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

描述(申请人提供)：关于一氧化氮在人体内作用的最新发现，引起了人们对具有生物活性的过渡金属亚硝基配合物的极大兴趣。其中，非血红素亚硝基铁络合物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，并被发现负责几个重要的生物学功能。然而，这些研究仅限于这些化合物在溶液中的EPR和IR鉴定，对这些化合物的结构没有很好的表征和了解。这项拟议的研究是通过使用特别选择的模拟蛋白质和DNA氨基酸的配体来合成模拟生物活性的非血红素铁亚硝酰基化合物。通过FT-IR、EPR、核磁共振、UV-Vis、X-射线结晶学和电化学等多种光谱手段对这些化合物的反应机理和结构进行了研究。我们将采用化学、光解和电化学的方法来实现这些络合物中NO的释放，并将应用纳秒激光光解技术来研究定量的NO释放动力学。这些结果将为生物活性的非血红素亚硝酸铁的结构提供信息，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各种生物学功能，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的金属络合物，这些络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。 与公共健康相关：拟议的研究是合成和分离模拟生物活性的非血红素铁-亚硝基配合物的化合物，研究它们的结构，并调查NO的释放条件。这项研究所产生的知识将有助于选择NO释放剂，不仅可以用于生物学家的药理研究，还可以作为药物用于平滑肌松弛、抑制血小板聚集、调节心脏功能和癌症治疗。

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.