栎精2，3-双加氧酶模型配体和配合物的合成、表征及其反应性
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摘要
本论文围绕当今国际上有关分子氧的活化及利用分子氧的生物氧化等研究热点,以分子水平上阐明Glu73的羧基、金属中心离子、配体的电子效应及空间效应等对栎精2,3-双加氧酶(Quercetin 2,3-dioxygenase简称2,3-QD)活性中心的结构、反应性、分子氧的活化机理的影响及其构-效关系为目的,开展了如下探索性的工作：
(1)设计、合成了1个新的分子内苯基侧壁的邻位导入羧基、两个吡啶环上6-位导入供电子基团-CH3的烷基二吡啶胺(bis(2-pyridylalkyl)amine)2,3-QD模型配体LH,并用IR、质谱、NMR、熔点测定等方法进行了表征。
(2)用所合成的模型配体LH设计、合成了6个新的过渡金属M(II/III)(M:Cu、Fe、Co、Ni)2,3-QD二元模型配合物,并用IR、UV-Vis、ESI/MS及X射线衍射等方法进行了表征,并解析了[FeⅡL(OAc)] (4)的X射线晶体结构,具有变形八面体配位环境。
(3)设计、合成了5个新的过渡金属M(Ⅱ/Ⅲ)(M:Cu、Fe、Co)包含底物的2,3-QD三元模型配合物,并用IR、UV-Vis、ESI/MS等方法进行了表征。
(4)用UV-Vis追踪的方法研究了所合成的二元和三元模型配合物与底物黄酮醇及分子氧的反应性,并通过比较研究初步探讨了金属中心离子、配体的电子效应、配体的空间效应及共配体对2,3-QD模型配合物的结构和反应性的影响及其构-效关系,得到了一些重要的结论。虽然模型配合物的结构类似但其反应性却明显不同,具体如下：
①金属离子效应：相同配体、金属离子不同时,反应性顺序为Cu>Fe>Co>Ni。
②电子效应：相同金属、不同配体时,苯环上羧基对位导入供电子基团-CH3的L8H的反应性较两个吡啶环上6-位导入CH3-的LH的好,反应性顺序为L8H>L1H>LH。
③空间效应：相同金属、配体不同时,吡啶环上6-位没有导入取代基的L1H反应性最好,两个吡啶环上6-位导入-CH3的LH的反应性次之,一个吡啶环的6-位导入苯基的L9H的反应性最差,即反应性顺序为L1H>LH>L9H。
④共配体效应：相同金属和配体,共配体为SO42-的反应性较OAc-的好。
有关系统探讨分子内导入的羧基、金属离子、配体的电子效应及共配体效应等对2,3-QD模型配合物的结构、反应性的影响及其构-效关系等方面的研究尚未见文献报道。
Dioxygen activation for the purpose of biomimetic oxidations has received considerable attention, owing to the possible application in catalysts for bioremediation of aromatic waste recently. In this paper, we focus on this active area, aiming at getting insights into the catalytic role of Glu73, metal ion effects, electronic effects and steric effects of the ligands, and co-ligands effects on the structure and reactivity of Quercetin 2,3-dioxygenase.
One new bis(6-methyl-2-pyridylmethyl)amine model ligand carrying ortho-benzoic acid derivative as the ligand sidearm (LH) has been designed, synthesized, and characterized by IR, UV-Vis, ESI/MS,1HNMR and melting point measurement.
Six novel binary model complexes and five ternary model complexes M(Ⅱ) (M:Fe, Co, Cu and Ni) have been designed, synthesized, and characterized as the structural and functional models for the active site of Quercetin 2,3-dioxygenase. Our design of model ligands and complexes focus on both catalytic site and substrate binding site of the enzyme. The structure of complex 4 has been determined by X-ray diffraction, which exhibits a distorted octahedral geometry.
The reactivities of the model complexes towards flavonol and dioxygen have been investigated by UV-Vis monitoring. The metal ion effects, electronic effects and steric effects of the ligands, co-ligands effects on the reactivity of the model complexes have been investigated. Although the structures of the model complexes are similar, the reactivities show notable differences. The conclusions of our study are as follows.
Metal ion effects:with the same ligand, the reactivities of model complexes with different metal ions are quite different and in the order Cu> Fe> Co> Ni.
Electronic effects:with the same ligand, the reactivities of model complexes with different ligands show notable differences and in the order L8H> L1H> LH.
