MECHANISM OF AROMATIC HYDROXYLATION IN A COPPER MONOOXYGENASE MODEL SYSTEM - 1,2-METHYL MIGRATIONS AND THE NIH SHIFT IN COPPER CHEMISTRY
MECHANISM OF AROMATIC HYDROXYLATION IN A COPPER MONOOXYGENASE MODEL SYSTEM - 1,2-METHYL MIGRATIONS AND THE NIH SHIFT IN COPPER CHEMISTRY
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DOI：
10.1021/ja00033a024
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发表时间：
1992-03-25
影响因子：
15
通讯作者：
KARLIN, KD
中科院分区：
文献类型：
--
作者：
NASIR, MS;COHEN, BI;KARLIN, KD
NIH的移位机制似乎是可操作的铜单加氧酶模型系统，涉及双铜离子络合物介导的芳烃底物的O2羟基化。先前的研究表明，当含有两个由间二甲苯基连接的三齿PY 2单元（PY 2 =双[2-（2-吡啶基）乙基]胺）的双铜（I）络合物，即，[Cu 2（XYL-H）]2+（1）与分子氧反应，形成Cu 2 O2中间体，并在中间的2-二甲苯基位置发生羟基化。在此，详细描述了2-甲基取代的类似物[CU 2（Me 2XYL-CH 3）]2+（4）和[CU 2（XYL-CH 3）]2+（5）的相应反应。这些的氧化导致二甲苯基羟基化反应产生新的苯酚产物，伴随着甲基的1，2-迁移，一个PY 2配体臂的损失和甲醛的形成。测压O2摄取实验和O-18（2）标记研究证实，这些反应的化学计量与单加氧酶的观察结果一致。使用在苄基位置被氘代的双核配体进行的反应证实了CH 2 O产物是由该碳原子衍生的，该结果也与2-甲基的迁移一致。一致地获得了小收率的甲基双[2-（2-吡啶基）乙基]胺（MePY 2），并且实验表明这可能来源于中间体亚胺鎓盐{CH 2 = N[CH 2CH 2 PY 12}+（PY = 2-吡啶基）的还原。在这里观察到的羟基化诱导的1，2-甲基迁移是让人想起以前只在铁羟化酶中观察到的NIH移位反应，并表明铜离子介导的反应进行的亲电攻击的Cu 2 O2中间体后，接近的芳香族底物。提出了详细的机制，并讨论了已知的O2反应性和这些双核铜配合物的结构。该单加氧酶模型系统的生物学相关性和意义也是
The NIH shift mechanism appears to be operative in a copper monooxygenase model system involving dicopper ion complex mediated O2 hydroxylation of an arene substrate. Previous studies have shown that when a dicopper(I) complex containing two tridentate PY2 units (PY2 = bis[2-(2-pyridyl)ethyl]amine) which are linked by a m-xylyl group, i.e., [Cu2(XYL-H)]2+ (1), is reacted with dioxygen, a CU2O2 intermediate forms and hydroxylation in the intervening 2-xylyl position occurs. Here, corresponding reactions of 2-methyl substituted analogues [CU2(Me2XYL-CH3)]2+ (4) and [CU2(XYL-CH3)]2+ (5) are described in detail. Oxygenation of these causes xylyl hydroxylation reactions producing new phenol products, with concomitant 1,2-migration of the methyl group, loss of one PY2 ligand arm, and formaldehyde formation. Manometric O2 uptake experiments and an O-18(2) labeling study confirm that the stoichiometry of these reactions are consistent with that observed for monooxygenases. A reaction carried out using a dinucleating ligand which has been deuterated in benzylic positions confirms that the CH2O product is derived from this carbon atom, a result also consistent with migration of the 2-methyl group. A small yield of methylbis[2-(2-pyridyl)ethyl]amine (MePY2) is consistently obtained, and experiments suggest this may be derived from the reduction of an intermediate iminium salt {CH2 = N[CH2CH2PY12}+ (PY = 2-pyridyl). The hydroxylation induced 1,2-methyl migrations observed here are reminiscent of the NIH shift reactions previously observed only in iron hydroxylases and suggest that the copper ion mediated reactions proceed by the electrophilic attack of a CU2O2 intermediate upon the proximate aromatic substrate. A detailed mechanism is proposed and discussed in terms of the known O2 reactivity and structure of these dinuclear copper complexes. The biological relevance and significance of this monooxygenase model system is also