Engineering supramolecular helical assemblies via interplay between carbon(sp) tetrel and halogen bonding interactions.

Building supramolecular helical structures is a challenge due to difficulties in the design and control of competitive noncovalent forces. Herein, we report three scaffolds (1a, 1b, and 1c) decorated with -CN and -Br groups. These groups known for their ability to form multiple noncovalent interactions and with efficient design can be utilized to achieve such complex structures. X-Ray analyses revealed that the crystal packing of 1a, 1b and 1c is dominated by highly directional Br⋯CN Csp-tetrel bonding (1a), Br⋯π, Br⋯N (1b) and Br⋯Br (1c) XB interactions, and these interactions have led to the formation of achiral P/M, chiral M and achiral P/M helical assemblies, respectively. A detailed structural and computational analysis was performed to clarify the nature and estimate the strength of these interactions in helical assemblies. MEP analyses of 1a, 1b, and 1c have shown that the potential of electron-deficient and electron-rich regions within the structures has similar values. Yet, the geometric accessibility of σ-holes has differed with each scaffold. Thus, dominant interactions have changed and consequently led to different helical assembly formations. The interaction energies are around -11.4 (1a), -4.0 (1b), and -4.6 (1c) kcal mol-1 and mainly driven by dispersion, followed by electrostatic interactions. To our surprise, the Csp-tetrel bonding (1a), considered the weakest among non-covalent interactions, is the strongest interaction among the three scaffolds, which shows the importance of accessibility of Sigma holes. These findings are expected to contribute to the future rational design of complex self-assembled materials, utilizing Csp-tetrel and XB interactions, in various applications such as crystal engineering, organic semiconductors, sensor devices, and medicinal chemistry.

The chemical and electrochemical stimuli viologen substituted phthalocyanine with tunable optical features1.

In this study, viologen-tetrasubstituted Zn(II) phthalocyanines (PcV1 and PcV2) were designed and synthesized to achieve the tunable optical features via redox-active viologen groups. Several parameters relevant to the evaluation of the tunable optical features have been investigated: UV-Vis, cyclic voltammetry (CV), EPR, square wave voltammetry (SWV), and theoretical analyses. The results showed that upon reductions and oxidations of viologen groups either chemically or electrochemically, the optical features of PcV1 and PcV2 change drastically with switchable processes. These outcomes indicate that achieving control over optical features of large organic chromophores such as Pc with our rational design can be used for the design of new complex organic electronic materials.

Development of AB3-Type Novel Phthalocyanine and Porphyrin Photosensitizers Conjugated with Triphenylphosphonium for Higher Photodynamic Efficacy.

There are a number of lipophilic cations that can be chosen; the triphenylphosphonium (TPP) ion is particularly unique for mitochondrion targeting, mainly due to its simplicity in structure and ease to be linked to the target molecules. In this work, mitochondrion-targeted AB3-type novel phthalocyanine and porphyrin photosensitizers (PSs) were synthesized and their photophysical photochemical properties were defined. Fluorescence quantum yields (ΦF) are 0.009, 0.14, 0.13, and 0.13, and the singlet-oxygen quantum yields (ΦΔ) are 0.27, 0.75, 0.57, and 0.58 for LuPcPox(OAc), AB 3 TPP-Pc, AB 3 TPP-Por-C4, and AB 3 TPP-Por-C6, respectively. To evaluate the photodynamic efficacy of the TPP-conjugated PS cell viabilities of A549 and BEAS-2B lung cells were comparatively measured and IC-50 values were determined. AB 3 TPP-Por-C4, AB 3 TPP-Por-C6, and AB 3 TPP-Pc compounds compared to the reference molecules ZnPc and H 2 TPP were found to be highly cytotoxic (sub-micromolar concentration) under the light. LuPcPox(OAc) is the most effective molecule regarding cell killing (the activity). The cell killing of the TPP-conjugated porphyrin derivatives exhibits a similar response compared to LuPcPox(OAc) when the light absorbing factor of the PS is normalized at 660 nm: TPP-conjugated porphyrins absorb less light (lower extinction coefficient) but produce more radical species (higher singlet-oxygen quantum yield) and therefore effectively kill the cells. The singlet oxygen-producing capacity of AB 3 TPP-Pc is almost 3 times higher compared to LuPcPox(OAc) and 50% more efficient with respect to ZnPc, suggesting that TPP-conjugated phthalocyanine may serve as a good photosensitizer for photodynamic therapy (PDT). The high singlet oxygen generation capacity of these novel TPP-conjugated porphyrin and phthalocyanine PS suggests that they might be useful for PDT requiring lower photosensitizer concentration and reduced energy deposited through less light exposure.

