Heme/Copper and Heme/Non-Heme Iron O2 and NO Reactivity

血红素/铜和血红素/非血红素铁 O2 和 NO 反应性

• 批准号: 7218067
• 负责人: KENNETH D. KARLIN
• 金额: $ 25.55万
• 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 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7218067
• 关键词: Acids; Active Sites; Aerobic; Behavior; Biochemistry; Bioenergetics; Biological; Biological Models; Biomimetics; Chemicals; Chemistry; Circular Dichroism; Cleaved cell; Complex; Condition; Copper; Detection; Development; Dioxygen; Electron Transport; Electronics; Electrons; Environment; Enzymes; Heme; Heme Iron; Histidine; Imidazole; Investigation; Iron; Isotopes; Kinetics; Ligands; Ligation; Literature; Metals; Modeling; Mononuclear; NMR Spectroscopy; Nitric Oxide; Nitrogen Oxides; Nitrous Oxide; Object Attachment; Organism; Oxidases; Phenols; Photochemistry; Process; Production; Property; Reducing Agents; Research; Research Personnel; Roentgen Rays; Source; Spectrum Analysis; Structure; Study models; Study of magnetics; System; Techniques; Thinking; absorption; adduct; base; carboxylate; circular magnetic dichroism; cofactor; cold temperature; copper oxidase; crosslink; cytochrome c oxidase; design; enzyme structure; heme O; heme a; inhibitor/antagonist; insight; irradiation; nitric oxide reductase; oxidation; phenoxy radical; protonation; pyridine

DESCRIPTION (provided by applicant): 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 (NORs). 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 (O2) 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 and characterization of discrete heme/M compounds, their reactivity studies with O2 and NO, the coordination chemistry and the photochemistry of heme/M complexes, and the reductive O-O bond cleavage of heme/Cu/O2 adducts. Specific aims include (1) further characterization and elucidation of the peroxo-connectivity and electronic structures of existing heme-peroxo- Cu complexes, (2) expanded studies on heme/Cu/O2 chemistry employing various tridentate Cu-ligands which include systems with a cross-linked imidazole-phenol moiety, (3) synthesis and characterization of low-spin heme-peroxo-Cu complexes, (4) investigation and elaboration of the chemistry of NOR model systems which produce nitrous oxide (N2O), (5) study of nitric oxide reactivity with heme/Cu complexes, (6) development of the coordination chemistry of heme-O(H)-M systems, (7) investigation of atom/ligand/electron transfer in heme/M complexes induced by photochemistry, and (8 & 9) study of reductive O-O bond cleavage of heme/Cu/O2 adducts either by controlling H+, e-, and/or H. sources, or by employing a cryoreduction, gamma-irradiation technique.

描述（由申请人提供）：长期研究目标是设计，合成和研究模型化合物系统，这可以帮助阐明结构，金属结合，光谱，光谱和反应性的基本方面，与血红素 - 碳酸氧化酶（例如细胞染料C氧化酶（CCOS）（CCOS））和NITRIC氧化酶相关的化学作用（例如，氧化酶）和NITRIC氧化酶（NITRIC氧化酶）。这些与进化相关的酶参与有氧和厌氧生物的生物能学，并具有血红素/M（M = Cu或非血红素FE）活性位点，分别还原二恶英（O2）或硝酸氧化物（NO）。这项研究可以更好地了解酶结构和机制，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化合物的合成和表征，其对O2和NO的反应性研究，血红素/M复合物的配位化学和光化学以及血红素/CU/CU/O2加和的还原性O-O键裂解。 Specific aims include (1) further characterization and elucidation of the peroxo-connectivity and electronic structures of existing heme-peroxo- Cu complexes, (2) expanded studies on heme/Cu/O2 chemistry employing various tridentate Cu-ligands which include systems with a cross-linked imidazole-phenol moiety, (3) synthesis and characterization of low-spin heme-peroxo-Cu complexes, （4）对产生一氧化二氮（N2O）的NOR模型系统的化学研究和阐述，（5）研究用血红素/CU复合物研究一氧化氧化物的反应性，（6）（6）HEME-O（H）-M系统的配位化学的发展，（7）由Atom/Ligand/Ligand/Electon/Memems的研究（7），（7）均及其复杂性的研究（7），均及其复杂的研究（7）。通过控制H+，E-和/或H.源或使用冷冻的γ-辐射技术，通过控制H+，E-和/或H的O-O键裂解。