Redox Behavior and Chemical Reactivity of Heme-HNOx Complexes

美国国家科学基金会化学部的化学结构、动力学机制B项目支持乔治B教授和俄克拉荷马州大学的Richter-Addo教授和南伊利诺伊大学爱德华兹维尔分校的Michael J. Shaw教授。 本研究的总体目标是制备和表征与全球氮循环和人类健康相关的活性生物中间体。 重点放在氮氧化物（NOx）的基本铁介导化学上，这些氮氧化物涉及各种过程，如大气污染，人类血压控制以及细菌存活或死亡。 虽然已知最简单的NOx物质，即一氧化氮（NO）调节正常血压，但对相关物质如硝酰基（HNO）和亚硝基烷烃（RNO）的产生和作用知之甚少。 这个合作小组在化学合成和电分析化学方面拥有共同的专业知识，并结合了博士学位。环境（在SIUE）和主要是本科生的环境（在SIUE）提供高层次的培训，以学生的多样化群体。 外展活动，涉及市中心的高中学生从低收入和弱势背景是这个项目的一个重要组成部分。血红素-HNO和-次硝酸盐化合物是重要的中间体的生物途径的整体全球氮循环。 例如，细菌使用二铁活性位点通过次硝酸盐中间体将双原子血管扩张剂分子NO转化为一氧化二氮，而真菌使用单铁活性位点进行类似的NO转化为一氧化二氮的反应。 真菌反应涉及对铁血红素亚硝酰基的初始氢化物攻击，以生成血红素-HNO中间体。 该研究小组最近成功地生成了一个合成模型系统，以证明通过氢化物攻击铁血红素亚硝酰基形成血红素-HNO，这提供了一个适当的框架来确定促进这些血红素-HNO物种进一步反应的因素。 该项目的目标是：（i）制备一系列具有代表性的亚铁血红素亚硝酰基，（ii）探索涉及亲核攻击结合亚硝酰基以生成血红素-XNO衍生物的反应（X = H，烷基/芳基），（iii）确定这些物质的氧化还原行为，特别是涉及质子耦合电子转移的那些，（iv）制备血红素模型-次硝酸盐化合物并建立它们的反应性模式，和（v）制备相关的血红素模型-NONOate衍生物，以确定促进这些物质分解产生血管扩张剂NO分子的因素。

The Chemical Structure, Dynamics & Mechanisms B Program of the Chemistry Division at the NSF supports the collaborative research between Professor George B. Richter-Addo at the University of Oklahoma (OU) and Professor Michael J. Shaw at Southern Illinois University Edwardsville (SIUE). The overall goal of this research is to prepare and characterize reactive biological intermediates of relevance to the global nitrogen cycle and human health. Emphasis is placed on the fundamental iron-mediated chemistry of the nitrogen oxides (NOx) that have been implicated in various processes such as atmospheric pollution, blood pressure control in humans, and in bacterial survival or death. Although the simplest NOx species, namely nitric oxide (NO) is known to regulate normal blood pressure, not much is known about the generation and action of related species such as nitroxyl (HNO) and nitrosoalkanes (RNO). This collaborative group has joint expertise in chemical synthesis and electroanalytical chemistry, and combines a Ph.D. environment (at OU) and a primarily undergraduate environment (at SIUE) to provide high-level training to a diverse group of students. Outreach activities involving inner-city high school students from low-income and disadvantaged backgrounds are an essential component of this project.Heme-HNO and -hyponitrite compounds are important intermediates in the biological pathways of the overall global nitrogen cycle. For example, bacteria convert the diatomic vasodilator molecule NO to nitrous oxide via a hyponitrite intermediate using a di-iron active site, whereas fungi perform a similar NO-to-nitrous oxide reaction using a mono-iron active site. The fungal reaction involves initial hydride attack at a ferric heme nitrosyl to generate a heme-HNO intermediate. This research team recently succeeded in generating a synthetic model system to demonstrate heme-HNO formation via hydride attack on a ferric heme nitrosyl, which provided an appropriate framework to determine factors that promote further reactions of these heme-HNO species. In this project, the aims are to: (i) prepare a representative range of ferric heme nitrosyls, (ii) explore reactions involving nucleophilic attack at the bound nitrosyls to generate heme-XNO derivatives (X = H, alkyl/aryl), (iii) determine the redox behavior of these species especially those involving proton-coupled electron transfers, (iv) prepare heme model-hyponitrite compounds and establish their reactivity patterns, and (v) prepare the related heme model-NONOate derivatives to determine the factors that promote decomposition of these species to generate the vasodilator NO molecule.