Water-soluble Phthalocyanine Research Articles

A set of highly water-soluble tetraethyleneglycol-substituted Zn(ii) phthalocyanines: synthesis, photochemical and photophysical properties, interaction with plasma proteins and in vitro phototoxicity

Three Zn(II) phthalocyanines substituted by hydroxyl-terminated tetraethylene glycol chains have been synthesized. In order to evaluate the potential of these highly water-soluble phthalocyanines as type II-photosensitisers for photodynamic therapy, their structure-activity relationship was assessed by determining relevant photophysical and photochemical properties, such as their aggregation behaviour in aqueous buffers, their fluorescence properties and their efficiency with regard to the generation of singlet oxygen. In addition, evidence for a negligible interaction with plasma proteins in undiluted human plasma was obtained using a recently developed bioanalytical method and compared with the fluorescence quenching approach. These results combined with in vitro data regarding the phototoxicity of these phthalocyanines against HT-29 cancer cells provide evidence for the relevance of the non-peripherally substituted derivative for further in vivo investigations.

Singlet molecular oxygen generation by water-soluble phthalocyanine dendrimers with different aggregation behavior

Phthalocyanines having hydrophilic or lipophilic dendrons were synthesized to investigate the efficiencies of singlet molecular oxygen (1Δg) formation. The introduction of higher generation of dendrons to the central metal ( Si ) of phthalocyanine in vertical direction to their ring plane has resulted in the successful improvement in avoiding aggregate formation that resulted in efficient generation of 1Δg even in water.

The photodegradation of a zinc phthalocyanine

A water-soluble zinc phthalocyanine (Pc), ZnPc (3), bearing 12 dimethylamino groups, which enhance the solubility of the macrocycle was synthesized and characterized. Photobleaching of the compound was examined both in vivo and in vitro. Laser irradiation causes photo-oxidation of the newly synthesized ZnPc. A photobleachable phthalocyanine can be an alternative in imaging; phthalocyanine dyes are used in imaging the cardiovascular system. Besides, it can be used in fluorescein angiography in some cases. When compared to stable ones, a photobleaching ZnPc (3) might be an attractive compound for imaging in medicine.

Monoglycoconjugated water-soluble phthalocyanines. Design and synthesis of potential selectively targeting PDT photosensitisers

A series of asymmetrically substituted phthalocyanines conjugated to four different carbohydrate units has been designed to be used as photosensitisers for potential selective recognition by targeted cells.

Electrochemical Characterization of Mixed Self-Assembled Films of Water-Soluble Single-Walled Carbon Nanotube-Poly(m-aminobenzene sulfonic acid) and Iron(II) Tetrasulfophthalocyanine

The redox activities of water-soluble iron(II) tetrasulfophthalocyanine (FeTSPc) and single-walled carbon nanotube- poly(-aminobenzene sulfonic acid) (SWCNT-PABS) adsorbed on a gold surface precoated with a self-assembled monolayer (SAM) of 2-dimethylaminoethanethiol (DMAET) have been described. Atomic force microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy were employed to probe the buildup and formation of their thin solid films on the gold surface. The solid films exhibited excellent electrochemical stability. The electrode based on the mixed hybrids (Au-DMAET-SWCNT-PABS/FeTSPc) exhibited the fastest electron transport compared to other electrodes , suggesting the ability of the SWCNT-PABS to act as efficient conducting species that facilitate electron transport between the integrated FeTSPc and the underlying gold substrate. Given the paucity of literature in the SAMs of water-soluble phthalocyanine complexes, the proposed fabrication strategy could potentially be extended to other water-soluble metallophthalocyanines and related organometallic complexes.

Photodynamic effects of isosteric water-soluble phthalocyanines on human nasopharynx KB carcinoma cells

The photodynamic activity of water-soluble cationic zinc(II) phthalocyanines using human nasopharynx carcinoma (KB cells) was investigated. A sulfur-linked cationic dye, named: 2,9(10),16(17),23(24)-tetrakis[(2-trimethylammonium)ethylsulfanyl]phthalocyaninatozinc(II) tetraioidide ( 13) is the most active of four sensitizer assays and shows a singlet oxygen quantum yield of 0.58 and a higher bathochromic shift of 10 nm for the Q-band as compared with the oxygen-linked cationic aliphatic phthalocyanine: 2,9(10),16(17),23(24)-tetrakis[(2-trimethylammonium)ethoxy]phthalocyaninatozinc(II) tetraioidide ( 11) and the best photo-stability in water in comparison with their tetra-α-substituted counterparts 1,8(11),15(18),22(25)-tetrakis[(2-trimethylammonium)ethoxy]phthalocyaninatozinc(II) tetraioidide ( 12) and 1,8(11),15(18),22(25)-tetrakis[(2-trimethylammonium)ethylsulfanyl]phthalocyaninatozinc(II) tetraioidide ( 14). Phthalocyanine 13, partially localized in lysosomes, led to cell photoinactivation in a concentration- and light dose-dependent manner. After photodynamic treatment, compound 13 induced an apoptotic response – as indicated by morphological cell changes – an increase in the activity of caspase-3 and the cleavage of poly-ADP-ribose-polymerase substrate (PARP).

