<p>In the present studies, aspects of some disease activity measures in rheumatoid arthritis (RA) have been investigated, including the effect of glucocorticoids on this activity. In RA, serum interleukin(IL)-6 levels were elevated and were shown to have a circadian rhythm, with peak levels in the morning, declining towards low or normal levels in the afternoon and evening. In contrast, serum levels of tumour necrosis factor(TNF) alpha were low and stable. In other connective tissue diseases, serum TNF alpha levels were elevated but without circadian variation, while IL-6 levels were low and stable. Nocturnal administration (at 2:00 a.m.) of low-dose prednisolone a few hours before the early morning peak of IL-6 was shown to be significantly more effective in reducing clinical symptoms of disease activity and serum IL-6 levels than the traditional morning administration (at 7:30 a.m.) of the same dose of prednisolone. Circulating monocytes are activated in RA, expressing receptors related to adhesion and phagocytosis. Treatment with glucocorticoids suppressed the expression of these receptors on monocytes, and this may be one mechanism of the beneficial effect of glucocorticoids in RA. Endogenous levels of cortisol seem to play a minor role in expression of monocyte receptors. The different acute phase markers used to assess disease activity in RA showed good corrrelations with each other and with serum IL-6 levels. There were especially strong corrrelations between C-reactive protein (CRP) and Serum amyloid protein A (SAA), and between fibrinogen and erythrocyte sedimentation rate (ESR). Fibrinogen and CRP showed stronger correlation than ESR with the Modified Health Assessment Questionnaire (MHAQ) score and with the neutrophil count. Four simple objective function tests were each compared with the HAQ score a with a radiological joint damage score (Larsen score). The objective function tests correlated with the MHAQ score, and each of these two methods of assessing physical disability correlated with pain, CRP and ESR. In addition, most of the objective function tests correlated significantly with radiological joint damage, while the MHAQ score did not.</p>

<p>This thesis describes how radical cyclization chemistry can be applied for the construction of heterocyclic compounds.</p><p>In the first part, a series of electron deficient α-phenylselenenylalkenes were prepared <i>via</i> a PhSeCl-addition/HCl-elimination sequence. Allyl- and propargylamines readily underwent conjugate addition to these species to produce pyrrolidines or dihydropyrrol derivatives, after triethylborane initiated reductive radical cyclization in the presence of tris(trimethylsilyl)silane.</p><p>The second part describes a convergent synthesis of the pineal hormone melatonin. The indole nucleus is secured <i>via</i> a tris(trimethylsilyl)silane mediated<i> 5-exo</i> radical cyclization. The protocol provides convenient and simple access to compounds useful for studies of biological activity and structure activity relationships.</p><p>The third part describes construction of substituted tetrahydrofuran-3-ones and pyrrolidin-3-ones. Regioselective ring-opening of epoxides or aziridines with benzeneselenolate/tellurolate, followed by Michael addition to electron deficient alkynes afforded the corresponding O/N-vinylated compounds. The tetrahydrofuran-3-ones and pyrrolidin-3-ones were secured <i>via </i>radical carbonylation/reductive cyclization using pressurized carbon monoxide (80 atm).</p><p>The fourth part is concerned with the effect of an N-protecting group on the cyclization of 2-substituted-3-aza-5-hexenyl radicals. Relative energies for reactants and transition states were determined using density functional calculations. Reactant and transition state conformers leading to <i>cis</i>-product were lower in energy than those leading to<i> trans</i>-product. The results can be explained by the unfavorable 1,2-strain present in chair-equatorial and boat-equatorial conformers.</p>

