AT-Specific DNA Binding of Binuclear Ruthenium Complexes at the Border of Threading Intercalation

The binuclear ruthenium complex [mu-bidppz(phen)(4)Ru-2](4+) has been extensively studied since the discover}, of its unusual threading intercalation interaction with DNA, a binding mode with extremely slow binding and dissociation kinetics. The complex has been shown to be selective towards long stretches of alternating AT base pairs, which makes it interesting, for example, as a model compound for anti-malaria drugs due to the high AT content of the genome of the malaria parasite P falciparum. We have investigated the effect of bridging ligand structure on threading intercalation ability and found that length and rigidity as well as the size of the intercalated ring system are all factors that affect the rate and selectivity of the threading intercalation. In particular, we discovered a new DNA-threading compound, [mu-dppzip(phen)(4)Ru-2](4+) which appears to be just at the border of being capable of threading intercalation and displays even greater selectivity for AT-DNA than the parent compound, [mu-bidppz(phen)(4)Ru-2](4+).