L.N. Gumilyov Eurasian National University, a dissertation defense for the degree of Doctor of Philosophy (PhD) by Turebayeva Pana on the topic «Synthesis and research of precursors and bambusuril itself and the production of new biocomposite materials based on it» to the educational program «8D05306 – Chemistry».
The dissertation was carried out at the «Chemistry» of L.N. Gumilyov Eurasian National University.
The language of defense is russian
Official reviewers:
Kalugin Sergey Nikolaevich – Doctor of Chemical Sciences, prpfessor, Professor of the Department of Chemistry and Technology of Organic Substances, Natural Compounds and Polymers, Al-Farabi Kazakh National University.
Appazov Nurbol Orynbasaruly– Candidate of Chemical Sciences, research professor at the Korkyt Ata Kyzylorda University.
Temporary members of the Dissertation Committee:
Pavlovsky Viktor Ivanovich – Professor of the N.M. Kizhner Scientific and Educational Center of Tomsk Polytechnic University (Tomsk, Russian Federation), Doctor of Chemical Sciences;
Yu Valentina Konstantinovna – Doctor of Chemical Sciences, Professor, Head of the Laboratory of Chemistry of Synthetic and Natural Medicinal Substances of the A.B. Bekturov Institute of Chemical Sciences JSC (Almaty, Republic of Kazakhstan);
Mashentseva Anastasia Alexandrovna – PhD, Professor, Head of the Technological Laboratory of Track Membranes of the AF Institute of Nuclear Physics of the Ministry of Energy of the Republic of Kazakhstan (Astana, Republic of Kazakhstan).
Scientific advisors:
Yerkassov Rakhmetulla Sharapidenovich – Doctor of Chemical Sciences, professor, Professor of the Department of Chemistry at the L. N. Gumilyov Eurasian National University;
Bakibaev Abdigali Abdimanapovich – Doctor of Chemical Sciences, Professor, Leading Researcher at the Laboratory of Organic Synthesis of Tomsk State University (Russia, Tomsk).
The defense will take place on February 12, 2025, at 03:00 PM in the Dissertation Council for the training direction «8D053 – Physical and chemical sciences» in the specialty «8D05306 – Chemistry» of L.N. Gumilyov Eurasian National University. The defense meeting is planned to be held offline and online.
Link: https://shorturl.at/C77vr
Address: Astana, K. Satpayev str., 2, L.N. Gumilyov ENU, educational and administrative (main) building, auditorium 302.
Abstract (English): General description of the work. The dissertation work is devoted to the study of the physico-chemical properties of the bambus[6]uril macromolecule and its precursors, as well as the development of methods for obtaining biocomposite and nanomaterials modified with bambus[6]uril and the study of their properties. The dissertation work is presented in the form of a series of articles published by a doctoral student in accordance with the requirements of paragraph 5-1 of the Rules for Awarding Degrees approved by Order No. 127 of the Minister of Education and Science of the Republic of Kazakhstan dated March 31, 2011 (registered in the Register of State Registration of Normative Legal Acts under No. 6951) as amended by Order No. 170 of the Minister of Education and Science of the Republic of Kazakhstan dated 30.04.2020 and in accordance with the Order of the Minister of Education and Science of the Republic of Kazakhstan dated 09.03.2021 No. 98, as amended by the Acting Minister of Science and Higher Education of the Republic of Kazakhstan dated 09.01.2023 No. 7. The relevance of the work. In the modern era of personalized medicine, there is a need to develop materials for implants, which requires finding optimal compromises with respect to their many characteristics. These characteristics include composition, shape, structure, mechanical properties, biocompatibility, as well as the ability to stimulate vascular or bone growth and possess antimicrobial activity. Previously, no one had used supramolecular glycoluryl compounds as bioactive molecules filling porous materials in order to increase biocompatibility and stimulate osteogenesis. An attractive substance for saturating the surface is bambus[6]uril, which is able to encapsulate therapeutic agents and release them in a prolonged manner under the influence of various factors. At the same time, there is no data in the scientific literature on studies aimed at establishing the interrelationships of the structure and properties of porous scaffolds modified with bambus[6]uril. The chemistry of bambus[6]uril is actively developing, however, to this day there are many questions about the study of their supramolecular properties. Bambus[6]uril is known to have host-guest properties, but its suitability for the synthesis and stabilization of metallic nanoparticles, in particular silver nanoparticles, has not yet been studied. It is relevant to conduct comprehensive studies of the effect of bambus[6]uril on the surface of porous materials and to obtain silver nanoparticles and determine their biomedical properties. This kind of research opens up a promising path to the development and creation of new biocomposite materials with desired properties. The purpose of the dissertation research. The purpose of the work is the synthesis of bambusuril and its precursors, the determination of their properties and the development of methods for obtaining nano- and biocomposite materials based on bambusuril and the study of their biomedical properties. Tasks: 1. To investigate the absorption/desorption ability of bambus[6]uril in relation to water. 