26 results on '"Kuznetsov DM"'
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2. Trends in green transformation economic policy: experience of leading countries and russia
- Author
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Alieva Inobbat, Omurova Saltanat, Kuznetsov Dmitry, Pankina Inga, and Shchepkova Irina
- Subjects
Environmental sciences ,GE1-350 - Abstract
Given the demand for green economic growth and sustainable development, many economic practices demonstrate different rates and characteristics of the transition to a green economy, which in one way or another are determined by the initial socio-economic factors and the economic policy implemented by the state. Stimulating green growth and increasing the well-being of society through the rational use of natural resources, natural capital and ecosystems require the elaboration and development of alternative measures for ensuring the rational use of natural resources, the development of environmental innovations and human capital. An equally important factor contributing to green growth is the formation of a state policy of green economic growth, as well as tools and mechanisms for its implementation. The conceptual foundations of a supranational green growth policy have already been developed and the methodological basis has been elaborated. The study of the experience and best practices of green growth in different countries allows us to identify certain shortcomings that require a deeper study and revision of state regulation documents. In addition, the post-Covid economy requires a separate consideration from the point of view of both the relevance of the policy of green growth and the measures and tools for its implementation. Thus, the study of modern trends and principles of the implementation of the state policy of green growth is a topical area of research that requires critical rethinking for the introduction of more constructive measures for reaching the set goals and objectives.
- Published
- 2021
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3. Global subsiding as a way to sustainable fishery
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Dorofeeva Viktoria, Klippenstein Elena, and Kuznetsov Dmitry
- Subjects
Environmental sciences ,GE1-350 - Abstract
Government subsidies affect many kinds of world’s fishery and are intended to restore troubled fisheries. The article shows that current information about global subsidies for fishery are fragmentary due to lack of its classification and accounting. But at the same time, many fishery countries allow overfishing, illegal, unreported and unregulated fishing. As a result, bioresources are overexploited, and economical indicators of fishing deteriorate. Depleted reserves of fish in seas, and also economical and social problems within fishery society is a result of exploiting of marine bioresources in terms of lack of proper fishing management system. We have made an attempt to summarize approaches of different organizations to classify global subsidies. The presented analysis shows that the largest share of subsidies falls on fuel, which is undoubtable a negative tendency. The assessment of subsidies level for the largest fishery countries is implemented. Scientific and practical recommendations are formulated, its compliance may provide the growth of economical state without accelerating the depletion of fish stocks.
- Published
- 2021
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4. Risk Analysis is a Prerequisite for Quality Management of Traction Rolling Stock Repairs
- Author
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Gaponov Vladimir, Kuznetsov Dmitriy, Khvostikov Andrey, and Alekhin Roman
- Subjects
Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
The paper considers a new version of IRIS ISO/TS 22163:2017 standard in relation to the quality of repair of complex equipment in the railway industry. It is shown that the new version of ISO/ TS 22163:2017 standard provides for the need of organizations to conduct risk analysis and accounting in their work. The authors propose to consider as an example a well-established analysis of the types and consequences of potential defects in FMEA process. The use of FMEA analysis made it possible to consider the significance of various risks of the quality of traction rolling stock repair, as well as to establish the importance of quality control operations for impregnation of a traction motor.
- Published
- 2021
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5. Using Steel-Smelting Slag as a Raw Material Component in the Production of Asphalt Concrete
- Author
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Kuznetsov Dmitry, Vysotskaya Marina, and Burgonutdinov Albert
- Subjects
Environmental sciences ,GE1-350 - Abstract
The possibility of using polydisperse steel-smelting slag for the production of type B asphalt concrete is investigated, the possibility of its use as a mineral powder, crushing screening and crushed stone is considered. As a result of the study, it was found that a promising area for the use of slag raw materials in the technology for the preparation of asphalt mixes is: as a mineral powder - without additional processing steps; crushing screening - with the development of additional technological operations. The use of raw materials as crushed stone is impractical because of the high average density of the final asphalt mixture. Based on the test results, the characteristics of the fatigue properties of asphalt concrete from fine-grained dense mixtures of type B made on mineral powders from slag and limestone were obtained. It was established that at the initial moment, a large number of cycles to failure are characterized by compositions on slag powder, however, samples from this series tested after 45 days showed a significant rigidity increase and were destroyed earlier than similar samples on limestone. Obviously, this phenomenon is associated with an increase in the brittle properties of the material due to the formation of crystallization-condensation bonds in the structure of asphalt concrete containing slag.
