The work presented in this thesis was carried out with the ultimate aim of learning about the photoionization dynamics of polyatomic molecules. This is a complex problem; in order to obtain sufficient experimental data to shed light on the dynamics careful measurement of photoelectron angular distributions (PADs) is required. Ideally these measurements are rotationally-resolved, and the angular distributions measured correspond to the formation of the molecular ion in a single rotational state. The ionization event, in the dipole approximation, can be completely described by the dipole matrix elements. If sufficient experimental data to determine the radial components of the matrix elements and associated phases, the dynamical parameters, can be obtained the photoionization experiment may be said to be complete. Analysis of such experiments requires that the initial state of the molecular system is also known, to this end resonance-enhanced multi-photon ionization (REMPI) schemes can be used in order to populate a single quantum state prior to ionization. The experiments presented here follow this methodology, with various REMPI schemes used to prepare (pump) and ionize (probe) the molecule under study, and the velocity-map imaging (VMI) technique used to (simultaneously) record the photoelectron spectra and angular distributions. Two molecules have been studied experimentally, acetylene (C2H2) and ammonia (NH3). In both cases dynamical parameters pertaining to the formation of specific states (vibronic or vibrational) of the molecular ion have been determined from experimental data. Additionally, in the ammonia work, rotationally-resolved photoelectron images were obtained.

Mass analysed ion kinetic energy (MIKE) spectra following collisions have been recorded using a double focusing mass spectrometer with 5 kV acceleration voltage. Metal complexes studied were formed by pick-up of metal atoms in mixed argon/solvent clusters made by supersonic expansion. DFT calculations were used to rationalise experimental data. Complexes of the form MLn+ where M = Mg, Ca, Mn, Cu, and Zn while L = NH3, CO2, benzene, pyridine, acetonitrile, and acetone have been collided with O2 and MgLn+ also with CO2, N2O, acetonitrile, and benzene. Complexes with few ligands are the most prone to oxidation due to their high speed which facilitates electron transfer. Calculated electron affinities, Mulliken populations, and natural bond orbitals of collision gases were used to rationalise electron transfer trends. Collision gases trap electrons more efficiently if they have π-bonds or adjacent electronegative atoms. Metal complex and molecular dications were collided with H2 and O2 to determine the stability of their reduced products. No systematic differences were found between collisions with the two gases at the collision energies examined. The fate of monocations formed in collision depends on their relaxation energy and the dissociation energy of relaxed monocations. LZ theory was unable to explain MIKE spectra. Metal complexes MLn+ and MLn2+ were collided with O2 to determine the propensity to form MXLn-m+ where M = Mg, Ca, Mn, Cu, and Zn while L = CH3X with X = F and Cl. Reactivity is determined by the IE of MLn+ which decrease with increasing n. Dications due to their high dissociation energy are much more likely to react as they can have enough internal energy to overcome potential barriers.

