Ru(II) polypyridine complexes: photophysics, photochemistry, eletrochemistry, and chemiluminescence

Ruthenium-based anticancer chemotherapies are making significant advances in clinical trials. Until recently, the focus has been on coordination complexes, and mechanisms such as "activation by reduction" and "transferrin-targeted delivery" have been proposed to account for the excellent cytotoxicity and low general toxicity of these complexes. More recently organoruthenium compounds, which to some extent appear not to follow the established rules, have started to be investigated. Despite such differences, similar activities between certain coordination and organometallic compounds suggest similar modes of action are present. DNA, the classic target, is believed to be the dominant mechanism for cytotoxicity with certain ruthenium drugs, while with others, non-classical targets are thought to be more important. In this article we describe these features and show how both ruthenium coordination complexes and organoruthenium compounds represent an ideal scaffold for further drug design and optimisation.

Classical and Non-Classical Ruthenium-Based Anticancer Drugs: Towards Targeted Chemotherapy

Organometallic complexes offer chemistry that is not accessible to purely organic molecules and, hence, potentially new mechanisms of drug action We show here that the presence of both an iodido ligand and a σ-donor/π-acceptor phenylazopyridine ligand confers remarkable inertness toward ligand substitution on the half-sandwich “piano-stool” ruthenium arene complexes [(η6-arene)Ru(azpy)I]+ (where arene = p-cymene or biphenyl, and azpy = N,N-dimethylphenyl- or hydroxyphenyl-azopyridine) in aqueous solution Surprisingly, despite this inertness, these complexes are highly cytotoxic to human ovarian A2780 and human lung A549 cancer cells Fluorescence-trapping experiments in A549 cells suggest that the cytotoxicity arises from an increase in reactive oxygen species Redox activity of these azopyridine RuII complexes was confirmed by electrochemical measurements The first one-electron reduction step (half-wave potential −02 to −04 V) is assignable to reduction of the azo group of the ligand In contrast, the unbound azopyridine ligands are not readily reduced Intriguingly the ruthenium complex acted as a catalyst in reactions with the tripeptide glutathione (γ-l-Glu-l-Cys-Gly), a strong reducing agent present in cells at millimolar concentrations; millimolar amounts of glutathione were oxidized to glutathione disulfide in the presence of micromolar ruthenium concentrations A redox cycle involving glutathione attack on the azo bond of coordinated azopyridine is proposed Such ligand-based redox reactions provide new concepts for the design of catalytic drugs

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Catalytic organometallic anticancer complexes

N,N′-Chelating biheteroaromatic ligands; a survey

Virtually all organosulfur compounds react with Fe(0) carbonyls to give the title complexes. These reactions are reviewed in light of major advances over the past few decades, spurred by interest in Fe2(μ-SR)2(CO)x centers at the active sites of the [FeFe]-hydrogenase enzymes. The most useful synthetic route to Fe2(μ-SR)2(CO)6 involves the reaction of thiols with Fe2(CO)9 and Fe3(CO)12. Such reactions can proceed via mono-, di-, and triiron intermediates. The reactivity of Fe(0) carbonyls toward thiols is highly chemoselective, and the resulting dithiolato complexes are fairly rugged. Thus, many complexes tolerate further synthetic elaboration directed at the organic substituents. A second major route involves alkylation of Fe2(μ-S2)(CO)6, Fe2(μ-SH)2(CO)6, and Li2Fe2(μ-S)2(CO)6. This approach is especially useful for azadithiolates Fe2[(μ-SCH2)2NR](CO)6. Elaborate complexes arise via addition of the FeSH group to electrophilic alkenes, alkynes, and carbonyls. Although the first example of Fe2(μ-SR)2(CO)6 ...

Synthesis of Diiron(I) Dithiolato Carbonyl Complexes

Synthesis of mixed complexes of ruthenium(II) with 2,2′-dipyridyl

Chemistry of bipyridyl-like ligands. Isomeric complexes of ruthenium(II) with 2-(phenylazo)pyridine

Chemistry of bipyridyllike ligands. 2. Mixed complexes of ruthenium(II) with 2-(phenylazo)pyridine: a new .pi.-bonding probe

Preparation des complexes et etude de l'effet d'un substituant sur le noyau phenyl. Spectres visibles

Chemistry of bipyridyl-like ligands. III: Complexes of ruthenium(II) with 2-((4-nitrophenyl)azo)pyridine

The majority of ruthenium(II) compounds which have been observed to be luminescent are complexes of aromatic heterocyclic chelating ligands. Methods of synthesizing such complexes are reviewed and recommendations made (where considered possible) as to the best procedures.

Ronald A. Krause

Papers

Synthesis of mixed complexes of ruthenium(II) with 2,2′-dipyridyl

Chemistry of bipyridyl-like ligands. Isomeric complexes of ruthenium(II) with 2-(phenylazo)pyridine

Chemistry of bipyridyllike ligands. 2. Mixed complexes of ruthenium(II) with 2-(phenylazo)pyridine: a new .pi.-bonding probe

Chemistry of bipyridyl-like ligands. III: Complexes of ruthenium(II) with 2-((4-nitrophenyl)azo)pyridine

Synthesis of ruthenium(II) complexes of aromatic chelating heterocycles: Towards the design of luminescent compounds