title: Luminescent ruthenium polypyridyl complexes with extended 'dppz' like ligands as DNA targeting binders and cellular agents.
abstract: Four new Ru(ii) polypyridyl complexes that contain an extended aromatic moiety derived from pyrazino[2,3-h]dipyrido[3,2-a:2',3'-c]phenazine and either 1,10-phenanthroline (phen) or 1,4,5,8-tetraazaphenanthrene (TAP) have been synthesized, their solid state X-ray crystal structure determined and their photophysical and biological properties evaluated. Their interactions with DNA have been studied, and they have been tested for their potential as photodynamic therapeutic (PDT) agents in the treatment of cancer. A practical modification of a method by Carter, Rodriguez and Bard has been introduced and used to calculate binding parameters for the complexes which show a strong affinity for DNA with binding constants in the order of 107M-1(in 10 mM phosphate buffer). The complexes containing phen as an ancillary ligand become emissive upon binding to DNA ("light switch effect"), but do not show selective cytotoxicity upon light irradiation. On the other hand, the TAP complexes, which show an inverse "light switch effect" (emission quenched upon binding to DNA), are strongly photo-toxic suggesting their use in Photodynamic Therapy (PDT). In HeLa cells the best PDT agent shows an IC50value (light) = 4 μM vs. IC50value (dark) = 62 μM.
authors: School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. gunnlaut@tcd.ie.
authors: Bjørn C
authors: BC
authors: Poulsen
authors: School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. gunnlaut@tcd.ie.
authors: Sandra
authors: S
authors: Estalayo-Adrián
authors: School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. gunnlaut@tcd.ie.
authors: Salvador
authors: S
authors: Blasco
authors: School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. gunnlaut@tcd.ie and School of Biochemistry and Immunology and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. Clive.Williams@tcd.ie.
authors: Sandra A
authors: SA
authors: Bright
authors: School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. gunnlaut@tcd.ie.
authors: John M
authors: JM
authors: Kelly
authors: School of Biochemistry and Immunology and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. Clive.Williams@tcd.ie.
authors: D Clive
authors: DC
authors: Williams
authors: School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. gunnlaut@tcd.ie.
authors: Thorfinnur
authors: http://orcid.org/0000-0003-4814-6853
authors: T
authors: Gunnlaugsson
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D004247:DNA / Q000187:drug effects*; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D049449:Luminescence; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010619:Phenazines / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007364:Intercalating Agents; D008024:Ligands; D009942:Organometallic Compounds; D010619:Phenazines; D017319:Photosensitizing Agents; D011810:Quinoxalines; C443808:dipyrido(3,2-a-2',3'-c)phenazine; C000598831:phenazine; D012428:Ruthenium; D004247:DNA