Synthesis, photo-physicochemical and biological properties of novel tetrahydropyrimidone-substituted metallo-phthalocyanines.

In this study, new peripherally substituted symmetric zinc and magnesium phthalocyanines (4 and 5) were successfully prepared by cyclotetramerization of the tetrahydropyrimidone (THPM)-linked phthalonitrile 3. The identity of the compounds were confirmed primarily through spectroscopic analysis including NMR, FT-IR, UV-Vis and MALDI-TOF mass spectroscopy. The photophysical and photochemical properties of the synthesized phthalocyanines (Pcs) were examined using UV-Vis absorption and fluorescence emission spectroscopy techniques. The quantum yields of singlet oxygen were found to be 0.50 and 0.33 for compounds 4 and 5 in DMSO, respectively. In addition to photo-physicochemical properties, the enhanced biological activities of compounds 4 and 5 were investigated using a range of biological assays, namely, antibiofilm, microbial cell viability, antioxidant, DNA cleavage, antimicrobial and photodynamic antimicrobial assays. The maximum DPPH inhibition of 4 and 5 was detected as 40.46% and 25.76% at 100 mg L-1, respectively. Fragmentation of the DNA molecule was observed at concentrations of 25 mg L-1, 50 mg L-1 and 100 mg L-1 for 4 and 5. Additionally, effective inhibition of microbial cell viability was observed with the targeted Pcs. The antibiofilm properties of these compounds were found to be concentration-dependent. The biofilm inhibition activities of 4 and 5 were found to be 96.01% and 92.04% for S. aureus, while they were 95.42% and 91.27%, for P. aeruginosa, respectively. The antimicrobial activities of 4 and 5 on different microorganisms were evaluated using the microdilution assay. In the case of photodynamic antimicrobial treatment, the newly synthesized Pcs showed more effective antimicrobial inhibition compared to the control. These findings suggest that compounds 4 and 5 can be used as promising photodynamic antimicrobial agents for the treatment of many diseases, particularly infectious diseases.

New AB3-type porphyrins with piperidine and morpholine motifs; synthesis and photo-physicochemical and biological properties.

In this study, new unsymmetrical meso-tetraaryl AB3-type porphyrins 1 and 2 were successfully synthesized by the reaction of p-bromobenzaldehyde and p-hydroxybenzaldehyde with pyrrole in propionic acid. AB3-type porphyrin building blocks with hydroxyl functionality (1 and 2) were further used to generate both covalently linked metal free and Zn(II) porphyrins 3-6 having piperidine and morpholine heterocyclic units. These novel compounds were characterized by using 1H NMR, 13C NMR, FT-IR and MALDI-TOF spectrophotometry. The photophysical and photochemical properties of compounds 1-6 were investigated by employing UV-vis absorption and fluorescence emission spectroscopy in tetrahydrofuran (THF). From the view of biological properties, the antioxidant capacities of porphyrins were determined by using DPPH radical scavenging activity and 2 was determined as the most potent porphyrin analog with a value of 98.42% at 200 mg L-1. All the targeted compounds displayed significant DNA nuclease activity. In addition, the antimicrobial potential of compounds 1-6 was also investigated by a micro-dilution process and 2 was found to be the most effective candidate against the tested microbial strains. The newly synthesized porphyrins also showed 100% microbial cell viability inhibition against E. coli at all examined concentrations. In terms of biofilm inhibition activity, the best results for the maximum photodynamic antimicrobial biofilm inhibition of S. aureus and P. aeruginosa were obtained by compound 2 with the values of 99.75% and 93.39%, respectively.

Chemo-photodynamic Activity of Silicon Phthalocyanines Bearing Cyclooxygenase Inhibitors on Colorectal Cancer Cell Lines.

