Cationic Phthalocyanine Research Articles

The in Vitro Photo-Sonodynamic Combinatorial Therapy Activity of Cationic and Zwitterionic Phthalocyanines on Mcf-7 and Hela Cancer Cell Lines

The in Vitro Photo-Sonodynamic Combinatorial Therapy Activity of Cationic and Zwitterionic Phthalocyanines on Mcf-7 and Hela Cancer Cell Lines

A Photochemical Study of Photo-Induced Electron Transfer from Dnas to a Cationic Phthalocyanine Derivative

A Photochemical Study of Photo-Induced Electron Transfer from Dnas to a Cationic Phthalocyanine Derivative

Peripherally Crowded Cationic Phthalocyanines as Efficient Photosensitizers for Photodynamic Therapy.

Photodynamic therapy is a treatment modality of cancer based on the production of cytotoxic species upon the light activation of photosensitizers. Zinc phthalocyanine photosensitizers bearing four or eight bulky 2,6-di(pyridin-3-yl)phenoxy substituents were synthesized, and pyridyl moieties were methylated. The quaternized derivatives did not aggregate at all in water and retained their good photophysical properties. High photodynamic activity of these phthalocyanines was demonstrated on HeLa, MCF-7, and EA.hy926 cells with a very low EC50 of 50 nM (for the MCF-7 cell line) upon light activation while maintaining low toxicity in the dark (TC50 ≈ 600 μM), giving thus good phototherapeutic indexes (TC50/EC50) above 1400. The compounds localized primarily in the lysosomes, leading to their rupture after light activation. This induced an apoptotic cell death pathway with secondary necrosis because of extensive and swift damage to the cells. This work demonstrates the importance of a bulky and rigid arrangement of peripheral substituents in the development of photosensitizers.

Effect of ultrasonic frequency and power on the sonodynamic therapy activity of cationic Zn(II) phthalocyanines

We report on the sonodynamic activity of cationic phthalocyanines (Pcs) and the effect of the variation of two parameters: ultrasound frequency and power (Par I (1 MHz, 1 W cm−2), Par II (1 MHz, 2 W cm−2), Par III (3 MHz, 1 W cm−2) and Par IV (3 MHz, 2 W cm−2)) on the efficiency of their reactive oxygen species generation and cancer eradication in vitro thereof. Where Par stands for the various combinations of these parameters. Four Pcs were investigated with substituents bearing diethylamine, ortho- and para-pyridine and morpholine groups. Overall, the para-pyridine and morpholine Pcs showed substantial sono-activity in the various ultrasound parameters with Par I and IV generally showing better singlet oxygen and hydroxyl radicals generation confirmed by electron paramagnetic resonance spectroscopy. In some cases, very high hydroxyl radicals' generation was observed at Par II. Furthermore, the fragmentation of the Pcs after Par II treatments was confirmed using UV–vis and magnetic circular dichroism spectroscopy. The reactive species generation efficacy decreased at Par III for all samples. Ultrasound assisted cytotoxicity of the Pcs was confirmed in vitro using the human (Michigan Cancer Foundation-7) breast cancer cell line.

Stepwise binding of a cationic phthalocyanine derivative to an all parallel-stranded tetrameric G-quadruplex DNA

Interaction between an Ga(III) phthalocyanine (Pc) derivative bearing eight N-methylpyridinium groups at peripheral β-positions (2,3,6,7,10,11,14,15-octakis-[N-methyl-(4-methylpyridinium-3-yloxy)phthalocyaninato] chloro gallium(III) iodide (GaPc)) and an all parallel-stranded tetrameric G-quadruplex formed from a heptanucleotide d(TTAGGGT) ([d(TTAGGGT)]4) has been investigated to elucidate the molecular recognition of G-quadruplex DNA by the Pc derivative, which provides a useful insight as to the design of G-quadruplex ligands suitable for various in vitro and in vivo applications. We found that GaPc binds to the A3G4 and G6T7 steps of [d(TTAGGGT)]4, with binding constants of (21 ± 2) × 106 and (0.09 ± 0.06) × 106 M−1, respectively, to form a 2:1 complex. Obviously, upon the binding of GaPc to each of the sites, the π-π stacking and electrostatic interactions of the Pc moiety and positively-charged side chains of GaPc with a G-quartet and the negatively-charged phosphate groups in nearby phosphodiester bonds of the DNA, respectively, are major driving forces for the complexation. Considering the similarity in the local structural environment between the A3G4 and G6T7 steps of [d(TTAGGGT)]4, the remarkably large difference in the GaPc-binding affinity between them is most likely accounted for by the effect of the polarity of the GaPc-binding site on the intermolecular electrostatic interaction. This finding provides valuable insights as to the design of Pc derivatives as G-quadruplex ligands.

