Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Inorg Chem. 2011 Nov 21;50(22):11437-45. doi: 10.1021/ic201244y. Epub 2011 Oct 26.
We synthesized a new photoactive dinuclear zinc(II) complex by linking two zinc centers with a ligand containing an azobenzene chromophore and investigated the DNA cleavage activities of its trans and cis forms. The trans structure of the dinuclear zinc complex was determined by X-ray crystallography, where each zinc center is situated in an octahedral coordination environment comprised of three nitrogen atoms from the ligand and three oxygen atoms from two nitrate ions. The dinuclear zinc complex containing the azobenzene chromophore was photoisomerizable between the trans and cis forms. The binding affinities of the trans and cis complexes with calf thymus (CT)-DNA were similar. Although the DNA cleavage activity of the trans complex was negligible, the cis complex was able to cleave DNA. We attribute the efficient activity of the cis complex to the cooperation of the two closely located zinc centers and the inactivity of the trans complex to the two metal centers positioned far away from each other. The DNA cleavage activity of the cis complex exhibited a pH-dependent bell-shaped profile, which has been observed in the hydrolytic cleavage of DNA by zinc complexes. The DNA cleavage activity was not inhibited by a major groove binder, methyl green, but decreased significantly by a minor groove binder, 4',6-diamidino-2-phenylindole, indicating that the dinuclear zinc complex binds to the minor groove of DNA. The present work shows the importance of the cooperation of two zinc ions for hydrolytic DNA cleavage, which can be photoregulated by linking the two metal centers with a photoisomerizable spacer, such as an azobenzene chromophore.
我们合成了一种新的光活性双核锌（II）配合物，通过将两个锌中心与一个含有偶氮苯发色团的配体连接起来，并研究了其顺式和反式构象的 DNA 切割活性。双核锌配合物的反式结构通过 X 射线晶体学确定，其中每个锌中心位于由配体的三个氮原子和两个硝酸盐离子的三个氧原子组成的八面体配位环境中。含有偶氮苯发色团的双核锌配合物可以在反式和顺式之间光致异构化。顺式和反式配合物与小牛胸腺（CT）-DNA 的结合亲和力相似。尽管反式配合物的 DNA 切割活性可以忽略不计，但顺式配合物能够切割 DNA。我们将顺式配合物的有效活性归因于两个紧密相邻的锌中心的协同作用，而反式配合物的无活性归因于两个金属中心彼此远离。顺式配合物的 DNA 切割活性表现出 pH 依赖性钟形轮廓，这在锌配合物对 DNA 的水解切割中已经观察到。DNA 切割活性不受主沟结合物甲基绿的抑制，但被小沟结合物 4'，6-二脒基-2-苯吲哚显著抑制，表明双核锌配合物与 DNA 的小沟结合。本工作表明，两个锌离子的协同作用对于水解 DNA 切割非常重要，通过用光致异构化间隔物（如偶氮苯发色团）将两个金属中心连接起来，可以对其进行光调控。
