title: Synthesis and Photobiological Activity of Ru(II) Dyads Derived from Pyrrole-2-carboxylate Thionoesters.
abstract: 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.
authors.affiliation: Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Smithen
authors.affiliation: Department of Chemistry, Acadia University , 6 University Avenue, Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Huimin
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Michael H R
authors.initials: MH
authors.lastname: Beh
authors.affiliation: Department of Chemistry, Acadia University , 6 University Avenue, Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Hetu
authors.affiliation: Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: T Stanley
authors.initials: TS
authors.lastname: Cameron
authors.affiliation: 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.
authors.forename: Sherri A
authors.initials: SA
authors.lastname: McFarland
authors.affiliation: Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Alison
authors.identifier: http://orcid.org/0000-0003-4231-3446
authors.initials: A
authors.lastname: Thompson