2. To establish the effect of silver modification on the physico-chemical properties of bambus[6]uril, to investigate the antibacterial activity and cytotoxicity of the resulting biomaterial. 3. To modify some porous materials with bambus[6]uril and to investigate their biomedical properties. 4. To investigate the complexation of precursors of bambus[6]uril – N-methylglycoluryl with nitrates of a number of rare earth elements. The objects of research are complexes of bambus[6]uril with bactericidal components, porous materials based on hydroxyappatite and diatomite modified with bambus[6]uril, complexes of N – methylglycolurils (precursors of bambus[6]uril) with nitrates of rare earth elements. The scientific novelty of the work. 1. For the first time, quantum chemical calculations of bambus[6]uril (Bu[6]) aquacomplexes were performed using the DFT method in order to study the possibilities for including water molecules in the cavity of a macrocycle. DFT calculations have shown that the binding of water molecules to bambus[6]uril occurs through the formation of hydrogen bonds of the equatorial hydrogen atoms Bu[6] and the oxygen atom of water molecules. The formation of a dihydrate is energetically more advantageous than the binding of two additional water molecules to form BU tetrahydrate[6]. The calculated data obtained are consistent with the results of the kinetic experiment. 2. It was established for the first time that the introduction of Ag+ silver ions into bambus[6]uril leads to the formation of BU[6]-Ag/AgCl nanoparticles with high antibacterial activity against S. aureus and E. coli: the average diameter of the bacterial growth suppression zones was 17.5 mm for S. aureus and 17.4 mm for E. coli. 3. For the first time, new biocomposites based on porous scaffolds (hydroxyapatite and diatomite) and bambus[6]uril were obtained. The obtained composite materials Bu[6] + HA, Bu[6] + IDА and Bu[6] + CDA were characterized using IR spectroscopy and SEM, and the hemolytic effect and adsorption of plasma protein on the surface were determined for them. 4. A new complex compounds of N-methylglycolurils - precursors of bambus[6]uril (N-monomethylglycoluryl, 2,4-N,N-dimethylglycoluryl, 2,6-N,N-dimethylglycoluryl, 2,4,6,8-N,N,N,N-tetramethylglycoluryl) with nitrate hydrates of trivalent rare earth elements (lanthanum, cerium, praseodymium, neodymium, samarium, terbium, dysprosium, erbium, ytterbium) have been synthesized. Based on the results of IR spectroscopy, it was found that due to the structural features of methylglycolurils, they tend to form binuclear complexes with rare earth elements with coordination through carbonyl groups of urea fragments. The main provisions of the dissertation submitted for defense. 1. Exposure to bambus[6]uril with argon passed through distilled water (gas flow rate - 30 l/h) leads to absorption of water vapor by bambus[6]uril (Bu[6]) (rate constants of absorption and desorption 0.166 min−1 and 0.0221 min−1, respectively), while the absorption capacity of bambus[6]uril is 4 moles of water per 1 mol of Bu[6], which is consistent with the results of theoretical calculations using the DFT method. 2. The introduction of silver Ag+ to bambus[6]uril under selected conditions (t – 30 min., T – 25 °C, solvent – DMSO/CHCl3) leads to the formation of Bu[6]-Ag/AgCl nanoparticles, the appearance of antibacterial activity in bambus[6]uril relative to gram-negative (E. coli) and gram-positive (S. aureus) microflora and an increase in its cytotoxicity relative to mononuclears. 3. Precipitation of bambus[6]uril using the immersion method on the surface of porous materials: hydroxyapatite and diatomite, leads to a decrease in plasma protein adsorption, a decrease in thrombogenicity and an increase in hemocompatibility of the obtained biomaterials. 4. The introduction of nitrates of rare earth elements to N-methylglycolurils (precursors of bambus[6]uril) under selected conditions (t – 10 min., T – 25 °C, solvent – acetone) leads to the formation of complex compounds, while N-methylglycolurils realize bidentate, chelating and bridging functions and tend to form binuclear complexes with rare earth elements with coordination through carbonyl groups urea fragments. The practical significance of the work. New results have been obtained in the field of synthesis of supramolecular compounds of fundamental importance in the field of chemistry and materials science. New data on the effect of bambus[6]uril on the biomedical properties of porous inorganic materials (scaffolds) have been obtained. The practical significance lies in the fact that in this dissertation research, a method was developed for the production of nanoparticles based on silver and bambus[6]uril, which have high antibacterial activity against gram-positive and gram-negative microflora, which can be used for various biomedical purposes. It also involves the development of a method for depositing bambus[6]uril on porous materials based on hydroxyapatite and diatomite. The results showed that materials containing bambus[6]uril on the surface of the material do