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Title: Self-assembly of synthetic and biological components in water using cucurbit[8]uril
Author: Zayed, Jameel Majed
ISNI:       0000 0004 2714 7133
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2012
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This thesis discusses progress made towards assembling molecular building blocks in the presence of our molecular host of choice, cucurbit[8]uril (CB[8]). Our studies on the self-assembly of synthetic and biological components in water bridge overlapping conceptsand techniques drawn from the fields of synthetic organic chemistry, supramolecular self-assembly, and applied NMR techniques. Chapter 1 introduces the reader to chemical complexity, and how supramolecular chemistshave advanced in their capability of assembling more complex molecular architectures. The discussion focusses particularly on self-assembly carried out in the aqueousphase, and how, like in biology, molecular design of the building blocks become criticalin enabling non-covalent assembly to occur in this dynamic, and relatively competitiveenvironment. The cucurbit[n]uril family of molecular hosts are then introduced with anoverview of their modes of binding, and affinities towards typical guests. Finally, a practicalintroduction to NMR methods gaining prominence in supramolecular chemistry ispresented. In particular, the use of diffusion NMR, a key tool for probing the solutiondynamics of molecular assemblies, is highlighted. Chapter 2 details work carried out on the CB[8]-mediated self-assembly of supramolecularblock copolymers from polymeric, and small molecule building blocks. Here, endgroup-functionalised polymer guests were shown to assemble with small molecule ditopicguests in the presence of CB[8] to form block copolymers. Copolymers of various molecularweights were assembled, and the supramolecular complexes were studied usingsolution viscometry and diffusion NMR. This study represented the first use of diffusionNMR for probing the assembly of polymeric guests with CB[8].Chapter 3 describes the self-assembly of CB[8] with complementary ditopic guests. Highmolecular weight supramolecular polymers are known to form through the step-growthassembly of complementary ditopic building blocks. Here we sought to probe CB[8]?sability to drive supramolecular polymerisation. Solution viscometry, ESI-MS, and diffusionNMR were used to investigate the self-assembly process, which indicated that cyclicoligomers had formed. The relatively low solubility of CB[8] in water was thought to bea major limitation to polymer formation in this instance. Important observations relating to the effect of salts on the solution viscosities and stabilitiesof the complexes, are also discussed. Chapter 4 places emphasis on the synthetic methods employed towards preparing multivalentguests for CB[8] binding studies. Our synthetic guests were based on watersolubleoligomers of ethylene glycol. A bidirectional elongation route is presented foraccessing higher molecular weight, and monodisperse ethylene glycol oligomers (n = 12)in suitable purity. Chapter 5 describes the assembly of protein-polymer conjugates, and the versatility ofdiffusion NMR as a means to probe the assembly process. Here, end group-functionalisedpoly(ethylene glycol) guests were appended to bovine serum albumin (BSA) through amixed chemical ligation-self assembly protocol. The NMR studies conducted are emphasisedhere, which served to complement other characterisation methods used thatare reported elsewhere. Chapter 6 discusses ongoing work on lipid-based guests, and the resulting liposome assembliesformed. Head group-functionalised phospholipid guests, and cholesterol-basedguests were synthesised. Phospholipid guests were obtained through an enzymatic route,a novelty in our group. Dye-encapsulated liposomes were then assembled, purified, andcharacterised by fluorescence microscopy. Finally, we sought to optimise lipid formulationsto enhance liposome stability, towards conducting molecular recognition studies inthe presence of CB[8].Chapter 7 then closes the thesis with concluding remarks that summarise the describedresearch, while highlighting points of note.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Supramolecular ; Diffusion/DOSY NMR ; Host-guest ; Chemistry ; Water ; Organic ; Self-assembly ; Complexity