The Swedish government has decided that waste containing more than 0.1% mercury is to be placed in a permanent repository in the bedrock1,10. To minimize the risk of spreading mercury, elemental mercury must first be converted into a practically insoluble compound. In a PhD investigation of stabilization attempts at SAKAB AB in Kumla favorable conditions for conversion of mercury to cinnabar (the sparingly soluble sulphide form of mercury and the naturally occurring mineral) was found. In a long-term study of diffusion of mercury it was found that water solubility of mercury varied much, from 0.05 to 5 μmolL-1. To be able to study the water solubility of mercury as detailed as possible a speciation method was developed and verified. This investigation includes how different parameters, like matrix properties and Hg0/solution ratios effects the solubility of mercury and how the different species are distributed in the water phase. The total solubility of mercury is very dependent of both the matrix properties and the Hg0/solution ratio. Aqueous elemental mercury (Hg0 aq) is not as matrix dependent as the oxidized species. However, trends show that a higher Hg0/solution ratio contributes to a higher solubility of Hg0 aq. Factors like time, pH, ionic strength and degree of stirring, greatly effects the total solubility of mercury. The concentration of the oxidized mercury species generated from elemental mercury increases over time and is very dependent on the properties of the matrix. After 18 hours the solubility of Hg0 aq ranges from 0.2 to 0.7 μmolL-1, depending on Hg0/solution ratio. The solubility for the oxidized species has a much larger variation, ranging from 0.1 to 28.6 μmolL-1. Among other things, because the composition and redox potential of the matrix plays an important role in what mercuric complexes can be expected to form, and contribute to the solubility. / Det har beslutats av regeringen att senast år 2010 skall kvicksilverhaltigt avfall med en kvicksilverhalt på mer än 0.1% slutförvaras i en stabiliserad from djupt ner i berggrunden. I en doktorsavhandling som genomförts på SAKAB AB i Kumla har det konstaterats att det är möjligt att överföra elementärt kvicksilver till cinnober, den stabila sulfidformen av kvicksilver som för övrigt är ett naturligt förekommande mineral. Experiment som pågått under lång tid för att studera det elementära kvicksilvrets diffusion under olika omständigheter har också utförts. De uppmätta halterna i vattenfasen har varierat mycket, från 0.05 till 5 μmolL-1. Det är vad som ligger till grund för det här arbetet. För att kvicksilvers löslighet skall kunna studeras fullt ut har en specierings metod vidareutvecklats och verifierats att den fungerar. Studien innefattar hur lösligheten av kvicksilver påverkas av olika parametrar, som till exempel; matriser med olika egenskaper och olika kvicksilver/vatten kvoter, samt hur fördelningen mellan oxiderade species och det elementära kvicksilvret är i vattenfasen (Hg0 aq). Den totala lösligheten av kvicksilver beror dels av matrisens egenskaper och mängden kvicksilver i förhållande till mängden vätska. Lösligheten av Hg0 aq är inte lika beroende av matrisen som de oxiderade species. Däremot finns trender som visar att högre Hg0/lösning kvot bidrar till en aningen högre löslighet av Hg0 aq. Tid, konduktivitet, pH och omrörning spelar stor roll för vilken totalhalt och hur stor andel oxiderade species man får i vattenfasen. Lösligheten av Hg0 aq, efter 18 timmar, varierar mellan 0.2 till 0.7 μmolL-1, beroende på Hg0/lösning kvoten. Efter 18 timmar är lösligheten för de oxiderade species mycket mer varierande, från 0.1 till 28.6 μmolL-1. Detta beror bland annat på att matrisens sammansättning och redoxpotential spelar en viktig roll för vilka komplex som kan bildas med kvicksilverjonerna och på så sätt bidra till en ökad löslighet.

