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Introduction. Intranasal delivery of in situ gel-forming systems is a complex but promising direction. Due to the high cost of developing a new chemical object or genetically engineered modification of biological molecules, pharmaceutical companies are focusing on developing technologies for new delivery systems for existing active pharmaceutical ingredients to improve their effectiveness and bioavailability. In situ systems for intranasal delivery, due to increased viscosity and mucoadhesion to the nasal mucosa, allow overcoming mucociliary clearance and ensuring complete absorption and prolonged release of drugs.Text. The article discusses the main advantages of intranasal in situ delivery systems shown in preclinical studies, as well as approaches to the technology of obtaining and standardization of these systems. The results of scientific research in this field over the past 15 years are summarized, the most promising polymers for creating thermoreversible and pH-sensitive compositions are identified, and modern methods for evaluating the sol-gel transition in situ are analyzed.Conclusion. The use of in situ systems for intranasal administration allows providing a high targeting of the delivery of synthetic and biological molecules to the brain. Currently, numerous pharmacokinetic and pharmacodynamic preclinical studies confirm the effectiveness of such systems, as well as their safety. Thermoreversible commercially available and directionally synthesized polymers (poloxamer 407, PLGA, NIPAAm, etc.), as well as chitosan, remain the most popular for the design of in situ delivery systems. In vitro and ex vivo methods with mucosa and artificial nasal fluid are widely used to assess the parameters of in situ gelation, but to increase the reproducibility of the methods and improve the correlation in vitro/in vivo, it is recommended to conduct modeling of the nasal cavity. Developing the technology and methods of screening of intranasal reversible systems will help to get closer to clinical trials and the entry of these delivery systems into the global pharmaceutical market.

Objective: Development of a technology for the production of a stable injectable dosage form (IDF) of indolocarbazole derivative LHS-1269. Methods: LHS-1269 is an active pharmaceutical ingredient that was synthesized in the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. The IDF includes dimethyl sulfoxide (DMSO), 95% ethanol, Kollidon® 17PF and water for injection. Magnetic stirrer and overhead stirrer with a propeller stirring element were used to prepare the model solution of the IDF of LHS-1269. Sterilizing filtration of the solution was performed with 0.2−0.22 um polycarbonate, cellulose, polyvinylidene fluoride, polyethersulfone and nylon membrane filters. The aqueous solution of LHS-1269 was lyophilized in Edwards Minifast DO.2 freeze dryer. Assay of LHS-1269 was performed by spectrophotometry at 320±3 nm. Potentiometry was used to measure pH, a viscosimetry method was used to measure the viscosity of the solutions. The average weight was estimated by weighing a sample of 10 vials with the concentrate. Results: 0.5% aqueous solution of LHS-1269 was produced by mixing the solution of the active substance in DMSO and ethanol with an aqueous solution of polyvinylpyrrolidone gradually at the ratio of LHS-1269/DMSO/ethanol/Kollidon® of 1/11/32/40 by weight. The aqueous solution of the study substance cannot be lyophilized, so a sequence of technological operations was presented to produce an anhydrous concentrate “LHS-1269, concentrate for solution for injection and infusion 25 mg”. Conclusion: A technology was developed to produce a stable IDF of a hydrophobic indolocarbazole derivative LHS-1269, a high-potential antitumor drug.

Introduction. Increasing of poorly soluble pharmaceutical substances bioavailability is one of important problems of pharmaceutical technology. Resveratrol is a plant origin polyphenol with a broad spectrum of biological effects. However, due to poor solubility and, as a result, low bioavailability, it is not promising for the development of oral drugs. Thus, today resveratrol is presented only as a biologically active substance that is component of biologically active food supplements.The objective of the research is selection of the optimal solubilizer to increase the solubility of resveratrol by determining the solubilization parameters.Materials and methods. The spectrophotometric characteristics of resveratrol were studied using three groups of solubilizers: poloxamers, polysorbates and cyclodextrins. Studies were carried out in 50 mM hydrochloric acid buffer(pH 1.2) and 50 mM phosphate buffer(pH 6.8). Spectrophotometric measurements were carried out on a spectrophotometer UV/VIS-3600 Shimadzu (Japan) in the wavelength range of 220–380 nm. The effect of solubilizers on the spectrophotometric characteristics of resveratrol was determined in buffer solutions containing the solubilizer and resveratrol in significantly less concentration of its own solubility in water. The used multiple excess of the solubilizer ensured the finding of all resveratrol in a solubilized form. During the determining parameters of solubilization, buffer solutions containing from 2 to 10 mM solubilizers were added to the obviously excess of resveratrol. The indicated amount of resveratrol ensured the presence of its precipitate in all experimentsto determine the completeness of solubilization of the studied polyphenol.Results. Based on the obtained spectrophotometric characteristics of solubilizers solutions with resveratrol, the most effective for the further development of solid dosage forms for oral administration are poloxamer 407, polysorbate 80 and modified methyl-beta-cyclodextrin, which ensure complete dissolution of resveratrol when its content in the composition with a solubilizer is about 10 %.Conclusion. Based on the data obtained on the spectrophotometric characteristics of resveratrol using solubilizers, it can be argued that it is possible to create drugs with improved solubility of the studied polyphenol. On the basis of its compositions with poloxamer 407, polysorbate 80 and modified methyl-beta-cyclodextrin, with the selection of appropriate excipients, solid dosage forms for oral intake can be developed.

Carbon dots keep attracting attention in multidisciplinary fields, motivating the development of new compounds. Phenylenediamine C6H4(NH2)2 dots are known to exhibit colorful emission, which depends on size, composition, and the functional surface groups, forming those structures. While quite a few fabrication protocols have been developed, the quantum yield of phenylenediamine dots still does not exceed 50% owing to undesired fragment formation during carbonization. Here, we demonstrate that an ethylene glycol-based environment allows obtaining multicolor high-quantum-yield phenylenediamine carbon dots. In particular, a kinetic realization of solvothermal synthesis in acidic environments enhances carbonization reaction yield for meta phenylenediamine compounds and leads to quantum yields, exciting 60%. Reaction yield after the product's purification approaches 90%. Furthermore, proximity of metal ions (Nd3+, Co3+, La3+) can either enhance or quench the emission, depending on the concentration. Optical monitoring of the solution allows performing an accurate detection of ions at picomolar concentrations. An atomistic model of carbon dots was developed to confirm that the functional surface group positioning within the molecular structure has a major impact on dots' physicochemical properties. The high performance of new carbon dots paves the way toward their integration in numerous applications, including imaging, sensing, and therapeutics.