Colorectal cancer ranks as the third most lethal cancer worldwide, resulting in over 1 million cases and 900 000 deaths per year. According to population-based studies, administration of long-term non-steroidal anti-inflammatory drugs (NSAIDs) was proven to reduce the risk of a subject developing colorectal cancer. In the present study, the anti-cancer activity of two different NSAIDs, sulindac- (Pc-1) or diclofenac-substituted (Pc-2) asymmetric silicon phthalocyanine derivatives, was evaluated in four different colorectal cancer cell lines bearing various carcinogenic mutations. In this context, the IC50 values of each compound after 24 and 48 h were determined on HCT116, SW480, LoVo, and HT29 cell lines, and the effects of the compounds on programmed cell death pathways apoptosis and autophagy, their impact on cell cycle progression, and the effect of NSAID moieties they bear on COX-1 and COX-2 proteins were analyzed. In addition, the photophysical and photochemical properties of a synthesized Pc derivative bearing axial diclofenac and triethylene glycol groups (Pc-2) have been investigated, and the compound has been characterized by using different analytical techniques. Our results indicated that both compounds inhibit COX protein expression levels, activate apoptosis in all cell lines, and lead to cell cycle arrest in the G2/M phase, depending on the COX expression profiles of the cell lines, indicating that NSAIDs can be coupled with Pc's to achieve increased anti-cancer activity, especially on cancer cells known to have high COX activity.

Triphenylamine substituted copper and zinc phthalocyanines as alternative hole-transporting materials for solution-processed perovskite solar cells.

In the present study, new peripheral substituted Zn(II) and Cu(II) phthalocyanine derivatives (p-ZnPc and p-CuPc) bearing bulky aromatic triphenylamine groups were synthesized as alternative hole-transporting materials (HTMs). The structures of the new phthalocyanine derivatives (p-ZnPc and p-CuPc) were illuminated by various spectroscopic techniques such as mass spectrometry and 1H, and 13C-NMR. After structural analysis, their photophysical properties in solution and the solid phase were examined by UV-Vis absorption and fluorescence spectroscopy. Using p-ZnPc and p-CuPc as HTMs, highly stable perovskite-based solar cells with the structure of FTO/SnO2/perovskite/p-ZnPc and p-CuPc/Ag have been developed and characterized. It was observed that our devices with p-ZnPc as the HTM maintain over 93% of the initial performance for more than 960 h under atmospheric conditions (22-27 °C) with 35-45% relative humidity. In addition, some strategies such as using various methylammonium iodide (MAI) and lead iodide (PbI2) blend ratios between 1 : 0.4 and 1 : 1.8 were employed to test the effect of the blend ratios on the long term stability of the perovskite-based solar cells. Our findings demonstrated that the spin-coated p-ZnPc based HTM demonstrated competitive power conversion efficiency and exhibited superior stability without encapsulation compared to commonly used HTMs.

Novel axially symmetric and unsymmetric silicon(IV) phthalocyanines having anti-inflammatory groups: synthesis, characterization and their biological properties.

