# Ru(II)-Dppz Derivatives and Their Interactions with DNA: Thirty Years and Counting
## 3 DNA Binding
### Ru(II) Complexes as Intercalators
Interaction of Ru(II) complexes with DNA usually generates an increase in luminescence intensity due to the reduced probability of:  
* non-radiative decay, because the intercalated luminophore is surrounded by the DNA hydrophobic environment and is therefore protected from water-induced deactivation;
* intersystem crossing to the \({}^{3}\)MC excited state, as the complex is caged into the double helix and its rigidity result is enhanced;
* O\({}_{2}\) luminescence quenching. Figure 1: Molecular structure of [Ru(\(\mathrm{bpy}\))\({}_{2}\)(dppz)]\({}^{2+}\). On the other hand, if there are photoinduced reactions between the metal complex and nucleobases, luminescence is quenched. Similar to the [Ru(bpy)\({}_{2}\)(dppz)]\({}^{2+}\) species, the two Ru(II) complexes reported in Figure 2 behave as luminescent DNA probes; they are based on TAP (1,4,5,8-tetra-azaphenan threne) and PHEHAT (1,10-phenanthroline[5,6-b]-1,4,5,8,9,12-hexa-azatriphenylene) ligands. Interestingly, in the presence of DNA, the behavior of these two complexes is different--the first complex acts as an ON-OFF molecular switch; the second one acts, instead, as an OFF-ON molecular switch [72]. [Ru(TAP)\({}_{2}\)(PHEHAT)]\({}^{2+}\) is a photo-oxidant complex (the two TAP ligands give it a high reduction potential) and shows a great affinity for the DNA, thanks to the PHEHAT ligand, which can intercalate. DNA efficaciously quenches its luminescence due to the 'electron transfer' process with guanine; which is a 'light-switch'ON-OFF'. [Ru(phen)\({}_{2}\)(PHEHAT)]\({}^{2+}\) in water solution at room temperature does not exhibit any luminescence; the lone pairs present on nitrogen atoms in the PHEHAT ligand, interacting with water molecules, stabilize a non-emistive excited state. When the complex intercalates into DNA, the PHEHAT ligand is surrounded by the DNA hydrophobic environment and the stabilization by water molecules cannot happen. Therefore, the non-emistive excited state is not stabilized and the complex exhibits luminescence; which is called 'light-switch OFF-ON'. A wide variety of dppz-based complexes were designed, synthesized, and studied by modifying the bipyridine ancillary ligand or the dppz ligand [73; 74; 75; 76; 77; 78], or changing the metal center to Re [79; 80; 81; 82], Co [83; 84], Cu [85; 86], Rh [87; 88; 89; 90], Os [91; 92], Pt [93; 94; 95], and Ir [96; 97; 98] cations. Many experiments were conducted in an attempt to rationalize and \"observe\" the light-switch mechanism. In the case of [Ru(phen)\({}_{2}\)(dppz)]\({}^{2+}\)[69], see Figure 3, the mechanism seems to occur in two distinct phases, the first involving intersystem crossing between the state called MLCT\({}^{\prime}\) (bright state) and the one called MLCT\" and subsequently by non-radiative deactivation from the latter. The MLCT\({}^{\prime}\) state represents the dominant state of [Ru(phen)\({}_{2}\)(dppz)]\({}^{2+}\) in aprotic organic solvent, and is the state that is initially populated in other solvents as well; see Scheme 3. Figure 3: Molecular structure of [Ru(phen)\({}_{2}\)(dppz)]\({}^{2+}\). Figure 2: Representation of [Ru(TAP)\({}_{2}\)(PHEHAT)]\({}^{2+}\) (**left**) and [Ru(phen)\({}_{2}\)(PHEHAT)]\({}^{2+}\) (**right**). The MLCT\" state (dark state), on the other hand, is a state involving the phenazine portion of dppz and its energy is a function of the solvent. In fact, by rationalizing the photophysical properties of [Ru(phen)\({}_{2}\)(dppz)]\({}^{2+}\) in a wide range of solvent environments, it can be inferred that both the polarity of the latter and the ability to form hydrogen bonds with the N atoms of the phenazine fragment govern the population of this dark state [48]. The light-switch behavior is also a function of temperature, which governs the extent of equilibration between the two states and thus the relative population.