Effects of Metal Coordination Geometry on Stabilization of Human Telomeric Quadruplex DNA by Square-Planar and Square-Pyramidal Metal Complexes

A series of square-planar and square-based pyramidal metal complexes (metal = Ni2+, Cu2+, Zn2+, and V4+) with salphen and salen derivatives as ligands have been prepared. The X-ray crystal structures of three of these complexes are reported, giving insight into the geometric properties of the compounds. The interactions of these complexes with duplex and human telomeric quadruplex DNA have been studied by fluorescence resonance energy transfer (FRET), fluorescent intercalator displacement assay, and in one case circular dichroism. These studies have shown the square-planar metal complexes to be excellent quadruplex DNA stabilizers. In addition, FRET competition assays have shown the complexes to have a high degree of selectivity for the DNA quadruplex versus duplex DNA. These studies have allowed us to establish the most important features that metal complexes should have to interact selectively with quadruplex DNA. This will be of value in defining the best strategy to prepare metal complexes as potential anticancer drugs.