- Published
- 2020
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6. The Role of Coal-Mining Museum in Kuzbass Coal Industry Development
- Author
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Kuznetsov Dmitry, Novoklinova Anna, Rabkina Nadezda, and Valko Olga
- Subjects
Environmental sciences ,GE1-350 - Abstract
A museum cluster is a phenomenon that did not acquire conceptual understanding until the late 1990s. Since then, numerous approaches to defining a museum cluster have been put to the test. It has been unanimously stated that a museum cluster is an environment-creating and culture-forming entity, which catches the spirit of the time/place and embodies the locus genii. The museum, thus, renews and strengthens itself in the urban, scientific and cultural thought. These apply well to Krasnaya Gorka, a museum cluster in Kemerovskaya oblast. Combining all ‘cluster’ characteristics, Krasnaya Gorka features very specific, historically and culturally valuable trends eventually transforming the urban environment and forming local traditions. The study is aimed at comprehensive research of a museum cluster contribution to the local culture, environment, science, economy and, most importantly, people. The study showed that: (1) the Krasnaya Gorka museum is justifiably the heart of a cluster; (2) the archival materials in city museums are valuable as integral historic documents in their own right, but more significant when regarded along with other papers and artefacts in the domain of the museums, forming the cluster; c) the Krasnaya Gorka museum is a culture-forming entity due to its aggregating people and organizing activities.
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- 2019
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7. Coal-Mining Industry as a Forming Factor of Social, Cultural, and Linguistic Environment of Kuzbass as Resource Region of Siberia
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Kuznetsov Dmitryi, Rabkina Nadezda, Ryabova Marina, and Valko Olga
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Environmental sciences ,GE1-350 - Abstract
The coal-mining industry ensures its sustainable development by forming the complex regional environment, embracing urban, social, cultural, linguistic, and academic components. The environment eventually exerts itself in a number of outcomes. It makes up a multiform regional cogniosphere (i.e. noosphere, ideosphere, logosphere, semiosphere, conceptosphere) responsible for increasing the regional population’s awareness of the coal mining specifics, as well as forms positive attitudes to the mining sector of economy and mining professions, and finally forges the regional identity. The environment is responsible for increasing the popularity of professional coal-mining education which enables the stability and survivability of the mining professions and efficient personnel change in due time. The environment affects adjacent economic spheres (tourism, service, recreation, production, etc.) so as they can make use of the regional specific features and diversify their products and services. Thus, the coal-mining industry and the above mentioned environment form a closed-cycle system whose constituents affect each other mutually and ensure efficient coexistence and development. The cultural, linguistic, and urban environment of the region can be viewed as additional means of supporting and promoting sustainable development of the regional economy and culture through its manipulative potential.
- Published
- 2019
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8. Poetic image of Kuzbass in the verses of regional authors
- Author
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Kuznetsov Dmitry, Rabkina Nadezda, and Valko Olga
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Social Sciences - Abstract
This research features the phenomenon of the so-called literature of space, namely amateur and professional poetic texts that together constitute a cultural supertext devoted to the Siberian coal mining region of Kuzbass. The article employed a multifaceted approach (statistical, pragmatic, textual and temporal/spatial vision analysis) to reconstruct the image of the region in the naïve worldview. Statistical analysis identified the key words and semantic models. The cognitive analysis reveals the basic cognitive structures, while the textual analysis makes it possible to reconstruct narrative and perception. The pragmatic analysis determines the communication role model and the predominant speech acts. The study exposes extended thematic nets of geographical, natural and meteorological terms, time description, and coal mining realia. The predominating cognitive models represent Kuzbass as a territory / a living being / treasure trove / home / family, while the most significant motif for professional oeuvre is legitimizing the peripheral area as an inseparable part of the Russian domain and history. Introspection, simultaneity, and strong modality appears to be the most significant text characteristics. Thus, the image of Kuzbass proves to be a complex comprehensive multitiered phenomenon based on different linguistic units and reflecting the results of the evaluative perception and processing.
