Various chemical properties can be used to characterise dissolving pulp. The quality of the pulp must be carefully controlled to ensure that it meets the requirements for its intended use and the further processes to be applied. If it is to be used to prepare viscose, or other cellulose derivatives, the key prop-erties of the pulp are its accessibility and reactivity. The studies described in this thesis investigated the potential utility of multivariate analysis of chemi-cal and spectral data for determining the properties of dissolving pulp. Dis-solving pulps produced by a two-stage sulfite process, both in the laboratory and a factory were produced pulps for this purpose. The analyses showed that pulp with high reactivity had short cellulose chains, low molecular weight, low polydispersity, low hemicellulose content, high content of ace-tone-extractable compounds, and high surface charge compared to pulp with low reactivity. Important chemical properties of the pulp, such as viscosity and alkali resistance, were successfully predicted from near infrared spectra. Predicting the reactivity, or the viscose filterability, of the pulp was more complex. Several chemical methods for analyzing the reactivity of the pulp were examined. The influence of the cellulose structure at the supermolecu-lar level on the reactivity of the pulp was explored by multivariate analysis of solid state 13C nuclear magnetic resonance spectra. Structural variables considered included: differences in hydrogen bonding, contents of hemicel-lulose, amorphous cellulose and crystalline cellulose I and II. Pulps with high reactivity have higher contents of cellulose I and amorphous cellulose than pulps with low reactivity, which have higher contents of cellulose II and hemicellulose.

This thesis describes water proton and deuterium relaxation processes, as seen by Nuclear Magnetic Resonance (NMR) spectroscopy, using Brownian Dynamics (BD) or Molecular Dynamics (MD) simulations. The MD simulations reveal new detailed information about the dynamics and order of water molecules outside of a lipid bilayer. This is very important information in order to fully understand deuterium NMR measurements in lipid bilayer systems, which require an advanced analysis, because of the complicated water motion (such as tumbling and self-diffusion). The BD simulation methods are combined with the powerful Stochastic Liouville Equation (SLE) in its Langevin form (SLEL) to give new insight into both 1H2O and 2H2O relaxation. The new simulation techniques which combine BD and SLEL can give important new information in cases where other methods do not apply. The deuterium relaxation is described in the context of a water/lipid interface and is in a very elegant way combined with the simulation of diffusion on curved surfaces developed by our research group. 1H2O spin-lattice relaxation is described for paramagneticsystems. With this we mean systems with paramagnetic transition metal ions or complexes, that are dissolved into a water solvent. The theoretical description of such systems are quite well investigated but such systems are not yet fully understood. An important consequence of the Paramagnetic Relaxation Enhancement (PRE) calculations when using the SLEL approach combined with BD simulations is that we obtain the electron correlation functions, which describe the relaxation of the paramagnetic electron spins. This means for example that it is also straight forward to generate Electron Spin Resonance (ESR) lineshapes.

This thesis describes synthesis and reactivity studies of 2-amino-2-siloxysilenes and 2-silenolates, species that are strongly influenced by reversed Si=C bond polarization, i.e. an Siδ-=Cδ+ polarization as compared to the natural Siδ+=Cδ- polarization. Because of the reversed polarization, the 2-amino-2-siloxysilenes are zwitterions and the 2-silenolates are predominantly described by the resonance structure with the negative charge at Si. Transient zwitterionic 2-amino-2-siloxysilenes are formed thermolytically from carbamylpolysilanes (tris(trimethylsilyl)silylamides) and trapped with 1,3-dienes in nearly quantitative yields. These silenes have structure and reactivity characteristics that differ from earlier studied Si=C bonded compounds. They are thermodynamically stable toward dimerization and react with 1,3-dienes to give exclusively [4+2] cycloadducts. Their reactions with 1,3-dienes proceed in accordance with inverse electron demand (IED) Diels-Alder reactions which is explained by the electron-rich nature of these silenes. The 2-amino-2-siloxysilenes are also less reactive toward alcohols than earlier silenes. Hence, alcohols do not react with 2-amino-2-siloxysilenes but with the silene precursor, the carbamylpolysilanes, leading to alkoxysilanes in high yields. The latter reaction represents a novel base-free synthetic protocol for protection of primary and secondary alcohols with the fluoride resistant but photolabile tris(trimethylsilyl)silyl group. Another class of formally Si=C bonded compounds, metal 2-silenolates, has been formed in high yields using a novel facile method. Reaction of acyl- and carbamylpolysilanes with potassium tert-butoxide in tetrahydrofurane gives potassium 2-silenolates. The potassium 2-silenolates are stable at room temperature, in contrast to earlier lithium 2-silenolates that degrade rapidly at ambient temperature. The first crystallisable complex of a 2-silenolate was formed and characterized by X-ray crystallography. This 2-silenolate has a pyramidal central Si (ΣSi = 317.8°), and an Si-C single rather than Si=C double bond (r(SiC) = 1.926 Å). The potassium 2-silenolates give exclusively Si alkylated products with alkyl halides and only [4+2] cycloadducts with 1,3-dienes.

