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Non-heme Iron Nitrosyl Complexes: Structures, NO Release & Applications

非血红素亚硝酰铁络合物：结构，NO 释放

基本信息

批准号：
9304240
负责人：
LIJUAN LI
金额：
$ 11.06万
依托单位：
CALIFORNIA STATE UNIVERSITY LONG BEACH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9304240
关键词：
Biological Biological Process Biological Testing Blood Pressure California Cardiac Cardiovascular system Cell Culture System Cell Culture Techniques Cell physiology Characteristics Chelating Agents Chemicals Collaborations Communities Complex Cytotoxic agent DNA Data Drug Kinetics Electrochemistry Environment Evolution Family Goals Human Imidazole Immune system In Situ In Vitro Investigation Kinetics Knowledge Lasers Ligands Measures Medicine Memory Metals Methods Mono-S Muscle relaxation phase Neurosciences Nitric Oxide Pharmaceutical Preparations Pharmacology Study Phenanthrolines Phosphines Physical Chemical Technique Physiology Platelet aggregation Play Property Reaction Research Role Series Smooth Muscle Sodium Sodium Chloride Structure Sulfhydryl Compounds Sulfonic Acids Techniques Test Result Testing Transition Elements Universities Washington Water X-Ray Crystallography base biological systems biosynthetic product cancer therapy in vivo insight interest iron nitrosyl long term memory metal complex nanosecond photolysis prevent public health relevance triphenylphosphine tris(2-carboxyethyl)phosphine

项目摘要

DESCRIPTION (provided by applicant): Recent discoveries in the roles of nitric oxide in humans have generated tremendous interest in biologically active transition metal nitrosyl complexes. Among them, the non-heme iron nitrosyl complexes have been identified as products of biosynthetic evolution of nitric oxide, suggested as nitric oxide storage, and found to be responsible for several important biological functions. However, these studies were limited to EPR and IR identification of these complexes in solution and the structures of these compounds were not well characterized and understood. The proposed research is to synthesize non-heme iron nitrosyl compounds that mimic biologically active non-heme iron nitrosyls by using specially selected ligands that are soluble in water and have the potential to interact with DNA. The reaction mechanisms and structures of these complexes will be studied using a combination of spectroscopic methods, such as FT-IR, EPR, NMR, UV-vis, X-ray crystallography and electrochemical techniques. Chemical, photolytic and electrochemical methods will be used to achieve the NO release from these complexes and the quantitative NO release kinetics will be investigated by applying nanosecond laser photolysis techniques. Potential biological activities will also be tested. These results will provide information on the structures of biologically activ non-heme iron nitrosyls, thus helping the neuroscience, physiology and medicinal research communities understand the diverse biological functions of nitric oxide and its metal complexes, some of which include controlling blood pressure, preventing platelet aggregation, acting as biological messengers and immune system cytotoxic agents, and playing a role in long-term memory. The kinetic data and the biological activity testing results will be used to identify the NO-releasing metal complexes, which can be used in cardiovascular muscle relaxation, cancer therapy, pharmacokinetic studies, and other medicinal applications.

描述（由申请人提供）：最近发现一氧化氮在人体中的作用，对具有生物活性的过渡金属亚硝酰络合物产生了极大的兴趣。其中，非血红素铁亚硝酰复合物已被鉴定为一氧化氮生物合成进化的产物，被认为是一氧化氮的储存，并发现负责几个重要的生物功能。然而，这些研究仅限于EPR和IR鉴定这些配合物在溶液中，这些化合物的结构没有得到很好的表征和理解。拟议的研究是合成非血红素铁亚硝酰化合物，通过使用特别选择的配体，这些配体可溶于水，并有可能与DNA相互作用，模拟生物活性的非血红素铁亚硝酰。将使用FT-IR、EPR、NMR、UV-vis、X射线晶体学和电化学技术等光谱方法的组合来研究这些配合物的反应机理和结构。化学，光解和电化学方法将被用来实现NO从这些复合物的释放和定量NO释放动力学将通过应用纳秒激光光解技术进行研究。还将测试潜在的生物活性。这些结果将提供有关生物活性非血红素铁亚硝基结构的信息，从而帮助神经科学，生理学和医学研究界了解一氧化氮及其金属络合物的多种生物学功能，其中一些包括控制血压，防止血小板聚集，作为生物信使和免疫系统细胞毒性剂，并在长期记忆中发挥作用。动力学数据和生物活性测试结果将用于鉴定释放NO的金属配合物，其可用于心血管肌肉松弛、癌症治疗、药代动力学研究和其他医学应用。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recent Advances in Multinuclear Metal Nitrosyl Complexes.

DOI：
10.1016/j.ccr.2015.03.026
发表时间：
2016-01-01
期刊：
Coordination chemistry reviews
影响因子：
20.6
作者：
Li L;Li L
通讯作者：
Li L

The Preparation, Structural Characteristics, and Physical Chemical Properties of Metal-Nitrosyl Complexes.

DOI：
10.1007/430_2013_101
发表时间：
2013
期刊：
Structure and bonding
影响因子：
0
作者：
Holloway LR;Li L
通讯作者：
Li L

A combined experimental and theoretical study of dinitrosyl iron complexes containing chelating bis(diphenyl)phosphinoX (X = benzene, propane and ethylene): X-ray crystal structures and properties influenced by the presence or absence of π-bonds in chelat

含有螯合双（二苯基）膦 X（X = 苯、丙烷和乙烯）的二亚硝基铁配合物的综合实验和理论研究：X 射线晶体结构和性质受螯合剂中存在或不存在 α 键的影响

DOI：
10.1016/j.poly.2013.12.019
发表时间：
2014
期刊：
Polyhedron
影响因子：
2.6
作者：
Holloway,LaurenR;Clough,AndrewJ;Li,JessicaY;Tao,EmilyL;Tao,Fu-Ming;Li,Lijuan
通讯作者：
Li,Lijuan