Generation and Solution Reactivity of Nitroxyl (HNO)

有机化学和高分子化学项目继续支持约翰·霍普金斯大学化学系约翰·托斯卡诺教授的工作。这项研究将把PI对活性中间体的研究扩展到涉及硝基(HNO)的生成和溶液反应性的研究。这项研究将致力于两个主要目标：(1)开发各种新的HNO光化学和热前驱体；(2)利用这些前驱体(以及现有的前驱体)来阐明HNO的基本溶液相化学。将研究的HNO的光化学前体包括HNO-二烯Diels-Alder加合物、羟基氮(HON)前体和光敏性O-取代磺基异羟肟酸衍生物。该项目将使用纳秒时间分辨红外光谱(TRIR)，以及更标准的实验和计算工具。将尝试在水溶液和有机溶剂中用三次红外光谱直接检测HNO。硝基体系的生物化学最近受到了极大的关注，特别是作为目前治疗心力衰竭的一种潜在的选择。尽管人们已经将独特的生物反应归因于氮氧基，但对这个看似简单的体系的基本溶液化学知之甚少。有关氮氧基的机制信息对许多生物体的生理学都有影响，对生物医学界来说将是非常有价值的。这项研究将为将获得广泛技能的学生提供广泛的培训。将强调本科生参与拟议的研究，约翰霍普金斯大学和附近的汤森大学的学生参与其中。

With this renewal award, the Organic and Macromolecular Chemistry Program continues its support of the work of Professor John Toscano of the Chemistry Department at Johns Hopkins University. The research will extend the PI's studies of reactive intermediates to research involving the generation and solution reactivity of nitroxyl (HNO). The research will address two main goals: (1) to develop a variety of new photochemical and thermal precursors to HNO and (2) to use these precursors (as well as existing ones) to elucidate the fundamental solution-phase chemistry of HNO. Photochemical precursors to HNO that will be examined include HNO-diene Diels-Alder adducts, hydroxynitrene (HON) precursors, and photosensitive O-substituted sulfohydroxamic acid derivatives. The project will involve the use of nanosecond time-resolved infrared (TRIR) spectroscopy, as well as more standard experimental and computational tools. The direct detection of HNO by TRIR spectroscopy in both aqueous and organic solvents will be attempted. The reactivity of HNO with various species of both fundamental and biological interest will also be examined by TRIR spectroscopy.The biochemistry of the nitroxyl system has recently received significant attention, especially as a potential alternative to current treatments of cardiac failure. Although unique biological responses have been attributed to nitroxyl, very little is known about the fundamental solution chemistry of this deceptively simple system. The mechanistic information concerning nitroxyl, which impacts upon the physiology of many organisms, will be extremely valuable to the biomedical community. This research will afford broad training for students who will acquire a wide range of skills. Undergraduate participation in the proposed research will be emphasized with students from Johns Hopkins University and nearby Towson University involved.