Objectives. Soy protein hydrolysates are now widely used in the food industry, fish farming, poultry farming, livestock farming, as well as in medical preparations. The most effective method for their production is enzymatic hydrolysis. However, even with optimal proteolysis parameters, it is not always possible to achieve the required degree of hydrolysis. For this reason, various technological approaches are used to more intensively break down soy proteins, including the addition of enzyme preparations and pretreatment of the protein substrate. β-Conglycinin, one of the main soy proteins, is a glycoprotein whose carbohydrate portion consists primarily of mannose residues. We hypothesize that deglycosylation of β-conglycinin by an enzyme preparation with mannanase activity as a pretreatment of the soy substrate will lead to change in the structure of its protein portion due to the destruction of the carbohydrate component to increase the accessibility of peptide bonds to proteolytic enzymes. Thus, the work sets out to study the effect of enzymatic deglycosylation on the efficiency of soy protein hydrolysis.Methods. Deglycosylation of β-conglycinin, hydrolysis of polysaccharides and lipids were performed by the Complex-concentrate enzyme preparation (Ferment, Republic of Belarus). Protein hydrolysis was carried out by the Protozyme C330 enzyme preparation (Ferment, Republic of Belarus). The formation of reducing sugars was confirmed by the Miller method. The degree of protein hydrolysis was determined by the pH-stat method. The molecular weight distribution of peptide fractions was analyzed by low-pressure liquid gel chromatography on a column with Sephadex® G-50 Medium. Computer processing of the elution profile of peptide fractions was performed in the OriginPro 8.5.1 program using the Gauss function.Results. It is established that the treatment of soy flour by the Complex-concentrate enzyme preparation (enzyme-substrate ratio 1 : 40, hydromodule 1 : 10) promotes the breakdown of both free oligo- and polysaccharides, as well as the carbohydrate component β-conglycinin. Proteolysis by the Protozyme C330 enzyme preparation (enzyme-substrate ratio 1 : 20, pH 7.5, 50°C, 3.5 h) carried out following 20 h of deglycosylation results in a product with a degree of hydrolysis of 56.3%. The content of low-molecular-weight peptides in soy hydrolysate is 83.9%. Proteolysis without enzymatic destruction of the carbohydrate part of β-conglycinin is shown to be characterized by a degree of hydrolysis of 9.2%.Conclusions. A pretreatment approach involving deglycosylation of enzymatic β-conglycinin can be used to significantly increase the degree of hydrolysis of soy proteins.
Objectives. The work set out to develop a chromatographic purification technology for drugs based on modified single-domain antibodies specific to the SARS-CoV-2 virus, as well as to select the optimal parameters for the purification process and scale up this technology for production.Methods. The study was conducted on a culture of Chinese hamster ovary (CHO) cells GAMP2C5 clone 78, CHO B5 clone 4, and CHO B10 clone 4, which were used to produce modified single-domain antibodies GAMP2C5, GAMB5, and GAMB10, respectively. Chromatographic purification was performed using AKTA pure 25 and AKTA Pilot 600s chromatographs. Quality control of the obtained drugs was carried out using high-performance liquid chromatography, capillary gel electrophoresis, dynamic light scattering, enzymelinked immunosorbent assay, and polymerase chain reaction.Results. Multimodal chromatography using CA++Pure-HA (TOSOH, Japan) resin based on type 1 ceramic hydroxyapatite can be effectively used for the removal of aggregated antibody forms. The drugs obtained after chromatography using CA++Pure-HA resin based on type 1 ceramic hydroxyapatite have a purity of more than 97%. The developed purification technology was scaled up to purify 200 L of culture fluid after cultivation in an STR 200 bioreactor.Conclusions. The described technology developed for purifying modified mono-domain antibodies using the CA++Pure-HA multimodal resin based on type 1 ceramic hydroxyapatite allows for the effective removal of low-molecular-weight impurities and aggregated forms of the antibody. The antibodies obtained using the developed technology are characterized by a high degree of purity and the absence of various impurities (residual protein of the producer strain, residual protein A, and residual DNA of the producer strain), as well as offering a hydrodynamic molecular radius corresponding to the theoretical value of monomeric forms of antibodies.
