# Ru(II)-Dppz Derivatives and Their Interactions with DNA: Thirty Years and Counting
## 3 DNA Binding
### Effects of Tuning the Photophysical and Redox Properties
The affinity of these species for DNA can also be modulated by peripheral ligands. Polypyridine ligands modified with carboxylic acids, as in the case of [Ru(bpy-COOH)\({}_{2}\)(dppz)]\({}^{2+}\) lead to a greater selectivity of duplex DNA to single-stranded DNA than the corresponding esterified ligands ([Ru(bpy-COOH)\({}_{2}\)(dppz)]\({}^{2+}\)) [128]. This type of behavior is due to the fact that deprotonation of the acidic groups results in the formation of a formally neutral species that induces greater repulsion between the ancillary ligands and the DNA surface and leads to duplex selectivity. The electronic effect of the ancillary ligands leads to a modulation of the redox potentials of these species, and as in the case of [Ru(tap)\({}_{2}\)(dppz)]\({}^{2+}\)[117], a photoinduced electron transfer process can occur with guanine, leading to the formation of a covalent bond between the species and the polynucleotide [109, 110, 111, 112]. Substitution on the ancillary ligands is also important to manage the selectivity of the light-switch. Indeed, by incorporating methyl groups on the phenanthrolines of the [Ru(phen)\({}_{2}\)(dppz)]\({}^{2+}\) system, a highly specific probe for a DNA mismatch was obtained. The selectivity was shown to be due to a higher binding affinity towards the mismatched DNA, which results in a much higher luminescence lifetime when bound to a mismatch [129]. It is very interesting to point out that the electron transfer processes involving DNA and metal complexes also depend on the type of interaction and thus on whether the reagents are metallo-intercalators or groove-binding agents. It was shown that photoinduced electron transfer and charge recombination (back electron transfer) becomes more efficient across the DNA base stack. The efficiency and yield of these processes are also a function of the base sequence into which the metal-binding agent fits, due to the different redox potentials of the transition metal complexes and the different bases [130; 131; 132]. A particularly interesting effect of substitution on the photophysical, and in particular, the photochemical properties of the polypyridyl ruthenium complexes is obtained by using a dppz analogue, i.e., 1,4,5,8-tetraazfaenanthrene (TAP) or 1,4,5,8,9,12-hexaazatriphenylene (HAT), see Figure 4[133]. In the case of the homoleptic [Ru(TAP)\({}_{3}\)]\({}^{2+}\) complex, it was shown that this complex is capable of forming covalent photoadducts with DNA. The ability of this type of complexes to give photochemistry with DNA is a function of the oxidizing power of the complex and becomes scarce in the case of the complex containing two TAP or HAT ligands, to the point of being absent in the case of the mono-substituted [Ru(bpy)\({}_{2}\)L]\({}^{2+}\) complex (L = TAP or HAT) [134; 135; 136]. The interest in this type of research is fundamentally based on the selectivity of the photochemical action with adduct formation, which is attributed to the reaction of the radical products formed by the initial electron transfer and the subsequent proton transfer. Both luminescence lifetime and time-resolved absorption spectroscopy confirmed that the excited states of these species were able to oxidize guanine, either as a free nucleotide (5-GMP) or in DNA, but not the other nucleobases. It was also shown that the photo-oxidation of guanine by [Ru(TAP)\({}_{2}\)(dppz)]\({}^{2+}\), and in particular its isomer \(\Lambda\), was a function of the nucleobase sequence. In fact, if bound to (CCGGATCCG)\({}_{2}\) or (CCGGTACCGG)\({}_{2}\), its behavior was different. In the case of the TA sequence, the electronic transfer was not very efficient [137]. However, after irradiation with visible light, the TAP containing complexes, exhibited both photocleavage and formation of mono- and bi-adducts with DNA [138]. In particular, the photochemical product of [Ru(TAP)\({}_{3}\)]\({}^{2+}\) with 5-GMP was isolated and identified by demonstrating that the adduct was formed by a bond between the TAP ligand and the external NH\({}_{2}\) group of guanine.