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The creation of combined nanomedicines and their controlled release under the influence of photoinduction is an actively developing branch of scientific research. This work is devoted to the development of models of solid lipid nanoparticles for a well-known antitumor drug – gefitinib in combination with a photoindicating agent – a photosensitizer from the phthalocyanine group. Nanoparticles were obtained by several methods: hot homogenization with stearic acid, sesame oil and Tween 80 and by one-step dispersion with copolymers of lactic and glycolic acids and polyvinyl alcohol. In vitro experiments when irradiating particles with a laser in the near-infrared range (about 730 nm) proved the advantage of using combined nanoparticles with gefitinib and a photosensitizer compared to monotherapy, while the activity in terms of IC50 was 5.1-8.7 times higher for gefitinib and 1.5-1.8 times for the photosensitizer.

Cannabis producers, consumers, and regulators need fast, accurate, point‐of‐use sensors to detect Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD) from both liquid and vapor source samples, and phthalocyanine‐based organic thin‐film transistors (OTFTs) provide a cost‐effective solution. Chloro aluminum phthalocyanine (Cl‐AlPc) has emerged as a promising material due to its unique coordinating interactions with cannabinoids, allowing for superior sensitivity. This work explores the molecular engineering of AlPc to tune and enhance these interactions, where a series of novel phenxoylated R‐AlPcs are synthesized and integrated into OTFTs, which are then exposed to THC and CBD solution and vapor samples. While the R‐AlPc substituted molecules have a comparable baseline device performance to Cl‐AlPc, their new crystal structures and weakened intermolecular interactions increase sensitivity to THC. Grazing‐incidence wide‐angle X‐ray scattering (GIWAXS) and atomic force microscopy (AFM) are used to investigate this film restructuring, where a significant shift in the crystal structure, grain size, and film roughness is detected for the R‐AlPc molecules that do not occur with Cl‐AlPc. This significant crystal reorganization and film restructuring are the driving force behind the improved sensitivity to cannabinoids relative to Cl‐AlPc and demonstrate that analyte–semiconductor interactions can be enhanced through chemical modification to create more responsive OTFT sensors. [ABSTRACT FROM AUTHOR]

[Display omitted] Water-soluble nanosized systems of aluminum phthalo- cyanine, which is a promising photosensitizer for photodynamic therapy and fluorescence diagnostics, were obtained by encapsulating it in biocompatible copolymers of N -vinylpyrrolidone with mono- and dimethacrylates. The physicochemical (water solubility, stability and size of nanoparticles) and photophysical (absorption and fluorescence) properties of the resulting nanoparticles in aqueous solution were determined. Quantum chemical modeling revealed the formation of coordination bonds between the Al atom of the dye and the oxygen atoms of all monomer units. [ABSTRACT FROM AUTHOR]

In a series of in vitro experiments, the optimum regimes of laser treatment were determined for effective photodynamic inactivation of Mycobacterium tuberculosis at a constant dose of aluminum phthalocyanine. Reference laboratory drug-susceptible strain H37Rv and clinical isolates of M. tuberculosis with varying degrees of resistance to antibiotics were used. Suspensions of M. tuberculosis were incubated with aluminum phthalocyanine in a concentration of 5 μg/ml and then subjected to photodynamic inactivation with high- or low- intensity laser irradiation at λ=662 nm at various parameters of light power density. Mycobacteria survival rate was assessed by CFU assay on solid media. It was shown that at the specified dose of the photosensitizer, the photodynamic inactivation of mycobacterium was characterized by inhibition and complete cessation of their growth depending on the dose density of the laser energy. Effective photodynamic inactivation started from a light dose density of 46.9 J/cm2 at a radiation power of 0.01 W and from 56.25 J/cm2 at a radiation power of 0.1 W. Photodynamic inactivation at low laser power is more effective against drug-susceptible strains of M. tuberculosis. [ABSTRACT FROM AUTHOR]

This work reports for the first time on the synthesis, characterization, and photodynamic therapy efficacy of the novel aluminium (III) chloride 2(3), 9(10), 16(17), 23(24)-tetrakis-(sodium 2-mercaptoacetate) phthalocyanine (AlClPcTS41) when alone and when conjugated to PEGylated copper–gold bimetallic nanoparticles (PEG-CuAuNPs) as photosensitizers on colon cancer cells (Caco-2). The novel AlClPcTS41 was covalently linked to the PEG-CuAuNPs via an amide bond to form AlClPcTS41-PEG-CuAuNPs. The amide bond was successfully confirmed using FTIR while the crystal structures were studied using XRD. The morphological and size variations of the PEG-CuAuNPs and AlClPcTS41-PEG-CuAuNPs were studied using TEM, while the hydrodynamic sizes and polydispersity of the particles were confirmed using DLS. The ground state electron absorption spectra were also studied and confirmed the typical absorption of metallated phthalocyanines and their nanoparticle conjugates. Subsequently, the subcellular uptake, cellular proliferation, and PDT anti-tumor effect of AlClPcTS41, PEG-CuAuNPs, and AlClPcTS41-PEG-CuAuNPs were investigated within in vitro Caco-2 cells. The designed AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs demonstrated significant ROS generation abilities that led to the PDT effect with a significantly decreased viable cell population after PDT treatment. These results demonstrate that the novel AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs had remarkable PDT effects against Caco-2 cells and may trigger apoptosis cell death pathway, indicating the potential of the AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs in enhancing the cytotoxic effect of PDT treatment. [ABSTRACT FROM AUTHOR]

