Dinuclear ruthenium(II) triple-stranded helicates: Luminescent supramolecular cylinders that bind and coil DNA and exhibit activity against cancer cell lines
Dinuclear ruthenium(II) triple-stranded helicates: Luminescent supramolecular cylinders that bind and coil DNA and exhibit activity against cancer cell lines
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DOI：
10.1002/anie.200700656
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Hannon, Michael J.
中科院分区：
文献类型：
--
作者：
Pascu, Gabriel I.;Hotze, Anna C. G.;Hannon, Michael J.
与DNA结合并影响其加工的合成试剂是分子设计中有吸引力的目标。小分子可以调节特定的基因表达[1]，并作为抗癌和抗病毒药物保持在临床应用的最前沿。[2]临床药物可以嵌入（蒽环类抗生素），[3]小沟结合（Berenil），[4]或与DNA形成配位键（顺铂）。[5]为了产生不同的活性谱并避免交叉耐药性，重要的是探索以新的和不同的方式与DNA相互作用的药物。我们以前描述了与蛋白质锌指大小和形状相似的合成金属超分子圆柱体。这些四阳离子圆柱体包含三个双（吡啶亚胺）配体链包裹在一个螺旋的方式约两个铁（II）中心。圆柱体不仅可以在DNA的大沟中强烈地和非共价地结合，在天然聚合物DNA中诱导戏剧性的和前所未有的分子内DNA卷曲，[2，6]而且可以在Y形DNA接头的中心结合，这是一种前所未有的和迄今为止意想不到的DNA识别模式。[7]将这些显著的DNA结合特征与钌化合物代表一类新的和有前途的抗癌药物[8-10]的事实相结合，导致开发三链钌圆柱体的目的，其将是研究其生物活性的少数非共价DNA识别金属化合物之一。这种设计仍然更有吸引力，因为发光的潜力（从MLCT状态），[11]这可能被用来探测DNA结合。我们在此描述了配体L的发光钌（II）三链螺旋物的合成（方案1），并探索其DNA结合和对癌细胞的活性。尽管用不稳定的第一行过渡金属合成三链螺旋化合物已经成熟[12]，但用惰性金属合成三链螺旋化合物，例如
Synthetic agents that bind to DNA and affect its processing are attractive targets in molecular design. Small molecules can regulate specific gene expression [1] and remain at the forefront of clinical application as anticancer and antiviral drugs.[2] Clinical drugs can intercalate (anthracycline antibiotics),[3] minor groove bind (berenil),[4] or form coordination bonds to DNA (cisplatin).[5] To create different spectra of activity and circumvent cross-resistance, it is important to explore drugs that interact with DNA in new and distinct ways.We have previously described synthetic metallo-supramolecular cylinders of a similar size and shape to protein zinc fingers. These tetracationic cylinders contain three bis (pyridylimine) ligand strands wrapped in a helical fashion about two iron (II) centers. The cylinders not only can bind strongly and noncovalently in the major groove of DNA, inducing dramatic and unprecedented intramolecular DNA coiling in natural polymeric DNAs,[2, 6] but also can bind at the heart of Y-shaped DNA junctions, an unparalleled and hitherto unexpected mode of DNA recognition.[7] Combining these striking DNA binding features with the fact that ruthenium compounds represent a new and promising class of anticancer drugs [8–10] led to the aim of developing a triple-stranded ruthenium cylinder that would be one of the few noncovalent DNA recognition metal compounds studied for its biological activity. This design was still more attractive because of the potential for luminescence (from MLCT states),[11] which might be used to probe the DNA binding. We describe herein the synthesis of the luminescent ruthenium (II) triple-stranded helicate of ligand L (Scheme 1) and explore its DNA binding and activity against cancer cells. Although the synthesis of triple-stranded helicates with labile first-row transition metals is well established,[12] the synthesis of triple-stranded helicates with an inert metal such