New RuII Complex for Dual Activity: Photoinduced Ligand Release and 1O2 Production

Loftus, Lauren M.; White, Jessica K.; Albani, Bryan A.; Kohler, Lars; Kodanko, Jeremy J.; Thummel, Randolph P.; Dunbar, Kim R.; Turró, Claudia

doi:10.1002/chem.201504800

Cited by 58 publications

(53 citation statements)

References 37 publications

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“…1–32 The utility of these complexes for these applications relies on their relatively strong absorption and emission intensity in the visible region, long-lived triplet metal-to-ligand charge transfer ( 3 MLCT) excited state lifetimes, and high stability under various experimental conditions. 1–33 In contrast, the efficient photoinduced ligand dissociation for the release of drugs or biological probes with spatiotemporal control necessitates the population of the dissociative metal-centered, ligand field states ( 3 LF), known to lead to nonradiative deactivation of the emissive 3 MLCT state.…”

Section: Introductionmentioning

confidence: 99%

Unusual Role of Excited State Mixing in the Enhancement of Photoinduced Ligand Exchange in Ru(II) Complexes

Loftus

Fillman

et al. 2017

J. Am. Chem. Soc.

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Four Ru(II) complexes were prepared bearing two new tetradentate ligands, cyTPA and 1-isocyTPQA, which feature a piperidine ring that provides a structurally rigid backbone and facilitates the installation of other donors as the fourth chelating arm, while avoiding the formation of stereoisomers. The photophysical properties and photochemistry of [Ru(cyTPA)(CH3CN)2]2+ (1), [Ru(1-isocyTPQA)(CH3CN)2]2+ (2), [Ru(cyTPA)(py)2]2+ (3), and [Ru(1-isocyTPQA)-(py)2]2+ (4) were compared. The quantum yield for the CH3CN/H2O ligand exchange of 2 was measured to be Φ400 = 0.033(3), 5-fold greater than that of 1, Φ400 = 0.0066(3). The quantum yields for the py/H2O ligand exchange of 3 and 4 were lower, 0.0012(1) and 0.0013(1), respectively. DFT and related calculations show the presence of a highly mixed 3MLCT/3ππ* excited state as the lowest triplet state in 2, whereas the lowest energy triplet states in 1, 3, and 4 were calculated to be 3LF in nature. The mixed 3MLCT/3ππ* excited state places significant spin density on the quinoline moiety of the 1-isocyTPQA ligand positioned trans to the photolabile CH3CN ligand in 2, suggesting the presence of a trans-type influence in the excited state that enhances ligand exchange. Ultrafast spectroscopy was used to probe the excited states of 1–4, which confirmed that the mixed 3MLCT/3ππ* excited state in 2 promotes ligand dissociation, representing a new manner to effect photoinduced ligand exchange. The findings from this work can be used to design improved complexes for applications that require efficient ligand dissociation, as well as for those that require minimal deactivation of the 3MLCT state through low-lying metal-centered states.

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Section: Introductionmentioning

confidence: 99%

Unusual Role of Excited State Mixing in the Enhancement of Photoinduced Ligand Exchange in Ru(II) Complexes

Loftus

Fillman

et al. 2017

J. Am. Chem. Soc.

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“…In addition, ruthenium complexes such as [Ru(tpy)(bpy)(L)] 2+ are photochemically active because visible‐light irradiation leads to ligand‐exchange reactions that do not occur in the dark . Such photosubstitution reactions have been proposed as a way to trigger the toxicity of anticancer metallodrugs with spatial and temporal resolution . Likewise, photosubstitution of the protecting monodentate ligand L in [Ru(tpy)(bpy)(L)] 2+ may activate the complex by producing [ 1 ] 2+ inside a cell.…”

Section: Introductionmentioning

confidence: 99%

Chemical Swarming: Depending on Concentration, an Amphiphilic Ruthenium Polypyridyl Complex Induces Cell Death via Two Different Mechanisms

