Zinc Phthalocyanine Derivatives Research Articles

Novel Hexadeca-Substituted Metal Free and Zinc(II) Phthalocyanines; Design, Synthesis and Photophysicochemical Properties.

The syntheses of a novel 1,4,8,11,15,18,22,25-octahexyloxy-2,3,9,10,16,17,23,24-octa-(4-trifluoromethoxyphenyl) phthalocyanine (3a) and its zinc(II) phthalocyanine derivative (3b) have been described and characterized by elemental analysis,1H NMR, 13C NMR, 19F NMR, mass, UV-Vis and FT-IR. The newly prepared metal-free phthalocyanine and its zinc(II) counterpart are soluble in most organic solvents. The photophysical and photochemical properties such as aggregation, fluorescence, singlet oxygen generation and photodegradation under light irradiation of these phthalocyanines have been investigated in DMF. The hexadeca-substituted phthalocyanines (3a and 3b) showed longer absorption and emission wavelength values when compared to that of reported phthalocyanine derivatives due to substitution of the all possible positions in the phthalocyanine framework. The zinc(II) phthalocyanine derivative does not only have a good singlet oxygen generation but also has other photophysicochemical properties that enables this phthalocyanine to be useful as a photosensitizer for cancer treatment using photodynamic therapy.

Immunostimulatory effect of Zinc Phthalocyanine derivatives on macrophages based on the pro-inflammatory TNFα and IL1β cytokine production levels

In this study, we examined the effect of halogen substitution on the ability of ZnPcs to stimulate or regulate the immune system cells. There have been studies focusing on the usage of Pcs as treatment option against different cancer types. More attention should be paid on their possible positive or negative effects on the immune system for better prognosis rates. We designed and synthesized unique ZnPcs with iodine substitution and further tested their effect on mammalian macrophage cell line. Macrophages are crucial cell types that can define the immune response by cytokine production as well as by antigen presentation to the other immune system cells after phagocytosis of the danger associated molecules. Our results suggest an immunostimulatory role for the iodine substituted ZnPc on macrophages based on the changes in pro-inflammatory cytokine production levels (TNFα, IL1β and IL6). This effect dependent on the presence of iodine; since non-substituted ZnPc did not exert such a stimulatory activity on the macrophages. These results support a possible use of the reagents against the tumor types that would get affected detrimentally by the pro-inflammatory environment.

Photodynamic therapy activity of zinc phthalocyanine linked to folic acid and magnetic nanoparticles

In this work, the photodynamic therapy (PDT) activities (using human carcinoma adherent MCF-7 cells) of zinc phthalocyanine derivatives: complexes 1 (Zn mono cinnamic acid phthalocyanine) and 2 (zinc mono carboxyphenoxy phthalocyanine) when covalently linked to folic acid (FA) and amine functionalized magnetic nanoparticles (AMNPs) are reported. The covalent linkage of asymmetric zinc cinnamic acid Pc (1) to FA (1-FA) through an amide bond is reported for the first time. Complex 1 is insoluble in water, but upon linkage to FA, (to form 1-FA) the molecule become water soluble, hence the UV–Vis spectrum and singlet oxygen quantum yield for 1-FA were also done in water since water solubility is essential for biological applications. The reported 2-FA is also water soluble. Linking complexes 1 and 2 to FA and AMNPs decreased the dark toxicity of 1 and 2 on MCF-7 cells. Pc-FA (1-FA and 2-FA) conjugates had better singlet oxygen quantum yields (Φ∆) in DMSO as compared to Pc-AMNPs (1-AMNPs and 2-AMNPs). The water- soluble 1-FA and 2-FA also achieved a better photodynamic therapy (PDT) activity as compared to 1-AMNPs and 2-AMNPs. Folic acid targeting on the tumor cells may have also facilitated better bioavailability of 1-FA and 2-FA and improved PDT activity on MCF-7 cells over AMNPs carriers.

DNA physical interaction mediated b-lymphoma treatment offered by tetra benzimidazole-substituted zinc (ii) phthalocyanine derivative.