A reduced supply of micronutrient vitamin D leads to a more severe course of coronavirus infection (COVID-19). Vitamin D deficiency is combined with a decrease in innate antiviral immunity and excess of inflammation. Vitamin D supplementation stimulates the synthesis of antibacterial peptides and is important for weakening the cytokine storm, reducing excessive acute and chronic inflammation, and also for compensating for chronic comorbid pathologies. Active forms of vitamin D (alfacalcidol, etc.) are of particular importance for compensating for vitamin D deficiency in elderly patients, endocrine-immune dysfunction, sarcopenia, chronic renal failure (in which the metabolism of vitamin D in the kidneys is disturbed).Сниженная обеспеченность микронутриентом витамином D приводит к более тяжелому течению коронавирусной инфекции (COVID-19). Недостаточность витамина D сочетается с понижением врожденного противовирусного иммунитета и избыточным воспалением. Дотации витамина D стимулируют синтез антибактериальных пептидов, они важны для ослабления цитокинового шторма, снижения избыточного острого и хронического воспаления, а также для компенсации хронических коморбидных патологий. Активные формы витамина D (альфакальцидол и др.) приобретают особое значение для компенсации недостаточности витамина D у пожилых пациентов, а также лиц с эндокринно-иммунной дисфункцией, саркопенией, хронической почечной недостаточностью (при которой нарушается метаболизм витамина D в почках).

Composite ceramics of titanium nitride grains incorporated in an aluminium nitride matrix have been synthesized by high pressure high temperature treatment of a mechanical mixture of AlN–TiN (3 mol % TiN) powders. The microstructure of the samples analysed by means of electron beam microanalysis and Raman spectroscopy shows that the formation of cubic AlN in the composite begins near titanium nitride grains. The areas of mixed chemical composition, which can be assigned to the formation of the solid solutions Al1−xTixN, have been observed at the phase interfaces. The luminescence properties of AlN–TiN ceramics have been considered focusing on the choice of high pressure and high temperature treatment conditions. Three main components at 2.0 eV, 2.4 eV and 3.1 eV are revealed in the cathodoluminescence spectra analysed quantitatively. The observed emission originates from the radiative transitions with participation of valence band states, oxygen-vacancy centres (VAl–ON), nitrogen vacancies VN, and shallow donors which form a complex system of energy levels in the bandgap of the wurtzite-type AlN.

Purpose: Reducing the undesirable systemic effect of photodynamic therapy (PDT) can be achieved by incorporating a photosensitizer in microparticles (MPs). This study is devoted to the preparation of biocompatible biodegradable MPs with the inclusion of the natural photosensitizer Radachlorin (RС) and an assessment of the possibility of their use for PDT. Methods: RC-containing MPs (RС MPs) with poly(lactic-co-glycolic acid) copolymer (PLGA) matrix were prepared by a double emulsion solvent evaporation methods. The size and morphology of RC MPs were surveyed using scanning electron microscopy, confocal laser scanning microscopy, and dynamic light scattering. The content of RC, its release from RC MPs, and singlet oxygen generation were evaluated by the optical spectroscopy. Cellular uptake and cytotoxic photodynamic effect of RC MPs were investigated with in vitro assays. Results: The average diameter of the prepared RC MPs was about 2-3 μm. The RC MPs prepared by the water/oil/oil method had a significantly higher inclusion of RC (1.74 μg/mg) then RC MPs prepared by the water/oil/water method (0.089 μg/mg). Exposure of the prepared RC MPs to PDT light radiation was accompanied by the singlet oxygen generation and a cytotoxic effect for tumor cells. The release of the RC from the RC MPs was prolonged and lasted at least two weeks. Conclusion: PLGA RC MPs were found to cause a photoactivated cytotoxic effect for tumor cells and can be used for local application in PDT of tumors. ispartof: ADVANCED PHARMACEUTICAL BULLETIN vol:11 issue:3 pages:458-468 ispartof: location:Iran status: published

Iodine evaporated from lead–bismuth eutectic (LBE) has been examined with respect to its adsorption behavior on stainless steel in various gases to establish a base for safety evaluations on LBE based nuclear reactors. In inert conditions the iodine forms a single species with an adsorption enthalpy between − 97 and − 106 kJ/mol. The adsorbed species is tentatively identified as bismuth monoiodide, BiI. Addition of moisture to the inert gas has no substantial influence on the adsorption behaviour. For the reducing hydrogen carrier gas depositions with adsorption enthalpies ranging from − 87 to − 134 kJ/mol were observed in dry and water saturated conditions. The larger variation of adsorption enthalpies compared to analogous experiments in helium likely result from surface effects induced by the reactive gas. Formation of highly volatile species such as hydrogen iodide HI was not observed. In oxidizing conditions multiple iodine species with adsorption enthalpies ranging from − 67 to − 83 kJ/mol were observed, with the exception of one experiment where only a lower limit of –ΔHads

A series of cyclometalated platinum(II) complexes with nitrile and isocyanide ligands (RCN and RNC; R = t-Bu, Bn, Ph) have been synthesized in 60–80% yields from the dimer [{Pt(ppy)Cl}2] (Hppy is 2-phenylpyridine) and the corresponding nitriles and isocyanides. The structure of the synthesized complexes was determined by mass spectrometry, IR and NMR spectroscopy, and X-ray diffraction. The contributions of different intermolecular interactions to the crystal packing were estimated by Hirshfeld surface analysis. Photophysical properties of the synthesized complexes in solution and solid state were studied.

