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Studies of new chemical model of cytochrome P-450 with phase-transfer system

相转移体系细胞色素P-450新化学模型的研究

基本信息

批准号：
04671318
负责人：
KITO Masahiro
金额：
$ 1.22万
依托单位：
Kyoto Pharmaceutical Univ.
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

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.

本研究的目的是开发新的化学模型，在更多的生理条件下，包括亲水和疏水相类似的细胞色素P-450的环境。首先，我们研究了在亲水性微晶纤维素存在下，锰卟啉配合物/NaBH_4对萘的氧化反应。萘氧化主要生成β-萘酚和2-萘酚，同时还生成少量的1，5-、1，5-、1，6-和1，7-萘二醇。在该体系中，1-萘酚氧化生成1，5-，1，6-和1，7-萘二醇，2-萘酚氧化生成1，6-，1，7-，2，6-和2，7-萘二醇。这表明萘是通过两步单氧化反应（萘-萘酚-二羟基萘）氧化的。在此基础上，我们建立了含锰卟啉配合物、硼氢化钠和苯乙烯-二乙烯基苯（XAD 2）疏水聚合物微粒的化学模型体系。得到了以下重要结果。(1)萘转化为1-萘酚和2-萘酚的生成比例（1-萘酚：2-萘酚）为80：20（微粒体系统为95：5）。此外，添加XAD 2导致产物增加，值得注意的是1-萘酚，表明通过添加XAD 2，萘的氧化更模拟微粒体氧化。(2)该模型系统可用于低水平底物的氧化，因为能够在活性催化剂相中积累疏水底物。(3)推测了超氧阴离子（O_2 ~*）的产生。超氧化物歧化酶（SOD）的加入抑制了55%的氧化反应，表明O_2 ~* 可能是本模型体系中的活性氧之一。(4)在疏水和亲水相的氧化同时发生本化学模型包含相转移系统。