This thesis describes the utilization of the matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) and electrospray ionization (ESI) MS techniques for analysis of complex brain tissue samples. Direct molecular profiling of biological samples using MALDI MS is a powerful tool for identifying phenotypic markers. MALDI MS-profiling of proteins and peptides directly on brain tissue sections was used for the first time to study experimental models of Parkinson’s disease (PD). The mass spectrometer was used to map the peptide and protein expression directly on 12 µm tissue sections in mass-to-charge (m/z) values, providing the capability of mapping specific molecules of the original sample, that is, localization, intensity and m/z ratio. Several protein and peptide expression profile differences were found in the dopamine denervated brains when compared to the corresponding controls, for example, calmodulin, cytochrome c, cytochrome c oxidase, and the neuroimmunophilin protein FKBP-12. The increased expression of FKBP-12 from the profiling experiments was supported by mRNA expression analysis and two-dimensional gel electrophoresis separation analysis. Multiple genetic deficits have linked impaired ubiquitin-conjugation pathways to various forms of familiar PD. This study showed for the first time an increased level of unconjugated ubiquitin specifically in the dorsal striatum of the dopamine depleted PD brain. The strength of the MALDI MS-profiling technique is that a minimum of sample handling and manipulation is necessary pre-analysis. This ensures preservation of the spatial localization of the biomolecules in the tissue section. Biological liquid samples often contain high amounts of salt that is non-compatible with the ESI MS technique. A nano-flow capillary liquid chromatography (nanoLC) system coupled on-line with ESI-MS was used to study the metabolism of the peptide LVV-hemorphin-7 in the brain and blood using in vivo microdialysis. The microdialysis technique provides capabilities for very precise sampling in specific brain regions. The combination of on-line desalting and pre-concentration by nanoLC with ESI MS is a powerful tool to detect minute concentration of metabolic fragments and endogenous biomolecules. The utilization of mass spectrometry in neuroscience applications provides a uniquely advantageous tool for the analysis of complex biochemical events that underlie the pathological symptoms expressed in different disease states. Furthermore, the MALDI-MS profiling technique shows great potential for the future with regards to proteome analysis and drug discovery.

This thesis describes mechanistic studies, rational ligand design, and synthesis of asymmetric transition metal catalysts. The topics addressed concerned [Papers I-VII]: [I] The asymmetric addition of diethyl zinc to N-(diphenylphosphinoyl)benzalimine catalyzed by bicyclic 2-azanorbornyl-3-methanols was studied. An efficient route to both diastereomers of new bicyclic 2-azanorbornyl-3-methanols with an additional chiral center was developed, in the best case 97% ee was obtained with these ligands. The experimental results were rationalized by a computational DFT-study. [II] An aza-Diels-Alder reaction of cyclopentadiene with chiral heterocyclic imines derived from (S)-1-phenylethylamine and different heteroaromatic aldehydes was developed. The cycloaddition proved to be highly diastereoselective and offers a very rapid access to possible biologically active compounds and interesting precursors for chiral (P,N)-ligands. [III] A convenient and high-yielding method for the preparation of (R)-tolterodine, utilizing a catalytic asymmetric Me-CBS reduction was developed. Highly enantio-enriched (R)-6-methyl-4-phenyl-3,4-dihydrochromen-2-one (94% ee) was recrystallized to yield practically enantiopure material (ee >99%) and converted to (R)-tolterodine in a four-step procedure. [IV] The reaction mechanism of the iridium-phosphanooxazoline-catalyzed hydrogenation of unfunctionalized olefins has been studied by means of DFT-calculations (B3LYP) and kinetic experiments. The calculations suggest that the reaction involves an unexpected IrIII-IrV catalytic cycle facilitated by coordination of a second equivalent of dihydrogen. On the basis of the proposed catalytic cycle, calculations were performed on a full system with 88 atoms. These calculations were also used to explain the enantioselectivity displayed by the catalyst. [V and VI] A new class of chiral (P,N)-ligands for the Ir-catalyzed asymmetric hydrogenation of aryl alkenes was developed. These new ligands proved to be highly efficient and tolerate a broad range of substrates. The enantiomeric excesses are, so far, the best reported and can be rationalized using the proposed selectivity model. [VII] The complex formed between the quincorine-amine, containing both a primary and a quinuclidine amino function, and [Cp*RuCl]4 catalyzes the hydrogenation of aromatic and aliphatic ketones in up to 90% ee approx. 24-times faster than previously reported Ru-diamine complexes. The reason for the lower but opposite stereoselectivity seen with the quincoridine-amine, as compared to the quincorine-amine, was rationalized by a kinetic and computational study of the mechanism. The theoretical calculations also revealed a significantly lower activation barrier for the alcohol mediated split of dihydrogen, as compared to the non-alchol mediated process. A finding of importance also for the diphosphine/diamine mediated enantioselective hydrogenation of ketones.

