Dinuclear ruthenium(II) complexes containing one inert metal centre and one coordinatively-labile metal centre: syntheses and biological activities
Li, Xin, Heimann, Kirsten, Li, Fangfei, Warner, Jeffrey M., Keene, F. Richard, and Collins, J. Grant (2016) Dinuclear ruthenium(II) complexes containing one inert metal centre and one coordinatively-labile metal centre: syntheses and biological activities. Dalton Transactions, 45. pp. 4017-4029.
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Abstract
A series of non-symmetric dinuclear polypyridylruthenium(II) complexes (Rubbₙ-Cl) that contain one inert metal centre and one coordinatively-labile metal centre, linked by the bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane ligand ("bbₙ" for n = 7, 12 and 16), have been synthesised and their potential as antimicrobial agents examined. The minimum inhibitory concentrations (MIC) of the ruthenium(II) complexes were determined 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). The Rubbₙ-Cl complexes displayed good antimicrobial activity, with Rubb₁₂-Cl being the most active complex against both Gram-positive and Gram-negative strains. Interestingly, Rubb₇-Cl was found to be eight- and sixteen-fold more active towards E. coli than against S. aureus and MRSA, respectively. The cytotoxicities of the Rubbₙ-Cl complexes against three eukaryotic cell lines − two kidney cell lines (BHK and HEK-293) and one liver cell line (HepG2) − were examined. The Rubbₙ-Cl complexes were found to be considerably less toxic towards eukaryotic cells than S. aureus, MRSA and E. coli, with Rubb₁₂-Cl being thirty- to eighty-times more toxic to the bacteria than to BHK, HEK-293 or HepG2 cells. Unexpectedly, Rubb₇-Cl was far more toxic to HepG2 cells (24h-IC₅₀ = 3.7 μM) and far less toxic to BHK cells (24h-IC₅₀ = 238 μM) than the Rubb₁₂-Cl and Rubb₁₆-Cl complexes. In order to understand the unexpected large differences in the cytotoxicities of the Rubbₙ-Cl complexes towards eukaryotic cells, a confocal microscopic study of their intracellular localisation was undertaken. The results suggest that the observed cytotoxicity might be related to the extent of DNA binding.
Item ID: | 42399 |
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Item Type: | Article (Research - C1) |
ISSN: | 1477-9234 |
Keywords: | antibacterial; polypyridylruthenium; cytotoxity; eukaryotic cells; confocal microscopy; cellular localisation |
Additional Information: | This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material. https://creativecommons.org/licenses/by/3.0/ Open Access through the Royal Society of Chemistry Gold for Gold Open Access. |
Funders: | University of New South Wales, Canberra |
Date Deposited: | 09 Feb 2016 04:49 |
FoR Codes: | 34 CHEMICAL SCIENCES > 3402 Inorganic chemistry > 340201 Bioinorganic chemistry @ 70% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 30% |
SEO Codes: | 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 70% 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 30% |
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