<p>Due to the small dimensions, nanoparticles and materials consisting of nano-sized building blocks exhibit unique — mostly superior — properties, well differing from their bulk counterpart. Most of the novel properties of nanoparticles (and nanomaterials) are size-dependent, while the majority of the common gasphase methods used for generation of nanopowders result in different, usually wide, size-dispersions. Further understanding of the fundamental processes leading to particle formation is therefore required, leading to better control of size and distribution of the nanoparticles, thus allowing engineering of the desired properties for both nanoparticles and nanomaterials.</p><p>In this present thesis, nanoparticles were produced by two different gasphase techniques activated by lasers, namely laser chemical vapor deposition (LCVD) and pulsed laser ablation (PLA). Optical emission spectroscopy (OES) was performed on thermal (blackbody-like) radiation originating from laser-excited particles during LCVD and coupled to measured size-distributions. In-situ monitoring of size-distributions by a differential mobility analyzer (DMA) was employed during PLA. In addition, deposited nanoparticles were characterized by a variety of standard techniques.</p><p>Different cooling mechanisms of the laser-excited gasphase particles were identified based on temperature and emitted intensity data extracted from OES measurements. The strong evaporation at elevated temperatures also allowed direct size manipulation of the particles. By monitoring the intensity of the emitted thermal radiation and the scattered laser line, strong indications about the so called coagulation limit, where a broadening of the size-distribution occurred, was obtained. The DMA monitoring, supported by modeling, gave information about different mechanisms (thermal and photochemical) of the ablation process, and particle condensation well below the ablation threshold was also found.</p>

<p>Future energy systems based on hydrogen as energy carrier require reliable ways for storing hydrogen gas in safe, clean and efficient ways. Metal hydrides absorb hydrogen gas reversibly, making them suitable for storage applications. Investigations of the crystal structures of these materials contribute to an understanding of the factors which can influence the absorption<i>. </i></p><p>Three systems, Ti₃Sn-D, Nb₄MSi-D (M=Co or Ni) and Pd-Ni-P, have been investigated in this thesis. Various solid state synthesis techniques have been used for sample preparation. The crystal structures have been studied using x-ray and neutron diffraction techniques.</p><p>Three metal hydride phases were found in the Ti₃Sn-D system upon hydrogenation. Deuterium occupies titanium octahedra and the applied deuterium pressure induces the phase transitions. The distances between the deuterium atoms increase from 2.47 Å in orthorhombic Ti₃SnD_0.80 to 4.17 Å in cubic Ti₃SnD.</p><p>The Nb₄MSi-D system (M=Co or Ni) readily absorbs deuterium at room temperature and 90 kPa deuterium pressure to give a deuterium content of Nb₄MSiD_~2.5. Two interstitial voids, both coordinated by four niobium atoms arranged in a tetrahedral configuration, accommodate deuterium atoms. </p><p>Two ternary phases and a solid solution of nickel in Pd₃P have been synthesised and the crystal structures determined. PdNi₂P is orthorhombic and crystallises in the MgCuAl₂-type structure: an ordered derivative of the Re₃B-type structure. Pd₈Ni₃₁P₁₆ is a tetragonal high-temperature phase stable at 700°C with 110 atoms in the unit cell. Pd_2.7Ni_0.3P_0.94 has the cementite-type structure with mixed occupancy of palladium and nickel at one of the two non-equivalent crystallographic metal positions.</p>

<p>The interactions between the molecular constituents in dye-sensitized solar cells were studied with UV-VIS and IR spectroscopy, Raman scattering, conductivity and electron accumulation measurements.</p><p>From stability studies of the dye, bis(tetrabutylammonium)cis-bis(thiocyanato) bis(2,2’-bipyridine-4-carboxylic acid, 4’-carboxylate) ruthenium(II), in the complete solar cell, the thiocyanate ion ligand was found to be lost from the dye. A method was developed to study mechanisms in a sealed dye-sensitized solar cell using resonance Raman scattering (RRS). RRS studies of a complete dye-sensitized solar cell including iodine and lithium iodide in the electrolyte indicate that triiodide exchange the SCN^- ligand of the dye. It was proposed that an ion pair Li⁺…I₃^- formation occurred, which, by a reduced electrostatic repulsion between I₃^- and SCN^- facilitated the exchange of these anions at Ru(II) of the dye. The additive 1-methylbenzimidazole suppressed the SCN^-/I₃^- ligand exchange by forming a complex with Li⁺.</p><p>In order to study charge transport in nanostructured TiO₂ films permeated with electrolyte, a technique was developed for determining activation energies of conduction, electron accumulation and effective mobility. Two regions were distinguished from the relation between conductivity and electron concentration. In the first region (~1-20 electrons per TiO₂ particle), which resembles best the region where the nanostructured dye-sensitized solar cell operates, the results can be fitted to some extent with a trapping/detrapping or a hopping model for charge transport, but not with a conduction band model. For the second region (> 20 electrons per TiO₂ particle), charge transport by electrons in the conduction band seems to be the most applicable model.</p><p>Through this work many effects from the interplay between the solar cell components were observed. These observations emphasize the importance of well-balanced interactions in dye-sensitized solar cells.</p>

