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具有生物活性的过渡金属亚硝酰络合物的极大兴趣。其中，非血红素铁亚硝酰复合物已被确定为一氧化氮的生物合成进化的产物，建议作为一氧化氮存储和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。本研究拟利用蛋白质和DNA中的氨基酸作为配体，合成具有生物活性的非血红素铁亚硝酰化合物。通过FT-IR、EPR、NMR、UV-vis、X-射线晶体学和电化学等光谱学方法对这些配合物的反应机理和结构进行了研究。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。这些结果将提供有关具有生物活性的非血红素铁亚硝基化合物的结构信息，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配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性剂以及参与长期记忆。动力学数据将用于鉴定释放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。 公共卫生相关性：拟开展的研究是合成和分离具有生物活性的非血红素铁-亚硝酰复合物，研究其结构，并研究NO释放的条件。从本研究中产生的知识将有助于选择NO释放剂，其不仅可以用于生物学家的药理学研究，而且还可以用作平滑肌松弛，抑制血小板聚集，调节心脏功能和癌症治疗的药物。

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.