Several new mixed-metal analogues of MIL-53 have been synthesised using iron and vanadium. The properties of the mixed-metal materials are affected greatly by the ratio of the two metals. Analysis of the EXAFS spectra of a mixed-metal MIL-53(Fe, Cr) sample was performed supporting the homogeneity of the material. The investigation of mixed ironcobalt materials was also studied. Several new lanthanide-organic frameworks are described. Through mediation of the reaction solvent and subsequent calcinations, several new ytterbium-organic frameworks have been synthesised and their properties investigated. Using a solvent mixture of between 1:0 and 6:4 DMF to water leads to the formation of MB2, [Yb2(BDC)3(DMF)2]∙2H2O, which contains ytterbium-carboxylate chains. Calcination of MB2 creates Yb2(BDC)3, a material that exhibits permanent porosity. Further decreasing the DMF to water ratio in synthesis leads to the formation of MB3, [Yb2(BDC)3(DMF)2(H2O)2], which contains ytterbium-carboxylate dimers. Although sharing similar chemical formulae, MB2 and MB3 vary greatly in terms of structure and properties. Despite of this, both MB2 and MB3 can be calcined into the same Yb2(BDC)3 material, seen from the calcination of MB2. Attempts to create analogues of MB2 and MB3 using other lanthanides were unsuccessful with the exception of lutetium. In spite of this, doping of MB2(Yb) with other lanthanides was successful and their luminescence properties studies. Synthesis of isoreticular analogues of MB2 and MB3 were partially successful with an isoreticular analogue of MB3, MB5, being formed. Crystallisation of several metal-organic frameworks were followed using both ex situ and in situ methods and it was shown these two sets of techniques can complement one another to enable the pathways of MOF formation to be monitored.

This thesis explores the synthesis of nucleobase-containing polymers by both reversible addition-fragmentation chain transfer (RAFT) polymerization and RAFT dispersion polymerization. In addition, self-assembly behavior of nucleobase-containing polymers is also described. Chapter 1 introduces main concepts and techniques used in this thesis. In addition, the study of nucleobase-containing materials is reviewed. Chapter 2 describes the synthesis of nucleobase-containing monomers and the use of RAFT polymerization to prepare nucleobase-containing homopolymers and copolymers. Moreover, the effect of nucleobase-interactions on the resultant copolymer composition was investigated in chloroform and DMF. Chapter 3 investigates RAFT dispersion polymerization of adenine-containing methacrylate monomer and a 1:1 mixture of adenine-containing and thymine-containing methacrylate monomers in both chloroform and 1,4-dioxane. Nucleobase-containing polymers with relatively good control were obtained and a range of nanostructures were observed that were solvent dependent. Chapter 4 investigates RAFT dispersion polymerization of a thymine-containing methacrylate monomer, which displayed different self-assembly behavior to the observations in Chapter 3. A range of parameters affecting the resultant morphologies was additionally studied. Chapter 5 investigates the self-assembly behavior of nucleobase-containing polymers in aqueous solution mainly using a solvent-switch method. Chapter 6 provides a summary of the key findings of Chapters 2 – 5 and outlines the further work.

Developing new routes towards precision and function in materials synthesis and properties / Dafni Moatsou This thesis explores three methods for the synthesis of materials with precise sequence and functions. Chapter 1 gives a brief introduction to the main concepts that underpin the methods used throughout the thesis. Chapter 2 examines the use of norbornenes for the synthesis of precision polymers via ring-opening metathesis polymerization by taking advantage of the different reactivity of different isomers of the monomers. Chapter 3 suggests the use of dioxepins for single monomer insertion in the ringopening metathesis polymerization of norbornenes. Chapter 4 describes the synthesis of a temperature-responsive protein-polymer bioconjugate and the study of its properties. Chapter 5 evaluates the synthetic parameters of L-proline-containing nanogels as a function of their ability to catalyze organic reactions. Chapter 6 discusses the attempt to modulate the cross-linking of nanogels by a photoreactive cross-linker based on thymine.