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%.

Phthalocyanine-Conjugated Glyconanoparticles for Chemo-photodynamic Combination Therapy.

Combination cancer therapy based on multifunctional nanomaterials has attracted great attention. The present work focuses on the preparation of the glycopolymeric nanoparticle, which contains a photosensitizer (zinc(II)phthalocyanine, ZnPc) and an anticancer drug (Doxorubicin, Dox). First, a novel mono azide-functional ZnPc-N3 with seven hydrophilic ethylene oxide chains was synthesized. Next, ZnPc alone or together with Dox bearing glycopolymers was synthesized via the RAFT polymerization method and then self-assembled into glyconanoparticles (GNPs) with narrow particle size distribution. Then the evaluation of the biological activity of GNPs (GNPs-ZnPc and GNPs-ZnPc/Dox) for dual photodynamic therapy (PDT) and chemotherapy against human breast cancer cells was investigated. The constructed GNPs were identified via general characterization methods, including dynamic light scattering (DLS) and transmission electron microscopy (TEM). The prepared GNPs-ZnPc/Dox demonstrated remarkable photophysical and photochemical properties, involving good colloidal stability in biological conditions, pH-responsive drug release, and the capacity to generate singlet oxygen under light irradiation. The outer layer of nanoparticles covered by fructose sugar moieties achieves a targeted cancer therapy owing to GLUT5 (a well-known fructose transporter) overexpression toward breast cancer cells. In vitro experiments were then performed to evaluate the chemo/phototoxicity, cellular uptake, and anticancer efficacy of GNPs-ZnPc/Dox. In comparison with free Dox, human breast cancer cells treated with GNPs-ZnPc/Dox exhibited a higher cellular internalization via GLUT5 targeting. In particular, the GNPs-ZnPc/Dox nanoplatform revealed an excellent synergistic anticancer activity in comparison with free ZnPc-N3 and free Dox, representing a novel and promising chemo-photodynamic combination therapeutic methodology to improve therapeutic efficacy.

Insight into the effects of the anchoring groups on the photovoltaic performance of unsymmetrical phthalocyanine based dye-sensitized solar cells.

Push-pull zinc phthalocyanine dyes bearing hexylsulfanyl moieties as electron donors and carboxyethynyl as mono- or di-anchoring groups have been designed, synthesized and tested as sensitizers in dye-sensitized solar cells (DSSCs). The effects of the anchoring groups on the optical, electrochemical and photovoltaic properties were investigated. The incorporation of a carboxyethynyl group in GT23 has a considerable effect on preventing dye aggregation due to its relatively non-planar structure. The mono-anchoring dye bearing a phenyl carboxyethynyl group, GT5, has a higher molar extinction coefficient and sufficient charge injection into the TiO2 conduction band. Therefore, GT5 achieved at least 90% higher power conversion efficiency than the di-anchoring dyes (GT31 and GT32). Time-dependent density functional theory (PBE0/6-31G(d,p)) was also used to calculate the electronic absorption spectra, which predicted very well the measured UV-Vis with an error of up to 0.11 eV for the Q bands and 0.3 eV for the B bands. The longest charge transfer bands are obtained in the visible light region and they correspond to a transfer phthalocyanine core → substituent with a carboxyethynyl group where the absorptions of GT32 (465 nm) and GT31 (461 nm) are red-shifted compared to GT23 (429 nm) and GT5 (441 nm). The interaction energy between the phthalocyanine and a cluster of anatase-TiO2 (H4Ti40O82) was calculated using density functional theory. For all phthalocyanines, the interaction favored is monodentate and corresponds to -O(OH)Ti(TiO2), where the stronger interaction occurs for GT32 (-2.11 eV) and GT31 (-2.25 eV). This study presents the molecular combination of the anchoring groups in zinc phthalocyanine sensitizers, which is one of the effective strategies for improving the performance of DSSCs.