Caspase-independent apoptosis, in human MCF-7c3 breast cancer cells, following photodynamic therapy, with a novel water-soluble phthalocyanine

A new water-soluble phthalocyanine derivative, 2,3,9,10,16,17,23,24-octakis(3-aminopropyloxy) phthalocyaninato zinc II ( PoII) was studied as a photosensitizer for photodynamic therapy (PDT) in MCF-7c3 cells. We report here that PoII and red light induces apoptosis. However, the precise mechanism appears to differ from that induced by PDT with other known phthalocyanines. The present study provides evidence that in the case of PoII, caspases do not participate in the apoptotic response. PoII-PDT-treated cells exhibited chromatin condensation and phosphatidylserine (PS) externalization. In the absence of light activation, PoII had no detectable cytotoxic effect. An early event upon PoII-PDT was photodamage to lysosomes, suggesting that they are the primary sites of action. Moreover, the treatment induces Bid activation, mitochondrial swelling and translocation of apoptosis-inducing factor (AIF) to the nucleus. An atypical proteolysis of poly(ADP-ribose) polymerase (PARP) indicative of calpain-like activation was observed. These data support the notion that an alternative mechanism of caspase-independent apoptosis was found in PoII-photosensitized cells.

Coordination of pyridine and piperidine by cobalt complexes of water-soluble porphyrin and phthalocyanines

The extracoordination reactions of nitrogen-containing bases pyridine and piperidine with cobalt complexes of water-soluble porphyrin and phthalocyanines were studied. The stability constants of the axial complexes of cobalt porphyrins and cobalt phthalocyanines with pyridine and piperidine were determined.

Novel ball-type four dithioerythritol bridged metallophthalocyanines and their water-soluble derivatives: Synthesis and characterization, and electrochemical, electrocatalytic, electrical and gas sensing properties

The phthalodinitrile derivative 3 was prepared by the reaction of 1,4-dithioerythritol 1 and 4-nitrophthalonitrile 2 in dry DMF as the solvent in the presence of K(2)CO(3) as the base by the method of nucleophilic substitution of an activated nitro group in an aromatic ring. The template reaction of compound 3 with the corresponding metal salts gave the novel binuclear MPcs of ball-type (M = Zn 4, Co 5, Cu 6) and their water soluble phthalocyanines 7-9 were obtained from refluxing a suspension of the compounds bearing eight OH side groups, in aqueous NaOH (%30) solution. Newly synthesized compounds were characterized by elemental analysis, UV/VIS, IR, MALDI TOF mass and (1)H-NMR spectroscopy techniques. The electronic spectra exhibit an intense π→π* transition of characteristic Q and B bands of the phthalocyanine core. The electrochemical measurements showed the formation of various mixed-valence oxidation and reduction species of 4 and 6 due to weak intramolecular interactions between the two MPc units. Complex 5 displayed a much higher catalytic activity than those of 4 and 6. It was found that oxygen reduction on the 5-based catalyst occurs through a direct 4-electron transfer pathway with a high water selectivity. However, the overpotential for oxygen reduction is high, probably due to a long distance between the two CoPc units in 5. A.c. and d.c. conductivity measurements were performed as a function of temperature (300-543 K) and frequency (40-10(5) Hz). It was found from d.c. measurements that the values of the pre-exponential factor σ(0) for the investigated samples are in the interval from 1.36 × 10(-3) to 6.20 × 10(2)Ω(-1) cm(-1), inferring that the conduction occurs most probably by hopping between the localized states in band tails. Based on the existing theory of a.c. conduction, it has been concluded that for the low frequency region the dominant conduction mechanism is multihopping at high temperatures (>390 K) whereas for the high frequency region the correlated barrier hopping model is the dominant mechanism. The sensing properties of the films for CO(2) gas were also investigated.

Synthesis, electrochemistry and in situ spectroelectrochemistry of water-soluble phthalocyanines

The synthesis, characterization and voltammetric and spectroelectrochemical properties of newly synthesized metal-free and metallo phthalocyanines (M = Co, Cu, Zn) containing four dialkylaminophenoxy or trialkylammoniumphenoxy substituents on peripheral positions have been presented in this work. The new compounds have been characterized by using elemental analysis, UV–Vis, FT-IR, 1H NMR and MS spectroscopic data. Phthalocyanines with trialkylammoniumphenoxy substituents are soluble in aqueous solution over a wide pH range, and these compounds are present as aggregated species in solution as confirmed by the blue shift of Q-bands in their electronic spectra. The electrochemical behavior of the phthalocyanines was investigated by cyclic voltammetry and differential pulse voltammetry on a platinum-working electrode in DCM and DMSO. The voltammetric and spectroelectrochemical measurements of the complexes show that while cobalt phthalocyanine gives both ligand- and metal-based redox processes, metal-free, zinc and copper phthalocyanine complexes give only ligand-based processes in harmony with common phthalocyanine complexes.