Objectives. The work sets out to model the ozone corrosion of vulcanizates as a percolation phase transition, similar in the scheme of development of continual percolation on a plane, during which the growing regions of the new phase form a single “spanning” cluster. In this case, the continuity of the sample is broken, being divided into two parts. In the presented model, the ozone corrosion process is divided into two stages. At the first stage, ozone corrosion of the material occurs mainly along the perimeters of already ozonized surface areas, which leads to their growth and subsequent merging. Upon contact of adjacent surface areas consisting of ozonolysis products loaded with two-dimensional tension, corrosion cracks begin to appear on the surface. At the second stage of the corrosion process, corrosion cracks that grow deeply into the material due to its stress state lead to the penetration of ozone into the internal regions of the sample. The article presents the results of computer-simulation and real experiments carried out on ozone corrosion of technical vulcanizates in a plane stressed state.Methods. Computer simulation of the time dependence of the total contact length of the areas of ozone corrosion products and the initial vulcanizate was carried out using a C++ program developed by the authors. Real experiments were carried out on a TOM-1000 setup. Samples for research by the TOM (technical ozone resistance of materials[1]) method comprise thin disks, which are clamped along the contour and subjected to one-sided two-dimensional tension by compressed air pressure. From the side of the opposite plane, the sample is exposed to the ozone flow. The installation makes it possible to create in the sample a relative deformation of up to 100% increase in the surface area.Results. Computer simulation allowed, in combination with direct measurements of the time dependence of ozone absorption, the dynamics of the destruction of vulcanizates in an ozone environment to be investigated. A numerical parameter of the ozone resistance of vulcanizates—the coefficient of ozone resistance—is proposed. This coefficient is almost linearly related to the time before the onset of cracking, but it is more accurate because it does not require visual observation of the ozonolysis process.Conclusions. The results of computer simulation are in good agreement with the results of real experiments.
Objectives. To study the effect of shape on the intensity of surface-enhanced Raman light scattering when depositing nanoparticles on track membranes. The resulting composite material can be further used as a substrate for sensors. The efficiency of such sensors is determined by the effect of surface-enhanced Raman scattering of light.Methods. Silver nanoparticles were obtained by reduction of silver ions in solution under various conditions. Nanoparticles from the obtained colloidal solutions were deposited on polyethylenimine-modified polyethylene terephthalate track-etched membranes. The samples were examined using absorption spectroscopy in the ultraviolet and visible region, scanning and transmission electron microscopy, dynamic light scattering, and Raman spectroscopy.Results. Silver nanoparticles of spherical, triangular, and nanowire shape were synthesized. The sizes and zeta potential of the nanoparticles were determined. The obtained nanoparticles were deposited on the surface of track-etched membranes. For the composite membrane samples, the relative enhancement factors of the Raman light scattering signal of the 4-aminothiophenol test substance were calculated based on the substrate with a known enhancement factor.Conclusions. The effect of surface-enhanced Raman light scattering was found to be greater when transitioning from spherical to various nonspherical-shaped nanoparticles. The highest value of the relative enhancement factor was 4 · 107 on the composite membrane with silver nanowires.
Objectives. To obtain data on the compatibility of a polymer blend based on poly-3-hydroxybutyrate and butadiene-nitrile rubber for the development of a biodegradable polymer with improved mechanical properties.Methods. Film samples of biodegradable plastic–elastomer blends, using mixtures of poly-3-hydroxybutyrate and butadiene-nitrile rubber as a case study, were investigated by means of optical and scanning electron microscopy with computer-aided image analysis, differential scanning calorimetry, mathematical analysis, and Fourier transform infrared spectroscopy.Results. The mixtures studied herein were found to have a heterogeneous heterophase structure. The interaction between the carbonyl group of poly-3-hydroxybutyrate and the nitrile group of acrylonitrile block of acrylonitrile butadiene-nitrile rubber is shown due to kinetic compatibility. A change in the crystalline regions of poly-3-hydroxybutyrate when it is mixed with rubber was also noted. The results of the Gibbs energy calculation of mixing confirmed the interaction of carbonyl and nitrile groups. Microscopy results show the localization of poly-3-hydroxybutyrate particles around rubber particles. The reasons for this phenomenon are discussed here.Conclusions. Studies have shown a relationship between morphology and component content of the samples. The change in composition affects the structure and properties of the surface and volume. The formation of associates leads to the formation of an interface which attracts the second component. The Flory–Huggins theory, Avrami equations, and microscopic data established a complex interaction mechanism: convergence and formation of chemical bonds, rearrangement of crystalline regions, transition of spherulitic particles into lamellar particles, diffusion of rubber macromolecules, association of poly-3-hydroxybutyrate particles around the rubber, and completion of chemical bonds.
Objectives. In this work, we consider the relationship between the tracer (k*) and chemical (kδ) oxygen exchange coefficients for Ba0.5Sr0.5(Co0.8Fe0.2)1−xMexO3−δ (Me = Ta, W) oxides. The aim is to analyze the experimental dependencies of the chemical (kδ) and tracer (k*) coefficients of oxygen exchange, evaluate the surface thermodynamic factor w0|x=±L , and compare its value with the bulk thermodynamic factor w0|x=0 determined from the dependence of oxygen content in oxides on the temperature and partial pressure of oxygen. Possible reasons for the discrepancy between these two thermodynamic factors are discussed.Methods. The oxygen exchange kinetics between the gas phase and the surface of oxide materials under nonequilibrium conditions was studied using the method of oxygen pressure relaxation. The surface thermodynamic factor was calculated based on data obtained under both equilibrium and nonequilibrium conditions.Results. Comparison of the tracer (k*) and chemical (kδ) oxygen exchange coefficients allowed the w0|x=±L surface thermodynamic factor to be estimated by the kδ = k*w0|x=±L equation.Conclusions. The surface thermodynamic factor was found to differ from the bulk thermodynamic factor of the oxide material, w0 = [1∂ln(pO2 )] / [2 ∂ln (3−δ)], which can be calculated from the dependence of oxygen content in oxides on the temperature and partial pressure of oxygen. This difference can be explained by the difference in the defect structure of the surface layers of oxide materials.