Animals, plants and bacteria can survive sub-zero environments by using specialist proteins that inhibit ice growth. There has been a great deal of work into trying to understand and exploit these proteins for use in cryopreservation, but several strategies fail as the protein’s mechanism for ice growth inhibition causes ice to grow into needle-like crystals, which cause mechanical damage to the cryopreserved material. A range of studies have shown that this shaping can be removed, without affecting ice growth inhibition activity. Synthetic mimics exist, the most interesting being the simple polymer, poly(vinyl alcohol), which alone amongst other synthetic macromolecules displays ice growth inhibition behaviour. The scientific principles behind ice growth, and the molecules that can inhibit this, are detailed in Chapter 1. Chapter 2 examines how the molecular weight of poly(vinyl alcohol) affects ice recrystallisation inhibition activity, and the importance of hydroxyl sequence, using post-polymerisation modification and co-polymerisation. Chapter 3 details the preparation of well-defined block co-polymers of poly(vinyl alcohol), and confirms the importance of the hydroxyl sequence. These polymers maintained their ice recrystallisation inhibition activity despite the addition of large non-active blocks. Chapter 4 demonstrates the synthesis and utility of a novel multifunctional chain transfer agent, which is used to prepare star polymers. The resultant star-poly(vinyl alcohol) was highly active, and activity profiles of these polymers provided further evidence that the mechanism of ice recrystallisation inhibition by poly(vinyl alcohol) does not involve direct binding to ice. Chapter 5 uses the techniques and methodologies developed in Chapter 2 and applies them to another lesser-known ability of poly(vinyl alcohol); thermoresponsivity. In summary, controlled radical polymerisation of vinyl acetate was employed in a range of different ways to prepare poly(vinyl alcohol) and its various co-polymers. These polymers were then tested for ice recrystallisation inhibition. Due to their well defined physical properties, and advanced architectures, new insights into the nature and mechanisms of their activity were available. This mechanistic understanding, and the materials developed for this thesis, display a great deal of potential in expanding the field of cryopreservation.

Mammalian skin is a highly-specialised organ, providing a robust barrier against environmental challenges. In order to maintain functional integrity and a healthy state, the skin’s constituent tissues undergo continuous renewal, controlled by finely-controlled homeostatic mechanisms. Skin disease is incredibly common, ranging from debilitating (but not life threatening) disorders such as acne or eczema to increasingly aggressive, pernicious disorders like psoriasis, through to neoplasms such as carcinomas and melanoma. Importantly, the skin may present manifestations of systemic disease such as in diabetes, obesity, cardiovascular diseases (CVD) and metabolic syndrome (Azfar and Gelfand, 2008, Van Hattem et al., 2008, Nawale et al., 2006). Such cutaneous alterations could be the first signs of the disease, and may precede diagnosis by many years. The integrity of the skin degrades with age, and numerous metabolic disorders lead to pathological conditions that exacerbate this process (Nikolakis et al., 2013). For example, the vast majority of individuals suffering from type 2 diabetes will experience skin complications during the natural history of their disease, especially with years of poorly- controlled plasma glucose (Romano et al., 1998, Levy and Zeichner, 2012). Problems range from the sub-clinical, such as neuropathy, chronic inflammation micro- and macrovascular damage and collagen disorganisation, which lead to potentially catastrophic events such as delayed wound healing, ulceration, infection and gangrene. Proactive control of the glycaemic state may prevent or delay many of these associated complications, but it may not reverse pathological changes once established. Obesity and related risk factors in humans are associated with increased fat deposition, with many studies documenting the abnormal structure and function of dermal adipose tissue. Impaired fibroblasts function may contribute to many dermatological changes, such as the loss of dermis or fibrosis, via mechanisms related to insulin signalling (Rivera-Gonzalez et al., 2014). However, the dysfunction of dermal adipocyte which is characterised by adipocyte hyperplasia and hypertrophy, hypoxia, elevated inflammation, and adipokines signalling are now emerging as a potential mediator of insulin-resistance (Klöting and Blüher, 2014). Thus it is possible that the chronic exposure of fibroblasts to adipokines underlies their impaired function. Although many reports describe the use of mouse skin to reveal insights into aspects of human disease pathology and aetiology, it remains a challenge to find a standard protocol that can create optimal sections, retaining the intrinsic structure of mouse skin effectively, and researchers tend to use human skin histology protocols. This is not necessarily acceptable when one considers the anatomical differences between human and mice (Treuting and Dintzis, 2011). Mouse skin is thinner and more fragile than human skin, and so loss of architecture during processing has implications for downstream applications. Obtaining good histology from diabetic mouse skin, and maintaining subcutaneous adipocytes architecture and the discrimination of components such as fine elastic fibres, present a considerable challenge. Therefore, great care must be taken when selecting the conditions, particularly fixative type, to ensure that meaningful conclusions may be drawn (Al-Habian et al., 2014). The skin sections from mouse models used in chapter 3 were prepared using best practice at the time for a retrospective study, but I was able to better histology at the cost of time and materials in sectioning and staining by using tissue macroarrays techniques. Thus, for prospective analysis of mouse skin histology I revised some histology methods. By evaluating the processing protocol and then four commonly used fixatives I enhanced IHC, and histomorphological analysis of normal mouse skin. Moreover, these histopathology techniques are applicable to different mouse tissues, and I recommend using these findings as a guideline not only for diabetic mouse skin histology but for many tissues derived from a variety of species. The dermatologic sequelae of type 2 diabetes mellitus are manifold. Murine models of insulin resistance are useful in elucidating molecular mechanisms of impaired wound healing, but little is known of other pathophysiological changes in these models. A variety of histological and in vitro techniques were used in this thesis to study skin organisation in environmental (diet-induced obesity) and genetic (C57BL/6 Lepob/Lepob and C57BLKS/J Leprdb/Leprdb) models of insulin resistance, type 2 diabetes mellitus, and in chronological age. An expanded subcutis was accompanied by progressive dermal erosion in which the papillary dermis was spared at the expense of the deeper reticular layer as insulin resistance increased. Elastosis was also observed in our models, but damage was not accompanied by an increase in immune infiltration, nor an increase in advanced glycation end products. Altered epidermal differentiation was associated only with the most extreme obese phenotype. Moreover, compromised fibroblast function was maintained in vitro, with C57BL/6 Lepob/Lepob cells displaying compromised growth and reduced collagen synthesis. While mouse skin does not necessarily model the range of cutaneous sequelae observed in human diabetic subjects, it is likely that underlying cellular mechanisms are shared. An improved understanding of the contribution of the layers of the skin, particularly the dermis during insulin resistance, and ageing and its pathological processes may provide new insights into the mitigation of damage. While impaired insulin signalling in skin is associated with disrupted skin homeostasis, and extra cellular matrix remodelling in ageing and type 2 diabetes mellitus (Nikolakis et al., 2013), a recent study has linked these changes to dermal fibroblast , and adipocyte dysfunction (Rivera-Gonzalez et al., 2014). Interestingly, our observation showed that both aged and Lepob/Lepob murine fibroblasts show lowered insulin receptor expression suggesting that this will be a fruitful area for future investigation for improving insulin sensitivity and glucose utilisation in the dermal layers could have important consequences for cutaneous health. This thesis reports a specific pattern of cutaneous damage that is initiated before the onset of frank diabetes and is exacerbated with increasing insulin resistance. This work provides a new insight into the consequences of metabolic disease on skin structure. Finally, further insights into how dermal damage in genetically modified and environmentally adapted diabetic mouse models and vice versa are likely to subserve in detecting early signs of cutaneous insulin resistance and may likely offer better approaches to prevent or at least cure the dermatological sequelae of type 2 diabetes mellitus.