Synthesis of Phthalocyanines−ALA Conjugates: Water-Soluble Compounds with Low Aggregation

Syntheses of two water-soluble phthalocyanines (Pc) containing 5-aminolevulinic acid (ALA) linked to the core structure are described. These compounds were prepared by using original functionalizations, and they present remarkable structural and photophysical features, indicating that they could be applied to photodynamic therapy (PDT).

Interaction of tetrasubstituted cationic aluminum phthalocyanine with artificial and natural membranes

A study of the properties of water-soluble tetrasubstituted cationic aluminum phthalocyanine (AlPcN(4)) revealed efficient binding of this photosensitizer to phospholipid membranes as compared with tetrasulfonated aluminum and zinc phthalocyanine complexes. This also manifested itself in enhanced photodynamic activity of AlPcN(4) as measured by the photosensitized damage of gramicidin channels in a planar bilayer lipid membrane. The largest difference in the photodynamic activity of cationic and anionic phthalocyanines was observed in a membrane containing negatively charged lipids, thereby pointing to significant contribution of electrostatic interactions to the binding of photosensitizers to a membrane. Fluoride anions suppressed the photodynamic activity and binding to membrane of both tetraanionic and tetracationic aluminum phthalocyanines, which supports our hypothesis that interaction of charged metallophthalocyanines with phospholipid membranes is mostly determined by coordination of the central metal atom with the phosphate group of lipid.

Water-soluble phthalocyanines mediated photodynamic effect on mesothelioma cells

The new peripherally 2-mercaptopyridine tetrasubstituted zinc phthalocyanine (2) and its quaternized derivative (3) have been synthesized and characterized by elemental analysis, IR, 1 H NMR spectroscopy, electronic spectroscopy and mass spectra. The quaternized compound (3) shows excellent solubility in water, which makes it a potential photosensitizer for use in photodynamic therapy (PDT) of cancer. Fluorescence and singlet oxygen quantum yield measurements were conducted on 2-mercaptopyridine appended zinc phthalocyanines in dimethylsulphoxide (DMSO) for both the non-ionic (2) and quaternized (3) derivatives, and in aqueous media for the water-soluble complex 3. General trends are described for fluorescence and singlet oxygen quantum yields of these compounds. In this study, the cells were incubated with a novel water-soluble zinc phthalocyanine derivative (3) and thereafter the cells were illuminated using broad-band incoherent light source of various energy levels. Cytotoxicity of PDT on two pleural malign mesothelioma cell lines was determined by colorimetric proliferation assay. In addition, after PDT treatment, determination of activity matrix metalloproteinases (MMPs) were evaluated using gelatine zymography.

Synthesis of water-soluble phthalocyanines bearing four or eight d-galactose units

The synthesis and structural characterization of two glycophthalocyanines with four or eight unprotected d-galactose units is reported. The sugar units are linked to the macrocycle via the hydroxyl group located at C-6. The water solubility promoted by the carbohydrate moieties provides a potential application of these phthalocyanine derivatives as photosensitizers in photodynamic therapy.

Layer-by-layer deposition films of copper phthalocyanine derivative; their photoelectrochemical properties and application to solution-processed thin-film organic solar cells

Ultrathin films serving as a light-harvesting and hole-transporting material were fabricated by layer-by-layer deposition of a water-soluble phthalocyanine derivative, copper(II) phthalocyanine-3,4′,4″,4″′-tetrasulfonic acid tetrasodium salt (CuPcTS), and poly(diallyldimethylammonium chloride). The blue-shift of absorption peak and the absorption dichroism of the Q band indicated that CuPcTS molecules in the layer-by-layer films form cofacial dimers or oligomers and that their molecular planes take a three- or two-dimensional orientation in a direction parallel to the substrate depending on a drying process of the film during the deposition. The diffusion constant of hole carriers among CuPcTS molecules in the film was evaluated to be 6.5 × 10 − 11 cm 2 s − 1 in an acetonitrile solution from potential step chronoamperometry measurement. Solution-processed thin-film organic solar cells with a triple-layered structure were developed by combining a hole-transporting layer made of poly(3,4-ethylenedioxythiophene) oxidized with poly(4-styrenesulfonate), a light-harvesting layer of CuPcTS, and an electron-transporting layer of fullerene, in this sequence. Photovoltaic properties of the cells strongly depended on the thickness of CuPcTS films and can be maximized by controlling the thickness at ca. 10 nm.

