Marta Pineiro

Photoacoustic Measurements of Porphyrin Triplet-State Quantum Yields and Singlet-Oxygen Efficiencies

Photoacoustic calorimetry was used to measure the quantum yields of singlet molecular oxygen production by the triplet states of tetraphenylporphyrin (TPP), ZnTPP and CuTPP in toluene, yielding values of 0.67 0.14, 0.68 0.19 and 0.03 0.01, respectively. We show that a novel dichlorophenyl derivative of ZnTPP is capable of singlet-oxygen production with a 0.90 0.07 quantum yield. The synthesis and characterisation of a new photostable chlorin with high absorptivity in the red that is capable of singlet-oxygen production with 0.54 0.06 quantum yield is described. Our results suggest that chlorinated chlorins may be interesting new sensitisers for photodynamic therapy.

Heavy-atom effects on metalloporphyrins and polyhalogenated porphyrins

The photophysics of halogenated and metallated tetrakisphenylporphyrins is investigated using single-photon counting, photoacoustic calorimetry and luminescence techniques. The radiationless transition rates in these and related molecules are interpreted with a quantum-mechanical tunnelling model modified to include the effect of spin–orbit coupling in the intersystem crossing rates. It is shown that tetrakisphenylporphyrins with halogens in the ortho positions have long-lived triplet states that are formed in high yields. 2002 Elsevier Science B.V. All rights reserved.

Halogen atom effect on photophysical and photodynamic characteristics of derivatives of 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin.

Brominated and iodinated derivatives of 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin were synthesised directly from the corresponding aldehydes. Photophysical and photochemical properties, singlet oxygen formation quantum yields, photobleaching and log P were measured. Cellular uptake measurements and cytotoxicity assays on WiDr and A375 tumour cell lines were performed. 5,10,15,20-Tetrakis(2-bromo-5-hydroxyphenyl)porphyrin showed the best cytotoxicity with values of IC(50) of 113 nM over WiDr cells and 52nM over A375 cells.

Photoacid for Extremely Long-Lived and Reversible pH-Jumps

The ability to change the acidity of an aqueous solution within the time of a short laser pulse and use the resulting low pH to drive acid-catalyzed reactions in the irradiated volume opens news perspectives for the spatial and temporal control of a variety of processes. Persistent and reversible acidification of an aqueous solution is achieved with a new molecule, 1-(2-nitroethyl)-2-naphthol, that combines the fast photoacid properties of an aromatic alcohol with the slow proton transfer rates of a nitroalkane. The protons released in a few nanoseconds by pulsed laser excitation of the photoacid last for nearly one second in aqueous solutions. We show that acid-base equilibria with other species is established at the lower pHs of the irradiated volume, that the process is reversible and that it can be maintained under continuous irradiation.

Ecofriendly Porphyrin Synthesis by using Water under Microwave Irradiation

Water, under microwave irradiation and at a temperature of 473 K, reaches pressures above 16 bar, being capable to act as catalyst, without the use of organic solvents and oxidants, for meso-substituted porphyrin synthesis. Sustainability of the reaction is proved by E Factor=35 and EcoScale value of 50.5, the highest so far obtained for porphyrin synthesis. Methodologys wide versatility is clearly demonstrated by the good yields obtained for both aryl and alkyl substituted porphyrins. These reaction conditions represent a huge development, not only by using very high concentrations, minimizing organic solvent usage, but also by eradicating toxic expensive solvents and oxidants.

In Vitro Photodynamic Activity of 5,15‐bis(3‐Hydroxyphenyl)porphyrin and Its Halogenated Derivatives Against Cancer Cells

5,15‐Diarylporphyrins (1‐5) with hydroxyl groups and halogens as substituents were prepared by condensation between unsubstituted dipyrromethane and halogenated m‐hydroxybenzaldehydes. Photophysical properties show that the nonhalogenated porphyrin 1 has higher fluorescence yield but lower singlet oxygen formation quantum yield than the halogenated derivatives due to the heavy atom effect. The in vitro activity of these derivatives was tested against WiDr colorectal adenocarcinoma and A375 melanoma cancer cells. All porphyrins present a much higher phototoxicity than Photofrin® with IC50 values lower than the 50 nm level for WiDr cells and 25 nm level for A375 cancer cells. The most photoactive compound is the nonhalogenated porphyrin 1 which also presents the highest uptake. Halogenated derivatives present much lower uptakes than 1. However, their photoactivity is similar to compound 1 showing that their intrinsic photoactivity (ISP) is very high. Iodinated compound 4 presents the highest ISP. The greater ability of these porphyrins to destroy cancer cells could be related to their photophysical and photochemical properties.