- Published
- 2019
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9. The heat loss calculating methods of external walls in the buildings reconstruction
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Vinnichenko Varvara, Gabitov Azat, Salov Aleksandr, Gaisin Askar, and Kuznetsov Dmitriy
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Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
Heat loss analysis in cladding of brick buildings under reconstruction is presented. Thermograms obtained under thermovision inspection and window systems operating experience in conditions of the Republic of Bashkortostan are thoroughly studied. Live issue of increasing buildings energy performance in public utilities sector may largely be solved by replacement of existing window units made of wood to new PVC profile windows equipped with multi-glazed glass units both in brick and frame-panel old buildings. Significant heat loss occurs in junctions between the window frames and the wall in jamb areas. Therefore for the heat conduction matrix for the finite element is used the heat balance equation. Use of the software application to choose certain measures to eliminate the thermal bridges enables to get the thermotechnical calculations in the junction between the window and the exterior wall in the form of temperature fields. Practical recommendations for arrangement of heat insulation in junctions between the window frames and the wall to eliminate actual defects and for normal room conditions are made under examinations. To get the heat conduction matrix for the finite element we will use the heat balance equation.
- Published
- 2018
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10. Investigation of the ultrasonic sound signals during the cementing materials induration
- Author
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Gaponov Vladimir, Kuznetsov Dmitry, Dudnik Vitaly, and Afanasieva Nadiia
- Subjects
Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
The paper is devoted to investigation mechanism of cement mixture setting and stiffening. Method for registration of the acoustic oscillations induced during the heterophase transitions executing in liquid medium was proposed (method of acoustic emission (AE)). Using of conical vessel serving as a resonator allows the amplification of registered acoustic signal and provides high sensitivity of the registration. The experimental results show that the using of AE-method allows remote monitoring of the dynamics of concrete mixtures condition during setting. Therefore, this method can be successfully applied in building as a non-destructive method for determining the start and end of the solidification of the cement solution.
- Published
- 2017
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11. Piperidinium surfactants functionalized with carbamate fragment: Aggregation, antimicrobial activity and cytotoxicity.
- Author
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Kushnazarova RA, Mirgorodskaya AB, Kuznetsov DM, Vasilieva EA, Amerhanova SK, Voloshina AD, and Zakharova LY
- Subjects
- Carbamates pharmacology, Anti-Bacterial Agents pharmacology, Micelles, Surface-Active Agents pharmacology, Surface-Active Agents chemistry, Anti-Infective Agents pharmacology, Anti-Infective Agents chemistry
- Abstract
The biomimetic nature of supramolecular systems, the structural similarity of synthetic surfactants to biomolecules (lipids, proteins), provide them with high membranotropy, the ability to overcome biological barriers, and affinity towards biosubstances. Despite rather high toxicity cationic surfactants are of importance as antimicrobial agents, gene nanocarriers and mitochondria targeted ligands. To minimize this limitation, cationic amphiphilic matrix undergoes modification with various functional groups. In this work, new piperidinium cationic surfactants containing one or two carbamate fragments were prepared; their aggregation behavior was systematically studied by tensiometery, spectrophotometry and fluorimetry. The presence of a carbamate fragment leads to a 2-3-fold decrease in critical micelle concentration and to a significant increase in solubilization capacity compared to unsubstituted analogue. Evaluation of the antimicrobial effect showed that all compounds exhibit high bactericidal and fungicidal activity against a wide range of pathogenic microorganisms, including their resistant forms. Importantly, the introducing carbamate moiety allows of decreasing hemolytic activity of cationic surfactants. The data obtained make it possible to recommend carbamate piperidinium surfactants as effective biocompatible and biodegradable nanocontainers for hydrophobic probes with high antimicrobial effect and moderate hemolytic activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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12. Asymmetric Catalytic Hydroboration of Enol Carbamates Enables an Enantioselective Matteson Homologation.
- Author
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Kuznetsov DM and Ready JM
- Abstract
Rh-catalyzed asymmetric hydroboration of enol carbamates yields α-boryl carbamates in good enantioselectivity. The enol carbamate starting materials can be prepared with moderate Z selectivity using a modified Juila olefination and used as an E/Z mixture, taking advantage of the faster reactivity of the major Z isomer in the directed hydroboration. Optically active α-boryl carbamates participate in a Matteson-type homologation with Grignard reagents in which the O-carbamate is substituted with high conservation of optical activity to provide enantioenriched secondary boronic esters., Competing Interests: Conflict of Interest The authors declare no conflict of interest.
