title: Oligonuclear polypyridylruthenium(II) complexes incorporating flexible polar and non-polar bridges: synthesis, DNA-binding and cytotoxicity.
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 (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.
authors.affiliation: James Cook University, Townsville, Queensland, Australia.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Mulyana
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Weber
authors.forename: Damian P
authors.initials: DP
authors.lastname: Buck
authors.forename: Cherie A
authors.initials: CA
authors.lastname: Motti
authors.forename: J Grant
authors.initials: JG
authors.lastname: Collins
authors.forename: F Richard
authors.initials: FR
authors.lastname: Keene
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011725:Pyridines; D012428:Ruthenium; D004247:DNA