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Design of Methods for Synthesis and Immobilization of Nitrogen Ligands Such as Pyridine onto the Mesoporous Silica Nanoparticles and Design of Pharmaceutical Structures Based on Amino Acids and Carbohydrates to Inhibit Polymerase Η for the Treatment of Leukemia and their Applications In Resins and Ionic Liquids

Kalhor, Sepideh | 2022

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 55341 (03)
  4. University: Sharif University of Technology
  5. Department: Chemistry
  6. Advisor(s): Matloubi Moghaddam, Firouz; Fattahi, Alireza
  7. Abstract:
  8. 1- Mesoporous silica materials have been found to possess pore sizes ranging from 2 -10 nm alongside 2D-hexagonal and 3D-cubic structural features. The specific properties of nanoparticles of the mesoporous silica family, such as the collected size, porosity, morphology, and high chemical stability, make them among the best drug delivery systems and catalysts. Designing the catalysts with advanced structures that effectively locate the transition metals and create active centres onto the surfaces of mesoporous silica materials has attracted extraordinary attention. According to many studies, mesoporous silica materials without organic functional groups cannot be used as catalysts in chemical reactions. Due to silanol groups, mesoporous silica materials are expected to bear mechanical and hydrothermal stability; the hydrophobicity of mesoporous silica materials can explain the mentioned characteristics. Additionally, if functionalised with organic groups, inorganic-organic mesotunnels, the Silica Wall of materials like the Ordered SBA-15 are expected to provide suitable surfaces for the interactions of transition metals and reactants in many chemical reactions. Besides, mesoporous silica nanoparticles can be separated from the reaction media and reused easily. Moreover, the area to volume ratio of mesoporous silica nanoparticles causes them to be a fine surface for the immobilisation of nitrogen-containing ligands and the synthesis of heterogeneous catalysts. According to what was mentioned above, one of the goals of our project was to design and synthesise a new class of nitrogen-containing mesoporous silica, which can play a role as an efficient ligand to form a complex with the transition metals, as expected from the principles of the Crystal Field Theory. Undoubtedly, these catalysts can function in synthesising biologically active compounds such as 1,2,4-Triazolo[1,5-a] pyridines.2- Furthermore, carbohydrate-based anticancer vaccines have gained much attention over the last decades. In addition to carbohydrates, therapeutic peptides have been applied as anticancer agents. These structures bear some desirable features, including the ability to penetrate cell membranes, high activity, specificity, affinity, and minimal drug-drug interaction. Also, therapeutic peptides are biologically diverse and easy to be synthesised. We designed structures including amino acids alongside monosaccharides to maintain both carbohydrate and amino acids building blocks in the suggested drugs. These structures can be synthesised by Amadori and Heyns methods. The clinical and experimental studies on the interactions of drugs and their receptors have proven effective. However, some problems associated with these experimental studies, including high costs, limited duration of effective treatment, and unwanted immunogenicity, have not been solved yet. First and foremost, we began our studies with Density functional theory (DFT) calculations of our designed structures. The designed structures were optimised at the B3LYP/6‐311++G (d, p) level. Finally, the obtained data from previous stages as inputs for MD simulation (The GROMACS 5.2). This study concentrated on molecular dynamic simulations because of their low cost. In recent years, molecular dynamic methods have enabled us to understand biomolecular hydrodynamic behaviours better. Also, we believe that these structures, which are based on carbohydrates and amino acids, can be used in resins.
  9. Keywords:
  10. Green Chemistry ; Computational Chemistry ; Amino Acid ; Silica ; Sugars ; Anticancer Drugs ; Mesoporous Silica Nanoparticles ; Leukemia

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