This Thesis investigates immobilised metal- and biocatalysts for continuous reactions in scC02. Chemical transformations with high atom economy and low E-factor (amount of waste per kg of product) are highly desired in the green chemical viewpoint. One of the approaches to decrease the production of waste is the use of catalysis (possibly highly selective). Another approach is the use of a 'green' reaction medium as a substitute for traditional solvents that can reduce the production of harmful solvent waste. How this Thesis encompasses by these topics is discussed in Chapter 1. The details of the apparatus, experimental and analytical equipment and procedures are reported in Chapter 2. The field of asymmetric catalytic hydrogenation is a currently important and expanding field of research. In Chapters 3 and 4, the continuous asymmetric hydrogenation of dimethyl itaconate is covered. High enantioselectivity (ees up to 83 %) was obtained in the continuous asymmetric hydrogenation of dimethyl itaconate catalysed by supported homogeneous chiral Rh catalysts on alumina in SCC02 (Chapter 3). This is one of the first examples of the use of chiral catalyst in a continuous flow system without the need for the addition of the chiral modifier. The continuous asymmetric hydrogenation of dimethyl itaconate was also examined with chiral Rh catalysts immobilised in ionic liquids in a biphasic system ionic liquid/scC02 (Chapter 4). High enantioselectivity was achieved in the continuous flow system: ees up to 76 %. Chapter 5 describes the kinetic resolution of secondary alcohols catalysed by immobilised Candida antarctica lipase B (Cal B) in a continuous flow scC02 system. The continuous kinetic resolution of a-tetralol with Cal B immobilised in the form of Cross-Linked Enzyme Aggregate (CLEA) gave excellent enantioselectivity (eeR to 99 %). Different acyl donors (vinyl acetate, phenyl acetate and p-nitrophenyl acetate) were investigated, and were shown to influence the enantioselectivity of the reaction. In Chapter 6, a two step catalytic cascade reaction is described in a continuous flow scC02 system: hydrogenation of acetophenone with a Pd catalyst (Pd Type 31) followed by the kinetic resolution of the product with Cal B CLEA. The series reaction gave good results even when un-optimised: • Step 1 (hydrogenation of acetophenone): conversion up to 91 % • Step 2 (kinetic resolution of (R/S)-l-phenylethanol): conversion of (R)-l-phenylethanol up to 22 %, enantioselectivity (R) > 99 %. Chapter 7 details the preparation of cholesterol oxidase CLEA and combi-CLEA of cholesterol oxidase and catalase, and their application for the continuous oxidation of cholesterol in scC02 with 'in-flow' cholesterol extraction. CLEA were successfully prepared with high retained activity: • Individual cholesterol oxidase CLEA: cholesterol oxidase activity up to 99 % (relative to native), • Combi-CLEA: cholesterol oxidase activity up to 99 % (relative to native), catalase activity up to 53 % (relative to native). Unfortunately, the activity of the CLEA in the continuous oxidation was low, however, the findings of this work will aid in improving the performance of the continuous catalytic oxidation of cholesterol in the future. The possible future directions of this research are presented in Chapter 8.

Biological methylation is defined as the transfer of a methyl group from S-adenosyl-L-methionine(SAM) to one of a wide range of potential acceptors such as DNA, RNA, protein, hormones and neurotransmitters. Protein arginine methylation is a common post-translational modification facilitated by protein arginine methyltransferases(e.g. PRMTI). The roles of these enzymes in vivo are currently poorly understood. The focus of the project is design and synthesis of PRMT inhibitors with the ultimate goal of evaluating their activities in cells. Preliminary work toward the synthesis of S-adenosyl-trifluoromethyl-L-homocystein and adenosyl 5'-[2-(tert-butoxycarbonylamino)ethyl-trifluoro methyl] thiophenium is described. The ternary crystal structure of PRMTI in complex with S-adenoSyl-L-homocystein(eSAH) and an arginine containing peptide (PBD IOR8) was used to design a series of potential bisubstrate inhibitors of PRMTI. The prototypical SAM analogues bearing guanidine group were sought to replace the reactive sulfonium centre with nitrogen. Analogue synthesis proceeded via successive reductive arnination of Y-arnino-Y-deoxyadenosine and deprotection in good overall yields. An alkyne SAM analogue, 5'-[(S-3-amino-3-carboxypropyl)-propargylaminol-5'-deoxyadenosine was prepared, which underwent efficient Cu(1) catalysed Huisgen reaction to yield a triazole derived SAM analogue 5'-[(S-3-amino-3-carboxypropyl)-[I-(2-guanidinoethyl)-IH-1,2,3-triazol-4-yl]methyl-amino]-5'-deoxyadenosine. Preliminary biological evaluation of the compounds by collaborators Professor Steve Ward and Dr Richard Parry at the University of Bath, confirmed that 5'-[(S-3-amino-3-carboxypropyl)- 3-guanidinopropyl-amino]-5'-deoxyadenosine and 5-[(S-3-amino-3-carboxypropyl)-5-guanidinopentyl-amino]-5'-deoxyadenosine are potent inhibitors of PRMTI but not the lysine methyltransferase SET7. A related N-6 modified SAM analogue 5'-[(S-3-amino-3-carboxypropyl)-3-guanidinopropylamino]-5'-deoxy-N6-(lI-azido-3,6,9-trioxaundecane)-amino adenosine bearing an azide tether was developed with the aim of allowing facile introduction of biotin or fluorescent dyes, using either Staudinger ligation, or Cu(1) catalysed Huisgen reaction to provide compounds that can be used for affinity purification of the target protein or study of its localisation in cells respectively. Finally, progress toward a novel, rapid and enantioselective synthesis of the natural product (+)-sinefungin is reported. Key dihydropyridazine intermediates were generated from adenosyl 5'-propaldehyde, commercially available azodicarboxylate derivatives and ester substituted vinyltriphenylphosphonium salt by successful extension of methodology first reported by Ley and co-workers. Deprotection and ring opening of clihydropyridazine compounds was attempted, and unfortunately we were not able to generate (+)-sinefungin, although it is hoped that this route can be developed to achieve this in the future.

