zn(ii)-phthalocyanine and aluminum-phthalocyanine

Topics: Cells, Cultured; Hematoporphyrin Photoradiation; Humans; Indoles; Isoindoles; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Soft Tissue Infections; Staphylococcal Infections; Streptococcal Infections; Suppuration; Zinc Compounds

This study investigated the activity of photosensitive phthalocyanines on promastigotes and amastigotes of Leishmania (L.) amazonensis. Aluminum phthalocyanine chloride (AlPcCl), Aluminum phthalocyanine hydroxide (AlPcOH) and zinc phthalocyanine (PcZn) were tested in the presence (matte red LED, potency of 2.5-2.3 μW for 30 min) and absence of light against L. amazonensis promastigotes and the parasite viability was evaluated after 24, 48 and 72 h. The amastigote forms were treated with AlPcCl and AlPcOH, following the same lighting protocols described for the promastigote forms, being evaluated after 24 h. Cytotoxicity to human erythrocytes and peritoneal macrophages was also evaluated. The results showed that AlPcCl and AlPcOH in the presence of light have antileishmania activity, with leishmanistatic effects on promastigotes and amastigotes of L. amazonensis, without causing cytotoxicity to peritoneal macrophages and erythrocytes. The concentrations that inhibited 50% of the promastigote forms after 24 h of light exposure were 0.21 ± 0.08 μM for AlPcCl and 0.23 ± 0.06 μM for AlPcOH. In 48 h and 72 h after the treatment, the IC

Topics: Animals; Erythrocytes; Humans; Indoles; Isoindoles; Leishmania; Macrophages; Mice; Mice, Inbred BALB C; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Zinc Compounds

The present work reports the synthesis, photophysical and photochemical characterization and photodynamic evaluation of zinc, aluminum and metal free-base tetracarboxy-phthalocyanines (ZnPc, AlPc and FbPc, respectively). To evaluate the possible application of phthalocyanines as a potential photosensitizer the photophysical and photochemical characterization were performed using aqueous (phosphate-buffered solution, PBS) and organic (dimethyl sulfoxide, DMSO) solvents. The relative lipophilicity of the compounds was estimated by the octanol-water partition coefficient and the photodynamic activity evaluated through the photooxidation of a protein and photohemolysis. The photooxidation rate constants (k) were obtained and the hemolytic potential was evaluated by the maximum percentage of hemolysis achieved (Hmax) and the time (t50) to reach 50% of the Hmax. Although these phthalocyanines are all hydrophilic and possess very low affinity for membranes (log PO/W=-2.0), they led to significant photooxidation of bovine serum albumin (BSA) and photohemolysis. Our results show that ZnPc was the most efficient photosensitizer, followed by AlPc and FbPc; this order is the same as the order of the triplet and singlet oxygen quantum yields (ZnPc>AlPc>FbPc). Furthermore, together, the triplet, fluorescence and singlet oxygen quantum yields of zinc tetracarboxy-phthalocyanines suggest their potential for use in theranostic applications, which simultaneously combines photodiagnosis and phototherapy.

Topics: Animals; Cattle; Dimethyl Sulfoxide; Erythrocyte Membrane; Hemolysis; Humans; Hydrophobic and Hydrophilic Interactions; Indoles; Isoindoles; Light; Models, Molecular; Organometallic Compounds; Oxidation-Reduction; Photolysis; Photosensitizing Agents; Serum Albumin, Bovine; Singlet Oxygen; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Water; Zinc Compounds

The effect of ionic substituents in zinc and aluminum phthalocyanine molecules and of membrane surface charge on the interaction of dyes with artificial membranes and enterobacterial cells, as well as on photosensitization efficiency was studied. It has been shown that increasing the number of positively charged substituents enhances the extent of phthalocyanine binding to Escherichia coli cells. This, along with the high quantum yield of singlet oxygen generation, determines efficient photodynamic inactivation of Gram-negative bacteria by zinc and aluminum octacationic phthalocyanines. The effect of Ca2+ and Mg2+ cations and pH on photodynamic inactivation of enterobacteria in the presence of octacationic zinc phthalocyanine has been studied. It has been shown that effects resulting in lowering negative charge on outer membrane protect bacteria against photoinactivation, which confirms the crucial role in this process of the electrostatic interaction of the photosensitizer with the cell wall. Electrostatic nature of binding is consistent with mainly electrostatic character of dye interactions with artificial membranes of different composition. Lower sensitivity of Proteus mirabilis to photodynamic inactivation, compared to that of E. coli and Salmonella enteritidis, due to low affinity of the cationic dye to the cells of this species, was found.