Objectives. To introduce the intermediate obtained from the disposal of unusable rocket propellant—1,1-dimethyl2-methylenehydrazone (DMH)—into the synthesis of pyrroloquinolines (and pyridines) with potential applications in medicine; to carry out reactions of DMH with tetracyanoethylated ketones (TCEKs) derived from acetone, methyl ethyl ketone, cyclohexanone, 4-propylcyclohexanone, and 2-methylcyclohexanone; to investigate the prospects for increasing the yields of target products by performing the same syntheses under microwave irradiation (MWI) and using an ultrasonic reactor.Methods. TCEKs were prepared from tetracyanoethylene (TCNE) and the corresponding ketone in dioxane, acetone, or ethanol, with the presence of concentrated hydrochloric or sulfuric acid as a catalyst. Pyrroloquinolines (and pyridines) were synthesized from DMH and the corresponding TCEK in ethyl acetate with base as a catalyst. Syntheses were carried out under standard conditions using a magnetic stirrer, an ultrasonic reactor (Vologda, Russia), and a UWave-2000 microwave reactor (Sineo Microwave Chemistry Technology Co., China). Reaction progress and product purity were monitored by thin-layer chromatography on Sorbfil plates (Sorbfil, Russia). The TCNE presence in the reaction mixture was determined by the hydroquinone test. Melting and decomposition points were measured using anOptiMeltMPA100 apparatus (OptiMelt, USA). Structural identification was performed by infrared spectroscopy (FSM-1202, SpektroLab, Russia), 1H and 13C nuclear magnetic resonance spectroscopy in dimethyl sulfoxide d6 on a Bruker AVANCE 400 WB spectrometer (Bruker Corporation, USA), and mass spectrometry using a quadrupole time-of-flight AB SCIEX TripleTOF 5600 spectrometer (AB SCIEX PTE. Ltd., Singapore) and a quadrupole gas chromatography–mass spectrometer GCMS-QP2020 NX (Shimadzu, Germany).Results. Reliable procedures developed for the synthesis of pyrrolopyridines from acetone and methyl ethyl ketone without tar formation under ultrasonic stirring and MWI demonstrated significantly increased yields. The highest conversion of DMH to pyrroloquinoline was achieved from cyclohexanone, providing the target product in 92% yield within the shortest reaction time of 2 min under MWI conditions. However, for derivatives of 4-propylcyclohexanone and 2-methylcyclohexanone, the described synthesis modifications did not give the desired results: in the former case, a decrease in yield was observed as compared to standard methods, while in the latter, only a slight increase was obtained.Conclusions. Ultrasonic stirring and MWI are effective for the conversion of DMH into pyrrolopyridines based on aliphatic TCEKs, but unsuitable for the synthesis of pyrroloquinolines derived from 4-propylcyclohexanone and 2-methylcyclohexanone. The high yield of pyrroloquinoline from cyclohexanone (92%) suggests potential for implementing the rapid MWI-promoted reaction between DMH and cyclohexanone-based TCEK in industrial production.
Objectives. In comparison with methyl tert-butyl ether (MTBE) and methanol mixtures, the separation of MTBE and tert-butanol (tert-butyl alcohol, TBA) mixtures represents a relevant challenge in chemical technology due to limited research in this area. Our aim was to evaluate the potential and efficiency of using choline chloride-based deep eutectic solvents (DESs) as green extractants for the separation of the MTBE–TBA system via liquid–liquid extraction (LLE).Methods. DESs were prepared by mixing and heating a hydrogen bond acceptor (choline chloride, ChCl) with hydrogen bond donors (HBDs) as follows: malonic acid (1 : 1 molar ratio), glutaric acid (1 : 1), urea (1 : 2), and glycerol (1 : 2). Liquid–liquid phase equilibrium was experimentally studied in four ternary systems containing MTBE, TBA, and DES at temperatures of 293.15 and 313.15 K and atmospheric pressure. The compositions of the equilibrium liquid phases were determined using 1H nuclear magnetic resonance spectroscopy (500 MHz, dimethyl sulfoxide-d6).Results. The experimental data allowed the key extraction parameters to be calculated: distribution coefficients for TBA and selectivity for MTBE–TBA separation for each investigated DES. A comparative analysis of the extraction capacity of the synthesized solvents toward the separated components was performed. The experimental phase equilibrium data confirm the fundamental possibility of using the ChCl-based DESs under study as extractants for separating the MTBE–TBA system. The calculated selectivity and distribution coefficient values allow the efficiency of various HBDs within the DES composition to be evaluated for solving this separation task. The comparative analysis of the DES extraction capacity showed a dependence of selectivity on the HBD and a slight dependence of selectivity on temperature. The highest selectivity values were observed for DESs based on ChCl/glycerol (1 : 2) and ChCl/urea (1 : 2) systems.Conclusions. The feasibility of using DESs based on choline chloride with malonic acid, glutaric acid, urea, and glycerol as extractants for separating the MTBE–TBA mixture by LLE method has been experimentally confirmed. The calculated distribution coefficients and selectivity values enable a quantitative assessment and comparison of the efficiency of different DESs for this task, identifying the most promising compositions. The results obtained can be used as the basis for further development and optimization of the LLE process for MTBE and TBA using promising green solvents.
