title: Tridentate N-donor palladium(II) complexes as efficient coordinating quadruplex DNA binders.
abstract: Fifteen complexes of palladium, platinum, and copper, featuring five different N-donor tridentate (terpyridine-like) ligands, were prepared with the aim of testing their G-quadruplex-DNA binding properties. The fluorescence resonance energy transfer melting assay indicated a striking positive effect of palladium on G-quadruplex DNA stabilization compared with platinum and copper, as well as an influence of the structure of the organic ligand. Putative binding modes (noncoordinative π stacking and base coordination) of palladium and platinum complexes were investigated by ESI-MS and UV/Vis spectroscopy experiments, which all revealed a greater ability of palladium complexes to coordinate DNA bases. In contrast, platinum compounds tend to predominantly bind to quadruplex DNA in their aqua form by noncoordinative interactions. Remarkably, complexes of [Pd(ttpy)] and [Pd(tMebip)] (ttpy = tolylterpyridine, tMebip = 2,2'-(4-p-tolylpyridine-2,6-diyl)bis(1-methyl-1H-benzo[d]imidazole)) coordinate efficiently G-quadruplex structures at room temperature in less than 1 h, and are more efficient than their platinum counterparts for inhibiting the growth of cancer cells. Altogether, these results demonstrate that both the affinity for G-quadruplex DNA and the binding mode of metal complexes can be modulated by modifying either the metal or the organic ligand.
authors: UMR176 CNRS, Institut Curie, Centre de Recherche, Centre Universitaire, 91405 Orsay, France.
authors: Eric
authors: E
authors: Largy
authors: Florian
authors: F
authors: Hamon
authors: Frédéric
authors: F
authors: Rosu
authors: Valérie
authors: V
authors: Gabelica
authors: Edwin
authors: E
authors: De Pauw
authors: Aurore
authors: A
authors: Guédin
authors: Jean-Louis
authors: JL
authors: Mergny
authors: Marie-Paule
authors: MP
authors: Teulade-Fichou
mesh_terms: D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D054856:G-Quadruplexes; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism*; D010165:Palladium / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; C570941:palladium(II)(2,2'-(4-p-tolylpyridine-2,6-diyl)bis(1-methyl-1H-benzo(d)imidazole)); C570940:palladium(II)(tolylterpyridine); D010165:Palladium; D003300:Copper