A novel catalysis platform has been developed that provides facile access to complex N-heterocyclic scaffolds via the generation and trapping of amino-substituted rhodacyclopentanones. A directing group-based strategy was employed that enabled regioselective generation of the desired rhodacyclopentanone intermediates from readily accessible substituted amino cyclopropane precursors. Incorporation of this strategy into a multicomponent protocol resulted in the development of (3+1 +2) cycloadditions between aminocyclopropanes, CO and tethered alkynes to deliver N-heterobicyclic enones. Studies exploring the reactivity of different Rh(I)-catalyst systems enabled expansion of the scope to highly diastereoselective (3+ 1 +2) carbonylative cycloadditions involving tethered alkenes. In this system, a novel strategy for achieving diastereocontrol was developed that relies upon reversible C-C bond activation and allows the synthesis of 'Sp3 -rich' chiral scaffolds. Integration of the n-unsaturated component with the directing group provided a new synthetic approach to azocane ring systems from acryloyl-substituted aminocyclopropanes. Studies towards the total synthesis of phantasmidine have been conducted and a synthetic route to the substrate required for the key catalysis step was established. In relation, the carbonylative ring expansion methodology was examined with the aim of developing an enantioselective route to aminocyclobutanones, however, at present, these studies have been unsuccessful.

Oligo(aniline)s (OAs) with at least four aniline units have analogous redox and doping properties to their parent poly(aniline) systems. Recently, the use of straightforward organic synthesis methods to introduce well-defined functionalities in OA molecules has been reported. Materials based on these functionalized OAs retain the properties exhibited by the parent polymer and show enhanced propel1ies such as processability and crystallinity. Moreover, a systematic control over these functionalities has yielded materials with tunable optoelectronic properties. In this thesis, OAs covalently functionalized with bio-inspired building blocks (biomotit) are used to form materials with well -defined assembly propel1ies. Short molecular weight biomolecules with well understood self-assembly properties are promising building blocks for the formation of specific supramolecular assemblies with anisotropic properties. Among these molecules, dipeptides and purines assemble into well -defined anisotropic morphologies, such as fibre-like nanostructures, by changing simple experimental conditions like concentration, solvent polarity and pH. The present research project aims to a) develop an effective synthetic strategy to yield OAs covalently functionalised with biomotifs, . i.e., dipeptides and guanine, b) the characterisation of their electroactive propel1ies, i.e., doping acid, and c) their self-assembly properties to produce anisotropic assemblies, i.e., nanofibres. The results demonstrate that OAs can be functionalized with biomotifs, i.e., dipeptides and guanine, using a Buchwald-Hartwig amination coupling reaction. The optimisation of the reaction conditions is strongly dependent on the chemical structure of the starting precursors, i.e., unprotected amine, imine, amide and carboxylic groups. The two series of as-synthesised biomotif-functionalised diblock OAs with different endfunctionalised biomotifblocks were doped with stoichiometry portions of acid dopant. These results demonstrate the retention of electroactive properties in the OA-based block after functionalization with biomoitifs.

This thesis describes investigations into metal-catalysed and metal-free dehydrogenation routes of amine-boranes.

Hen egg-white lysozyme (HEWL), a paradigmatic glycoside hydrolase (GH), is a retaining β-glycosidase catalysing the cleavage of β-glycosidic bonds found in the cell wall of Grampositive bacteria. Despite extensive research, the nature and role of substrate distortion in catalysis is still unclear. Here, MM and QM/MM modelling was performed on a HEWL trisaccharide (NAM-B-β(1→4)-NAG-C-β(1→4)-NAM-D) product complex to investigate distortion and reactivity of the NAM-D ring bound in the -1 site of the enzyme.

Palladium- and copper-catalysed aza-Heck cyclisations of oxime esters with pendant olefins, have been developed for the synthesis of chiral nitrogen heterocycles. Initial studies explored palladium-catalysed cyclisations onto 1,1-disubstituted alkenes to afford α,α-disubstituted dihydropyrroles. A wide range of functional groups are tolerated in this process, showcasing the versatility of this approach. A complementary copper-catalysed aza-Heck has also been developed. Mechanistic studies of these two processes revealed two distinct pathways. Cyclisations employing an electron deficient palladium catalyst proceed via oxidative addition of Pd(O) into the N-O bond of the oxime ester to generate a key imino-Pd(II) intermediate. Migratory insertion of the olefin into the Pd-N bond and subsequent β-hydride elimination delivers α,α-disubstituted dihydropyrroles. Under copper-catalysed conditions, cyclisations proceed via a radical type pathway, involving oxidative initiation at the N-O bonds of oxime esters to generate an iminyl radical or radical-like species. After cyclisation, an alkyl-radical is generated which undergoes oxidative elimination to afford the Nheterocyclic products. An enantioselective palladium-catalysed aza-Heck cyclisation is also described herein. Employment of spirocyclic P,N-based SIPHOX ligands is crucial for efficient cyclisation, which delivered enantioemiched α,α-disubstituted dihydropyrroles in high yield and enantioselectivity. In an alternative strategy for achieving alkene 1,2-carboaminations, cascade aza-Heck cyclisations have been developed. Aza-Heck cyclisation of oxime esters enables access to a versatile alkyl-Pd(II) species, which can be trapped with a variety ofnucleophiles. Olefin 1,2-amino-acylation -carboxylation, -arylation, -vinylation and -alkynylation reactions have been established. An ambitious palladium-catalysed aza-Heck cascade cyclisation has been proposed for the total synthesis of (+)-cylindricine C and studies have examined three key aspects: 1) azaHeck spirocyclisation of oxime esters, 2) asymmetric aza-Heck cyclisations and 3) a carbonylative cascade of oxime esters. Proof-of-concept has been achieved on model substrates and fmiher research is ongoing to realise this challenging total synthesis.

Many of the roles of carbohydrates in biology derive from their interaction with proteins, through which they effect intra- and intercellular signalling and the modulation of the structure and activity of proteins. Understanding proteincarbohydrate interactions in atomistic detail is essential to allow the manipulation and exploitation of these processes. The first part of this thesis utilises the many published protein X-ray crystal structures that contain carbohydrates. A database of protein- carbohydrate interactions was generated to elucidate the nature of carbohydrate-based interactions at the atomistic and molecular levels. The particular focus is on the carbohydrate-aromatic interaction, involving the positioning of aromatic aminoacid side chains over carbohydrate C-H bonds. This reveals an important role for electrostatics in carbohydrate-aromatic interactions, and in CH-1[ interactions in general, which is distinct from the hydrophobic effect. These findings are supported by solution-phase studies of carbohydrate-aromatic interactions by NMR spectroscopy. The second part describes the development of carbohydrates as tools for tissue engineering, given the recognised importance of carbohydrates in both signalling and structural roles in biology. The nature of the scaffold upon which artificial tissues are grown is of great importance, as the cellular environment influences development through its physical properties and the presence of biological cues. Carbohydrates are a promising and largely under-exploited class of biomolecules with the potential to modulate material properties and stimulate biological responses. A modifiable derivative of a system based upon complementary synthetic peptides that self-assemble into hydrogels was used as the core scaffold. This was functionalisable with biological cues via copper I click' chemistry. Alkynyl monosaccharides were synthesised and used to verify the applicability of carbohydrates as modifiers, both in terms of maintaining the key properties of the hydrogel and providing an appropriate support for cell culture. Enzymatic techniques enabled synthesis of complex alkyne-functionalised oligosaccharides chosen to be applicable to neural tissue engineering.

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