The use of polymeric materials as drug carriers has several advantages, such as prolongation of drug action and reduction of drug side effects. In this study, we consider the methods for the preparation of polylactideco-glycolide (PLGA) polymeric nanoparticles with the anti-tuberculosis drug (ATD), isoniazid, by nanoprecipitation. Polymeric nanocarriers were obtained by varying individual parameters such as the nature of solvent and non-solvent, drug/polymer ratio, and stabilizer concentration. It was determined that the average particle size depends on the type of non-solvent. When alcohols were used, the average size increased in the sequence: ethanol < isopropanol < isobutanol. The type of solvent is an important factor in the formation of nanoparticles and their final characteristics. With an increase in the drug/polymer ratio, the average size of nanoparticles also increased. The size of obtained nanoparticles varied from 93 to 869 nm. Thermogravimetric and differential scanning calorimetry analyses were carried out to confirm the incorporation of the drug into the polymer matrix. In addition, polymer degradation and the degree of release of isoniazid from the polymeric matrix at different pH were studied. It was identified that the nanoprecipitation method can be used not only for hydrophobic but also for hydrophilic drugs.
Tuberculosis (TB) is a leading cause of death worldwide from a single infectious agent, Mycobacterium tuberculosis (MTB), especially due to the development of resistant strains and its co-infections in HIV. Quantitative-structure activity relationship (QSAR) studies aid rapid drug discovery. In this work, 2D and 3D QSAR studies were carried out on a series of nitrobenzamide derivatives to design newer analogues for antitubercular activity. 2D QSAR was performed using MLR on a data set showing antitubercular activity. The 3D-QSAR studies were performed by kNN–MFA using simulated annealing variable selection method. Alignment of given set of molecules was carried out by the template-based alignment method and then was used to build the 3D-QSAR model. Robustness and predictive ability of the models were evaluated by using various traditional validating parameters. Different physiochemical, alignment-based, topological, electrostatic, and steric descriptors were generated, which indicated the key structural requirements for optimizing the pharmacophore for better antitubercular activity. For 2D QSAR, the best statistical model was generated using SA-MLR method (r2 = 0.892, q2 = 0.819) while 3D QSAR model was derived using the SA KNN method (q2 = 0.722). The positively contributing descriptors can be incorporated to design new chemical entities for future study
5-(Benzylidene)pyrimidine-2,4,6-triones with different substituents on the phenyl rings: 5-(4’-dimethyl-aminobenzylidene) barbituric acid and 5-(4’-methoxybenzylidene) barbituric acid were synthesized, and their spectral-luminescent properties were investigated. A decreasing fluorescence efficiency in the solid-state is general and is mainly attributed to the intermolecular vibronic interactions, which induce the nonradiative deactivation process. Whereas the isolated dye molecules are virtually non-luminescent in dilute solutions, they become highly emissive upon solution thickening or aggregation in poor solvents or in the solid-state, show an increase of luminescence intensity, the phenomenon of the aggregation-induced emission (AIE phenomenon). The development of efficient luminescent materials is a topic of great current interest. The emission color is changed from red (maximum at 630 nm) to green (maximum at 540 nm) by varying the substituent on the phenyl ring from dimethylamino to the methoxy group. Theoretical calculation shows that the dye molecules' aggregation-induced emission characteristics result from intermolecular interactions. Utilizing such features, the molecules can be employed as fluorescent probes for the detection of the ethanol content in aqueous solutions.
The interpolyelectrolyte complex of the composition [chitosan]:[alginate] = [1]:[4] was prepared by mixing a hydrochloric acid solution of cationic polyelectrolyte chitosan and an aqueous solution of anionic polyelectro-lyte sodium alginate. The complex of chitosan and sodium alginate biopolymers was first used as a soil structurizer. Due to low humus and light mechanical composition, the dark chestnut soil of the dry-steppe zone of the East Kazakhstan region is subjected to erosion. Introducing a polymer complex into the specified soil contributed to the improvement of wind resistance, an increase in humidity, and a decrease in water per-meability. The soil surface treated with a complex of biopolymers showed pronounced resistance to the action of planar and trickle water erosion due to aggregation of particles with a diameter of < 0.01 mm. The fraction of soil particles obtained by mechanical destruction of structured aggregates with a diameter of 3-1 mm has a well-expressed ability to self-aggregate during the humidification - drying process. The results of the vegeta-tion and field experience in tillage with an interpolyelectrolyte complex showed a positive effect of the com-plex on the growth and development of radish of the Rubin variety and, as a result, an increase in radish yield by 2 times was achieved. The obtained results indicate the effectiveness of the structuring action of the chi-tosan-alginate complex for poorly structured soils.
