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 CuII, PtII, and ZnII) with terpyridine-based ligands have been prepared and fully characterized. The X-ray crystal structures of two of the complexes (monometallic CuII and ZnII 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 CuII) or square planar (with PtII) 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).