The research project presented in this thesis deals with the development of the alkylation of protected aldimines using organoaluminium and organozinc compounds as alkylating agents. To this end, efforts have been focused into the methylation reaction using trimethylaluminium and dimethylzinc. It was hoped to establish promising conditions using the methylate group and then to extend the catalytic system to other interesting nucleophiles. In the case of organoaluminium alkylation the reaction was extended to other nucleophiles, namely to the allyl and propargyl groups. The identificaton of suitable metal catalysts as well as diphosphine ligands was carried out by means of extensive high throughput screening. On the one hand [IrCl(COD)]2 proved to be very efficient when associated to AlMe3 or DABAL-Me3 in the non-enantioselective 1,2-addition reactions to aldimines (100% conversion in 3 h). On the other hand, [RhCl(COD)]BF4 was found to be able to efficiently catalyse the enantioselective 1,2-addition of Me2Zn to aldimine substrates (100% conversion in 3 h - up to 99% e.e.). A preliminary screening of a range of aldimines bearing different protecting groups aimed at selecting the most interesting substrate in terms of reactivity and ease of cleavage of the protecting group. Once this substrate had been identified, a range of derivatives was synthesised in order to appraise the scope of the newly developed reaction. The diphenylphosphinoyl (dpp) protecting group turned out to be the best activating group for aldimines tested within the framework of this study. In addition to being easy to introduce, the dpp group can also be removed easily under mild conditions. What is more, the presence of a phosphorus atom on this protecting group is a feature which was used to determine the enantiomeric excess by 31P NMR spectroscopy, thus providing a novel and efficient screening tool at disposal. In the course of this investigation, various issues were faced and tackled. One of them was the unexpected non-reproducibility taking place in the Rh-catalysed Me2Zn addition reaction; however, a deeper thinking of the reaction mechanism enabled us to solve this problem to eventually get a more robust catalytic system. Another one was the formation of a reduction product as a by-product of the Rh-catalysed Me2Zn addition reaction. Finally, several interesting attempts (Et2Zn addition, aliphatic imine synthesis), findings (effect of ligand bite angle) and hypotheses (testing of the BPM ligand) made during this study deserve to be studied further for improvement and optimisation.

This thesis describes the development and application of a rapid and sensitive electrospray ionization-mass spectrometry (ESI-MS) method to study the weak hydrophobic interactions seen in many Ub-Ub-binding domain (UBD) complexes. A range of UBDs has been screened against mono-Ub, di-Ub (Ub2) and tetra-Ub (Ub4). Affinities in the 2-200 J.lM range were found to be in excellent agreement with data obtained from other biophysical techniques. Insights into the UBD's preference for poly-Ub chain linkage and length are also provided by this methodology. Detection of a ternary complex involving Ub interacting simultaneously with two different UBDs demonstrated the co-existence of multisite interactions. A simple, clean and effective method for reducing charge states observed in ESI-MS without the use of any solution additives or instrumental modifications is also reported; with the charge reduction method ultimately promoting the investigation ofthe Ub-UBD interactions. Moreover, the development and application of a top-down proteomics approach to characterize the topology of an unanchored Ub dimer purified from rat skeletal muscle is also described in this thesis. This study has identified the topology of the Ub2 to be Lys48-linked. In addition, ESI-MS of endogenous Ub2 species has revealed the presence of cyclic Lys48-linked Ub2 and demonstrates for the first time that cyclisation of poly-Ub can also occur in vivo. Further to these studies, the inhibitory activity of small peptides against the complex formed by Ub with the ZnF domain of isopeptidase T (IsoT) is also investigated. Finally, the unusual effects of cation adduction upon the gas-phase conformation of three-helix bundle UBDs are revealed by ESI-IMS-MS and reported in this thesis.

