Zhang, Qiang (2013) Novel strategies in the synthesis of functional glycopolymers. PhD thesis, University of Warwick.

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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.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Glycoconjugates, Polymers, Polymerization
Official Date:	July 2013
Dates:	Date Event July 2013 Submitted
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Haddleton, David M.
Sponsors:	University of Warwick; China Scholarship Council (CSC)
Extent:	xxx, 245 leaves : illustrations.
Language:	eng

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