In recent years, the development of methods of photodynamic therapy (PDT) and photodynamic photodiagnostics (PD) in Russia is characterized by an intensive rise, steadily growing interest of specialists from various medical specialties in the method of specialists from various medical specialties, an increase in the level of equipment number of hospitals with the necessary equipment for performing PD and PDT, the and the emergence of new photosensitizers on the pharmaceutical market, and an increasing increase in the level of patients’ confidence in these methods. This study analyzes the dynamics of the development of the clinical application and scientific developments of PD and PDT over the past decade in Russia in terms of the volume of public procurement of photosensitizers, as well as the activity of research work in the field of PD and PDT, the number of candidate and doctoral dissertations theses on this topic and the number of scientific publications in the RSCI. 688 contracts for the supply of photosensitizers for clinical use were analyzed. The analysis showed a stable annual growth in the volume of public procurement of photosensitizers, an increase in the number of subjects of the Russian Federation and clinical centers that purchase photosensitizers through the portal www.zakupki.gov.ru. From 2014 to 2020, the total volume of public procurement of all photosensitizers increased by 8 times (from 36.42 million rubles (3.58 thousand packages) to 307.37 million rubles (18.99 thousand packages)). The annual increase in the volume of public procurement in numerical terms over the previous 6 years ranged from 9.4% to 63.2% in different years. The main share of state purchases of photosensitizers falls on Moscow and St. Petersburg, h. However, in recent years there has been a noticeable trend towards an increase in sales of photosensitizers in the regions. Thus, in recent years, the share of purchases of photosensitizers in the constituent entities of the Russian Federation with a population of less than 1 million people has significantly increased (from 2.9% of the total number of purchases in 2014 to 25.3% in 2020). Also, in recent years, there has been a significant increase in the activity of research work activity in the field of PD and PDT. The number of defended candidate and doctoral dissertations theses defended in the field of PD and PDT photodynamic therapy and fluorescent diagnostics has been steadily high in recent years and, in some scientific specialties, reaches 2-3% of the total number of defended dissertations theses defended in these specialties. The increase in the total number of publications over 10 years according to the RSCI was 224% (from 218 publications in 2014 to 489 publications in 2019), according to the RSCI. The results obtained confirm the growing demand for photosensitizers for photodynamic therapy and fluorescence diagnostics in clinical practice, the expansion of the geography of the use of methods, as well and the stable interest in this topic in the research environment.

Today, fluorescent diagnostics and photodynamic therapy are promising methods for diagnosing and treating oncological diseases. The development of new photosensitizers (PS) is one of the most important tasks to improve the efficiency of both laser-induced diagnostics and therapy. In our study, we conjugated PS with AIS/ZnS triple quantum dots (QDs) to obtain non-aggregated complexes. It was shown that the conjugation of PS with QDs does not change the PS fluorescence lifetime, which is a marker of the preservation of PS photophysical properties. In particular, efficient resonant Förster energy transfer (FRET), from QDs to PS molecules in the conjugate, increases the PS luminescence response. The FRET from QD to PS molecules with different ratios of donor and acceptors are shown. It has been demonstrated that the average efficiency of FRET depends on the ratio of PS and QD and reaches a maximum value of 80% at a ratio of 6 PS molecules per 1 QD molecule. Thus, these studies could help to contribute to the development of new complexes based on QD and PS to improve the efficiency of phototheranostics. [ABSTRACT FROM AUTHOR]

The study of phthalocyanines, known photosensitizers, for biomedical applications has been of high research interest for several decades. Of specific interest, nanophotosensitizers are crystalline aluminum phthalocyanine nanoparticles (AlPc NPs). In crystalline form, they are water-insoluble and atoxic, but upon contact with tumors, immune cells, or pathogenic microflora, they change their spectroscopic properties (acquire the ability to fluoresce and become phototoxic), which makes them upcoming agents for selective phototheranostics. Aqueous colloids of crystalline AlPc NPs with a hydrodynamic size of 104 ± 54 nm were obtained using ultrasonic dispersal and centrifugation. Intracellular accumulation and localization of AlPc were studied on HeLa and THP-1 cell cultures and macrophages (M0, M1, M2) by fluorescence microscopy. Crystallinity was assessed by XRD spectroscopy. Time-resolved spectroscopy was used to obtain characteristic fluorescence kinetics of AlPc NPs upon interaction with cell cultures. The photodynamic efficiency and fluorescence quantum yield of AlPc NPs in HeLa and THP-1 cells were evaluated. After entering the cells, AlPc NPs localized in lysosomes and fluorescence corresponding to individual AlPc molecules were observed, as well as destruction of lysosomes and a rapid decrease in fluorescence intensity during photodynamic action. The photodynamic efficiency of AlPc NPs in THP-1 cells was almost 1.8-fold that of the molecular form of AlPc (Photosens). A new mechanism for the occurrence of fluorescence and phototoxicity of AlPc NPs in interaction with cells is proposed. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is regarded as an alternative anti-tumor therapy which involves the administration of photosensitizers (PSs) and irradiation with specific light. However, conventional PDT therapy has been limited to the efficiency of PS delivery. A nanocarrier system could provide an effective platform for PS delivery and improve the efficiency of antitumor PDT. In this article, we prepared a complex consisting of aluminum phthalocyanine (AlPcS) and CdSe/CdZnS core-shell structure QDs and investigated the interaction between the complex and tumor cells. A more significant internalization of the conjugation was observed compared to free AlPcS via confocal fluorescence imaging. The tumor cells exhibited an obvious apoptotic trend after QD–AlPcS-mediated PDT.