Here, the synthesis of holey carbonylated (C-ny) graphene derivative and its application for gas sensing is demonstrated. The carbonylation of graphene oxide leads to the 3-fold increase in the concentration of carbonyl groups’ up to 9 at.% with a substantial elimination of other oxygen functionalities. Such a chemical modification is accompanied by the perforation of the graphene layer with the appearance of matrices of nanoscale holes, leading to corrugation of the layer and its sectioning into localized domains of the π-conjugated network. Combined with the predominant presence of carbonyls, granting the specificity in gas molecules adsorption, these features result in the enhanced gas sensing properties of C-ny graphene at room temperature with a selective response to NH3. Opposite chemiresistive response towards ammonia when compared to other analytes, such as ethanol, acetone, CO2, is demonstrated for the C-ny graphene layer both in humid and dry air background. Moreover, a selective discrimination of all of the studied analytes is further approached by employing a vector signal generated by C-ny multielectrode chip. Comparing the experimental results with the calculations performed in framework of density functional theory, we clarify the effect of partial charge transfer caused by water and ammonia adsorption on the chemiresistive response.

Based on published data and experimental studies of formation regularities of aluminium hydroxide, a reproducible technique for synthesis of bayerite-structured aluminium hydroxide by precipitation was developed as a part of the creation of preparation technology of chromia-alumina dehydrogenation catalyst. A possibility of synthesis of high purity bayerite (above 90 wt.%) with different particle sizes depending on synthesis conditions was shown. A correlation between dispersion of the sediments and synthesis temperature was shown, the optimal precipitation temperature – which allows obtaining bayerite with a sufficiently large particle size and high purity – was found. Based on the experiments, a fundamental difference between technologies and products of precipitation by sodium hydroxide and aqueous ammonia was shown. The influence of duration of precipitation stages on the properties of sediments is analyzed from the standpoint of theory of relative supersaturation

Lyotropic myelin figures (MFs), i.e., long cylindrical structures formed by certain surfactants, owe their name to their resemblance to the biological membrane that covers nerve fibers. Herein, we used a strong bilayer-forming zwitterionic phospholipid stained by the Nile Red dye to study lamellar mesophases. Polarized optical microscopy and fluorescence confocal microscopy allowed us to investigate the morphology of myelin structures and determine the orientational order of amphiphilic molecules. The cross-sectional views reveal significant differences in the configurations of MFs within the liquid crystalline cell, as well as the details of a spontaneous and stimulated formation of branched lipid tubes. Our results provide insights into small-scale morphology and out-of-equilibrium structural changes in the multilamellar structures.

A new approach to the synthesis of luminescent soft media using a terbium β-diketonate complex and substituted p-tert-butylthiacalix[4]arene containing quaternary ammonium fragments with amino acid substituents in the lower rim was developed. The synthesized heteroligand complex was incorporated into the framework of the lyotropic mesophase P123-C2H6O2. The liquid crystal properties of the P123-C2H6O2 binary system were studied and the concentration limits of the complex incorporation into the lyomesophase were determined. The long-period ordered structures of lyomesophases was confirmed by small-angle X-ray scattering measurements. The intermolecular interactions of the system components were estimated by IR spectroscopy. The luminescent properties of lyomesophases including a hetero-ligand macrocyclic complex and a low-molecular-weight analog based on an ionic liquid were analyzed. Enhanced luminescence efficiency was observed for lyomesophases with the macrocyclic complex.

Chemistry of macrocyclic compounds is one of the rapidly developing areas of modern organic chemistry. These macrocycles have become widespread due to the high availability of parents compounds, the possibility of synthesis of ligands based on them for highly selective recognition, ion-selective membranes, electrodes, sensors and nanocontainers for targeted drug delivery. Moreover, in the past few years, attention of researchers has again been riveted on mechanically interlocked molecules (rotaxanes and pseudorotaxans) and supramolecular polymers, which can be explained by their potential application as molecular machines and materials. Mechanically interlocked molecules are molecular architectures consisting from two or more components which mechanically bind due to their own topology. Supramolecular polymers are comprise ordered monomer units combined via non-covalent bonds (hydrogen bonds or electrostatic interactions). Thus, this manuscript presents an approach to the synthesis of monosubstituted pillar[5]arenes containing N-(aminoalkyl)amide fragments with various substituent lengths. The formation of self-inclusion complexes by synthesized macrocycles was established by one- and two-dimensional NMR spectroscopy. According to NMR data, only four carbon atoms of the alkyl fragment were included in the macrocyclic cavity regardless of the alkyl chain length. Formation of self-inclusion complexes becomes possible due to the intramolecular hydrogen bond between the NH protons and the oxygen atom of methoxyl fragment, which is confirmed by IR spectroscopy. It was shown by dynamic light scattering that the synthesized pillar[5]arenes in chloroform form aggregates with an average hydrodynamic diameter of 316-640 nm and polydispersity index from 0.18 to 0.20, while polydisperse systems are formed in dimethyl sulfoxide.

Improving building energy performance requires the development of new highly insulative materials. An affordable retrofitting solution comprising a thin film could improve the resistance to heat flow in both residential and commercial buildings and reduce overall energy consumption. Here, we propose cellulose aerogel films formed from pellicles produced by the bacteria Gluconacetobacter hansenii as insulation materials. We studied the impact of the density and nanostructure on the aerogels' thermal properties. A thermal conductivity as low as 13 mW/(K·m) was measured for native pellicle-based aerogels that were dried as-is with minimal post-treatment. The use of waste from the beer brewing industry as a solution to grow the pellicle maintained the cellulose yield obtained with standard Hestrin-Schramm media, making our product more affordable and sustainable. In the future, our work can be extended through further diversification of food wastes as the substrate sources, facilitating higher potential production and larger applications.

Optical gas sensing attracts growing attention in the recent years. This is governed by progressive availability of optical nanostructures fabrication and complex techniques of optical spectrum processing. In the present paper, a room-temperature optical humidity sensor based on a hydrophilic polymer Nafion is theoretically and experimentally investigated. Sensor geometry is optimized for maximum sensitivity of an angle-resolved ATR dip in the Kretschmann configuration. The reflectance dip is attributed to the 2nd order Nafion layer leaky waveguide mode hybridized with the surface plasmon-polariton at the silver/Nafion interface. Results of the relative humidity (RH) retrieval with the regression of the physical model parameters is compared to these obtained with different machine learning (ML) techniques. It is shown that a limited raw data set is enough for using ML algorithms. Accuracy of 0.3% has been demonstrated in RH measurements.