New asymmetric Si(IV)Pc (1), monomeloxicammonotriethyleneglycolmonomethylether (phthalocyaninano)silicone, axially ligated with meloxicam as a non-steroidal anti-inflammatory drug (NSAID), or triethylene glycol monomethyl ether and symmetric Si(IV)Pc (2), diclofenac(phthalocyaninano)silicone, axially ligated with two diclofenac as NSAID, were synthesized and characterized as antioxidant and antimicrobial agents together with polyoxo-SiPc (3), ditriethyleneglycolmonomethylether(phthalocyaninano)silicone, and SiPc(OH)2 (4), dihydroxy(phthalocyaninano)silicone. The photophysical and photochemical properties of these compounds were investigated. Then, antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferrous ion chelating activities, were performed for these Si(IV) phthalocyanine derivatives (1, 2, 3 and 4). The highest DPPH scavenging activity of 73.48% was achieved with compound 2 and the highest ferrous chelating ability of 66.42% was obtained with compound 3. The results of the antioxidant assays indicated that Pc derivatives 1, 2 and 3 have remarkable superoxide radical scavenging activities, and moderate 2,2-diphenyl-1-picrylhydrazyl activities and metal chelating activities. The antimicrobial effects of the Si(IV) phthalocyanine compounds were studied against six pathogenic bacteria and two pathogenic microfungi. The results for the antimicrobial activity of these compounds indicated that Enterococcus faecalis (ATCC 29212) was the most sensitive microorganism and Pseudomonas aeruginosa (ATCC 27853) and Legionella pneumophila subsp. pneumophila (ATCC 33152) were the most resistant microorganisms against the tested compounds. The DNA cleavage ability and microbial cell viability of these compounds were studied. The studied compounds demonstrated excellent DNA nuclease activity and exhibited 100% cell viability inhibition at 500 mg L-1. Also, the antimicrobial photodynamic therapy of the compounds was tested against Escherichia coli (ATCC 25922) and significant photodynamic antimicrobial activity was observed. In addition, the effect of phthalocyanines on biofilm inhibition produced by Staphylococcus aureus (ATCC 25923) was also tested and 3 showed excellent biofilm inhibition of 82.14%.

Evaluation of histone deacetylase inhibitor substituted zinc and indium phthalocyanines for chemo- and photodynamic therapy.

In this study, we synthesized and characterized 3-hydroxypyridin-2-thione (3-HPT) bearing zinc (ZnPc-1 and ZnPc-2) and indium (InPc-1 and InPc-2) phthalocyanine (Pc) derivatives, either non-peripherally or peripherally substituted as photosensitizer (PS) agents and evaluated their anti-cancer efficacy on two breast cancer cell lines, MDA-MB-231 and MCF-7 as well as a human endothelial cell line, HUVEC. Our results indicated different localization patterns between ZnPcs and InPcs in addition to enhanced effects on the mitochondrial network for InPcs. Moreover, peripheral or non-peripheral substitution of HDACi moieties altered cellular localization between ZnPc-1 and ZnPc-2, leading to increased IC50 values along with decreased anti-cancer activity for non-peripheral substitution. When considering the compounds' differential effects in vitro, our data indicates that further research is required to determine the ideal Pcs for anti-cancer PDT treatments since the core metals of the compounds have affected the cellular localization, and positioning of the chemotherapeutic residues may inhibit cellular penetrance.

A Translational Study of a Silicon Phthalocyanine Substituted with a Histone Deacetylase Inhibitor for Photodynamic Therapy.

In this study, we synthesized and characterized a silicon phthalocyanine substituted with 3-hydroxypyridin-2-thione (SiPc-HDACi), designed to be a chemophotodynamic therapy agent acting as a histone deacetylase inhibitor, and we determined its photophysical, photochemical, and photobiological properties. Next, we evaluated its anticancer efficacy on MCF-7, double positive and MDA-MB-231, triple negative breast cancer cell lines, as well as on a healthy human endothelial cell line (HUVEC). Our results indicate that SiPc-HDACi can target nucleoli of cells, effectively inducing apoptosis while promoting cell cycle arrest thanks to its high singlet oxygen yield and its histone deacetylase downregulating properties, suggesting a powerful anticancer effect on breast cancer in vitro. Our further studies will be conducted with primary breast cancer cell culture to give a better insight into the anticancer mechanism of the compound.

Synthesis, characterization and oxygen sensitivity of cyclophosphazene equipped-iridium (III) complexes.

