Combining nitric oxide and calcium sensing for the detection of endothelial dysfunction.

Cardiovascular diseases are the leading cause of death worldwide and are not typically diagnosed until the disease has manifested. Endothelial dysfunction is an early, reversible precursor in the irreversible development of cardiovascular diseases and is characterized by a decrease in nitric oxide production. We believe that more reliable and reproducible methods are necessary for the detection of endothelial dysfunction.

Photosubstitution in a trisheteroleptic ruthenium complex inhibits conjunctival melanoma growth in a zebrafish orthotopic xenograft model.

data are rare but essential for establishing the clinical potential of ruthenium-based photoactivated chemotherapy (PACT) compounds, a new family of phototherapeutic drugs that are activated ligand photosubstitution. Here a novel trisheteroleptic ruthenium complex [Ru(dpp)(bpy)(mtmp)](PF) ([2](PF), dpp = 4,7-diphenyl-1,10-phenanthroline, bpy = 2,2'-bipyridine, mtmp = 2-methylthiomethylpyridine) was synthesized and its light-activated anticancer properties were validated in cancer cell monolayers, 3D tumor spheroids, and in embryonic zebrafish cancer models. Upon green light irradiation, the non-toxic mtmp ligand is selectively cleaved off, thereby releasing a phototoxic ruthenium-based photoproduct capable notably of binding to nuclear DNA and triggering DNA damage and apoptosis within 24-48 h.

Cytotoxicity of Metal-Based Photoactivated Chemotherapy (PACT) Compounds.

Metal-based compounds have been used to treat cancer for decades, with cisplatin being the most common and widely used. Photodynamic therapy (PDT) is another clinical modality used to fight cancer, which uses a photosensitizer (PS) that localizes in cancer tissues. This PS is activated by the illumination of the tumor with visible light.

Ruthenium-based PACT agents based on bisquinoline chelates: synthesis, photochemistry, and cytotoxicity.

The known ruthenium complex [Ru(tpy)(bpy)(Hmte)](PF) ([1](PF), where tpy = 2,2':6',2″-terpyridine, bpy = 2,2'-bipyridine, Hmte = 2-(methylthio)ethanol) is photosubstitutionally active but non-toxic to cancer cells even upon light irradiation. In this work, the two analogs complexes [Ru(tpy)(NN)(Hmte)](PF), where NN = 3,3'-biisoquinoline (i-biq, [2](PF)) and di(isoquinolin-3-yl)amine (i-Hdiqa, [3](PF)), were synthesized and their photochemistry and phototoxicity evaluated to assess their suitability as photoactivated chemotherapy (PACT) agents. The increase of the aromatic surface of [2](PF) and [3](PF), compared to [1](PF), leads to higher lipophilicity and higher cellular uptake for the former complexes.

The two isomers of a cyclometallated palladium sensitizer show different photodynamic properties in cancer cells.

This report demonstrates that changing the position of the carbon-metal bond in a polypyridyl cyclopalladated complex, i.e. going from PdL1 (N^N^C^N) to PdL2 (N^N^N^C), dramatically influences the photodynamic properties of the complex in cancer cells.

Absolute upconversion quantum yields of blue-emitting LiYF:Yb,Tm upconverting nanoparticles.

The upconversion quantum yield (ΦUC) is an essential parameter for the characterization of the optical performance of lanthanoid-doped upconverting nanoparticles (UCNPs). Despite its nonlinear dependence on excitation power density (Pexc), it is typically reported only as a single number. Here, we present the first measurement of absolute upconversion quantum yields of the individual emission bands of blue light-emitting LiYF4:Yb3+,Tm3+ UCNPs in toluene.

Why develop photoactivated chemotherapy?

Photoactivated chemotherapy is an approach where a biologically active compound is protected against interaction with the cell environment by a light-cleavable protecting group, and unprotected by light irradiation. As such, PACT represents a major scientific opportunity for developing new bioactive inorganic compounds. However, the societal impact of this approach will only take off if the PACT field is used to address real societal challenges, i.

Controlling with light the interaction between trans-tetrapyridyl ruthenium complexes and an oligonucleotide.

Three new trans-ruthenium(ii) complexes coordinated to tetrapyridyl ligands, namely [Ru(bapbpy)(dmso)Cl]Cl ([2]Cl), [Ru(bapbpy)(Hmte)](PF) ([3](PF)), and [Ru(biqbpy)(Hmte)](PF) ([4](PF)), were prepared as analogues of [Ru(biqbpy)(dmso)Cl]Cl ([1]Cl), a recently described photoactivated chemotherapy agent. The new complexes were characterized, and their crystal structures showed the distorted coordination octahedron typical of this family of complexes. Their photoreactivity in solution was analyzed by spectrophotometry and mass spectrometry, which showed that the sulfur ligand was substituted upon blue light irradiation.

Frontier orbitals of photosubstitutionally active ruthenium complexes: an experimental study of the spectator ligands' electronic properties influence on photoreactivity.

The synthesis and characterization of [Ru(tpy)(Rbpy)(L)](X) complexes (tpy = 2,2':6',2''-terpyridine, Rbpy = 4,4'-dimethyl-2,2'-bipyridine (dmbpy), or 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (tfmbpy), X = Cl or PF, and n = 1 or 2) are described. The dmbpy and tfmbpy bidentate ligands allow for investigating the effects of electron-donating and electron-withdrawing ligands, respectively, on the frontier orbital energetics as well as the photoreactivity of these ruthenium polypyridyl complexes for five prototypical monodentate ligands L = Cl, HO, CHCN, 2-(methylthio)ethanol (Hmte), or pyridine. According to spectroscopic and electrochemical studies, the dmbpy analogues displayed a singlet metal-to-ligand charge transfer (MLCT) transition at higher energy than the tfmbpy analogues.

