Design of Dioxygen Activating Agents and Active Oxygen Deactivating Agents and Their Medicinal Application

合成了一系列新的大环多胺配体，它们被设计为激活O_2或失活活性氧。其中，大环四胺和咪唑悬垂的三胺分别模拟血红素样的O_2摄取功能和超氧化物歧化酶功能。我们原来的大环二氧苯二胺镍（II）配合物已被证明形成1:1的O_2加合物，从而在室温下激活水溶液中的O_2。长期以来，由于Ni（II）配合物及其O_2加合物的不稳定性，我们在研究这些新的反应机理方面遇到了极大的困难。然而，我们现在已经成功地分离了一个稳定的复合前体，这为机理研究带来了一个光明的突破。博莱霉素是一种通过O_2激活机制杀死癌细胞的抗生素。铜(I)是否可以作为中心金属离子一直存在争议。为了解决这个争论，我们合成了两个模型化合物。通过这个模型研究，我们可以证明有两种同分异构体Cu(I)配合物是由类博莱霉素配体形成的，其中只有一种能像Fe（II）配合物一样激活O_2。用我们现在的方法解决这样一个问题，可以像激活Fe（II）络合物一样激活O_2。这一问题的解决将有助于开发新的O_2活化剂、催化剂和药物。

New series of macrocyclic polyamine ligands have been synthesized, which were designed to activate O_2 or deactivate active oxygen species. Among these, a macrocyclic tetraamine and a triamine with an imidazole-pendant are of interest, which mimic a heme-like O_2 uptake function and a superoxide dismutase function, respectively.Our original nickel(II) complex of a macrocyclic dioxopentaamine has been shown to form a 1:1 O_2 adduct and thereby activate O_2 in aqueous solution at room temperature. We have long met an extreme difficulty in studying these novel reaction mechanisms due to instability of the Ni(II) complex and its O_2 adduct. However, we have now succeeded in isolation of a stable complex precursor that brings a bright breakthrough for the mechanistic study.Bleomycin is an antibiotic that kills cancer cells via an O_2 activation mechanism. It has been long disputed whether copper(I) can be the central metal ion. To settle this debate, we have synthesized two model compounds. Through this model study, we could demonstrate that there are two isomeric Cu(I) complexes formed by the bleomycin-like ligands, of which only one species can activate O_2 as much as the Fe(II)complex. The solution of such a question with our present can activate O_2 as much as the Fe(II)complex. The solution of such a question with our present study will lead to development of new O_2 activating agents, catalysis and medicines.