Electrochemical analysis using mercury electrodes has been a prominent methodology since the beginning of voltammetry, however, due to its toxic nature their use is being slowly phased out in favour of environmentally friendlier alternatives. In this thesis, carbon electrodes feature heavily as a means to provide a cheaper and non-toxic approach to voltammmetric sensing. Pulse techniques have been used for the sensitive detection of commonly studied analytes, including antimony and iron. A simple fabrication of a vibrating electrode is presented by modifying a commercially available vibrating toothbrush with platinum foil as a means to enhance mass transport for electroanalytical work. Finally, pH determination at carbon electrodes is investigated. Carbon electrodes have been proposed as a simple sensor for pH determination by exploiting the pH sensitive nature of surface quinone groups intrinsic within carbon edge-plane like sites. Using this approach, both EPPG and GC electrodes are suggested as new materials for pH determination and can be used in aqueous solutions over the pH range 1.0 to 13.0, as a cheap and simple alternative to the classic glass electrode.

The behavior of colloidal liquid crystals in confinement is addressed on the single particle level using laser scanning confocal microscopy. We seek to disentangle how equilibrium director fields are controlled by the complex interplay between confinement, elasticity and surface anchoring. First, we study the nematic phase confined to wedge structured channels. Varying the wedge opening angle leads to a splay to bend transition mediated by a defect in the bulk of the wedge. Our results are in quantitative agreement with lattice Boltzmann simulations, and we show that comparison between experiments and simulation yields a new method to obtain the splay-to-bend elasticity ratios of colloidal and biological liquid crystals. Next, we extend our study of the wedge structured channels to the cholesteric phase, and measure a splay to twist transition with increasing wedge angle. We directly visualise the 3D nature of the twisted state, and explain how the transition is intricately determined by the anchoring strength and the splay, bend, and twist elasticities. Next, we investigate the effect of rectangular confinement on the nematic phase. The rectangle aspect ratio is systematically varied and we observe five distinct director fields. Comparison with computations of the Frank-Oseen energies yields the extrapolation length, which we find to be of the order of the rod length. Next, we confine the nematic phase to annular geometries of varying dimensions, and observe the novel director fields that are adopted. We approach a level of confinement which is of the order of the particle size. Interpreting our observations with Monte Carlo simulations, which take into account the finite size of the particles, illuminates the applicability of continuum theories down to microscopic lengthscales. We finish with a study of the isotropic-nematic interface in bulk and confinement. We show that parallel anchoring occurs at the interface, and measure the width of the interface to be of the order of the rod length.

Uniformly dimpled colloidal particles are studied using laser scanning confocal microscopy and optical tweezing, alongside real-space image analysis. In particular, a comparison is made between the behaviour of these particles with that of isotropic spherical particles of the same size and polydispersity. We begin by detailing the synthetic techniques as well as the methods used for both experiments and simulations in this work. We then probe the structures and ordering exhibited by the dimpled particles and their spherical counterparts at a single featureless wall. Only the first layer at the wall is observed, and pronounced differences in both the translational and orientational order between the two types of particle is found. Furthermore, we show that the presence of the dimple leads to disordered structures that develop over time. Next, we reduce the dimensionality of the system to quasi-two and study the depletion induced interactions in a monolayer of colloidal particles at a single featureless wall. Using both confocal microscopy and Monte Carlo simulations, we illustrate the selectivity of the depletion interaction with regard to particle shape and polymer size. A level of complexity is then added to the problem by introducing a second colloidal system of small spherical particles. The resulting binary mixture, still with additional non-adsorbing polymer and in a monolayer at a wall, allows us to investigate so-called “lock and key” binding. We show that the inclusion of a lock particle cavity, whose shape and size is complementary to those of the key particle, significantly favours binding behaviour, which is further improved by using a depletant consisting of a small polymer and charge-screening salt. Finally, the depletion induced force between lock and key particles at contact is directly measured using optical tweezers. The dependence of the force due to depletion upon the overlap volume between the particles is illustrated, and we find that the strongest force is produced when the key is held within the cavity of the dimpled lock, demonstrating semiquantitative agreement with theoretical predictions.

