Abstract
The design and preparation of selective artificial biomimetic receptors that function in aqueous media, has proven to be a formidable challenge. In this thesis, biomimetic molecules will be deliberated, including the ideas behind the designs and the path towards their creation. The first chapter is a short introduction and motivation to the overall thesis encountering the importance of exploring supramolecular chemistry. The remaining thesis is divided into two main parts. The first part concerns carbohydrate recognition in aqueous solution and is covered in three chapters. The second part describes the development of a foldamer for peptide interaction.
Chapter 2 serves as an introduction to carbohydrate recognition. The primary focus in this chapter is the design strategies presented in the literature during the last decades, which provides a background to the designs presented within this thesis. Of particular importance were the temple rector designs.
Chapter 3 presents the design, synthesis, and application of a macrocyclic carbohydrate receptor. Structural considerations on both receptor design and carbohydrates are detailed to find complementary carbohydrates for the receptor cavity. An ethenoanthracene backbone was synthesised and used as a building block of the macrocyclic receptor. Water-solubility of the receptor was encountered by providing appropriate functionalities on a spacer unit of the macrocycle. The receptor was finally assembled in a one-pot reaction, where three types of components were brought together to yield a macrocycle with two of each component in reasonable yields. The receptor was applied in binding studies with a range of carbohydrates in water, where affinities towards carbohydrates with an axial substituent and in particular towards amino sugars were found.
Chapter 4 describes the development of another carbohydrate receptor as a variety of the one described in Chapter 3. Here, the ethenoanthracene backbone was functionalised with the water-soluble groups through a succinimide unit for which the synthesis is discussed. A rigid macrocycle was assembled using a sulfonyl chloride spacer reagent to gain sulfonamide linkers to participate in a possible binding event. The final receptor was applied in binding studies with carbohydrates in water, which also showed higher affinity towards charged amino sugars, suggesting the presence of cation-π interactions in the binding event.
Chapter 5 concerns the second part of this thesis. Another type of a biomimetic compound was investigated, the so-called foldamers. Two different twelve units long foldamers were synthesised by solid-phase synthesis, consisting of quinoline units with intramolecular interactions forming helical structures. The quinoline units have functional side chains in the 4-position, which were exploited to make foldamers with a one-sided binding site for peptide interactions in water. The synthesis of two of the quinoline derivatives is described within this work, which were functionalised with a tyrosine-like and a phenylalanine-like side chain. The binding studies were investigated by ITC experiments, which indicated interactions towards selected peptides.
The final Chapter 6 gives an overall conclusion of the thesis and reflects on future prospects.
Chapter 2 serves as an introduction to carbohydrate recognition. The primary focus in this chapter is the design strategies presented in the literature during the last decades, which provides a background to the designs presented within this thesis. Of particular importance were the temple rector designs.
Chapter 3 presents the design, synthesis, and application of a macrocyclic carbohydrate receptor. Structural considerations on both receptor design and carbohydrates are detailed to find complementary carbohydrates for the receptor cavity. An ethenoanthracene backbone was synthesised and used as a building block of the macrocyclic receptor. Water-solubility of the receptor was encountered by providing appropriate functionalities on a spacer unit of the macrocycle. The receptor was finally assembled in a one-pot reaction, where three types of components were brought together to yield a macrocycle with two of each component in reasonable yields. The receptor was applied in binding studies with a range of carbohydrates in water, where affinities towards carbohydrates with an axial substituent and in particular towards amino sugars were found.
Chapter 4 describes the development of another carbohydrate receptor as a variety of the one described in Chapter 3. Here, the ethenoanthracene backbone was functionalised with the water-soluble groups through a succinimide unit for which the synthesis is discussed. A rigid macrocycle was assembled using a sulfonyl chloride spacer reagent to gain sulfonamide linkers to participate in a possible binding event. The final receptor was applied in binding studies with carbohydrates in water, which also showed higher affinity towards charged amino sugars, suggesting the presence of cation-π interactions in the binding event.
Chapter 5 concerns the second part of this thesis. Another type of a biomimetic compound was investigated, the so-called foldamers. Two different twelve units long foldamers were synthesised by solid-phase synthesis, consisting of quinoline units with intramolecular interactions forming helical structures. The quinoline units have functional side chains in the 4-position, which were exploited to make foldamers with a one-sided binding site for peptide interactions in water. The synthesis of two of the quinoline derivatives is described within this work, which were functionalised with a tyrosine-like and a phenylalanine-like side chain. The binding studies were investigated by ITC experiments, which indicated interactions towards selected peptides.
The final Chapter 6 gives an overall conclusion of the thesis and reflects on future prospects.
| Originalsprog | Engelsk |
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| Forlag | Department of Chemistry, Faculty of Science, University of Copenhagen |
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| Antal sider | 174 |
| Status | Udgivet - 2020 |