Mononuclear polypyridylruthenium(II) complexes with high membrane permeability in gram-negative bacteria—in particular Pseudomonas aeruginosa
Journal Publication ResearchOnline@JCUAbstract
Ruthenium(II) complexes containing the tetra dentate ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane ("bb(n)"; n=10 and 12) have been synthesised and their geometric isomers separated. All [Ru(phen)(bb(n))]²⁺ (phen=1,10-phenanthroline) complexes exhibited excellent activity against Gram-positive bacteria, but only the cis-a-[Ru(phen)(bb₁₂)]²⁺ species showed good activity against Gram-negative species. In particular, the cis-a-[Ru(phen)(bb₁₂)]²⁺ complex was two to four times more active than the cis-b-[Ru(phen)(bb₁₂)]²⁺complex against the Gram-negative strains. The cis-a- and cis-b-[Ru(phen)(bb₁₂)]²⁺ complexes readily accumulated in the bacteria but, significantly, showed the highest level of uptake in Pseudomonas aeruginosa. Furthermore, the accumulation of the cis-a- and cis-b-[Ru(phen)(bb₁₂)]²⁺ complexes in P. aeruginosa was considerably greater than in Escherichia coli. The uptake of the cis-a-[Ru(phen)(bb₁₂)]²⁺ complex into live P. aeruginosa was confirmed by using fluorescence microscopy. The water/octanol partition coefficients (log P) were determined to gain understanding of the relative cellular uptake. The cis-a- and cis-b-[Ru(phen)(bb(n))]²⁺ complexes exhibited relatively strong binding to DNA (Kb≈10⁶M⁻¹ ), but no significant difference between the geometricisomers was observed.
Journal
Chemistry - A European Journal
Publication Name
Chemistry: a European journal
Volume
21
ISBN/ISSN
1521-3765
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N/A
Issue
29
Pages Count
10
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Publisher
Wiley-VCH
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DOI
10.1002/chem.201500385