title: Unexpected DNA binding properties with correlated downstream biological applications in mono vs. bis-1,8-naphthalimide Ru(II)-polypyridyl conjugates.
abstract: The synthesis, spectroscopic characterisation and biological evaluation of mono- and bis-1,8-naphthalimide-conjugated ruthenium(ii)-polypyridyl complexes is presented. Spectroscopic DNA titrations, together with denaturation studies, show strong binding of both species to DNA through the naphthalimide arms. Linear and circular dichroism (LD and CD) spectroscopy reveal close association of the Ru(bpy)3(2+) core with DNA in the case of the mono-naphthalamide complex, [Ru(bpy)2(bpy-NAP)](2+). Significantly, binding by the second naphthalimide arm in the [Ru(bpy)2(bpy-NAP2)](2+) complex is found to displace the Ru(bpy)3(2+) centre from the DNA backbone. This 'negative allosteric effect' is found to have a dramatic influence on the photoinduced damage of plasmid DNA, and the viability of HeLa cancer cells upon photoactivation. Overall the study clearly maps and correlates the relationship between molecular structure, in vitro binding and activity, and in cellulo function.
authors: School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, Dublin 2, Ireland. gunnlaut@tcd.ie.
authors: Gary J
authors: GJ
authors: Ryan
authors: Fergus E
authors: FE
authors: Poynton
authors: Robert B P
authors: RB
authors: Elmes
authors: Marialuisa
authors: M
authors: Erby
authors: D Clive
authors: DC
authors: Williams
authors: Susan J
authors: SJ
authors: Quinn
authors: Thorfinnur
authors: T
authors: Gunnlaugsson
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D053644:Naphthalimides / Q000737:chemistry; D009691:Nucleic Acid Denaturation; D010782:Photolysis / Q000528:radiation effects; D012428:Ruthenium / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D044366:Transition Temperature; D014466:Ultraviolet Rays
chemical_list: D056831:Coordination Complexes; D053644:Naphthalimides; D012428:Ruthenium; D004247:DNA