Supramolecular chemistry involves the study of noncovalent interactions that take place between molecules. A supramolecule or host-guest complex is formed when a noncovalent binding or complexation event occurs between two such molecules. Hydrogen bonds, electrostatics, pi-stacking, hydrophobic effects, solvatophobic effects and van der Waals forces are all types of noncovalent interactions. Biological systems have provided much of the inspiration for the development of supramolecular chemistry, and many synthetic supramolecular systems have been designed to mimic biological and enzymatic processes. Biomimetic modelling involves the synthesis of compounds containing similar functional groups to that of the specific enzyme?s protein and cofactor. Subsequent analysis using chemical, physical or computational techniques can be used to gain a better understanding of the interactions taking place. This study involves the investigation of various biomimetic redox enzyme systems. Firstly, model systems containing the 1- and 5-deazaflavin cofactor have been synthesised and studied to probe how their redox behaviour compares to that of riboflavin in a supramolecular environment using physical, electrochemical and computational techniques. Secondly, this study has focussed on the flavin cofactor but has expanded upon what factors influence its redox behaviour, and ability to noncovalently interact with other molecules, by examining how the presence of different dendritic architectures can affect its redox properties and noncovalent behaviour. A series of dendrons have been synthesised and studied that have a water-soluble dendron architecture attached to the flavin moiety, as well as a series of dendrons with branching designed to encapsulate the flavin unit. Finally, a biomimetic model of the pyrroloquinoline quinone cofactor has also been synthesised and studies carried out to investigate its redox behaviour in a supramolecular environment, and ability to noncovalently interact with other molecules. The results of this study will hopefully contribute significantly to the body of chemical research in the area of supramolecular chemistry and biomimetics. Of particular interest will be the results from the flavin-based dendron research, as the prospect of purpose-built synthetic enzymes, designed and synthesised for whatever role is required, would surely be of great significance.

