Format

Send to

Choose Destination
Dalton Trans. 2016 Nov 15;45(45):18208-18220.

Luminescent ruthenium polypyridyl complexes with extended 'dppz' like ligands as DNA targeting binders and cellular agents.

Author information

1
School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. gunnlaut@tcd.ie.
2
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.
3
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.

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 107 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 IC50 value (light) = 4 μM vs. IC50 value (dark) = 62 μM.

PMID:
27796397
DOI:
10.1039/c6dt03792e
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Royal Society of Chemistry
Loading ...
Support Center