RNA and DNA binding of inert oligonuclear ruthenium(II) complexes in live eukaryotic cells

Li, Xin, Gorle, Anil K., Ainsworth, Tracy D., Heimann, Kirsten, Woodward, Clifford E., Collins, J. Grant, and Keene, F. Richard (2015) RNA and DNA binding of inert oligonuclear ruthenium(II) complexes in live eukaryotic cells. Dalton Transactions, 44 (8). pp. 3594-3603.

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Abstract

Confocal microscopy was used to study the intracellular localisation of a series of inert polypyridylruthenium(II) complexes with three eukaryotic cells lines – baby hamster kidney (BHK), human embryonic kidney (HEK-293) and liver carcinoma (Hep-G2). Co-staining experiments with the DNA-selective dye DAPI demonstrated that the di-, tri- and tetra-nuclear polypyridylruthenium(II) complexes that are linked by the bis[4(4'-methyl-2,2'-bipyridyl)]-1,12-dodecane bridging ligand ("bb12") showed a high degree of selectivity for the nucleus of the eukaryotic cells. Additional co-localisation experiments with the general nucleic acid stain SYTO 9 indicated that the ruthenium complexes showed a considerable preference for the RNA-rich nucleolus, rather than chromosomal DNA. No significant differences were observed in the intracellular localisation between the ΔΔ and ΛΛ enantiomers of the dinuclear complex. Cytotoxicity assays carried out over 72 hours indicated that the ruthenium complexes, particularly the tri- and tetra-nuclear species, were significantly toxic to the eukaryotic cells. However, when the activity of the least cytotoxic compound (the ΔΔ enantiomer of the dinuclear species) was determined over a 24 hour period, the results indicated that the ruthenium complex was approximately a 100-fold less toxic to liver and kidney cells than to Gram positive bacteria. Circular dichroism (CD) spectroscopy was used to examine the effect of the ΔΔ and ΛΛ enantiomers of the dinuclear complex on the solution conformations of RNA and DNA. The CD experiments indicated that the RNA maintained the A-type conformation, and the DNA the B-type structure, upon binding by the ruthenium complexes.

Item ID: 35889
Item Type: Article (Refereed Research - C1)
Keywords: RNA; DNA; eukaryotic cells; polypyridyl ruthenium complexes; oligonuclear; confocal microscopy; circular dichroism
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This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

ISSN: 1477-9234
Date Deposited: 22 Oct 2014 05:03
FoR Codes: 03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030201 Bioinorganic Chemistry @ 50%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060106 Cellular Interactions (incl Adhesion, Matrix, Cell Wall) @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 40%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 30%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 30%
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