Search

Highlights: [•] Photodynamic activity of cationic and non-charged porphyrins was compared in different media. [•] Porphyrin interactions were determined in β-cyclodextrin and AOT reverse micelles. [•] Anthracene derivatives were used as molecule trap of singlet molecular oxygen. [•] Efficient photosensitized oxidation of tryptophan was found using non-charged porphyrin. [•] Porphyrin substituted by aliphatic amine groups represents an interesting agent to photoinactivate microbes. [Copyright &y& Elsevier]

A covalently linked porphyrin–fullerene C 60 dyad 6 was conveniently synthesized by 1,3‐dipolar cycloaddition using 5‐(4‐carbonylphenyl)‐10,15,20‐tris(4‐methoxylphenyl)porphyrin 5, N ‐methylglycine and fullerene C 60 . Spectroscopic studies show that dyad 6 is a promising architecture with potential application as photoactive organic material. [ABSTRACT FROM AUTHOR]

A covalently linked porphyrin-fullerene C60 dyad 5 was synthesized by 1,3-dipolar cycloaddition using 5-(4-formylphenyl)-10,15,20-tris[3-(N-ethylcarbazoyl)]porphyrin, N-methylglycine and fullerene C60. Methylation of 5 was used to obtain a cationic dyad 6. Spectroscopic properties were compared in toluene, N,N-dimethylformamide (DMF) and toluene/sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/water reverse micelles. Absorption spectra of the dyads were essentially a superposition of the spectra of the porphyrin and fullerene reference compounds, indicating a very weak interaction between the chromophores in the ground state. The fluorescence emission of the porphyrin moiety in the dyads was strongly quenched by the attached fullerene C60 unit. The singlet molecular oxygen, O2(¹Δg), productions (ΦΔ) were strongly dependent on the solvent polarity. Similar ΦΔ values were obtained for 5,10,15,20-tetrakis[3-(N-ethylcarbazoyl)]porphyrin (TCP) in both solvents. Also, dyad 5 showed a high O2(¹Δg) generation in toluene. However, O2(¹Δg) production mediated by 5 considerably diminished in the more polar solvent DMF. Also, a high photodynamic activity involving O2(¹Δg) was found for both dyads in a simple biomimetic system formed by AOT reverse micelles. The photoinactivation ability of these dyads was investigated in Staphylococcus aureus cell suspensions. Photosensitized inactivation of S. aureus by dyad 6 exhibits a 4.5 log decrease of cell survival (99.997% cell inactivation), when the cultures are treated with 5 µM photosensitizer and irradiated with visible light (350-800 nm) for 30 min. Under these conditions, a lower photocytotoxic effect was found for 5 (3.2 log decrease). Furthermore, photoinactivation induced by 6 was higher than those obtained with the separate moieties of the dyad. Therefore, molecular structures formed by porphyrin-fullerene C60 dyads represent interesting photosensitizers to inactivate S. aureus. [ABSTRACT FROM AUTHOR]

Abstract: The spectroscopic properties and photodynamic activity of a novel porphyrin covalently linked to an antifungal fluconazole structure were investigated in DMF and different biomimetic systems, results being compared with those obtained for the non-fluconazole homologoue. Absorption and fluorescence studies indicated that the tetrapyrrolic macrocycle retained its individual spectroscopic properties. Photosensitization ability was first evaluated using 9,10-dimethylanthracene; in microheterogenic media, the porphyrin interacted with sodium bis(2-ethylhexyl)sulfosuccinate reverse micelles and also β-cyclodextrin, photosensitized decomposition of l-tryptophan being observed in these systems. The in vitro photodynamic activity of the photosensitizers when associated with β-cyclodextrin, as tested against Candida albicans, revealed that growth delays imparted by fluconazole alone and the unsubstituted porphyrin were almost additive when the two compounds were used together. However, when the fluconazole was covalently linked to a porphyrin nucleus and exposed to light, reduction in growth delay efficacy was observed relative to the mixed system. [Copyright &y& Elsevier]

