We synthesized and fully characterized a series of mononuclear ruthenium(II) complexes containing the tetradentate ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane ligand and examined their biological properties. 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, the highly strained cis-β isomers were unstable and converted to the more thermodynamically stable cis-α isomer. The incorporation of particular substituents on the ligand did affect the antimicrobial activities. The antimicrobial activity of the [Ru(phen’)(bb7)]2+ complexes could be potentially improved through an increase of the lipophilicity. However, increased lipophilicity could also increase the toxicity to eukaryotic cells. An alternative approach is to increase the electron density at the ruthenium center through the incorporation of electron-donating groups on the 1,10-phenanthroline ligand. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(II) complexes were determined against two Gram-positive strains and four Gram-negative strains of bacteria. The results suggested that the antimicrobial activity is strongly related to the electron density on the 1,10-phenanthroline ligand. The cis-α-[Ru(Me4phen)(bb7)]2+ complex with four electron donating groups on the 1,10-phenanthroline ligand exhibited good cellular accumulation while the cis-α-[Ru(5-NO2phen)(bb7)]2+ complex had little or no activity against any of the bacterial 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).

New class of mononuclear ruthenium complexes as antimicrobial agents

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.