This thesis details the synthesis of molecular species designed for a variety of nanotechnological applications. The first chapter gives a brief introduction to nanotechnology and explains the concepts of supramolecular chemistry and self-assembly which are the basis on which this project is built. Special attention is given to non-covalent bonding interactions such as hydrogen-bonding and π- π interactions which drive the formation of complex architectures. The discussion is followed by many examples from the literature describing work that has been accomplished in various fields of supramolecular chemistry. The second chapter describes the synthesis, characterization and surface deposition studies of 1,4-diphenyl-1,3-butadiyne-3,3’-5,5’-tetracarboxylic acid (DPBDTC). Recent work on surface deposition studies of terphenyl-tetracarboxylic acid (TPTC) has shown the formation of a 2D network that resembles an aperiodic tiling structure that shows orientational order but no translational symmetry. DPBDTC was designed in order to improve the aperiodic characteristics of the network formed. An experimental exploration of the phase space of interacting random tilings was also possible using the network obtained from DPBDTC deposited from nonanoic acid along with networks obtained with different molecules and under different conditions. The third chapter focuses on the synthesis, characterization and surface deposition studies of a series of porphyrin molecules functionalised with isophthalic acid and ferrocene groups at the meso-positions. The isophthalic acid groups are incorporated to encourage intermolecular interactions while the ferrocene groups are designed as potential carriers of binary information in the form of the redox states of the iron center. The above molecules were designed in order to study their potential use in molecular memory systems. The series of molecules consisted of porphyrins having the acetylene spacer in various positions. The diethyl-ester protected derivatives of the carboxylic acids and their zinc and magnesium metal complexes were studied using spectroelectrochemistry in order to reveal the qualitative redox properties of these systems. The fourth chapter discusses the design, synthesis and characterization of a series of metallated homoleptic and heteroleptic dypyrrinato complexes, using the dipyrrin 5-ethynyl-ferrocenyl dipyrrin. These molecules were synthesized with the prospect of validating the role of such complexes as a part of a dye or an electrolyte in dye-sensitized solar cells. Electrochemical and spectroelectrochemical studies in solution were also performed.

This thesis describes the investigation of phase behaviour of binary and ternary mixtures at high pressure. The particular applications chosen to be explored in this phase behaviour investigation were supercritical fluid electrodeposition (SCFED) and carbon capture and storage (CCS). Chapter 1 introduces the phase behaviour of mixtures. Chapter 2 describes the equipment and analytical techniques used throughout this thesis including the high-pressure variable-volume view cell, electrical conductivity cell, high pressure FTIR cell, and high-pressure optical fiber phase analyser. Chapter 3 details the solubility and conductivity investigation of several supporting electrolytes in difluoromethane (CH2F2), which provided an electrochemical bath with sufficient conductivity for electrodeposition in supercritical fluids. The most effective supporting electrolyte amongst the eight ionic compounds tested was [N(nC4H9)4][Al(OC(CF3)3)4] which was found to give a moderate solubility and the highest conductivity (222 Scm2mol-1) in CH2F2. [N(nC4H9)4][Al(OC(CF3)3)4] was followed by [N(nC4H9)4][FAP] and [N(nCH3)4][FAP], , making all of them to be satisfactory potential supporting electrolytes for SCFED. Chapter 4 describes the investigation of water solubility in CO2/N2 mixtures relevant to the CCS process. The scope of the investigation covers a wide pressure range and two levels of N2 (xN2= 0.05 and xN2= 0.10). This experimental study was conducted by using the FTIR technique as described in further detail in Chapter 2. It was found that the presence of N2 in CO2 lowered the solubility of H2O in supercritical CO2 with N2 compared to pure CO2. The solubility of water also decreases significantly when the concentration of N2 is increased from 5% to 10%. Chapter 5 further explores the role of phase behaviour in the application of CCS with the investigation of the phase envelope of the ternary mixtures of CO2 and permanent gases (Ar, N2, and H2). Three ternary mixtures were measured (90% CO2 + 5% N2 + 5% Ar, 98% CO2 + 1% N2 + 1% Ar, and 95% CO2 + 3% H2 + 2% Ar) by using the fiber optic reflectometer, as described in further detail in Chapter 2. The experimental data presented in this part also have been used to validate the equation of state for the CCS applications. It was found that the phase envelope of CO2 shifted to a higher pressure and the two-phase region become broader with the presence of permanent gases. Overall, both GERG-2004 and gSAFT provide a good agreement between the predicted and experimental data for all the ternary mixtures investigated, with the exception of the bubble-point line for the 3%H2 + 2%Ar + 95% CO2 mixture. Finally, Chapter 6 summarises the research that was conducted in this thesis. It also evaluates the progress made towards achieving the aims initially set-up in Chapter 1.

No description available.

No description available.