Topics: Cations; Enterobacteriaceae; Escherichia coli; Fluorescent Dyes; Hydrogen-Ion Concentration; Indoles; Isoindoles; Organometallic Compounds; Photosensitizing Agents; Singlet Oxygen; Static Electricity; Zinc Compounds

Photophysical parameters for zinc and aluminium tetracarboxylphthalocyanines (ZnTCPc and AlTCPc, respectively) and their octacarboxy substituted counterparts (ZnOCPc and AlOCPc) were studied. Data for the fluorescence quenching of the complexes by benzoquinone (BQ) were treated using the Stern-Volmer analysis, and the quenching was found to follow a diffusion-controlled (dynamic) bimolecular mechanism. Theoretical values of bimolecular rate constant for complex-BQ interactions were determined using the Stokes-Einstein-Smoluchowski model; and the values, together with the Stern-Volmer quenching constants were used in calculating the fluorescence lifetimes of the complexes. The thermodynamics of the MPc-BQ interaction, in terms of solvent reorientation energy is also discussed.

Topics: Benzoquinones; Carboxylic Acids; Electrons; Indoles; Isoindoles; Molecular Conformation; Organometallic Compounds; Solvents; Spectrometry, Fluorescence; Zinc Compounds

Photodynamic therapy is a two-step procedure, involving the use of photosensitizing agents followed by selective illumination of the target lesion with visible light. It produces highly reactive oxygen species and subsequent cellular damage.. This study was designed to determine whether Leishmania chagasi and L. panamensis promastigotes were sensitive to photodynamic therapy in vitro.. Leishmania promastigotes were treated with aluminium phthalocyanine chloride and zinc phthalocyanine photosensitizers before illumination with visible light at 670 nm. The parasite photoactivity was calculated by sigmoidal regression analysis.. Leishmania chagasi promastigotes were highly photosensitive to aluminium phthalocyanine chloride treatment with effective inhibitory dose50 (ED50) concentration values of 0.0033, 0.0083 and 0.0093 microM upon exposure to 10.0, 5.0, and 2.5 J/cm2 light intensities respectively. By contrast, the activity of aluminium phthalocyanine chloride on L. panamensis was significantly lower (P < 0.01) with ED50 values of 0.17, 0.25, 0.34 microM at the same light intensities. Zinc phthalocyanine activity was significantly (P < 0.01) less active than aluminium phthalocyanine chloride on both strains of these two species and no differences in zinc phthalocyanine activity were found between them. A dose-response phototoxic effect with both phthalocyanines was observed. Parasite inhibition was not observed after aluminium phthalocyanine chloride or zinc phthalocyanine treatment in the dark. The reference drugs hexadecylphosphocholine and amphotericin B were not photoactive.. Treatment of Leishmania promastigotes with aluminium phthalocyanine chloride and zinc phthalocyanine followed by illumination with visible light at 670 nm inhibited in vitro growth of promastigotes of L. chagasi and L. panamensis. Photodynamic therapy against Leishmania could be a promising strategy for leishmaniasis treatment.

Topics: Animals; Indoles; Isoindoles; Leishmania; Organometallic Compounds; Photochemotherapy; Zinc Compounds

The photodynamic effects of sulphonated zinc and aluminum phthalocyanine derivatives as well as phosphonated aluminum phthalOcyanine on the firing of isolated crayfish mechanoreceptor neurons were studied. After 30 min staining neurons were irradiated with He-Ne laser (632.8 nm, 0.3 W/cm2) and changes in neuron firing frequency were recorded. Neuron firing was found to be very sensitive to photodynamic effect and could serve as a sensitive indicator of cell photodamage. It changed the firing level and then died at nanomolar concentrations of phthalocyanines. The dynamics of the neuron responses to photodynamic effects included stages of firing activation and/or inhibition prior to irreversible firing abolition. The order of these stages depended on photosensitizer type and concentration. The comparison of the dependencies of neuron lifetime on photosensitizer concentrations showed ZnPcS2 to be the most effective photosensitizer.