Ternary planar heterojunction organic solar cells (PHJ-OPVs) were fabricated using three organic small molecules, alpha-sexithiophene (α-6T), aluminum phthalocyanine chloride (AlPcCl) and fullerene (C60). These molecules can be easily sublimated under a vacuum; they have complementary optical absorption spectra and their energy band structure alignment is favorable for electronic charge transfers. Moreover, α-6T and AlPcCl have almost the same HOMO, which is desirable to avoid any decrease in open circuit voltage. The AlPcCl intercalated layer bridges the energy levels of the electron donor, α-6T, and the electron acceptor, C60, which facilitates charge transport through the energy cascade effect. Moreover, the charge carrier mobility measurements of AlPcCl, using the space charge limited current method, demonstrated that it iss ambipolar. All these properties combine to improve the power conversion efficiency (PCE) of PHJ-OPVs by moving from binary structures (α-6T/C60, α-6T/AlPcCl and AlPcCl/C60) to ternary ones (α-6T/AlPcCl/C60). We show, in this study, that both interfaces of the ternary PHJ-OPVs are efficient for carrier separation. After optimization of the different layer thickness, we show that, by comparing the optimum efficiencies of the binary PHJ-OPVs, the realization of ternary PHJ-OPVs, based on the active layers α-6T/AlPcCl/C60, using the following optimized method, allows us to achieve a PCE of 4.33%. [ABSTRACT FROM AUTHOR]

In this study, we have assessed the potential application of group 13 and 14 metal and metalloid phthalocyanines ((X)n-MPcs) and their axially substituted derivatives as hole-transporting layers in organic light emitting diodes (OLEDs). OLEDs studied herein have the generic structure of glass/ ITO/(N,N′-di(1-naphthyl)-N,N0-diphenyl-(1,1′-biphenyl)-4,4′-diamine (NPB) or (X)n-MPc)(50 nm)/Alq3 (60 nm)/LiF (1 nm)/Al (80 nm), where X is an axial substituent group. OLEDs using chloro aluminum phthalocyanine (Cl-AlPc) showed good peak luminance values of 2620 ± 113 cd/m² at 11 V. To our knowledge, Cl-AlPc has not previously been shown to work as a hole transport material (HTL) in OLEDs. Conversely, the di-chlorides of silicon, germanium, and tin phthalocyanine (Cl2-SiPc, Cl2-GePc, and Cl2-SnPc, respectively) showed poor performance compared to Cl-AlPc, having peak luminances of only 38±4 cd/m² (12 V), 23±1 cd/m² (8.5 V), and 5965 cd/m² (13.5 V), respectively. However, by performing a simple axial substitution of the chloride groups of Cl2-SiPc with pentafluorophenoxy groups, the resulting bis(pentafluorophenoxy) silicon phthalocyanine (F10-SiPc) containing OLED had a peak luminance of 5141±941 cd/m² (10 V), a two order of magnitude increase over its chlorinated precursor. This material showed OLED characteristics approaching those of a baseline OLED based on the well-studied triarylamine NPB. Attempts to attach the pentafluorophenoxy axial group to both SnPc and GePc were hindered by synthetic difficulties and low thermal stability, respectively. In light of the performance improvements observed by simple axial substitution of SiPc in OLEDs, the use of axially substituted MPcs in organic electronic devices remains of continuing interest to us and potentially the field in general. [ABSTRACT FROM AUTHOR]

The μ-(oxo)bis[tetra-tert-butylphthalocyaninato] aluminum(III) [(tBu)4PcAl]2O films with the crystallites oriented preferably in one direction were obtained via chemical transformation of tetra-tert-butylsubstituted chloroaluminum(III) phthalocyanine (tBu)4PcAlCl film upon its annealing in magnetic field. A comparative analysis of the influence of post-deposition annealing process without and under applied magnetic field of 1 T, on the orientation and morphology of (tBu)4PcAlCl and [(tBu)4PcAl]2O films, has been carried out by the methods of UV-vis, Infrared and Raman spectroscopies, XRD as well as atomic force microscopy. The formation of [(tBu)4PcAl]2O films with elongated crystallites having preferential orientation was observed upon heating of the films in magnetic field while annealing without magnetic field under the same conditions does not demonstrate any effect on the structure and morphology of these films. The reasons of the sensitivity of this reaction to the presence of such magnetic field is discussed and studied by electronic paramagnetic resonance spectroscopy. [ABSTRACT FROM AUTHOR]

Early diagnosis of caries and tooth enamel microcracks is of great importance for preventing the destruction of healthy tooth enamel. Inorder to detect microcracks in the enamel and pathogenic microflora foci that can cause caries, nanoform of aluminum phthalocyanine (AlPc) can be used as a marker. In a colloidal solution, the nanoparticles do not fluoresce, unlike their molecular form. To convert the particle into its molecular form, it is necessary to have a solvent or specific environment (bacteria, macrophages, etc.). That is why the hydrophobic nanoparticles of aluminum phthalocyanine (nAlPc) can act as markers for detecting hidden pathogenic microflora during fluorescent diagnostics. Further reduction of the diagnosis time and increase the efficiency can be achieved by using biologically compatible surfactants as additional activators of nAlPc.In order to carry out local fluorescence spectroscopy of enamel microcracks and pathogenic microflora foci on the enamel surface, a model compound containing surfactants, auxiliary components and nAlPc colloid at a concentration of 10 mg/l was prepared.Studies on the interaction of the model compound with nAlPc and Protelan MST-35 with tooth enamel ex vivo have shown this surfactant to be a promising auxiliary activator of the nanoparticles, allowing conducting local fluorescence spectroscopy of the tooth enamel surface 3 min after application. In addition, statistical processing of the results showed the effectiveness of using the model compound for local fluorescence spectroscopy of the enamel surface in order to detect the enamel microcracks and the pathogenic microflora accumulation foci that can lead to the development of a cariogenic process.