- Published
- 2023
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13. Role of Polyanions and Surfactant Head Group in the Formation of Polymer-Colloid Nanocontainers.
- Author
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Vasilieva EA, Kuznetsova DA, Valeeva FG, Kuznetsov DM, and Zakharova LY
- Abstract
Objectives: This study was aimed at the investigation of the supramolecular systems based on cationic surfactants bearing cyclic head groups (imidazolium and pyrrolidinium) and polyanions (polyacrylic acid (PAA) and human serum albumin (HSA)), and factors governing their structural behavior to create functional nanosystems with controlled properties. Research hypothesis. Mixed PE-surfactant complexes based on oppositely charged species are characterized by multifactor behavior strongly affected by the nature of both components. It was expected that the transition from a single surfactant solution to an admixture with PE might provide synergetic effects on structural characteristics and functional activity. To test this assumption, the concentration thresholds of aggregation, dimensional and charge characteristics, and solubilization capacity of amphiphiles in the presence of PEs have been determined by tensiometry, fluorescence and UV-visible spectroscopy, and dynamic and electrophoretic light scattering., Results: The formation of mixed surfactant-PAA aggregates with a hydrodynamic diameter of 100-180 nm has been shown. Polyanion additives led to a decrease in the critical micelle concentration of surfactants by two orders of magnitude (from 1 mM to 0.01 mM). A gradual increase in the zeta potential of HAS-surfactant systems from negative to positive value indicates that the electrostatic mechanism contributes to the binding of components. Additionally, 3D and conventional fluorescence spectroscopy showed that imidazolium surfactant had little effect on HSA conformation, and component binding occurs due to hydrogen bonding and Van der Waals interactions through the tryptophan amino acid residue of the protein. Surfactant-polyanion nanostructures improve the solubility of lipophilic medicines such as Warfarin, Amphotericin B, and Meloxicam., Perspectives: Surfactant-PE composition demonstrated beneficial solubilization activity and can be recommended for the construction of nanocontainers for hydrophobic drugs, with their efficacy tuned by the variation in surfactant head group and the nature of polyanions.
- Published
- 2023
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14. Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes.
- Author
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Vasilieva EA, Kuznetsova DA, Valeeva FG, Kuznetsov DM, Zakharov AV, Amerhanova SK, Voloshina AD, Zueva IV, Petrov KA, and Zakharova LY
- Abstract
Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular weights, and its arginine derivative was developed and optimized. The use of the polymer modification led to an increase in the encapsulation efficiency toward rhodamine B (RhB; ~85%) and 2-PAM (~60%) by 20% compared to conventional liposomes. The formation of monodispersed and stable nanosized particles with a hydrodynamic diameter of up to 130 nm was shown using dynamic light scattering. The addition of the polymers recharged the liposome surface (from -15 mV to +20 mV), which demonstrates the successful deposition of Cs on the vesicles. In vitro spectrophotometric analysis showed a slow release of substrates (RhB and 2-PAM) from the nanocontainers, while the concentration and Cs type did not significantly affect the chitosome permeability. Flow cytometry and fluorescence microscopy qualitatively and quantitatively demonstrated the penetration of the developed chitosomes into normal Chang liver and M-HeLa cervical cancer cells. At the final stage, the ability of the formulated 2-PAM to reactivate brain AChE was assessed in a model of paraoxon-induced poisoning in an in vivo test. Intranasal administration of 2-PAM-containing chitosomes allows it to reach the degree of enzyme reactivation up to 35 ± 4%.
- Published
- 2022
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15. Complexation of Oligo- and Polynucleotides with Methoxyphenyl-Functionalized Imidazolium Surfactants.
