Synthesis, Structural Characterization, and Quadruplex DNA Binding Studies of Platinum(II)-Terpyridine Complexes

Three new substituted terpyridine ligands and their corresponding platinum(II) complexes have been prepared and fully characterized (including the X-ray crystal structures of two of the complexes). These compounds have shown to stack via pi-pi interactions both in the solid state and in solution. The interactions of these compounds with quadruplex DNA (both HTelo and c-myc sequences) have been studied by fluorescent indicator displacement (FID) assays, surface plasmon resonance (SPR), and in one case by circular dichroism (CD). The complexes have shown to interact strongly with quadruplex DNA (with binding constants of ca. 10(6) and DC50 values between 2.24 and 0.26, as determined by SPR and FID, respectively). We have also investigated the interaction between the complexes and a sequence of duplex DNA to gain some insight into the selectivity of the compounds for quadruplex structures. FID and SPR studies have shown that the complexes have a modest selectivity (1 order of magnitude) for quadruplex, particularly c-myc, versus duplex DNA.