Hirohama Tomoya, Kuranuki Yuko, Ebina Eriko, Sugizaki Takashi, Arii Hidekazu, Chikira Makoto, Tamil Selvi Pitchumony, Palaniandavar Mallayan
Department of Applied Chemistry, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
J Inorg Biochem. 2005 May;99(5):1205-19. doi: 10.1016/j.jinorgbio.2005.02.020.
A series of copper(II) complexes of the type [Cu(L)]2+, where L = N,N'-dialkyl-1,10-phenanthroline-2,9-dimethanamine and R = methyl (L1), n-propyl (L2), isopropyl (L3), sec-butyl (L4), or tert-butyl (L5) group, have been synthesized. The interaction of the complexes with DNA has been studied by DNA fiber electron paramagnetic resonance (EPR) spectroscopy, emission, viscosity and electrochemical measurements and agarose gel electrophoresis. In the X-ray crystal structure of [Cu(HL2)Cl2]NO3, copper(II) is coordinated to two ring nitrogens and one of the two secondary amine nitrogens of the side chains and two chloride ions as well and the coordination geometry is best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). Electronic and EPR spectral studies reveal that all the complexes in aqueous solution around pH 7 possess CuN3O2 rather than CuN4O chromophore with one of the alkylamino side chain not involved in coordination. The structures of the complexes in aqueous solution around pH 7 change from distorted tetragonal to trigonal bipyramidal as the size of the alkyl group is increased. The observed changes in the physicochemical features of the complexes on binding to DNA suggest that the complexes, except [Cu(L5)]2+, bind to DNA with partial intercalation of the derivatised phen ring in between the DNA base pairs. Electrochemical studies reveal that the complexes prefer to bind to DNA in Cu(II) rather than Cu(I) oxidation state. Interestingly, [Cu(L5)]2+ shows the highest DNA cleavage activity among all the present copper(II) complexes suggesting that the bulky N-tert-butyl group plays an important role in modifying the coordination environment around the copper(II) center, the Cu(II)/Cu(I) redox potential and hence the formation of activated oxidant responsible for the cleavage. These results were compared with those for bis(1,10-phenanthroline)copper(II), [Cu(phen)2]2+.
已合成了一系列通式为[Cu(L)]2+的铜（II）配合物，其中L = N,N'-二烷基-1,10-菲咯啉-2,9-二甲胺，R = 甲基（L1）、正丙基（L2）、异丙基（L3）、仲丁基（L4）或叔丁基（L5）基团。通过DNA纤维电子顺磁共振（EPR）光谱、发射光谱、粘度和电化学测量以及琼脂糖凝胶电泳研究了这些配合物与DNA的相互作用。在[Cu(HL2)Cl2]NO3的X射线晶体结构中，铜（II）与两个环氮原子、侧链两个仲胺氮原子中的一个以及两个氯离子配位，其配位几何结构最好描述为三角双锥畸变四方锥（TBDSBP）。电子光谱和EPR光谱研究表明，在pH约为7的水溶液中，所有配合物都具有CuN3O2而非CuN4O发色团，其中一个烷基氨基侧链不参与配位。随着烷基尺寸的增加，在pH约为7的水溶液中配合物的结构从畸变四方结构变为三角双锥结构。观察到的配合物与DNA结合时物理化学特征的变化表明，除了[Cu(L5)]2+之外，其他配合物通过衍生化的菲咯啉环部分插入DNA碱基对之间与DNA结合。电化学研究表明，这些配合物更倾向于以Cu（II）而非Cu（I）氧化态与DNA结合。有趣的是，[Cu(L5)]2+在所有现有的铜（II）配合物中显示出最高的DNA切割活性，这表明庞大的N-叔丁基基团在修饰铜（II）中心周围的配位环境、Cu（II）/Cu（I）氧化还原电位以及因此负责切割的活性氧化剂的形成中起着重要作用。将这些结果与双（1,10-菲咯啉）铜（II），即[Cu(phen)2]2+的结果进行了比较。