Phthalocyanine-DNA origami complexes with enhanced stability and optical properties.

In this communication, electrostatically assembled phthalocyanine (Pc)-DNA origami (DO) complexes are formed and their optical properties are demonstrated. The formation of the complex prevents the Pc aggregation, thus yielding an enhanced optical response and photooxidative resilience towards aggregation in biologically relevant media. Simultaneously, the Pc protects the DO against enzymatic digestion. Both features solve previous drawbacks associated with phthalocyanine photosensitizers and DNA nanocarriers. The studied complexes may find use in technologies related to the photogeneration of singlet oxygen, e.g., photocatalysis, diagnositic arrays and photodynamic therapy.

Multilayer assemblies of a Cu-phthalocyanine with Dawson type polyoxometalates (POMs) for the electrocatalytic reduction of phosphate

A series of multilayer electrode assemblies have been fabricated through the layer by layer (LBL) technique composed of the water soluble Cu-phthalocyanine (Alcian Blue 8GX) cationic species and a range of Dawson type polyoxometalates (POMs) on glassy carbon electrodes in pH 7.0. Electrochemistry for both the cationic phthalocyanine and the incorporated POMs is clearly visible. The layers were characterized by cyclic voltammetry, AC impedance, X-ray photoelectron spectroscopy (XPS), Field Emission-Scanning Electron Microscopy (FE-SEM) and Atomic Force Microscopy (AFM). The layers were found to electrocatalytically reduce phosphate at pH 7.

Photoinactivation of microorganisms with sub-micromolar concentrations of imidazolium metallophthalocyanine salts

The increasingly limited therapeutic options for the treatment of infections caused by multi-resistant Gram-negative bacteria due to the alarming increase in bacteria resistance, renewed interest in photodynamic inactivation (PDI) of bacteria. We address PDI of multi-resistant bacteria with a new family of cationic tetra-imidazolyl phthalocyanines bearing a diversity of cationizing alkylic chain sizes, degrees of cationization and coordinating metals. The antimicrobial activities of the phthalocyanines under white light against Gram-positive and Gram-negative bacteria have remarkable differences in efficacy. We relate their spectroscopic and photophysical properties with the generation of reactive oxygen species (ROS), biological performance and structural features. We show that sub-micromolar concentrations of a Zn(II) tetra-ethyl cationic phthalocyanine reduce colonies of Gram-negative bacteria (E. coli, P. aeruginosa) and C. albicans by 7 log units while leaving mammalian cells unharmed. This is a new lead to address hard-to-treat localized infections.

Phthalocyanine-Virus Nanofibers as Heterogeneous Catalysts for Continuous-Flow Photo-Oxidation Processes.

The generation of highly reactive oxygen species (ROS) at room temperature for application in organic synthesis and wastewater treatment represents a great challenge of the current chemical industry. In fact, the development of biodegradable scaffolds to support ROS-generating active sites is an important prerequisite for the production of environmentally benign catalysts. Herein, the electrostatic cocrystallization of a cationic phthalocyanine (Pc) and negatively charged tobacco mosaic virus (TMV) is described, together with the capacity of the resulting crystals to photogenerate ROS. To this end, a novel peripherally crowded zinc Pc (1) is synthesized. With 16 positive charges, this photosensitizer shows no aqueous aggregation, and is able to act as a molecular glue in the unidimensional assembly of TMV. A step-wise decrease of ionic strength in mixtures of both components results in exceptionally long fibers, constituted by hexagonally bundled viruses thoroughly characterized by electron and confocal microscopy. The fibers are able to produce ROS in a proof-of-concept microfluidic device, where they are immobilized and irradiated in several cycles, showing a resilient performance. The bottom-up approach also enables the light-triggered disassembly of fibers after use. This work represents an important example of a biohybrid material with projected application in light-mediated heterogeneous catalysis.