Metal phthalocyanine-based porous organic polymers have gained increasing attention in numerous areas, but their application potential has yet to be comprehensively explored. In this study, a planar polymer (AlPc-CC POP) with excellent electrochemical capabilities was prepared using a straightforward substitution method. The electrocatalytic activity of AlPc-CC POP towards nifedipine (NIF) was investigated using electrochemical analysis. Under optimal conditions, the electrochemical sensor response to NIF was linearly positively correlated at concentrations ranging from 0.04 to 50 μM with a detection threshold of 0.0273 μM. Moreover, the sensor performed well in terms of reproducibility, stability, and selectivity. Notably, the constructed sensing platform enabled the determination of NIF levels in pharmaceuticals and human sera. This work provides a generalized platform for the detection of antihypertensive NIF and validates the potential of phthalocyanine-based porous organic polymer for sensing. [Display omitted] • Synthesis of cellular aluminum phthalocyanine-based porous organic polymer (AlPc-CC POP). • AlPc-CC POP/GCE sensor successfully used for the first time in electrochemistry. • The proposed device performed well in terms of reproducibility, stability, and selectivity. • The sensor was successfully applied to monitor nifedipine in pharmaceutical and biological samples with good accuracy and precision. [ABSTRACT FROM AUTHOR]

New hybrid graphene and aluminum phthalocyanine structures are synthesized (graphene is prepared with the sonochemical method in N,N-dimethylformamide). The physicochemical properties of these hybrid systems are studied with transmission electron microscopy, Raman spectroscopy, and optical spectroscopy. We show that graphene in the system prevents the aggregation of aluminum phthalocyanine and leads to its stabilization in monomeric form. The results may be used to obtain new materials for various sciences and technologies. [ABSTRACT FROM AUTHOR]

The development and the spectral research of unique coating as crystalline nanoparticles of IR photosensitizers were performed for the creation of hydroxyapatite implants with photobactericidal properties. It has been proved that by the interaction of nanoparticles covering implant with the polar solvent, which simulates the interaction of the implant with the biocomponents in vivo (fast proliferating and with immunocompetent cells), photosensitizers nanoparticles change the spectroscopic properties, becoming fluorescent and phototoxic. Thus, the developed coating based on crystalline photosensitizer nanoparticles with studied specific properties should have antibacterial, anti-inflammatory effect by the photodynamic treatment in the near implant area. This research opens the prospect of the local prevention of inflammatory and autoimmune reactions in the area of implantation. The results of the study suggest a promising this technology in order to create implants with photobactericidal properties.

This work is dedicated to the study of the photoluminescence kinetics of aluminum phthalocyanine nanoparticles in colloidal solutions at different pH and in the interaction with immune cells (macrophages). For measurements we used a registration system based on Hamamatsu streak camera (C10627-13 Hamamatsu Photonics) with picosecond temporal resolution (15 ps), conjugated with the fiberoptic spectrometer and picosecond laser pumping. The changes in fluorescence decay kinetics as additional lifetime components of fluorescence were found during the experiment. The number of components and duration of lifetimes changed while interacting with cells and depends on pH. At pH 2 the presence of two fluorescence lifetimes was recorded: the first one was 5 ns, which corresponded to the molecular form in solution, and 1.5 ns, which corresponded to bound state of phthalocyanine molecules. Due to the absence of other possible objects for bounding in the solution except of the nanoparticles we can suggest with a high degree of accuracy that the bounding occurs with the very these nanoparticles. Analysis of the fluorescence lifetimes of aluminum phthalocyanine nanoparticles in macrophages indicated the presence of two components: 9 ns and 4.5 ns. A model of surface molecules transitions from parallel to perpendicular position, regarding to the plane of the crystal nanoparticle was proposed.

Synthesis of 1-substituted tetrahydrocarbazole is accomplished by TfOH catalyzed reaction of 3-substituted indoles tethered with secondary and tertiary alcohols. The reaction was generalized for a variety of substrates and was extended to the synthesis of 2,3,3a,6-tetrahydro-1 H -pyrido[3,2,1- jk ]carbazole and carbazoles. [ABSTRACT FROM AUTHOR]

The monocyte/macrophage cell lineage reveals an enormous plasticity, which is required for tissue homeostasis, but is also undermined in various disease states, leading to a functional involvement of macrophages in major human diseases such as atherosclerosis and cancer. We recently generated in vivo evidence that crystalline, nonfluorescent nanoparticles of the hydrophobic porphyrin-related photosensitizer Aluminum phthalocyanine are selectively dissolved and thus may be used for specific fluorescent labelling of rejected, but not of accepted xenotransplants. This led us to hypothesize that nanoparticles made of planar photosensitizers such as porphyrins and chlorins were preferentially taken up and dissolved by macrophages, which was verified by in vitro studies. Here, using an in vitro system for macrophage differentiation/polarization of the human monocyte THP-1 cell line, we demonstrate differential uptake/dissolution of Temoporfin-derived nanoparticles in polarized macrophages, which resulted in differential photosensitivity. More importantly, low dose photodynamic sensitization using Temoporfin nanoparticles can be used to trigger M1 re-polarization of THP-1 cells previously polarized to the M2 state. Thus, sublethal photodynamic treatment using Temoporfin nanoparticles might be applied to induce a phenotypic shift of tumor-associated macrophages for the correction of an immunosuppressive microenvironment in the treatment of cancer, which may synergize with immune checkpoint inhibition. [ABSTRACT FROM AUTHOR]

In the frames of this review article the recently obtained data on new synthetic approaches to fluorinated indoles, as well as their biological properties are considered. [ABSTRACT FROM AUTHOR]