Objectives. The effects of positive and negative temperature coefficients (PTC and NTC, respectively) in carbon black-filled conductive polymer composites based on high-density polyethylene grade 277-73 and polypropylene grade 01050 were investigated. Carbon black electrically conducting grade OMCARB C-140 (UM-76) was used as the filler.Methods. To study the electrical characteristics of the compositions, plates were pressed with brass contact electrodes at the plate ends to simulate polymer heaters. The electrical resistance of the samples was evaluated using an ohmmeter DT9208A (RESANTA, Latvia). Tests at elevated temperatures were carried out in an SNOL 3.5 heat chamber (NPF TherMIX, Russia) with a heating rate of ~3℃/min. The crystallinity of the samples during heating was assessed by differential scanning calorimetry on a DSC 204F1 Phoenix device (NETZSCH, Germany) with a heating rate of 3℃/min.Results. The complex PTC and NTC mechanisms in mixed polymer compositions are not solely related to thermal expansion and melting of the polymer. While changes in the electrical resistance of carbon-filled polymer composites are associated with the presence of crystalline regions with defects, the destruction of the conductive channels occurs at the earliest stages of polymer melting due to the formation of expanding amorphous “microdroplets” of the hot melt. For a carbon-filled, electrically conductive mixture of polyethylene and polypropylene, the magnitude and nature of the change in the peak temperature of the PTC depends on the melting onset temperature of the lowest-melting phase of polyethylene. At the same time, the heterogeneity of the mixtures of crystallizing polymers with technical carbon increases the thermal stability of the material by expanding the PTC zone into the melting region of the higher-melting phase of polypropylene. When comparing electrically conductive compositions of polymers with different melting points and carbon black, the low-melting polymer determines the temperature of self-regulation and the nature of PTC, while the high-melting polymer shifts the jump in electrical conductivity to the region of elevated temperatures.Conclusions. The activation energies of carbon-filled mixtures of polyethylene and polypropylene, which are weakly dependent on the mixing method, are approximately 44 ± 3 kJ/mol. The obtained values are consistent with the activation energy values for the viscous melt flow process. The method of mixing the components in mixtures of carbon-filled compositions based on crystallizing polymers was found to have little effect on PTC. The use of carbon-filled polymer compositions with a mixed matrix of polyethylene and polypropylene allows for the regulation of the intensity of PTC and NTC.
Objectives. Gene therapy involves the administration of various types of therapeutic nucleic acids into the organism, in order to treat severe hereditary diseases, as well as cancer. Furthermore, the COVID-19 pandemic demonstrated the possibility of rapid development and the effectiveness of both DNA and mRNA vaccines for the prevention of viral diseases. Numerous studies in the field of gene therapy have revealed that in most cases successful delivery of nucleic acids requires a special delivery system which protects nucleic acids from the effects of external and internal biological factors. Among the various types of such tools, non-viral delivery systems have proven to be the most versatile and safe ones. In the case of mRNA delivery, such systems are usually called mRNA vaccines, consisting of cationic or ionizable lipids. The purpose of this review is to justify the choice of the optimal structure of lipid components of mRNA vaccines and highlight the current prospects for their clinical use.Results. In this review, we have considered the evolution of lipid structures, from cationic to ionizable, as the main components of mRNA delivery systems. Furthermore, the study demonstrated the necessity to use other types of lipids in mRNA vaccines. It also presents a review of clinical trials of mRNA vaccines against viral and oncological diseases, and provides recommendations for the design of the optimal structure of both cationic and ionizable lipids.Conclusions. The most promising lipids for the development of mRNA vaccines are ionizable. They do not have a permanent positive charge which reduces their cytotoxicity and undesirable binding to components of the immune system. In general, mRNA vaccines can be universal and effective means for treating various types of diseases. However, their composition needs to be careful optimized.
