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，用于活化O_2或失活活性氧物种。其中，大环四胺类化合物和含咪唑基团的三胺类化合物分别模拟了类血红素吸氧功能和超氧化物歧化酶功能。我们的原始镍(II)大环二氧戊胺配合物在室温下形成1：1的O_2加合物，从而在水溶液中活化O_2。长期以来，由于Ni(II)络合物及其O2加合物的不稳定性，我们在研究这些新的反应机理时遇到了极大的困难。然而，我们现在已经成功地分离出一种稳定的复杂前体，这为机制研究带来了光明的突破。博莱霉素是一种通过氧激活机制杀死癌细胞的抗生素。铜(I)能否成为中心金属离子一直备受争议。为了解决这场争论，我们合成了两种模型化合物。通过这个模型研究，我们可以证明博莱霉素类配体形成了两个异构体的铜(I)络合物，其中只有一个物种对O_2的活化作用与Fe(II)络合物的作用相当。用我们目前的方法解决这个问题，可以激活O_2和Fe(II)络合物。这一问题的解决将导致新的氧气活化剂、催化剂和药物的开发。

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.