Role of heterocyclic compounds with nitrogen substitution in therapeutic frontiers is well established. The efforts made in this study are directed to dissect the biological significance of benzimidazole-substituted zinc phthalocyanine derivative. Its capacity to act as an anticancer agent against the 2 B-lymphoma cell lines (low-grade and high-grade malignancy) was found out by recording florescence using Alamar blue dye. Further cytotoxic effect at the DNA level was analyzed by performing agarose gel electrophoresis. Molecular docking studies made mechanistic details crystal clear by showing potential dual binding modes employed for interaction with DNA that include minor groove binding and intercalation between bases. This advocates this derivative as potential anticancer agent and deserves further rounds of mechanistic study for its final journey to serve as a marketed drug.

Photosensitization of zinc phthalocyanine bearing 15-crown-5 ether moieties on carbon nitride for H2 production: Effect of co-existing alkali metal ions

A zinc phthalocyanine derivative (ZnPc) with one carboxyl group and three 15-crown-5 ether moieties has been synthesized and used as photosensitizer of Pt-loaded graphitic carbon nitride (Pt/g-C3N4) for visible-light-driven H2 production. By adding alkali metal ions (Li+, Na+, or K+) in the ZnPc solution before the dye-sensitization process, the photosensitization for H2 production on Pt/g-C3N4 can be improved with an increasing sequence of Li+ < Na+ < K+. Especially, the co-existing K+ ions cause the H2 production activity enhancing from 163 to 476 μmol h−1 with a turnover number (TON) from 3105 to 9067 h−1. Besides, the coexisting Li+, Na+ and K+ ions exhibiting an impressive apparent quantum yield (AQY) of 2.06%, 2.41% and 2.74% at 700 nm, respectively. All those AQY values are higher than that (1.88%) of the ZnPc-Pt/g-C3N4 without addition of alkali metal ion. The further investigation results indicate that the combination of ZnPc's 15-crown-5 ethers with ions are able to enhance the electron transfer ability and then the photoactivity for H2 production. Our finding may open a way to highly efficient dye-sensitized semiconductor-based photocatalysis for solar energy conversion by using ZnPc derivative bearing purposeful substituents which can be interacted with proper ions.

Near-Infrared Activatable Phthalocyanine-Poly-L-Glutamic Acid Conjugate: Enhanced in Vivo Safety and Antitumor Efficacy toward an Effective Photodynamic Cancer Therapy.

We previously developed a new zinc(II) phthalocyanine (ZnPc) derivative (Pc 1) conjugated to poly-L-glutamic acid (PGA) (1-PG) to address the limitations of ZnPc as part of an antitumor photodynamic therapy approach, which include hydrophobicity, phototoxicity, and nonselectivity in biodistribution and tumor targeting. During this study, we discovered that 1-PG possessed high near-infrared (NIR) light absorptivity (λmax = 675 nm), good singlet oxygen generation efficiency in an aqueous environment, and enhanced photocytotoxic efficacy and cancer cell uptake in vitro. In the current study, we discovered that 1-PG accumulated in 4T1 mouse mammary tumors, with a retention time of up to 48 h. Furthermore, as part of an antitumor PDT, low dose 1-PG (2 mg of Pc 1 equivalent/kg) induced a greater tumor volume reduction (-74 ± 5%) when compared to high dose ZnPc (8 mg/kg, -50 ± 12%). At higher treatment doses (8 mg of Pc 1 equivalent/kg), 1-PG reduced tumor volume maximally (-91 ± 6%) and suppressed tumor size to a minimal level for up to 15 days. The kidney, liver, and lungs of the mice treated with 1-PG (both low and high doses) were free from 4T1 tumor metastasis at the end of the study. Telemetry-spectral-echocardiography studies also revealed that PGA (65 mg/kg) produced insignificant changes to the cardiovascular physiology of Wistar-Kyoto rats when administered in vivo. Results indicate that PGA displays an excellent cardiovascular safety profile, underlining its suitability for application as a nanodrug carrier in vivo. These current findings indicate the potential of 1-PG as a useful photosensitizer candidate for clinical PDT.