Electrocatalytic water oxidation for oxygen gas evolution has been widely studied from the perspective of sustainable technology. However, the use of organic polymers as catalyst layers for this reaction remains un-developed. We discuss, here, the prerequisites, characteristics, and advantages of π-conjugated polymers as electrochemical catalysts to modify anodic current collectors for water oxidation, including some examples by citing the previous works in literature. In section 3, we present our latest results, the use of an organic pol-ymer complex of poly(ethylenedioxythiophene) and phytic acid supported by a hydrophilic poly(hydroxy-ethyl methacrylate) platform, which efficiently generates oxygen gas through anodic water oxidation.
The article presents the results of a chemical study of Tanacetopsis pjataevae, which is an endemic plant in Kazakhstan. The number of extractive substances was obtained by extraction with chloroform from the air-dry crushed above-ground part of the plant collected in the flowering phase. Isolation of compounds was carried out by column chromatography on a column of silica gel brand KSK at a ratio of sum - carrier = 1:20. A colorless crystalline substance of the composition C15H18O4 with m.p. 189–191°C (recrystallized from diethyl ether) was found when the column was eluted with a mixture of petroleum ether-ethyl acetate (87.5:12.5). The structure of the obtained new compound (3-oxo-10β-hydroxy-5,7α(Н),6β(Н)-guai-1,11(13)-diene-6,12-olide) was established based on IR, NMR analysis and mass spectra. The spatial structure was determined by the X-ray diffraction method. It was established that the 3-oxo-10β-hydroxy-5,7α(Н),6β(Н)-guai-1,11(13)-diene-6,12-olide molecule in the crystal is disordered over two conformational states in the 6 :4 ratio. The stability of these conformers was confirmed by semi-empirical quantum-chemical calculations. It was established that the difference in the heat of formation of two conformers was 6.3 kJ/mol for a free molecule.
The research purpose is to prove the probability of a direct quantitative correlation between proportion of these clusters and liquid viscosity. A quasi-polycrystalline clustering model of the liquid (in particular, melts) should be used. The Boltzmann distribution, the concepts of the chaotic particles and the virtual cluster size distribution should be applied to achieve this purpose. This study analyzed the complete reference data on the temperature dependences of the dynamic viscosity for the alkali metals. As a result, a directly proportional correlation between viscosity and cluster content in liquid has been determined. It has provided the probabil-ity for the quantitative concept of the quasi-polycrystalline clustering model on the liquid state of matter due to its properties. The concept of the chaotic particles in direct correlation to the Boltzmann distribution has been used as a basis. The Boltzmann energy spectrum has been used for the kinetic energy of the chaotic thermal particle motion in the solid, liquid and gaseous states of matter. As a result, their three energy classes have been distinguished with their presence in all aggregate states and in the sum constantly equal to one. Formulas to calculate the proportion of the virtually ordered clustering and complete chaotic fluid compo-nents were deduced. These formulas have been derived with using the particle distributions by the energy class and cluster sizes.
