Efficient DNA Cleavage Induced by Copper(II) Complexes of Hydrolysis Derivatives of 2,4,6‐Tri(2‐pyridyl)‐1,3,5‐triazine in the Presence of Reducing Agents
Efficient DNA Cleavage Induced by Copper(II) Complexes of Hydrolysis Derivatives of 2,4,6‐Tri(2‐pyridyl)‐1,3,5‐triazine in the Presence of Reducing Agents
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DOI：
10.1002/ejic.200600821
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发表时间：
2007-02
影响因子：
2.3
通讯作者：
J. Borrás;G. Alzuet;M. González-Álvarez;J. García-Giménez;B. Macías;M. Liu-González
中科院分区：
文献类型：
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作者：
J. Borrás;G. Alzuet;M. González-Álvarez;J. García-Giménez;B. Macías;M. Liu-González
2,4,6-三(吡啶基)-1,3,5-三嗪 (ptz) 和铜(II)盐在 DMF/水 (1:1) 中反应，导致 ptz 水解并形成阴离子双(2-吡啶基羰基)酰胺 (ptO2–) 和双(2-吡啶胺)酰胺 (ptN2–)，这些阴离子存在于 配合物 [Cu(ptN2)(OAc)]·3H2O (1)、[Cu(ptO2)(OAc)(H2O)]·H2O (2)、[Cu(ptN2)(for)]·3H2O (3)（for = 甲酸盐）、[Cu(ptO2)(for)(H2O)] (4)、 [Cu(ptO2)(苯并)]·H2O (5)（苯=苯甲酸盐）和[Cu(ptO2)F(H2O)]2·3H2O (6)。该报告包括所有这些配合物的化学和光谱表征以及 4-6 的晶体结构。 4 和 5 中 CuII 的配位球最好描述为前者为扭曲的四角锥体，后者为扭曲的方形平面。 6 的晶体结构显示晶体学不对称单元中存在两个离散单体 [Cu(ptO2)F(H2O)] 实体，其中两个铜 (II) 离子均具有扭曲的方锥体配位几何形状。借助粘度和热变性研究，研究了复合物与 DNA 的结合，这两者都表明相互作用可能是由于外球机制。这些化合物切割 DNA 的能力也经过了测试。在温和还原剂（抗坏血酸）和双氧存在下观察到有效的氧化裂解。活性氧（ROS）清除剂的机理研究证实，过氧化氢、羟基自由基、类单线态氧和超氧阴离子是断裂过程中必要的可扩散中间体。提出了一种涉及 Fenton 或 Haber-Weiss 反应以及铜氧烯物质形成的机制，用于由这些化合物介导的 DNA 切割。（© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, German, 2007）
The reaction of 2,4,6-tri(pyridyl)-1,3,5-triazine (ptz) and copper(II) salts in dmf/water (1:1) results in the hydrolysis of ptz and formation of the anions bis(2-pyridylcarbonyl)amide (ptO2–) and bis(2-pyridylamine)amide (ptN2–), which are found in the complexes [Cu(ptN2)(OAc)]·3H2O (1), [Cu(ptO2)(OAc)(H2O)]·H2O (2), [Cu(ptN2)(for)]·3H2O (3) (for = formate), [Cu(ptO2)(for)(H2O)] (4), [Cu(ptO2)(benz)]·H2O (5) (benz = benzoate), and [Cu(ptO2)F(H2O)]2·3H2O (6). This report includes the chemical and spectroscopic characterization of all these complexes along with the crystal structures of 4–6. The coordination spheres of CuII in 4 and 5 are best described as distorted tetragonal square pyramidal for the former and distorted square planar for the latter. The crystal structure of 6 shows the presence of two discrete monomeric [Cu(ptO2)F(H2O)] entities in the crystallographic asymmetric unit in which both copper(II) ions have a distorted square-pyramidal coordination geometry. The binding of the complexes to DNA has been investigated with the aid of viscosity and thermal denaturation studies, both of which indicate that the interaction is probably due to the outer-sphere mechanism. The ability of the compounds to cleave DNA has also been tested. Efficient oxidative cleavage was observed in the presence of a mild reducing agent (ascorbate) and dioxygen. Mechanistic studies with reactive oxygen species (ROS) scavengers confirm that hydrogen peroxide, the hydroxyl radical, singlet oxygen-like species, and the superoxide anion are necessary diffusible intermediates in the scission process. A mechanism involving either the Fenton or theHaber–Weiss reaction plus the formation of copper oxene species is proposed for the DNA cleavage mediated by these compounds.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)