Phthalocyanines formed from several precursors: synthesis, characterization, and comparative fluorescence and quinone quenching

We have synthesized a new phthalonitrile with different substituents in 4- and 5-positions (1). Cyclotetramerization of 1 yielded phthalocyanines with cobalt(II) (2), zinc(II) (3), gallium(III)chloride (4), and indium(III)chloride (5) containing diethylamino-phenoxy and hexylsulfanyl substituents on each benzene unit. Elemental analyses, Fourier transform infrared spectra, 1H-nuclear magnetic resonance spectra, mass spectra, and ultraviolet-visible spectra were used for characterization of the phthalocyanines. The aggregation behavior of the zinc phthalocyanine derivative was studied in different concentrations. Also four chloro and four diethyllaminophenoxy substituted zinc phthalocyanine (6) and octa-diethylaminophenoxy substituted zinc phthalocyanine (7) were synthesized. These phthalocyanines (3, 6, and 7) were compared for electronic absorption spectra, fluorescence quantum yields, fluorescent lifetimes, and fluorescence quenching in the presence of benzoquinone. The fluorescence quantum yield gives the efficiency of the fluorescence process. The fluorescence lifetime is an important parameter for practical applications of fluorescence such as fluorescence resonance energy transfer and fluorescence-lifetime imaging microscopy.

New peripherally and non-peripherally tetra-substituted metal-free, magnesium(II) and zinc(II) phthalocyanine derivatives fused chalcone units: Design, synthesis, spectroscopic characterization, photochemistry and photophysics

Chalcone containing new peripherally and non-peripherally tetra-substituted metal-free and metallophthalocyanine derivatives were designed and synthesized (Schemes 1 and 2). The structures of chalcone-phthalocyanines were characterized by a combination of common spectroscopic techniques such as LC–MS/MS (for new phthalonitrile derivative 3a), ground state electronic absorption spectra (for all new phthalocyanines), 1H NMR spectroscopy (for all new compounds), 13C NMR spectroscopy (for new phthalonitrile and metal-free phthalocyanine derivatives), Fourier transform infrared (FT–IR with ATR sampling accessory) (for all new compounds) and MALDI–TOF mass spectral data (for all new phthalocyanines and new phthalonitrile derivative 3b) as well as elemental analysis. In addition, the effects of the presence of different kinds of metal ions [magnesium(II) or zinc (II)] in the phthalocyanine core and the effects of the introduction of (3,4-dimethoxyphenyl)-3-oxoprop-1-en-1-yl)phenoxy units at both peripheral and non-peripheral positions of the phthalocyanine skeleton on photophysical and photochemical properties of the new substituted magnesium(II) and zinc(II) phthalocyanines have also been examined in DMF. The obtained results were compared with each other and with unsubstituted magnesium(II) and zinc(II) phthalocyanines. All newly synthesized phthalocyanines are soluble in common organic solvents as well as no type of aggregation was observed in these solvents. Moreover; the chalcone fused magnesium(II) and zinc(II) phthalocyanines also showed excellent fluorescence properties. Specifically, the new non-peripheral zinc(II) and magnesium(II) chalcone-phthalocyanines have the remarkable potential to be used as Type II photosensitizers for the treatment of cancer in PDT owing to their good singlet oxygen and appropriate photodegradation quantum yields. Since chalcones and their derivatives show a broad range of biological and pharmaceutical activities, these products are promising candidates for various applications, particularly as photosensitizers for photodynamic therapy in combination with fluorescence imaging.

In vitro photodynamic activity of lipid vesicles with zinc phthalocyanine derivative against Enterococcus faecalis

Zinc(II) phthalocyanine bearing eight non-peripheral 2-propoxy substituents was subjected to physicochemical study and, after incorporation in lipid vesicles, assessed as a potential photosensitizer for antibacterial photodynamic therapy. The phthalocyanine derivative obtained in the macrocyclization reaction was characterized by MS and NMR techniques. Moreover, its chemical purity was confirmed by HPLC analysis. X-ray structural analysis revealed that overcrowding of the phthalocyanine derivative leads to a strong out-of-plane distortion of the π-system of the macrocycle core. In the UV–Vis absorption spectra of zinc(II) phthalocyanine two characteristic bands were found: the Soret (300–450 nm) and the Q band (600–800 nm). Photophysical properties of mono- and diprotonated forms of phthalocyanine derivative were studied with time-resolved fluorescence spectroscopy. Its tri- and tetraprotonated forms could not be obtained, because compound decomposes in higher acid concentrations. The presented zinc(II) phthalocyanine showed values of singlet oxygen generation ΦΔ = 0.18 and 0.16, the quantum yield of the photodecomposition ΦP = 3.06∙10−4 and 1.23∙10−5 and the quantum yield of fluorescence ΦFL = 0.005 and 0.004, designated in DMF and DMSO, respectively. For biological studies, phthalocyanine has been incorporated into modified liposome vesicles containing ethanol. In vitro bacteria photoinactivation study revealed no activity against Escherichia coli and 5.7 log reduction of the Enterococcus faecalis growth.