Overall this thesis describes the study of the ability of the tetracationic cyclophane CBPQT4+ to form inclusion complexes with electron-rich moieties such as tetrathiafulvalene (TTF) and dioxynaphthalene. These complexes are strengthened by π-stacking and charge transfer interactions, which give rise to coloured complexes. The complexes are fully reversible and can be decomplexed by the addition of a stimulus that can be chemical, electrochemical, and thermal. In addition we have exploited the ability of ferrocene to form inclusion complexes with cyclodextrins in aqueous media. The host-guest interactions that occur between these molecules were investigated using a number of techniques such as UV-Vis, fluorescence, NMR spectroscopy and cyclic voltammetry. Isothermal titration calorimetery (ITC) was also be used to measure the Ka of the complexes. Chapter two describes the synthesis of naphthalene and ferrocene functionalised dihydroimidazophenanthridines (DIPs). These materials were synthesised in order to create DNA intercalating agents that could undergo further host-guest interactions with either CBPQT4+ or β-cyclodextrin. These interactions were studied using ITC in a number of aqueous buffers with calf thymus DNA and the synthetic Dickerson dodecamer D-DNA. Additionally, the host-guest interactions for the naphthalene functionalised DIP with CBPQT4+ were studied using UV-Vis, fluorescence and NMR spectroscopy. The cytotoxic nature of the functionalised DIPs were investigated using MDCK epithelial cell culture experiments. Chapter three describes the synthesis and analysis of silane and disulfides modified with chosen electron rich substrates for the production of functionalised surfaces where self-assembled monolayers were produced on either glass or gold surfaces. These functionalised surfaces were then utilised in cell adhesion experiments with MDCK cells where the modulation of adhesion was attempted by the formation of pseudorotaxanes with either CBPQT4+ or β-cyclodextrin and by changing the oxidation state of the functional group in the case of ferrocene. Chapter four describes the synthesis of functionalised diacetylenes for the formation of polydiacetylene liposomes in aqueous conditions. The liposomes successfully formed were analysed by DLS. UV-Vis spectroscopy and cyclic voltammetry were used to investigate the dual response chromophoric sensing applications of these materials. Chapter five describes the synthesis of functionalised surfactant compounds for the formation of mixed micelles in aqueous conditions with sodium dodecyl sulfate (SDS). The interactions between the surfactant and CBPQT4+ were measured by ITC, NMR, UV-Vis, and fluorescence spectroscopy. Chapter six describes the modification of the protein BSA with a naphthalene functionalised chloroacetate. The modified protein was analysed by ITC, MALDI TOF, UV-Vis, and fluorescence spectroscopy in order to identify the degree of functionalisation that had occurred and whether complexation was possible with CBPQT4+. Chapter seven describes the synthesis of a naphthalene, and two ferrocene functionalised biotin conjugates with a view to investigate the interactions with avidin proteins. The interactions were measured by ITC and UV-Vis spectroscopy. The effect of changing the chain length on binding to neutravidin and β-cyclodextrin was studied in the ferrocene biotin conjugates where the interactions were assessed using ITC, cyclic voltammetry, and NMR spectroscopy. The interactions between the naphthalene based conjugate and CBPQT4+ was measured by UV-Vis and fluorescence spectroscopy.

Transition metal phosphides remain relatively unexplored as water-gas shift catalysts; however the little that has been done has produced promising results in terms of performance due to the presence of oxygen rich phases. They can be produced through a number of approaches, the most common being reduction of the phosphate precursor using hydrogen. Bimetallic phosphides have also generated interest recently, e.g. with the addition of cerium there are improvements to the phosphides' activity and with the addition of palladium a decrease in reduction temperature is evident in the precursor material. Nickel phosphide and a range of bimetallic derivatives on a silica support were investigated for their activity in both high and low temperature water-gas shift reactions. All of the catalysts were tested using a continuous flow, fixed bed reactor. Characterization of the catalysts was carried out using XRD, EXAFS, XPS, FTIR, SEM and TEM. The comparison of supported nickel phosphide and an iron based industrial catalyst shows supported nickel phosphide to have good mass normalized activity in comparison to the industrial counterpart under high temperature water-gas shift conditions. The results complement previous studies with regards to potential of nickel phosphide as a water-gas shift catalyst. In view of the results obtained so far for other transition metal phosphides, Ni2P appears to be superior for the water-gas shift reaction. One of the most promising aspects of using nickel phosphide in the water-gas shift reaction is its potential resistance to sulfur. Catalyst poisoning caused by impurities such as sulfur are known to deactivate current commercial catalysts for both high and low temperature shift conditions, therefore a catalyst which is resistant to sulfur is an attractive prospect. The sulfur resistant properties of the nickel phosphide catalysts were highlighted by testing them under high temperature water-gas shift conditions in the presence of sulfur. Whilst the catalysts deactivated under the conditions, they showed some residual catalytic activity still remained after sulfur was removed from the feed. Compared with the industrial catalyst, nickel phosphide displayed greater resistance to deactivation.

