Bioinorganic Copper Coordination Chemistry

生物无机铜配位化学

基本信息

  • 批准号:
    7501398
  • 负责人:
  • 金额:
    $ 37.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1991
  • 资助国家:
    美国
  • 起止时间:
    1991-04-01 至 2011-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The goal of the proposed research is to further develop fundamental aspects of copper coordination chemistry relevant to its essential role in the biochemical processing of dioxygen (O2) and nitrogen oxides (NOx). Many questions remain concerning copper(l)/O2 interactions, dynamics & energetics of O2-adduct formation, as well as questions concerning structure, associated spectroscopy, O-O bond cleavage (i.e., O2- activation) and substrate oxidation chemistries. These may also be relevant to situations of oxidative stress, e.g., in neurological disorders such as Alzheimer's disease. Copper-NOx investigations are relevant to the active site chemistry in nitrite and nitrous oxide (N2O) reductases, and to the possible role of copper ion in nitrogen monoxide ("NO) biochemistry, including mediation of O2 with -NO peroxynitrite (O=NOO~) chemistry and oxidative (and/or nitrative) stress. The research methods divide into sub-projects, directed along various themes or chemical systems. These include (1) study of O2 and carbon monoxide (CO, as O2-surrogate) kinetics and thermodynamics of binding to tetradentate ligand Cu(l)-chelates, (2) study of key ligand- Cu2+(O2-) (superoxide) solvent hydrogen bonding and photochemistry, (3) a major effort to unravel mechanistic details of ligand-Cu2+(O2-) substrate reactivity involving hydrogen-atom transfer chemistry, (4) study of new tetradentate ligand-Cu complexes including with thioether donors, of relevance to certain Cu- monooxygenases, emphasizing O2 & CO binding kinetics-thermodynamics and structural-spectroscopic comparisons to other systems, (5) transient absorption spectroscopic detection of previously unobserved primary Cu/O2 =1:1 adducts and elucidation of their kinetics-thermodynamics and spectroscopy, employing highly reactive tridentate ligand Cu complex systems, (6) investigation of copper ion complexation, structure, binding and chemical reactivity with histidine-histidine peptide moieties (novel binding motifs in copper biochemistry), emphasizing previously un-researched copper(l) coordination chemistry of HisHis and the known metal binding portion (residues 6-14) of the Alzheimer's disease associated amyloid ??peptide, (7) elaboration of Cu-sulfide chemistry, including generation and characterization of new cluster compounds relevant to the active site of nitrous oxide reductase, with additional emphasis placed on the complexes' ability to reductively activate N2O, and (8) investigation of ligand Cu+ reactions with NO and O2, leading to peroxynitrite-derived chemistry. The proposed studies contribute to a broader understanding of copper biochemistry, other metalloprotein (e.g., heme or non-heme iron) activation/reduction of O2 and NOx in biology and associated disease states. Potential long-term applications of this basic research include development of enzyme inhibitors and relevant disease therapeutic strategies.
描述(由申请人提供):拟议研究的目标是进一步发展铜配位化学的基本方面,与其在二氧化碳(O2)和氮氧化物(NOx)的生化处理中的重要作用相关。关于铜(L)/O2的相互作用,O2-加合物形成的动力学和能量学,以及结构、缔合光谱、O-O键断裂(即O2-活化)和底物氧化化学等问题,仍然存在许多问题。这些也可能与氧化应激的情况有关,例如,在阿尔茨海默病等神经疾病中。铜-NOx的研究涉及亚硝酸盐和一氧化二氮(N2O)还原酶的活性中心化学,以及铜离子在一氧化氮(NO)生物化学中的可能作用,包括O2与-NO过氧亚硝酸盐(O=NOO~-)化学和氧化(和/或亚硝化)应激。研究方法分为不同主题或化学体系的子项目。这些工作包括(1)氧和一氧化碳(CO,作为O2-替代物)与四齿配体铜(L)-络合物结合的动力学和热力学的研究,(2)关键配体-Cu2+(O2-)(超氧化物)溶剂氢键和光化学的研究,(3)揭示配体-Cu2+(O2-)底物反应机理的主要工作,涉及氢原子转移化学,(4)新的四齿配体-铜配合物的研究,包括与某些铜单加氧酶相关的硫醚供体的研究,强调氧和CO结合的动力学热力学和结构光谱与其他体系的比较,(5)利用高活性的三齿配体铜配合物体系,对以前未观察到的初级铜/氧=1:1加合物进行瞬时吸收光谱检测,并阐明其动力学-热力学和光谱学,(6)铜离子与组氨酸-组氨酸多肽部分(铜生物化学中的新结合基序)的络合、结构、结合和化学反应的研究,强调以前未研究的组氨酸-组氨酸多肽的铜(L)配位化学和阿尔茨海默病相关淀粉样多肽的已知金属结合部分(残基6-14),(7)铜-硫化物化学的阐述,包括与一氧化二氮还原酶活性中心相关的新簇合物的生成和表征,以及(8)研究配体铜+与NO和O2的反应,导致过氧亚硝酸根衍生的化学。拟议的研究有助于更广泛地了解铜的生物化学、其他金属蛋白(例如,血红素或非血红素铁)在生物学和相关疾病状态下的O2和NOx的激活/还原。这项基础研究的潜在长期应用包括开发酶抑制剂和相关的疾病治疗策略。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

KENNETH D. KARLIN其他文献

KENNETH D. KARLIN的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('KENNETH D. KARLIN', 18)}}的其他基金

Reactivity-Activation of O(2) or NO in Copper and Heme-Cu Coordination Complexes
铜和血红素-Cu 配位络合物中 O(2) 或 NO 的反应活性活化
  • 批准号:
    10322111
  • 财政年份:
    2021
  • 资助金额:
    $ 37.7万
  • 项目类别:
Reactivity-Activation of O(2) or NO in Copper and Heme-Cu Coordination Complexes
铜和血红素-Cu 配位络合物中 O(2) 或 NO 的反应活性活化
  • 批准号:
    10389306
  • 财政年份:
    2021
  • 资助金额:
    $ 37.7万
  • 项目类别:
Reactivity-Activation of O(2) or NO in Copper and Heme-Cu Coordination Complexes
铜和血红素-Cu 配位络合物中 O(2) 或 NO 的反应活性活化
  • 批准号:
    10551343
  • 财政年份:
    2021
  • 资助金额:
    $ 37.7万
  • 项目类别:
Bioinorganic Copper Coordination Chemistry
生物无机铜配位化学
  • 批准号:
    7922771
  • 财政年份:
    2009
  • 资助金额:
    $ 37.7万
  • 项目类别:
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
  • 财政年份:
    2000
  • 资助金额:
    $ 37.7万
  • 项目类别:
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:
    6520128
  • 财政年份:
    2000
  • 资助金额:
    $ 37.7万
  • 项目类别:
Heme/Copper and Heme/Nonheme Iron O(2) and NO Reactivity
血红素/铜和血红素/非血红素铁 O(2) 和 NO 反应性
  • 批准号:
    7934676
  • 财政年份:
    2000
  • 资助金额:
    $ 37.7万
  • 项目类别:
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
  • 财政年份:
    2000
  • 资助金额:
    $ 37.7万
  • 项目类别:
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:
    6387045
  • 财政年份:
    2000
  • 资助金额:
    $ 37.7万
  • 项目类别:
Heme/Copper and Heme/Nonheme Iron O(2) and NO Reactivity
血红素/铜和血红素/非血红素铁 O(2) 和 NO 反应性
  • 批准号:
    9980910
  • 财政年份:
    2000
  • 资助金额:
    $ 37.7万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了