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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：
8742964
负责人：
LIJUAN LI
金额：
$ 10.91万
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 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8742964
关键词：
Biological Biological Process Biological Testing California Cardiac Cardiovascular system Cell Culture System Cell Culture Techniques Cell physiology Characteristics Chemicals Collaborations Communities Complex Cytotoxic agent DNA Data Drug Kinetics Electrochemistry Environment Evolution Family Goals Heme Iron Human Hydrochloride Salt Imidazole Immune system In Situ In Vitro Investigation Iron Kinetics Knowledge Lasers Ligands Measures Medicine Memory Metals Methods Mono-S Muscle relaxation phase Neurosciences Nitric Oxide Pharmaceutical Preparations Phenanthrolines Phosphines Physical Chemical Technique Physiology Platelet aggregation Play Property Reaction Research Role Series Smooth Muscle Sodium Sodium Chloride Solutions Structure Sulfhydryl Compounds Sulfonic Acids Techniques Test Result Testing Transition Elements Universities Washington Water X-Ray Crystallography base biological systems biosynthetic product blood pressure regulation 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）：最近关于一氧化氮在人类中的作用的发现引起了人们对生物活性过渡金属亚硝酰络合物的极大兴趣。其中，非血红素亚硝酰基铁络合物已被鉴定为一氧化氮生物合成进化的产物，被认为是一氧化氮储存，并发现负责多种重要的生物学功能。然而，这些研究仅限于溶液中这些复合物的 EPR 和 IR 鉴定，并且这些化合物的结构没有得到很好的表征和理解。拟议的研究是通过使用专门选择的可溶于水并具有与 DNA 相互作用的潜力的配体来合成模拟生物活性非血红素亚硝酰基铁的非血红素亚硝酰基化合物。这些配合物的反应机理和结构将结合光谱方法（如 FT-IR、EPR、NMR、UV-vis、X 射线晶体学和电化学技术）进行研究。将使用化学、光解和电化学方法来实现从这些复合物中释放NO，并且将通过应用纳秒激光光解技术来研究定量NO释放动力学。潜在的生物活性也将得到测试。这些结果将提供有关生物活性非血红素亚硝酰基铁结构的信息，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，其中包括控制血压、防止血小板聚集、充当生物信使和免疫系统细胞毒剂以及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。