Chlorido-containing ruthenium(II) and iridium(III) complexes as antimicrobial agents.
A series of polypyridyl-ruthenium(II) and -iridium(III) complexes that contain labile chlorido ligands, [{M(tpy)Cl}(2){μ-bb(n)}](2/4+) {Cl-Mbb(n); where M = Ru or Ir; tpy = 2,2':6',2''-terpyridine; and bb(n) = bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane (n = 7, 12 or 16)} have been synthesised and their potential as antimicrobial agents examined. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of the series of metal 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. All the ruthenium complexes were highly active and bactericidal. In particular, the Cl-Rubb(12) complex showed excellent activity against all bacterial cell lines with MIC values of 1 μg mL(-1) against the Gram positive bacteria and 2 and 8 μg mL(-1) against E. coli and P. aeruginosa, respectively. The corresponding iridium(III) complexes also showed significant antimicrobial activity in terms of MIC values; however and surprisingly, the iridium complexes were bacteriostatic rather than bactericidal. The inert iridium(III) complex, [{Ir(phen)(2)}(2){μ-bb(12)}](6+) {where phen = 1,10-phenanthroline) exhibited no antimicrobial activity, suggesting that it could not cross the bacterial membrane. The mononuclear model complex, [Ir(tpy)(Me(2)bpy)Cl]Cl(2) (where Me(2)bpy = 4,4'-dimethyl-2,2'-bipyridine), was found to aquate very rapidly, with the pK(a) of the iridium-bound water in the corresponding aqua complex determined to be 6.0. This suggests the dinuclear complexes [Ir(tpy)Cl}(2){μ-bb(n)}](4+) aquate and deprotonate rapidly and enter the bacterial cells as 4+ charged hydroxo species.
School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Australian Defence Force Academy, Canberra, ACT 2600, Australia.
Mallesh
M
Pandrala
Fangfei
F
Li
Marshall
M
Feterl
Yanyan
Y
Mulyana
Jeffrey M
JM
Warner
Lynne
L
Wallace
F Richard
FR
Keene
J Grant
JG
Collins
D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007495:Iridium / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010618:Phenanthrolines / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*
C560551:4,4'-dimethyl-2,2'-bipyridine; D000890:Anti-Infective Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D011725:Pyridines; D007495:Iridium; D012428:Ruthenium; C025205:1,10-phenanthroline