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A series of mononuclear ruthenium(ii) complexes containing the tetradentate ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. In the synthesis of the [Ru(phen')(bb 7 )] 2+ complexes (where phen' = 1,10-phenanthroline and its 5-nitro-, 4,7-dimethyl- and 3,4,7,8-tetramethyl- derivatives), both the symmetric cis-α and non-symmetric cis-β isomers were formed. However, upon standing for a number of days (or more quickly under harsh conditions) the cis-β isomer converted to the more thermodynamically stable cis-α isomer. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(ii) complexes were determined against six strains of bacteria: Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA); and the Gram-negative Escherichia coli (E. coli) strains MG1655, APEC, UPEC and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the [Ru(5-NO 2 phen)(bb 7 )] 2+ complex had little or no activity against any of the bacterial strains. By contrast, for the other cis-α-[Ru(phen')(bb 7 )] 2+ complexes, the antimicrobial activity increased with the degree of methylation. In particular, the cis-α-[Ru(Me 4 phen)(bb 7 )] 2+ complex showed excellent and uniform MIC activity against all bacteria. By contrast, the MBC values for the cis-α-[Ru(Me 4 phen)(bb 7 )] 2+ complex varied considerably across the bacteria and even within S. aureus and E. coli strains. In order to gain an understanding of the relative antimicrobial activities, the DNA-binding affinity, cellular accumulation and water-octanol partition coefficients (log P) of the ruthenium complexes were determined. Interestingly, all the [Ru(phen')(bb 7 )] 2+ complexes exhibited stronger DNA binding affinity (K a ≈ 1 × 10 7 M -1 ) than the well-known DNA-intercalating complex [Ru(phen) 2 (dppz)] 2+ (where dppz = dipyrido[3,2-a:2',3'-c]phenazine).

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Synthesis, isomerisation and biological properties of mononuclear ruthenium complexes containing the bis[4(4′-methyl-2,2′-bipyridyl)]-1,7-heptane ligand