Metal phthalocyanines are promising components in photodynamic therapy. Aluminum phthalocyanine chloride (AlClPc) has been used to treat oral cancer in mice, human carious tissue, lung cancer cells and other conditions. To overcome the high hydrophobicity of AlClPc, phthalocyanine is often encapsulated in nanoformulations. Despite increased usage, little is known about the pharmacokinetics and biodistribution of AlClPc. The aim of this study was the development and validation of a UHPLC-MS method for the determination of AlClPc in solution after extraction from nanoformulations and biological matrices such as plasma and tissue. The described method has been assayed as to selectivity, linearity, limits of detection and quantification, precision and recovery. The present study is the first to describe the behavior of AlClPc in biological matrices with mass spectrometry as well as the first to describe the chromatographic behavior of AlClPc contaminants. Molecular mass analysis identified dechlorination of AlClPc by both LC/MS and MALDI-MS and an adduct formation in LC/MS. The parameters observed indicated that the method has applicability and robustness for use in biodistribution studies. [ABSTRACT FROM AUTHOR]

Considering the feasibility of the aluminum phthalocyanine chloride (AlPcCl) application in the topical photodynamic therapy of cutaneous tumors and the lack of HPLC methods capable of supporting skin permeation experiments using this compound, the aim of this study was to obtain a simple and selective chromatographic method for AlPcCl determination in skin matrices. A HPLC-UV/Vis method was developed using a normal-phase column operating at 30°C, an isocratic mobile phase of methanol : phosphoric acid (0.01 M) at 1.5 mL/min, and detection at 670 nm. The method exhibited (i) selectivity against various contaminants found in the different skin layers, (ii) high drug extraction capacity from the hair follicle (>70%) and remaining skin (>80%), and (iii) low limits of detection and of quantification (0.03 and 0.09 μg/mL, resp.). The method was also linear in the range from 0.1 to 5.0 µg/mL (r = 0.9994) and demonstrated robustness with regard to experimental chromatographic parameters according to a factorial design. Lastly, the developed method was successfully tested in in vitro skin permeation studies of AlPcCl, proving its effectiveness in the development of pharmaceutical delivery systems containing this drug for topical photodynamic therapy of skin cancers. [ABSTRACT FROM AUTHOR]

Biologically active indole derivative was synthesized and screened for its cytotoxicity against breast cancer cell line (MCF-7) with the IC equals 17.5 µg/mL. Docking study showed its high binding affinity to the COX-2 enzyme. It's radiolabeling with Tc and showed high radiochemical yield (92.10 ± 0.57%) and in vitro stability in serum up to 10 h. Biodistribution studies of a novel Tc-NSIC complex in tumor-bearing mice showed high T/NT ratio (6.17 ± 0.08 at 30 min. post-injection), suggesting this complex could be used as a solid tumor imaging agent. [ABSTRACT FROM AUTHOR]

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that is highly overexpressed in various cancer cells and antigen-presenting cells. It has emerged as an attractive therapeutic target for cancer immunotherapy, which has prompted high interest in the development of small-molecule inhibitors. To discover novel IDO1 inhibitors, we designed and synthesized a series of N'-hydroxyindazolecarboximidamides. Among the compounds synthesized, compound 8a inhibited both tryptophan depletion and kynurenine production through the IDO1 enzyme. Molecular docking studies revealed that 8a binds to IDO1 with the same binding mode as the analog, epacadostat (INCB24360). Here, we report the synthesis and biological evaluation of these hydroxyindazolecarboximidamides and present the molecular docking study of 8a with IDO1. [ABSTRACT FROM AUTHOR]

The authors describe a dual-use sorbent for solid phase extraction (SPE) in combination with surface-enhanced Raman spectroscopy (SERS). The sorbent consists of calcium carbonate microparticles with incorporated silver nanoparticles (AgNPs) and magnetic nanoparticles (FeO). It can be simply prepared, is cost-effective, disposable, and possesses high sorption capabilities together with a Raman enhancement of 10 in the best case. Following magnetic separation of the microsphere from the liquid sample, the sorbent matrix (CaCO) is dissolved in acid so that the AgNPs and the analyte are released. This provides an optimal interaction between them and warrants a strong SERS signal. A new SPE-SERS protocol was worked out and applied to the following model analytes: Rhodamine 6G (a fluorescent dye; R6G), Photosens (a photodynamic dye), and sulfadimethoxine (an antibiotic). The first two possess a high Raman cross-section, while the last one displays comparatively low intrinsic Raman intensity. It is found that coating the surface of the sorbent with polyethyleneimine (a cationic polyelectrolyte) leads to a 2-fold increase in the sorption of Photosens (from 40% to 90%) and to a 6-fold enhancement of the SERS signal. The limits of detection for R6G, Photosens, and sulfadimethoxine (with 78%, 94%, and 41% sorption values, respectively) are 29 pM, 12 nM, and 69 nM, respectively. Raman enhancements are in the range between 10 and 10 depending on the analyte. [ABSTRACT FROM AUTHOR]

Benzene ring functionalization provides useful alternatives to access indole derivatives and has received much attention in recent years. In this work, the mechanism of Pt(II)-catalyzed cyclization/alkynylation of benziodoxole with pyrrole homopropargylic ethers to generate C5-alkenylated indole derivatives has been studied with the aid of density functional theory (DFT) calculations. We found that five-membered-ring cyclization/six-membered-ring cyclization is competitive in the formation of an indole skeleton. The following aromatization stage prefers the reaction sequence bicarbonate-assisted deprotonation at the C3a position, H2CO3-promoted methoxy elimination at the C7 position, and bicarbonate-assisted deprotonation at the C6 position. In the last alkynylation stage, the oxidative substitution mechanism assisted by H2CO3 is found to be favored over the previously proposed 1,2-iodo shift and oxidative addition. The overall rate-determining step is oxidative substitution. Additionally, an interesting substituent effect on chemoselectivity was investigated. The electronic and steric effects caused by methyl result in reverse chemoselectivity. [ABSTRACT FROM AUTHOR]