- Author
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Kuznetsova DA, Kuznetsov DM, Vasileva LA, Amerhanova SK, Valeeva DN, Salakhieva DV, Nikolaeva VA, Nizameev IR, Islamov DR, Usachev KS, Voloshina AD, and Zakharova LY
- Abstract
Interaction between cationic surfactants and nucleic acids attracts much attention due to the possibility of using such systems for gene delivery. Herein, the lipoplexes based on cationic surfactants with imidazolium head group bearing methoxyphenyl fragment (MPI-n, n = 10, 12, 14, 16) and nucleic acids (oligonucleotide and plasmid DNA) were explored. The complex formation was confirmed by dynamic/electrophoretic light scattering, transmission electron microscopy, fluorescence spectroscopy, circular dichroism, and gel electrophoresis. The nanosized lipoplex formation (of about 100-200 nm), contributed by electrostatic, hydrophobic interactions, and intercalation mechanism, has been shown. Significant effects of the hydrocarbon tail length of surfactant and the type of nucleic acid on their interaction was revealed. The cytotoxic effect and transfection ability of lipoplexes studied were determined using M-HeLa, A549 cancer cell lines, and normal Chang liver cells. A selective reduced cytotoxic effect of the complexes on M-HeLa cancer cells was established, as well as a high ability of the systems to be transfected into cancer cells. MPI-n/DNA complexes showed a pronounced transfection activity equal to the commercial preparation Lipofectamine 3000. Thus, it has been shown that MPI-n surfactants are effective agents for nucleic acid condensation and can be considered as potential non-viral vectors for gene delivery.
- Published
- 2022
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16. Oxime Therapy for Brain AChE Reactivation and Neuroprotection after Organophosphate Poisoning.
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Kuznetsova DA, Gaynanova GA, Vasilieva EA, Pavlov RV, Zueva IV, Babaev VM, Kuznetsov DM, Voloshina AD, Petrov KA, Zakharova LY, and Sinyashin OG
- Abstract
One of the main problems in the treatment of poisoning with organophosphorus (OPs) inhibitors of acetylcholinesterase (AChE) is low ability of existing reactivators of AChE that are used as antidotes to cross the blood-brain barrier (BBB). In this work, modified cationic liposomes were developed that can penetrate through the BBB and deliver the reactivator of AChE pralidoxime chloride (2-PAM) into the brain. Liposomes were obtained on the basis of phosphatidylcholine and imidazolium surfactants. To obtain the composition optimized in terms of charge, stability, and toxicity, the molar ratio of surfactant/lipid was varied. For the systems, physicochemical parameters, release profiles of the substrates (rhodamine B, 2-PAM), hemolytic activity and ability to cause hemagglutination were evaluated. Screening of liposome penetration through the BBB, analysis of 2-PAM pharmacokinetics, and in vivo AChE reactivation showed that modified liposomes readily pass into the brain and reactivate brain AChE in rats poisoned with paraoxon (POX) by 25%. For the first time, an assessment was made of the ability of imidazolium liposomes loaded with 2-PAM to reduce the death of neurons in the brains of mice. It was shown that intravenous administration of liposomal 2-PAM can significantly reduce POX-induced neuronal death in the hippocampus.
- Published
- 2022
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17. Enhancement of the Transdermal Delivery of Nonsteroidal Anti-inflammatory Drugs Using Liposomes Containing Cationic Surfactants.
- Author
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Kuznetsova DA, Vasilieva EA, Kuznetsov DM, Lenina OA, Filippov SK, Petrov KA, Zakharova LY, and Sinyashin OG
- Abstract
New hybrid liposomes based on cationic amphiphiles with different structures of the head group (cetyltrimethylammonium bromide (CTAB), 3-hexadecyl-1-hydroxyethylimidazolium bromide (IA-16(OH)), 1-(butylcarbamoyl)oxyethyl-3-hexadecylimidazolium bromide (IAC 16(Bu)), and hexadecylmethylpyrrolidinium bromide (PR-16)) were developed for transdermal administration of nonsteroidal anti-inflammatory drugs. The different surfactant/lipid compositions were studied to obtain stable liposomes with high functionality. The hydrodynamic diameter of cationic liposomes was ∼110 nm. An admixture of cationic surfactants and PC liposomes improves the physicochemical properties of vesicles and transdermal diffusion rate and prolongs the release of drugs. Liposomal diclofenac sodium (DS) and ketoprofen (KP) were tested (using Franz cells) for transdermal penetration. Drug diffusion monitoring for 48 h demonstrated that the maximum DS and KP penetration through the synthetic membranes (Strat-M) is characterized by values of 255 ± 2 and 186 ± 3 μg/cm
2 , respectively. The influence of the surfactant head group on the properties (stability, release profile, permeability) of cationic liposomes was shown for the first time. While the drug specificity is evident for the rate of release, the permeability increases as follows: conventional liposomes < CTAB/PC < PR-16/PC < IAC-16(Bu)/PC < IA-16(OH)/PC for both medicines. The rat paw edema model was used to assess the anti-inflammatory effect of the IA-16(OH)/PC leader formulation in vivo . It was found that liposomal DS and KP are effective for relieving rat paw edema. It should be noted that DS-loaded hybrid liposomes demonstrated the highest therapeutic efficacy compared to conventional vesicles., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)- Published
- 2022
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18. Cationic Imidazolium Amphiphiles Bearing a Methoxyphenyl Fragment: Synthesis, Self-Assembly Behavior, and Antimicrobial Activity.