Turning on the red phosphorescence of a [Ru(tpy)(bpy)(Cl)]Cl complex by amide substitution: self-aggregation, toxicity, and cellular localization of an emissive ruthenium-based amphiphile.

Coupling the notoriously non-emissive complex [Ru(tpy)(bpy)Cl]Cl (tpy = 2,2':6',2''-terpyridine, bpy = 2,2'-bipyridine) to a C alkyl chain via an amide linker on the 4' position of the terpyridine yielded a new amphiphilic ruthenium complex showing red emission and chloride-dependent aggregation properties. This emissive complex is highly cytotoxic in A549 non-small lung cancer cells where it can be followed by confocal microscopy. Uptake occurs within minutes, first by insertion into the cellular membrane, and then by migration to the peri-nuclear region.

To cage or to be caged? The cytotoxic species in ruthenium-based photoactivated chemotherapy is not always the metal.

In metal-based photoactivated chemotherapy (PACT), two photoproducts are generated by light-triggered photosubstitution of a metal-bound ligand: the free ligand itself and an aquated metal complex. By analogy with cisplatin, the aquated metal complex is usually presented as the biologically active species, as it can typically bind to DNA. In this work, we show that this qualitative assumption is not necessarily valid by comparing the biological activity, log P, and cellular uptake of three ruthenium-based PACT complexes: [Ru(bpy)(dmbpy)], [Ru(bpy)(mtmp)], and [Ru(Phphen)(mtmp)].

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

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.

Imaging Upconverting Polymersomes in Cancer Cells: Biocompatible Antioxidants Brighten Triplet-Triplet Annihilation Upconversion.

Light upconversion is a very powerful tool in bioimaging as it can eliminate autofluorescence, increase imaging contrast, reduce irradiation damage, and increase excitation penetration depth in vivo. In particular, triplet-triplet annihilation upconverting (TTA-UC) nanoparticles and liposomes offer high upconversion efficiency at low excitation power. However, TTA-UC is quenched in air by oxygen, which also leads to the formation of toxic singlet oxygen.

An in vitro cell irradiation protocol for testing photopharmaceuticals and the effect of blue, green, and red light on human cancer cell lines.

Traditionally, ultraviolet light (100-400 nm) is considered an exogenous carcinogen while visible light (400-780 nm) is deemed harmless. In this work, a LED irradiation system for in vitro photocytotoxicity testing is described. The LED irradiation system was developed for testing photopharmaceutical drugs, but was used here to determine the basal level response of human cancer cell lines to visible light of different wavelengths, without any photo(chemo)therapeutic.

Stabilization of the Low-Spin State in a Mononuclear Iron(II) Complex and High-Temperature Cooperative Spin Crossover Mediated by Hydrogen Bonding.

The tetrapyridyl ligand bbpya (bbpya=N,N-bis(2,2'-bipyrid-6-yl)amine) and its mononuclear coordination compound [Fe(bbpya)(NCS)2 ] (1) were prepared. According to magnetic susceptibility, differential scanning calorimetry fitted to Sorai's domain model, and powder X-ray diffraction measurements, 1 is low-spin at room temperature, and it exhibits spin crossover (SCO) at an exceptionally high transition temperature of T1/2 =418 K. Although the SCO of compound 1 spans a temperature range of more than 150 K, it is characterized by a wide (21 K) and dissymmetric hysteresis cycle, which suggests cooperativity.

Triplet-triplet annihilation upconversion followed by FRET for the red light activation of a photodissociative ruthenium complex in liposomes.

Upconversion is a promising way to trigger high-energy photochemistry with low-energy photons. However, combining upconversion schemes with non-radiative energy transfer is challenging because bringing several photochemically active components in close proximity results in complex multi-component systems where quenching processes may deactivate the whole assembly. In this work, PEGylated liposomes were prepared that contained three photoactive components: a porphyrin dye absorbing red light, a perylene moiety emitting in the blue, and a light-activatable ruthenium prodrug sensitive to blue light.

Imaging the lipid bilayer of giant unilamellar vesicles using red-to-blue light upconversion.

Red-to-blue triplet-triplet annihilation upconversion was obtained in giant unilamellar vesicles. The upconverted light was homogeneously distributed across the membrane and could be utilized for the imaging of individual giant vesicles in three dimensions. These results show the great potential of TTA-UC for imaging applications under anoxic conditions.

Yellow-light sensitization of a ligand photosubstitution reaction in a ruthenium polypyridyl complex covalently bound to a rhodamine dye.

The ruthenium complex [Ru(terpy)(bpy)(Hmte)](2+) ([1](2+)), where terpy is 2,2';6',2''-terpyridine, bpy is 2,2'-bipyridine, and Hmte is 2-methylthioethan-1-ol, poorly absorbs yellow light, and although its quantum yield for the photosubstitution of Hmte by water is comparable at 570 nm and at 452 nm (0.011(4) vs. 0.

Ruthenium-decorated lipid vesicles: light-induced release of [Ru(terpy)(bpy)(OH2)]2+ and thermal back coordination.

Electrostatic forces play an important role in the interaction between large transition metal complexes and lipid bilayers. In this work, a thioether-cholestanol hybrid ligand (4) was synthesized, which coordinates to ruthenium(II) via its sulfur atom and intercalates into lipid bilayers via its apolar tail. By mixing its ruthenium complex [Ru(terpy)(bpy)(4)](2+) (terpy = 2,2';6',2''-terpyridine; bpy = 2,2'-bipyridine) with either the negatively charged lipid dimyristoylphosphatidylglycerol (DMPG) or with the zwitterionic lipid dimyristoylphosphatidylcholine (DMPC), large unilamellar vesicles decorated with ruthenium polypyridyl complexes are formed.