Cocrystals have generated a lot of interest due their ability to influence: physiochemical properties, optical properties etc. These properties are important in the pharmaceutical and food industry. In this thesis, the scale up of cocrystal synthesis is studied using a novel slurry cocrystallisation approach involving an anti-solvent and solvent mixture. The anti-solvent composition is typically > 97 %, with the solvent comprising the rest. This counter-intuitive approach resulted in > 95 % caffeine-oxalic acid cocrystal yield in less than 2 hrs. The mixed anti-solvent/solvent approach was applied successfully to four other cocrystal systems and a salt. The level of caffeine-oxalic acid cocrystal yield observed varied with the solvent used in the mixture. Using statistical analysis, it was shown that the hydrogen bonding Hansen solubility parameter (δH) of the solvent and oxalic acid solubility were the two most important factors for increasing cocrystal yield. The parameter Ra/(Oxalic acid) , however, showed even better correlation (94.2 %) with caffeine-oxalic acid cocrystal yield than both δH (78 %) and oxalic acid solubility (88 %). Ra is the Hansen solubility distance between the solvent and the coformer (oxalic acid) and includes all three Hansen solubility parameters (δD, δP, δH). Four new cocrystals (A-D) of 2-aminopyrimdine-glutaric acid were crystallised from three different solvents and their crystal structures reported. Two of them (A and B) are 1:1 polymorphs. The glutaric acid molecule in A has a linear conformation but it is twisted in B. Variable temperature PXRD analysis indicates that A and B are monotropic polymorphs, with A transforming to B at ≈73C, prior to the melting of B. D is a cocrystal-salt hybrid. D was crystallised from the same solvent as cocrystal B supporting the idea of a cocrystal-salt continuum when both the neutral and ionic forms are present in appreciable concentrations in solution.

This thesis describes the development of a range of polydentate phosphorus-containing ligands relevant to catalysis. The focus is on developing a fundamental understanding of how changes to the substituents on a ligand impact on the environment at a coordinated metal centre. Chapter 2 reports the synthesis and coordination chemistry of the phosphine-alkene ligands N-R2P-7-aza-benzobicyclo[2.2.1]hept-2-ene, R = Ph (2-1) and iPr (2-2). The electronic properties of 2-1 and 2-2 are probed by a variety of methods, which reveals them to be electron deficient. The coordination chemistry of 2-1 to various transition metal fragments is then explored, exhibiting a range of coordination geometries including tetrahedral ([Ni(κ2-P,C-2-1)2] (2-6)), square based pyramidal ([RhCl(κ2-P,C-2-1)2] (2-7)) and trigonal bipyramidal ([IrCl(κ2-P,C-2-1)2] (2-8)). Chapter 3 introduces the problem of slow reductive elimination in some palladium-catalysed catalytic transformations along with methods of promoting this process, before describing the application of the electron deficient 2-1 in enhancing reductive elimination reactions. A detailed study of the formation of ethane by reductive elimination from a palladium dimethyl complex of phosphine-alkene ligand 2-1 has been undertaken. The mechanism of this process has been probed by a combination of experimental and computational studies and revealed that the mechanism proceeded via an associative mechanism through a 5-coordinate intermediate. Chapter 4 describes the synthesis and systematic study of the steric and electronic impact of a range of POCOP pincer ligands 1,3-{(tBu2PO)2C6H4} (4-1) and 1,3-{(R2PO)2C14H20}, R = tBu (4-7), OiPr (4-8), NEt2 (4-9), morpholine (4-10) and pyrrole (4-12). The coordination chemistry of these ligands is then appraised to probe the steric impact of the ligand crystallographically. Subsequently, the electronic impact of the ligands are assessed by 31P{1H} NMR and infrared spectroscopy of the corresponding phosphine selenide compounds and palladium carbonyl complexes. Chapter 5 reports exploratory reactions of a novel palladium hydride complex [PdH(κ3-P,C,P-4-1)] (5-1). The insertion of C=C (ethylene) and C=O (acetone, CO2) bonds into the Pd-H bond of 5-1 is attempted, notably showing facile insertion of CO2 to form the metal formate complex [Pd(OC(H)O)(κ3-P,C,P-4-1)] (5-4). Complex 5-1 is shown to be a catalyst for palladium-catalysed alkene isomerisation and aldehyde hydrosilylation, but the activity in both reactions is low.

