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  • Title: Two metals are better than one: investigations on the interactions between dinuclear metal complexes and quadruplex DNA.
    Author: Suntharalingam K, White AJ, Vilar R.
    Journal: Inorg Chem; 2010 Sep 20; 49(18):8371-80. PubMed ID: 20795697.
    Abstract:
    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 × 10(6) 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).
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