Abstract: The photokilling activity of a porphyrin-C60 (P-C60) dyad was evaluated on a Hep-2 human larynx-carcinoma cell line. This study represents the first evaluation of a dyad, with high capacity to form a photoinduced charge-separated state, to act as agent to inactivate cells by photodynamic therapy (PDT). Cell treatment was carried out with 1μM P-C60 incorporated into liposomal vesicles. No dark cytotoxicity was observed using 1μM P-C60 concentration and during long incubation time (24h). The uptake of sensitizer into Hep-2 was studied at different times of incubation. Under these conditions, a value of 1.5nmol/106 cells was found after 4h of incubation showing practically no change even after 24h. The cell survival after irradiation of the cells with visible light was dependent upon light exposure level. A high photocytotoxic effect was observed for P-C60, which inactivated 80% of the cells after 54J/cm2 of irradiation. Moreover, the dyad kept a high photoactivity even under argon atmosphere. Thus, depending on the microenviroment where the sensitizer is localized, this compound could produce a biological photodamage through either a 1O2-mediated photoreaction process or a free radical mechanism under low oxygen concentration. The mechanism of cell death was analyzed by Hoechst-33258, toluidine blue staining, TUNEL and DNA fragmentation. Cell cultures treated for 24h with P-C60 and irradiated with a dose of 54J/cm2 showed a great amount of apoptotic cells (58%). Moreover, changes in cell morphology were analyzed using fluorescence microscopy with Hoechst-33258 under low oxygen concentration. Under this anaerobic condition, necrotic cellular death predominated on apoptotic pathway. There were more apoptotic cells under air irradiation condition than under argon irradiation condition. To determine the apoptotic pathway, caspase-3 activation was studied by caspase-3 activity detection kits. The last results showed that P-C60 induced apoptosis by caspase-3-dependent pathway. These results indicated that molecular dyad, which can form a photoinduced charge-separated state, is a promising model for phototherapeutic agents and they have potential application in cell inactivation by PDT. [Copyright &y& Elsevier]

A novel 5,10,15,20-tetrakis[4-(3- N , N -dimethylaminopropoxy)phenyl]chlorin (TAPC) was synthesized by reduction of the corresponding porphyrin TAPP with p -toluenesulfonhydrazide, followed by selective oxidation with o -chloranil. Spectroscopic properties and the photodynamic activity of these photosensitizers were compared in N , N -dimethylformamide. An increase in the absorption band at 650 nm was found for the chlorin derivative with respect to TAPP. These photosensitizers emit red fluorescence with quantum yields of 0.15. Both compounds were able to photosensitize singlet molecular oxygen with quantum yields of about 0.5. Also, the formation of superoxide anion radical was detected in the presence of TAPC or TAPP and NADH. Photodynamic inactivation was investigated on a Gram-positive bacterium Staphylococcus aureus , a Gram-negative bacterium Escherichia coli and a fungal yeast Candida albicans cells. In vitro experiments showed that TAPC or TAPP were rapidly bound to microbial cells at short incubation periods. These photosensitizers, without intrinsic positive charges, contain four basic amino groups. These substituents can be protonated at physiological pH, increasing the interaction with the cell envelopment. Photosensitized inactivation improved with an increase of both photosensitizer concentrations and irradiation times. After 15 min irradiation, a 7 log reduction of S. aureus was found for treated with 1 μM photosensitizer. Similar result was obtained with E. coli after using 5 μM photosensitizer and 30 min irradiation. Also, the last conditions produced a decrease of 5 log in C. albicans cells. Therefore, TAPC was highly effective as a broad-spectrum antimicrobial photosensitizer. [ABSTRACT FROM AUTHOR]

Abstract: Novel photoactive bridged polysilsesquioxane films were prepared by doped with a porphyrin derivative. The films were formed by acid-catalyzed polycondensation reaction of a precursor of a bridged silsesquioxane, based on the reaction product of (glycidoxypropyl)trimethoxysilane with n-dodecylamine in the presence of 5-(4-carboxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin, followed by solvent evaporation. This procedure allowed obtaining flexible thin films. Absorption and fluorescence spectroscopic analysis showed the characteristic bands of the porphyrin in the visible region indicating that the photosensitizer is mainly embedded as monomer in the films. Photodynamic properties of the polymeric films were studied in solution containing photooxidizable substrates. Singlet molecular oxygen, O2(1Δg), production was observed by the reaction with 9,10-dimethylanthracene and 9,10-anthracenediyl-bis(methylene)dimalonic acid in different media. Also, these films photosensitized the decomposition of l-tryptophan. In vitro investigations showed that these films produce photodynamic inactivation of Candida albicans cells in aqueous suspensions and on their surfaces. These films exhibit a photosensitizing activity causing a ∼2.5 log (99.7%) decrease of cellular survival after 60min of irradiation with visible light. Also, the photocytotoxicity of the surfaces was tested under condition of microbial growth. Yeast cells exposed to the film and illuminated showed growth delay compared with controls. Studies of photodynamic action mechanism showed that the photoinactivation increased in D2O, while cells were protected in the presence of azide ion. In contrast, the addition of mannitol produced a negligible effect on the cellular phototoxicity. These results provide evidence that O2(1Δg) produced by the polymeric film doped with porphyrin can successfully inactivate C. albicans in cell suspensions and deposited on the film surface. [Copyright &y& Elsevier]