In order to reduce reliance on fossil oil, and it’s associated problems, there is a need to develop new platform chemicals, fuels and products, in a sustainable way, from biomass. In this thesis the catalytic upgrading of fatty acids, derived from the lipid fraction of biomass, through deoxygenation reactions is studied. Chapter 1 reviews the general area of catalytic upgrading of biomass into biofuels and bioproducts. The history and motivation for alternative sources of fuels and materials are introduced, followed by a summary of the reaction processes currently utilised for biofuels and bioproducts production. It is shown that the demand for alternative fuel sources initially led to the mass commercial production of ethanol, via fermentation of sugars, and biodiesel, through trans-esterification of lipids present in vegetable and algal oils. A selection of the catalysts and mechanisms for trans-esterification reactions is reviewed and, following an outline of the fuel properties and processes, an evaluation of “green diesel” production is given, whereby fatty acids are converted directly into hydrocarbons through decarboxylation reactions. This review culminates in an analysis of alternative conversion of fatty acids into long chain ketone bioproducts, namely ketonic decarboxylation, which details the catalysts and processes involved to date. Chapter 2 describes the analytical methods utilised in this thesis to investigate heterogeneous catalysis of biomass conversion, along with the relevant background theory and describes the type of data that can be obtained using the techniques. The techniques include powder X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, inductively coupled plasma optical emission spectroscopy, surface area analysis, Hammett basicity, elemental analysis, Fourier-transform infra-red spectroscopy and gas chromatography. Chapter 3 introduces a class of materials known as layered double hydroxides (LDHs) of general formula Mz+1–xM3+x (OH)2]q+(Xn–)q/n•yH2O. The ease with which these mixed oxide materials may be prepared offers significant scope for the variation of the metal cations; the M2+:M3+ ratio (denoted R-value); the counter anion(s); and crystal morphology. These LDHs consist of positively charged layers, with negatively charged counter-anions and water residing in the interlayer. A review of the commonly used synthesis methods for LDHs is given, along with the advantages and disadvantages associated with each method. Following this, the synthesis of the Mg-Al LDHs and their calcined counterparts, mixed metal oxides (MMOs) (for R-values 1-6) via a readily scalable co-precipitation (CoP) and a more environmentally-friendly co-hydration (CoH) route is described. A range of techniques, outlined in chapter 2, are utilised to study the LDH and MMO crystal and chemical structures, surface topography, surface area, pore volume and relative basicities. The crystal structures of two of the CoP-LDHs were refined to the 3R-polytype using DICVOL, however the other LDHs were not significantly ordered and could not be refined. Upon calcination from LDHs to MMOs, the interlayer counter-anions and water are lost, along with the layered structure, leading to a commensurate increase in surface area and pore volume. In chapter 4, investigations undertaken to deoxygenate stearic acid, a free fatty acid model biomass compound, are described. As a catalyst, 5 % Pd/C was used, adapting a method found in the literature. These reactions were undertaken at 230 °C, with decarboxylation of stearic acid producing straight-chain n-heptadecane at up to 58 % conversion by gas chromatography analysis. However, in this study, issues arose due to catalyst instability and an ensuing loss of catalyst activity was observed. In chapters 5 and 6, to increase catalyst stability and recyclability, while also reducing costs relative to the Pd/C catalyst used in chapter 4, (due to the use of precious metals), LDHs and their calcined derivatives, MMOs, were utilised for deoxygenation of the model stearic acid biomass. Thermal reactions of stearic acid controls, without catalyst, were not observed to occur, however, stearic acid conversions between 83-97 % at 250 °C were observed to occur with both LDH and MMO catalysts. However, unlike the Pd/C reaction, no decarboxylated product was evidenced and, instead, a waxy solid formed, which was subsequently analysed and found to be the ketonic decarboxylation product, stearone. A protocol was developed to separate the stearone from the catalyst. Gas chromatography analysis showed the LDH and MMO materials catalysed the conversion of stearic acid to a similar degree, allowing for the error within the extraction and analysis processes employed. The reasons for similarity in reactivity are discussed, and it is suggested that an intermediate state of catalyst is present in the reactor. Comparing synthesis methods, the CoH materials were as effective as their CoP counterparts, despite the presence of Mg(OH)2 secondary-phases. Within the LDH phases, an indication of catalytic dependence on pore size was also recorded, with the smaller pore-sized materials leading to lower conversions of stearic acid, resulting from the bulky size and required head alignment of the long-chain fatty acid molecules. In terms of control reactions, calcined MgO led to 90 % conversion of stearic acid to stearone, however very little reaction occurred with uncalcined MgO (0.5 %) and zero reaction with the acidic Al2O3 (both uncalcined and calcined). Hence activated MgO is also an effective catalyst for ketonic decarboxylation. Chapter 7 summarises the results and discussion given within this thesis, highlighting the milestones achieved such as the first ketonic decarboxylation reactions involving MMO catalysts and concluding that LDHs and MMOs catalyse the conversion of stearic acid via ketonic decarboxylation of free fatty acids to high value ketones, to a similar degree, within the associated errors. In addition the LDH synthesis method employed does not play a significant role in the degree of catalysis, resulting in the recommendation that the more environmentally-friendly co-hydration synthesis method should be employed for the catalyst involved in the conversion of stearic acid derived from biomass. The MMO catalysts were found to behave akin to the calcined MgO material during the ketonic decarboxylation of stearic acid, while the catalytic reactions involving LDH catalysts were potentially involving the interaction of their interlayer anions and cations. Finally, a summary of additional work for further developing this process is discussed.

