Pushing the limits of structurally-diverse light-harvesting Ru(II) metal-organic chromophores for photodynamic therapy

Abstract

The synthesis of Ru(II) derivatives [(AnthbpyMe)(bpy)Ru(dpp)] 2+ (2) and [(AnthbpyMe) 2 Ru(dpp)] 2+ (3), and the analysis of their excited state properties as well as their photocytotoxicity against glioma cells are reported. Complexes 2 and 3 absorb visible light with metal-to-ligand charge transfer (MLCT) transitions at λ max = 459 nm (16,000 M-1 cm-1) and λ max = 461 nm (21,000 M-1 cm-1), respectively. The complexes exhibit bichromatic properties with the 3 MLCT emission centered at λ em = 661 nm and λ em = 663 nm for 2 and 3, respectively, while the anthracene motif(s) has emission from 450-560 nm. The anthracene unit(s) quench the 3 MLCT to give quantum yields (lifetime, τ) of Φ em = 0.0059 (τ = 398 ns) and Φ em = 0.0011 (τ = 414 ns) for 2 and 3, respectively. The quenching rates were found to be 6.61 × 10 5 s-1 for 2 and 5.64 × 10 5 s-1 for 3. Electrochemistry reveals an irreversible anthracene oxidation at 1.23-1.28 V, while the Ru III/II oxidation process occurs at a potential of 1.53-1.55 V. The complexes displayed a quasi-reversible reduction couple attributed to dpp 0/-1 at 0.98 V. Cytotoxicity of both complexes towards F98 glioma cells was moderate in the absence of light and substantially enhanced with visible light.

A new class of Ru(ii) polyazine agents with potential for photodynamic therapy

“…8 We have shown that complexes 2 and 3 efficiently absorb light throughout the visible region, facilitated by several MLCT transitions with λ max = 459 nm (ε = 16,000 M −1 cm −1 ) and 461 nm (ε = 21,000 M −1 cm −1 ), respectively. 7 Upon excitation the anthracene-[Ru]-dpp hybrid arrangement provides multiple pathways, singlet-singlet, triplet-triplet, and/or singlet-triplet, for deactivation from the 3 MLCT excited state through energy/electron transfer, which is speculated to enhance the PDT potency that was observed for these complexes against mammalian cells in preliminary experiments, 7 as also recently suggested for anthracene-[Ru]-bpy complexes. 6 …”

“…7 The PAH, anthracene, has shown substantial promise for enhancing the PDT reactivity of Ru(II) complexes. 7–8 Anthracene can by itself intercalate into the DNA double helix and, upon irradiation with UV light, oxidize adjacent sites in the DNA molecule though reactive oxygen species (ROS) or anthracene-derived cation radicals.…”

“…7 The PAH, anthracene, has shown substantial promise for enhancing the PDT reactivity of Ru(II) complexes. 7–8 Anthracene can by itself intercalate into the DNA double helix and, upon irradiation with UV light, oxidize adjacent sites in the DNA molecule though reactive oxygen species (ROS) or anthracene-derived cation radicals. 9 When appended to Ru(II) PSs, anthryl groups have been shown to promote enhanced binding to calf-thymus (CT) DNA by intercalative π-stacking, while facilitating DNA photocleavage by •OH and by sensitized 3 O 2 mechanisms via the anthracene and Ru(II) units, respectively.…”

“…Anthracene-derived radicals are hypothesized to occur via a known 3 anthracene excited state that readily photooxidizes across the 9,10 position of the molecule. 7, 13 …”

Transition Metal Intercalators as Anticancer Agents—Recent Advances

“…Complexes of the type [Ru(bpy) 2 (R-dppz)] 2+ (where R is either NH 2 , Ru6 or OMe, Ru7 , Figure 10) intercalated with DNA via the R-dppz ligand and achieved phototoxic indices of >150 and 42, respectively, against HeLa cells when irradiated with light at 420 nm (Table 4) [62]. A polypyridyl ruthenium complex incorporating an appended anthracene demonstrated photocleavage of DNA through both ruthenium-derived singlet oxygen and anthracene-derived radicals, as well as light-induced cytotoxicity in F98 glioma cells [65,66]. Ruthenium arene “piano-stool” complexes are very prominent anticancer agents, and some studies have reported a dual-binding mode in which ruthenation occurs through a leaving group while the p -cymene group intercalates between nearby bases [67].…”