Herein, we report a mechanistic exploration of the unusual FeCl3-mediated hydroarylation of N-Ac indoles. Electron density topology analysis of a crystal, in situ IR monitoring, Hammett and Taft studies as well as DFT computations allowed us to determine that activation of acetyl with FeCl3 and of the C2=C3 bond with a proton is involved. [ABSTRACT FROM AUTHOR]

An efficient process involving the catalytic kinetic resolution of racemic spiro-epoxyoxindoles with the simultaneous enantioselective Friedel-Crafts alkylation of indoles has been realized using a chiral phosphoric acid catalyst. The reaction provides two useful intermediates in high yields and excellent enantioselectivities. Performing the catalysis on a gram scale led to (R)-3-(3-indolyl)-oxindole-3-methanol, which was used in the asymmetric formal total synthesis of (+)-gliocladin C. Notably, the enantiomers (S)-3-(3-indolyl)-oxindole-3-methanol can be obtained easily by the reaction of the resolved spiro-epoxyoxindole with indole. [ABSTRACT FROM AUTHOR]

Background and Objective Emerging evidence suggests that photodynamic therapy (PDT) can exhibit immunomodulatory activity. The purpose of the present study was to analyse cytokine profiles after application of PDT in gingival tissues of rats with ligature-induced periodontal disease (PD). Study Design/Material and Methods Periodontal disease was induced through the introduction of a cotton thread around the first left mandibular molar, while the right side molars did not receive ligatures. After 7 days of PD evolution, ligatures were removed from the left side, and the animals were randomically divided into the following treatment groups: I, rats without treatment; II, rats received chloro-aluminum phthalocyanine (AlClPc); III, rats received low-level laser alone; and IV, rats received AlClPc associated with low-level laser (PDT). The animals were killed 7 days after the treatments, and the mandibles were histologically processed to assess morphological and immunohistochemical profile, while gingival tissues were removed for quantification of tumor necrosis factor (TNF)-α, interleukin (IL-)1β and IL-10 expression (by ELISA). Results Histomorphological analysis of periodontal tissues demonstrated that PDT-treated animals show tissue necrosis, as well as lower TNF- α expression, compared to ligatured animals treated with AlClPc alone. Conclusions It was concluded that PDT using AlClPc entrapped in a lipid nanoemulsion may be useful in therapies, because of immunomodulatory effects that decreased the inflammatory response and cause tissue destruction. [ABSTRACT FROM AUTHOR]

The use of lectins can play an important role for tracking modification on cell surface components, since lectins can be easily complexed with radioisotopes, biotin or fluorescein, facilitating the evaluation of carbohydrates distribution in the cell and mitochondrial activity. The aim of this study was to evaluate photodynamic therapy effects on indirect distribution of N-acetyl-glucosamine terminal glycoproteins, in human laryngeal carcinoma HEp-2 cell line surface, using lectin wheat germ agglutinin (WGA) and on mitochondrial activity, for the same cell line, using MitoTracker. The photosensitizer Aluminum Phthalocyanine Tetrasulfonate (AlPcS) was administrated at 10 μM/mL, followed by an incubation period for its accumulation in the tumor cells, which were irradiated with laser diode λ = 685 nm and energy density of 4.5 J/cm. Our results indicated that, after Photodynamic Therapy (PDT), it was observed N-acetyl glucosamine terminal glycoprotein expression and mitochondrial O production, compared to the control group. Based on these results, we suggest that PDT influences the O mitochondrial production and the presence of surface glycoproteins N-acetyl glucosamine terminals. [ABSTRACT FROM AUTHOR]

Tetrasulfonated aluminum phthalocyanine (AlS4Pc), a strongly red emitting compound, shows high detection sensitivity, little effect of photobleaching, and photochemical stability, making it an excellent red fluorescent probe. We have observed that in acid media, a low concentration of poly-L-lysine (PLL) has a strong fluorescence quenching effect on AlS4Pc, forming the ion-pair complex as AlS4Pc-PLL with almost no fluorescence. However, in the presence of Bi3+, the fluorescence of AlS4Pc-PLL dramatically recovers and the emission is visual because of the remarkable recovery. Screening experiments with other metal ions reveal that only Bi3+ can restore the fluorescence of the AlS4Pc-PLL complex. The presence of other metal ions does not result in the recovery of fluorescence, indicating the high specificity of the response to Bi3+ of AlS4Pc-PLL. This is the key finding of the present study. It was also observed that the response to Bi3+ of AlS4Pc-PLL exhibits a linear relationship over a large concentration range (three orders of magnitude). Based on these findings, we have established a new quantitative analysis method for Bi3+ with high specificity and high sensitivity, using the ion pair AlS4Pc-PLL complex as a red fluorescent probe, and we discuss the reaction mechanism. The detection limit of this method is 0.0021 mg L-1. The linear relationship applies to the range of 0.007 34.9 mg L-1 with a correlation coefficient of 0.9993. The method established addresses the complex operation and time consuming problems in traditional methods and is thus suitable for real applications. Satisfactory results have been obtained when the method was applied to the measurement of real samples. This study further expands the scope of new applications of phthalocyanine-based red-fluorescent probes in analytical sciences. [ABSTRACT FROM AUTHOR]

