Two metals are better than one: investigations on the interactions between dinuclear metal complexes and quadruplex DNA.
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).
Suntharalingam
Kogularamanan
K
Department of Chemistry, Imperial College London, London SW7 2AZ, UK.
White
Andrew J P
AJ
Vilar
Ramon
R
D000588:Amines / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D054856:G-Quadruplexes; D006801:Humans; D019216:Metals, Heavy / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D010710:Phosphates / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity; D044366:Transition Temperature
D000588:Amines; D019216:Metals, Heavy; D009942:Organometallic Compounds; D010710:Phosphates; D011725:Pyridines; D004247:DNA; C023666:pyridine