This thesis details the synthesis, characterisation and photophysical properties of various fluorinated emitters for triplet-triplet annhilation up-conversion systems. The theory and mechanism of TTAUC is evaluated and the molecular design of the annihilating emitter molecule reviewed to allow improvement of the external up-conversion quantum yield and overall energy efficiency of the process. Three main series of chromaphores were investigated, based on diphenylanthracenes, bisphenylperylenes, and 3,5,8-triphenylBODIPYs. These were synthesised by metal catalysed aryl-aryl coupling (Suzuki-Miyaura) or nucleophilic substitution reactions and, when paired with appropriate sensitizing molecules, allowed the up-conversion of green to blue; red to green; and near IR/red to orange respectively. The effect of increasing fluorination on the ease of synthesis and photophysical properties of these emitter systems was studied with a view to their application in up-conversion systems. Fluorinated emitter molecules were shown to be highly resistant to degradation by UV light compared to their non-fluorinated analogues. The up-conversion ability of these systems was evaluated and novel fluorinated BODIPY based dyes were produced that have high fluorescence quantum yields of over 90%. Finally the up-conversion of up-converting nanoparticles incorporating fluorinated emitters was evaluated.

We have developed a flexible approach to the synthesis of surfactants with an ‘Anchor Linker-Head’ (ALH) architecture. These ALH surfactants are designed for the dispersion of multi-walled carbon nanotubes (MWNTs) and exfoliation of graphite in water. Four series of surfactants have been synthesised, all with a pyrene anchor group, which binds strongly to graphitic surfaces through π-π interactions, and hydrophilic head groups based on a carboxylate moiety, carboxylate dendron, crown ether or podand. These are joined by oligoethylene glycol (OEG) linker groups. The anionic surfactants PyrB-PEGn-CH2COONa (n = 2, 4, 6, 12) PyrB-PEGn-CH2COG1(ONa)3 (n = 2, 4, 6) all disperse MWNTs at least as well as commercial surfactants in Millipore water and achieve higher dispersion levels than comparable amide linker surfactants. Non-ionic surfactants are more effective, dispersing up to 61% of the MWNT feedstock. Exfoliation of graphite has been achieved using anionic and non-ionic surfactants. We examined the effect of salts, including NaCl, KCl and CaCl2, on the ability of surfactants to disperse MWNTs and found the choice of linker and head group to be significant. MWNT dispersing ability in 0.6 M NaCl increases with OEG linker length. Structural variation gives surfactants which show improved, reduced, or comparable dispersion levels in 0.6 M NaCl vs. Millipore water, due to the effects of ionic screening and cation coordination. MWNTs dispersed using anionic surfactants can be precipitated by addition of acid, and re-dispersed by addition of base. Eleven non-ionic surfactants have a lower critical solution temperature (LCST), which is tuned by structural changes. We demonstrate using PyrB-PEG4-CH2CO(15-c-5) that LCST surfactants with a pyrene anchor can be used to repeatedly and reversibly precipitate dispersed MWNTs without harsh re-processing. We believe this to be the first report of such behaviour using a small molecule dispersant.

This thesis tackles several two-component liquids where we currently have a poor understanding of their fundamental structures and influence on properties. A novel approach was taken to investigate hydrophobic interactions.1 Rather than studying the aqueous liquid, for which only very low hydrophobe concentrations are possible, the metastable glassy state formed by thermally annealing a H2O/C60 fullerene vapour deposit was examined. These ‘trapped solutions’ of fullerene in an amorphous solid water (ASW) matrix were prepared in newly built apparatus (Chapter 3) using deposition rates of about 5 H2O monolayers per second to give a total mass > 1 g without crystalline ice contamination. H2O desorption rate analysis indicated that the limits of ASW growth are associated with the influence of deposition rate on porosity and consequent decreases in deposit to cooling plate heat transfer with increasing deposit thickness. Characterisations by FT-IR, Raman, optical absorbance and photoluminescence spectroscopies, as well as by X-ray and neutron diffraction showed unexpected continual structural relaxation until their crystallisation to ice I at 150–160 K (Chapter 4).2 Contrary to Frank and Evans’s description of ‘iceberg’ hydration structures,3 for C60 in ASW there is a weakening of the average hydrogen bonding interaction and increases in dynamics of the first hydration layer. The present work tentatively supports theories of hydrophobic hydration forces involving a disconnection of water in the hydration shell from the extended hydrogen bonding network (Chapter 5).4-5 The intermolecular interactions in the chloroform–acetone (negative) and benzene–methanol (positive) azeotropes were investigated by Raman spectroscopy and neutron diffraction. Structural models of pure liquid chloroform and the chloroform-acetone azeotrope were prepared by Empirical Potential Structural Refinement6 of experimental data and described using radial distribution functions, spatial density functions, orientation correlation functions and Kirkwood correlation factors. These analyses revealed that ‘super dipole’ Cl3H - Cl3H - Cl3H self-associations in pure liquid chloroform (29 % molecules) may contribute to its good solvent quality and anaesthetic properties (Chapter 6),7 and that C2H6O - HCCl3 hydrogen bonding interactions are present in the chloroform-acetone azeotrope (Chapter 7). Through comparisons of radial distribution functions between ‘like’ and ‘unlike’ species in the azeotropes it is revealed that the azeotropic vapour pressure condition is not only characterised by the non-ideality of intermolecular interaction but also by significant deviations in mixing character from that of a regular mixture; the benzene-methanol azeotrope exhibit microscopic statistical demixing and the chloroform-acetone azeotrope exhibits transient complexation.

