Water-soluble Zinc Phthalocyanine Research Articles

Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques.

Phthalocyanines are ideal candidates as photosensitizers for photodynamic therapy (PDT) of cancer due to their favorable chemical and photophysical properties. However, their tendency to form aggregates in water reduces PDT efficacy and poses challenges in obtaining efficient forms of phthalocyanines for therapeutic applications. In the current work, polyvinylpyrrolidone (PVP) and micellar formulations were compared for encapsulating and monomerizing a water-soluble zinc phthalocyanine bearing four non-peripheral triethylene glycol chains (Pc1). 1H NMR spectroscopy combined with UV-vis absorption and fluorescence spectroscopy revealed that Pc1 exists as a mixture of regioisomers in monomeric form in dimethyl sulfoxide but forms dimers in an aqueous buffer. PVP, polyethylene glycol castor oil (Kolliphor RH40), and three different triblock copolymers with varying proportions of polyethylene and polypropylene glycol units (termed P188, P84, and F127) were tested as micellar carriers for Pc1. 1H NMR chemical shift analysis, diffusion-ordered spectroscopy, and 2D nuclear Overhauser enhancement spectroscopy was applied to monitor the encapsulation and localization of Pc1 at the polymer interface. Kolliphor RH40 and F127 micelles exhibited the highest affinity for encapsulating Pc1 in the micellar core and resulted in intense Pc1 fluorescence emission as well as efficient singlet oxygen formation along with PVP. Among the triblock copolymers, efficiency in binding and dimer dissolution decreased in the order F127 > P84 > P188. PVP was a strong binder for Pc1. However, Pc1 molecules are rather surface-attached and exist as monomer and dimer mixtures. The results demonstrate that NMR combined with optical spectroscopy offer powerful tools to assess parameters like drug binding, localization sites, and dynamic properties that play key roles in achieving high host-guest compatibility. With the corresponding adjustments, polymeric micelles can offer simple and easily accessible drug delivery systems optimizing phthalocyanines' properties as efficient photosensitizers.

The synthesis of novel water-soluble zinc (II) phthalocyanine based photosensitizers and exploring of photodynamic therapy activities on the PC3 cancer cell line.

In this study, Schiff base substituted phthalocyanine complexes (Zn1c, Zn2c) and their quaternized derivatives (Q-Zn1c, Q-Zn2c) were synthesized for the first time. Their structures have been characterized by FT-IR, 1H-NMR, UV-Vis, mass spectrometry and elemental analysis as well as. The photophysicochemical properties (fluorescence, singlet oxygen and photodegradation quantum yield) of these novel complexes were investigated in dimethylsulfoxide (DMSO) for both non-ionic and quaternized cationic phthalocyanine complexes and in aqueous solution for quaternized cationic phthalocyanine complexes. Water soluble cationic phthalocyanine compounds gave good singlet oxygen quantum yield (0.65 for Q-Zn1c, 0.66 for Q-Zn2c in DMSO; 0.65 for Q-Zn2c in aqueous solution). The binding of Q-Zn1c and Q-Zn2c to BSA/DNA was studied by using UV-Vis and fluorescence spectroscopy and these. Studies indicate that the mechanism of BSA quenching by quaternized zinc(II) phthalocyanines was static quenching. Quaternized zinc(II) phthalocyanines interacted with ct-DNA by intercalation. Quaternized zinc(II) phthalocyanines caused a decrease in cell viability and triggered apoptotic cell death after PDT was applied at a concentration that did not have a toxic effect on their own. Q-Zn1c and Q-Zn2c mediated PDT reduced the activity of SOD, CAT, GSH while increased MDA level in the prostate cancer cells. Furthermore, expression of apoptotic proteins after PDT was examined. The results revealed that the synthesized water soluble quaternized zinc(II) phthalocyanine complexes (Q-Zn1c and Q-Zn2c) are promising potential photosensitizers for PDT.

Assembling Artificial Photosynthetic Models in Water Using β-Cyclodextrin-Conjugated Phthalocyanines as Building Blocks.