Siewert

Rixel

Rooden

et al. 2016

Chemistry A European J

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The crystal structure and in vitro cytotoxicity of the amphiphilic ruthenium complex [3](PF6)2 are reported. Complex [3](PF6)2 contains a Ru−S bond that is stable in the dark in cell‐growing medium, but is photosensitive. Upon blue‐light irradiation, complex [3](PF6)2 releases the cholesterol–thioether ligand 2 and an aqua ruthenium complex [1](PF6)2. Although ligand 2 and complex [1](PF6)2 are by themselves not cytotoxic, complex [3](PF6)2 was unexpectedly found to be as cytotoxic as cisplatin in the dark, that is, with micromolar effective concentrations (EC50), against six human cancer cell lines (A375, A431, A549, MCF‐7, MDA‐MB‐231, and U87MG). Blue‐light irradiation (λ=450 nm, 6.3 J cm−2) had little influence on the cytotoxicity of [3](PF6)2 after 6 h of incubation time, but it increased the cytotoxicity of the complex by a factor 2 after longer (24 h) incubation. Exploring the unexpected biological activity of [3](PF6)2 in the dark elucidated an as‐yet unknown bifaceted mode of action that depended on concentration, and thus, on the aggregation state of the compound. At low concentration, it acts as a monomer, inserts into the membrane, and can deliver [1]2+ inside the cell upon blue‐light activation. At higher concentrations (>3–5 μm), complex [3](PF6)2 forms supramolecular aggregates that induce non‐apoptotic cell death by permeabilizing cell membranes and extracting lipids and membrane proteins.

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“…In a process called "photoactivated chemotherapy" (PACT) [1][2][3][4][5], excitation with visible light transforms these non-toxic compounds into cytotoxic species via photosubstitution reactions. Like in photodynamic therapy (PDT), ruthenium-based PACT agents may greatly reduce undesired side effects for cancer patients by the excellent spatio-temporal control over activation.…”

Section: Introductionmentioning

confidence: 99%

Red Light Activation of Ru(II) Polypyridyl Prodrugs via Triplet-Triplet Annihilation Upconversion: Feasibility in Air and through Meat

et al. 2016

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Triplet-triplet annihilation upconversion (TTA-UC) is a promising photophysical tool to shift the activation wavelength of photopharmacological compounds to the red or near-infrared wavelength domain, in which light penetrates human tissue optimally. However, TTA-UC is sensitive to dioxygen, which quenches the triplet states needed for upconversion. Here, we demonstrate not only that the sensitivity of TTA-UC liposomes to dioxygen can be circumvented by adding antioxidants, but also that this strategy is compatible with the activation of ruthenium-based chemotherapeutic compounds. First, red-to-blue upconverting liposomes were functionalized with a blue-light sensitive, membrane-anchored ruthenium polypyridyl complex, and put in solution in presence of a cocktail of antioxidants composed of ascorbic acid and glutathione. Upon red light irradiation with a medical grade 630 nm PDT laser, enough blue light was produced by TTA-UC liposomes under air to efficiently trigger full activation of the Ru-based prodrug. Then, the blue light generated by TTA-UC liposomes under red light irradiation (630 nm, 0.57 W/cm 2 ) through different thicknesses of pork or chicken meat was measured, showing that TTA-UC still occurred even beyond 10 mm of biological tissue. Overall, the rate of activation of the ruthenium compound in TTA-UC liposomes using either blue or red light (1.6 W/cm 2 ) through 7 mm of pork fillet were found comparable, but the blue light caused significant tissue damage, whereas red light did not. Finally, full activation of the ruthenium prodrug in TTA-UC liposomes was obtained under red light irradiation through 7 mm of pork fillet, thereby underlining the in vivo applicability of the activation-by-upconversion strategy.

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New Ru^II Complex for Dual Activity: Photoinduced Ligand Release and ¹O₂ Production

Cited by 58 publications

References 37 publications

Unusual Role of Excited State Mixing in the Enhancement of Photoinduced Ligand Exchange in Ru(II) Complexes

Unusual Role of Excited State Mixing in the Enhancement of Photoinduced Ligand Exchange in Ru(II) Complexes

Chemical Swarming: Depending on Concentration, an Amphiphilic Ruthenium Polypyridyl Complex Induces Cell Death via Two Different Mechanisms

Red Light Activation of Ru(II) Polypyridyl Prodrugs via Triplet-Triplet Annihilation Upconversion: Feasibility in Air and through Meat

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