一氧化氮及其分子亲属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.