In this work, synthesis, characterization and oxygen sensing abilities of the cyclophosphazene-free and phenyl and naphtoxy-substituted cyclophosphazene bearing iridium (III) complexes (Ir-I, Ir-II and Ir-III) were presented. The complexes were characterized by NMR, absorption and emission spectroscopies, luminescence lifetime and quantum yield measurements. The molecules were successfully embedded in the ethyl cellulose matrix to fabricate the oxygen sensing electrospun mats via electrospinning technique. Oxygen induced luminescence of the iridium complexes around 600 nm has been followed as the analytical signal during oxygen sensitivity studies. They exhibited blue shifted, quenched emission towards triplet oxygen. The napthoxy substituted derivative exhibited 2.70 fold enhanced I0/I100 ratio compared to the free form in terms of the relative signal change. Room-temperature luminescence abilities, high photostabilities, large Stoke's shift values extending to 200 nm and high spectral response, especially between 0 and 10% pO2 make them promising candidates as oxygen probes. The test materials can be stored at the ambient air of the laboratory for at least 24 months.

Photodynamic therapy of hepatocellular carcinoma using tetra-triethyleneoxysulfonyl zinc phthalocyanine as photosensitizer.

The palliative treatment options for advanced hepatocellular carcinoma (HCC) are currently not satisfying. The use of photodynamic therapy (PDT) has gained much attention in the treatment of several cancers and has been approved as an alternative approach in treating different forms of cancers. We investigated for the first time the PDT effects of tetra-triethyleneoxysulfonyl zinc phthalocyanine (ZnPc) on HCC cells. Photoactivation of ZnPc loaded HCC cells resulted in a dose- and time- dependent growth inhibitory effect, the production of reactive oxygen species (ROS), induced cytotoxic effects and the induction of apoptosis in the investigated HCC cells (HepG2 and Huh-7). ZnPc-PDT inhibited the proliferation of HCC cells by up to 90% accompanied by a down-regulation of the activity and expression of the proliferation relevant mitogen-activated protein kinase (MAPK)-protein extracellular signal-regulated (ERK ½). Moreover, an up-regulation of proapoptotic BAX and a down-regulation of antiapoptotic B-cell lymphoma 2 (Bcl-2) expressions were observed with both proteins implicated in mitochondria-driven apoptosis. The investigation of the anti-tumor effect of ZnPc-PDT in vivo using the chicken chorioallantoic membrane assays (CAM) revealed a strong reduction in the size of HCC tumor plagues >80% after 4 days of PDT-treatment without affecting the survival of the developing embryo. The pronounced anti-proliferative and anti-tumor effects of ZnPc-PDT both in vitro and in vivo render ZnPc-PDT as a promising palliative treatment option for hepatocellular carcinoma.

Novel Silicon Phthalocyanines Bearing Triethylene Glycol Groups: Photophysical and Photochemical Properties as well as pH-Induced Spectral Behaviour.

Herein, novel silicon (IV) phthalocyanines peripherally substituted by triethylene glycol groups and bearing axial hydroxyl groups were synthesized and fully characterized by using different analyses techniques. The photophysical and photochemical properties of octa (2a) and tetra (2b) derivatives were investigated in DMF and DMSO. The effect of octa or tetra substitution on fluorescence quantum yield, singlet oxygen generation and photodegradation were examined, and the differences were evaluated regarding their potential efficiency in photodynamic therapy (PDT). Their pH-responses were investigated to determine the influence of protonation of azomethine nitrogen atoms on singlet oxygen generation efficiencies. Dramatic optical changes were observed by protonation of azomethine bridges of 2a and 2b. They exhibited signal decrease from pH 4.0 to 1.0 for 2a (pKa = 2.6) and pH 3.0 to 1.0 for 2b (pKa = 1.8). Besides, the compounds exhibited no aggregation tendency, moderate fluorescence quantum yield, solubility in common organic solvents, high singlet oxygen quantum yield and high photostability in DMF and in DMSO, these favorable properties making them good candidates as photosensitizer for PDT.

Synthesis, Photophysical and Photochemical Properties of a Set of Silicon Phthalocyanines Bearing Anti-Inflammatory Groups.