<p>Conjugated polymers that exhibit high electronic conductivities play key roles in the emerging field of molecular electronics. In particular, linking metal centres with useful electrochemical, photophysical, or catalytic properties to the backbone, or within the polymer chain itself, is a topic which has attracted a significant amount of interest lately. Structurally rigid monomers that can be electropolymerised to form highly conducting molecular wires may provide new insights into conduction mechanisms, e.g., exploiting resonant superexchange (electron-hopping) by tuning the energies of redox centre and bridge states. The focus of this thesis lies on the electrochemical investigation of preparation, growth dynamics, and charge transport dynamics of oligothiophene/transition metal hybrid materials. The incorporation of ruthenium(II) and osmium(II) terpyridine complexes into such polymeric assemblies was accomplished by an electropolymerisation procedure, to produce rod-like oligothienyl-bridged metallopolymers. The properties of the monomers used were characterised by optical spectroscopy and electrochemical techniques. Charge transport was studied in detail for some of the materials created, and it was found that the electron transport rate and dc conductivity was enhanced by up to two orders of magnitude compared to relevant non-conjugated polymers, demonstrating the usefulness of this approach for optimization of charge transport in metallopolymers. The charge transport diffusion coefficent was determined to (2.6 ± 0.5) x 10^-6 cm² s^-1 for a quaterthienyl-bridged {Os(tpy)₂} polymer by use of an electrochemical steady-state method carried out using a transistor-like experimental geometry. It was found that charge transport in these materials is concentration-gradient driven. The rate limiting step of the charge transport process was investigated using electrochemical impedance spectroscopy. The electropolymerisation dynamics of one of the monomers was studied using microelectrodes, and the results obtained shows that electropolymerisation is highly efficient, and indicate that mass transport controls this process. Through a combination of controlled potential deposition and SEM imaging it was demonstrated that it is possible to exploit the edge effect of microelectrodes to promote film growth in a direction co-planar with the electrode surface.</p>

<p>The development of more advanced materials forms the basis of technological progress. One group of fascinating compounds with many potential applications in spintronic devices are the mixed-valence perovskite manganites. These have attracted considerable interest during the last decade through their very large magnetoresistance near the Curie Temperature. Although the properties of a material determinie any application, the development of reliable and flexible synthesis methods is crucial, as is the understanding of these methods. Knowledge of how different materials are formed is also of general importance in tailoring new materials. The aim of this project has therefore been not only to develop a new synthesis route, but also to understand the mechanisms involved.</p><p>This thesis describes the synthesis and characterization of a novel manganese alkoxide and its use in sol–gel processing of magnetoresistive perovskite manganites. In searching for a soluble manganese alkoxide for sol–gel processing, we found that the methoxy-ethoxide, [Mn₁₉O₁₂(moe)₁₄(moeH)₁₀]·moeH, has a high solubility in appropriate organic solvents. Being 1.65 nm across, it is one of the largest alkoxides reported; it is also of interest because of its (for oxo-alkoxides) rare planar structure. After mixing with La, Nd, Ca, Sr, and Ba methoxy-ethoxides, [Mn₁₉O₁₂(moe)₁₄(moeH)₁₀]·moeH was used in the first purely alkoxide based sol–gel processing of perovskites manganites. The phase evolution on heating xerogel powders to 1000°C was studied, and thin films were prepared by spin-coating.</p><p>It was found that the easily oxidised Mn-alkoxide facilitates the formation of high oxygen-excess modifications of the perovskites. The reactive precursor system yields fully hydrolysed gels almost without organic residues, but the gel absorbs CO₂ from the air, leading to carbonate formation. The carbonate decomposition is the limiting step in oxide formation. Transport measurements of La_0.67Ca_0.33MnO₃ films on LaAlO₃ substrate show that all-alkoxide sol–gel derived films can compete with PLD films in terms of quality of epitaxy and transport. The somewhat different behaviour of the sol–gel derived films compared to PLD films is attributed to differences in morphology and oxygen stoichiometry.</p>

