The antimicrobial activity of inert oligonuclear polypyridylruthenium(ii) complexes against pathogenic bacteria, including MRSA

Abstract

The minimum inhibitory concentrations (MIC) of a series of synthetic inert polypyridylruthenium(II) complexes against four strains of bacteria – Gram positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) – have been determined. The results demonstrate that for the dinuclear ruthenium(II) complexes ΔΔ/ΛΛ-[{Ru(phen)₂}₂{μ-bb_n}]⁴⁺ {where phen = 1,10-phenanthroline; bb_n = bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (n = 2, 5, 7, 10, 12 or 16)} the complexes linked by the bb₁₂, bb₁₄ and bb₁₆ ligands are highly active, with MIC values of 1 μg mL⁻¹ against both S. aureus and MRSA, and 2–4 and 8–16 μg mL⁻¹ against E. coli and P. aeruginosa, respectively. The mononuclear complex [Ru(Me₄phen)₃]²⁺ showed equal activity (on a mole basis) against S. aureus compared with the Rubb₁₂, Rubb₁₄ and Rubb₁₆, but was considerably less active against MRSA and the two Gram negative bacteria. For the dinuclear Rubb_n family of complexes, the antimicrobial activity was related to the octanol–water partition coefficient (logP). However, the highly lipophilic mononuclear complex Δ-[Ru(phen)₂(bb₁₆)]²⁺ was significantly less active than Rubb₁₆, highlighting the importance of the dinuclear structure. Preliminary toxicity assays were also carried out for the ΔΔ isomers of Rubb₇, Rubb₁₀, Rubb₁₂ and Rubb₁₆ against two human cells lines, fresh red blood cells and THP-1 cells. The results showed that the dinuclear ruthenium complexes are significantly less toxic to human cells compared to bacterial cells, with the HC₅₀ and IC₅₀ values 100-fold higher than the MIC for the complex that showed the best potential – ΔΔ-Rubb₁₂.