- Author
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Kuznetsova DA, Kuznetsov DM, Amerhanova SK, Buzmakova EV, Lyubina AP, Syakaev VV, Nizameev IR, Kadirov MK, Voloshina AD, and Zakharova LY
- Subjects
- Anti-Bacterial Agents pharmacology, Cations, Hydrophobic and Hydrophilic Interactions, Micelles, Surface-Active Agents chemistry, Surface-Active Agents pharmacology
- Abstract
Novel cationic amphiphiles of the 3-alkyl-1-(4-methoxyphenyl)-1 H -imidazol-3-ium bromide series bearing methoxyphenyl fragments (MPI- n ) have been synthesized. Their aggregation properties in aqueous solutions, solubilization capacity, and hemolytic and antimicrobial activities have been investigated by a number of physicochemical methods. Using tensiometry, conductometry, and fluorescence spectroscopy, it was shown that the MPI- n have lower CMCs than their nonfunctionalized counterparts. The unusual alkyl-chain-length-dependent morphology of aggregates is testified for this homological series. Amphiphiles with 12, 14, and 16 alkyl tails are characterized by the formation of micellar aggregates, while a surfactant with a decyl tail is characterized by the formation of larger aggregates with lower surface curvature. The MPI-10 aggregate morphology was rationalized in terms of the packing parameter consideration and was supported by size measurements and the fluorescence probe techniques, which showed that vesicle-like aggregates in close-packing mode probably occur. MPI- n aggregates have exhibited a high solubilization capacity toward hydrophobic azo dye Orange OT. Importantly, amphiphiles studied showed (i) high bacteriostatic activity at the level of ciprofloxacin; (ii) high bactericidal action against all Gram-positive bacteria, including methicillin-resistant strains; (iii) bactericidal properties against Gram-negative bacteria; and (iv) low hemolytic activity.
- Published
- 2022
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19. Polymer-Colloid Complexes Based on Cationic Imidazolium Amphiphile, Polyacrylic Acid and DNA Decamer.
- Author
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Kuznetsova DA, Gabdrakhmanov DR, Kuznetsov DM, Lukashenko SS, Zakharov VM, Sapunova AS, Amerhanova SK, Lyubina AP, Voloshina AD, Salakhieva DV, and Zakharova LY
- Subjects
- Cell Line, Tumor, Flow Cytometry, HeLa Cells, Humans, Hydrophobic and Hydrophilic Interactions, Imidazoles chemistry, Microscopy, Fluorescence, Acrylic Resins chemistry, Cations chemistry, Colloids chemistry, DNA chemistry, Polymers chemistry
- Abstract
The solution behavior and physicochemical characteristics of polymer-colloid complexes based on cationic imidazolium amphiphile with a dodecyl tail (IA-12) and polyacrylic acid (PAA) or DNA decamer (oligonucleotide) were evaluated using tensiometry, conductometry, dynamic and electrophoretic light scattering and fluorescent spectroscopy and microscopy. It has been established that PAA addition to the surfactant system resulted in a ca. 200-fold decrease in the aggregation threshold of IA-12, with the hydrodynamic diameter of complexes ranging within 100-150 nm. Electrostatic forces are assumed to be the main driving force in the formation of IA-12/PAA complexes. Factors influencing the efficacy of the complexation of IA-12 with oligonucleotide were determined. The nonconventional mode of binding with the involvement of hydrophobic interactions and the intercalation mechanism is probably responsible for the IA-12/oligonucleotide complexation, and a minor contribution of electrostatic forces occurred. The latter was supported by zeta potential measurements and the gel electrophoresis technique, which demonstrated the low degree of charge neutralization of the complexes. Importantly, cellular uptake of the IA-12/oligonucleotide complex was confirmed by fluorescence microscopy and flow cytometry data on the example of M-HeLa cells. While single IA-12 samples exhibit roughly similar cytotoxicity, IA-12-oligonucleotide complexes show a selective effect toward M-HeLa cells (IC
50 1.1 µM) compared to Chang liver cells (IC50 23.1 µM).- Published
- 2021
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20. Addressing the Challenges of Structure Elucidation in Natural Products Possessing the Oxirane Moiety.
