| Co-Investigator(Kenkyū-buntansha) |
TAKESHIMA Shigeo Kyoto pharmaceutical university, Pharm.dept., Assistant, 薬学部, 助手 (60236461)
SAKURAI Hiromu Kyoto pharmaceutical university, Pharm.dept., Professor, 薬学部, 教授 (30065916)
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| Research Abstract |
The purpose of this study is to development of the new chemical model in more physiological conditions consisting of both hydrophilic and hydrophobic phases analogous to the environment of cytochrome P-450. First, we investigated the oxygenation of naphthalene by the Mn-porphyrin complex/NaBH_4 in the presence of hydrophilic microcrystalline celluose. Naphthalene was oxygenated mainly to u-naphthol and 2-naphthol, together with the formations of small amounts of 1, 5-, of 1, 5-, 1,6- and 1, 7-naphthalenediols. When 1-naphthol was oxygenated in this system, 1, 5-, 1, 6- and 1, 7-naphthalenediols were produced, and 2-naphthol was convedrted to 1, 6-, 1, 7-, 2, 6- and 2, 7-naphthalenediols. These indicate that naphthalene is oxidized by two step monooxygenations(naphthalene->naphthols->dihydroxynaphthalenes). Then we developed the chemical model system containing Mn-porphyrin complex, NaBH_4 and hydrophobic polymer particles of stylene-divinylbenzene(XAD2). The following important results are obtained. (1) Naphthalene is converted to 1-naphthol and 2-naphthol at a formation ratio (1-naphtho : 2-naphthol) of 80 : 20 (that of microsomal system 95 : 5). Also, addition of XAD2 results in an increase in the products, notable 1-naphthol, indicating that the oxygenation of naphthalene is more mimics microsomal oxygenation by addition of XAD2. (2) This model system is useful for the oxygenation of the low level of substrate, because of the ability to accumulate hydrophobic substrate in the active catalyst phase. (3) The production of superoxide anion(O_2*) was presumed. Also, addition of superoxide dismutase suppresses the oxygenation be about 55%, suggesting that O_2*) is one of the possible active oxygen species in the present model system. (4) Oxygenations in the hydrophobic and hydrophilic phases occur simultaneously by the present chemical model containing the phase-transfer system.
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