Objectives. The work set out to describe the main physicochemical properties of new perfluorinated compounds (perfluoro-N-butylmorpholine, perfluoro-N-butylpiperidine, and perfluoro-N-ethylpiperidine) developed at the Russian Research Center “Applied Chemistry” (GIPH), and to evaluate the potential of their use as perfluorinated technical liquids by studying the temperature dependencies of their density, viscosity, and heat capacity in low temperature regions, as well as their applicability as media for syntheses involving strong Lewis acids using tris(pentafluoroethyl)difluorophosphorane as an example.Methods. Perfluorinated tertiary amines (perfluorotriethylamine, perfluorotributylamine, perfluoro-N-butylmorpholine, perfluoro-N-butylpiperidine, perfluoro-N-ethylpiperidine) were synthesized by electrochemical fluorination in anhydrous hydrogen fluoride. The composition, purity, and structure of the perfluoroamines were determined by gas–liquid chromatography (Kristall 2000M) and confirmed by nuclear magnetic resonance spectroscopy (Bruker AVANCE III HD 400 MHz) and chromatography–mass spectrometry (Agilent Technologies 7890B/5977A). The thermal characteristics of the samples were determined by differential scanning calorimetry (NETZSCH DSC 214 Polyma). The density and kinematic viscosity of the samples were studied using a Stabinger viscometer (Anton Paar Stabinger Viscometer SVM 3000). Metal tris(pentafluoroethyl)trifluorophosphates were obtained by the fluorination of tris(pentafluoroethyl)difluorophosphorane by fluorides of the alkali metals—lithium, sodium, and potassium.Results. Electrochemical fluorination produced tert-amines of various structures: perfluorotriethylamine, perfluorotributylamine, perfluoro-N-butylmorpholine, perfluoro-N-butylpiperidine, and perfluoro-N-ethylpiperidine with current yields from 29 to 61%. The dependencies of the heat capacity, density, and kinematic viscosity of new perfluorinated alkylmorpholines and alkylpiperidines in comparison with noncyclic perfluoroamines were studied over a wide temperature range. In the media of the obtained perfluoroamines, tris(pentafluoroethyl)difluorophosphorane salts of lithium, sodium, and potassium were synthesized at a yield of 38 to 95%.Conclusions. The analysis of the physicochemical properties of heterocyclic perfluorinated tert-amines obtained in this work (perfluoro-N-butylmorpholine, perfluoro-N-butylpiperidine, and perfluoro-N-ethylpiperidine) indicates that these compounds are not inferior to noncyclic perfluorinated tert-amines in a number of characteristics, thus indicating their potential use as perfluorinated technical fluids thanks to their high heat capacity and potentially low conductivity. The key parameters determining their applicability as media for syntheses involving perfluorinated reagents are identified as physicochemical similarity, high density, and low viscosity at subzero temperatures.
Objectives. The work set out to develop epoxy multicomponent binders for polymer composite materials by interrelating the rheological properties and the curing kinetics of the epoxy modified with thermoplastic. Changes in the rheological properties of binders are determined by the competition between two processes: the curing reaction of modified epoxy oligomers with an amine curing agent, and phase separation, which leads to a loss of compatibility between thermosetting components and modifier.Methods. During the curing process, rotational and oscillational rheometry were used. The kinetic patterns of the curing process of epoxy-amine binders based on a mixture of trifunctional and bifunctional epoxy resins modified with polysulfone were studied.Results. The dependence of viscosity on curing time of an epoxy binder at various temperatures and polysulfone content was experimentally studied. Gelation and vitrification time, viscosity growth constants, and activation energies values were determined. It was shown that phase separation induced by curing results in the formation of a polysulfone-rich phase. Moreover, the phase separation time decreases with higher modifier content.Conclusions. It has been established that the adding of polysulfone into the composition of a multicomponent epoxy-amine binder leads to an enhancement in the gelation time by 8–15 min, depending on the curing temperature and the thermoplastic content, which is explained by an increase in the viscosity of the binder.
Objectives. Current methods for testing nasal spray dosage forms during development fail to fully assess the behavior of the drug following its release from the container, including subsequent distribution, retention, and permeability across the mucosal barrier. Existing in vitro models typically overlook the critical factor of drug interaction with nasal mucus, which substantially limits their predictive power and physiological relevance. The study set out to develop a physiologically based analytical method that addresses this gap by employing representative simulated nasal mucus compositions to evaluate the key performance parameters of the spray.Methods. The pH of the investigated compositions was determined potentiometrically in accordance with the requirements of the 15th Russian State Pharmacopoeia, OFS.1.2.3.0032, using a pH meter (Econix-Expert, Russia) equipped with an ESK-10601 glass electrode (Izmeritelnaya Tekhnika, Russia). The dynamic viscosity of the compositions was measured using a Brookfield DV2T RV rotational viscometer (Brookfield, USA) with a thermostatically controlled measuring unit ofthe coaxial cylinder type within a temperature range of 25–37°C. The contact angle was determined by the sessile drop method using an EasyDrop Standard instrument (Krüss, Germany). The distribution of nasal sprays was evaluated with a silicone model of the human nasal cavity (Koken Co. Ltd., Japan).Results. Representative simulated nasal mucus compositions were developed and characterized that reliably reproduce the key physicochemical and rheological properties of human nasal secretions under both normal and pathologically inflamed conditions. An experimental setup combining an anatomical silicone nasal cavity model with an applied layer of simulated nasal mucus was created and validated. The developed model permits quantitative assessment of key parameters, such as the distribution and coverage area of the drug substance upon contact with mucus of varying viscosity. As such, it provides a physiologically relevant platform for studying nasal sprays during dosage form development.Conclusions. The proposed approach offers a valuable tool for optimizing the composition and design of nasal sprays, enabling comparative analysis under conditions that closely mimic physiological realities.