Using the previously developed rabbit model of perioperative dry eye syndrome (PDES) and quantitative mass spectrometric technique it is shown that the development of corneal erosion under conditions of general anesthesia is associated with changes in the content of inflammatory metabolites, namely, derivatives of linoleic (LA), alpha-linolenic (ALA), and arachidonic (AA) acids in tear fluid. The increase in the content of the metabolites of LA and ALA is found to be the most significant, while the content of AA derivatives (with the exception of 12-HETE) remains almost unchanged, indicating the key roles of the LA and ALA cascades in the inflammatory response in PDES. The increase in the concentration of oxylipins that can be formed by nonenzymatic oxidation of LA (9-KODE) or its processing by cytochromes (12,13-EpOME) under oxidative conditions indicates a significant contribution of oxidative stress to the development of PDES. The majority of metabolites of LA (13-HODE and 9-HODE), ALA (9-HOTrE and 13-HOTrE) and AA (12-HETE), the tear content of which was changed in PDES, are generated by the enzymes of lipoxygenase family. By contrast, the concentration of cyclooxygenase products does not exhibit any significant fluctuations. These data suggest a low therapeutic potential of cyclooxygenase inhibitors (such as nonsteroidal anti-inflammatory drugs) and a high therapeutic potential of antioxidants and lipoxygenase inhibitors in PDES, which should be taken into account upon developing a complex therapy for this disease.

Dispersions of non-toxic compounds characterized by an intense absorbance in the near-IR range find use in photodynamic therapy as effcient antibacterial and anticancer agents. An approach to the preparation of aqueous dispersions of nanoparticles with controlled morphology is described. 3,7-Bis(arylamino)phenothiazin-5-ium derivatives containing the ester and carboxylic groups were synthesized for the first time by the oxidative addition of methyl anthranilate to phenothiazin-5-ium tetraiodide with subsequent hydrolysis of the ester groups. The association with 3-phenylimino-7-phenylaminophenothiazine was studied for the synthesized bis(carboxyl)phenothiazinium derivative. The obtained 1: 1 associate is characterized by the bathochromic shift. The nanoprecipitation of the obtained nanoassociate in a methanol-water system was studied, and the morphology of the prepared dispersions was characterized: 3-phenylimino-7-phenylaminophenothiazine forms nanofiber structures, bis(carboxyl) derivative forms spherical particles, and the two-component associate forms facet-shaped particles

In this work, we present the design, fabrication, optimization, and experimental results of a high-efficiency planar solar thermophotovoltaic (STPV) system utilizing a micro-textured absorber and a nanostructure multilayer metal-dielectric coated selective emitter fabricated on a tungsten (W) substrate. Light absorptance of more than 90% was achieved at visible and near-infrared wavelengths using the microtextured absorbing surface. The nanostructure selective emitter consists of two thin-film optical coatings of silicon nitride (Si3N4) and a layer of W in between to increase the surface emissivity in spectral regimes matching the quantum efficiency of the thermophotovoltaic (TPV) cells. Gallium antimonide (GaSb)-based TPV cells are used in our STPV design. The experiment was conducted at different operating temperatures using a high-power continuous wave laser diode stack as a simulated source of concentrated incident radiation. Our experimental setup measured a maximum electrical output power density of 1.71 W/cm2 at 1676 K STPV temperature, and the overall power conversion efficiency of 8.4% after normalizing the output power density to the emitter area. This is the highest STPV system efficiency reported so far for any experimental STPV device. The incident optical laser power on the absorber side was 131 W. This is equivalent to a solar concentration factor of ~2100, which is within the practical limit and readily achievable with Fresnel lens setup.

Nanoscale lipid drug delivery systems are widely used due to their high efficiency and possibility to increase the drug bioavailability. The size, shape and morphology of these systems can significantly impact their activity. We report the synthesis of new amphiphilic pillar[5]arenes and their use for the preparation of solid lipid nanoparticles (SLN) dispersed in water. The encapsulation of fluorescent dyes (fluorescein, rhodamine B, rhodamine 6G) in the particles made it possible for the first time to obtain dye-loaded SLNs (SLN-Flu, SLN-RhB, SLN-Rh6G) with distinctive morphology and low toxicity to A549 cells. Thus, the discovery of this ability of amphiphilic pillar[5]arenes allows creating new targeted delivery systems with high-precision morphology and advantageous properties.

New uncharged water-soluble pillar[5]arene derivatives bearing 2-hydroxyethylamide and 2-hydroxypropylamide moieties have been for the fi rst time synthesized via aminolysis. A detailed analysis performed for the spectral data (UV, IR; and 1H, 13C, NOESY, and HSQC NMR) allowed us to determine the spatial structure of the synthesized macrocycles. Aggregation properties of the obtained compounds with water-soluble tetrazole-containing polymers, viz. poly-5-vinyltetrazole (PVT) and polyvinyl(tetrazolyl)ethyl ether (PVTE), were evaluated. Pillar[5]-arene containing 2-hydroxyethylamide moieties formed monodisperse nanoscale aggregates with an average hydrodynamic diameter of 117 nm in the presence of PVTE in aqueous solution. The morphology of resulting particles was determined by scanning electron microscopy.

A convenient method for the synthesis of the first generation PAMAM dendrimers based on the thiacalix[4]arene has been developed for the first time. Three new PAMAM-calix-dendrimers with the macrocyclic core in cone, partial cone, and 1,3-alternate conformations were obtained with high yields. The interaction of the obtained compounds with salmon sperm DNA resulted in the formation of the associates of the size up to 200 nm, as shown by the UV-Vis spectroscopy, DLS, and TEM. It was demonstrated by the CD method that the structure of the DNA did not undergo significant changes upon binding. The PAMAM-calix-dendrimer based on the macrocycle in cone conformation stabilized DNA and prevented its degradation.