Synthesis, spectral properties of aluminum polymeric phthalocyanine carboxyl with low aggregation in aqueous solution

A water soluble poly-[tetrakis-(2,3-dicarboxylate phenoxy) methyl methan] aluminum phthalocyanine (AIPPc.(COOH)x) has been synthesized from the cyclization of tetranuclear phthalonitrile and successive hydrolysis of cyano in alkaline solution. The absorption spectra showed low aggregation of this compound in pH 9.18 buffer than that of existing water soluble phthalocyanine compounds. With the addition of Triton X 100, an enhancement of fluorescence emission with quantum yield from 0.4 to 0.83 was observed; contrarily, it was thoroughly quenched by the addition of CATB in suit. A longer life time of singlet state was also detected in presence of Triton X 100. The result indicates that AIPPc.(COOH)x is desired to investigate in fluorescent probe or in fluorescence imaging diagnose.

Immobilization of substituted metall phthalocyanines by nonwoven polypropylene

The specifics of immobilization of water-soluble phthalocyanines on a nonwoven polypropylene (PP), depending on the nature of substitutents and the metal, was studied. The spectral characteristics of the phthalocyanines adsorbed on PP were analyzed.

Syntheses and Properties of a Series of Cationic Water-Soluble Phthalocyanines

A series of symmetrical cationic phthalocyanines (Pcs) with either Zn(II) or Si(IV) metal ions and two bulky axial ligands on the silicon complexes was synthesized in high yields. The photophysical (absorption, emission, fluorescence, and singlet oxygen quantum yields) and cellular (uptake, toxicity, and subcellular localization) properties of this series of Pcs were investigated. The Si(IV)-Pcs exist mainly as monomers in aqueous media and have higher fluorescent quantum yields in protic solvents (methanol and water) than the Zn(II)-Pcs. The presence of eight short PEG groups at the periphery of a Zn(II)-Pc significantly increases its solubility in protic solvents, but a centrally chelated silicon ion and associated bulky axial ligands were more efficient in preventing aggregation of the Pc macrocycles. The singlet oxygen quantum yields for this series of Pcs in DMSO are in the range 0.09-0.15. All Pcs were readily taken up by human HEp2 cells, and the extent of their accumulation within cells depends on their hydrophobic character. Intracellularly, all Pcs localized preferentially within the cell lysosomes. The Zn(II)-Pc 11 and Si(IV)-Pcs 12 and 14 were found to be the most phototoxic (IC50 = 2.2 microM at a 1 J cm(-2) light dose) of this series of compounds.

Synthesis and spectroscopic properties of new water-soluble phthalocyanines containing pyridinium hydrochloride fragments

New 2,9,16,23-tetra[o-(hydroxymethyl)benzyloxy]-substituted phthalocyanines were synthesized. Their reaction with 4-bromopyridine afforded 2,9,16,23-tetra[o-(4-pyridyloxymethyl)benzyloxy]-substituted analogs, treatment of which with HCl led to water-soluble pyridinium salts. Spectroscopic properties of the phthalocyanines obtained were studied and a hypsochromic shift of the Q-band of the hydrochloride as compared with the corresponding pyridinium analogs was observed.

Synthesis and properties of a highly soluble dihydoxo(tetra- tert-butylphthalocyaninato)antimony(V) complex as a precursor toward water-soluble phthalocyanines

The title complex cation, [Sb(tbpc)(OH) 2] + (where tbpc denotes tetra( tert-butyl)phthalocyaninate, C 48 H 48 N 8 2 - ), has been prepared by oxidizing [Sb(tbpc)]I 3 with tert-butyl perbenzoate in CH 2Cl 2, CHCl 3, o-dichlorobenzene and also without solvent in the range of 20–80 °C. This species has been isolated as I 3 - salt and characterized by elemental analysis, ESI-MS, FT-IR, optical absorption and emission, and magnetic circular dichroism spectroscopy. This compound is quite well soluble in common polar organic solvents (e.g., CH 2Cl 2, acetonitrile, acetone) without detectable aggregation at least up to ca. 10 −4 M while much less soluble (e.g., benzene, chloronaphthalene) or insoluble (hexane) in non-polar solvents. Although this compound is insoluble in water, it makes hydrophilic colloids in acetone–water mixtures. The most intense absorption band (Q-band) in a specific solvent red-shifts with an increase in the refractive index of the solvent. However, considerable deviation of the Q-band positions in donor-solvents from linear correlation between the positions and Onsager’s solvent polarity function suggests that there are significant specific chemical interactions between the axial hydroxyl groups and the surrounding donor molecules. The low fluorescence quantum yield (ca. 0.01) for [Sb(tbpc)(OH) 2] + suggests that the singlet excited state of this species is considerably quenched by the presence of antimony ion in the chromophore.