Redox Behavior and Chemical Reactivity of Heme-HNOx Complexes

美国国家科学基金会化学部化学结构、动力学和机制B项目支持俄克拉荷马大学(OU)的George B.Richter-Addo教授和南伊利诺伊大学Edwardsville(SIUE)的Michael J.Shaw教授之间的合作研究。这项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。重点放在铁介导的氮氧化物(NOx)的基本化学上，这些氮氧化物参与了各种过程，如大气污染、人类血压控制和细菌生存或死亡。尽管已知最简单的NOx物种，即一氧化氮(NO)可以调节正常血压，但对相关物种如氮氧基(HNO)和亚硝烷(RNO)的产生和作用却知之甚少。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，并结合博士环境(在OU)和以本科生为主的环境(在SIUE)，为不同的学生群体提供高水平的培训。让来自低收入和弱势背景的市内高中生参加的外展活动是该项目的重要组成部分。亚硝酸亚铁和亚硝酸盐化合物是整个全球氮循环生物途径中的重要中间体。例如，细菌通过使用二铁活性中心的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中心进行类似的NO到一氧化二氮的反应。真菌反应包括初始的氢化物攻击亚硝酰亚铁，生成亚硝酸亚铁中间体。该研究小组最近成功地生成了一个合成模型系统，证明了通过氢化物对亚硝酸铁的攻击形成血红素-HNO，这为确定促进这些血红素-HNO物种进一步反应的因素提供了一个适当的框架。在这个项目中，目标是：(I)制备一系列具有代表性的亚硝酸铁，(Ii)探索在结合的亚硝基上涉及亲核攻击的反应以生成亚铁血红素-xNO衍生物(X=H，烷基/芳基)，(Iii)确定这些物种的氧化还原行为，特别是涉及质子耦合电子转移的那些物种的氧化还原行为，(Iv)制备亚硝酸亚硝酸盐的血红素模型化合物并建立它们的反应模式，以及(V)制备相关的亚硝酸亚铁血红素模型-NONOate衍生物以确定促进这些物种分解以产生血管扩张剂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.