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    The Synthesis of Functionalized Glycosides: Coordination Chemistry, Antiparasitic Activity, Precursors to Conformationally Constrained Macrocyclic Architectures and Photophysical Properties


    Reddy, Andrew (2017) The Synthesis of Functionalized Glycosides: Coordination Chemistry, Antiparasitic Activity, Precursors to Conformationally Constrained Macrocyclic Architectures and Photophysical Properties. PhD thesis, National University of Ireland Maynooth.

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    Abstract

    The research presented in this thesis focuses on the synthesis of functional glycosides and the investigation of their properties. This included the study of their ability to form metal complexes and the study of the antiparasitic activity of both the free glycosides and metal complexes, the use of glycosides to serve as precursors to conformationally constrained macrocyclic molecules and a preliminary investigation of the photophysical properties of a collection of glycosidic compounds. Two novel classes of glycosylated chelators were synthesized and characterized; one containing a dinitrogen aminopyridyl chelating motif and another containing a dinitrogen/oxygen phenoxy-iminopyridyl metal binding unit. The ability of these compounds to form stable metal complexes with several metals (Cu(II), Zn(II) and Fe(II)) was investigated and the coordination complexes obtained were characterized. The anti-chagasic and anti-leishmanial activity of a selection of these compounds were evaluated in collaboration with the group of Prof André Luis Souza dos Santos at the Microbiology Institute Paulo de Góes in Universidade Federal do Rio de Janeiro (UFRJ), in addition to their toxicity towards mammalian macrophage cells. Several compounds with antiparasitic activity with excellent selectivity indexes were identified. From the analysis of these preliminary investigations, structural features were identified that appear to be necessary for their antiparasitic activity. Preliminary investigations into the probably mode of action involving the study of the susceptibility of the glycosylated compounds to enzymatic hydrolysis by β-glycosidase were carried out. The toxicity of the most potent compounds was also investigated using the Galleria Mellonella model. The use of carbohydrates as scaffolds to synthesize conformationally constrained macrocycles was also explored. To this end, several galactosyl donors were synthesized and their reactivity towards glycosylation with a serine derivative and 2- chloroethanol was investigated. Two different synthetic strategies were compared to highlight the intramolecular glycosylation as the most suitable route for macrocyclization. Finally, the photophysical properties of a collection of glycosides and structural analogues was examined. This involved the synthesis of a family of substituted iminopyridyl compounds and the preliminary analysis of their fluorescent properties. Based on these studies, a plausible explanation for the fluorescent behaviour of glycoside functionalised iminopyridyl compounds is proposed.

    Item Type: Thesis (PhD)
    Keywords: Synthesis; Functionalized Glycosides; Coordination Chemistry; Antiparasitic Activity; Precursors; Conformationally Constrained; Macrocyclic Architectures; Photophysical Properties;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 12100
    Depositing User: IR eTheses
    Date Deposited: 08 Jan 2020 12:14
    URI:

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