Synthesis and some optical results of long chain substituted phthalocyanines

Four metallo (zinc, copper, vanadyl, and indium) phthalocyanine derivatives bearing four aliphatic (hexylthio) groups were prepared from corresponding phthalonitrile compounds. The metallophthalocyanines were characterized with ultraviolet–visible spectroscopy (UV-Vis), proton nuclear magnetic resonance (1H NMR), Fourier transform-infrared spectroscopy (FT-IR), and mass and elemental analyses techniques. Aggregation properties of metallophthalocyanines in solution were studied in varied concentration ranges. Thin films of metallophthalocyanines were obtained by spin coating technique. Optical measurements showed that transmittance values of metallophthalocyanine thin films obviously changed with respect to the metal ion in the phthalocyanines. Transmittance spectra of the phthalocyanines synthesized using different metal ions showed a variation of about 8% and 15% in transmittance spectra of the Q band region was obtained by mixing the two metal phthalocyanine (indium and zinc) solutions.

Zinc(II) and chloroindium(III) phthalocyanines bearing ethyl 7-oxy-6-chloro-4-methylcoumarin-3-propanoate groups: Synthesis, characterization and investigation of their photophysicochemical properties

In this study, ethyl 7-hydroxy-6-chloro-4-methylcoumarin-3-propanoate (1), ethyl 7-(2,3-dicyanophenoxy)-6-chloro-4-methylcoumarin-3-propanoate (2), ethyl 7-(3,4-dicyanophenoxy)-6-chloro-4-methylcoumarin-3-propanoate (3), ethyl 4-chloro-5-(7-oxy-6-chloro-4-methylcoumarin-3-propanoate)phthalonitrile (4) were synthesized. The phthalonitrile derivatives (2, 3 and 4) were converted to their peripheral tetra, non-peripheral tetra and peripheral chlorocta substituted zinc(II) and chloroindium phthalocyanine derivatives. All novel compounds were characterized by elemental analysis, FT-IR, [Formula: see text]H-NMR, MALDI-TOF mass spectrometry and UV-vis spectral data. Additionally, the spectral, photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen generation and photodegradation under light irradiation) properties of the resulting substituted phthalocyaninatozinc(II) and indium(III) chloride complexes (5–10) were investigated in DMF, and the obtained results were compared for determination of the effects of the substituents’ positions and the variety of the central metal atom on these properties. The fluorescence quenching behavior of these phthalocyanines (5–10) were also investigated using 1,4-benzoquinone as a quencher. The obtained ethyl 7-oxy-6-chloro-4-methylcoumarin-3-propanoate bearing phthalocyaninatozinc(II) (5, 7 and 9) and indium(III) chloride (6, 8 and 10) complexes showed excellent solubility in most organic solvents. They produced high singlet-oxygen and showed appropriate photodegradation which is very important for photodynamic therapy applications.

Effects of charge on the photophysicochemical properties of zinc phthalocyanine derivatives doped onto silica nanoparticles

Herein we report on the photophysicochemical properties of neutral, positively and negatively charged metallophthalocyanines (MPcs) when doped onto silica nanoparticles. The MPcs are: unsubstituted ZnPc (complex 1, neutral), Zn tetraaminophenoxy phthalocyanine (ZnTAPhPc, complex 2, neutral), tetrakis[4-(iodo-N-methylpyridinium)thio] phthalocyanine (ZnTMPyPc, complex 3, cationic), and Zn tetra sulfophenoxy phthalocyanine (ZnTSPhPc, complex 4, anionic). Following doping onto SiNPs, the triplet quantum yields increased for neutral complex 1 and positively charged complex 3. However, singlet oxygen quantum yields increased for positively charged 3 (in 3-SiNPs) and the negatively charge 4 (in 4-SiNPs) and not for complex 1 (in 1-SiNPs), compared to Pcs alone, due to the screening effect.