Ten years ago, the first protease inhibitor targeting the human immunodeficiency virus (HIV) was approved for clinical use. Highly active antiretroviral therapy (HAART), which combined protease and reverse transcriptase inhibitors, quickly became the standard therapy for treating patients infected with HIV and Acquired Immune Deficiency Syndrome (AIDS). Nevertheless, last year the AIDS pandemic reached its highest level ever. Many infected patients, mainly in the developing countries, are still without treatment. Among those patients who receive treatment, an increase in drug resistance and new-infection with drug-resistant strains are seen. To come to terms with these problems, new drugs that are efficient against resistant strains and can be produced at low cost are needed. In this study, we have focused our research efforts on cyclic sulfamides active as HIV-1 protease inhibitors. Distinctive to this compound class, as compared to the inhibitors so far approved for clinical use, was the incorporation of a water mimic that displaces the structural water (W301) observed in the X-ray crystal co-complexes. The first part of the study was aimed at understanding the rationale behind the nonsymmetric binding mode that the inhibitor adopted when bound to the enzyme. Symmetric and nonsymmetric inhibitors were synthesized and the structure-activity relationships and preferable binding modes were rationalized with the help of Comparative Molecular Field Analysis (CoMFA). In the second part of the study, an attempt was made to reduce the size of these inhibitors. As a result, the traditional P1/P1' substituents were removed, while the P2/P2' substituents were elongated in an attempt to reach between the binding sites. The design hypothesis was shown to be successful and inhibitors possessing nanomolar activity were identified.

This thesis is based on six papers, Papers I-VI, focusing on the interplay between the stabilizing elements of nucleic acids self-assembly; hydrogen bonding, stacking and solvent effects. In Paper I we investigate how the substitution of the O4' for CH2 in the sugar moiety of adenosine (2'-deoxyaristeromycin) at the A6 position of the Dickerson-Drew dodecamer makes the two modified bases exist in a dynamic equilibrium between Hoogsteen and Watson-Crick base pairing in the NMR time scale. Paper II is a structural study of the incorporation of 1-(1',3'-O-anhydro-β-D-psicofuranosyl)thymine in the T7 position of the Dickerson-Drew dodecamer. NMR constrained molecular dynamics and hydration studies show the base-base distortions caused by the introduction of a North-type locked sugar in an otherwise B-type DNA•DNA duplex. Paper III shows that the stacking distortion caused by the 1-(1',3'-O-anhydro-β-D-psicofuranosyl)thymine building block perturbs the charge transfer similar to a DNA mismatch. Paper IV highlights how the sequence context affects the physico-chemical properties, monitored by the pKa of guanine itself as well as how the charge perturbation is experienced by the neighboring bases, in ssDNA and ssRNA. Paper V focuses on the differences between the structural equilibria of single-stranded ssDNA and ssRNA. Directional differences in single-stranded stacking between ssDNA and ssRNA are identified and provide a basis to explain directional differences in pKa modulation and dangling-end stabilization. In Paper VI the thermodynamic gains of dangling ends on DNA and RNA core duplexes are found to correlate with the X-ray geometries of dangling nucleobases relative to the hydrogen bonds of the closing base pairs.

Nanomaterials have attracted great interest in recent years, and are now also being considered for battery applications. Reducing the particle size of some electrode materials can increase battery performance considerably, especially with regard to capacity, power and rate capability. This thesis presents a study focused on the performance of such a material, vanadium oxide nanotubes, as cathode material for rechargeable lithium batteries. These nanotubes were synthesized by a sol-gel process followed by hydrothermal treatment. They consist of vanadium oxide layers separated by structure-directing agents, normally amines or metal ions, e.g., Na+, Ca2+, Mn2+ and Cu2+. The layers are arranged in a scroll-like manner, allowing the interlayer structure to expand and contract, depending on the size of the embedded guest. This tubular form of vanadium oxide was able to insert lithium ions reversibly, making it a candidate cathode material. The structural and electrochemical response to lithium ion insertion was carefully studied to define optimal performance criteria and probe the lithium insertion mechanism. This was done using several characterization techniques, including X-ray diffraction, a variety of spectroscopic methods and electrochemical testing. Galvanostatic measurements show that the material can be charged and discharged reversibly for >100 cycles with a capacity of 150-200 mAh/g. The electrochemical performance is, however, dependent on the electrode film preparation technique, the choice of salt in the electrolyte and the nature of the embedded guest. Results from photoelectron spectroscopy, and soft X-ray emission and absorption spectroscopy confirm that vanadium is reduced during lithium insertion and that three oxidation states (V5+, V4+ and V3+) co-exist at potentials below 2.0 V. In situ X-ray diffraction, performed during potential stepping, identifies two separate processes during lithium insertion: a fast decrease of the interlayer distance followed by a slow two-dimensional relaxation of the vanadium oxide layers.

