New Nonheme Iron Complexes for Nitric Oxide Reactivity

在化学系化学合成项目的支持下，约翰霍普金斯大学化学系David Goldberg教授的研究小组开发了一种新的含铁化合物家族，可以激活氮氧化物或氮氧化物。氮氧化物的化学变化，包括一氧化氮及其相关分子硝基（HNO）和亚硝酸盐离子（NO2-），对许多生化过程至关重要，包括细胞信号传导、免疫反应和治疗策略。一氧化氮是大脑和整个神经系统的关键神经递质。目前人们对HNO在大脑中的作用以及它是如何产生的也很感兴趣。在这个项目中，Goldberg博士和他的团队构建了新的铁配合物，可以与氮氧化物结合并发生反应。它们对这些与酶促过程有关的分子进行化学变化。研究生和本科生接受实验化学科学方面的教育和培训。巴尔的摩市一所高中正在开展一项针对科学领域代表性不足的学生的拓展计划。一个新的多齿配体家族及其相关的非血红素铁配合物的合成正在研究中，以结合和激活氮氧化物。几种形式的氮氧化物的氧化和还原转化进行了检查。观察到的反应性与发生在含铁一氧化氮还原酶、亚硝酸盐还原酶和一氧化氮双加氧酶中的酶促过程有关。此外，作为一种强有力的信号分子，氮氧化物的基本反应性对大脑和神经系统的一系列过程至关重要。通过配体设计，控制了金属中心的空间和电子性质。这些配合物的研究可以提供关于结构如何与铁介导的NOx反应性的功能相关的见解。具体工作将集中在将NO还原为NO-/HNO和N2O，将NO氧化为NO2-和NO3-，以及通过生物相关还原剂还原亚硝酸盐（NO2-）。教育计划包括一个延伸到当地巴尔的摩市高中的项目，提供动手实验的经验。

The support provided by the Chemical Synthesis Program of the Chemistry Division allows the research group of Professor David Goldberg in the Department of Chemistry at Johns Hopkins University to develop a new family of iron-containing compounds that activating nitrogen oxide or NOx species. The chemical changes of NOx species, including nitric oxide and its related molecules nitroxyl (HNO) and nitrite ion (NO2-), are critically important for a number of biochemical processes, including cell signaling, immune response, and therapeutic strategies. Nitric oxide is a key neurotransmitter in the brain and throughout the nervous system. There is also significant current interest in the role of HNO in the brain and how it is generated. In this project, Dr. Goldberg and his group construct new iron complexes that bind and react with NOx species. They carry out chemical changes on these molecules related to enzymatic processes. Graduate and undergraduate students are educated and trained in experimental chemical science. An outreach program for students underrepresented in science involving a Baltimore City high school is underway.The synthesis of a new family of polydentate ligands and their related nonheme iron complexes is under investigation for the binding and activation of NOx species. The oxidative and reductive transformations of several forms of NOx are examined. The observed reactivity is related to enzymatic processes that occur in iron-containing nitric oxide reductases, nitrite reductases, and nitric oxide dioxygenases. In addition, the fundamental reactivity of NOx species, which are potent signaling molecules, is important to a range of processes in the brain and nervous system. Through ligand design, the steric and electronic properties at the metal center are controlled. The study of these complexes may provide insights regarding how structure relates to function in iron-mediated NOx reactivity. Specific efforts will focus on the reduction of NO to NO-/HNO and N2O, the oxidation of NO to NO2- and NO3-, and the reduction of nitrite (NO2-) by biologically relevant reducing agents. The educational plans include an outreach program to a local Baltimore City high school that provides a hands-on laboratory experience.