Non-Heme Iron(II)-Nitrosyl and -Nitroxyl Complexes: Key Intermediates in Nitric Oxide Reductases

有了这个奖项，化学部的生命过程化学计划正在资助密歇根大学的Nicolai Lehnert博士为细菌一氧化氮还原酶（NORs）活性位点的单核和双核非血红素铁中心制备模型复合物，并研究相应的亚硝酰基（NO）和硝酰基（NO-/HNO）复合物在这些酶的机制中发挥的作用。将采用先进的动力学和光谱方法，包括共振拉曼和磁性圆二色性。 NORs存在于细菌和病原菌中，并且被认为在它们感染哺乳动物宿主的能力中发挥作用，因为NORs使这些细菌对NO具有抗性，NO是哺乳动物中的主要免疫防御剂。此外，非血红素铁酶可能通过形成Fe（II）-NO/HNO中间体参与生物系统中硝酰基的产生和感测，但这些物种的性质还不清楚。Lehnert博士和他的团队将着手确定这些物种的几何结构和电子结构，并研究它们的生物相关反应性。一氧化氮（NO）在哺乳动物中作为信号分子生物合成，并作为免疫防御剂（由巨噬细胞）对抗入侵的病原体。然而，某些细菌已经进化出称为一氧化氮还原酶（NORs）的酶，通过还原为无毒的一氧化二氮（N2 O）和水来有效地解毒NO。因此，NORs被认为会促进人体感染，导致慢性疾病。尽管NORs对细菌致病的重要性，但这些酶还原NO的基本机制还不清楚。拟议的研究旨在阐明这些酶的机制。这种追求将使研究生和本科生获得先进的合成和光谱方法和计算化学的专业培训。 计划提出，包括一个推广计划，介绍高中学生从传统上代表性不足的群体在STEM学科动手研究的基础科学。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Nicolai Lehnert from the University of Michigan to prepare model complexes for the mono- and dinuclear non-heme iron centers in the active sites of bacterial nitric oxide reductases (NORs), and to investigate the mechanistic role that corresponding nitrosyl (NO) and nitroxyl (NO-/HNO) complexes play in the mechanisms of these enzymes. Advanced kinetic and spectroscopic methods, including resonance Raman and magnetic circular dichroism, are to be employed. NORs are found in both denitrifying and pathogenic bacteria, and are thought to play a role in their ability to infect mammalian hosts, as NORs equip these bacteria with resistance to NO, which is a primary immune defense agent in mammals. In addition, non-heme iron enzymes may be involved in the generation and sensing of nitroxyl in biological systems via formation of Fe(II)-NO/HNO intermediates, but the properties of these species are not well understood. Dr. Lehnert and his team will set out to determine the geometric and electronic structures of these species and investigate their biologically relevant reactivity.Nitric oxide (NO) is biosynthesized in mammals as a signaling molecule, and as an immune defense agent (by macrophages) to fight off invading pathogens. However, certain bacteria have evolved enzymes called nitric oxide reductases (NORs), which efficiently detoxify NO by reduction to non toxic nitrous oxide (N2O) and water. Hence, NORs are thought to promote infection of the human body, leading to chronic diseases. Despite this importance of NORs for bacterial pathogenesis, the fundamental mechanism of NO reduction by these enzymes is not well understood. The proposed studies seek to elucidate the mechanisms of these enzymes. This pursuit will allow graduate students and undergraduates to acquire specialized training in advanced synthetic and spectroscopic methods and computational chemistry. Plans are put forward to include an outreach program to introduce high school students from groups traditionally underrepresented in the STEM disciplines to hands-on research in the fundamental sciences.