Anion recognition with biotin[6]uril derivatives

Nicolaj Nylandsted Andersen

Abstract

This thesis is divided into 9 chapters. Chapters 1 and 2 serve as introductions to the field of anion recognition while chapters 3 to 9 describes the work carried out and the results obtained throughout the project. Chapter 1 gives an overview of the field of anion recognition. Examples from the research area of the hemicucurbiturils and their derivatives bambusurils and cyclohexylhemicucurbiturils are given. The anion recognition of these macrocycles are contextualised by comparison to other macrocyclic anion receptors that use different recognition motifs. Chapter 2 provides an overview of how to determine stoichiometry and association constants in supramolecular chemistry using titration. Expressions for 1:1 and 1:2 host:guest stoichiometries are derived in detail and reported with the expressions for the 2:1 fit. The Job Plot is discussed in detail with focus on the criteria for when the method is applicable, and a dimerisation fit is derived. Specifics for the design of an NMR titration and a calorimetric isothermal titration (ITC) are also discussed. The chapter concludes with a guide on how to construct an iterative fitting function in OriginPro 9.1, and a short discussion of the advantages of global data fitting is given. Chapter 3 acts as the aim and scope for the remaining chapters providing a short overview of the themes of each. Chapter 4 serves as an introduction to the anion recognition of biotin[6]uril. This host recognises monocharged anions in aqueous buffer at neutral pH and selects guests based on their sizes. Chapter 5 describes the anion recognition of biotin-L-sulfoxide[6]uril. In water, this host was found to be a poorer host than biotin[6]uril, but in organic medium its anion recognition is stronger than biotin[6]uril. This peculiar result is discussed in detail with focus on host and guest solvation and an enthalpy-entropy-compensation study is carried out to assess the relative magnitude of the hydrophobic effect between the two hosts. Chapter 6 describes the superior anion recognition of biotinsulfone[6]uril compared to biotin[6]uril. The novel 2:1 stoichiometry observed for this host is discussed in detail with focus on justification of the new binding motif. This also ties into the attenuated size selectivity of this host compared to biotin[6]uril. Chapter 7 describes the synthetic work carried out to covalently link two biotinsulfone[6]uril moieties. This receptor recognises anions in the expected 1:1 stoichiometry, and with a gain in entropic contribution to the Gibbs free energy of association that is due to the preorganisation of the two macrocycles. Chapter 8 concludes the thesis with the introduction of a new host, the biotin[6]uril hexahydrazide. This positively charged host is investigated for both its anion recognition in comparison to negatively charges biotin[6]uril. Its anion recognition was found to be constant over a range of pH values in a mixture of water and THF. Chapter 9 serves as the appendix of the thesis.
Original languageEnglish
PublisherDepartment of Chemistry, Faculty of Science, University of Copenhagen
Publication statusPublished - 2018

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