Effect of hyaluronic acid on the State and photoactivity of Zn(II) phthalocyanine cationic derivative in mixed aqueous solutions

The effect of the hyaluronic acid (HA) on the state and photoactivity of the cationic phthalocyanine photosensitizer in mixed solutions was studied by UV–vis absorption, fluorescence, FT-IR spectroscopy and dynamic light scattering methods. As a cationic photosensitizer, the Cholosens® (ChS) was used, which is Zn phthalocyanine choline derivative and is designed for photodynamic therapy of cancer and infectious diseases. It was found that the state of mixed solutions depends on the molar ratio HA/ChS. In mixtures with HA/ChS ≤ 7.0, with an increase in the HА content the fluorescence intensity decreases up to complete quenching at HA/ChS = 7.0 and precipitation is observed due to the formation of a supramolecular complex. The hydrodynamic radius and zeta potential of complex primary particles in the metastable state preceding the phase separation are determined. Mixtures with HA/ChS > 7.5 are stable solutions with no signs of phase separation. The fluorescence intensity increases with an increase in HA/ChS from 7.0 to 20, and with a further increase in the HА content remains constant and is about 80% relative to ChS fluorescence without HA. Gamma-irradiation of HA causes a decrease in its ability to complexate with ChS due to a decrease in the polymer chain length.

Synthesis and Biological Uses of A3B Type Water‐Soluble Phthalocyanine Alternate to Alcian Blue

AbstractThis study describes the synthesis and characterization of new non‐symmetric cationic phthalocyanine derivatives and their capability for use in staining of microscopic normal and pathological tissue sections, polyacrylamide gel staining, and spectrophotometric analyses. These new synthesized compounds have specifically stained the glycosaminoglycans (GAGs) in the matrix of cartilage tissue of the trachea. In addition, the mucus produced by the stomach, the small intestine and the colon tissue were stained with non‐symmetrical cationic phthalocyanines comparable to the Alcian Blue 8GX. In addition, the determination of GAGs and glycoproteins in polyacrylamide gels has also been evaluated. Besides, the usage of these compounds to spectrophotometrically measure GAGs in biological fluids was also investigated. We have found that 6 and 7 are good alternatives to Alcian Blue 8GX due to comparable staining performance and interaction with biological molecules, especially acidic components such as acidic GAGs and mucin. These dyes have good solubility with quaternary ammonium groups effecting their binding performance to biological molecules.

Synthesis and Aggregation of Cationic Zinc and Magnesium Phthalocyanines Containing 4-(3,5-Dimethyl-1H-pyrazol-1-yl)phenoxy Groups

Tetracationic metal phthalocyanines were synthesized by the quaternization of the Cs-regioisomers of tetrasubstituted zinc and magnesium phthalocyanines containing 3,5-dimethylpyrazole fragments. The individuality of the synthesized compounds was confirmed by HPLC‒mass spectrometry. The aggregation of the cationic metal phthalocyanines in water and aqueous-organic media, as well as in the presence of Triton X- 100 was studied. The dependence of the dimerization constant on the polarity of mixed solvents was determined.

Photophysicochemical properties and photodynamic therapy activity of highly water-soluble Zn(II) phthalocyanines

The syntheses of two zinc(II) phthalocyanines (ZnPcs) having either imidazole (ZnPc 1) or pyridiloxy (ZnPc 2) moieties as their macrocycle substituents are reported. Quaternization of the ZnPcs with methyl iodide afforded water soluble cationic phthalocyanines. The photophysical, photochemical properties and photodynamic therapy (PDT) activity of the ZnPcs were studied in solution. The fluorescence quantum yield and lifetime of ZnPc 1 were higher as compared to ZnPc 2. ZnPc 2 afforded higher triplet state (ΦT) and singlet oxygen quantum yields (ΦΔ) in comparison to ZnPc 1. The PDT activity of ZnPcs was investigated against human breast adenocarcinoma cells (MCF–7). The two compounds afforded a very minimal in vitro dark cytotoxicity with 85% viable cells at concentration ≤80 μM. On irradiation of the cells having the ZnPcs, ≥50% cell death was recorded for ZnPc 1 which was also evidenced by the cells photo–micrograph.

Spectroscopic and thermodynamic approach to the interaction of nonperipherally substituted cationic phthalocyanines with calf thymus (CT)-DNA

Novel, nonperipherally tetrasubstituted cationic metal-free and metallophthalocyanines (Zn, In) were synthesized in the present study. The binding constants, the disappearance of quenching effect of all cationic phthalocyanines on the fluorescence intensity of SYBR Green--disodium salt of deoxyribonucleic acid (DNA) from calf thymus complex, and the changes in T$_{m}$ of double helix DNA with thermal denaturation profile were investigated by UV-Vis and fluorescence spectrophotometric methods. To investigate the spontaneity of the reactions between DNA and novel quaternized phthalocyanines in buffer, thermodynamic parameters were employed.

Development of Functional Phthalocyanine-Based Associate towards an Effective Fluorimetric Detection of Hg(II).