Objectives. The work set out to obtain cyclic tert-amines by alkylation of dimethylaminopropylamine (DMAPA) and aminoethylpiperazine (AEP) with cis-1,4-dichloro-2-butene and cis-2,3-di(chloromethyl)-gem-dichlorocyclopropane. Quaternary ammonium salts were synthesized from a cyclic amine base and the resulting compounds evaluated as substances influencing the hemostasis process. The effect of structural fragments in the resulting substances on their anticoagulation and antiplatelet properties was evaluated.Methods. The target compounds were obtained by a classical method of organic synthesis: by alkylation of DMAPA and AEP with cis-1,4-dichloro-2-butene and cis-2,3-di(chloromethyl)-gem-dichlorocyclopropane. The qualitative and quantitative compositions of the reaction mixtures were determined by chromatography with a Khromatek-Kristall 5000M chromatograph fitted with a 30 m × 0.25 mm × 0.5 μm capillary column containing 5% phenyl/95% polydimethylsiloxane as the stationary phase, as well as by nuclear magnetic resonance spectroscopy using a Bruker AM-500 spectrometer having operating frequencies of 500 and 125 MHz.Results. The corresponding tertiary amines were obtained upon heating with 70–88% yield by alkylation of DMAPA and AEP with cis-1,4-dichloro-2-butene and cis-2,3-di(chloromethyl)-gem-dichlorocyclopropane. It was determined that the synthesized amines react with benzyl bromide to form salts with a yield of more than 80%. Quaternary ammonium salts were found to exhibit anticoagulation activity at the level of the reference standard, acetylsalicylic acid, and the highest activity is demonstrated by the amide 1-benzyl-4-[2-(2,5-dihydro-1H-pyrrol-1-yl)ethyl]piperazine. Analysis of the structure–property relationship showed that, in the series of DMAPA derivatives, the presence of a benzyl group increases the antiplatelet activity (the value of the maximum amplitude of platelet aggregation), whereas for the AEP derivatives, the presence of a benzyl group reduces by more than half the maximum amplitude of platelet aggregation, thereby reducing antiplatelet activity.Conclusions. DMAPA and AEP condense with cis-1,4-dichloro-2-butene and cis-2,3-di(chloromethyl)-gem-dichlorocyclopropane to form the corresponding spirocyclic derivatives with high yields. The resulting amines are shown to undergo a quaternization reaction under thermal heating to form quaternary ammonium salts. The synthesized salts are found to exhibit anticoagulation activity comparable to that of the acetylsalicylic acid reference standard.
Objectives. To investigate the specific features of tetraethoxysilane (TEOS) hydrolysis in associated media of saturated diols and their esters in acidic media. Propylene- and butylene glycols and ethylcarbitol were selected as associated systems.Methods. Association, hydrolysis, and condensation processes in the TEOS–diol system were studied by potentiometry, infrared spectroscopy, and dynamic light scattering in liquid media. The acidic environment was created by adding HCl in the amount not exceeding 0.3 wt %.Results. The hydrolysis of TEOS in associated alcohol media is limited by the reaction that yields silanol (RO)3SiOН, which further interacts with the associated diol. This results in the incorporation of (RO)3SiO groups into the hydrogen bond network of diols. This is confirmed by a decrease in the self-association of diols with a decrease in size in the diol–(RO)3SiO domains of up to 1–7 μm.Conclusions. The use of diols as a reaction medium for TEOS with a low content of H2O in acidic media limits the depth of hydrolysis and condensation, which increases the possibility of esterification reactions of diol with alkoxy derivatives of silanols. The decreased number of hydroxyl groups during the transition from diols to their esters has a significant effect on the degree of association.
Objectives. The study set out to develop a stable lyophilized formulation of the monoclonal antibody Eculizumab, comprehensively characterize the resulting material, and assess its stability for qualifying it as a reference material. This involved developing a matching placebo formulation, determining the optimal lyophilization conditions, and conducting a rigorous stability study.Methods. In the development of the formulation and lyophilization conditions for Eculizumab, we tested various buffer systems and cryoprotectants. The residual moisture content in the resulting lyophilized samples was determined by Karl Fischer titration. Peptide mapping was performed using reversed-phase high-performance liquid chromatography (RP-HPLC) following enzymatic hydrolysis with trypsin. The structural, physicochemical, and biological properties were analyzed using various analytical methods, including RP-HPLC, high-performance liquid chromatography mass spectrometry, capillary sodium dodecyl sulfate electrophoresis, size-exclusion high-performance liquid chromatography, and enzyme-linked immunosorbent assay.Results. A placebo solution for lyophilization of Eculizumab was selected with the following composition: 20 mM sodium phosphate, 4% trehalose, 0.2% polysorbate 80, pH 7.0. The results demonstrated a high degree of similarity between the candidate reference material and Eculizumab EU. Stability studies under storage conditions at 2–8°C demonstrated the material’s stability for one year, with control points at 3, 6, 9, and 12 months.Conclusions. The absence of any effect of the drying process on the primary and spatial structure, post-translational modifications, content of related impurities, composition of isoforms, and specific activity was confirmed. Furthermore, stability studies demonstrated no significant changes in protein quality during storage at 2–8°C for at least 12 months, which represents the entire available data period at the time of manuscript preparation. The results indicate that the developed lyophilized material is a viable candidate for an international reference material, although its official qualification would require additional collaborative trials and long-term stability data.
