title: Synthesis, characterization, and biological evaluation of new Ru(II) polypyridyl photosensitizers for photodynamic therapy.
abstract: Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl-2,2':6',2″-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of 2 (IC50(light): 25.3 μM, 420 nm, 6.95 J/cm(2); PI >4) and particularly of 1 (IC50(light): 0.62 μM, 420 nm, 6.95 J/cm(2); PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(-) E. coli (>4 log10 CFU reduction).
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Angelo
authors.initials: A
authors.lastname: Frei
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rubbiani
authors.forename: Solmaz
authors.initials: S
authors.lastname: Tubafard
authors.forename: Olivier
authors.initials: O
authors.lastname: Blacque
authors.forename: Philipp
authors.initials: P
authors.lastname: Anstaett
authors.forename: Ariane
authors.initials: A
authors.lastname: Felgenträger
authors.forename: Tim
authors.initials: T
authors.lastname: Maisch
authors.forename: Leone
authors.initials: L
authors.lastname: Spiccia
authors.forename: Gilles
authors.initials: G
authors.lastname: Gasser
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D008027:Light; D050296:Microbial Viability / Q000187:drug effects / Q000528:radiation effects; D018613:Microscopy, Confocal; D008956:Models, Chemical; D015394:Molecular Structure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000528:radiation effects
chemical_list: D056831:Coordination Complexes; D017319:Photosensitizing Agents; D012428:Ruthenium