Cross-linked polyampholyte nanogels consisting of neutral N-isopropylacrylamide (NIPAM), negatively charged sodium salt of 2-acrylamido-2-methylpropanesulfonate (AMPS), and positively charged (3-acryl-amidopropyltrimethylammonium chloride (APTAC) monomers were synthesized via conventional redox ini-tiated free radical copolymerization using N,N-methylenebis(acrylamide) (MBAA) as a cross-linking agent. The resulting nanogels were characterized by means of FTIR and 1H NMR spectroscopy, dynamic light scat-tering (DLS) and zeta-potential measurements. Surface morphology was analyzed using scanning electron microscopy. Due to the presence of thermally responsive NIPAM units and varying molar ratios of anionic (AMPS) and cationic (APTAC) units, the resulting nanogels were responsive to multiple stimuli in aqueous media and can be used for controlled delivery of dyes. Thus, the NIPAM90-APTAC7.5-AMPS2.5 nanogel with an excess of the cationic units was chosen for immobilization of the anionic dye, methyl orange (MO), whereas the NIPAM90-APTAC2.5-AMPS7.5 nanogel with an excess of the anionic units was chosen for immo-bilization of the cationic dye, methylene blue (MB). The release kinetics of the dyes from the nanogel was studied depending on the phase transition temperature and the salt content. Mechanism of the dye release from the nanogel matrix was determined using the Ritger-Peppas equation. Disappearance of the ionic con-tacts between the charged groups of the nanogels and the ionic dyes was suggested to be the main reason for the diffusion of the dyes through the dialysis membrane into the external solution.
The interaction of the superoxide radical ion O2 – with the active site of Cu, Zn-superoxide dismutase is studied by computer simulation using the ORCA software package version 5.0.2 at the level of density functional theory using the PBE functional and the basis sets of functions def2-SVP, def2-SVPD and def2-TZVPD. The main characteristics for two processes of electron transfer in the catalytic cycle of radical ion deactivation are obtained: reaction potential ΔG0, total reorganization energy λtot, activation energy ΔG≠, overlap matrix element HDA, and transfer rate constant k according to Marcus. The variable factor in the modeling is the presence of the Zn2+ ion at the active site of the enzyme. Two variants of the electron transfer mechanism are considered: one carried out through ligands and another occurring in the immediate vicinity of an oxygencontaining particle and a copper ion. It has been established that the presence of the Zn2+ ion contributes to a large extent only to the second electron transfer from the Cu+ ion to the protonated form of the radical ion, to the hydroperoxide radical HO2. Other things being equal, the zinc ion increases the electron transfer rate constant by five times through specific interactions.
Polymer flooding is a promising and effective chemical Enhanced Oil Recovery (cEOR) technology. Polymer flooding is especially cost-effective, whereas other chemical flooding methods, such as Alkaline Surfactant Polymer (ASP), are not profitable and cause serious on-site problems (scaling, uptime decrease, injectivity is-sue, hard-breaking emulsions). Recent papers in the literature mention ~30 field polymer floods. Most of them reported technical success. Although, polymer flooding has been applied ~60 years and it still requires further investigation to provide improvements. Thus, this paper describes important aspects and performances during polymer flooding based on a review of recent projects, combined with the Kalamkas field experience. A comprehensive literature review examines the applicability range in temperature, brine salinity, water source selection, oil properties, formation type, and permeability. Water source selection has an essential role during pilot/field project design and is one of the most responsible technical and economic success decisions. Polymer slug design has been extensively analyzed especially for the high viscosity oil fields; the selected oil/polymer viscosity ratio was usually much less than one. We placed significant emphasis on clarifying ob-served high polymer injectivities. We conducted feasibility studies of some reported ASP floods to clarify that this technology is not profitable at current oil prices. Also, we performed TAN analysis of three Kazakh-stan oil fields for screening of ASP flood.
