Active site models for galactose oxidase. Electronic effect of the thioether group in the novel organic cofactor
Active site models for galactose oxidase. Electronic effect of the thioether group in the novel organic cofactor
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DOI：
10.1021/ic961144a
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发表时间：
1997-03-26
影响因子：
4.6
通讯作者：
Fukuzumi, S
中科院分区：
文献类型：
--
作者：
Itoh, S;Takayama, S;Fukuzumi, S
Tyr 272和Cys 228之间硫醚键的电子效应半乳糖氧化酶（新的有机辅因子）已通过使用模型化合物，2-（甲硫基）-对甲酚（1H），2-（甲硫基）-4，6-二甲基苯酚（2 H），和2-（甲硫基）-4-甲基-6-[[双[2-（三氟甲基）苯基]氨基]甲基]-2-（三氟甲基）苯并[d]咪唑（2-吡啶基）乙基]氨基]甲基]苯酚（3 H），将其物理化学性质与2-[[双[2-（2-吡啶基）乙基]氨基]甲基]甲基苯酚（4 H）和对甲酚（5 H）的物理化学性质进行比较。1H-1 NMR和电化学研究表明，甲硫基基本上具有给电子的性质。另一方面，与5 H相比，1H和2 H的pK（a）值较低，表明甲硫基也具有2 p π-3d π电子共轭效应，稳定酚氧上的负电荷。此外，ESR研究和半经验分子轨道计算清楚地证明了自由基状态下取代基的共电子共轭效应。合成了二聚铜配合物[Cu（II）2（3（-））（2）]（PF 6）（2）（7）和[Cu-2（II）（4-）（2）]（PF 6）（2）（8），用X射线衍射法测定了其晶体结构。对通过加入吡啶（py）等外部配体原位生成的单体[Cu-II（3（-））（py）]（PF 6）（9）和[Cu-II（4（-））（py）]（PF 6）（10）的电化学分析表明，铜配合物中的甲硫基取代基显示出与游离配体类似的电子效应，稳定了Cu（II）中辅因子部分的苯氧基自由基状态复杂.
The electronic effect of the thioether linkage between Tyr 272 and Cys 228 (the novel organic cofactor) of galactose oxidase has been examined by using model compounds, 2-(methylthio)-p-cresol (1H), 2-(methylthio)-4,6-dimethylphenol (2H), and 2-(methylthio)-4-methyl-6-[[bis[2-(2-pyridyl)ethyl]amino]methyl]phenal (3H), the physicochemical properties of which are compared to those of 2-[[bis[2-(2-pyridyl)ethyl]amino]methyl] methylphenol (4H) and p-cresol (5H). H-1 NMR and electrochemical studies indicate that the methylthio group has essentially an electron-donating nature. On the other hand, the lower pK(a) values of 1H and 2H as compared to that of 5H suggest that the methylthio group also has a 2p pi-3d pi electron conjugative effect, stabilizing the negative charge on the phenolate oxygen. Furthermore, the electron-sharing conjugative effect of the substituent in the radical state has been clearly demonstrated by ESR studies and semiempirical molecular orbital calculations. Dimer copper(II) complexes [Cu(II)2(3(-))(2)](PF6)(2) (7) and [Cu-2(II)(4-)(2)](PF6)(2) (8) were prepared, and the crystal structures were determined by the X-ray diffraction method. Electrochemical analyses of the monomeric species [Cu-II(3(-))(py)](PF6) (9) and [Cu-II(4(-))(py)](PF6) (10) generated in situ by adding an external ligand such as pyridine (py) reveal that the methylthio substituent in the copper complex shows electronic effects similar to those of the free ligand stabilizing the phenoxyl radical state of the cofactor moiety in the Cu(II) complex.