DNA base recognition and reaction with polynuclear metal complexes

为了开发氧化或水解切割DNA的试剂，我们合成了以下列出的多核金属配合物，并通过各种光谱测量、x射线晶体学、质量分析和琼脂糖凝胶电泳研究了它们的结合结构、对DNA的亲和力和DNA切割反应。与相应的单核金属配合物的结果进行比较，分析了影响金属配合物取向和反应活性的因素。(1)含组氨酸肽双核铜（II）配合物。(2)具有不同配位位的杂核铜（II）配合物。(3)水溶性水杨醛席夫碱双核Ni（II）配合物。(4)含顺式，顺式-1,3,5-三氨基环己烷的双核铜（II）配合物。(5) 2,9取代菲罗啉衍生物的三核锌（II）配合物。在(1)的情况下，表明肽的氨基酸序列对结合结构和切割有很大影响。测定了(2)中合成的配合物的晶体结构，并确定了两个不同配位位点的存在。用DNA纤维ESR光谱研究了与DNA结合的复合物的结构。合成了含四氨基二苯基（配合物1）和氨基醇、吡唑基（配合物2）的双核Ni（II）希夫碱配合物(3)。与相应的单核复合物相比，复合物1的氧化DNA裂解活性增加，而复合物2的氧化DNA裂解活性降低。在(4)的情况下，在配合物与过氧化氢的反应中检测到μ-η2:η2过氧化物络合物，表明氢过氧化物形式是DNA切割反应的活性物质。最后，一种新型的三核Zn（II）配合物(5)显示出比相应的单核Zn（II）配合物更强的水解DNA切割反应性。

To develop reagents for oxidative or hydrolytic cleavage of DNA, we have synthesized polynuclear metal complexes listed below and investigated their binding structure, the affinity to DNA, and the DNA cleaving reaction by using various spectroscopic measurements, X-ray crystallography, mass analysis, and agarose gel electrophoresis. Comparing the results with those of the corresponding mononuclear metal complexes, we have tried to analyze the factors that govern the specific orientation of the metal complexes and the reactivity.(1)Histidine-containing peptide dinuclear copper(II) complexes.(2)Hetero dinuclear copper(II) complexes with different coordination sites.(3)Water-soluble salicylaldehyde Schiff base dinuclear Ni(II) complexes.(4)Dinuclear copper(II) complex containing cis,cis-1,3,5-triaminocyclohexane (tach).(5)Trinuclear zinc(II) complex of a 2,9-substituted phenanthroline derivative.In the case of (1), it was shown that amino acid sequences of the peptides influence considerably the binding structure and cleavage. The crystal structure of the complex synthesized in (2) was determined and the presence of two different coordination sites was confirmed. The structure of the complex bound to DNA was investigated by DNA fiber ESR spectroscopy. Dinuclear Ni(II) Schiff base complexes (3) with tetraaminodiphenyl group (complex 1) and with aminoalcohol and pyrazole groups (complex 2) were synthesized and characterized. The oxidative DNA cleavage activity increased for complex 1 but decreased for complex 2, compared with those of the corresponding mononuclear complexes. In the case of (4), μ-η2:η2 peroxide complex was detected in the reaction of the complex with hydrogen peroxide, indicating that the hydroperoxo form was the active species for DNA cleaving reaction. Finally, a novel trinuclear Zn(II) complex (5) showed hydrolytic DNA cleaving reactivity much stronger than the corresponding mononuclear Zn(II) complex.