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Title: Biofunctionalised coordination cages and quantified speciation in supramolecular mixtures
Author: Kieffer, Marion
ISNI:       0000 0004 7968 4731
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2019
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Coordination cages formed by supramolecular self-assembly are excellent candidates for the selective encapsulation of molecules and sheltering these guests from their environment after uptake. The easily tuneable nature of these 3D-structures can make them versatile carriers in applications such as drug delivery. However, to achieve this, the capsules need to be converted into biocompatible vehicles by the conjugation of biomolecules onto the cages' surface for example. This thesis describes initial efforts towards this goal. Firstly, the compatibility and influence of coordination cages on a simple biomaterial was studied by the incorporation of tetrahedral cages in a peptide-based supramolecular gel. Rheological changes of the macroscopic material were observed while the host-guest properties of the cages remained unchanged, enabling the chemical segregation of guests. Secondly, bioconjugation of single amino acids and a tripeptide gelator onto coordination cages were investigated, showing that the properties of the peptide such as chirality and gelation were transferred to the whole system. Addition of a photoacid generator to the organo-gel formed triggered the reversible gel-sol transition of the material under alternating cycles of light irradiation and darkness. Finally, a water-soluble cage was synthesised using N-acetylatedgalactoamine building blocks. The geometry and organisation of the sugar biotags were engineered to allow ligation of the cage onto the asialoglycoprotein receptor of hepatocytes with the goal of realising the cellular internalisation of the complex and its cargo. In synthetic supramolecular systems, molecules can interact in different ways to yield complex self-assembled libraries. Multiple components combined can result in the integrative formation of single products or, most often, multiple self-assembled products. Deciphering the self-assembly rules within such systems involves new characterisation challenges: dynamic, low-symmetry products are difficult to detect and identify by NMR spectroscopy and labile species can re-equilibrate after chromatographic separation. Hence, in this thesis the potential to assess individual outcomes of self-sorting experiments by mass spectrometric techniques was investigated in three case-studies. A new methodology to calculate the relative energies of heteroleptic structures compared to the more stable homoleptic was developed, allowing for the quantification of each ligand's structural preferences. Following a similar approach, the effect of anion binding on a dynamic library of self-assembled tetrahedra was probed. Finally, quantitative information on speciation within mixtures was obtained for a complex system of self-assembled scalenohedra and pseudo-octahedra.
Supervisor: Nitschke, Jonathan Russell Sponsor: European Union's Horizon 2020 Marie Sklodowska-Curie Actions
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Supramolecular Chemistry ; host-guest chemistry ; Mass-spectrometry ; Biofunctionalisation ; Coordination Cages