The results ofthe sorption properties of cellulose acetate (CA) with different degrees of substitution (SD) are summarised. It has been shown that the sorption capacity of CA in water vapour decreases naturally with increasing content of acetate groups in monomeric units of cellulose ethers. The experimental isotherms are analysed according to the double sorption model. Hydrate numbers of hydroxyl and acetate groups were determined. The paired parameters of the Flory–Huggins interaction were calculated. It is shown that the decrease of the Langmuir component is due to the replacement of hydroxyl groups by ester groups, whose local sorption capacity by water vapour is lower than the sorption capacity of OH groups. In the area of high humidity, there is an increase in vacancy sizes due to plasticisation of the sorbents.

The results of the development of combined eye gel with interferon alpha-2-beta are presented. Experimental samples of the gel based on different gelling agents were prepared and their biotechnological and technological characteristics (the absence of the cytotoxic effect, aggregation stability, osmotic activity, bioadhesion, and rheological parameters) were evaluated. The composition with hydroxyethyl cellulose, Natrosol 250HHX, in a concentration of 1.5% as a gelling agent showed the best results and the best one-year stability.

Due to their chemical inertness, wide operating temperature range, and low volatility, non-polar dimethyl-and methylphenyl polysiloxanes are some of the most frequently used stationary phases in gas chromatographic practice. Commercial multicapillary columns with polydimethylsiloxanes SE-30 (or OV-1) and phenyldimethylsiloxanes SE-54 (or OV-5) are well known, but their upper operating limit is 250°C, which is significantly lower than the stated thermal stability of the stationary phases themselves. The high-efficientmulticapillary column preparation method using the polyethylene glycol stationary phase and the sol-geltechnology was proposed earlier. This method allows to increase the thermal stability and to reduce the column bleed. The possibility of coating the multicapillary columns with non-polar silicone stationary phasesusing the sol-gel method was examined in order to prepare the columns with improved performance characteristics.In the current study, straight multichannel hexagonal tubes with an apothem of 2.2 mm and a capillarydiameter of ~40 μm were used as the source material. The precursor used for the application of polydimethylsiloxane was prepared from OH-terminated polysiloxane PS 347.5 and polymethylhydrosiloxane, with trimethoxymethylsilane as a crosslinking agent, and trifluoroacetic acid as a catalyst. The precursor composed of the stationary phase SE-54, trimethoxymethylsilane and trifluoroacetic acid and methylene chloride was used for the applying of SE-54. After adding all the components, the mixture was kept for a while for the sol-gel to be ready.The static low-pressure application of the PS 347.5 stationary phase from a solution obtained by dilutingof the corresponding precursor with hexane or chloroform led to an unsatisfactory result, due to capillaryblockage during the solvent removal. Under similar conditions, the use of the SE-54 stationary phasebased sol-gel provided for the smooth coating procedure, however the obtained columns lacked efficiency.The stationary phase immobilization degree for various columns ranged within 49-77%, which is less than isdesirable for the stable work of the column. Since the static coating method did not allow to produce multicapillary columns with satisfactory characteristics, attempts were made to use the dynamic method of applying stationary phases to multicapillary columns.It is theoretically shown that dynamic coating performed by moving a short plug of a stationaryphase solution along a multicapillary is correlated, that is, the thickness of the resulting film in the capillarydepends on its cross-section, and a thicker film of the stationary phase forms in the wider capillary.It was established experimentally that with the speed of the undiluted precursor plug within14-20 and 37-45 mm/s for the stationary phases PS 347.5 and SE-54, respectively, after dynamic coating andsubsequent conditioning, multicapillary columns with high efficiency were obtained (3200-3500 theoreticalplates on dodecane). In both cases, the process suffered from insufficient reproducibility, often inefficientcolumns were obtained, and the shape of chromatographic peaks also frequently differed from the Gaussiancurve. A comparison of the commercial SE-30 column with one of the columns prepared with the PS 347.5stationary phase showed the closeness of their chromatographic characteristics. However, the latter hadslightly higher polarity.Using a freshly prepared sol-gel, the immobilization degree of the stationary phase for the studiedcolumns was 86-92 and 90-97% for silicones PS347.5 and SE-54, respectively. The prepared columnsshowed a slight activity to alcohols. This may be due to the presence of free silanol groups in the products ofthe hydrolysis and polycondensation of trimethoxymethylsilane.It was shown that columns with both types of stationary phases withstand heating in an inert gasflow for several hours at 300°C without significant loss of efficiency. It was established that for the sol-gelmulticapillary columns at 300°C the bleed level (caused by stationary phase breaking down) is about an orderof magnitude lower than that of commercial columns with similar stationary phases. The increased thermalstability and lower bleed of the columns can be explained by the formation of a stable spatial organicinorganic copolymer of polysilicic acid and polysiloxanes on the capillary surface.

A new nanocomposite material based on gold nanorods and polyurethane foam was obtained, and a method for the determination of catecholamines with the use of this nanocomposite modified with silver nitrate was developed. The determination is based on the measuring hypsochromic shift of a short-wave surface plasmon resonance band in a diffuse reflection spectrum of the nanocomposite. This shift is caused by reduction of silver from silver ions on the surface of gold nanorods under the influence of catecholamines. Effects of time, pH, volume of the reaction mixture, concentration of silver ions, and catecholamines on the interaction were examined. The proposed method allows to determine dobutamine, epinephrine, norepinephrine and dopamine with the detection limits of 0.1, 0.07, 0.07, and 0.05 μg mL−1, respectively. The developed method can be applied to analysis of medicines.

The paper reports the first synthesis of positively charged hybrid organic-inorganic silicon dioxide nanoparticles with an average particle diameter of 28 nm modified with 1-[3-(diethylamino)propyl]-3-[3-(triethoxysilyl)propyl]urea and pillar[5]arene derivatives containing negatively charged groups, which form nanoparticles with an average diameter of 40 nm in an aqueous solution. These nanoparticles were utilized in a new procedure developed for the preparation of mixed polyelectrolyte particles. Spectroscopic studies (UV spectroscopy, dynamic light scattering) showed that the resulting compounds are able to recognize biopolymers, proteins (bovine serum albumin and lysozyme).

