The aim of this project was to generate a new type of therapeutic delivery system and immunogenic vector, based on calixarenes, that is able to not only deliver immunogenic peptide but also act as a potential cancer vaccine. The introduction presents calixarenes derivatives in the context of supramolecular chemistry. Their properties on the nanoscale allow them to be potential adjuvants for cancer immunotherapeutics. The synthetic study of these materials presented in Chapter II compares traditional synthetic protocols and a new greener approach utilising microwave irradiation. Initial studies in this area concentrate on alkyl-footed derivatives of both the resorcin[4]arene and pyrogallol[4]arene macrocycles but have also been expanded to the previously problematic aromatic derivatives. This microwave method has been optimised to produce the rccc diastereoisomer for both the alkyl and aromatic derivatives, showing that the nature of the substituent on the pendant chains does not have a great effect on the conformation using this green protocol. The solution and solid state studies of these new aromatic pyrogallol[4]arene macrocycles, in the rccc cone conformation, have been investigated and demonstrate their future potential application in hydrogen storage. The synthesis of polar analogues, described in Chapter III, was achieved by functionalising the pendant chains with polar groups, including amines, alcohols and carboxylic acids. The importance of the solvent in the crystallisation process is highlighted by single crystal X-ray diffraction study, showing that it can act as templating agent or guest. Access to polar footed calixarenes has enabled the project to investigate their potential to link bioactive therapeutics including amino acids and peptides, towards nano-vectors exposed in Chapter IV. The traditional synthesis in solution was challenging due to purification issues, and only succeeded in the attachment of three trialanines. The method was therefore tuned towards solid phase synthesis, which opened up to the new development of Merrifield resin functionalised with calixarenes. As the macrocycle will be considered for immunisation in the future, the lead macrocycle from this study have been screened for potential downstream biological applications. Preliminary studies, including haemolytic properties and cytotoxicity studies did not show any toxicity at the workable concentrations.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:629233 |
| Date | January 2011 |
| Creators | Funck, M. |
| Publisher | Nottingham Trent University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://irep.ntu.ac.uk/id/eprint/56/ |
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