In this study, a series of novel silicon (IV) phthalocyanines conjugated axially with anti-inflammatory (sulindac) and triethylene glycol groups has been synthesized. Different synthetic strategies were attempted to obtain the targeted molecules in high yield. The compounds were fully characterized by using different analyses techniques. Our objectives were to generate a system with sulindac group which enhances the singlet oxygen generation and exhibits anti-cancer effect. Therefore, photophysical and photochemical properties of these compounds were investigated in different solvents. The substituent effect on fluorescence quantum yield and singlet oxygen generation was evaluated for efficiency in photodynamic therapy (PDT) as photosensitizer. The molecules exhibited no aggregation tendency, solubility in common organic solvents, high singlet oxygen quantum yield and high photostability in DMSO so these favourable properties make them good candidates as photosensitizer for PDT. In addition, their stabilities were investigated in DMSO, THF, acetonitrile and DMF.

Peptide-substituted phthalocyanine photosensitizers: design, synthesis, photophysicochemical and photobiological studies.

A series of phthalocyanine-peptide-quencher conjugates (6-9) were synthesized as photosensitizers for photodynamic therapy in cancer treatment. The photophysical, photochemical and photobiological properties of these activatable molecular beacons were also investigated in this study. For this purpose, the fluorescence, singlet oxygen and photodegradation quantum yields and fluorescence lifetime values of the compounds were determined in DMSO solutions. The phototoxicity and cytotoxicity of the systems were studied against the cervical cancer cell line named HeLa for an evaluation of their suitability for photodynamic therapy. The results showed that a maximum of 80% of HeLa cells were killed following light irradiation with photodynamic efficiency. All of the results showed that the novel activatable molecular beacons could be suitable candidates for cancer treatment via PDT technique.

Tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine for photodynamic cancer therapy.

Photodynamic therapy (PDT) has emerged as an effective and minimally invasive treatment option for several diseases, including some forms of cancer. However, several drawbacks of the approved photosensitizers (PS), such as insufficient light absorption at therapeutically relevant wavelengths hampered the clinical effectiveness of PDT. Phthalocyanines (Pc) are interesting PS-candidates with a strong light absorption in the favourable red spectral region and a high quantum yield of cancer cell destroying singlet oxygen generation. Here, we evaluated the suitability of tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as novel PS for PDT. ZnPc-induced phototoxicity, induction of apoptosis as well as cell cycle arresting effects was studied in the human gastrointestinal cancer cell lines of different origin. Photoactivation of ZnPc-pretreated (1-10 µM) cancer cells was achieved by illumination with a broad band white light source (400-700 nm) at a power density of 10 J/cm(2). Photoactivation of ZnPc-loaded cells revealed strong phototoxic effects, leading to a dose-dependent decrease of cancer cell proliferation of up to almost 100%, the induction of apoptosis and a G1-phase arrest of the cell cycle, which was associated with decrease in cyclin D1 expression. By contrast, ZnPc-treatment without illumination did not induce any cytotoxicity, apoptosis, cell cycle arrest or decreased cell growth. Antiangiogenic effects of ZnPc-PDT were investigated in vivo by performing CAM assays, which revealed a marked degradation of blood vessels and the capillary plexus of the chorioallantoic membrane of fertilized chicken eggs. Based on our data we think that ZnPc may be a promising novel photosensitizer for innovative PDT.

Modulation of the electronic and spectroscopic properties of Zn(II) phthalocyanines by their substitution pattern.

Four isomerically pure octasubstituted zinc phthalocyanines with variations in the attachment atom and positions of the substituents were selected for a systematic investigation of the effect of the substitution pattern on their electronic and spectroscopic properties. Effects which were investigated are the position, the electron donating and withdrawing properties, and the donating force of the substituent. The results are discussed and interpreted based on theoretical and experimental determination of the orbital levels. This work allows us to highlight which substitution patterns are the most suitable considering different common applications of phthalocyanines.

Assessing the dual activity of a chalcone-phthalocyanine conjugate: design, synthesis, and antivascular and photodynamic properties.