Objectives. The development of technological solutions aimed at increasing the efficiency of supercritical fluid extraction of polar biologically active substances from plant materials is a priority direction due to the demand for such substances in the food and pharmaceutical industries. The aim of this study is to develop an approach for stabilizing extractant composition by continuously feeding a polar cosolvent into a supercritical carbon dioxide flow.Methods. The study was carried out on blackcurrant (Ribes nigrum L.) fruits, which contain polyphenols, one of the most difficultto-extract compounds. Two types of prepared raw materials were used: heat-dried at 50°C for 48 h; freeze-dried at a pressure of 68 Pa and a temperature of up to 25°C for 48 h. Extracts were obtained by supercritical fluid extraction in a 250-mL high-pressure extractor. The process was carried out at a temperature of 50°C and a pressure of 200 bar in different modes: using pure CO2; with the addition of ethanol; with the addition of acetone; and employing different methods for feeding the extractant into the high-pressure extractor.Results. The highest efficiency of polyphenol extraction was achieved using heat drying of the raw materials in combination with a continuous supply of ethanol as a cosolvent, which enabled the highest yields of extract (22.47 wt %) and polyphenols (4.95 wt %). The experiments confirmed that the modes using acetone provide a high yield of extractive substances; however, their use is limited by the toxicity of the solvent, whereas a continuous supply of ethanol is a more promising and safer method for process intensification. Рeat-dried samples consistently demonstrated higher yields of both extract and target polyphenols in comparison with freeze-dried raw materials in all extraction modes studied.Conclusions. The choice of drying method at the stage of raw material preparation is shown to have a significant impact on extraction efficiency: heat drying provides a higher extract yield than freeze drying. The experiments confirmed that the addition of polar cosolvents increased the solubility of polyphenols. While the highest efficiency among single-addition modes was achieved using acetone, ethanol is recommended due to its non-toxicity. By using a continuous flow of a cosolvent instead of its a single addition, the total extract yield is increased by 6.4 times, and the polyphenol content by 17 times. The proposed universal approach can be applied to the extraction of a wide range of polar compounds; even higher efficiency is expected for less polar substances.
Objectives. To investigate the properties of intumescent fire-retardant materials based on plasticized polyvinyl chloride and oxidized graphite as functions of their content of nitrile butadiene rubber.Methods. Intumescent fire-retardant materials with different contents of nitrile butadiene rubber (from 0 to 20 wt %) were obtained. The materials were prepared in the form of a sheet 38–52 mm wide and 1.5–1.9 mm thick by means of flat-die extrusion using a twin-screw compounding extruder. The raw materials used were plasticized polyvinyl chloride with a K-value of 71, nitrile butadiene rubber with a bound acrylonitrile content of 31–35%, oxidized graphite, and ultrafine aluminium hydroxide. The properties of the raw materials and the resulting fire-retardant materials were investigated using infrared spectroscopy, thermal analysis, scanning electron microscopy, as well as mechanical tests, flammability tests, and thermal shock foaming tests.Results. The mechanical, thermal, and fire-retardant properties of the obtained materials were studied as functions of their contents of nitrile butadiene rubber. The dynamics of foaming in the temperature range from 300 to 800°C were also explored. The flammability rating was determined. The dependence of fire-retardant properties on the melt viscosity of fire-retardant materials was described. The thermal properties were found to be in the temperature range of 40 to 900°C.Conclusions. The study found that the introduction of nitrile butadiene rubber into fire-retardant materials leads to a change in a number of properties: a decrease in density and hardness; a decrease in tensile strength; an increase in relative elongation; an increase in melt viscosity by 16 times; and, accordingly, a decrease in foaming rate by a factor of 1.43–1.65. It was established that the foaming rate has a linear dependence on the viscosity of the melt of fire-retardant materials. The introduction of rubber leads to an increase in the strength of foamed char by a factor of 4.8. Thermal analysis showed that increasing the rubber content leads to an increase in heat resistance from 222 to 236°C, and resistance to oxidation of foamed graphite in the composition of foamed char from 601 to 659°C. The presence of rubber does not have a noticeable effect on flammability. The established flammability rating for all compositions is V-0.