This thesis contains two parts. In the first part, general and versatile palladium-mediated 11C-C bond forming reactions for use in the production of radiotracers for Positron Emission Tomography (PET) were explored. Two complimentarty approaches were investigated: the coupling of [11C]methyl iodide with a vinyl stannane and the reaction of a [11C]methylated stannane with various organohalides. The former approach resulted in an improved, fully automated method for the synthesis of the potential cell proliferation tracer 1-(2’-deoxy-2’-fluoro-β-D-arabinofuranosyl)-[methyl-11C]- thymine. The tracer was obtained in an isolated decay-corrected radiochemical yield of 28% at 25 min after end of radionuclide production. In the latter approach, a [11C]methylated tricyclic stannane (5-[11C]methyl-1-aza- 5-stannabicyclo[3.3.3]undecane) was synthesised in 47% decay-corrected radiochemical yield, starting from [11C]methyl iodide. This stannane was successfully employed in palladium-mediated coupling reactions with aryl, heteroaryl and vinyl halides. In the second part, effects of the osmolytes glycine betaine, trimethylamine N-oxide (TMAO) and urea on Ribonuclease A (RNase A) were investigated using Nuclear Magnetic Resonance (NMR) spectroscopy. Changes in the enzymatic activity in the presence of these osmolytes at concentrations of ≤1 M were observed by monitoring the RNase A-catalysed degradation of polyuridylic acid using 31P NMR spectroscopy. The decrease in activity caused by urea was counteracted by both glycine betaine and TMAO at a molar ratio of 1:1.4 and 1:1, respectively. To investigate if the observed activity changes were accompanied by any detectable alteration in the gross conformation of RNase A, diffusion coefficients for the enzyme in the various osmolyte solutions were measured using pulsed-field gradient NMR. A pulse sequence suitable for diffusion measurements in highly concentrated aqueous osmolyte solutions was developed and assessed. The diffusion of RNase A was measured relative to a new internal standard, 2,2,5,5,-tetramethyl-1,4-dioxane. No clear, detectable change in the relative diffusion of RNase A was observed in these media.

Methods for the 11C-labeling of carbonyl compounds applicable in the preparation of radiotracers for Positron Emission Tomography (PET) are described. To this end [11C]carbon monoxide at low concentration was used in transition metal- mediated reactions. Stille couplings were employed in the synthesis of [carbonyl-11C]ketones from methyl and aryl halides with [11C]carbon monoxide. The synthesized [carbonyl-11C]ketones were obtained from the corresponding organostannanes with analytical radiochemical yields up to 98%. A number of synthetic routes were designed using [11C]carbon monoxide and rhodium complexes. Nitrene intermediates were generated from azides and reacted via a rhodium-mediated carbonylation reaction as a general synthetic route to [carbonyl-11C]isocyanates, versatile precursors. [carbonyl-11C]Isocyanate reacted via nucleophilic attack of an amine to form N,N’-diphenyl[11C]urea in 82% analytical radiochemical yield, ethyl phenyl[11C]carbamate was synthesized by the same route, using ethanol as the nucleophile, in 70% radiochemical yield. [11C]Isocyanate was also able to react in a [2+3] cycloaddition with ethylene oxide to form 3-phenyl[carbonyl-11C]oxazolidin-2-one in over 80% analytical radiochemical yield. This method was applied to the synthesis of a potential efflux system tracer [11C]hydroxyurea in 38% isolated radiochemical yield and the derivative 1-hydroxy-3-phenyl[11C]urea in 35% isolated radiochemical yield. Carbene intermediates, generated from diazo compounds, were reacted with [11C]carbon monoxide in the rhodium-mediated synthesis of [carbonyl-11C]ketenes. [carbonyl-11C]Ketene intermediates were utilised in the synthesis of diethyl[carbonyl-11C]malonate, from ethyl diazoacetate and ethanol. The product was obtained with a 20% isolated radiochemical yield. Alkylation of diethyl[carbonyl-11C]malonate, with ethyliodide and tetrabutylammonium fluoride, was successfully accomplished and diethyl diethyl[carbonyl-11C]malonate was synthesized in 50% analytical radiochemical yield. Several (carbonyl-13C)compounds were also synthesized using the described methods as a way of characterizing the position of the label using 13C-NMR.