Products Cited in Publications Worldwide Multifaceted Ru (II) arene systems for phototherapy display activity in lung cancer and melanoma

Multifaceted Ru (II) arene systems for phototherapy display activity in lung cancer and melanoma

Spiconardi, Joseph; Havrylyuk, Dmytro; Shi, Ge; Talgatov, Alisher; Cameron, Colin G; Heidary, David K; McFarland, Sherri A; Glazer, Edith C

DOI: PMID:

Abstract

Phototherapy approaches include photodynamic therapy (PDT), which utilizes chemically stable photocatalysts to sensitize the conversion of endogenous molecules such as oxygen (O2) to form transient reactive species such as 1O2, and photopharmacology, a complementary approach that relies on molecules that undergo self-modifying photochemistry, such as bond cleavage reactions or isomerization, for the creation of biologically active products. While Ru(II) polypyridyl systems have demonstrated utility for both approaches, related organometallic systems are relatively less explored. Here, the photochemistry and photobiological responses were compared for five Ru(II) arene compounds containing photolabile monodentate azine ligands and the π-expansive bidentate ligands dipyrido[3,2-a:2′,3′-c]phenazine (dppz), 4,5,9,16-tetraaza-dibenzo[a,c]naphthacene (dppn), and α-terthienyl-appended imidazo[4,5-f][1,10]phenanthroline (IP-3T). The compounds demonstrated significant light-mediated photocytotoxicity in lung cancer and melanoma cell lines, with up to 6000-fold increases in cytotoxicity upon irradiation. The arene systems were capable of partitioning between different excited state relaxation pathways, both releasing the monodentate ligand and generating 1O2, but with notably low yields that did not correlate with the photocytotoxicity of the systems. The organometallic compounds exhibit less mixing of the metal-associated and ligand-centered excited states than analogous polypyridyl coordination compounds, providing a structurally, photochemically, and photobiologically distinct class of compounds that can support both metal- and ligand-centered reactivity.

Keywords

hypoxia ; lung cancer ; melanoma ; oligothiophene ; photodynamic therapy ; photopharmacology ; photosubstitution ; ROS

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A55295719535-47-898%

Dipyrido[3,2-a:2',3'-c]phenazine

54.0/1g

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