Air-unstable magnetic aluminum phthalocyanine (AlPc) molecules are prepared by an on-surface metalation reaction of phthalocyanine with aluminum (Al) atoms on Au(111) in ultrahigh vacuum. Experiments and density functional theory calculations show that an unpaired spin is located on the conjugated isoindole lobes of the molecule rather than at the Al position. [ABSTRACT FROM AUTHOR]

Aluminum phthalocyanine chloride (AlClPc) is a second-generation photodynamic therapy (PDT) photosensitizer characterized for its high hydrophobicity and self-aggregation tendency in aqueous media, which hamper its potential application. Aiming at AlClPc solubilization we proposed here the use of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at different proportions to form mixed lipid vesicles (LVs) as a drug delivery system. LVs were prepared by ethanol injection method and formed nano-sized vesicles (about 100 nm) with suitable polydispersity index, negative zeta potential, and stable in aqueous medium for at least 50 days. AlClPc strongly interacts with LV (high binding constant values), especially due to aluminum–phosphate specific interactions, which gives a surface localization to AlClPc molecules as demonstrated by fluorescence quenching data. Anisotropy, static and time-resolved fluorescence measurements corroborated with these results and demonstrated that AlClPc self-aggregation occurred even in the liposomes. However, formulation uptake by oral squamous cell carcinoma (OSCC) the AlClPc was distributed in cellular organelles and suffered a disaggregation process demonstrated by fluorescence life-time imaging microscopy. This amazing behavior is new and increases the scientific knowledge about the intracellular mechanism of action of PDT photosensitizers. In addition, these results open a new perspective to the potential use of AlClPc-LV formulations for photodynamic treatment. [ABSTRACT FROM AUTHOR]

In this work, we report a combined experimental and theoretical study of aluminum phthalocyanine chloride (AlPcCl). The FT-IR and Raman spectra of AlPcCl were recorded and analyzed. The density functional theory (DFT) computations have been performed at B3LYP/6-31g and B3LYP/6-311g to derive equilibrium geometry, vibrational wavenumbers, intensity and NLO properties. All the observed vibrational bands have been discussed and assigned to normal mode or to combinations on the basis of our DFT calculations as a primary source of attribution and also by comparison with the previous results for similar compounds. The natural bond orbital (NBO) calculations were performed to study the atomic charge distribution of the investigated compound. The calculated results showed that dipole moment of the investigated compound was 4.68 Debye and HOMO-LUMO energy gap was 2.14 eV. The lowering of frontier orbital gap appears to be the cause of its enhanced charge transfer interaction. [ABSTRACT FROM AUTHOR]

We report a fabrication method of controlling the doped concentration of phosphorescent dye to induce the trap-site in an emitting layer (EML) for an efficient near-infrared (NIR) organic upconversion device (OUD). Such an OUD was used as a device configuration of ITO/mixed layer of chloroaluminum phthalocyanine and C 60 /1,1-bis(di-4-tolylaminophenyl) cyclohexane/4,4′ -Bis(N-carbazolyl)-1,1′ -biphenyl doped with fac-tris (2-phenylpyridine) iridium (III) [Ir(ppy) 3 ]/4,7-diphenyl-l,10-phenanthroline/CS 2 CO 3 /Ag to provide a green emission under NIR illumination. Our optimized OUD with a high Ir(ppy) 3 doped concentration of ∼13 wt% exhibited a higher electroluminescent efficiency in the display unit and was suitable for inducing a large amount of trap-sites in the EML, which effectively blocked the hole and electron carrier in the EML. To induce the trap-site in the EML by the doping process, we used a hole- and electron-only device to examine the OUD with a lower dark current density. As a result, an optimal OUD with a current gain as high as 21,300 (defined as the light current density divided by dark current density) at a driving voltage of 3 V was successfully achieved. [ABSTRACT FROM AUTHOR]

Background Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS) with high fluorescence ability. Its use in photodynamic therapy (PDT) is hampered by hydrophobicity and poor biodistribution. Methods AlPc was converted to a biocompatible nanostructure by incorporation into amphiphilic polyethylene glycol-polycaprolactone (PECL) copolymer nanoparticles, allowing efficient entrapment of the PS in the hydrophobic core, water dispersibility and biodistribution enhancement by PEG-induced surface characteristics. A series of synthesized PECL copolymers were used to prepare nanophotosensitizers with an average diameter of 66.5–99.1 nm and encapsulation efficiency (EE%) of 66.4–78.0%. One formulation with favorable colloidal properties and relatively slow release over 7 days was selected for in vitro photophysical assessment and in vivo biodistribution studies in mice. Results The photophysical properties of AlPc were improved by encapsulating AlPc into PECL-NPs, which showed intense fluorescence emission at 687 nm and no AlPc aggregation has been induced after entrapment into the nanoparticles. Biodistribution of AlPc loaded NPs (AlPc-NPs) and free AlPc drug in mice was monitored by in vivo whole body fluorescence imaging and ex vivo organ imaging, with in vivo imaging system (IVIS). Compared to a AlPc solution in aqueous TWEEN 80 (2 w/v%), the developed nanophotosensitizer showed targeted drug delivery to lungs, liver and spleen as monitored by the intrinsic fluorescence of AlPc at different time points (1 h, 24 h and 48 h) post iv. administration. Conclusions The AlPc-based copolymer nanoparticles developed offer potential as a single agent-multifunctional theranostic nanophotosensitizer for PDT coupled with imaging-guided drug delivery and biodistribution, and possibly also fluorescence diagnostics. [ABSTRACT FROM AUTHOR]