Synthesizing and evaluating the photodynamic efficacy of asymmetric heteroleptic A7B type novel lanthanide bis-phthalocyanine complexes.

In this study heteroleptic A7B type novel Lu(iii) and Eu(iii) lanthanide phthalocyanines (LnPc(Pox)[Pc'(AB3SH)]) with high extinction coefficients have been synthesized as candidate photosensitizers with reaction yields higher than 33%. The singlet oxygen quantum yields of LuPc(Pox)[Pc'(AB3SH)] and EuPc(Pox)[Pc'(AB3SH)], respectively, were measured 17% and 1.4% by the direct method in THF. The singlet oxygen quantum yield of LuPc(Pox)[Pc'(AB3SH)] in THF is the highest among lutetium(iii) bis-phthalocyanine complexes to date. The photodynamic efficacy of the heteroleptic lanthanide phthalocyanines was evaluated by measuring cell viabilities of A549 and BEAS-2B lung cells, selected to representing in vitro models for testing cancer and normal cells against potential drugs. The cell viabilities demonstrated concentration dependent behavior and were varied by the type of phthalocyanines complexes. Irradiation of the cells for 30 minutes with LED array at 660 nm producing flux of 0.036 J cm-2 s-1 increased cell death for LuPcPox-OAc, LuPc(Pox)[Pc'(AB3SH)] and ZnPc. The IC50 concentrations of LuPc(Pox)[Pc'(AB3SH)] and ZnPc were determined to be below 10 nM for both cell lines, agreeing very well with the singlet oxygen quantum yield measurements. These findings suggest that LuPc(Pox)[Pc'(AB3SH)] and particularly LuPcPox-OAc are promising drug candidates enabling lowered dose and shorter irradiation time for photodynamic therapy.

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.

Halogen-Bonded BODIPY Frameworks with Tunable Optical Features*.

The ability to tune the optical features of BODIPY materials in the solid state is essential for their photorelated application and requires efficient control of the crystal packing. In this study, such control of BODIPY supramolecular assemblies was achieved by deliberate design and synthesis of a BODIPY containing a strong halogen-bond (XB) acceptor (-NO2 ) and donor (I, Br) to mediate XB interactions. The di-halogenated structures formed isostructural mono-coordinate motif B3, B4 (1D tubular structure) and symmetric bifurcated motif B4-II (1D zigzag chains structure) through N-O⋅⋅⋅I, Br XB interactions. These XB interactions promote singlet-to-triplet intersystem crossing and triplet-to-singlet reverse intersystem crossing due to partial delocalization of oxygen electrons onto Br and I, which leads to unexpected fluorescence enhancement of B4-II. Finally, the indirect optical band gaps of B3, B4 and B4-II were amenable to tuning in the range of 1.85-2.50 eV by XB-driven crystal packings.

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.

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.

Effect of the Substitution Pattern (Peripheral vs Non-Peripheral) on the Spectroscopic, Electrochemical, and Magnetic Properties of Octahexylsulfanyl Copper Phthalocyanines.

