Polylactide (PLA) is a biodegradable and biocompatible alternative to traditional petrochemicalbased polymers. Synthesised by the ring-opening polymerisation of lactide (LA), the dehydrated form of lactic acid, PLA sits within a renewable cycle, and can be used in many commodity and biomedical applications. The intrinsic stereochemistry of LA can lead to a variety of polymer microstructures, and current industrially used initiators allow no control over this. Within this thesis a series of investigations into the use of amine tris(phenolate) metal complexes as stereoselective initiators for the ROP of LA are discussed. Chapter 1 introduces the field of ring-opening polymerisation (ROP) via a coordination insertion mechanism, presents previously reported initiators, and examines the influence of stereocomplexation on the physical properties of PLA chains. This introductory chapter also includes an in-depth review of recent developments in poly(phenolate) complexes of Group 4 and rare earth metals. Chapter 2 describes the synthesis of a series of isopropoxide and zwitterionic Group 4 complexes featuring the amine tris(phenolate) ligand motif, with emphasis on the effect of ligand variation on complex structure. The potential of the resulting complexes as initiators for the ROP of LA is also investigated, with in depth kinetic studies allowing for a proposed diastereoselective mechanism of stereocontrol. Chapter 3 details the synthesis of a series of borohydride and amide Group 4 amine tris(phenolate) complexes, and investigates their potential as initiators for the ROP of rac-LA. Chain-end analysis and kinetic studies are included, providing the basis for mechanistic discussions. Chapter 4 focuses on the synthesis of stereoblock PLA materials in a stereospecific manner, and co-block PLA-PEG materials by the reinitiation of short-chain macroinitiators. The effect of stereocomplexation on the thermal properties of these materials is investigated. Chapter 5 concerns the synthesis of a series of isopropanol and zwitterionic rare earth complexes featuring the amine tris(phenolate) ligand motif. The potential of these complexes as initiators for the ROP of rac-LA is also investigated, but only slight stereocontrol was observed in selected cases. Chapter 6 provides details of procedures employed in the synthesis of ligands, complexes and polymers within this thesis, as well as details of the analytical techniques used in their characterisation.

Polyamides are versatile polymers and includes naturally occurring macromolecules such as proteins as well as purely synthetic materials such as Nylon-3 and Nylon-6 polymers. While there are different ways to prepare polyamides, polyamide synthesis using anionic ring opening polymerization of lactams is the most widely used technique, due to the ease in preparation, excellent control in molecular weight and availability of wide variety of monomers. Our group reported the preparation of carbohydrate-based polyamides called poly-amido-saccharides (PASs) using anionic ring opening polymerization of sugar b-lactam monomers. The PASs reported so far includes glucose, galactose, altrose and maltose PASs, and functional PASs with n-octyl, carboxylate and amine functionalities. Sulfated or block poly-amido-saccharides on the other hand are unknown. In this thesis, I describe the synthesis of sulfated and block poly-amidosaccharides as well as evaluation of their biomedical applications. Naturally occurring sulfated polysaccharides play important roles in anticoagulation, lubrication of cartilage, and in developmental processes. New glucose-based non-regioselectively and regioselectively sulfated poly-amido-saccharides are prepared by the polymerization of protected glucose b-lactams, followed by post-polymerization modification reactions. All polymers are water soluble, non-cytotoxic, and adopt helical conformations. I evaluated the anticoagulant activity of the sulfated polymers using in vitro, ex vivo, and in vivo methods as well as determined the mechanism of anticoagulation by amidolytic activity inhibition assays. Additionally, I synthesized new block copolymers as block copolymers are used for various applications including latex paints and pressure sensitive adhesives. Specifically, carbohydrate-based amphiphilic polymers are of interest for drug delivery applications, due to favorable properties such as cytocompatibility, low immunogenicity, and longer circulation time. We prepared PAS-based amphiphilic block polymers with varied polymer length, hydrophobic to hydrophilic ratio, and stereochemistry of hydrophilic component. I characterized these amphiphilic polymers by NMR, IR, GPC, DSC, TGA and CD, and they self-assemble in water to form nanostructures as determined by DLS, SEM, and cryo-TEM, and are non-cytotoxic. / 2024-11-16T00:00:00Z

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