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Nitric oxide reactivity with synthetic iron-sulfur clusters

一氧化氮与合成铁硫簇的反应性

基本信息

批准号：
7649346
负责人：
Zachary J Tonzetich
金额：
$ 4.99万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-02 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7649346
关键词：
Biochemical Biochemistry Biological Biological Process Biomimetics Chemicals Chemistry Classification Complex Cysteine Disease Electron Spin Resonance Spectroscopy Electron Transport Environment Enzyme Interaction Enzymes Gases Glean Goals Health Human Human body Immune response Investigation Ions Iron Knowledge Lead Ligation Mass Spectrum Analysis Mediating Methodology Modeling Molecular Monitor Nature Nitric Oxide Nitric Oxide Donors Nitrogen Organism Oxygen Pathology Physiological Physiology Play Positioning Attribute Preparation Process Protein Binding Proteins Protocols documentation Reaction Research Respiration Role Route Signal Transduction Site Sulfur Sulfur Compounds Techniques Toxin Transition Elements Vasodilation Work X-Ray Crystallography analog base chemical reaction dinitrosyl iron complex infrared spectroscopy interest neurotransmission pathogen small molecule

项目摘要

DESCRIPTION (provided by applicant): Nitric oxide is an important pathogen and signaling agent that has been implicated in a number of important physiological functions. The overreaching goal of the proposed research plan is to forward the understanding of nitric oxide by examining its interaction with iron sites of biological relevance. Work from the biochemical and physiological fields have implicated the role of nitric oxide in the breakdown of iron- sulfur clusters. These clusters serve as electron transfer agents in a variety of proteins and are therefore critical to the proper function of enzymes and the overall health of the organism (including humans). The proposed research will focus on the chemical aspects of cluster degradation by scrutinizing the elementary steps that take place when nitric oxide encounters synthetic analogs of iron-sulfur clusters. In this way, the processes that take place biologically may be examined in greater depth than previously possible. The specific aims of the proposed research are as follows: (1) to synthesize and explore the reactivity of synthetic [2Fe-2S] clusters with nitric oxide, (2) to extend these findings to the examination of larger [3Fe- 4S] and [4Fe-4S] clusters, and (3) to concurrently explore the reactivity of modified clusters bearing non- thiolate ligation. Preparation of the target iron-sulfur compounds will involve new synthetic methodologies as well as existing protocols for the preparation of iron-sulfur clusters. The work will focus on identifying new intermediates, and on applying bioinorganic techniques such as infrared spectroscopy, EPR spectroscopy, and X-ray crystallography to monitor chemical reactions. Through these investigations, the proposed research plan will seek to develop a coherent mechanism for nitric oxide reactivity with iron-sulfur clusters. RELEVANCE: The health and well being of humans depends critically upon a myriad of chemical reactions that take place within the human body. When these reactions fail to proceed in the intended way, problems can arise that may ultimately lead to disease. One compound of great relevance to proper biological function is nitric oxide. The goal of the proposed research is to understand the role of nitric oxide in the context of its interaction with biologically relevant compounds. Through this understanding, the proposed work will seek to identify what chemical processes take place when proper nitric oxide function is disturbed, and ultimately, how these processes may be reversed.

描述（由申请人提供）：一氧化氮是一种重要的病原体和信号传导剂，涉及许多重要的生理功能。拟议的研究计划的过度目标是通过检查其与生物相关的铁位点的相互作用来促进对一氧化氮的理解。来自生物化学和生理学领域的工作已经暗示了一氧化氮在铁硫簇的分解中的作用。这些簇在各种蛋白质中充当电子转移剂，因此对酶的正常功能和生物体（包括人类）的整体健康至关重要。拟议的研究将集中在集群降解的化学方面，通过仔细检查当一氧化氮遇到铁硫集群的合成类似物时发生的基本步骤。通过这种方式，可以比以前更深入地研究生物学上发生的过程。所提出的研究的具体目标如下：（1）合成并探索合成的[2Fe-2S]簇与一氧化氮的反应性，（2）将这些发现扩展到较大的[3Fe- 4S]和[4Fe-4S]簇的检查，以及（3）同时探索具有非硫醇连接的修饰簇的反应性。目标铁硫化合物的制备将涉及新的合成方法以及现有的铁硫簇合物的制备方案。这项工作将集中在识别新的中间体，并应用生物无机技术，如红外光谱，EPR光谱和X射线晶体学来监测化学反应。通过这些调查，拟议的研究计划将寻求开发一氧化氮与铁硫簇反应的连贯机制。相关性：人类的健康和福祉关键取决于人体内发生的无数化学反应。当这些反应未能以预期的方式进行时，可能会出现问题，最终可能导致疾病。一氧化氮是一种与正常生物功能密切相关的化合物。拟议研究的目标是了解一氧化氮在其与生物相关化合物相互作用的背景下的作用。通过这种理解，拟议的工作将寻求确定当适当的一氧化氮功能受到干扰时会发生什么化学过程，以及最终如何逆转这些过程。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Detecting and understanding the roles of nitric oxide in biology.

DOI：
10.1021/ic9022757
发表时间：
2010-07-19
期刊：
INORGANIC CHEMISTRY
影响因子：
4.6
作者：
Tonzetich, Zachary J.;McQuade, Lindsey E.;Lippard, Stephen J.
通讯作者：
Lippard, Stephen J.

Singlet-Triplet Gaps of Cobalt Nitrosyls: Insights from Tropocoronand Complexes.

亚硝酰钴的单重态-三重态间隙：来自原冠络合物的见解。

DOI：
10.1021/acs.inorgchem.5b00901
发表时间：
2015
期刊：
Inorganic chemistry
影响因子：
4.6
作者：
Hopmann,KathrinH;Conradie,Jeanet;Tangen,Espen;Tonzetich,ZacharyJ;Lippard,StephenJ;Ghosh,Abhik
通讯作者：
Ghosh,Abhik

Dinitrosyl iron complexes relevant to Rieske cluster nitrosylation.