title: Mononuclear Polypyridylruthenium(II) Complexes with High Membrane Permeability in Gram-Negative Bacteria-in particular Pseudomonas aeruginosa.
abstract: Ruthenium(II) complexes containing the tetradentate ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane ("bbn "; n=10 and 12) have been synthesised and their geometric isomers separated. All [Ru(phen)(bbn )](2+) (phen=1,10-phenanthroline) complexes exhibited excellent activity against Gram-positive bacteria, but only the cis-α-[Ru(phen)(bb12 )](2+) species showed good activity against Gram-negative species. In particular, the cis-α-[Ru(phen)(bb12 )](2+) complex was two to four times more active than the cis-β-[Ru(phen)(bb12 )](2+) complex against the Gram-negative strains. The cis-α- and cis-β-[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-α- and cis-β-[Ru(phen)(bb12 )](2+) complexes in P. aeruginosa was considerably greater than in Escherichia coli. The uptake of the cis-α-[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-α- and cis-β-[Ru(phen)(bbn )](2+) complexes exhibited relatively strong binding to DNA (Kb ≈10(6)  M(-1) ), but no significant difference between the geometric isomers was observed.
authors.affiliation: School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Australian Defence Force Academy, Canberra, ACT 2600 (Australia).
authors.forename: Anil K
authors.initials: AK
authors.lastname: Gorle
authors.affiliation: College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, 4811 (Australia).|Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville, QLD 4811 (Australia).
authors.forename: Marshall
authors.initials: M
authors.lastname: Feterl
authors.affiliation: College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, 4811 (Australia).|Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville, QLD 4811 (Australia).
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Warner
authors.affiliation: College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, 4811 (Australia).
authors.forename: Sebastian
authors.initials: S
authors.lastname: Primrose
authors.affiliation: College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, 4811 (Australia).
authors.forename: Constantin C
authors.initials: CC
authors.lastname: Constantinoiu
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville, QLD 4811 (Australia). richard.keene@adelaide.edu.au.|College of Science, Technology and Engineering, James Cook University, Townsville, QLD 4811 (Australia). richard.keene@adelaide.edu.au.|School of Physical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia). richard.keene@adelaide.edu.au.
authors.forename: F Richard
authors.initials: FR
authors.lastname: Keene
authors.affiliation: School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Australian Defence Force Academy, Canberra, ACT 2600 (Australia). g.collins@adfa.edu.au.
authors.forename: J Grant
authors.initials: JG
authors.lastname: Collins
mesh_terms: D002463:Cell Membrane Permeability; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000737:chemistry* / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000378:metabolism*; D012428:Ruthenium / Q000737:chemistry
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D012428:Ruthenium; D004247:DNA
keywords: N ligands; bioinorganic chemistry; biological activity; cellular uptake; lipophilicity; ruthenium