PHYSICAL STUDIES OF METALLOPORPHYRINS & THEIR REACTIONS

金属卟啉的物理研究

基本信息

批准号：
3229304
负责人：
DWIGHT A SWEIGART
金额：
$ 11.02万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-07-01 至 1989-06-30
项目状态：
已结题

项目摘要

The project concerns important aspects of the chemistry of metalloporphyrin that serve as good models for hemoproteins such as hemoglobin, myoglobin, cytochromes, and peroxidases. These proteins function in a variety of processes, including oxygen transport and storage, electron transfer catalysis, peroxide utilization, and detoxification. There are several project goals. (1) We plan to investigate the influence of hydrogen-bonding from coordinated imidazole and propionic acid side chains on the heme redox potetials and the reactivity of coordinated ligands. (2) 59 Co NMR will be used to probe the electronic environment about the metal in cobalt(III) porphyrins with respect to ring substituent and axial ligand variation, and hydrogen-bonding to/from axial ligands. We shall attempt to define a correlation between 59C0 and 57Fe NMR chemical shifts so that 57Fe chemicals shifts can be predicted for iron porphyrins and, ultimately, hemoproteins. (3) Electrochemistry at ca. -90 degrees C in relatively nonpolar solvent (e.g., dichloromethane) will be applied to thermally unstable species that model intermediates in peroxidase and cytochrome P-450 mediated reactions. The compounds to be studied include prophyrins (TPP,PPIX, PPIXDME, chelated hems) with the following relevant links: M-O2(M = Fe,Co), Fe-O-O-Fe, Fe-O, and Co(SR)O2. The purpose here is to study the redox behavior of these species and relate this to the protein reactions. (4) The applicability of pulsed laser optoacoustic spectroscopy to problems in metalloporphyrin and other biochemical dynamics will be tested. This may allow reactions to be studied at far lower reactant concentractions that previously possible. A variety of techniques are to be utilized. The kinetics will be followed via stopped-flow methods at temperatures from +50 degrees C to -70 degrees C. Others will be followed by the optoacoustics methods; this has never before been attempted and may be highly significant for studying protein reactions because only ca. 10-8 M concentrations are required. The electrochemistry will entail cyclic voltammetry, coulometry, and various polarographic techniques. The most promising is our recently develped method for doing cyclic voltammetry at very low temperatures in unreactive solvents. This may be extended to nonpolar solvents (e.g., toluene) by using microelectrode technology. 59Co NMR will be done at various field strengths to ascertain the importance of chemical shift anisotropy on the chemical shifts and linewidths, which relate to the d-d excitation energies in the porphyrin complexes. The proposed experiments offer an opportunity to delineate several important aspects of hemoprotein models. These include (1) the role of hydrogen-bonding on reactivity and redox behavior, (2) the electron transfer chemistry of reaction intermdiates, and (3) the electronic influence of the prophyrin ligand in comparison to other donor molecules.

该项目涉及金属卟啉化学的重要方面作为血红蛋白、肌红蛋白等血红蛋白的良好模型细胞色素和过氧化物酶。这些蛋白质具有多种功能过程，包括氧传输和储存、电子转移催化、过氧化物利用和解毒。有几个项目目标。（1）我们计划调查影响配位咪唑和丙酸侧链的氢键血红素氧化还原电位和配位配体的反应性。 (2) 59 Co NMR将用于探测金属的电子环境在钴(III)卟啉中关于环取代基和轴向配体变化，以及与轴向配体的氢键作用。我们将尝试定义 59C0 和 57Fe NMR 化学位移之间的相关性，使得 57Fe 可以预测铁卟啉的化学变化，并最终，血红素蛋白。 (3) 电化学-90℃相对非极性溶剂（例如二氯甲烷）将被施加到热模拟过氧化物酶和细胞色素中间体的不稳定物种 P-450 介导的反应。待研究的化合物包括卟啉（TPP、PPIX、PPIXDME、螯合下摆）具有以下相关链接： M-O2(M = Fe,Co)、Fe-O-O-Fe、Fe-O 和 Co(SR)O2。这里的目的是研究这些物种的氧化还原行为并将其与蛋白质联系起来反应。 (4)脉冲激光光声光谱的适用性金属卟啉和其他生化动力学问题已测试。这可能允许在低得多的反应物下研究反应以前可能的浓度。将使用多种技术。动力学将遵循在 +50 摄氏度至 -70 摄氏度的温度下通过停流方法 C.其他的依次采用光声学方法；这从来没有之前曾尝试过，对于研究蛋白质可能非常重要反应，因为只有大约。需要 10-8 M 浓度。这电化学将涉及循环伏安法、库仑法和各种极谱技术。最有前途的是我们最近开发的在非常低的温度下进行循环伏安法的方法溶剂。这可以扩展到非极性溶剂（例如甲苯）：采用微电极技术。 59Co NMR将在各个领域进行确定化学位移各向异性对化学位移和线宽，与 d-d 激发能相关在卟啉配合物中。拟议的实验提供了一个机会来描述几个血红素蛋白模型的重要方面。其中包括 (1) 的作用氢键对反应性和氧化还原行为的影响，(2) 电子反应中间体的转移化学，以及（3）电子与其他供体分子相比，卟啉配体的影响。