Dinuclear ruthenium(ii) antimicrobial agents that selectively target polysomes in vivo

Abstract

Wide-field fluorescence microscopy at high magnification was used to study the intracellular binding site of Rubb₁₆ in Escherichia coli. Upon incubation of E. coli cells at the minimum inhibitory concentration, Rubb₁₆ localised at ribosomes with no significant DNA binding observed. Furthermore, Rubb₁₆ condensed the ribosomes when they existed as polysomes. It is postulated that the condensation of polysomes would halt protein production, and thereby inhibit bacterial growth. The results of this study indicate that the family of inert dinuclear ruthenium complexes Rubb_n selectively target RNA over DNA in vivo. Selective RNA targeting could be advantageous for the development of therapeutic agents, and because of differences in ribosome structure between bacteria and eukaryotic cells, the Rubb_n complexes could be selectively toxic to bacteria. In support of this hypothesis, the toxicity of Rubb₁₆ was found to be significantly less to liver and kidney cell lines than against a range of bacteria.