Oligonuclear polypyridylruthenium(II) complexes incorporating flexible polar and non-polar bridges: synthesis, DNA-binding and cytotoxicity

Mulyana, Yanyan, Weber, Daniel K., Buck, Damian P., Motti, Cherie A., Collins, J. Grant, and Keene, F. Richard (2011) Oligonuclear polypyridylruthenium(II) complexes incorporating flexible polar and non-polar bridges: synthesis, DNA-binding and cytotoxicity. Dalton Transactions, 40 (7). pp. 1510-1523.

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Abstract

The paper reports the synthesis and characterisation of a series of flexible di-bidentate bridging ligands in which two 4-methyl-2,2'-bipyridine groups are linked at the 4'-position by polymethylene (bbn), linear polyether (bbOn) or linear alkylamine (bbNn) chains of varying length (n). The enantiomers (ΔΔ/ΛΛ) of the rac forms of the ruthenium(II) dinuclear complexes incorporating these ligands – i.e. [{Ru(phen)2}2(μ-BL)]4+ (phen = 1,10-phenanthroline; BL = bbn, bbOn or bbNn) – have been isolated by reaction of Δ- or Λ-[Ru(phen)2(py)2]2+ (py = pyridine) with the respective bridging ligands. Mononuclear species - in which only one of the bidentate moieties of the bridging ligand is coordinated – have also been isolated, as well as trinuclear and tetranuclear species involving the bb7 bridge. Fluorescence displacement studies of the DNA-binding of the dinuclear complexes containing the bbOn and bbNn bridges generally revealed a lower affinity than their bbn analogues for an oligonucleotide containing a single bulge site; the mononuclear complexes showed a lower affinity - and the trinuclear and tetranuclear complexes a higher affinity – than the dinuclear species, revealing an interesting interplay of lipophilicity, electrostatics and size in the complex/nucleic acid interaction. Cytotoxicity studies of these complexes against a murine leukaemia cell line revealed that the presence of the polyether or polyamine links in the chain lowered the cytotoxicity compared with their polymethylene analogues, and that the bb7-bridged trinuclear and tetranuclear complexes showed considerably enhanced cytotoxicity compared with the dinuclear Rubb7 analogue.

Item ID: 15567
Item Type: Article (Refereed Research - C1)
ISSN: 1477-9234
Funders: Australian Research Council
Date Deposited: 07 Jun 2011 05:51
FoR Codes: 03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030207 Transition Metal Chemistry @ 50%
03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030201 Bioinorganic Chemistry @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 100%
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