Two water-soluble zinc(II) phthalocyanines substituted with two or four permethylated β-cyclodextrin (β-CD) moieties at the α positions have been utilized as building blocks for the construction of artificial photosynthetic models in water. The hydrophilic and bulky β-CD moieties not only can increase the water solubility of the phthalocyanine core and prevent its stacking in water but can also bind with a tetrasulfonated zinc(II) porphyrin (ZnTPPS) and/or sodium 2-anthraquinonesulfonate (AQ) in water through host-guest interactions. The binding interactions of these species have been studied spectroscopically, while the photoinduced processes of the resulting complexes have been investigated using steady-state and time-resolved spectroscopic methods. In the ternary complexes, the ZnTPPS units serve as light-harvesting antennas to capture the light energy and transfer it to the phthalocyanine core via efficient excitation energy transfer. The excited phthalocyanine is subsequently quenched by the electron-deficient AQ units through electron transfer. Femtosecond transient absorption spectroscopy provides clear evidence for the singlet-singlet energy transfer from the photo-excited ZnTPPS to the phthalocyanine core with a rate constant (kENT ) in the order of 109 s-1 . The population of phthalocyanine radical cations indicates the occurrence of electron transfer from the excited phthalocyanine to the AQ moieties, forming a charge-separated state.

NIR-Photocontrolled Aqueous RAFT Polymerization with Polymerizable Water-Soluble Zinc Phthalocyanine as Photocatalyst

In order to give an answer for the challenges of long wavelength-photocontrolled radical polymerization in aqueous solutions and to address the shortcomings of conventional near-infrared (NIR) photocatalysts (PCs) that are difficult to subject to post-treatment, we designed and synthesized a series of β-tetra-substituted water-soluble zinc phthalocyanines (β-TS-Zns) as the NIR PCs for reversible addition-fragmentation chain transfer (RAFT) polymerization successfully under irradiation with NIR (λmax = 730 nm) light at room temperature. Importantly, the NIR PCs can also be designed as polymerizable monomers and covalently loaded on the polymer chains, which are endowed with permanent NIR photocatalysis of the resultant polymers. Moreover, the polymerization can not only be carried out in water but also in phosphate buffer saline (PBS) solution, yielding polymers with controlled molar mass and narrow dispersities (Đ = 1.03-1.25). Therefore, this NIR-photocontrolled aqueous RAFT polymerization system may provide a charming strategy for possible applications in tissue engineering biomaterial in situ benefiting from the high penetration ability of NIR light.

Novel highly water soluble zinc(II) phthalocyanines: Synthesis, photochemistry and DNA binding behaviours

Novel highly water soluble Zn(II)Pcs containing twelve quaternizable pyridinium groups were designed by taking advantage of the existence of the pentaerythritol hub in each substituted group. In the synthetic pathway, first the peripheral and non-peripheral tetra-2,2,2-tris[(pyridin-2-ylthio)methyl]ethoxy-substituted neutral Zn(II)Pcs (4 and 5) were synthesized and then quaternizations of twelve pyridine groups gave rise to reach highly water soluble novel Zn(II)Pcs (6 and 7). The three-branched bulky nature of substituted groups was effective in preventing aggregation and increasing dissolution. The photophysical, photochemical and singlet oxygen-producing properties of all studied compounds and also the DNA binding behaviours of quaternized Zn(II)Pcs were presented here.

Water soluble octa-imidazolium zinc phthalocyanine for nucleus/nucleolus cell fluorescence microscopy and photodynamic therapy.

A poly-cationic theranostic macrocycle was developed to perform confocal microscopy imaging and photodynamic therapy studies on a model of melanoma cancer, one of the most aggressive cancer. Hence, an octa-imidazolium zinc phthalocyanine was conveniently synthesized in large amount in three steps in a 44% overall yield: upon double nucleophilic aromatic substitution, cyclo-tetramerization and quaternization reactions. Such an octa-cationic molecule was readily soluble in physiological media, reaching concentrations beyond 1mM. It showed fluorescence properties in aqueous medium (ΦF = 0.31) with no noticeable aggregation, spectroscopy studies showed. In vitro confocal fluorescence microscopy studies carried out on murine melanoma model (B16F10 cells) showed that the fluorophore was mainly located in the cell nucleolus, an organelle of interest for the treatment of cancer. The anticancer photodynamic potential of the octa-cationic photosensitizer could be measured (IC50 = 5.4µM) using the MTS viability assay. Both fluorescence microscopy studies and photodynamic studies demonstrate the octa-cationic molecule is theranostic and could be further developed for future photodynamic diagnosis (PDD) and photodynamic inactivation of micro-organisms (PDI).