The genus Chondrilla L. comprises 22 species on the CIS territory. 16 species of them grow in Kazakhstan. All species of the genus Chondrilla L. are rubber-bearing herbaceous plants that belong to the Asteraceae family. We picked Chondrilla brevirostris Fisch. & C.A. Mey. for the chemical study. It is a perennial herb that grows in desert steppes and forest meadows. The aboveground parts of Ch. brevirostris were extracted with ethanol at room temperature. Several fractions were obtained by separating ethanol extract on column chromatography. Rechromatography and preparative thin-layer chromatography were used to further study the obtained fractions and the isolation of flavonoids. As a result of preparative thin-layer chromatography, the flavonoid 5,7,4'-trihydroxy-3'-methoxyflavone (compound 1) was isolated. The chemical structure of 1 was established by spectroscopic data. Compound 1 was isolated for the first time from the species of Chondrilla. Compound 1 was subjected to a molecular docking study against COVID–19 main protease (Mpro) to investigate its expected activity against SARS-CoV-2. In this case, the substance showed a good binding mode with a free energy of –6.22 kcal/mol, while the binding energy of the co-crystallized ligand was –7.83 kcal/mol
Glycoluril (2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione) and its derivatives have a special place in chemis-try of heterocyclic compounds. The macrocyclic derivatives of glycoluril, namely cucurbit[n]urils have re-cently attracted the greatest interest due to their unique properties. Cucurbit[n]urils are usually synthesized by the condensation reaction of glycoluril with paraformaldehyde using strong mineral acids as a catalyst. In this work, 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) was used for the first time as a catalyst for “Green chemistry” in the synthesis of cucurbit[6]uril in an aqueous medium. The reaction of glycoluril and paraform-aldehyde in a ratio of 1: 2 with two equivalents of 1-hydroxyethylidene-1,1-diphosphonic acid as a catalyst was carried out, in which the hexamer of cucurbituril (n = 6) was obtained in 25 % yield. The clathrate of cu-curbit[6]uril with acetone was obtained by treating the cucurbituril hexamer with acetone. The reaction of glycoluril with paraformaldehyde in the presence of HEDP can be used as a competitive method for the syn-thesis of cucurbit[6]uril. The structures of the obtained compounds were proven by NMR and IR spectrosco-py methods. The phase composition of isolated crystals of cucurbit[6]uril hydrate was analyzed by the pow-der X-ray diffraction (XRD).
The purpose of this work is to study the production process of titanium dioxide during anode polarization in sulfuric acid and hydrochloric acid solutions. The studies were carried out by recording cyclic voltammogram and by measuring the titanium oxidation current with a change in the voltage between the electrodes. It has been established that with a change in the concentration of sulfuric acid in the range of 50–250 g/l and the voltage between the electrodes in the range of 0–25 V, the magnitude of the titanium oxidation current in-creases and reaches 29.4 mA. With an increase in the concentration of hydrochloric acid from 35 to 100 g/l and a change in the voltage between the electrodes, the titanium oxidation rate increases evenly, but in the voltage range of 10–12 V, a sharp increase in the current magnitude up to 360 mA is observed. A change in the oxidation current indicates an increase in the rate of titanium dissolution. With an increase in the duration of electrolysis, the magnitude of the anode current generally decreases. In all probability, at a voltage of 14 V and higher, a breakdown of the oxide semiconductor film of titanium dioxide is observed in the hydrochloric acid solution. In this regard, a noticeable dissolution of titanium occurs and, subsequently, an oxide film is not produced, but titanium ions are produced. Visual observations have shown that titanium passes into solu-tion in the form of titanium (IV).
Simple, sensitive high performance thin layer chromatography method for the estimation of gallic acid and quercetin in in-house polyherbal blend has been developed and validated. Methanolic solution of herbal blend comprising of Emblica officinalis, Camellia sinensis and Garcinia cambogia was used for analysis. The sepa-ration was performed on TLC aluminum plates precoated with silica gel G60 F254 and toluene: ethyl ace-tate: formic acid (5:1.5:1 v/v/v) at 254 nm scanning wavelength. The system gave well resolved peaks for gal-lic acid and quercetin at Rf 0.14 and Rf 0.29 respectively. The method validated as per ICH Q2R1 guidelines which shows regression co-efficient 0.9939 for gallic acid and 0.9988 for quercetin in range of 2–6 μg/ml. Recovery of gallic acid and quercetin was found in range of 98–102 % which confirms the accuracy of meth-od. Precision study (interday & intraday) showed that the relative standard deviation is less than 2 %, show-ing method is well precise. Proposed validated HPTLC method is simple, precise, specific, robust and accu-rate, and could find application in routine quality-control analysis. The method was used for quantitative es-timation of gallic acid and quercetin in the polyherbal blend and was found as 1.648 % w/w and 3.165 % w/w respectively.
