Effect of metal coordination on the interaction of substituted phenanthroline and pyridine ligands with quadruplex DNA.

A series of new mono-carboxamido phenanthrolines and bis-carboxamido pyridines have been prepared and their coordination chemistry to platinum(II) and palladium(II) investigated. Both the ligands and metal complexes have been designed with the appropriate geometric requirements to favour pi-pi interactions with guanine quartets, which are the core motif in quadruplex structures formed by folding single-stranded telomeric DNA. The interactions of these compounds with quadruplex-DNA have been investigated. The results show that some of these compounds induce the stabilisation of quadruplex-DNA (e.g. DeltaTm at 1 microM of 20 degrees C for one of the platinum(II) complexes) while there is no measurable interaction with duplex DNA at similar concentrations. In addition, the important role played by the metal centre in increasing the interaction of these planar molecules with quadruplex-DNA is highlighted.