1989 Fiscal Year Final Research Report Summary
Design of Dioxygen Activating Agents and Active Oxygen Deactivating Agents and Their Medicinal Application
| Project/Area Number |
63470128
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Coordination Chemistry Laboratories, Institute for Molecular Science |
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Principal Investigator |
KIMURA Eiichi Coordination Chemistry Laboratories, Institute for molecular Science, Professor, 分子科学研究所・錯体化学実験施設(広島大学・医学部・併任), 教授 (30034010)
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| Co-Investigator(Kenkyū-buntansha) |
SHIONOYA Mitsuhiko Coordination Chemistry Laboratories, Institute for Molecular Science Research As, 分子科学研究所・錯体化学実験施設, 助手 (60187333)
KOIKE Tohru Hiroshima University School of Medicine Associate Professor, 医学部, 平成1. 縲怩W月講師, (90186586)
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| Project Period (FY) |
1988 – 1989
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| Keywords | activation of O_2 / active oxygen species / superoxide dismutase / macrocyclic polyamine / heme-like function / bleomycine / model ligands / catalysis |
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| Research Abstract |
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.
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[Publications] E. Kimura, T. Koike, M. Kodama, and Dan Meyerstein,: "A Copper(I)-N, N, N' , N" , N" -Pentamethylenetriamine Complex and Its Carbon Monoxide Addult in Aqueous Solutions" Inorg.Chem., 28, 2998-3001, 1989.
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