- Author
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Kutateladze AG, Kuznetsov DM, Beloglazkina AA, and Holt T
- Subjects
- Density Functional Theory, Models, Molecular, Molecular Conformation, Stereoisomerism, Biological Products chemistry, Ethylene Oxide chemistry
- Abstract
NMR data for natural products containing the epoxy moiety have been revisited and reanalyzed with the help of a recently developed parametric/DFT hybrid computational method, DU8+. More than 20 structures needed revision, which points to challenges in NMR solution structure assignment for molecules possessing this structural feature. Among the revised structures are achicretin 2, acremine P, aromaticane I, artanomalide B, botryosphaerihydrofuran, chloroklotzchin, crithmifolide, crotodichogamoin A, emervaridone C, 9α,15-epoxyafricanane, fischambiguine B, grandilobalide B, guaianolide A, guatterfriesols A and B, juncenolide G, roscotane D, secoafricane 7, taccalonolides AJ and AF, and related compounds.
- Published
- 2018
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21. Step-Economical Photoassisted Diversity-Oriented Synthesis: Sustaining Cascade Photoreactions in Oxalyl Anilides to Access Complex Polyheterocyclic Molecular Architectures.
- Author
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Kuznetsov DM and Kutateladze AG
- Abstract
Atom- and step-economy in photoassisted diversity-oriented synthesis (DOS) is achieved with a versatile oxalyl linker offering rapid access to complex alkaloid mimics in very few experimentally simple steps: (i) it allows for fast tethering of the photoactive core to the unsaturated pendants, especially important in the case of (hetero)aromatic amines-essentially a one-pot reaction with no isolation of intermediates; (ii) the α-dicarbonyl tether acts as a chromophore enhancer, extending the conjugation chain and facilitating the "harvest" of the lower energy photons for the primary and secondary photoreactions; (iii) it enhances the quantum yield of intersystem crossing (ISC), i.e., it is capable of sensitizing secondary photochemical processes in the cascade; and (iv) the tether forms an additional heterocyclic moiety, imidazolidine-4,5-dione, a known pharmacophore. The overall photoassisted cascade is an efficient complexity-building process as quantified by computed step-normalized complexity indices, leading to extended polyheterocyclic molecular architectures comparable in complexity to natural products such as paclitaxel while requiring only 2-4 simple synthetic steps from readily available chemical feedstock.
- Published
- 2017
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22. Triquinanes and Related Sesquiterpenes Revisited Computationally: Structure Corrections of Hirsutanols B and D, Hirsutenol E, Cucumin B, Antrodins C-E, Chondroterpenes A and H, Chondrosterins C and E, Dichrocephone A, and Pethybrene.
- Author
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Kutateladze AG and Kuznetsov DM
- Subjects
- Molecular Structure, Quantum Theory, Sesquiterpenes chemistry
- Abstract
NMR data for 90+ natural sesquiterpenes possessing triquinane cores were examined with the help of a relatively fast parametric/DFT hybrid computational method, DU8+. Thirteen of these compounds, i.e., approximately 14% of the sample, required structure correction. This rate of misassignment is similar to the percentage of misassigned halogenated sesquiterpenes reported previously.
- Published
- 2017
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23. Photoassisted Synthesis of Complex Molecular Architectures: Dearomatization of Benzenoid Arenes with Aza-o-xylylenes via an Unprecedented [2+4] Reaction Topology.
