Ru II and III

Changes in Acidity of Hypoxanthine Complexes on Coordination of 0SH3)5Rnai and III) (U) 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

Since ammlneruthenlum Ions can coordinate the exo-N sites of cytosine and adenine as well as ring nitrogens, a variety of options for Inter- and Intrastrand crosslinking of DNA become available (11). However, the stability of these various modes of binding depends both on pH and the oxidation 

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Figure 7. ApKa values of isomers of 7-[(MeeXan)(NH3),Ru(II and III)] (14). Values are reported in ApK, units relative to the free ligand. Numbers in parentheses are for the Ru(II) complexes.

The potential of ruthenium complexes has been extensively explored along with fundamental studies on their interactions with molecules of biological interest [27—30]. The most studied series are structurally related to cisplatin and, in principle, ruthenium offers the exploitable property of access to two oxidation states, Ru(II) and (III), which differ in their rates of substitution the higher oxidation state is more inert and allows the possibility of introduction of a relatively inert and thus inactive complex which could be activated by reduction in vivo. This is of particular relevance with respect to the hypoxic or oxygen-deficient areas of tumours which occur at distances from the vascular system as a result of the enhanced respiration of rapidly growing cells (see Chapter 8). The potential for activation of Ru(III) complexes by reduction in this environment has been succintly reviewed [28]. 

The virtual identity of the Ru-N bonds and coordination geometries in the ruthenium(II and III) complexes is noteworthy and accounts for the... 

A number of ruthenium(II) complexes have been prepared. Cole-Hamilton and Stephenson isolated cts-[Ru(Me2dtc)2L2] (L = PPhj, PMe2, Ph, PPhMe2, or P(OPh)3) from Ru(II) and Ru(III) tertiary phosphine and phosphite complexes with NaMe2dtc, and found that they undergo rearrangements (288). 

The first experiments characterizing DNA-mediated CT over a precisely defined distance between covalently appended redox probes were reported in 1993 [95]. Remarkably, the luminescence of a photoexcited Ru(II) intercala-tor was quenched by a Rh(III) intercalator fixed to the other end of a 15-mer DNA duplex over 40 A away (Fig. 4). Furthermore, non-intercalating, tethered Ru(II) and Rh(III) complexes did not undergo this quenching reaction. In this way the importance of intercalative stacking for efficient CT was demonstrated. 

Fig. 4 Coupling of the redox participants to the DNA w-stack is requisite to DNA-mediated charge transport. Rapid (>109 s 1) photoinduced electron transfer occurs between the metallointercalators, [Ru(phen)2dppz]2+ and [Rh(phi) 2phen]3+, when they are tethered to opposite ends of a DNA duplex over 40 A apart. Conversely, electron transfer does not occur between non-intercalated Ru(II) and Rh(III) complexes tethered to DNA...

Linkage isomerism has been discussed for 0,S and N,O ligands both at Ru(II) and at Ru(III), with particular mention of relevance to redox reactions of DMSO complexes (31). 

These results suggest that the critical factor in the substrate-mediated intermolecular interactions which occur within the close-packed DHT layer is the inherent strong reactivity of the diphenolic moiety with the Pt surface. The interaction of adsorbates with each other through the mediation of the substrate is of fundamental importance in surface science. The theoretical treatment, however, involves complicated many-body potentials which are presently not well-understood (2.). It is instructive to view the present case of Pt-substrate-mediated DHT-DHT interactions in terms of mixed-valence metal complexes (2A) For example, in the binuclear mixed-valence complex, (NH3)5RU(11)-bpy-Ru(111) (NH 3)5 (where bpy is 4,4 -bipyridine), the two metal centers are still able to interact with each other via the delocalized electrons within the bpy ligand. The interaction between the Ru(II) and Ru(III) ions in this mixed-valence complex is therefore ligand-mediated. The Ru(II)-Ru(III) coupling can be written schematically as ... 

Both Ru(II) and Ru(III) complexes are known to bind DNA preferentially at N7 of G but also to A and C bases (182, 183). Although most ruthenium antitumor agents have two reactive coordination sites, GG intrastrand cross-links on DNA do not appear to form readily. The only example appears to be the adduct of 27 with GpG, which has been structurally characterized by NMR spectroscopy (184). In this complex, the two N7-coordinated guanines adopt a head-to-head conformation and the two bases are strongly destacked. 

In the present treatment, attention will be focused on localized systems. It is convenient to break the localized classification down even further, where the basis for the distinction lies in experimental observations. In the bpy dimer, where the bridging ligand is pyrazine, the rate of electron oscillation between Ru(II) and Ru(III) sites is slower than the vibrational timescale, at least for those vibrational levels... 

The standard ruthenium modification procedure involves the reaction of aquopentaammineruthenium(II) (ajRu " ) with the imidazole of a surface histidine of a protein [5, 13, 14]. The a5Ru(histidine)-modified proteins are stable in both the Ru(II) and the Ru(III) oxidation states and, although ajRu slowly dissociates from surface histidines [15], the ajRu complex stays attached for at least two months under appropriate conditions [16]. 

One of the very few exceptions to the rule that the acidity of the complexed ligand exceeds that of the free ligands involves the Ru(II) complexes shown in Table 6.5. It is believed that back bonding from the filled iig orbitals of Ru(II) to unoccupied tt-antibonding orbitals of the ligands more than compensates for the usual electrostatic effects of the metal that makes the nitrogen less basic. This tt-bonding is less likely with the Ru(III) complex and its is lower than that for the protonated pyrazine (see also Sec. 6.3.3. for the effects of Ru(II) and Ru(III) on hydrolysis of nitriles). ... 

During the last ten years, studies of luminescence and photochemistry of polypyridyl Ru(II), Rh(III) and Co(III) complexes, porphyrins and uranyl salts, in the presence of biological macromolecules such as DNA, have been the focus of increasing research work. The interest in such coordination compounds stems from their easily tunable properties. Not only their size and shape but also their... 

In the presence of DNA reactions (17) and (18) that generate the excited complex directly or indirectly via reaction (19), become much slower or do not take place, and therefore the ECL disappears. This is due to the fact that the Ru(II) and Ru(III) complexes, physically bound to DNA, are protected by the negatively charged phosphate backbone from the reduction by C02. Thus the ECL titration of the metal complex in the presence of DNA has allowed the determination of the equilibrium constant and binding-site size for association of Ru(phen)3 to DNA [82]. 

In the solid state, the equilibrium is in favor of the hydrido complex (III), and its crystal structure and that of the osmium(II) analog have been determined (38). Chatt also observed that, on heating the equilibrium mixture of (II) and (III), naphthalene was eliminated and the product Ru(dmpe)2 was also a tautomeric mixture. Here the tautomer-ism involves breaking and re-formation of carbon-hydrogen bonds in the methyl groups of the phosphine ligands (IV and V) ... 

Hydrogenation of r/wu-cinnamaldehyde (Figure 14 I Ri=H, R2=Ph) to phenylpropanol (IV Ri=H, R2=Ph) catalysed by Ru/tppms and Ru/tppts proceeds via two different routes in an aqueous/organic two phase system.492 With HRuCl(CO)(tppms)3 the reaction proceeds exclusively via the hydro-cinnamaldehyde III whereas with HRuCl(CO)(tppts)3 both II and III are involved (Figure 14, Ri=H, R2=Ph) 492... 

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