<p>Peptide secondary structure mimetics are important tools in medicinal chemistry, as they provide analogues of endogeneous peptides with new physicochemical and pharmacological properties. The <i>β</i>-hairpin motif has been shown to be involved in numerous physiological processes, among others in regulation of eucariotic gene transcription. This thesis addresses the design, synthesis and conformational analysis of photoswitchable <i>β</i>-hairpin mimetics.</p><p>The developmental work included the establishment of an improved procedure for cross coupling of aryl halides with terminal alkynes. Microwave mediated Sonogashira couplings in closed vessels were optimized under homogeneous and solid-phase conditions furnishing excellent yields for a large variety of substrates within 5 – 25 minutes. In addition, microwave heating was shown not to have any non-conventional effect on the reaction rate.</p><p>Furthermore, the most important factors affecting <i>β</i>-hairpin stability were evaluated. Studies of tetrapeptide and decapeptide analogues revealed the essential role of the <i>β</i>-turn in initiation of hairpin folding. Moreover, hydrogen bonding was shown to be the main interchain stabilizing force, whereas hydrophobic interactions were found to be relatively weak. Nevertheless, hydrophobic packing appears to provide an important contribution to the thermodynamic stability of <i>β</i>-hairpins.</p><p>Photoswitchable peptidomimetics were prepared by incorporation of various stilbene moieties into tetra- and decapeptides. Synthesis, photochemical isomerisation and spectroscopic conformational analysis of the compounds were performed.</p>

<p>The combination of capillary electrophoresis (CE) and mass spectrometry (MS) constitutes a powerful microanalytical system in the fields of biology, medicine and chemistry. This thesis describes the development of three novel capillary coatings and demonstrates how these extend the utility of CE as a high-efficiency separation technique in protein analysis and biopharmaceutical drug screening.</p><p>Due to the rapidly growing interest in characterizing the human proteome, there is an increased need for rapid protein separations. The use of CE in protein analysis is, however, nontrivial due to problems with protein adsorption to the fused-silica capillary walls. In this thesis, this problem was addressed by developing two novel, physically adsorbed, cationic polymer surface coatings, denoted PolyE-323 and Q-agarose. By using simple rinsing protocols, highly reproducible coatings, stable over a wide range of pH 2-11 were generated. Successful protein separations using cationic-coated capillaries in CE-MS, equipped with either electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI), has been demonstrated.</p><p>In the pharmaceutical industry, favorable pharmacokinetic properties of a candidate drug, such as high bioavailability after oral administration, are crucial for a high success rate in clinical development. Tools for prediction of biopharmaceutically relevant drug properties are important in order to identify and discard poor candidate drugs as soon as possible. In this thesis, a membrane mimetic coating was developed by electrostatically immobilizing liposomes to the capillary wall, via an anchoring sublayer of Q-agarose. The liposome-coated capillaries were demonstrated in on-line CE-MS for prediction of drug membrane permeability.</p>

<p>In microscale separations, such as capillary electrophoresis and -liquid chromatography, the liquid flow rates are in the order of nanoliters per second. If such flow rates are to be interfaced with a mass spectrometer (MS) using electrospray (ES) ionization, without loss of separation efficiency, each fraction of the analyte zone must remain undisturbed by the high voltage contact necessary for ES. One design that accomplishes this is the pure sheathless approach, where a thin, vapor deposited metal film covers the outside of the electrospray emitter tip. </p><p>This thesis describes the development of such sheathless emitters. The lifetimes of polymer embedded gold (“fairy dust”) or graphite (“black dust”) emitters were shown to by far exceed those of previously used conductive films. In addition, the production of emitters with these coatings was substantially simplified. The increase in durability was found to be due to enhanced resistance towards the electrochemical processes associated with ES. In analogy, the reasons for the limited durability of previously used methods were correlated with their tendency to oxidize, or be mechanically removed, during electrochemical reactions. </p><p>Electrochemical processes associated with the electrospray potential were also found to seriously disturb analyses in which porous graphitic carbon was used as the separation medium. A proper choice of grounding point locations eliminated these disturbances.</p><p>At last, the differences regarding analytical performance of several sheathless interface configurations, used in capillary liquid chromatography, were examined. The best performance was obtained when a pure sheathless emitter with a conductive layer of polyimide and graphite was coupled to the LC column through a Teflon sleeve.</p>