Generation and Solution Reactivity of Nitroxyl (HNO)

有了这个更新的奖项，有机和大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。该研究将扩展PI对反应性中间体的研究，以研究硝基（HNO）的生成和溶液反应性。该研究将解决两个主要目标：(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）阐明HNO的基本溶液化学。将研究的HNO光化学前体包括HNO-二烯Diels-Alder加合物，羟基硝基烯（HON）前体和光敏o取代磺羟肟酸衍生物。该项目将涉及使用纳秒时间分辨红外（TRIR）光谱，以及更多标准的实验和计算工具。将尝试用TRIR光谱法直接检测水溶液和有机溶剂中的HNO。HNO与各种具有基础和生物意义的物种的反应性也将通过TRIR光谱进行研究。硝基系统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潜在替代方法。虽然独特的生物反应归因于硝基，但对这个看似简单的系统的基本溶液化学知之甚少。硝基对许多生物的生理产生影响，有关其机理的信息对生物医学界具有极大的价值。这项研究将为获得广泛技能的学生提供广泛的训练。约翰霍普金斯大学和附近的陶森大学的学生将重点参与拟议的研究。

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.