Non-Heme Iron-Nitrosyl Complexes: Their Structures and Nitric Oxide Release Kinet

非血红素亚硝酰铁络合物：其结构和一氧化氮释放动力学

基本信息

批准号：
8473227
负责人：
LIJUAN LI
金额：
$ 10.35万
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 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8473227
关键词：
Adenine Amino Acids Base Pairing Benzimidazoles Biological Biological Process California Cardiac Cardiovascular system Cell physiology Characteristics Chemicals Collaborations Communities Complex Cytotoxic agent DNA Data Development Drug Kinetics Electrochemistry Evolution Future Grant Guanine Heme Iron Human Imidazole Immune system In Situ In Vitro Investigation Iron Kinetics Knowledge Lasers Ligands Medicine Memory Metals Methods Modeling Muscle relaxation phase Neurosciences Nitric Oxide Paper Pharmaceutical Preparations Phenanthrolines Physical Chemical Technique Physiology Platelet aggregation Play Property Proteins Publications Publishing Purines Pyrazines Reaction Research Role Series Smooth Muscle Solutions Structure Students Sulfhydryl Compounds Techniques Theophylline Transition Elements Universities Work X-Ray Crystallography base benzimidazole biosynthetic product blood pressure regulation cancer therapy in vivo interest iron nitrosyl long term memory metal complex nanosecond photolysis prevent programs public health relevance purine undergraduate student

项目摘要

DESCRIPTION (provided by applicant): Recent discoveries on the roles of nitric oxide in human 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 model amino acids of protein and DNA. The reaction mechanisms and structures of these complexes will be studied by 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. These results will provide information on the structures of biologically active non-heme iron nitrosyls, thus helping the neuroscience, physiology and medicinal research communities to 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 involving in long-term memory. The kinetic data will be used to identify the NO releasing metal complexes, which could be used in cardiovascular muscle relaxation, cancer therapy, pharmacokinetic studies, and other medicinal applications.

描述（由申请人提供）：关于人类一氧化氮在人类中的作用的最新发现对生物活性过渡金属亚硝基复合物产生了极大的兴趣。其中，非血红素亚硝基复合物已被鉴定为一氧化氮的生物合成进化产物，被认为是一氧化氮的储存，并被发现负责几种重要的生物学功能。但是，这些研究仅限于EPR，并且在溶液中对这些复合物的IR鉴定，这些化合物的结构没有很好地表征和理解。拟议的研究是合成非血红素亚硝基化合物，通过使用特殊选择的配体模拟蛋白质和DNA的氨基酸，模仿生物活性非血红素亚硝基基。这些复合物的反应机理和结构将通过光谱方法的组合进行研究，例如FT-IR，EPR，NMR，UV-VIS，X射线晶体学和电化学技术。化学，光解和电化学方法将用于从这些复合物中释放NO，并且定量NO释放动力学将通过应用纳秒激光光解技术研究。这些结果将提供有关生物活性非血红素亚硝基铁结构的信息，从而帮助神经科学，生理学和药物研究群落了解一氧化氮及其金属复合物的多样化生物学功能，其中一些包括控制血压，可预防血小板聚集，可预防血小板，使生物学伴随系统和免疫系统的记忆力进行长期氧化，并参与了长期的良好和氧有良好的人，并参与了涉及良好的媒介物，并参与了涉及良好的媒介物。动力学数据将用于识别无释放金属复合物，该复合物可用于心血管肌肉松弛，癌症治疗，药代动力学研究和其他药用应用。