Topics: Aluminum; Animals; Astacoidea; In Vitro Techniques; Indoles; Isoindoles; Lasers; Mechanoreceptors; Neurons; Organometallic Compounds; Photosensitizing Agents; Structure-Activity Relationship; Zinc; Zinc Compounds

Confocal fluorescence microscopy, using a newly constructed laser line-scanning confocal microscope, was applied to an investigation of the early stages of photoinduced destruction of V79-4 Chinese hamster fibroblasts using aluminum and zinc phthalocyanines as photosensitizers. Results obtained in this work show that aluminum and zinc phthalocyanines, once internalized, localize in perinuclear sites that are disrupted upon light exposure resulting in fluorescence redistribution. The combination of laser-line scanning with charge-coupled device detection used in the confocal microscope developed in this work can enable rapid high-resolution sequential imaging, which is ideal for studying photoinduced intracellular fluorescence dynamics.

Topics: Animals; Cell Line; Cricetinae; Cricetulus; Indoles; Isoindoles; Lasers; Microscopy, Confocal; Microscopy, Fluorescence; Organometallic Compounds; Photobiology; Photochemotherapy; Photosensitizing Agents; Zinc Compounds

In order to obtain information concerning the mechanism(s) of metallo-phthalocyanine (MePcS4) photosensitized damage of DNA constituents, the EPR-spin trapping method in conjunction with liquid chromatography was used to study thymidine (dThd) free radicals formed during photosensitization or exposure to gamma-radiation in solution. Under specified conditions two dThd free radical species, 5-hydroxy-5,6-dihydrothymidine-6-yl and 6-hydroxy-5,6-dihydrothymidine-5-yl, were formed both during exposure to ionizing radiation and photosensitization. These results imply that identical reactive intermediates (*OH radicals) are involved in the radiolytic and photosensitized oxidation of dThd. A light-dependent, Fenton-type mechanism is proposed to explain the generation of hydroxyl radicals during MePcS4 photosensitization.

Topics: Electron Spin Resonance Spectroscopy; Free Radicals; Gamma Rays; Indoles; Isoindoles; Organometallic Compounds; Photosensitizing Agents; Thymidine; Zinc Compounds

The photodynamic inactivation of retroviruses was investigated using aluminium and zinc phthalocyanine (Pc) derivatives. The N2 retrovirus packaged in either of the two murine cell lines, Psi2 and PA317, was used as a model for enveloped viruses. AlPc derivatives were found to be more effective photodynamically for inactivation of the viruses than the corresponding ZnPc derivatives. Sulphonation of the Pc macrocycle reduced its photodynamic activity progressively for both AlPc and ZnPc. Fluoride at 5 mM during light exposure completely protected viruses against inactivation by AlPc. In the presence of F-, inactivation by the sulphonated derivatives AlPcS1 and AlPcS4 was reduced 2.5- and twofold respectively. In a biological membrane (erythrocyte ghosts), F- had no significant effect on AlPcS4-sensitized lipid peroxidation. Under similar conditions, cross-linking of spectrin monomers in ghosts is drastically inhibited (E. Ben-Hur and A. Orenstein, Int. J. Radiat. Biol., 60 (1991) 293-301). Since Pc derivatives do not inactivate non-enveloped viruses, it is hypothesized that inactivation occurs by photodynamic damage to envelope protein(s). Substitution of sulphonic acid residues reduces the binding of Pc derivatives to the envelope protein(s), thereby diminishing their photodynamic efficacy and the ability of F- to modify it.

Topics: Aluminum; Animals; Cell Line; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Erythrocyte Membrane; Humans; Indoles; Isoindoles; Light; Lipid Peroxidation; Mice; Organometallic Compounds; Retroviridae; Zinc; Zinc Compounds