Li, Xin, Heimann, Kirsten, Li, Fangfei, Warner, Jeffrey M., Keene, F. Richard, and Collins, J. Grant (2016) Dinuclear ruthenium(II) complexes containing one inert metal centre and one coordinatively-labile metal centre: syntheses and biological activities. Dalton Transactions, 45. pp. 4017-4029.

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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 (24h-IC₅₀ = 3.7 μM) and far less toxic to BHK cells (24h-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.

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