HEME/COPPER AND HEME/NONHEME IRON O2 AND NO REACTIVITY

血红素/铜和血红素/非血红素铁 O2，无反应性

• 批准号: 6031285
• 负责人: KENNETH D. KARLIN
• 金额: $ 28.15万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6031285
• 关键词: Mossbauer spectrometry; Raman spectrometry; chemical kinetics; chemical reaction; chemical synthesis; copper; cytochrome oxidase; enzyme activity; heme; hemoprotein; iron compounds; iron oxide; iron sulfur protein; metal complex; metalloenzyme; nitric oxide; nuclear magnetic resonance spectroscopy; protonation; stoichiometry; stop flow technique; thermodynamics

The long-term research objective is to design, synthesize and investigate model compound systems which can help elucidate fundamental aspects of structure, metal-ligation, spectroscopy and reactivity relevant to the chemistry utilized by heme-copper oxidases (e.g., cytochrome c oxidases (CcOs)) and nitric oxide reductases. These evolutionarily related enzymes are involved in the bioenergetics of aerobic and anaerobic organisms, and have in common a heme/M (M = Cu or non-heme Fe) active site which reductively cleaves dioxygen (OZ) or nitric oxide (NO), respectively. The research can contribute to a better understanding of enzyme structure and mechanism, and provide fundamental insights into biological O2-activation, NO and nitrogen oxide chemistry and biochemistry, and issues related to nitrogen oxides in the environment. Major themes are the synthesis of discrete heme/M compounds, O2-chemistry of reduced heme/Cu assemblies, the coordination chemistry of heme/M complexes, NO reactivity studies, and use of phenol chemistry in heme/Cu mediated O2-reduction. Specific aims include (1) spectroscopic and structural characterization of heme-O2-Cu (peroxo) complexes using varied conditions of heme, axial base, or Cu-ligand, (2) study of heme/Cu/O2 adducts assembled from mononuclear components, (3) systematic comparisons of the reactivity of varying Fe-O2-Cu moieties, (4) development of the coordination chemistry of heme/M systems with mu-oxo, mu-OH- and other ligands (e.g., C1-, CN-) of interest as biochemical probes, (5) study of reduced heme/M complexes and their CO and isocyanide adducts, (6) thorough investigation and elaboration upon a NO reductase model system which produces nitrous oxide (N2O), (7) generation of new heme/Fe systems having varied Fe-ligands with three N-donors and/or with one O-donor, (8) study of nitric oxide reactivity with these and heme/Cu systems, since NO is a reversible inhibitor of CcO, (9) use of phenols as electron-proton donors and Cu-ligands in O2-reduction with heme/Cu assemblies, and (10) probing of the chemistry relevant to formation and function of an imidazole-phenol (His-Tyr) covalent link found in CcO.

长期研究目标是设计，合成和研究模型化合物系统，这些系统可以帮助阐明结构，金属结合，光谱和反应性的基本方面与血红素 - 铜氧化酶（例如细胞色素氧化酶（CCOS）（CCOS）（CCOS）和二氧化氧化物还原酶相关的化学作用相关。 这些与进化相关的酶参与有氧和厌氧生物的生物能学，并具有共同的血红素/M（M = Cu或非血红素FE）活性位点，该位点分别还原了分别裂解二氧化碳（OZ）或硝酸氧化物（NO）。 这项研究可以有助于更好地了解酶的结构和机制，并为生物O2激活，NO和氮氧化物化学和生物化学以及与环境中氮氧化物相关的问题提供基本见解。 主要主题是离散血红素/M化合物的合成，血红素/CU组件降低的O2化学，血红素/M复合物的配位化学，无反应性研究以及在血红素/CU介导的O2还原中使用苯酚化学。 具体目的包括（1）使用血红素，轴向基碱或Cu-rigand的各种条件的血红素-O2-Cu（Peroxo）复合物的光谱和结构表征，（2）（2）研究来自单核成分的血红素/CU/CU/CU/O2加合物组装的联合，（3）Vary-fe-fe-fe-fe-fe-of-ofer fe fe-fe-fe-otioties fe-os2-cuiiities，2-cuiiities，2-cuiiities，2-cuiiities，（3）具有Mu-oxo，Mu-Oh-和其他兴趣作为生物化学探针的感兴趣的血红素/M系统（例如C1-，CN-），（5）研究血红素/M复合物的减少及其CO和它们的CO和它们的CO和它们的异氰化物加合物，（6）对NO还原型系统的彻底研究和对NITRES oxe ox exide ox exide ox exide oxiide oxe the niTros oxide的彻底研究（6）的研究（6）具有三个n符合物和/或一个o含量的不同fe-配体，（8）对这些和血红素/CU系统的氮氧化物反应性的研究，因为NO是CCO的可逆抑制剂，（9）将苯酚用作电子构型供体和Cu-ligands在O2-Rectional o2-Rectiontion和Cu组装中的相关性和CU组装和（10）的形成（10），（10）的形成（10）咪唑 - 苯酚（His-Tyr）共价链接在CCO中发现。