A gold(I)-catalyzed cascade [3,3]-propargylic rearrangement and [4+2] cycloaddition reaction of 2-vinylindoles with propargylic esters is reported. The reaction leads to the synthesis of highly substituted tetrahydrocarbazole derivatives in high yields and diasteroselectivities. Furthermore, a preliminary screening for an asymmetric version of this reaction is described. [ABSTRACT FROM AUTHOR]

Aluminum phthalocyanine tetrasulphonate (AlPcS 4 ) is a well characterized water soluble phthalocyanine dye having structural similarities with porphyrin and has immense applications as a photosensitizer in photodynamic therapy (PDT). The present article embodies the exploration of physicochemical properties of PDT active AlPcS 4 and its interaction with DNA alkylating quinone in biomimicking micellar microenvironments to overcome the limitation of PDT that is caused by the hypoxic nature of solid tumor. UV–vis absorption, steady state emission and time resolved fluorescence spectroscopy reveal that the AlPcS 4 does not undergo considerable interaction with anionic SDS as well as uncharged Triton X-100 micelle, whereas in case of the series of a cationic surfactant (DTAB, TTAB, CTAB) it shows a significant columbic attraction toward the positively charged head group of the surfactant molecule. In premicellar concentration, surfactant induced aggregation of the probe molecule is observed, which subsequently disaggregates into its monomeric form above critical micellar concentration. The anionic dye localizes itself in the Stern layer of cationic micelles. The escalation of the fluorescence anisotropy value ( r ) with increase in the surfactant concentration is explained by the rise in compactness around the probe with increasing chain length of the cationic surfactant. However, the compactness has a reverse effect on the extent of water penetration or micellar hydration, which in turn decreases the polarity of microenvironment in the Stern layer. The fully micellized PDT active AlPcS 4 experiences stronger interaction with DNA alkylating quinone in confined medium as compared to the aqueous solution and the above said interaction intensifies with decrease in the micellar hydration. This spectroscopic research described herein may provide relevant addition to the usefulness of this bioactive dye–quinone system for the application in photodynamic therapy. [ABSTRACT FROM AUTHOR]

Cubic NaY 1 − x − y Yb x Er y F 4 solid solutions which are capable of more than 4% up-conversion luminescence energy yields (excitation by 974 nm laser radiation; 1 W/cm 2 excitation power density) have been prepared for a broad range of Yb and Er concentrations. Estimates for the up-conversion luminescence energy yields for the appropriate NaY 1 − x − y Yb x Er y F 4 solid solutions are also presented. Successful conjugation of AlPc(C 2 O 3 ) 4 aluminum phthalocyanine with NaY 0.885 Yb 0.1 Er 0.015 F 4 specimen and photodynamic activity of this conjugate under laser excitation at 974 nm have also been reported. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT), or ultrasound combined with sonosensitization, is a promising approach because it is noninvasive and penetrates deeper than light does in photodynamic therapy. We examined whether bleomycin (BLM) could improve the efficacy of SDT. We performed an in vitro study using Colon-26 cells, which are derived from mouse colon cancer. SDT with BLM was significantly more cytotoxic than SDT alone both in vitro and in vivo. We also observed an ultrasound intensity-dependent cytotoxic effect of SDT with BLM. These findings suggest that SDT with BLM might provide a novel noninvasive treatment for deep-seated tumors. [ABSTRACT FROM AUTHOR]

AC conductivity and the related dielectric properties of bulk aluminum phthalocyanine chloride (AlPcCl) have been studied over a temperature range (303–403 K) and frequency range (42–10 6 Hz). The universal power law σ ac ( ω )= Aω s has been used to investigate dependence of AC conductivity on frequency. The variation of the frequency exponent ( s ) with temperature was analyzed in terms of different conduction mechanisms; the predominant conduction mechanism was found to be the correlated barrier hopping (CBH) model. The barrier height was calculated by using (CBH) model, it was found to be 1.41 eV. Dependence of σ ac ( ω ) on temperature refers to a linear increase with increasing temperature at different frequencies. The density of states N ( E F ) was calculated to be equal 4.11×10 19 cm −3 using Elliott model. It has been found that AC activation energy decreases with increasing frequency. Dielectric values were analyzed using complex permittivity and complex electric modulus for bulk AlPcCl at different temperatures. The obtained value of HOMO–LUMO energy gap was found to be 1.48 eV. [ABSTRACT FROM AUTHOR]

Novel organic–inorganic hybrid materials comprising nanoscaled layered silicates and native aluminium hydroxide phthalocyanine (Al(OH)Pc) allowed for the first time the exploitation of their unique photophysical properties in aqueous ambience. In particular, we were able to observe the efficient emission of Al(OH)Pc–nanoclay hybrids and generation of singlet oxygen in aqueous solution. [ABSTRACT FROM AUTHOR]

Cu-catalyzed cyanation of indoles with acetonitrile for the synthesis of 3-cyanoindoles has been developed. The Cu/TEMPO/(Me3Si)2 system has been identified to promote highly efficient and selective C-H cyanation of indoles by use of unactivated acetonitrile as a cyano source via a sequential iodination/cyanation process in one pot. This reaction furnishes 3-cyanoindoles in moderate to good yields and tolerates a series of functional groups. Moreover, low-cost copper catalysts and hazardless acetonitrile as a cyano source feature the practicability of this reaction. [ABSTRACT FROM AUTHOR]

[MediaObject not available: see fulltext.]We describe the synthesis of N-ethoxycarbonyl-, N- tert-butoxycarbonyl-, and N-acetyl-3-iodo-5-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[ b]indoles, as well as N-acetyl-3-iodo-5-methyl-7-nitro- and N-acetyl-3-iodo-7-methyl-5-nitro-1,2,3,3a,4,8b-hexahydrocyclopenta[ b]indoles. [ABSTRACT FROM AUTHOR]