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

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Sun, Biyun;Southam, Hannah M.;Butler, Jonathan A.;Poole, Robert K.;Burgun, Alexandre;Tarzia, Andrew;Keene, F. Richard;Collins, J. Grant
Abstract

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 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-NO2phen)(bb7)]2+ complex had little or no activity against any of the bacterial strains. By contrast, for the other cis-α-[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 DNA intercalating complex [Ru(phen)2(dppz)]2+ (where dppz = dipyrido[3,2-a:2',3'- c]phenazine).

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Dalton Transactions

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47

ISBN/ISSN

1477-9234

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Pages Count

13

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Publisher

Royal Society of Chemistry

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DOI

10.1039/c7dt04595f