# Ru(II)-Dppz Derivatives and Their Interactions with DNA: Thirty Years and Counting
## 3 DNA Binding
### Effects of Tuning the Photophysical and Redox Properties
In the case of the [Ru(HAT)\({}_{2}\)(phen)]\({}^{2+}\) species, however, the photochemical reaction with 5-GMP resulted in the formation of a bond between HAT and the 6-O atom of guanine [139]. Similar behavior was observed with the [Ru(bpy)\({}_{2}\)(tpphz)]\({}^{2+}\) complex, see Figure 5 (tpphz = tetrapyridyl[3,2+:2^{\prime}\)/-:3^{\prime\prime}\)/2^#-:2^#-:2^#-:3^#-:j]-phenazine). In particular, this species demonstrated that the light-switch ON effect could be cycled OFF and ON through the successive introduction of Co\({}^{2+}\) and EDTA. The presence of a further chelating site on the dppz-like ligand results in the coordination of cobalt ions that affect the energy of the two \({}^{3}\)MLCT state, promoting the population of the non-emissive state [126; 127]. Figure 4: Molecular structure of HAT and TAP ligands. The interaction of these molecules with the particular structure of DNA was also studied. Both [Ru(bpy)\({}_{2}\)(dppz)]\({}^{2+}\) and [Ru(phen)\({}_{2}\)(dppz)]\({}^{2+}\) were shown to induce the human single-stranded telomeric repeat 5\({}^{\prime}\)-AGGGTTAGGTTAGGG-3\({}^{\prime}\)(22 AG) to fold into an intramolecular quadruplex [140,141]. In contrast, a cytosine-rich filament oligomer 5\({}^{\prime}\)-CCCTAACCCTAACTAACCCT-3\({}^{\prime}\)(22 CT) could self-associate into an i-motif structure; see Scheme 4. In general, Ru-dppz-type complexes only weakly interact at the i-motif, making them somewhat selective for G-quadruplexes. This type of behavior was palpably attributable to the interaction of [Ru(phen)\({}_{2}\)(dppz)]\({}^{2+}\), which stacked on the ends of G-quadruplexes, while it might bind to the i-motif only by non-specific interaction [142]. Similar to the G-quadruplex DNA structures (containing essential guanine residues), i-motifs (intercalated motifs) consist of a fragment of oligodeoxynucleotides strands, mostly based on cytosine residues. I-motif forming DNA was recently identified as a key step in the recognition and regulation of transcriptional proteins in cells. It was also present in many promoter regions of oncogenes [143,144]. Although the interaction seemed too weak to be studied in detail, recently, [Ru(phen)\({}_{2}\) (dppz)]\({}^{2+}\) was used to collect information on the binding sites to i-motif structures. IR transient spectroscopy made it possible to distinguish the presence of different bases in loops (as was shown for the human telomeric sequence), demonstrating that this archetype species, together with advanced spectroscopic techniques, has a great potential for identifying binding for biologically-relevant sequences [145,146]. Figure 5: Molecular structure of the tpphz ligand. The electronic effect becomes even more pronounced by making changes to the dppz ligand. Conjugation with an active redox fragment was able to activate photoinduced intramolecular electron transfer processes that led to the quenching of luminescence (e.g., Ru-qdppz and Ru-qdpq, see Figure 6). An external redox input (chemical or electrochemical) could modify the active redox fragment and restore the light-switch effect. This was the case, for example, with the quinone/hydroquinone pair. The former was, in fact, able to switch off the luminescence through a process of oxidative electron transfer involving the \({}^{3}\)MLCT state characteristic of Ru-dppz. Electrochemical or chemical reduction of the quinone fragment restores luminescence, thus allowing dual-input operation of the molecular probe [121; 123]. In general, the low luminescence quantum yield and short excited-state lifetimes led to less interest in ruthenium dppz complexes carrying the tridentate ligand tpy (tpy = 2,2':6',2'':-terpyridyl) than in complexes based on bipyridine and phenanthroline ligands, despite the fact that the absence of a metal stereocenter eliminated the need to separate racemic mixtures typical of tris-bidentate systems.