1989 Fiscal Year Final Research Report Summary
Construction of Heterocyclic N-oxides possessing Highly Photooxidative Capacity and its Application
| Project/Area Number |
63570999
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
MAKI Yoshifumi Gifu Pharmaceutical University, Professor, 薬学部, 教授 (00082959)
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| Co-Investigator(Kenkyū-buntansha) |
KITADE Yukio Gifu Pharmaceutical University, Assistant Professor, 薬学部, 助手 (20137061)
SAKO Magoichi Gifu Pharmaceutical University, Assistant Professor, 薬学部, 助手 (10137060)
HIROTA Kosaku Gifu Pharmaceutical University, Associate Professor, 薬学部, 助教授 (90082982)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Heterocyclic N-oxide / Photooxidation / Oxygenation / Dehydrogenation / Pyrimidopteridine N-oxide / Chemical model / Photo-induced single-electron transfer / Functional molecule |
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| Research Abstract |
Photooxygenation by heterocyclic N-oxides has been considered to be a simple model reaction of monooxygenases in the biometabolism. The complexity of photoreactions in the N-oxides so far employed, however, results in the inefficient photooxygenation and makes it difficult to clarify the mechanism of the photooxygenation.
In this research project, we searched the heterocyclic N-oxide which possesses a high capacity only for the photooxidation among complex photoreactions and discovered pyrimido[5,4-g]pteridine-10-oxide (PPO) as such a functional X-oxide. On the basis of chemical and physicochemical studies on its photochemical reactivities, it was proved that PPO behaves an electron acceptor under the photochemical conditions and functions as an agent for oxygen-atom transfer or dehydrogenation depending upon the nature of substrates. The observed photochemical reactivities are unique among heterocyclic N-oxides and its photooxidation mode formally parallels that of an active oxygen species (Fe^<IV>=0)^+ in hemin-catalyzed biooxidation with respect to involvement of an initial single-electron-transfer process.
Some drugs, carcinogens, and biological substances such as amino acids and nucleosides were photochemically oxidized by PPO. The results demonstrated that these photooxidations provide a complementary tool for the study on the biometabolism and can be applied as a method for the chemical modification of these substrates.
As outlined above, the present research attained to a great extent our initial purposes and pointed out the presence of interesting projects, in particular, in the construction of N- oxides with the more prominent function, the chemical modification of proteins and nucleic acids by the N-oxides, and their physiological activities, which should be studied in the future.
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