This thesis presents two contrasting implementations of the optical-feedback cavity-enhanced absorption spectroscopy (OF-CEAS) technique. OF-CEAS com- bines passive optical-feedback locking of semiconductor lasers with cavity-enhanced absorption spectroscopy, and is well suited to sensitive detection of pressure- broadened trace gases. Chapters 1 and 2 set the work in this thesis in context, by describing the theory and discussing the motivations behind trace gas sensing by tuneable laser spectroscopy in the near- and mid-IR. Chapter 3 reviews the theory of OF-CEAS, prior to presenting the results of an experimental implementation based on a near-IR DFB diode laser setup following the traditional V-cavity methodology to spatially decouple the optical- feedback beam from the direct back reflection. The capabilities of the system are demonstrated by accurate determination of a self-broadened half-width at half- maximum of a CO 2 transition, and by detection of acetylene in a car exhaust sample. Chapter 4 describes the design and implementation of the linear cavity method- ology for QCL OF-CEAS, which is the significant contribution of this work. Successful OF-CEAS locking with the linear cavity is shown for two different DFB-QCLs, with close operating wavelengths (5.5 and 5.2 µm) but quite different operating powers and facet size. Chapter 5 presents quantitative spectroscopic results from the linear cavity OF-CEAS instrument, using both lasers. Spec- troscopy on mixes of N 2 O and NO returned sensitivities, quantified by the α min , of 2.7 × 10 −8 cm −1 in 1 s at 0.28 atm and 2.4 × 10 −8 cm −1 in 1 s at 0.19 atm respectively. Limited by etalon fringing on the baseline, the α min compared well with those obtained with V-cavity QCL OF-CEAS instruments. The temporal stability was investigated by Allan variance calculations and the best minimum detectable concentrations for the linear QCL OF-CEAS instrument were 32 ppm for N 2 O (35 s) and 5 ppb for NO (2 s). For NO, this detection limit compares favourably with other mid-IR QCL-based NO sensors, and is sufficient for mon- itoring NO in polluted urban environments. With the Maxion DFB-QCL, mon- itoring of NO in air outside the laboratory was attempted, and an air sample drying system benchmarked. Although this experiment proved unsuccessful, it was possible detect trace amounts of NO desorbing from the walls of the gas cell. Over the course of one hour the concentration rose from 3.8 ± 0.7 ppb to 28.4 ± 0.2 ppb, leading to a rate of desorption of 6.76 ± 0.01 × 10 −3 ppb s −1 . The sensitivity (α min ) of these spectra was 7.0 × 10 −9 cm −1 in 1 s, improved due to the higher mirror reflectivity at the lasing wavelength of the Maxion DFB-QCL, although still limited by etalon fringing.

Many animals on earth need to navigate in their own environments for breeding and foraging. The ability to determine a correct heading and the current location for a migratory bird is critical for its survival. Animals that are sensitive to the Earth’s magnetic field can use it to obtain their direction of travel. In 2000, a paper suggested that radical pair reaction could form the basis for magnetoreception in migratory birds and a flavoprotein, cryptochrome, was proposed as the candidate for the radical pair precursor. Recent in vivo experimental results strongly support the hypothesis that radical pairs formed in the eyes of migratory birds are responsible for their magnetic compass sense. Cryptochrome has also been located in the UV-cones in the retinas of two different species of bird. Radical pairs in living cells are influenced mainly by Zeeman interaction, hyperfine interaction, rotational modulation, etc., and together they influence the recombination reactions of the radical pairs. This thesis considers the possible role of radical pairs in avian magnetoreception, using computer simulations of the quantum mechanical evolution of a radical pair under a variety of conditions. Chapter 1 contains the introductions to spin chemistry, avian magnetoreception, and the mathematical description of the quantum evolution of a radical pair. Chapter 2 describes the four different theoretical models for a general non-diffusion-controlled radical pair reaction and the product yields of a radical pair reaction predicted by these four models are analysed and compared. Chapter 3 introduces a model for avian magnetoreception that integrates photoselection with the radical pair reaction and the model is used to predict the retinal patterns that a bird may be able to use for magnetoreception. The anisotropic singlet product yields of a radical pair comprises the flavin chromophore and the tryptophan of a cryptochrome are also presented in this chapter. A paper based on some parts of this chapter is published [1] in the Journal of The Royal Society Interface. Chapter 4 describes a modified version of an algorithm that is used to calculate the product yields detected in a reaction yield detected magnetic resonance (RYDMR) experiment. The new algorithm is used to analyse the results of two sets of RYDMR experiments in which two radical pair systems, pyrene/1,3-dicyanobenzene and chrysene/1,4-dicyanobenzene, were used. The modulated detection technique used in the RYDMR experiments is also discussed in this chapter.

