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Thermal Stability and Solid State Cyclization of Dipeptides

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Title: Thermal Stability and Solid State Cyclization of Dipeptides
Author: Ali, Farukh Iftakhar
Department: Department of Chemistry
Program: Chemistry
Advisor: Soldatov, Dmitriy V.
Abstract: In this thesis, the thermal stability and thermally induced transformations of solid dipeptides were studied in a systematic way. Overall, 49 dipeptides were used with 15 different amino acids, including 10 hydrophobic and 5 hydrophilic, 14 standard (6 essential) and 1 non-standard, as well as 15 L- and 4 D-isomeric residues. The thermally induced reactions and their products were studied by TGA, TGA-FTIR, DSC, FTIR, NMR, ESI+, GC-MS, XRD and other methods. The steps of thermal decomposition were identified and the dependencies of the thermal stability and decomposition pathways on molecular structure, crystal composition and solid state structure were studied. In the TGA experiments, mass loss events <120°C were due to the dehydration producing dry dipeptides from their hydrates. Further heating resulted in the mass loss events due to chemical decomposition of the dry dipeptides producing the corresponding cyclodipeptides and water. It was followed by the sublimation or evaporation of the cyclic products, accompanied by irreversible decomposition side reactions. The chemical decomposition is a solid state endothermic process yielding a stereochemically pure cyclic product. For several dipeptides series, it was observed that: i) the higher the degree of hydration, the lower the temperature of the chemical decomposition; ii) the greater the number of hydrogen bonds in the dipeptide solid, the higher its thermal stability; iii) the smaller the side groups, the higher the thermal stability. The solid state synthesis of the cyclodipeptides, or diketopiperazines (DKPs), from the corresponding dipeptides was developed in this work as a new synthetic method. It is highly efficient, solvent free, producing no side products, stereospecific and environmentally friendly. The solid state synthesis of DKPs at microscale level was conducted in TGA, whereas at macroscale level it was achieved in oven. Both methods produced pure DKPs with quantitative yields. In contrast, the sublimed products of the dipeptides were mixtures of diastereomers of the corresponding DKPs. The solid state syntheses of DKPs were often complicated by polymorphism where two to three polymorphic forms of a DKP were detected and characterized.
URI: https://hdl.handle.net/10214/21341
Date: 2020-10
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Embargoed Until: 2021-09-23


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