The novel corona virus infection had become a global epidemic due to its rapid spread. So, there is an urgent need to treat COVID-19 patients. The aim of this research was to hypothesize and examine vitamin drug con-jugate as targeted moiety. The present scaffold may have potential role to fight against COVID-19 infection due to its antimicrobial, antioxidants and immunomodulatory activities. Here, we've highlighted the term Vit-amin Drug Conjugate as possible therapy approach for SARS-COV-2 infection. As a result, we synthesize, characterized, and evaluated a Hydroxychloroquine — Folic Acid conjugate (HCQ-FA) by esterification mechanism to provide effective treatment against SARS-CoV-2 infection by enhancing therapeutic effect through synergistic mechanism, masking undesired side effects, and improving cellular internalization. By us-ing prodrug, the efficacy and bioavailability of existing antiviral drugs could be improved. The structure of the conjugate was determined by spectroscopic data like IR, NMR, and mass spectra, which indicates that HCQ-FA conjugate formed by esteric conjugation. Molecular docking studies revealed that HCQ-FA conju-gate shows good level of docking as well as binding interaction with main protease moiety. Molecular dy-namic stimulation revealed that this conjugate shows good stability at the binding site of SARS main protease moiety and exhibits inhibitory activity against COVID-19 infection.
The thermal decomposition of low-temperature coal tar (LTCT) obtained from the coals of Shubarkol Komir JSC of the Republic of Qazaqstan in the presence of nanocatalysts with metal oxides (iron, cobalt and nickel) supported on microsilicate was studied for the first time. Microsilicate acts as a carrier and catalyst. Microsil-icate is a product of the Karaganda silicon plant of “Tau-Ken.temir” LLP. The main chemical component of the original microsilicate is silicon oxide. The individual and chemical phase composition of the microsilicate was determined using X-ray spectral analysis. The particle size of the initial microsilicate and the mixture of microsilicate with metal oxide catalysts (nickel, cobalt, and iron) was determined using a nanosizer. Stages of thermal decomposition of LTCT and a mixture of LTCT with catalysts under conditions of programmed heat-ing up to 640 °С in a nitrogen atmosphere have been established. On the basis of thermogravimetric analysis, the kinetic parameters (activation energy, mass loss rate, and pre-exponential factor) of LTCT pyrolysis and mixture with added catalysts were determined. The modeless integral isoconversion Ozawa–Flynn–Wall method was used to determine the kinetic parameters. The values of the activation energy for the thermal de-struction of the LTCT in the absence and presence of the nanocatalyst ranged from 54.04 to 297.5 kJ/mol. A kinetic compensation effect was revealed, probably due to the multicomponent composition of the LTCT and the influence of added catalysts to the LTCT. The thermogravimetry method showed a high effect of the sup-ported catalysts on the thermal degradation of LTCT. This method was used to determine the values of the ac-tivation energy and the pre-exponential degradation factor for the LTCT and the mixture with catalysts at dif-ferent heating rates, which allows a detailed interpretation of the thermal analysis data. The obtained results of the kinetics of decomposition of LTCT can be used to create a database for mathematical modeling of the process of processing this type of raw material.
The results of adsorption purification of used industrial oil in the presence of natural aluminosilicates, benton-ite and mordenite, are discussed. It was found that the maximum degree of purification was achieved in the presence of mordenite and reached 61.68 % at an oil, adsorbent ratio of 2.3 at a temperature of 70 °C. The da-ta of the structural-group analysis of the oil showed that the main share of the hydrocarbon components re-moved during purification is accounted for by highly condensed aromatic ones. The supposed reasons for the different adsorption activity of bentonite and mordenite samples were judged from the data of chemical, min-eralogical, textural, and IR spectroscopic analysis. Based on the results of the IR spectra of mordenite sam-ples, it was concluded that energetically active hydroxyl groups can be responsible for their increased adsorp-tion activity. The used oil before purification is characterized by a high cyclicity of the hydrocarbons which included in the composition (aromatic hydrocarbons account for 38 % of the total), while the oil subjected to adsorption purification with mordenite (M-50) mainly becomes free of aromatic rings (the proportion of aro-matic hydrocarbons decreases up to 19.6 %). This is a consequence of the high polarizability of aromatic hy-drocarbons, in which, compared with other oil components, a dipole moment is easily induced under the in-fluence of the electrostatic field of the adsorbent.
