含锰酶模型化合物的合成表征及其催化机理探索
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摘要
含金属锰酶因其独特的生物功能吸引了越来越多的研究兴趣。基于含锰酶的活性中心结构,通过设计并合成与酶活性中心结构类似的金属配合物,模拟酶的催化反应,借此来研究其催化机理,成为研究这些含锰酶的有效方法之一。本论文旨在通过对模型化合物的研究,特别是研究小分子对模型化合物的催化活性的影响,深入了解含锰酶的催化机理。
基于锰过氧化氢酶及锰超氧化物歧化酶的活性中心,合成了两类希夫碱锰配合物：含Salen类配体的锰配合物以及含Hbap类配体的锰配合物(salen为N,N'-二(亚水杨基)-1,2-乙二胺,Hbap为N-(2-亚水杨基)氨基吡啶)。其中配合物Mn(Brbap)Im、Mn(MeObap)Im、以及还原的Mn(bap)Py为新配合物。应用X-射线单晶衍射、紫外光谱、电喷雾质谱、元素分析和电化学等方法对配合物的结构进行了表征。
对上述所合成的配合物的锰过氧化氢酶活性及其机理进行了研究。详细分析了配体中苯环上取代基、溶液的酸碱性、小分子有机碱,如咪唑,吡啶等轴向配位对活性的影响。研究发现苯环上给电子基团可以提高配合物的过氧化氢酶活性,而吸电子基团却没有明显的影响。溶液的pH值也可以明显调控salen类锰配合物的催化活性。
通过结合了小分子碱的配合物与原配合物的比较,我们认为有机小分子碱增强配合物催化活性的机理为：当等当量的小分子碱存在时,它首先与配合物的金属离子配位,形成了一个活性较高的中间体；当过量的碱存在时,除了与金属离子配位外,它们还起到了分子内碱的作用,协助底物质子化作用。
而对于双核的salen类锰配合物的催化作用是通过不同的机理完成的,它的结构更接近于锰过氧化物酶的活性中心,所以它的活性稍高于单核的类似配合物。
通过对模拟配合物的结构和催化反应的研究促进了我们对锰过氧化氢酶及锰超氧化物歧化酶的催化反应机理的了解,而且有望在不久的将来将具有催化活性的配合物取代相应的酶运用于实际应用中。
Manganese containing enzymes have attracted much interest due to their unique biological functions. Many information about catalytic mechanisms of these enzymes were obtained with the assistances of their model compounds based on mimic the structure of their activity sites, therefore model compounds study is one of the important method for enzymes research. This study is try to through research the model complex especially the influence of small molecule of the activity of the model complex that to learn the function of the amino residue in the activity site of enzyme during the catalyze reaction.
Two types of manganese models were synthesized based on the activity sites of the manganese catalase and manganese superoxide dismutase. They are manganese salen complexes and Manganese Hbap complexes. Among them Mn(Brbap)Im, Mn(MeObap)Im and reduced Mn(bap)Py are new compounds which havn't been reported yet. The structures of these compounds were characterized with X-ray diffraction, UV-vis spectroscopy, element analysis, mass spectrometry and cyclic voltammetry.
The catalytic activities of MnCAT and MnSOD of these compounds were investigated in detail. The influence on catalytic activity by salen ring substitution, pH of the solution, small molecule coordination to the axial site like imidazole or pyridine were discussed. We found that electron-donating groups enhance the reaction rate. And the activity could also tuned by the pH value. Through compare we found that some small molecule organic base like imidazole could enhance the activity. We found that the dinuclear [Mn(salen)]2 showed different catalytic reaction intermediates in the presence and absence of sodium hydroxide.
The discovery of the catalase-like activity and the base enhancement of these complex provide valuable information for improvement and optimization of the catalase-like activity of any manganese salen complexes.
基于锰过氧化氢酶及锰超氧化物歧化酶的活性中心,合成了两类希夫碱锰配合物：含Salen类配体的锰配合物以及含Hbap类配体的锰配合物(salen为N,N'-二(亚水杨基)-1,2-乙二胺,Hbap为N-(2-亚水杨基)氨基吡啶)。其中配合物Mn(Brbap)Im、Mn(MeObap)Im、以及还原的Mn(bap)Py为新配合物。应用X-射线单晶衍射、紫外光谱、电喷雾质谱、元素分析和电化学等方法对配合物的结构进行了表征。
对上述所合成的配合物的锰过氧化氢酶活性及其机理进行了研究。详细分析了配体中苯环上取代基、溶液的酸碱性、小分子有机碱,如咪唑,吡啶等轴向配位对活性的影响。研究发现苯环上给电子基团可以提高配合物的过氧化氢酶活性,而吸电子基团却没有明显的影响。溶液的pH值也可以明显调控salen类锰配合物的催化活性。
通过结合了小分子碱的配合物与原配合物的比较,我们认为有机小分子碱增强配合物催化活性的机理为：当等当量的小分子碱存在时,它首先与配合物的金属离子配位,形成了一个活性较高的中间体；当过量的碱存在时,除了与金属离子配位外,它们还起到了分子内碱的作用,协助底物质子化作用。
而对于双核的salen类锰配合物的催化作用是通过不同的机理完成的,它的结构更接近于锰过氧化物酶的活性中心,所以它的活性稍高于单核的类似配合物。
通过对模拟配合物的结构和催化反应的研究促进了我们对锰过氧化氢酶及锰超氧化物歧化酶的催化反应机理的了解,而且有望在不久的将来将具有催化活性的配合物取代相应的酶运用于实际应用中。
Manganese containing enzymes have attracted much interest due to their unique biological functions. Many information about catalytic mechanisms of these enzymes were obtained with the assistances of their model compounds based on mimic the structure of their activity sites, therefore model compounds study is one of the important method for enzymes research. This study is try to through research the model complex especially the influence of small molecule of the activity of the model complex that to learn the function of the amino residue in the activity site of enzyme during the catalyze reaction.
Two types of manganese models were synthesized based on the activity sites of the manganese catalase and manganese superoxide dismutase. They are manganese salen complexes and Manganese Hbap complexes. Among them Mn(Brbap)Im, Mn(MeObap)Im and reduced Mn(bap)Py are new compounds which havn't been reported yet. The structures of these compounds were characterized with X-ray diffraction, UV-vis spectroscopy, element analysis, mass spectrometry and cyclic voltammetry.
The catalytic activities of MnCAT and MnSOD of these compounds were investigated in detail. The influence on catalytic activity by salen ring substitution, pH of the solution, small molecule coordination to the axial site like imidazole or pyridine were discussed. We found that electron-donating groups enhance the reaction rate. And the activity could also tuned by the pH value. Through compare we found that some small molecule organic base like imidazole could enhance the activity. We found that the dinuclear [Mn(salen)]2 showed different catalytic reaction intermediates in the presence and absence of sodium hydroxide.
The discovery of the catalase-like activity and the base enhancement of these complex provide valuable information for improvement and optimization of the catalase-like activity of any manganese salen complexes.
引文
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