A Molecular Combination of Zinc(II) Phthalocyanine and Tamoxifen Derivative for Dual Targeting Photodynamic Therapy and Hormone Therapy.

The combination of photodynamic therapy and other cancer treatment modalities is a promising strategy to enhance therapeutic efficacy and reduce side effects. In this study, a tamoxifen-zinc(II) phthalocyanine conjugate linked by a triethylene glycol chain has been synthesized and characterized. Having tamoxifen as the targeting moiety, the conjugate shows high specific affinity to MCF-7 breast cancer cells overexpressed estrogen receptors (ERs) and tumor tissues, therefore leading to a cytotoxic effect in the dark due to the cytostatic tamoxifen moiety, and a high photocytotoxicity due to the photosensitizing phthalocyanine unit against the MCF-7 cancer cells. The high photodynamic activity of the conjugate can be attributed to its high cellular uptake and efficiency in generating intracellular reactive oxygen species. Upon addition of exogenous 17β-estradiol as an ER inhibitor, the cellular uptake and photocytotoxicity of the conjugate are reduced significantly. As shown by confocal microscopy, the conjugate is preferentially localized in the lysosomes of the MCF-7 cells.

An effective zinc phthalocyanine derivative against multidrug-resistant bacterial infection

Bacterial skin and soft tissue infections are abundant worldwide. The rise in the incidence of multidrug-resistant (MDR) bacterial infections has made the need for alternative means of treatment more pressing. We herein report a zinc phthalocyanine derivative, pentalysine [Formula: see text]-carbonylphthalocyanine zinc (ZnPc-(Lys)[Formula: see text] and its strong capability of killing nosocomial MDR bacteria, including MDR-Escherichia coli and MDR-Acinetobacter baumannii. In vitro studies, we observed that ZnPc-(Lys)5 in micromolar concentrations killed above MDR bacteria in 6~6.5 log10 orders with only 5-min illumination of red light at a dosage of 12.75 J/cm[Formula: see text]. Further in vivo studies on a mouse infection model demonstrated that ZnPc-(Lys)5 efficiently inhibited the MDR bacterial growth after one-time photodynamic antibacterial therapy and, interestingly, significantly accelerated the wound healing. Putting together, our findings establish ZnPc-(Lys)5 as a potent antimicrobial candidate for the clinical test on localized infection.

Synthesis, characterization of symmetrical and unsymmetrical naphthoxy substituted metallophthalocyanines

ABSTRACTWe have designed and synthesized novel symmetrical (4a, 4b) and unsymmetrical (6) copper (II), zinc (II) Phthalocyanine derivatives with (4-methoxynaphthalen-1-yl)oxy) and fluoro substitution. For this synthesis we started from nucleophilic substitution of fluorine atoms in tetrafluorophthalonitrile by 4-methoxy naphthoxy groups. The resulting three phthalocyanines have been fully characterized by a series of spectroscopic methods including electronic absorption, elemental analysis, MALDI-TOF mass, and IR spectroscopy. These phthalocyanine complexes were investigated by cyclic voltammetric measurements to observe the both metal-based and phthalocyanine ring-based reduction and oxidation electron transfer processes.

Photoinduced Cross-Linking of Short Furan-Modified DNA on Surfaces.

We report for the first time the formation of site-specific interstrand cross-linked (ICL) surface-immobilized furan-modified DNA duplexes via singlet oxygen. 1O2, necessary for effecting furan-mediated ICL formation, was produced in situ using methylene blue or a zinc phthalocyanine derivative (TT1) as a photosensitizer. Via surface plasmon resonance spectroscopy, we show that surface ICL was achieved, and a robust link formed that enhances the stability of the 12-mer duplex even after surface regeneration. The described method represents a novel platform technology based on surfaces with addressable and stable DNA duplexes requiring only short oligonucleotides.

Photoantimicrobial Biohybrids by Supramolecular Immobilization of Cationic Phthalocyanines onto Cellulose Nanocrystals.