- Author
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Kuznetsov DM, Mukhina OA, and Kutateladze AG
- Subjects
- Cycloaddition Reaction, Heterocyclic Compounds chemistry, Hydroxyquinolines chemistry, Molecular Structure, Photochemical Processes, Stereoisomerism, Aza Compounds chemistry, Benzene Derivatives chemistry, Heterocyclic Compounds chemical synthesis, Hydroxyquinolines chemical synthesis, Xylenes chemistry
- Abstract
A new method was developed for the photoinduced dearomatization of arenes through an intramolecular cycloaddition with aza-o-xylylenes generated by excited-state intramolecular proton transfer (ESIPT) in the readily available photoprecursors. The [2+4] topology of this cycloaddition is unprecedented for photo-dearomatizations of benzenoid aromatic carbocycles. It provides rapid access to novel heterocycles, cyclohexadieno-oxazolidino-quinolinols, as valuable synthons for a broad range of post-photochemical transformations., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2016
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24. Amino Azaxylylenes Photogenerated from o-Amido Imines: Photoassisted Access to Complex Spiro-Poly-Heterocycles.
- Author
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Mukhina OA, Kuznetsov DM, Cowger TM, and Kutateladze AG
- Subjects
- Cyclization, Photochemistry, Heterocyclic Compounds chemistry, Imines chemistry, Xylenes chemistry
- Abstract
Upon irradiation, cyclic imines containing o-amido groups are shown to produce reactive intermediates, amino azaxylylenes, which undergo intramolecular cycloadditions to tethered unsaturated pendants to yield complex N,O-heterocycles having an additional spiro-connected nitrogen heterocyclic moiety. Modular assembly of the photoprecursors allows expeditious increase of the complexity of the target poly-heterocyclic scaffolds with a minimal number of experimentally simple reaction steps. The photocyclization and subsequent postphotochemical transformations are accompanied by an increase of Lovering's fsp3 factor, thus producing unprecedented three-dimensional molecular architectures, and offering extended sampling of chemical space., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
- View/download PDF
25. Intramolecular cycloadditions of photogenerated azaxylylenes with oxadiazoles provide direct access to versatile polyheterocyclic ketopiperazines containing a spiro-oxirane moiety.
- Author
-
Kumar NN, Kuznetsov DM, and Kutateladze AG
- Abstract
Photogenerated azaxylylenes undergo intramolecular cycloadditions to 1,3,4-oxadiazole pendants, which are accompanied by concomitant release of dinitrogen, yielding functionalized ketopiperazinoquinolinols containing an oxirane moiety fused to the quinolinole moiety while spiro-connected to diketopiperazine. These primary photoproducts are reactive versatile intermediates which can be further derivatized under nucleophilic SN1- or SN2-like ring opening of the oxirane moiety. The oxidized quinolinones undergo new rearrangements under the conditions of the Schmidt reaction, leading to unprecedented triazacanoindolinones.
- Published
- 2015
- Full Text
- View/download PDF
26. An acetyl-methyl switch drives a conformational change in p53.
- Author
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Tong Q, Mazur SJ, Rincon-Arano H, Rothbart SB, Kuznetsov DM, Cui G, Liu WH, Gete Y, Klein BJ, Jenkins L, Mer G, Kutateladze AG, Strahl BD, Groudine M, Appella E, and Kutateladze TG
- Subjects
- Crystallography, X-Ray, DNA Damage physiology, Humans, Lysine metabolism, Magnetic Resonance Spectroscopy, Protein Conformation, DNA Methylation genetics, Ligands, Models, Molecular, Protein Processing, Post-Translational genetics, Tumor Suppressor Protein p53 chemistry, Tumor Suppressor Protein p53 metabolism
- Abstract
Individual posttranslational modifications (PTMs) of p53 mediate diverse p53-dependent responses; however, much less is known about the combinatorial action of adjacent modifications. Here, we describe crosstalk between the early DNA damage response mark p53K382me2 and the surrounding PTMs that modulate binding of p53 cofactors, including 53BP1 and p300. The 1.8 Å resolution crystal structure of the tandem Tudor domain (TTD) of 53BP1 in complex with p53 peptide acetylated at K381 and dimethylated at K382 (p53K381acK382me2) reveals that the dual PTM induces a conformational change in p53. The α-helical fold of p53K381acK382me2 positions the side chains of R379, K381ac, and K382me2 to interact with TTD concurrently, reinforcing a modular design of double PTM mimetics. Biochemical and nuclear magnetic resonance analyses show that other surrounding PTMs, including phosphorylation of serine/threonine residues of p53, affect association with TTD. Our findings suggest a novel PTM-driven conformation switch-like mechanism that may regulate p53 interactions with binding partners., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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