Novel Highly Water Soluble Zinc(Ii) Phthalocyanines: Synthesis, Photochemistry and DNA Binding Behaviours

Novel Highly Water Soluble Zinc(Ii) Phthalocyanines: Synthesis, Photochemistry and DNA Binding Behaviours

Novel Highly Positive Charged Water Soluble Zinc(Ii) Phthalocyanines: Synthesis, Singlet Oxygen Generation and DNA Binding Behaviours

Novel Highly Positive Charged Water Soluble Zinc(Ii) Phthalocyanines: Synthesis, Singlet Oxygen Generation and DNA Binding Behaviours

Schiff base containing pyridine groups functionalized water-soluble phthalocyanine: Synthesis, photo-physicochemical properties, and bovine serum albumin binding behavior.

The novel pyridine bearing schiff base substituted metal-free (9), zinc(II) phthalocyanine (10), and its quaternized derivative (11) were designed and synthesized. These phthalocyanines were fully characterized by spectroscopic methods (FT-IR, UV-Vis, MALDI-TOF, and 1H NMR). The photo-physicochemical properties of these phthalocyanines were investigated in both DMSO and DMF for 10 and in both DMSO and aqueous solution for 11. The addition of pyridine bearing Schiff base groups as peripheral ligands showed an improvement in the photophysical and photochemical properties. In addition, a spectroscopic investigation of the binding behavior of the water-soluble zinc (II) phthalocyanine complex to bovine serum albumin (BSA) was also studied in this work.

BSA/DNA binding behavior and the photophysicochemical properties of novel water soluble zinc(II)phthalocyanines directly substituted with piperazine groups

BSA/DNA binding behavior and the photophysicochemical properties of novel water soluble zinc(II)phthalocyanines directly substituted with piperazine groups

Evaluation of carbonic anhydrase and paraoxonase inhibition activities and molecular docking studies of highly water-soluble sulfonated phthalocyanines.

The investigation of carbonic anhydrase and paraoxonase enzyme inhibition properties of water-soluble zinc and gallium phthalocyanine complexes ( 1 and 2 ) are reported for the first time. The binding of p-sulfonylphenoxy moieties to the phthalocyanine structure favors excellent solubilities in water, as well as providing an inhibition effect on carbonic anhydrase (CA) I and II isoenzymes and paraoxonase (PON1) enzyme. According to biological activity results, both complexes inhibited hCA I, hCA II, and PON1. Whereas 1 and 2 showed moderate hCA I and hCA II (off-target cytosolic isoforms) inhibitory activity (Ki values of 26.09 µM and 43.11 µM for hCA I and 30.95 µM and 33.19 µM for hCA II, respectively), they exhibited strong PON1 (associated with high-density lipoprotein [HDL]) inhibitory activity (Ki values of 0.37 µM and 0.27 µM, respectively). The inhibition kinetics were analyzed by Lineweaver–Burk double reciprocal plots. It revealed that 1 and 2 were noncompetitive inhibitors against PON1, hCA I, and hCA II. These complexes can be more advantageous than other synthetic CA and PON inhibitors due to their water solubility. Docking studies were carried out to examine the interactions between hCA I, hCA II, and PON1 inhibitors and metal complexes at a molecular level and to predict binding energies.

The new water soluble zinc(II) phthalocyanines substituted with morpholine groups- synthesis and optical properties

Two new tetra- or octa-substituted zinc(II) phthalocyanines (1 and 2) bearing 3-(morpholinomethyl)phenyl groups were synthesized via Suzuki-Miyaura coupling method. These phthalocyanines (1 and 2) were converted to their water-soluble derivatives (1Q and 2Q) by quaternization of nitrogen atoms on the morpholine groups. The photochemical and photophysical properties of the non-ionic zinc(II) phthalocyanines (1 and 2) were explored in DMSO. On the other hand, these properties of the quaternized cationic derivatives (1Q and 2Q) were studied in both DMSO and aqueous solutions for determination of their photosensitizing capabilities in photodynamic therapy. The ct-DNA interaction of synthesized 1Q and 2Q were investigated and binding constants were found as 6.3 × 104 and 1.5 × 105 M, respectively. The binding constant values were found at similar levels of ethidium bromide (EB), which is a well-known intercalator. The spontaneous and exothermic nature of binding mechanisms were proved according to the calculated thermodynamic constants. Strong interactions of 1Q and 2Q with ct-DNA were also found with EB displacement assay and gel electrophoresis. Additionally, the bovine serum albumin (BSA) binding behavior of the new compounds (1Q and 2Q) were determined in water solution to verify the transporting capability of these phthalocyanines in the circulatory system and these values were found as 7.0 × 105 and 1.6 × 107 M−1 for 1Q and 2Q, respectively.