Antioxidants are widely used to protect organic materials from damages caused by autoxidation, an oxidation process that occurs under normal aerobic conditions. In this thesis, novel multifunctional organoselenium and organotellurium antioxidants were designed, synthesized, and evaluated in search for compounds with better radical-trapping capacity, regenerability, and hydroperoxide-decomposing ability. Selenium was incorporated into ebselenols and hydroxy-2,3-dihydrobenzo[b]selenophenes and tellurium into diaryl disulfides and aryltellurophenols. All newly developed antioxidants were evaluated in a chlorobenzene/water two-phase lipid peroxidation system containing suitable co-antioxidants in the aqueous phase. Ebselenol carrying a hydroxyl group (OH) ortho to selenium showed a two-fold longer inhibition time than the reference α-tocopherol in the presence of aqueous-phase ascorbic acid. 2,3-Dihydrobenzo[b]selenophenes carrying a 5- or 7-OH outperformed α-tocopherol both when it comes to radical-trapping capacity and regenerability. Alkyltellurothiophenols, in situ formed from their corresponding disulfides by tris(2-carboxyethyl)phosphine, were also efficient regenerable radical-trapping antioxidants. The consumption of N-acetylcysteine in the water phase was followed and found to be limiting for the duration of the inhibition. The hydroperoxide-decomposing ability of all organoselenium antioxidants was evaluated. Ebselenols were often better glutathione peroxidase mimics than the parent. In an effort to find out more about antioxidant mechanisms, aryltellurophenols carrying electron donating and electron withdrawing groups in the phenolic or aryltelluro parts were synthesized and OH bond dissociation enthalpies, BDEO-Hs, were calculated. Compounds carrying electron donating groups in the phenolic or aryltelluro part of the molecule showed the best radical-trapping capacity. Deuterium labelling experiments suggested that hydrogen atom transfer could be the rate-limiting step in the antioxidant mechanism.

This thesis presents the synthesis, properties, and applications of two important classes of metal-organic frameworks (MOFs); lanthanide MOFs and hierarchical porous zeolitic imidazolate frameworks (ZIFs). The materials have been characterized using a wide range of techniques including diffraction, imaging, various spectroscopic techniques, gas sorption, dynamical light scattering (DLS) and thermogravimetric analysis (TGA). In Chapter 1, the unique features of MOFs and ZIFs as well as their potential applications are summarized. In Chapter 2, different characterization techniques are presented. Chapter 3 describes a family of new isoreticular lanthanide MOFs synthesized using tri-topic linkers of different sizes, H3L1-H3L4, denoted SUMOF-7I-IV (Ln) (SU; Stockholm University, Ln = La, Ce, Pr, Nd, Sm, Eu and Gd, Paper I). The SUMOF-7I-III (Ln) contain permanent pores and exhibit exceptionally high thermal and chemical stability. The luminescence properties of SUMOF-7IIs are reported (Paper II). The influences of Ln ions and the tri-topic linkers as well as solvent molecules on the luminescence properties are investigated. Furthermore, the potential of SUMOF-7II (La) for selective sensing of Fe (III) ions and the amino acid tryptophan is demonstrated (Paper III).  Chapter 4 presents a simple, fast and scalable approach for the synthesis of hierarchical porous zeolitic imidazolate framework ZIF-8 and ZIF-67 using triethylamine (TEA)-assisted approach (Paper IV). Organic dye molecules and proteins are encapsulated directly into the ZIFs using the one-pot method. The photophysical properties of the dyes are improved through the encapsulation into ZIF-8 nanoparticles (Paper IV). The porosity and surface area of the ZIF materials can be tuned using the different amounts of dye or TEA. To further simplify the synthesis of hierarchical porous ZIF-8, a template-free approach is presented using sodium hydroxide, which at low concentrations induces the formation of zinc hydroxide nitrate nanosheets that serve as in situ sacrificial templates (Chapter 5, Paper V). A 2D leaf-like ZIF (ZIF-L) is also obtained using the method. The hierarchical porous ZIF-8 and ZIF-L show good performance for CO2 sorption. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 5: Manuscript.</p>