Steric effects:with the same ligand, the reactivities of model complexes with different ligands are quite different and in the order L1H> LH> L9H.
Co-ligands effects:with the same metal ion and ligand, the reactivity of the complex with SO42- is much higher than the complex with OAc.
(1)设计、合成了1个新的分子内苯基侧壁的邻位导入羧基、两个吡啶环上6-位导入供电子基团-CH3的烷基二吡啶胺(bis(2-pyridylalkyl)amine)2,3-QD模型配体LH,并用IR、质谱、NMR、熔点测定等方法进行了表征。
(2)用所合成的模型配体LH设计、合成了6个新的过渡金属M(II/III)(M:Cu、Fe、Co、Ni)2,3-QD二元模型配合物,并用IR、UV-Vis、ESI/MS及X射线衍射等方法进行了表征,并解析了[FeⅡL(OAc)] (4)的X射线晶体结构,具有变形八面体配位环境。
(3)设计、合成了5个新的过渡金属M(Ⅱ/Ⅲ)(M:Cu、Fe、Co)包含底物的2,3-QD三元模型配合物,并用IR、UV-Vis、ESI/MS等方法进行了表征。
(4)用UV-Vis追踪的方法研究了所合成的二元和三元模型配合物与底物黄酮醇及分子氧的反应性,并通过比较研究初步探讨了金属中心离子、配体的电子效应、配体的空间效应及共配体对2,3-QD模型配合物的结构和反应性的影响及其构-效关系,得到了一些重要的结论。虽然模型配合物的结构类似但其反应性却明显不同,具体如下：
①金属离子效应：相同配体、金属离子不同时,反应性顺序为Cu>Fe>Co>Ni。
②电子效应：相同金属、不同配体时,苯环上羧基对位导入供电子基团-CH3的L8H的反应性较两个吡啶环上6-位导入CH3-的LH的好,反应性顺序为L8H>L1H>LH。
③空间效应：相同金属、配体不同时,吡啶环上6-位没有导入取代基的L1H反应性最好,两个吡啶环上6-位导入-CH3的LH的反应性次之,一个吡啶环的6-位导入苯基的L9H的反应性最差,即反应性顺序为L1H>LH>L9H。
④共配体效应：相同金属和配体,共配体为SO42-的反应性较OAc-的好。
有关系统探讨分子内导入的羧基、金属离子、配体的电子效应及共配体效应等对2,3-QD模型配合物的结构、反应性的影响及其构-效关系等方面的研究尚未见文献报道。
Dioxygen activation for the purpose of biomimetic oxidations has received considerable attention, owing to the possible application in catalysts for bioremediation of aromatic waste recently. In this paper, we focus on this active area, aiming at getting insights into the catalytic role of Glu73, metal ion effects, electronic effects and steric effects of the ligands, and co-ligands effects on the structure and reactivity of Quercetin 2,3-dioxygenase.
One new bis(6-methyl-2-pyridylmethyl)amine model ligand carrying ortho-benzoic acid derivative as the ligand sidearm (LH) has been designed, synthesized, and characterized by IR, UV-Vis, ESI/MS,1HNMR and melting point measurement.
Six novel binary model complexes and five ternary model complexes M(Ⅱ) (M:Fe, Co, Cu and Ni) have been designed, synthesized, and characterized as the structural and functional models for the active site of Quercetin 2,3-dioxygenase. Our design of model ligands and complexes focus on both catalytic site and substrate binding site of the enzyme. The structure of complex 4 has been determined by X-ray diffraction, which exhibits a distorted octahedral geometry.
The reactivities of the model complexes towards flavonol and dioxygen have been investigated by UV-Vis monitoring. The metal ion effects, electronic effects and steric effects of the ligands, co-ligands effects on the reactivity of the model complexes have been investigated. Although the structures of the model complexes are similar, the reactivities show notable differences. The conclusions of our study are as follows.
Metal ion effects:with the same ligand, the reactivities of model complexes with different metal ions are quite different and in the order Cu> Fe> Co> Ni.
Electronic effects:with the same ligand, the reactivities of model complexes with different ligands show notable differences and in the order L8H> L1H> LH.
Steric effects:with the same ligand, the reactivities of model complexes with different ligands are quite different and in the order L1H> LH> L9H.
Co-ligands effects:with the same metal ion and ligand, the reactivity of the complex with SO42- is much higher than the complex with OAc.
引文
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