A series of new ligands — N-acyl-N'-mesylhydrazines (MSH) — of the general formula RC(O)NHNHSO2CH3 has been obtained and considered as reagents for ionic flotation (IF) of non-ferrous metals (M(II). Reagents with a radical length of C6H13 and above form hardly soluble complexes with M(II) so it is possible to implement a kind of the ionic flotation techniques — “precipitate flotation”. The ranges of pH values of the most complete precipitation of cations from solutions have been determined. Precipitates of the metal complexes were isolated; their composition was confirmed by IR spectroscopy and elemental anal-ysis. The conditional values of the solubility product (SP) of the complexes [M(HL)2] were calculated. The dependence –lg SP = 11.8 + 0.61N is fulfilled for the MSH series and Cu(II) ions. The surface-active proper-ties of compounds with R > C6H13 were established. The reagents with optimal radical length for ionic flota-tion were selected. The ionic flotation of non-ferrous metals with N-nonanoyl-N'-mesylhydrazine was carried out. The up to 95–99 % recovery of metal ions, separation of copper and associated metal ions in diapason of pH 5–6.5 was shown to be possible.
Covid-19, a SARS-CoV virus-based disease, was identified in Wuhan, China, in December 2019. Initially, it was considered just an infection of the respiratory system, but due to its transmittable nature, it was declared a pandemic. A variety of treatment options were implemented, including antivirals like remdesvir, favipiravir along with vitamins and antioxidants. Further investigations revealed that the Covid-19 infection results in thrombotic cardiovascular complications, which are the major concern for the increased mortality associated with this disease. This study investigates the in Silico design of hybrid molecules with antiviral and an-tithrombotic properties. A docking study was performed using Autodock Vina software, and binding energies of the designed compounds were determined for papain-like protease (PDB: 3E9S) and 3-chymotrypsin-like cysteine protease (PDB: 6LU7). The docked poses and amino acids interactions were verified using Biovia Discovery studio 4.5. The binding energies of all designed compounds were compared with the standards, Compound RL1 (2-(5-(3-carbamoyl-1H-1,2,4-triazol-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-carbonyl)amino)(hydroxy)methyl)carbamoyl)phenyl acetate) and Compound FL2 (8-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-6-yl(2-(6-flouro-3-oxo-3,4-dihydropyrazine-2-carboxamido)-1-hydroxy-3-phenylpropyl)carbamate) proved to be promising agents with strong binding interactions. Hybrid molecules that inhibit viral replication, possibly as transition state inhibitors, can be investigated further for use in the treatment of SARS-Co-V infection and its associated complications.
Three different nanogels possessing anionic, cationic and amphoteric character were synthesized via conven-tional redox initiated free radical copolymerization of N-isopropylacrylamide (NIPAM), 2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt (AMPS) and (3-acrylamidopropyl) trimethylammonium chloride (APTAC). The negatively charged [NIPAM]:[AMPS] = 90:10 mol.%, positively charged [NIPAM]:[APTAC] = = 90:10 mol.%, and charge-balanced amphoteric nanogels [NIPAM]:[APTAC]:[AMPS] = 90:5:5 mol.% ab-breviated as NIPAM90-AMPS10, NIPAM90-APTAC10, and NIPAM90-APTAC5-AMPS5, respectively, were characterized by FTIR spectroscopy, TGA, UV-Vis spectroscopy and DLS measurements. The temperature and salt responsive properties of nanogels in aqueous and aqueous-salt solutions were studied in the tempera-ture range of 25–60 °C and ionic strength (μ) of 0.001–1.0 M NaCl. Anionic NIPAM90-AMPS10 and cationic NIPAM90-APTAC10 nanogels, exhibit a pronounced polyelectrolyte effect in aqueous-salt solution due to screening of the negative or positive charges by low-molecular-weight salt. Whereas the charge-balanced amphoteric nanogel NIPAM90-APTAC5-AMPS5 exhibits an antipolyelectrolyte effect due to the screening of electrostatic attraction between opposite charges by low-molecular-weight salt. The difference between the temperature-dependent behaviors of anionic, cationic and amphoteric nanogels is explained by shrinking (polyelectrolyte effect) and expanding (antipolyelectrolyte effect) of macromolecular chains in aqueous-salt solutions.