A range of computational and experimental techniques have been applied to the study of four metal cluster systems. Decorated rhodium clusters Rh n O m (N 2 O) + ( n = 4 − 8, m = 0 − 2) have been investigated both experimentally by IR-MPD and computationally using DFT. The effect of cluster size as well as oxygen coverage on the spectroscopy of the N 2 O bend are analyzed. The infrared-induced decomposition of N 2 O on Rh n O + m is observed on all cluster sizes, with marked differences as a function of size and oxygen coverage, particularly in the case of Rh 5 (N 2 O) + . The oxidation of CO was studied on the surface of small platinum cluster cations Pt n O + m ( n = 3 − 7, m = 2 , 4) by IR-MPD at 400 – 2100cm −1 . Spectroscopically, oxygen is found to be bound both dissociatively and molecularly on the cluster surface, while the CO band is found to red shift in cluster size, and blue shift with oxygen coverage. Oxidation of CO proceeds on all cluster sizes, with a constant branching ratio of 40% : 60% . DFT calculations identified key stationary points and barriers on the Pt 4 O 2 CO + reaction pathway. The one-colour Ta 2 photodissociation is studied by photoionization and VMI in the range 23500 – 24000cm −1 , finding clear evidence of a fragmentation process producing Ta , which is interpreted as fragmentation of cationic Ta + 2 at the two photon level. A majority of the observed channels produce either atomic ( Ta( 4 F 3/2 ) ) or cationic ( Ta + ( 5 F 1 ) ) ground state. An improved value for the dissociation energy D 0 ( Ta + 2 ) is obtained, in agreement with computational predictions. The anisotropies observed show weak evidence of a perpendicular transition being involved in the photodissociation process. Finally, the photodissociation dynamics of Cu 2 are studied by spectroscopy in the range 36000 – 38200cm −1 as well as VMI. Clear evidence for resonant photolysis of Cu 2 is obtained, as a result of both direct dissociation of the Cu + 2 2 Π ion state as well as dissociation of doubly excited Cu 2 states, which leads to a determination of dimer dissociation energies. Finally, the production of Cu + 2 is interpreted as evidence of photolysis of Cu 3 , from which a Cu 3 dissociation energy is derived.

In recent years the pharmaceutical industry has seen a rise in the number of drug compounds with low aqueous solubility, and consequently poor oral bioavailablility. One potential solution to this problem is to formulate such compounds as solid dispersions, whereby the drug is dispersed in a carrier matrix in the solid state. In this thesis, the hypothesis that a number of drug-drug and drug-polymer intermolecular interactions influence the physical stability and dissolution performance of solid dispersions is considered. The aim is to use correlations between drug molecular structure and solid dispersion performance to develop a platform to rapidly assess whether drug compounds will have favourable properties when formulated as a solid dispersion. Amorphous felodipine/copovidone solid dispersions are used as a model system to develop a suitable testing regime with regards to physical stability and dissolution performance. A laser light scattering technique developed in this work shows that morphological changes in felodipine/copovidone films exposed to water are due to polymer swelling. A combination of dissolution testing methodologies is also used to suggest a mechanism for the dissolution of bulk solid dispersion samples. Contributions of individual functional groups in the felodipine analogues to the physical stability and dissolution performance of their amorphous solid dispersions are assessed. Blocking of the felodipine amine hydrogen-bond-donor with an N-methyl, and the removal of chlorine substituents are both shown to reduce the physical stability of the solid dispersions. Correlations between molecular descriptors and data from the above experiments show that drug compounds are more likely to crystallise from solid dispersions with copovidone if they have a low log P, low relative molecular mass and low polarizability. Such correlations can form the basis of a screening method for the molecular design of analogous drug compounds likely to form high-performance solid dispersions with copovidone.