In this thesis, a polypeptide binder concept is illustrated. By conjugation to a set of sixteen polypeptides, a small binding molecule can evolve into a polypeptide binder with increased affinity and selectivity. The concept was applied to 2-oxo-1,2-dihydroquinoline-8-carboxylic acid (DQ) and acetazolamide (AZM) for development of high affinity binders targeting human C-reactive protein (CRP) and human carbonic anhydrase (HCA) II and IX respectively. In addition, peptididic macrocycles were developed as inhibitors of lysine specific demethylase 1 (LSD1). CRP is a well-known biomarker of inflammation in humans and binders recognizing it are therefore of large interest as medical diagnostics. Until now, phosphocholine (PCh) and derivatives are the only known small molecule binders for CRP, but they have low μM affinity and bind CRP in a Ca2+ dependent manner. The small molecule DQ was designed as a CRP binder that is structurally unrelated to PCh. Its polypeptide conjugate, 4-C25l22-DQ, was demonstrated as a strong, Ca2+ independent binder for CRP, and had an affinity approximately three orders of magnitude higher than DQ itself. HCA IX is a protein that is interesting for diagnosis of cancer. AZM is a small molecule inhibitor of HCAs with a dissociation constant of 38 nM for HCA II and 3 nM for HCA IX. Interestingly, polypeptide conjugate 4-C10L17-AZM displayed stronger binding to both HCA II (KD 4 nM) and HCA IX (KD 90 pM). This result provided evidence that the binder concept can be applied also for small molecules which already have high affinity for their protein receptors. LSD1 is an enzyme that regulates the methylation of Lys 4 of histone 3 via a PPI-like interaction and which is of therapeutic interest in certain cancers. Based on the structures of two peptidic ligands bound to LSD1, we sequentially prepared truncated, mono-substituted and macroyclic peptides in order to develop reversible inhibitors of LSD1. Some stapled cyclic peptides bound to LSD1 with 10-fold higher affinity than the corresponding linear parent peptide. Changing the staple into a lactam further improved the binding potency and the best lactams inhibited the enzymatic activity of LSD1 at low μM Ki values.

This thesis covers the development of catalytic methodologies for the mild and chemoselective hydrosilylation of amides. The first part describes the investigation of the Mo(CO)6-catalyzed reduction of carboxamides. It was found that the reduction could be controlled by tuning the reaction temperature and either amines or aldehydes could be obtained selectively. The system showed an unprecedented chemoselectivity and the amide reduction could take place in the presence of other reducible functional groups such as ketones, aldehydes, and imines. Moreover, the transformation could be performed on a preparative scale and was further employed in the synthesis of Donepezil, a pharmaceutical drug used in the treatment of Alzheimer´s disease. The third chapter concerns the development of the Mo(CO)6-mediated hydrosilylation protocol for the reduction of carboxamides containing acidic α-hydrogens. In this case, enamines were formed and a high level of chemoselectivity was observed. Enamines containing sensitive functional groups such as ketones, aldehydes and imines were generated. The enamines were not isolated but used in subsequent catalytic reductive functionalization of amides, which is described in the last part of the thesis (Chapters 4 – 7). The in situ formed enamines were reacted with a wide variety of electrophiles, generating heterocyclic compounds as triazolines, triazoles, 4,5-dihydroisoxazoles and pyrimidinediones. N-sulfonylformamidines as well as thioacrylamides could also be prepared with this approach. The protocols for the synthesis of triazolines, triazoles and N-sulfonylformamidines could additionally be performed on a preparative scale, showing the practicality of the methodology.

This work is a cooperation with Boliden Minerals AB, who recently has been interested in recovering more valuable elements from their byproducts. For this case, solvent extraction was chosen as a potential method of recovering these valuables, as it is a method considered to be ideal for separation of trace elements from large amounts of other substances. The goal for this work was to execute manual extraction experiments as a preparation for a bigger project at LTU. The objectives of this thesis included the investigation of the selectivity for extraction of tin and antimony, using different concentrations of hydrochloric acid in the feed solution, analysis of the equilibrium isotherms for Sn and Sb at 8M of HCl as well as the evaluation of the number of steps needed for future extraction experiments, using the McCabe- Thiele method. By executing manual experiments with a speiss precipitate dissolved in hydrochloric acid, the results obtained indicated that the selectivity increased with a higher content of HCl in the feed solution. Using different ratios between the aqueous and organic phase, the equilibrium curves denoted a pushback effect, causing antimony to migrate back into the aqueous phase at the saturation level of tin. By constructing a McCable-Thiele diagram according to the equilibrium curves, the number of steps could be evaluated to three.

