title: Dinuclear ruthenium(ii) complexes containing one inert metal centre and one coordinatively-labile metal centre: syntheses and biological activities.
abstract: A series of non-symmetric dinuclear polypyridylruthenium(ii) complexes (Rubbn-Cl) that contain one inert metal centre and one coordinatively-labile metal centre, linked by the bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane ligand ("bbn" for n = 7, 12 and 16), have been synthesised and their potential as antimicrobial agents examined. The minimum inhibitory concentrations (MIC) of the ruthenium(II) complexes were determined against four strains of bacteria--Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). The Rubbn-Cl complexes displayed good antimicrobial activity, with Rubb12-Cl being the most active complex against both Gram-positive and Gram-negative strains. Interestingly, Rubb7-Cl was found to be eight- and sixteen-fold more active towards E. coli than against S. aureus and MRSA, respectively. The cytotoxicities of the Rubbn-Cl complexes against three eukaryotic cell lines--two kidney cell lines (BHK and HEK-293) and one liver cell line (HepG2)--were examined. The Rubbn-Cl complexes were found to be considerably less toxic towards eukaryotic cells than S. aureus, MRSA and E. coli, with Rubb12-Cl being thirty- to eighty-times more toxic to the bacteria than to BHK, HEK-293 or HepG2 cells. Unexpectedly, Rubb7-Cl was far more toxic to HepG2 cells (24 h-IC50 = 3.7 μM) and far less toxic to BHK cells (24 h-IC50 = 238 μM) than the Rubb12-Cl and Rubb16-Cl complexes. In order to understand the unexpected large differences in the cytotoxicities of the Rubbn-Cl complexes towards eukaryotic cells, a confocal microscopic study of their intracellular localisation was undertaken. The results suggest that the observed cytotoxicity might be related to the extent of DNA binding.
authors: School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Australian Defence Force Academy, Canberra, ACT 2600, Australia. g.collins@adfa.edu.au.
authors: Xin
authors: X
authors: Li
authors: Kirsten
authors: K
authors: Heimann
authors: Fangfei
authors: F
authors: Li
authors: Jeffrey M
authors: JM
authors: Warner
authors: F
authors: F
authors: Richard Keene
authors: J
authors: J
authors: Grant Collins
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D001692:Biological Transport; D060326:Chemistry Techniques, Synthetic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D012428:Ruthenium