Two Metals Are Better than One: Investigations on the Interactions between Dinuclear Metal Complexes and Quadruplex DNA

详细信息    查看全文

• 作者：Kogularamanan Suntharalingam ; Andrew J. P. White ; Ramon Vilar
• 刊名：Inorganic Chemistry
• 出版年：2010
• 出版时间：September 20, 2010
• 年：2010
• 卷：49
• 期：18
• 页码：8371-8380
• 全文大小：994K
• 年卷期：v.49,no.18(September 20, 2010)
• ISSN：1520-510X

文摘

Twelve mono- and dimetallic complexes (the metals being Cu^II, Pt^II, and Zn^II) with terpyridine-based ligands have been prepared and fully characterized. The X-ray crystal structures of two of the complexes (monometallic Cu^II and Zn^II complexes with a morpholino-substituted terpyridine ligand) are reported. The affinities of the 12 complexes toward duplex and quadruplex (HTelo and c-myc) DNA have been investigated using a combination of techniques including fluorescent indicator displacement (FID) assay, UV−vis spectroscopy and circular dichroism (CD). These studies revealed that the dicopper and diplatinum complexes 11 and 12 bind very strongly to quadruplex DNA (up to K = 7.97 × 10⁶ M⁻¹) and with good selectivity (up to 100-fold) over duplex DNA. In these dimetallic complexes, one of the metals is coordinated to a terpyridine moiety yielding square based pyramidal (with Cu^II) or square planar (with Pt^II) geometries. The second metal is coordinated to a dipicolyl amine linked to terpyridine by a three-atom spacer. We propose that these complexes bind to quadruplex DNA via a combination of interactions: π−π end-stacking between the metal-terpyridine fragment and the guanine quartet, and electrostatic/metal-phosphate interactions (between the metal-dipicolyl amine fragment and DNA’s backbone).