SYNTHESIS AND CHARACTERISATION OF NOVEL BIOPOLYMERS VIA CLICK CHEMISTRY

Abstract

The work throughout is the exploitation of copper catalysed Huisgen 1,3-dipolar azide–alkyne cycloaddition, as an efficient Click reaction, for the synthesis of novel biopolymers with a broad range of potential medical/industrial applications. The strategy is to develop a powerful tool for the synthesis of libraries of materials, which will be discussed in separate chapters.
Chapter one is a general introduction on biopolymers and Click chemistry with emphasis on the related literature to the present work.
Chapter two involves the application of Click chemistry on model compounds; 3-methyl benzyl alcohol and phenol. The resulting products were successfully prepared via Click chemistry. NMR spectroscopy was found to be a good choice for characterisation of the resulting products.
Chapter three describes the application of Click chemistry on a disaccharide compound, α,α-D-trehalose. The di-azide functionalised trehalose was synthesised by tosylation followed by acetylation and subsequent reaction with sodium azide. Different functionalities such as ester, acrylate and epoxide groups were successfully introduced via Click chemistry. NMR and FT-IR spectroscopies were found to be efficient characterisation tools to follow up the Click modification reactions. The di-acrylate functionalised trehalose showed a great potential as a cross-linker in the free radical polymerisation of HEMA to generate hydrogels.
Chapter four presents the utilisation of Click chemistry to produce trehalose-based glycopolymers which have a wide range of potential applications. Biodegradable glycopolymers containing PCL or PLA were synthesised via combination of ring opening polymerisation (ROP) and Click chemistry. The ROP of lactide and ε-caprolactone, using stannous octoate and propargyl alcohol, was carried out to synthesise alkyne end capped PLA and PCL which were then coupled with di-azide
functionalised trehalose by Click reaction. NMR and IR were used to prove the structure of the materials. A new class of temperature responsive glycopolymers was also synthesised via copper wire catalysed Click-polymerisation of di-azide
functionalised trehalose with di-alkyne terminated PEG. The cloud point of the aqueous solution of glycopolymer was evaluated and showed an LCST at ~39 oC, known as fever temperature. In addition, the phase transition was shown to be reversible.
Chapter five involves the modification of 2-hydroxyethyl cellulose (HEC) via Click chemistry. For the first time, the azide functionalisation reaction of HEC was disclosed using a one pot reaction procedure. Neutral and ionic compositions of HEC were successfully synthesised by introducing different functionalities on HEC. The compositions containing carboxylic acid or 1ry amine functionalities can be treated in basic or acidic media to give polyelectrolytes based on HEC. The compositions containing both functionalities, carboxylic acid and 1ry amine, could produce polyampholytes. Sequential Click reactions were implemented to synthesise polydimethylsiloxane (PDMS) grafted HEC as well as potentially charged functionalities. These compositions are expected to receive a great interest in personal care and cosmetics applications. Mainly, solid state 13C-NMR and FT-IR spectroscopies were used to characterise these materials. Hydrophobically and hydrophilically modified HEC were also prepared by grafting PLA, PCL or PEG onto HEC using Click coupling reaction. AFM analysis showed that some exhibit a brushlike architecture.
Chapter six describes the combination of Click chemistry and ROMP to synthesise various graft polymers. Two different grafting techniques; "grafting through" (the macromonomer approach) and "grafting onto" were involved in the synthesis. The "grafting through" method involved the synthesis of oxanorbornenyl di-PEG macromonomer by Click coupling of azide terminated PEG with di-alkyne functionalised oxanorbornene. The macromonomer was then subjected to ROMP to produce PEG grafted polyoxanorbornene. Polynorbornene-g-PCL and polynorbornene-g-PEG were prepared by "grafting onto" process. This was achieved by ROMP of bromide functionalised norbornene followed by reaction with sodium azide and then Click reaction with alkyne terminated PCL and PEG. The surface analysis of these graft polymers were studied using AFM. Random graft copolymer containing PEG and PCL side chains was also prepared by ROMP of a mixture of oxanorbornenyl di-PEG and bromide functionalised norbornene followed by reaction with sodium azide and then
Click reaction with alkyne end capped PCL.
Chapter seven entails general conclusions and suggestions for future work.