In order to investigate the substitution position effect on the spectroscopic, electrochemical, and magnetic properties of copper phthalocyanines, a detailed structure-property analysis has been performed by examining two copper phthalocyanines that are octasubstituted by hexylsulfanyl chains respectively in the peripheral (Cu-P) and non-peripheral (Cu-NP) positions. Cu-NP showed a marked near-IR maximum absorption compared to Cu-P and, accordingly, a smaller HOMO-LUMO energy gap, calculated via the electrochemical results and simulations in the gas phase, as well as for Cu-NP from its crystallographic data. An electron-spin resonance (ESR) technique is used to extract the g values from the powder spectra that are taken at room temperature. The g values were determined to be g∥ = 2.160 and g⊥ = 2.045 for Cu-P and g∥ = 2.150 and g⊥ = 2.050 for Cu-NP. These values indicate that the paramagnetic copper center in both phthalocyanines has axial symmetry with a planar anisotropy ( g∥ > g⊥). The ESR spectra in solution could be obtained only for Cu-P. Curie law is used to fit the experimental data of the magnetic susceptibility versus temperature graphs, and the Curie constant ( C) and diamagnetic/temperature-independent paramagnetic (α) contributions are deduced as 0.37598 (0.39576) cm3·K/mol and -23 × 10-5 (25 × 10-5) cm3/mol respectively for Cu-P and Cu-NP. The room temperature magnetic moment value (1.70 µB) is close to the spin-only value (1.73 µB) for the peripheral complex, showing that there is no orbital contribution to µeff. In contrast, at room temperature, the value of the magnetic moment (1.77 µB) is above the spin-only value, showing an orbital contribution to the magnetic moment. Cu-NP's room temperature magnetic moment value is larger than the value for Cu-P, demonstrating that the orbital contribution to the magnetic moment depends upon the substituent position. The magnitudes of the effective magnetic moment values also support that both Cu-P and Cu-NP complexes have square-planar coordination. This result is consistent with the determined g values. The spin densities were determined experimentally, and the results suggest that the positions of the substituents affect these values (0.469 for Cu-P and 0.490 for Cu-NP).

Novel zinc­ and silicon­phthalocyanines as photosensitizers for photodynamic therapy of cholangiocarcinoma.

Photodynamic therapy (PDT) has emerged as an effective and minimally invasive cancer treatment modality. In the present study, two novel phthalocyanines, tetra­triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) and dihydroxy­2,9(10),16(17),23(24)­tetrakis(4,7,10­trioxaundecan­1­sulfonyl) silicon phthalocyanine (Pc32), were investigated as photosensitizers (PS) for PDT of cholangiocarcinoma (CC). ZnPc showed a pronounced dose­dependent and predominantly cytoplasmic accumulation in EGI­1 and TFK­1 CC cell lines. Pc32 also accumulated in the CC cells, but this was less pronounced. Without photoactivation, the PS did not exhibit any antiproliferative or cytotoxic effects. Upon photoactivation, ZnPc induced the formation of reactive oxygen species (ROS) and immediate phototoxicity, leading to a dose­dependent decrease in cell proliferation, and an induction of mitochondria­driven apoptosis and cell cycle arrest of EGI­1 and TFK­1 cells. Although photoactivated Pc32 also induced ROS formation in the two cell lines, the extent was less marked, compared with that induced by ZnPc­PDT, and pronounced antipoliferative effects occurred only in the less differentiated EGI­1 cells, whereas the more differentiated TFK­1 cells did not show sustained growth inhibition upon Pc32­PDT induction. In vivo examinations on the antiangiogenic potency of the novel PS were performed using chorioallantoic membrane (CAM) assays, which revealed reduced angiogenic sprouting with a concomitant increase in nonperfused regions and degeneration of the vascular network of the CAM following induction with ZnPc­PDT only. The study demonstrated the pronounced antiproliferative and antiangiogenic potency of ZnPc as a novel PS for PDT, meriting further elucidation as a promising PS for the photodynamic treatment of CC.

Novel zinc phthalocyanine as a promising photosensitizer for photodynamic treatment of esophageal cancer.

