Polypyridylruthenium(II) complexes as therapeutic agents

A series of dinuclear ruthenium(II) complexes containing labile chlorido ligands (Cl-Rubbn) have been synthesised and their potential as anticancer agents examined. Some of the Cl-Rubbn species showed good anticancer activity against breast cancer cell lines, with the Cl-Rubb₁₂ complex being four-times more active than cisplatin. The results of this study suggest that the cytotoxicity of the dinuclear ruthenium complexes is a combination of covalent and reversible binding with DNA. A series of inert mono-, tri- and tetra-nuclear polypyridylruthenium(II) complexes have been synthesised and their potential as antimicrobial agents examined. Geometric isomers of the mononuclear complexes were separated. The minimum inhibitory concentrations (MIC) of the ruthenium(II) complexes were determined against a range of Gram positive and Gram negative bacteria. The linear tetranuclear complexes were generally more active, with MIC values < 1 μM against Gram positive bacteria. Of particular note, the cellular accumulation of the oligonuclear ruthenium complexes was greater in the Gram negative strains compared to that in the Gram positive strains. The mononuclear complexes [Ru(phen)(bbn)]²⁺ (phen=1,10-phenanthroline) exhibited excellent activity against Gram positive bacteria, but only the cis-α-[Ru(phen)(bb₁₂)]²⁺ species showed good activity against Gram negative species. In particular, the cis-α-[Ru(phen)(bb₁₂)]²⁺ complex was two to four times more active than the cis-β-[Ru(phen)(bb₁₂)]²⁺ complex against the Gram negative strains. The cis-α- and cis-β-[Ru(phen)(bb₁₂)]²⁺ complexes readily accumulated in the bacteria, but significantly, showed the highest level of uptake in P. aeruginosa. The antimicrobial activities of a series of di-, tri- and tetra-nuclear ruthenium complexes against a wider range of clinically relevant pathogenic bacteria were examined. The toxicity of some of these complexes against eukaryotic cells was also investigated. Results of this study indicate that these complexes are highly active against Gram positive bacteria but they were less active against Gram negative bacteria. The dinuclear Rubb₁₂complex exhibits less toxicity to liver and kidney cells when compared to the tri- and tetra-nuclear complexes. In addition, in vivo experiments demonstrate serum level concentrations for both Rubb₁₆ and Rubb₁₂-tetra were lower than the MIC values against Gram positive and Gram negative bacteria, with both complexes accumulating mainly in the liver and kidney after dosing