Assembly of Palladium(II) and Platinum(II) Metallo-Rectangles with a Guanosine-Substituted Terpyridine and Study of Their Interactions with Quadruplex DNA

Sushobhan Ghosh (1) , Oscar Mendoza (1) , Leticia Cubo (1) , Frederic Rosu (2) , Valérie Gabelica (3) , Andrew J P White (1) , Ramon Vilar (1, 4)

1 Department of Chemistry [Imperial College London]
2 Soutien à la Recherche de l'Institut Européen de Chimie Biologique
3 ARNA - Régulations Naturelles et Artificielles
4 Institute of Chemical Biology [London, U.K.]

Two novel [2+2] metallo-assemblies based on a guanosine-substituted terpyridine ligand (1) coordinated to palladium(II) (2a) and platinum(II) (2b) are reported. These supramolecular assemblies have been fully characterized by NMR spectroscopy, ESI mass spectrometry and elemental analyses. The palladium(II) complex (2a) has also been characterized by single crystal X-ray diffraction studies confirming that the system is a [2+2] metallo-rectangle in the solid state. The stabilities of these [2+2] assemblies in solution have been confirmed by DOSY studies as well as by variable temperature 1H NMR spectroscopy. The ability of these di-nuclear complexes to interact with quadruplex and duplex DNA was investigated by Fluorescent Intercalator Displacement (FID) assays, Fluorescence Resonance Energy Transfer (FRET) meting studies, and electrospray mass spectrometry (ESI-MS). These studies have shown that both these assemblies interact selectively with quadruplex DNA (human telomeric DNA and the G-rich promoter region of c-Myc oncogene) over duplex DNA, and are able to induce dimerization of parallel G-quadruplex structures.

Mots clés: Mass spectrometry; Coordination complex; G-quadruplex DNA; G-quadruplex ligands; Supramolecular chemistry

Domaines: Biochimie, Biologie Moléculaire

Sushobhan Ghosh, Oscar Mendoza, Leticia Cubo, Frederic Rosu, Valérie Gabelica, et al.. Assembly of Palladium(II) and Platinum(II) Metallo-Rectangles with a Guanosine-Substituted Terpyridine and Study of Their Interactions with Quadruplex DNA. Chemistry - A European Journal, 2014, 20 (16), pp.4772 - 4779. ⟨10.1002/chem.201304905⟩. ⟨inserm-01387138⟩