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Synthesis of Novel Iron Complexes with Superoxide Dismutase Activity

具有超氧化物歧化酶活性的新型铁配合物的合成

基本信息

批准号：
06453191
负责人：
NAGANO Tetsuo
金额：
$ 4.67万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06453191/
关键词：
Superoxide Superoxide Dismutase Ion Complex Spin Crossover Complex Anti-inflammation Paraquat Anti-oxidant 鉄-錯体

项目摘要

Recently it has been reported that superoxide (O_2) correlates with a cause of several diseases such as inflammation and carcinogenesis. Superoxide dismutase (SOD) serves a defensive role by catalyzing the conversion of O_2 to hydrogen peroxide and dioxygen. Therefore SOD and SOD mimics, which are complexes with SOD activity, are thought to be effective. We reported the first iron complexes, Fe (II)・TPEN (TPEN : N,N,N', N'-tetrakis (2-pyridylmethyl) ethylene diamine) Fe (III)・TPAA (TPAA : tris (N-(2-pyridylmethy)-2-amminoethyl)amine), which has high SOD activity not only in vitro but also in vivo. We also showed by X-ray structure analysis that Fe (II)・TPEN has two different structures, one of which is expressed as FeN6, the other as FeN5O.In order to clarify the relationship between these structures and SOD activity, we designed and synthesized TPEN analogues and investigated SOD activity, stability of oxygen and redox potentials of Fe (II) complexes of these chelators. The result suggested that,1)it is necessary for SOD activity that complexes are labile and interact directly with O2-. Therefore FeN5O structrue of Fe (II)・TPEN is the important intermediate in the reaction with O2-.2)the methyl group of the pyridine coordinated to Fe (II) has the influence on SOD activity and the stability to oxygen, but that of the uncoordinated pyridine has no effect on SOD activity.

最近有报道称，超氧化物（O_2）与炎症和致癌等多种疾病的病因有关。超氧化物歧化酶（SOD）通过催化 O_2 转化为过氧化氢和分子氧来发挥防御作用。因此，SOD 和 SOD 模拟物（具有 SOD 活性的复合物）被认为是有效的。我们报道了第一个铁络合物Fe (II)·TPEN (TPEN : N,N,N', N'-四(2-吡啶甲基)乙二胺) Fe (III)·TPAA (TPAA : 三(N-(2-吡啶甲基)-2-氨乙基)胺)，其不仅在体外而且在体内都具有高SOD活性。我们还通过X射线结构分析表明，Fe(II)·TPEN有两种不同的结构，一种表示为FeN6，另一种表示为FeN5O。为了阐明这些结构与SOD活性之间的关系，我们设计合成了TPEN类似物，并研究了这些螯合剂的SOD活性、氧稳定性和Fe(II)配合物的氧化还原电位。结果表明：1)复合物不稳定并能直接与O2-相互作用，这是SOD活性所必需的。因此Fe(II)·TPEN的FeN5O结构是与O2-反应的重要中间体。2)与Fe(II)配位的吡啶的甲基对SOD活性和对氧的稳定性有影响，而未配位的吡啶的甲基对SOD活性没有影响。