This thesis is concerned with the synthesis of a range of perfluoroalkylated monomers that can be used as ‘drop in’ additives in commercial paint coatings, with the aim of improving coating lifetime and performance.

1,1-Diphenylethylene (DPE) and functional derivatives of DPE have been used to prepare a variety of novel copolymers by living anionic polymerization. This research focuses on exploiting reactivity ratios to prepare copolymers with a variety of structures including alternating, tapered, statistical and telechelic copolymers. The copolymers were analysed by a variety of techniques including 1D and 2D NMR spectroscopy, MALDI-ToF mass spectrometry, differential scanning calorimetry and transmission electron microscopy.

Retinoids are a class of signalling molecules that includes vitamin A along with its natural and synthetic analogues. Retinoids regulate important biological pathways from embryogenesis through to adult homeostasis, and influence the proliferation and differentiation of a variety of cell types. The effects of retinoids are primarily mediated through binding to and activation of the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Three subtypes of RARs exist: RARα, RARβ and RARγ. Isoforms for each of these receptor subtypes are known, with the RARβ2 isoform in particular known to stimulate neurite outgrowth. The design of isoform-selective ligands is thus an important area to allow investigation into the mechanism of activity of the individual RAR isoforms. Syntheses of the proposed RARβ2 agonists containing phenyl- and tetramethyltetrahydronaphthyl-substituted side chains are described herein. These thiazole-containing small molecules were assessed for activity in inducing the differentiation of human pluripotent TERA2.cl.SP12 embryonal carcinoma (EC) cells, with the more bulky tetramethyltetrahydronaphthyl analogue able to induce differentiation of this cell line to a level comparable to that of the natural retinoid, ATRA. Furthermore, at 0.1 µM, this analogue promoted enhanced neural commitment and neurite outgrowth over ATRA, with levels similar to that observed with the synthetic retinoid EC23. The second part of this thesis concerns the synthesis of a fluorescent retinoid, GZ108, and preliminary assessments of its fluorescence and biological activities. In an effort to optimise the synthetic route and to improve compound stability, the preparation of N-acetyl, amide, and oxazoline analogues are also discussed.

As the world population rises and the availability of land for cultivation decreases, there is an ever-growing demand on food production. However, the persistent use of herbicides in order to sustain food production has resulted in the emergence of resistance. The most serious form of resistance is multiple herbicide resistance (MHR) in which plants become resistant to all herbicides regardless of their mode of action. Previous work involving the weed black grass identified a key glutathione S-transferase (GST), AmGSTF1, involved in the development of MHR. Small molecule inhibitors of the benzoxadiazole motif have been shown to disrupt the function of this enzyme and consequently suppress resistance. This work describes the synthesis of 4-substituted-7-nitrobenzofurazan derivatives and structurally related 6-halopurine analogues to investigate SAR. Assessment of these compounds through in vitro and in vivo studies revealed that alkoxy and thiol leaving groups were preferred for activity in the benzofurazan series, whilst 8-substituted-6-halopurine analogues were favoured in the purine series. However, no significant enhancement in activity over the parent structures was observed with these pharmacophores. Further studies identified a new class of small molecule inhibitors through ligand fishing in which AmGSTF1 was immobilised on a streptactin column and washed with a cocktail of inhibitors. This method revealed flavonoid compounds to be potent binders of AmGSTF1. The subsequent synthesis and SAR evaluation of flavones highlighted 5,7-dihydroxyflavone as a key pharmacophore. Additional work revealed a fatty acid quercetin derivative to be a potent inhibitor of AmGSTF1, and was subsequently shown to be capable of synergising the effects of herbicides in MHR black grass.