Photodynamic therapy (PDT) has gathered much attention in the field of cancer treatment and is increasingly used as an alternative solution for esophageal cancer therapy. However, there is a constant need for improving the effectiveness and tolerability of the applied photosensitizers (PS). Here, we propose tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as a promising PS for photodynamic treatment of esophageal cancer. ZnPc-induced phototoxicity was studied in two human esophageal cancer cell lines: OE-33 (adenocarcinoma) and Kyse-140 (squamous cell carcinoma). In vitro studies focused on the uptake and intracellular distribution of the novel ZnPc as well as on its growth inhibitory potential, reactive oxygen species (ROS) formation and the induction of apoptosis. The chicken chorioallantoic membrane assay (CAM assay) and studies on native Wistar rats were employed to determine the antineoplastic and antiangiogenic activity of ZnPc-PDT as well as the tolerability and safety of non-photoactivated ZnPc in vivo. ZnPc was taken up by cancer cells in a dose- and time-dependent manner and showed a homogeneous cytoplasmic distribution. Photoactivation of ZnPc-loaded (1-10 µM) cells led to a dose-dependent growth inhibition of esophageal adenocarcinoma and squamous cell carcinoma cells of >90%. The antiproliferative effect was based on ROS-induced cytotoxicity and the induction of mitochondria-driven apoptosis. In vivo studies on esophageal tumor plaques grown on the CAM revealed pronounced antiangiogenic and antineoplastic effects. ZnPc-PDT caused long-lasting changes in the vascular architecture and a marked reduction of tumor feeding blood vessels. Animal studies confirmed the good tolerability and systemic safety of ZnPc, as no changes in immunological, behavioral and organic parameters could be detected upon treatment with the non-photoactivated ZnPc. Our findings show the extraordinary photoactive potential of the novel ZnPc as a photosensitizer for PDT of esophageal cancer.

Mechanism of the Zn(II)Phthalocyanines' Photochemical Reactions Depending on the Number of Substituents and Geometry.

In this work, the synthesis and the nonlinear absorption and population dynamics investigation of a series of zinc phthalocyanines (ZnPcs) dissolved in chloroform are reported. In order to determine the relevant spectroscopic parameters, such as absorption cross-sections of singlet and triplet excited states, fluorescence relaxation times, intersystem crossing, radiative decay and internal conversion, different optical and spectroscopic techniques were used. By single pulse and pulse train Z-scan techniques, respectively, singlet and triplet excited states' absorption cross-section were determined at 532 nm. Furthermore, the intersystem crossing time was obtained by using both techniques combined with the fluorescence lifetime determined by time-resolved fluorescence. The radiative and internal conversion rates were determined from the fluorescence quantum yield of the samples. Such spectroscopy parameters are fundamental for selecting photosensitizers used in photodynamic therapy, as well as for many other applications.

Antimicrobial activity of a quaternized BODIPY against Staphylococcus strains.

A novel BODIPY derivative was designed for biomedical applications. Its mono-quaternized structure ensured its water-solubility and suitable amphiphilicity. Showing no singlet oxygen generation to avoid damage to healthy cells, this new derivative proved to be an extremely promising antimicrobial agent, with activity equal or superior to ampicillin against MRS Staphylococcus strains with no short-term resistance issue. Its activity against MSS Staphylococcus strains was largely superior to those of ampicillin and reached the activity of vancomycin against MSS S. epidermidis. This latter result is in particular extremely promising for the treatment of hospital-acquired infections. Also the fluorescence properties of BODIPY allowed imaging of the uptake.

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.

Copper Phthalocyanine Functionalized Single-Walled Carbon Nanotubes: Thin Films for Optical Detection.

Thin films of non-covalently hybridized single-walled carbon nanotubes (SWCNT) and tetra-substituted copper phthalocyanine (CuPcR4) molecules have been produced from their solutions in dimethylformamide (DMF). FTIR spectra revealed the 7π-7π interaction between SWCNTs and CuPcR4 molecules. DC conductivity of films of acid-treated SWCNT/CuPcR4 hybrid has increased by more than three orders of.magnitude in comparison with conductivity of CuPcR4 films. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements have shown that films obtained from the acid-treated SWCNTs/CuPcR4 hybrids demonstrated more homogenous surface which is ascribed to the highly improved solubility of the hybrid powder in DMF Using total internal reflection ellipsometry spectroscopy (TIRE), thin films of the new hybrid have been examined as an optical sensing membrane for the detection of benzo[a]pyrene in water to demonstrate the sensing properties of the hybrid.