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’)(bb7)]2+ complexes (where phen’ = 1,10-phenanthroline and its 5-nitro-, 4,7-dimethyland
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-NO2phen)-
(bb7)]2+ complex had little or no activity against any of the bacterial strains. By contrast, for the other cisα-[Ru(phen’)(bb7)]2+
complexes, the antimicrobial activity increased with the degree of methylation. In
particular, the cis-α-[Ru(Me4phen)(bb7)]2+ complex showed excellent and uniform MIC activity against all
bacteria. By contrast, the MBC values for the cis-α-[Ru(Me4phen)(bb7)]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’)-
(bb7)]2+ complexes exhibited stronger DNA binding affinity (Ka ≈ 1 × 107 M−1
) than the well-known DNAintercalating
complex [Ru(phen)2(dppz)]2+ (where dppz = dipyrido[3,2-a:2’,3’-c]phenazine).
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)