Oxidative DNA cleavage promoted by multinuclear copper complexes: activity dependence on the complex structure.
Oxidative DNA cleavage promoted by multinuclear copper complexes: activity dependence on the complex structure.
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DOI：
10.1002/chem.200600044
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发表时间：
2006-08
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影响因子：
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通讯作者：
Yongmei Zhao;Jianhui Zhu;Weijiang He;Zhenghao Yang;Yangguang Zhu;Yi-zhi Li;Junfeng Zhang;Zijian Guo-Z
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文献类型：
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作者：
Yongmei Zhao;Jianhui Zhu;Weijiang He;Zhenghao Yang;Yangguang Zhu;Yi-zhi Li;Junfeng Zhang;Zijian Guo-Z
具有两个或三个Cu（BPA）的多核铜配合物（BPA，双（2-吡啶基甲基）胺）基序，[Cu 2（mTPXA）Cl 4]3 H2O（1），[Cu 2（pTPXA）Cl 4]3 H2O（2），[Cu 3（HPTAB）Cl 5] Cl 3 H2O（3）（mTPXA = N，N，N ′，N ′-四-（2-吡啶基甲基）-间苯二甲胺; pTPXA = N，N，N ′，N ′-四-（2-吡啶基甲基）-间苯二甲胺;（2-吡啶甲基）-对苯二甲胺（HPTAB = N，N，N '，N'，N“，N”-六（2-吡啶甲基）-1，3，5-三（氨甲基）苯）的合成与表征。化合物2和3的晶体结构表明，每个Cu（BPA）基序都具有4+1四方锥配位环境，其中一个氯原子占据顶端位置，三个来自同一BPA基序的N原子与另一个Cl原子一起形成基面。荧光光谱和圆二色光谱研究表明，化合物与DNA的结合遵循3>2>1的顺序。这些复合物在有氧条件下通过使用巯基丙酸（MPA）作为还原剂的氧化机制切割质粒pUC 19 DNA。双核Cu ~（2+）配合物1和2在相同的[Cu ~（2+）]浓度下比单核类似物[Cu（bpa）Cl ~ 2]表现出更高的裂解效率，表明Cu ~（2+）中心的协同效应。此外，配合物1中的间双铜中心促进了线性DNA的形成。有趣的是，复合物3中的间位双铜基序的额外铜中心降低了复合物1中间位双铜基序的切割效率，尽管它能够在较高的[Cu 2 +]浓度下将DNA切割成线性形式。因此，复合物3的较高DNA结合能力并不导致较高的切割效率。这些发现与DNA结合模式和Cu 2+络合物活化氧（O2）的能力相关。这一工作为合理设计多核Cu ~（2+）人工核酸酶提供了一个很好的例子，其活性可以通过金属中心的几何形状和数量来控制。
Polynuclear copper complexes with two or three Cu(BPA) (BPA, bis(2-pyridylmethyl)amine) motifs, [Cu2(mTPXA)Cl4]3 H2O (1), [Cu2(pTPXA)Cl4]3 H2O (2), [Cu3(HPTAB)Cl5]Cl3 H2O (3) (mTPXA = N,N,N',N'-tetra-(2-pyridylmethyl)-m-xylylene diamine; pTPXA = N,N, N',N'-tetra-(2-pyridylmethyl)-p-xylylenediamine; HPTAB = N,N,N',N',N'',N''-hexakis(2-pyridylmethyl)-1,3,5-tris-(aminomethyl)benzene) have been synthesized and characterized. The crystal structures of compounds 2 and 3 showed each Cu(BPA) motif had a 4+1 square-pyramidal coordination environment with one chloride occupying the apical position and three N atoms from the same BPA moiety together with another Cl atom forming the basal plane. Fluorescence and circular dichroism (CD) spectroscopy studies indicated that the DNA binding followed an order of 3>2>1 in the compounds. These complexes cleave plasmid pUC19 DNA by using an oxidative mechanism with mercaptopropionic acid (MPA) as the reductant under aerobic conditions. Dinuclear Cu2+ complexes 1 and 2 showed much higher cleavage efficiency than their mononuclear analogue [Cu(bpa)Cl2] at the same [Cu2+] concentration, suggesting a synergistic effect of the Cu2+ centers. Moreover, the meta-dicopper centers in complex 1 facilitated the formation of linear DNA. Interestingly, the additional copper center to the meta-dicopper motif in complex 3 decreased the cleavage efficacy of meta-dicopper motif in complex 1, although it is able to cleave DNA to the linear form at higher [Cu2+] concentrations. Therefore, the higher DNA binding ability of complex 3 did not lead to higher cleavage efficiency. These findings have been correlated to the DNA binding mode and the ability of the Cu2+ complexes to activate oxygen (O2). This work is a good example of the rational design of multinuclear Cu2+ artificial nuclease and the activity of which can be manipulated by the geometry and the number of metal centers.