The novel Zn(II) phthalocyanines: Synthesis, characterization, photochemical, DNA interaction and cytotoxic/phototoxic properties

In this study, peripherally and non-peripherally tetra substituted water soluble zinc(II) phthalocyanines (5a and 5b) were synthesized and characterized. Their photochemical and ct-DNA binding properties of them were investigated by UV–Vis spectroscopy. DNA cleavage effects of 5a and 5b were examined using supercoiled pBR322 plasmid DNA on agarose gel electrophoresis. In photochemical studies, the singlet oxygen quantum yields of 5a and 5b were found as 0.76 and 0.78, respectively and the photostability ratios of 5a and 5b were found as 82.12% and 85.28%. The Kb values of 5a and 5b were calculated as 2.92 ± (0.20) × 105 and 1.30 ± (0.16) × 106 M−1, respectively. In addition, 5a and 5b had low cleavage effect in dark but they showed significant photocleavage effect against plasmid DNA under light irradiation in the absence and presence of H2O2. The cytotoxic and phototoxic effects of 5b against A549 and HCT-116 cell lines were investigated using MTT cell viability assay. 5b showed significant phototoxic effects at 1, 5 and 10 μM concentrations and under irradiation on A549 and HCT-116 cell lines. These results showed that compound 5b could be used as a photosensitizer agent in PDT applications.

Phthalocyanine-sensitized evolution of hydrogen and degradation of organic pollutants using polyoxometalate photocatalysts.

In this study, 2 (3), 9 (10), 16 (17), 23 (24)-tetrakis-(8-quinoline-oxy) phthalocyanine zinc(II) (ZnQPc) was prepared and then quaternized to obtain water soluble zinc phthalocyanine (ZnQPc4+). Then, ZnQPc4+ was used as a photosensitizer for a series of POM catalysts, including Dawson type K6[α-P2W18O62]·14H2O (P2W18) and K10[α-P2W17O61]·20H2O (P2W17) and Keggine type H3PW12O40·xH2O (PW12). The Keggin type PW12 showed higher efficiency with 18.2μmol of H2 evolution (turnover number (TON) = 14,550) for 6h upon ZnQPc4+ sensitization in relation to two Dawson P2W17 and P2W18 in a visible light-driven water-soluble system with isopropanol and H2PtCl6·6H2O. In addition, the complexes of ZnQPc4+ with a series of POM catalysts (P2W17, P2W18, and PW12) were also used as photocatalysts for the degradation of methylene blue (MB) in water, and it was found that the complexes of ZnQPc4+ with P2W17 and PW12 showed improved photocatalytic activity, and the degradation rates of MB reached 100% at a small dosage under natural pH and visible light. The high efficacy of POM catalysts for H2 evolution and the degradation of MB were attributed to the sensitization of POMs by ZnQPc4+, which was enabled by the transfer of photogenerated electrons of ZnQPc4+ to the lowest unoccupied molecular orbital (LUMO) of POM.

Synthesis and characterization of new partially-aggregated water-soluble polyether-triazole linked zinc(II) phthalocyanines as photosensitizers for PDT studies

Peripheral and non-peripheral octa-carboxylated water-soluble zinc(II) phthalocyanines with clicked polyethylene glycol linkers have been prepared. Different multistep reaction pathways have been attempted and compared for the preparation of the phthalonitrile precursors. Novel compounds have been characterized by combination of elemental analysis, 1H and 13C NMR, FT-IR, U–vis and MS spectral data. Both phthalocyanines were proved to be water soluble. Their singlet oxygen generation was determined in both water and DMSO to assess their potential of photosensitizers for photodynamic therapy.

A highly water-soluble zinc(II) phthalocyanines as potential for PDT studies: Synthesis and characterization

New zinc(II) phthalocyanines cotaining octa triazole linked tetraethylene glycol derived from peripheral or non-peripheral bis-{3-[4-(2-{2-[2-(2-hydroxy-ethoxy)-ethoxy]-ethoxy}-ethoxymethyl]-[1,2,3] triazol-1-yl]-propylsulfanyl}-phthalonitriles (9, 12) have been synthesized by multi-step reaction sequence and characterized. Phthalonitriles have been prepared by the reaction of 3,6-bis(3-azido-propylsulfanyl) phthalonitrile (7) or 4,5-bis(3-azido-propylsulfanyl)phthalonitrile (11). The new water-soluble zinc (II) phthalocyanines were synthesized by the tetramerization reaction of substituted dicarbodinitrile compounds. Singlet oxygen quantum yields of the complexes have been determined. These new compounds have been characterized by a combination of elemental analysis, FT-IR, 1H and 13C NMR, MS spectrometer and UV–vis spectrophotometer techniques.