Objectives. To analyze the properties, dispersion structure, and intermolecular interactions in oil disperse systems (ODSs) of various component compositions, and to consider the possibilities of controlling phase transitions in an ODS to achieve the most favorable dispersion properties for carrying out technological processes of refining hydrocarbons, upgrading petroleum products, or recycling oil waste. Phase transitions are proposed to be controlled by low-energy wave action (low-frequency ultrasound, constant magnetic field with low induction).Results. The following features of oil disperse systems are considered and substantiated with literature data and the results of our own research: multiplicity of phases; diversity of hydrocarbon components and heteroatomic compounds contained in them; the nature of intermolecular interactions (the absence of charge interactions and the presence of charge–polarization and exchange spin-spin interactions); spin activity or paramagnetism of oil, petroleum products, and their various components; homolytic dissociation of highmolecular-weight and heteroatomic organic compounds, resulting in an increase in paramagnetism; as well as the presence of trace elements contained in organometallic compounds and in salts dissolved in emulsified water. An equation is presented for intermolecular interactions in ODSs, in which a decisive role is played by the exchange interactions caused by the presence of spin and spin-polarized molecules. Two-component models are described for the shells of complex structural units of the oil disperse system, their structure, and their interaction with the dispersion medium. Methods for controlling phase transitions and dispersity of ODSs are shown. Special attention is paid to low-energy wave technologies (ultrasonic waves with a frequency of 20–100 kHz with an intensity of up to 0.4 W/cm2 and a constant magnetic field with an induction of less than 0.4 T). Examples are given for the intensification of such technological processes as separation of water–oil emulsions, removal of mechanical impurities, atmospheric and vacuum distillation, selective purification of oil fractions, degassing of heavy fuel oil to remove hydrogen sulfide, visbreaking, and others. Positive results are demonstrated for the application of low-energy technologies for reduction of the viscosity and pour point of oil and petroleum products in oil refining equipment. The study proposes a mechanism of the influence of a constant magnetic field on the flow of petroleum product or hydrocarbon raw material.Conclusions. The study of the features of ODSs is key to the qualified colloid-chemical approach to processes of production, transportation, and processing of hydrocarbon raw materials. They are seen from the standpoint of ODS theory on the basis of the consideration of the dispersion structure and phase transitions in ODSs. Low-energy technologies in the petroleum industry are an effective tool for resource saving in various processes and optimization of their parameters without significant material costs.
Objectives. To summarize the results from studies of plasma processes for the production of specified composition powder materials; to implement plasma processes: plasma-chemical synthesis of nanopowders, granulation of nanopowders, plasma spheroidization of microgranules and micropowders in order to perform nanotechnologies and additive technologies tasks.Methods. Thermal plasma generation was used at the A.A. Baikov IMET RAS by means of direct-current electric arc plasmatrons with a rated power up to 45 kW with self-adjusting arc length and gas stabilization of discharge, as well as plasmatrons with an interelectrode insert. In order to carry out the processes of nanopowders synthesis and metal powders spheroidization, the plasma reactor design with confined jet flow using thermal plasma of reducing, oxidizing, and inert media was used.Results. The use of electric arc plasmatron in the processes of plasma chemical synthesis of nanopowders and plasma spheroidization of powders enabled productivity of 0.5 and 10 kg/h, respectively, to be achieved for various metals, alloys, compounds, and their compositions. In the case of the implemented processes of producing nanopowders, where the formation of particles depends on various macro-mechanisms, it was established that the average size of the particles obtained is controlled. This also depends on the synthesis parameters—the initial concentration of the precursor, enthalpy, and flow rate of the plasma jet, cooling rate and vapor condensation. The study shows the results of examining the processes of producing spheroidized powders in thermal plasma flows. These include (Ti, Ta, Fe, Ni, Mo, W), alloys (based on Fe, Ti, Ni, Co, Nb, W, Mg, including stainless, heat-resistant, refractory, hard), compounds (borides, oxides) and compositions (W–Ni–Fe, ZrB2–SiC, Ni–TiCN, etc.). The possibility of obtaining nonporous spherical powders of various dispersity was also shown: for particles of about 10–100 μm and for granules having a particle size of less than 1 μm. The study described the main process parameters determining the quality of spheroidization, including dispersity of precursor, plasma enthalpy, gas composition, characteristics of plasma flow, and their mixing with initial powders.Conclusions. The research and development results presented here show the possibilities of plasma processes and apparatuses for producing nanopowders of various metal, inorganic compounds and compositions with given properties. The study also confirmed that powders of metals and alloys, compounds and compositions obtained by a variety of methods can be spheroidized in a plasma reactor with confined jet flow in a wide range of melting points, particle sizes, and morphology. The demonstrated approach using successive stages of plasma-chemical synthesis of nanopowders, their granulation and subsequent plasma spheroidization of microgranules enables tungsten-based composite micropowders with dense spherical particles and submicron structure to be obtained.