The review considers methods for modifying oligo- and polymers of lactic acid by macrocyclic moieties (cyclodextrin, tetrapyrrole, and calixarene) and the effect of modifiers on the complexing, thermal, and aggregation properties. Analytical characteristics of oligolactide-based sensors and biosensors are discussed, with particular emphasis on the mechanism of signal generation and the contribution of modified materials to the selectivity and sensitivity of analysis.

An approach to p-tert-butylthiacalix[4]arene derivatives functionalized with lactic acid fragments in three conformations (cone, partial cone, 1,3-alternate) was developed. The use of tetraglyme as a solvent and magnesium sulfate with p-toluenesulfonic acid as co-condensation catalysts made it possible to obtain the desired products without admixtures of oligolactic acid. The structure of the synthesized macrocycles was characterized by a complex of physico-chemical methods. The thermal properties of the synthesized lactic acid copolyesters were studied by simultaneous thermogravimetry and differential scanning calorimetry analysis. Significant effect of the p-tert-butylthiacalix[4]arene platform on the thermal stability of the obtained products was demonstrated. Nanoscale particles of the synthesized macrocycles with a low polydispersity index were obtained using nanoprecipitation from methanol or acetone into a buffer solution.

The final stage of the diagnostic of primary hyperaldosteronism is to identify the causes of excessive secretion of aldosterone and determination of its variants. Based on the analysis of literature data, the diagnostic value, sensitivity and specificity of the methods of radiation diagnostics for primary hyperaldosteronism were assessed: ultrasound, computed tomography, magnetic resonance imaging, photon emission tomography, magnetic resonance spectroscopy, scintigraphy with iodine radiopharmaceuticals. The causes of false-positive and false-negative evaluations of changes in adrenal glands in the application of these diagnostics have been analyzed. There are many genetic and morphological studies when searching the literature data on the principles and methods of distinguishing the nosological forms of primary hyperaldosteronism based on the results of the aldosterone level estimation in the separated blood from the central veins of both adrenal glands or segmental veins of one gland with subsequent determination of the concentration gradient. It was noted that topical diagnostics and, especially, the determination of nosological forms of primary hyperaldosteronism are complex and expensive, but their results allow choosing an appropriate treatment approach for each particular case.

An impedimetric DNA sensor is developed for the highly sensitive determination of doxorubicin; the signal is charge transfer resistance recorded by electrochemical impedance spectroscopy using a glassy carbon electrode modified by electropolymerized Neutral Red or polyaniline and polyelectrolyte complexes including DNA. The nature of the polymer layer and the composition of the polyelectrolyte complex affect the sensitivity of the determination of doxorubicin. The role of a macrocycle capable of shielding the DNA negative charge and interacting with cationic centers of the substrate is shown. With an optimal composition of polyelectrolytes, the DNA sensor ensures the determination of down to 0.1 nM of doxorubicin.

The interaction of (L)-lactic acid with p-tert-butylthiacalix[4]arene containing ethoxycarbonyl fragments in the 1,3-alternate conformation was studied in tetraglyme. For the first time, the lactic acid oligomer was obtained by polycondensation with the macrocycle and characterized by 1H, 13C NMR, IR spectroscopy, MALDI mass spectrometry and gel permeation chromatography. Thermal stability of the obtained copolyester of lactic acid and thiacalix[4]arene was studied by TG/DSC analysis and the effect of the macrocyclic platform on its thermal properties was shown. Copolyester obtained was thermally more stable than oligolactic acid. Self-assembly of synthesized oligomer was studied by dynamic light scattering method. It was shown that monodisperse particles (PDI = 0.13) with the size of 208 ± 4 nm are formed in CH3CN solution at 2.5 × 10−5 M concentration.

Quantum chemical calculations of substituted α-Cumyl and tBu bis(phenoxy-imine) titanium catalysts were performed at the RBP86/SVP level. The impact of para-substitution in the phenoxy-imine ligands on the electronic structure of the titanium complexes was studied within the framework of the Conceptual density functional theory. We found that such a reactivity descriptor as local hyper-softness on titanium correlates well with the Hammett constant for a series of substituents. The effect of the substitution in three para-positions of the phenoxy-imine ligand for the Cumyl catalysts weakens while passing from the α-Cumyl through the salicylic and further to the aniline moiety. By contrast, in the tBu complexes the presence of a substituent in the salicylic part has similar influence on the local hyper-softness on titanium as compared with the aniline moiety. Moreover, placement of the groups with opposite electronic effects at the termini of the phenoxy-imine framework was shown to provide electronic flexibility in both the α -Cumyl and the tBu complexes. Within the framework of the "ligand-oriented" concept, such flexibility increases the activity of a bis(phenoxy-imine) catalyst. In addition, we demonstrated that the hyper-conjugation between the π-system of the phenoxy-imine ligand and the α-Cumyl group raises the energy of the highest occupied molecular orbital keeping the lowest unoccupied orbital almost unchanged. This makes the α-Cumyl complexes chemically softer than their tBu analogs and thereby more active in ethylene polymerization.

In this paper, we propose and develop an approach to synthesize an interpolyelectrolyte mixed nanoparticles of cationic and anionic thiacalix[4]arene derivatives, capable to selective recognition of model biopolymers (DNA from calf thymus, lysozyme, bovine serum albumin). Some ammonium and sulfonate derivatives of the p-tert-butylthiacalix[4]arene were chosen as supramolecular building blocks of these nanoparticles. In addition, we synthesized sulfobetaine-functionalized macrocycle where anionic and cationic groups are included in one molecular platform. Depending on conformation of macrocyclic platform (cone, 1,3-alternate) interpolyelectrolyte mixed nanoparticles with different size, stability and morphology were synthesized. We showed that the recognition of biopolymers is selective and depends on the ability to forming of nano-associates and the nature (charge) of the functional groups on the surface of the interpolyelectrolyte mixed nanoparticles. Negatively charged interpolyelectrolyte mixed nanoparticles form associates with lysozyme, while positively charged interpolyelectrolytes compact the high molecular DNA from calf thymus. The sulfobetaine derivatives of the thiacalix[4]arene stabilize monomeric form of BSA.