Surface chemical modifications are presented for supporting primary neurons in culture. The initial substrates for culture were glass and gold. The surface modifications were based on self assembled monolayer (SAM) approaches. Glass surfaces were initially modified by silanisation with either 3-aminopropyltrimethoxysilane (APTMS) or 3-aminopropyldimethylethoxysilane (APDES), to present amino-terminated surfaces. Gold surfaces were initially modified by thiol SAMs of either 11-amino-1-undecanethiol (AUT) or a peptide fragment of laminin (PA22-2), to present an amino- or peptide-terminated surface respectively. The amine-terminated surfaces of both glass and gold were subject to further modification. A heterobifunctional linker, containing a polyethylene glycol (PEG) spacer, was used to couple the peptide PA22-2 to the amino-terminated surfaces. Surface modifications were characterised using WCA, XPS and ToF-SIMS. The heterobifunctional linker bound homogeneously across the AUT SAM surface, however the linker was not distributed evenly on either of the amino silanisations of glass. Primary neurons from dissociated embryonic rat hippocampi were cultured on the modified glass and gold surfaces. The cell viability was measured during a 3 week long culture using calcein and ethidium homodimer fluorescence. Neuronal cell cultures were viable on all the gold surface modifications. The only viable glass surface was a control surface of adsorbed poly-l-lysine (PLL) on glass. Cell viability on the AUT and the Peptide-PEG-AUT modified gold surfaces was equivalent to the PLL coated glass. Inclusion of the PEG linker reduced protein adsorption from the media to the peptide modified gold surface, allowing cells to recognise the peptide rather than an adsorbed protein layer and improving their viability. The presented gold surface modifications provide suitable substrates for neural cultures which can be used in existing applications for investigating neural activity, such as; multi-electrode arrays, micro-fluidics devices, and surface plasmon resonance.

This thesis is concerned with coherent effects in high resolution mid-infrared gas phase spectroscopy using quantum cascade lasers (QCLs). An introductory chapter explains the importance of QCLs as radiation sources in the mid-infrared region of the spectrum and goes on to detail their development and structure. A discussion of coherent effects in spectroscopy follows, leading into the second chapter which discusses the theories relevant to the experimental sections of the thesis. In chapter 2 the theory underpinning direct and velocity selective, Doppler-free spectroscopy is discussed and a density matrix formalism is followed to derive the equations of motion that govern coherent excitation effects in two-level systems. In the final part of the chapter this treatment is extended to three-level systems. The equations derived in this chapter form the basis of quantitative interpretations of the phenomena observed in experimental data and presented in the remainder of the thesis. In chapter 3 the characterisation of a high power, narrow linewidth QCL is carried out. This laser is then used to perform direct and sub-Doppler resolution spectroscopy on NO, demonstrating non-linear absorption at high laser intensities and providing a measurement of the laser linewidth in the limit of slow frequency tuning. As the slow tuning rate increases, evidence of coherent transient effects is presented and density matrix theory used to model this behaviour. The data presented include the first observations of asymmetric Lamb dips and the onset of rapid passage oscillations from a Lamb dip. Pump-probe experiments on NO, utilising two cw QCLs are presented in chapter 4. The high level of velocity selection afforded by QCL excitation leads to coherent transient signals at far lower probe scan rates than previously reported. The effect of altering both the scan rate and the gas pressure and the importance of hyperfine structure are presented. A radio frequency noise source applied to one of the lasers is shown to broaden the laser linewidth, leading to rapid dephasing. A two-colour polarisation spectroscopy experiment is also presented which allows the measurement of both the absorption and the Doppler-free dispersion signals and the three-level density matrix formalism presented at the end of chapter 2 used to model the non-linear response of the system. The final chapter details the use of an acousto-optic modulator to create a pulse of mid-IR light using a cw QCL and the application of this to time resolved pump-probe spectroscopy. This capability suggests the prospect of achieving coherent population transfer by stimulated Raman adiabatic passage (STIRAP) using two such pulses. Simulations based on a simple three-level model and including Zeeman coherences are presented, which take the measured properties of the lasers used in this thesis as inputs to predict the potential population transfer achievable in NO as well as providing useful information about the angular momentum polarisation of the excited molecules. An experimental realisation of STIRAP would require the lasers to be stabilised, and so the final part of the chapter details experimental attempts to achieve stabilisation of an external cavity QCL, and suggests future avenues for improved implementation.

Organophosphorus-mediated reactions are important tools in organic chemistry and are used in the synthesis of highly desirable drug targets, such as morphine.1 A major drawback of traditional phosphorus-mediated reactions is the formation of stoichiometric amounts of phosphine oxide by-products; this renders the product purification difficult and reduces the atom efficiency of these transformations. For these reasons, catalytic variants become desirable; there being two potential strategies to achieve the catalysis; i) redox-driven and ii) redox-neutral.2-4 The redox-driven catalytic cycle requires a reductant for the turnover whilst the redox-neutral system uses a sacrificial reagent to directly turn over the phosphine oxide to the active phosphorus (V) reagent. This thesis will report upon a new class of Hydroxylmethyl-Aryl phosphine 1 and phosphine oxide 3 catalyst for use in a redox-driven catalytic reaction; the Staudinger reduction Scheme 1, and routes to a potential redox-neutral catalytic Mitsunobu reaction Scheme 2.