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

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 (bb(n)), linear polyether (bbO(n)) or linear alkylamine (bbN(n)) 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 = bb(n), bbO(n) or bbN(n)) - 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 bb(7) bridge. Fluorescence displacement studies of the DNA-binding of the dinuclear complexes containing the bbO(n) and bbN(n) bridges generally revealed a lower affinity than their bb(n) 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 bb(7)-bridged trinuclear and tetranuclear complexes showed considerably enhanced cytotoxicity compared with the dinuclear Rubb(7) analogue.