A DNA sensor was developed on the basis of glassy carbon electrode coated with polymeric forms of thionine and Azure B. Introduction of carbon black and pillar[5]arene into the electrode composition increases the efficiency of polymerization and the oxidation peak currents of dyes due to the mediating effect of the macrocycle. The addition of DNA onto the sensor surface and into the reaction mixture differently influences the electrochemical activity of poly(Azure B) and polythionine. The control of changes in current-voltage characteristics allowed us to identify the heat denaturation of DNA and its oxidation by reactive oxygen species generated upon the reaction of hydrogen peroxide and copper(II) salt. The DNA sensors can find application in the diagnosis of DNA damage on exposure to carcinogens and in screening of cytotoxic anticancer drugs.

Hybrid aminated and sulfonated nanoparticles were synthesized by surface modification of silica nanopowder with 3-aminopropyltriethoxysilane and 1,3-propanesultone, respectively. The developed protocols for the synthesis of three types of "buffer" mixed submicron particles with corresponding ζ-potentials (–21.4±1.3, 4.7±0.4, 12.4±0.8) were based on various methods of nanoprecipitation of synthesized silica nanoparticles modified by amino- and sulfonate groups, and on various conditions of these precepitation (solvent, temperature). Hybrid SiO2 particles, as well as self-assembling associates based on sulfonated and aminated particles, were examined in extraction of biologically important macromolecules. It was established that the efficiency of adsorption of calf thymus DNA increased with increasing zeta potentials of the modified silica particles studied. The interaction of the studied model proteins (bovine serum albumin and lysozyme) with the synthesized silica nanoparticles modified by sulfonate groups increased as the pH of the medium decreased.

A new acetylcholinesterase biosensor has been developed for the determination of anticholinesterase drugs applied for neurodegenerative disease treatment. For this purpose, silver nanosendrites were deposited by potentiostatic electrolysis on a glassy carbon electrode covered with oligolactides cross-linked with p-tert-butylthiacliax[4]arene core in the cone, partial cone, and 1,3-alternate configurations. The roles of macrocycle configuration and electrolysis conditions on the silver depostion were characterized and optimal conditions selected for the subsequent immobilization of acetylcholinesterase. Silver nanoparticles provide higher response at low working potential (0.05 V) due to the electrostatic accumulation of silver ions and prevention of their leaching after reoxidation. The biosensor allows the determination of 10−12 – 10−7 M donepezil, berberine, and huperzine A within 20-30 s by the relative decay of the current related to the oxidation of thiocholine formed in enzymatic reaction. T...

As a result of our research, we propose the chromatographic conditions for the separation of arbutin and the conditions for the sample preparation of the raw material of Malus sylvestris leaves for HPLC analysis. According to the conducted studies, the content of arbutin should not be less than 0.7%.

The effect of product inhibition on yeast hinders the production of wine with ethanol concentration above 80.0 g L−1 (∼10°GL) in the industrial ethanol production process commonly performed at 34 °C. Lowering the fermentation temperature is a way to produce wines with higher ethanol contents. In this work, batch fermentations were carried out at temperatures of 28, 30, 32, and 34 °C, with initial substrate concentration of 180.0 g L−1, using industrial yeast under conditions reproducing those found in industry. The Andrews-Levenspiel hybrid kinetic model, considering viable cells, showed an excellent fit to the experimental data. Kinetic parameters were determined for the different temperatures. The model was used to simulate fed-batch fermentations at different temperatures, with the same total substrate concentration, resulting in satisfactory descriptions of the process behaviors. A new optimization strategy to obtain the maximum possible ethanol production, based on the CEmax parameter of the Andrews-Levenspiel kinetic model, provided ethanol production of up to 134.7 g L-1 (17.1°GL) at 28 °C and 305.4 g L−1 substrate. A modification was made to the Andrews-Levenspiel kinetic model, relating the n parameter to the final ethanol concentration (CEf), in order to enable the model to describe the behavior of fed-batch fermentations performed with high substrate concentration and at temperatures from 28 to 34 °C.

Monosubstituted pillar[5]arenes containing a phosphonate fragment were successfully obtained in good yields. It was found that the introduction of bulky fragments containing tetra-coordinated pentavalent phosphorus atoms prevents self-assembly of monosubstituted pillar[5]arenes and the formation of supramolecular polymers. Pillar[5]arenes with phosphonate and 1-aminophosphonate substituents demonstrated recognition towards Na+, K+, Cs+ and Pb2+. Their ability to form complexes with these cations was evaluated by UV spectroscopy. Dynamic light scattering (DLS) revealed the formation of aggregates with K+, Cs+ and Pb2+. It was established that the substituent at the α-carbon atom of the aminophosphonate fragment played a significant role in Pb2+ binding. DLS and transmission electron microscopy revealed that Pb2+-induced aggregation formed particles with a monodisperse distribution of 0.02–0.23 and a hydrodynamic diameter of 58–178 nm.

The technique of the quantitative determination of the sum of flavonoids based on rutin in the Canadian Goldenrod herb is modified by the method of differential spectrophotometry. Optimal conditions for the extraction of flavonoids from the Canadian Goldenrod are chosen depending on the concentration of the extracting solvent, the fineness factor of the raw materials, and the concentration of the complexing agent. The method is validated for accuracy, reproducibility, repeatability, and linearity.

