Synthesis, isomerisation and biological properties of mononuclear ruthenium complexes containing the bis[4(4′-methyl-2, 2′-bipyridyl)]-1, 7-heptane ligand. Issue 7 (30th January 2018)

• Record Type: Journal Article
• Authors: Sun, Biyun; Southam, Hannah M.; Butler, Jonathan A.; Poole, Robert K.; Burgun, Alexandre; Tarzia, Andrew; Keene, F. Richard; Collins, J. Grant
• Is Part Of: Dalton transactions. Volume 47:Issue 7(2018)
• Page Start: 2422
• Page End: 2434
• Publication Date: 2018-01-30
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c7dt04595f
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : The strained complexes cis -β-[Ru(phen′)(bb7 )] 2+ isomerise to the corresponding cis -α isomers, with cis -α-[Ru(Me4 phen)(bb7 )] 2+ showing good antibacterial activity. 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-NO2 phen)(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(Me4 phen)(bb7 )] 2+ complex showed excellent and uniform MIC activity against all bacteria. By contrast, the MBC values for the cis -α-[Ru(Me4 phen)(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 ( 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).