Novel porphyrins and a chlorin as efficient singlet oxygen photosensitizers for photooxidation of naphthols or phenols to quinones

Four porphyrins and one chlorin having aromatic groups at the meso position have been synthesized and tested as potential sensitizers for the photooxidation of phenols. The yields of conversion of 1,5-dihydroxynaphthalene and 2,3,5-trimethylphenol to their corresponding quinones have been determined following photolysis in air-saturated acetonitrile–dichloromethane solutions in the presence of these compounds, and are higher than those obtained using other photosensitizers. The reactions are shown to proceed via formation of singlet oxygen (1Δg), followed by its addition to the phenol. A mechanism is presented. Rates of reaction of singlet oxygen with the substrates were determined by studying the decay of the 1O2* emission. Singlet oxygen quantum yields and formation efficiencies for the photosensitizers have been determined by laser flash photolysis and photoacoustic calorimetry. In addition, for two of the porphyrins, these were also measured using time-resolved luminescence. In all cases, highly efficient singlet oxygen formation is observed. The stabilities of the sensitizers to prolonged photolysis were studied. The compound 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin was found to be a particularly efficient photosensitizer for oxidation of phenols. It is suggested that this is due both to its high singlet oxygen yield and to its good photostability.

Solventless metallation of low melting porphyrins synthesized by the water/microwave method

Herein, we unveil a new ecofriendly methodology for the synthesis of low melting point meso-substituted metalloporphyrins. The water/microwave (MW) synthetic method was used to prepare low melting point unsymmetrical meso-aryl substituted porphyrins and meso-alkyl substituted porphyrins, which uses water under MW irradiation, acting as the solvent/acid catalyst/oxidant in sub-critical conditions. A straightforward conceptual method for the preparation of their metal complexes in very high yields, in the absence of either solvent or base was followed. Thermomicroscopy studies were carried out to assess the metallation reaction, showing that the process is a typical solventless reaction. Calculation of sustainability classifications such as E factors and EcoScale values (as low as 283 and as high as 82 respectively, for the metallation procedure) and very favorable EHS classification establishes this methodology as one presenting the best sustainability classification on porphyrin synthesis.

Atropisomers of 5,10,15,20-tetrakis(2,6-dichloro-3-sulfamoyl-phenyl)porphyrins

The ratio, resolution and photophysical characterization of atropisomers of 5,10,15,20-tetrakis(2,6-dichloro-3-N-butylsulfamoylphenyl)porphyrin, 5,10,15,20-tetrakis(2,6-dichloro-3-(N-1-(L)-ethoxycarbonyl-2-methyl-propyl-sulfamoyl)phenyl)porphyrin and 5,10,15,20-tetrakis(2,6-dichloro-3-(N-1-(L)-methoxycarbonyl-3-methyl-butyl-sulfamoyl)phenyl)porphyrin are reported.

2-Bromo-5-hydroxyphenylporphyrins for photodynamic therapy: Photosensitization efficiency, subcellular localization and in vivo studies

BACKGROUND Photodynamic therapy (PDT) is a therapeutic modality capable of inducing cell death by oxidative stress through activation of a sensitizer by light. Aryl-porphyrin with hydroxyl groups are good photosensitizers and presence of bromine atoms can enhance the photodynamic activity through heavy atom effect. These facts and our previous work made pertinent to compare the photodynamic capacity of tetraaryl brominated porphyrin (TBr4) with the corresponding diaryl (BBr2) derivative. METHODS Cell cultures were incubated with the sensitizers, ranging from 50nM to 10μM and irradiated until 10J. Cell proliferation was analysed by MTT assay. Flow cytometry studies evaluated cell death pathways, mitochondrial membrane potential and ROS. For in vivo studies Balb/c nu/nu mice were injected with 4×10(6)cells. After PDT, monitoring was carried out for 12 days to establish Kaplan-Meier survival curves. Tumours were excised and histological analysis was performed. RESULTS Both sensitizers seem to accumulate in the mitochondria. The molecules have no intrinsic cytotoxicity or in non-tumour cells at therapeutic concentrations. Both sensitizers induced a significant decrease of cell proliferation and growth of xenografts of melanoma and colorectal adenocarcinoma. Diaryl BBr2 is more efficient than tetraaryl TBr4, concerning intracellular ROS production, mitochondrial disruption and induction of cell death. The main cell death pathway is necrosis. CONCLUSIONS TBr2 and BBr4 are promising sensitizers with good photodynamic properties and have the ability to induce cell death in human melanoma and colorectal adenocarcinoma in vitro and in vivo. We consider that BBr2 is a molecule that should be the subject of extensive studies towards clinical use.