In acidic media, cationic phthalocyanine Alcian blue 8GX, has an efficient fluorescence quenching effect on anionic phthalocyanine tetrasulphoaluminium phthalocyanines (AlS4Pc), forming an almost non-fluorescent associate. Based on this discovery, a red-emitting fluorescent probe consisted of AlS4PC and Alcian blue 8GX has been developed through molecular assembly. Further studies indicated that the presence of Hg(II) ion has a significant fluorescence recovery effect of the probe. Notably, only Hg(II) can significantly restore the fluorescence of AlS4Pc-Alcian blue 8GX system which was revealed from the screening experiments of common metal ions, which confirmed that the fluorescence recovery by other metal ions is very weak or even unrestored, showing high specificity and sensitivity AlS4Pc-Alcian blue 8GX to Hg(II). Thus, a new fluorimetry for Hg(II) with high specificity and high sensitivity in a wide concentration range has been established using AlS4Pc-Alcian blue 8GX associate as a red-emitting fluorescent probe. It is more noteworthy that this study opens a new way for development and application of functional phthalocyanine based red-emitting fluorescent probes.

Correction: Cationic phthalocyanine dendrimers as potential antimicrobial photosensitisers.

Correction for 'Cationic phthalocyanine dendrimers as potential antimicrobial photosensitisers' by Rubén Ruiz-González et al., Org. Biomol. Chem., 2017, 15, 9008-9017.

Photodynamic inactivation of multiresistant bacteria (KPC) using zinc(II)phthalocyanines

The worldwide increase in antibiotic resistance has led to search of alternatives anti-microbial therapies such as photodynamic inactivation. The aim of this paper was to evaluate the photodynamic activity in vitro of a neutral and two cationic Zn phthalocyanines. Their photokilling activity was tested on Escherichia coli ATCC 25922 and Klebsiella pneumoniae Carbapenemase (KPC)-producing. After treating bacteria with phthalocyanines, the cultures were irradiated with white light. As a result, the bacteria were inactivated in presence of cationic phthalocyanines. The photoinactivation was dependent of the irradiation time and phthalocyanine concentration. The most effective photosensitizer on KPC-producing was Zinc(II)tetramethyltetrapyridino[2,3-b:2′,3′-g:2″,3″-l:2‴,3‴-q]porphyrazinium methylsulfate (ZnTM2,3PyPz). After irradiation using the water soluble ZnTM2,3PyPz (3μM) the viability of KPC (30min of irradiation) and E. coli (10min of irradiation) decreased ≈99.995%.

Antimicrobial and anticancer photodynamic activity of a phthalocyanine photosensitizer with N-methyl morpholiniumethoxy substituents in non-peripheral positions

Photodynamic therapy involves the use of a photosensitizer that is irradiated with visible light in the presence of oxygen, resulting in the formation of reactive oxygen species. A novel phthalocyanine derivative, the quaternary iodide salt of magnesium(II) phthalocyanine with N-methyl morpholiniumethoxy substituents, was synthesized, and characterized. The techniques used included mass spectrometry (MALDI TOF), UV–vis, NMR spectroscopy, and photocytotoxicity against bacteria, fungi and cancer cells. The phthalocyanine derivative possessed typical characteristics of compounds of the phthalocyanine family but the effect of quaternization was observed on the optical properties, especially in terms of absorption efficiency. The results of the photodynamic antimicrobial effect study demonstrated that cationic phthalocyanine possesses excellent photodynamic activity against planktonic cells of both Gram-positive and Gram-negative bacteria. The bactericidal effect was dose-dependent and all bacterial strains tested were killed to a significant degree by irradiated phthalocyanine at a concentration of 1×10−4M. There were no significant differences in the susceptibility of Gram-positive and Gram-negative bacteria to the applied photosensitizer. The photosensitivity of bacteria in the biofilm was lower than that in planktonic form. No correlation was found between the degree of biofilm formation and susceptibility to antimicrobial photodynamic inactivation. The anticancer activity of the novel phthalocyanine derivative was tested using A549 adenocarcinomic alveolar basal epithelial cells and the human oral squamous cell carcinoma cells derived from tongue (HSC3) or buccal mucosa (H413). No significant decrease in cell viability was observed under different conditions or with different formulations of the compound.

An overview on the impact of cationic phthalocyanine complexes for inactivation of drug-resistant microorganisms

An overview on the impact of cationic phthalocyanine complexes for inactivation of drug-resistant microorganisms

Photodynamic antimicrobial chemotherapy with cationic phthalocyanines against Escherichia coli planktonic and biofilm cultures

Cationic phthalocyanines (Pcs) combine with photodynamic antimicrobial chemotherapy (PACT) presents excellent antibacterial activity to Gram-negative bacteriaE. coli.