The primary objective of this study was to characterise standard iron based Fischer- Tropsch catalysts by using the hydrogenation of CO at elevated temperatures and ambient pressure as a test reaction. The reaction test data is supplemented by the following analytical techniques; X-ray diffraction (XRD), Raman scattering, temperature programmed oxidation (TPO), transmission electron microscopy (TEM) and also inelastic neutron scattering (INS). The aim of these studies is to characterise the hydrocarbonaceous species present on the catalyst surface after reaction and to propose what role these hydrocarbonaceous species may play in the Fe/CO/H2 surface chemistry; be it active or not. These initial characterisation studies of the reacted iron catalysts were then extended to study the temporal dependence of these species with increasing reaction time. The application of inelastic neutron scattering is shown to provide a great deal of information regarding the hydrocarbonaceous component present in these types of systems. Therefore the application of INS and the subsequent result constitute the majority of the discussion of this study. The research objectives for this study can be listed as follows; 1. To prepare an iron oxide catalyst using a reproducible and controlled method and to characterise this material using the methods outlined previously. 2. To react the iron oxide catalysts using a representative test reaction for the purpose of characterising the surface species present after reaction. 3. To use inelastic neutron scattering to probe and gain a vibrational spectroscopic insight to the hydrocarbonaceous species present. 4. To study the temporal dependence of the hydrocarbonaceous species and how they alter with increasing time-on-stream. The thesis will begin with an introduction to Fischer-Tropsch catalysis, with a focus on iron-based Fischer-Tropsch catalysis. The discussion will move to some heightened analysis of some previously reported INS measurements of iron Fischer-Tropsch catalysts. This prelude will be followed by the main discussion of results, that is the characterisation of the reacted iron oxide catalyst using inelastic neutron scattering and the temporal study with increasing time-on-stream. The thesis will then finish with a discussion on a brief study investigating the role of promoters in iron based Fischer-Tropsch catalysts, which constitutes future work.

This thesis is focused on the links between charge transfer (CT) at metalorganic (MO) interfaces, creation of surface dipoles and two-dimensional supra- molecular assembly. Although several examples can be found in the literature where molecular self-assembly on surfaces was in uenced by the formation of interfacial dipoles, only in a few cases were the results fully rationalised and only a posteriori. The MO interface resulting from the deposition of the molecules used for these studies (chosen for their relevance as building blocks for applications in organic opto-electronic, photovoltaic, or proposed organic spintronics devices) is usually very complex. This is mainly due to the chemical structure of these molecules and to their strong interaction with the substrate. A clear identification of the different fundamental processes (such as CT and formation of interfacial dipoles) is thus highly difficult. The approach followed in this thesis is markedly different: specific molecules were rationally designed and subsequently synthesised in order to obtain model systems where the different parameters could be clearly isolated and identified. The presented work is the result of a close collaboration with other two research groups: the organic synthetic chemistry group of Prof. D. Bonifazi and the theoretical group of Prof. A. De Vita. The study was addressed through a complementary multi-disciplinary theoretical and experimental investigation, including the synthesis of new molecules, the analysis of their self-assembly by scanning tunnelling microscopy and spectroscopy and the use of density functional theory calculations and Monte Carlo simulations for the theoretical modelling of the systems. A balance between omnipresent short-range van der Waals attractive forces and long-range repulsive interactions generated by CT at MO interfaces was found to be responsible for the spontaneous formation of novel classes of supramolecular structures. By selecting different metal substrates and by carefully modifying the molecular species through chemical synthesis, the CT was selectively inhibited or enabled. This strategy represents a new paradigm for predicting and controlling the molecular self-assembly at surfaces. Conversely, the appearance of specific molecular linkage patterns is used to reveal the occurrence of CT and provides a novel means for obtaining crucial information on the electronic properties and the energy level alignment of MO interfaces.