The hippocampus is one of the most challenging brain regions for proton MR spectroscopy (MRS) applications. Moreover, quantification of J-coupled species such as myo-inositol (m-Ins) and glutamate + glutamine (Glx) is affected by the presence of macromolecular background. While long echo time (TE) MRS eliminates the macromolecules, it also decreases the m-Ins and Glx signal and, as a result, these metabolites are studied mainly with short TE. Here, we investigate the feasibility of reproducibly measuring their concentrations at a long TE of 120 ms, using a semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence, as this sequence was recently recommended as a standard for clinical MRS. Gradient offset-independent adiabatic refocusing pulses were implemented, and an optimal long TE for the detection of m-Ins and Glx was determined using the T2 relaxation times of macromolecules. Metabolite concentrations and their coefficients of variation (CVs) were obtained for a 3.4-mL voxel centered on the left hippocampus on 3-T MR systems at two different sites with three healthy subjects (aged 32.5 ± 10.2 years [mean ± standard deviation]) per site, with each subject scanned over two sessions, and with each session comprising three scans. Concentrations of m-Ins, choline, creatine, Glx and N-acetyl-aspartate were 5.4 ± 1.5, 1.7 ± 0.2, 5.8 ± 0.3, 11.6 ± 1.2 and 5.9 ± 0.4 mM (mean ± standard deviation), respectively. Their respective mean within-session CVs were 14.5% ± 5.9%, 6.5% ± 5.3%, 6.0% ± 3.4%, 10.6% ± 6.2% and 3.5% ± 1.4%, and their mean within-subject CVs were 17.8% ± 18.2%, 7.5% ± 6.3%, 7.4% ± 6.4%, 12.4% ± 5.3% and 4.8% ± 3.0%. The between-subject CVs were 25.0%, 12.3%, 5.3%, 10.7% and 6.4%, respectively. Hippocampal long-TE sLASER single voxel spectroscopy can provide macromolecule-independent assessment of all major metabolites including Glx and m-Ins.

The synthesis of new phenothiazine derivatives, analogs of Methylene Blue, is of particular interest in the design of new drugs, as well as in the development of a new generation of agents for photodynamic therapy. In this study, two new derivatives of phenothiazine, i.e., 3,7-bis(4-aminophenylamino)phenothiazin-5-ium chloride dihydrochloride (PTZ1) and 3,7-bis(4-sulfophenylamino)phenothiazin-5-ium chloride (PTZ2), are synthesized for the first time and characterized by NMR, IR spectroscopy, HRMS and elemental analysis. The interaction of the obtained compounds PTZ1 and PTZ2 with salmon sperm DNA is investigated. It is shown by UV-Vis spectroscopy and DFT calculations that substituents in arylamine fragments play a crucial role in dimer formation and interaction with DNA. In the case of PTZ1, two amine groups promote H-aggregate formation and DNA interactions through groove binding and intercalation. In the case of PTZ2, sulfanilic acid fragments prevent any dimer formation and DNA binding due to electrostatic repulsion. DNA interaction mechanisms are studied and confirmed by UV-vis and fluorescence spectroscopy in comparison with Methylene Blue. The obtained results open significant opportunities for the development of new drugs and photodynamic agents.

Bioinspired fluorescence, being widely explored for imaging purposes, faces challenges in delivering bright biocompatible sources. While quite a few techniques have been developed to reach this goal, encapsulation of high-quantum yield fluorescent dyes in natural biological forms suggest achieving superior light-emitting characteristics, approaching amplified spontaneous emission and even lasing. Here we compare gain capabilities of highly concentrated Rhodamine B solutions with a newly synthesized biocompatible peptide derivative hybrid polymer/peptide material, RhoB-PEG1300-F6, which contains the fluorescent covalently bound dye. While concentration quenching effects limit the maximal achievable gain of dissolved Rhodamine B, biocompatible conjugation allows elevating amplification coefficients towards moderately high values. In particular, Rhodamine B, anchored to the peptide derivative material, demonstrates gain of 22–23 cm−1 for a 10−2 M solution, while a pure dye solution possesses 25% smaller values at the same concentration. New biocompatible fluorescent agents pave ways to demonstrate lasing in living organisms and can be further introduced to therapeutic applications, if proper solvents are found.

For the first time, a series of catechol-containing Schiff bases, tetrasubstituted at the lower rim thiacalix[4]arene derivatives in three stereoisomeric forms, cone, partial cone, and 1,3-alternate, were synthesized. The structure of the obtained compounds was proved by modern physical methods, such as NMR, IR spectroscopy, and HRMS. Selective recognition (Kb difference by three orders of magnitude) of copper (II) cation in the series of d-metal cations (Cu2+, Ni2+, Co2+, Zn2+) was shown by UV-vis spectroscopy. Copper (II) ions are coordinated at the nitrogen atom of the imine group and the nearest oxygen atom of the catechol fragment in the thiacalixarene derivatives. High thermal stable organic-inorganic copper-based materials were obtained on the base of 1,3-alternate + Cu (II) complexes.

In this work, we have proposed a novel universal stimulus-sensitive nanosized polymer system based on decasubstituted macrocyclic structures—pillar[5]arenes and tetrazole-containing polymers. Decasubstituted pillar[5]arenes containing a large, good leaving tosylate, and phthalimide groups were first synthesized and characterized. Pillar[5]arenes containing primary and tertiary amino groups, capable of interacting with tetrazole-containing polymers, were obtained with high yield by removing the tosylate and phthalimide protection. According to the fluorescence spectroscopy data, a dramatic fluorescence enhancement in the pillar[5]arene/fluorescein/polymer system was observed with decreasing pH from neutral (pH = 7) to acidic (pH = 5). This indicates the destruction of associates and the release of the dye at a pH close to 5. The presented results open a broad range of opportunities for the development of new universal stimulus-sensitive drug delivery systems containing macrocycles and nontoxic tetrazole-based polymers.

Decasubstituted pillar[5]arenes containing amidopyridine fragments have been synthesized for the first time. As was shown by UV-vis spectroscopy, the pillar[5]arenes with p-amidopyridine fragments form supramolecular associates with Cu(II) and Pd(II) cations in methanol in a 2:1 ratio. Using a sol-gel approach these associates are transformed into metallo-supramolecular coordination polymers (supramolecular gels) which were characterized as amorphous powders by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The powders are able to selectively adsorb up to 46% of nitrophenols from water and were incorporated into an electrochemical sensor to selectively recognize them in aqueous acidic solution.