Luminescent ruthenium polypyridyl complexes with extended 'dppz' like ligands as DNA targeting binders and cellular agentsElectronic supplementary information (ESI) available: Characterisation, data-fitting and X-ray crystallographic information. CCDC 1489206 and 1489207. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6dt03792e

• Main Authors: Poulsen, Bjørn C, Estalayo-Adrián, Sandra, Blasco, Salvador, Bright, Sandra A, Kelly, John M, Williams, D. Clive, Gunnlaugsson, Thorfinnur
• Format: Article
• Language: English
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c6dt03792e

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 10 7 M −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 IC 50 value (light) = 4 μM vs . IC 50 value (dark) = 62 μM. DNA-binding and phototoxicity of Ru( ii ) complexes with ligands derived from pyrazinodipyridophenazine and either phen or TAP as ancillary ligands are reported.