Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589899
Title: Novel strategies in the synthesis of functional glycopolymers
Author: Zhang, Qiang
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2013
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Abstract:
In chapter one, recent progress in the synthesis of functional glycopolymers was described. In chapter two, combination of catalytic chain transfer polymerisation (CCTP) with both thiol-ene and copper catalysed alkyne azide coupling (CuAAC) click chemistry has been employed to give a new route to functional glycopolymers for applications in bioconjugation and biological targeting. Ring opening of poly (glycidyl methacrylate) with sodium azide and subsequent reaction with alkyne functional carbohydrates, as prepared by Fischer glycosylation, has been exploited. This combination of a range of efficient chemistry gives a route to multi gram quantities of glycopolymers avoiding the need for living radical polymerisation chemistry. In chapter three, multi-block glycopolymers made of mannose, glucose, fucose and di(ethylene glycol) ethyl ether acrylate monomers were synthesized by Cu(0) wire mediated single electron transfer living radical polymerization (SET-LRP). These highly narrow disperse glycopolymers were then tested for binding and inhibition of DC-SIGN, a protein important for HIV infection. In chapter four, a series of cyclodextrin-based glycoconjugates, including glycoclusters and star glycopolymers, were synthesised via combination of CuAAC click reaction and copper-mediated living radical polymerization. These glycoconjugates show high affinity in binding with human DC-SIGN lectin and could be used as inhibitor to prevent the binding of HIV envelope protein gp120 to DCSIGN at nanomolar concentration. The star block glycopolymer show high loading capacity of hydrophobic anti-cancer and anti-HIV drugs, indicating promising application in HIV-therapeutic and smart drug delivery. In chapter five, a new approach to perform SET-LRP in pure water is described. The key step in this process is to allow full disproportionation of CuBr/Me6TREN (Me6TREN = tris(dimethylamino)ethyl amine) to Cu(0) powder and CuBr2 in water prior to addition of both monomer and initiator. This provides an extremely powerful tool for the synthesis of functional water-soluble polymers with controlled chain length and narrow molecular weight distributions (PDI approx. 1.10), including poly- NIPAM, DMA, PEG acrylate, HEA and glycomonomers. The polymerizations are performed at or below ambient temperature with quantitative conversions attained in minutes. Polymers have high chain end fidelity capable of undergoing chain extensions to full conversion or multi-block copolymerization via iterative monomer addition after full conversion. Activator generated by electron transfer atom transfer radical polymerization (AGET ATRP) of NIPAM in water was also conducted as a comparison with the SET-LRP system. This shows that the addition sequence of Lascorbic acid is crucial in determining the onset of disproportionation, or otherwise. This robust technique was applied to polymerizations under biologically relevant conditions (PBS buffer), a complex ethanol/water mixture (Tequila) and a truly biological condition: sheep blood serum. Finally, double hydrophilic diblock glycopolymers composed of mannose glycopolymer block and LCST PNIPAM or PDEGEEA block were successfully synthesized by this aqueous SET-LRP technique.
Supervisor: Not available Sponsor: University of Warwick ; China Scholarship Council (CSC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.589899  DOI: Not available
Keywords: QD Chemistry ; QP Physiology
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