The development of photoactive and biocompatible nanostructures is a highly desirable goal to address the current threat of antibiotic resistance. Here, we describe a novel supramolecular biohybrid nanostructure based on the non-covalent immobilization of cationic zinc phthalocyanine (ZnPc) derivatives onto unmodified cellulose nanocrystals (CNC), following an easy and straightforward protocol, in which binding is driven by electrostatic interactions. These non-covalent biohybrids show strong photodynamic activity against S. aureus and E. coli, representative examples of Gram-positive and Gram-negative bacteria, respectively, and C. albicans, a representative opportunistic fungal pathogen, outperforming the free ZnPc counterparts and related nanosystems in which the photosensitizer is covalently linked to the CNC surface.

Tetrakis{2-[N-((3-morpholino)propyl)carbamate]oxyethyl} zinc(II) phthalocyanine and its water soluble derivatives: Synthesis, photophysical, photochemical and protein binding properties

Abstract In this study, the novel water soluble derivatives of 2-[ N -((3-morpholino)propyl)carbamate]oxyethyl substituted zinc(II) phthalocyanine ( 1 ) bearing different type of groups such as sulfobetaine ( 2 ), betaine ( 3 ), N-Oxide ( 4 ) and quaternized methyl ( 5 ) on the morpholine core were synthesized for the first time. All newly synthesized zinc(II) phthalocyanine derivatives were characterized by different spectroscopic techniques such as UV–vis, FT-IR, 1 H NMR, mass and elemental analysis as well. They showed excellent solubility in aqueous media due to their zwitterionic and ionic characters which makes them promising candidates for treatment of cancer by photodynamic therapy (PDT). The photophysical and photochemical properties were investigated in DMSO for tetrakis{2-[ N -((3-morpholino)propyl)carbamate]oxyethyl} substituted zinc(II) phthalocyanine ( 1 ) and in both DMSO and water + Triton X-100 solutions for its water soluble ionic derivatives ( 2-5 ). The binding behaviors of ionic zinc(II) phthalocyanines by bovine serum albumin (BSA) protein were investigated for determination of transportation ability of these phthalocyanines in the blood circulation.

Synthesis of asymmetric zinc phthalocyanine with bulky diphenylthiophenol substituents and its photovoltaic performance for dye-sensitized solar cells

Abstract Asymmetric zinc phthalocyanine derivative ( Zn- tri -PcNc-9 ) bearing one carboxylic and six bulky diphenylthiophenol groups was synthesized as a sensitizer for dye-sensitized solar cells. The obtained Zn- tri -PcNc-9 exhibits strong and expanded Q-band absorption peak (at ∼741 nm) in the red/near-IR light (600–800 nm) range, and its photovoltaic performance in sensitizing TiO 2 -based solar cell can be significantly improved by using chenodeoxycholic acid (CDCA) as co-adsorbent due to the retarded charge recombination. Under an optimal sensitization condition, the corresponding solar cell exhibits an efficiency of 3.61%, which is improved by 144% as compared to the solar cell without CDCA. Moreover, Zn- tri -PcNc-9 -sensitized solar cell shows a maximum incident photo-to-current conversion efficiency of 31.6% at ∼730 nm, red-shifted by ∼20 nm as compared to that (∼710 nm) of its O-substituted analog ( Zn- tri -PcNc-8 ) bearing six diphenylphenoxy groups, suggesting an effective solution to expand the red/near-IR responsive range of the ZnPc-sensitized solar cell, and also demonstrating a possibility for future panchromatic sensitizing agents in dye-sensitized solar cells.

Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivatives in treatment of bacterial skin infection.

Photodynamic antimicrobial chemotherapy (PACT) is an effective method for killing bacterial cells in view of the increasing problem of multiantibiotic resistance. We herein reported the PACT effect on bacteria involved in skin infections using a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5). Compared with its anionic ZnPc counterpart, ZnPc-(Lys)5 showed an enhanced antibacterial efficacy in vitro and in an animal model of localized infection. Meanwhile, ZnPc-(Lys)5 was observed to significantly reduce the wound skin blood flow during wound healing, indicating an anti-inflammation activity. This study provides new insight on the mechanisms of PACT in bacterial skin infection.