not exhibit their own antibacterial and hemolytic effects, which provides a reliable basis for their use as biocompatible materials. The results obtained are a promising alternative for the creation of stable and effective biocomposites, which in the future allow the implementation of supramolecular strategies involving encapsulated bambus[6]uriles in such processes. The author's personal contribution to the dissertation research consists in analyzing literary sources, conducting experimental and computational work, interpreting and discussing the experimental results obtained, and preparing manuscripts of articles. Approbation of the work. The main provisions, conclusions and scientific results of the dissertation were reported and discussed at international conferences: The International Scientific and Practical Conference "Current trends in the development of science and education in the field of natural sciences" (Almaty, 2022), The international scientific and technical online conference (Norway, 2024), the XII International Scientific and Practical Conference "Actual Problems of Natural Sciences Sciences" (Petropavlovsk, 2024) and International Scientific Conference "Modern scientific technology" (Stockholm, Sweden, 2024). Publications. The main results of the dissertation research are reflected in 10 published works, including 3 articles in scientific publications included in the first and/or second quartile of the impact factor according to the Journal Citation Reports of Clarivate Analytics; 1 publication in a foreign scientific publication, 6 works in the materials of the republican and international conferences. In the article Turebayeva, P.; Luchsheva, V.; Fedorishin, D.; Yerkassov, R.; Bakibaev, A.; Bolysbekova, S.; Tugambayeva, T.; Sergazina, S.; Nurmukhanbetova, N. Nanoparticles Based on Silver Chloride and Bambus[6]uril[6] for the Fine-Tuning of Biological Activity. Int. J. Mol. Sci. 2023, 24, 16126 the applicant is the first author. The International Journal of Molecular Sciences for 2023 has an Impact Factor of 4.9, and has a quartile in biochemistry and molecular biology – Q1; in chemistry, multidisciplinary – Q2. For 2023, CiteScore has a score of 8.1, the percentile in inorganic chemistry is 90; the percentile in organic chemistry is 87; the percentile in spectroscopy is 86; the percentile in physical and theoretical chemistry is 82; the percentile in computer science applications is 80; the percentile in molecular biology is 70; the percentile in catalysis is 65. The doctoral student participated in conducting experiments and interpreting the results, was engaged in the preparation and design of the original draft of the article. In addition, P.D. Turebayeva was engaged in the design of the article in accordance with the requirements of the journal. The doctoral student is the first author in the article Turebayeva, P.; Guslyakov, A.N.; Novikova, S.A.; Khlebnikov, A.I.; Befus, E.A.; Meshcheryakov, E.P.; Bakibaev, A.A.; Kusepova, L.; Kassenova, N.; Sharipova, S.; et al. Absorption of Water Vapor by Bambus[6]uril and a Density Functional Theory Study of Its Aqua Complexes. Molecules 2023, 28, 7680. The journal "Molecules" for 2023 has an Impact Factor of 4.2, and the quartile for biochemistry and molecular biology, chemistry, multidisciplinary is Q2. The CiteScore for 2023 is 7.4, the percentile in chemistry (miscellaneous) is 83; the percentile in organic chemistry is 81; the percentile in physical and theoretical chemistry is 80; the percentile in analytical chemistry is 78; the percentile in pharmaceutical science is 81; the percentile in drug discovery is 73; the percentile in molecular medicine is 68. P.D. Turebayeva took an active part in conducting research, in collecting literature and processing data and in the design of the article. In the article Zhumabayeva, G.; Turebayeva, P.; Ukhov, A.; Fedorishin, D.; Gubankov, A.; Luchsheva, V.; Kurzina, I.; Bakibaev, A.; et al. Development of Novel Composite Biocompatible Materials by Surface Modification of Porous Inorganic Compounds Using Bambus[6]Uril. Materials 2023, 16, 7257. the doctoral student is a corresponding author. The «Materials» journal has an Impact Factor for 2023 equal to 3.1 and a quartile in physical chemistry – Q3; in materials science, multidisciplinary – Q2; in metallurgy and metallurgical engineering – Q1; in applied physics – Q2; in physics, condensed matter – Q2. It has a CiteScore for 2023 equal to 5.8, a percentile in condensed matter physics – 73; a percentile in general materials science – 67. P.D. Turebayeva was directly involved in obtaining exp erimental data, processing and interpreting experimental results, and writing conclusions on the experiment for the design of the article. The applicant was also involved in submitting an article to the journal, maintained contact and corresponded with the editorial board of the journal during the review and publication of the article. The doctoral student was directly involved in obtaining experimental data, processing and interpreting the results for the preparation of materials and abstracts of 6 reports at national and international scientific conferences.
Conclusion of the Research Ethics Committee
Defense of the dissertation: https://www.youtube.com/watch?v=V9QDCb8onLg
