| Autor: |
Smithen DA; Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada., Yin H; Department of Chemistry, Acadia University , 6 University Avenue, Wolfville, Nova Scotia B4P 2R6, Canada., Beh MH; Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada., Hetu M; Department of Chemistry, Acadia University , 6 University Avenue, Wolfville, Nova Scotia B4P 2R6, Canada., Cameron TS; Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada., McFarland SA; Department of Chemistry, Acadia University , 6 University Avenue, Wolfville, Nova Scotia B4P 2R6, Canada.; Department of Chemistry and Biochemistry, University of North Carolina at Greensboro , 301 McIver Street, Greensboro, North Carolina 27402, United States., Thompson A; Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada. |
| Abstrakt: |
The synthesis and characterization of a series of heteroleptic ruthenium(II) dyads derived from pyrrole-2-carboxylate thionoesters are reported. Ligands bearing a conjugated thiocarbonyl group were found to be more reactive toward Ru(II) complexation compared to analogous all-oxygen pyrrole-2-carboxylate esters, and salient features of the resulting complexes were determined using X-ray crystallography, electronic absorption, and NMR spectroscopy. Selected complexes were evaluated for their potential in photobiological applications, whereupon all compounds demonstrated in vitro photodynamic therapy effects in HL-60 and SK-MEL-28 cells, with low nanomolar activities observed, and exhibited some of the largest photocytotoxicity indices to date (>2000). Importantly, the Ru(II) dyads could be activated by relatively soft doses of visible (100 J cm -2 , 29 mW cm -2 ) or red light (100 J cm -2 , 34 mW cm -2 ), which is compatible with therapeutic applications. Some compounds even demonstrated up to five-fold selectivity for malignant cells over noncancerous cells. These complexes were also shown to photocleave, and in some cases unwind, DNA in cell-free experiments. Thus, this new class of Ru(II) dyads has the capacity to interact with and damage biological macromolecules in the cell, making them attractive agents for photodynamic therapy. |