Photodynamic therapy (PDT) and vascular-disrupting agents (VDA) each have their advantages in the treatment of solid tumors, but also present drawbacks. In PDT, hypoxia at the center of the tumor limits conversion of molecular oxygen into singlet oxygen, while VDAs are deficient at affecting the rim of the tumor. A phthalocyanine-chalcone conjugate combining the VDA properties of chalcones with the PDT properties of phthalocyanines was designed to address these deficiencies. Its vascular targeting, photophysical, photochemical, photodynamic activities are reported herein.

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.

Volatile organic compounds sensing properties of tetrakis(alkylthio)-substituted lutetium(III) bisphthalocyanines thin films.

The effect of volatile organic compounds (VOCs) such as acetone, methanol, ethanol, chloroform, carbon tetrachloride, dichloromethane, and hexane on electrical conductivity of thin films of bis[tetrakis(alkylthio)phthalocyaninato]lutetium(III) double decker complexes [(C(n)H(2n+1)S)(4)Pc](2)Lu(III) was investigated. The [(C(n)H(2n+1)S)(4)Pc](2)Lu(III) molecules substituted with different alkylthia chains (n=6, 8, 10, 12, and 16) were coated on interdigital transducers using a jet spray technique. A change (increase or decrease) in the conductivity of the [(C(n)H(2n+1)S)(4)Pc](2)Lu(III) films was observed depending on the concentration of the VOCs, which was ranging from 500 to 5000 ppm. The decrease in the conductivity of the sensors for the dissolvent of the compounds (chloroform, carbon tetrachloride, dichloromethane and hexane) could be related to swelling of the films. On the other hand, the increase in the conductivity of the sensors for the other VOCs (acetone, methanol and ethanol) could be resulted from that the VOCs act as electron donors and/or acceptors in the films. A linear relationship between the sensor response and concentration of the VOC vapors is obtained. The sensitivities of the [(C(n)H(2n+1)S)(4)Pc](2)Lu(III) films were in the range of 2.10(-4)-3.10(-3)%/ppm.

Evaluation of a fast wastewater odour characterisation procedure using a chemical sensor array.

Sewage treatment works are one of the major sources that cause atmospheric odour pollution. The increase in the number of complaints about odour nuisance is due to the increase in environmental concerns. Unfortunately, the legislation on odour nuisance from sewage treatment works is very limited. In order to determine suitable thresholds on which to base legal standards, reliable and efficient odour measurement methods need to be defined. A chemical sensor array was developed for the purpose of measuring wastewater odour. This paper describes the development of the chemical sensor system which is specifically tuned to odours of wastewater origin and which can give an electronic measure of the wastewater odours. Odour emissions from a wastewater treatment facility were detected by using a quartz crystal microbalance (QCM) sensor array. The array consists of nine sensor elements, which were coated with different materials. In this paper, the usage of these novel instruments in the water industry was shown.

Synthesis, photophysical and photochemical properties of poly(oxyethylene)-substituted zinc phthalocyanines.

The synthesis, photophysical and photochemical properties of the tetra- and octa-poly(oxyethylene)substituted zinc (II) phthalocyanines are reported for the first time. The new compounds have been characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy, electronic spectroscopy and mass spectra. General trends are described for photodegradation, singlet oxygen, triplet state and fluorescence quantum yields, and triplet and fluorescence lifetimes of these compounds in dimethylsulfoxide (DMSO). Photophysical and photochemical properties of phthalocyanine complexes are very useful for PDT applications. The effects of the substituents on the photophysical and photochemical parameters of the zinc(II) phthalocyanines (3a, 5a and 6a) are also reported. The singlet oxygen quantum yields (Phi(Delta)), which give an indication of the potential of the complexes as photosensitizers in applications where singlet oxygen is required (Type II mechanism) ranged from 0.60 to 0.72. Thus, these complexes show potential as Type II photosensitizers. The fluorescence of the complexes was quenched by benzoquinone (BQ).