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

描述（由申请人提供）：最近关于一氧化氮在人体中的作用的发现引起了人们对生物活性过渡金属亚硝基配合物的极大兴趣。其中，非血红素铁亚硝基配合物已被确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物，并被发现具有几种重要的生物学功能。然而，这些研究仅限于溶液中这些配合物的EPR和IR鉴定，并且这些化合物的结构尚未得到很好的表征和了解。拟建的研究是通过特殊选择的配体来模拟蛋白质和DNA的氨基酸，合成模拟生物活性的非血红素铁亚硝基化合物。这些配合物的反应机理和结构将通过光谱方法，如FT-IR， EPR， NMR, UV-vis， x射线晶体学和电化学技术的组合来研究。将采用化学、光解和电化学等方法来实现这些配合物的NO释放，并利用纳秒激光光解技术来研究NO的定量释放动力学。这些结果将提供具有生物活性的非血红素铁亚硝基的结构信息，从而帮助神经科学、生理学和医学研究团体了解一氧化氮及其金属配合物的多种生物学功能，其中一些功能包括控制血压、防止血小板聚集、作为生物信使和免疫系统细胞毒性剂，以及参与长期记忆。动力学数据将用于鉴定一氧化氮释放金属配合物，可用于心血管肌肉松弛，癌症治疗，药代动力学研究和其他医学应用。

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. PUBLIC HEALTH RELEVANCE: The proposed research is to synthesize and isolate compounds that mimic biologically active non-heme iron-nitrosyl complexes, to study their structures, and to investigate the conditions for NO release. The knowledge generated from this study will assist in selecting NO releasing agents, which can not only be used in pharmacological studies by biologists, but can also be used as medicine in smooth muscle relaxation, inhibiting platelet aggregation, regulating cardiac function, and cancer therapy.