Breaching the wall: morphological control of efficacy of phthalocyanine-based photoantimicrobials.

An efficient treatment of infections using antimicrobial photodynamic therapy (aPDT) anticipates that uptake of photosensitizer (PS) by bacterial cells is very fast and effective. In this work, the design, synthesis, characterization, and photodynamic activity of amphiphilic, water-soluble zinc(ii)phthalocyanine (Zn(ii)Pc) molecules bearing none, three or six thiophenyl moieties are described. We show that PSs that contain no or flexible substituents on non-peripheral positions can photoinactivate microbes at very low loading concentrations and low light doses. In contrast, a PS derivative that contains non-flexible substituents is rendered less effective, despite an increased generation of cytotoxic singlet oxygen, higher lipophilicity and a lower tendency to aggregate. Our unexpected finding emphasizes the role of the morphology of PSs in bacterial cell-molecule interactions and suggests another relevant and hitherto disregarded characteristic to improve PS design.

Construction and amperometric biosensing performance of a novel platform containing carbon nanotubes-zinc phthalocyanine and a conducting polymer

A novel glucose oxidase (GOx) based amperometric biosensor utilizing a conducting polymer (CP), multi walled carbon nanotubes (MWCNTs) and a novel water soluble zinc phthalocyanine (ZnPc) was constructed. For this purpose, a novel ZnPc was synthesized to examine the role of being a part of support material for enzyme deposition. High water solubility was achieved with the introduction of tetra quaternized imidazolyl moieties at the peripheral positions of phthalocyanine. In order to fabricate the proposed biosensor, a graphite electrode was firstly modified with poly[9,9-di-(2-ethylhexyl)- fluorenyl-2,7-diyl] end capped with N,N-Bis(4- methylphenyl)-4-aniline (PFLA) and MWCNTs. Then, GOx was co-immobilized with ZnPc onto the modified surface. To the best our knowledge, a sensor design which combines conjugated polymer/MWCNTs/ZnPc was attempted for the first time and this approach resulted in improved biosensor characteristics. The constructed biosensor showed a linear response for glucose between 0.025–1.0mM with a detection limit of 0.018mM. KMapp and sensitivity values were calculated as 0.53mM and 82.18μAmm−1cm−2, respectively. Moreover, scanning electron microscopy (SEM) and cyclic voltammetry (CV) techniques were used to investigate the surface modifications. Finally, fabricated biosensor was tested on beverages for glucose detection successfully.

Aggregation Control of Robust Water-Soluble Zinc(II) Phthalocyanine-Based Photosensitizers.

A water-soluble zinc phthalocyanine (ZnPc) complex with four negatively charged electron-withdrawing sulfonic acid substituents at the nonperipheral positions (α-ZnTSPc) is found to have a high singlet oxygen (1O2) quantum yield and exhibits high photostability. The formation of aggregates is hindered and the highest occupied molecular orbital is significantly stabilized, making α-ZnTSPc potentially suitable for its use as a photosensitizer for photodynamic therapy and photoimmunotherapy. Atomic force microscopy (AFM) reveals that mixtures of the negatively charged α-ZnTSPc complex with a similar positively charged ZnPc were found to result in the self-assembly of one-dimensional accordion-like fibers. Supramolecular fibers can be formed in aqueous solutions through intermolecular electrostatic and donor-acceptor interactions between the two water-soluble ZnPcs.

The synthesis of novel directly conjugated zinc(II) phthalocyanine via palladium-catalyzed Suzuki–Miyaura cross-coupling reaction and its quaternized water-soluble derivative: Investigation of photophysical and photochemical properties

The novel zinc(II) phthalocyanine directly conjugated with 4-(diethylamino)phenyl groups (2) via CC bond formation using Suzuki-Miyaura coupling reaction was synthesized for the first time. This phthalocyanine was converted to the quaternized derivative (3) to enhance its water solubility. The photochemical (singlet oxygen quantum yield and photodegradation quantum yield) and photophysical (fluorescence quantum yield and lifetime) properties of the synthesized novel zinc(II) phthalocyanines (2 and 3) were investigated in DMSO (for both phthalocyanines 2 and 3) and in aqueous solution (for only phthalocyanine 3) for determination of their photodynamic therapy abilities. Additionally, the bovine serum albumin (BSA) binding behavior of the water soluble zinc(II) phthalocyanine (3) was investigated in aqueous solution for determination of transporting capability of this phthalocyanine in the circulatory system.