Electron crystallography has been proven to be effective for structure determination of nano- and micron-sized crystals. In the past few years, 3D electron diffraction (3DED) techniques were used for the structure solution of various types of complex structures such as zeolites, metal-organic frameworks (MOF) and pharmaceutical compounds. However, unlike X-ray crystallography, electron diffraction has not yet become an independent technique for a complete structure determination due to relatively poorer diffraction intensities and often powder X-ray diffraction data are used for structure validation and refinement. Electron beam damage to the structures that are sensitive to high energy electrons and dynamical scattering are important factors to lead to the deviation of electron diffraction intensities from the squared amplitudes of the structure factors. In this thesis, we investigate various aspects around the 3D electron diffraction data quality and strategies for obtaining better data and structure models. We combined 3D electron diffraction methods and powder X-ray diffraction to determine the structure of an open-framework material and discussed the difficulties and limitations of electron diffraction for beam sensitive materials. Next, we illustrated the structure determination of a pharmaceutical compound, bismuth subgallate, using 3D electron diffraction. While severe beam damage and diffuse scattering were observed in the dataset collected with the conventional rotation electron diffraction (RED) method, the continuous rotation electron diffraction (cRED) method coupled with sample cooling significantly improved the data quality and made the structure solution possible. In order to better understand the potentials and limitations of the continuous rotation method, we collected multiple datasets from different crystals of a known structure and studied the data quality by evaluating the accuracy of the refined structure models. To tackle dynamical scattering in electron diffraction data, we explored a routine for structure refinement with dynamical intensity calculation using RED data from a known structure and discussed its potentials and limitations. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>

The work in this thesis describes the development of new heteroarylation methodology based on transition metal-catalysed C-H functionalisation and the properties of organomain group compounds. The underlying reaction mechanisms and reactivity patterns of the (hetero)arene substrates are also investigated. The selective C2-H arylation indoles, which are key pharmaceutically-relevant units, was achieved using N-pyrimidyl directing groups, RuII catalysis and arylboronic acids as the coupling reagents (paper I). The use of this set of conditions enabled a remarkable functional group tolerance, highlighted by the preservation of halide substituents on both coupling partners. Mechanistic experiments suggest that cleavage of the C2-H bond occurs through an electrophilic aromatic substitution type pathway. The dehydrogenative C2-H silylation of unprotected gramine and tryptamine alkaloids and other related heteroarenes using hydrosilanes under Ru0 catalysis is described in paper II. The protocol does not require protecting groups and undirected C2-H silylation of heteroarenes is possible at higher temperatures. Significantly, H/D-exchange studies revealed deuterium incorporation at the C4 and C7 positions of the indole unit, apart from C2-H silylation. This study represents the first account of C4-H activation using an electron-rich metal catalyst. Paper III describes an unexpected and profound influence of boronate substituents on the regioselectivity of aryne trapping reactions. The boronates may be introduced easily to the backbone of established fluoride-activated precursors via Ir-catalysed C-H functionalisation. Optimisation and mechanistic studies on the unprecedented level of regioselectivity control these substituents permit using external additives is presented.

The chemical bond – a corner stone in science and a prerequisite for life – is the focus of this thesis. Fundamental and applied aspects of chemical bonding are covered including the development of new computational methods for the characterization and rationalization of chemical interactions. The thesis also covers the study of corrosion of copper-based materials. The latter is motivated by the proposed use of copper as encapsulating material for spent nuclear fuel in Sweden. In close collaboration with experimental groups, state-of-the-art computational methods were employed for the study of chemistry at the atomic scale. First, oxidation of nanoparticulate copper was examined in anoxic aqueous media in order to better understand the copper-water thermodynamics in relation to the corrosion of copper material under oxygen free conditions. With a similar ambition, the water-cuprite interface was investigated with regards to its chemical composition and reactivity. This was compared to the behavior of methanol and hydrogen sulfide at the cuprite surface. An overall ambition during the development of computational methods for the analysis of chemical bonding was to bridge the gap between molecular and materials chemistry. Theory and results are thus presented and applied in both a molecular and a solid-state framework. A new property, the local electron attachment energy, for the characterization of a compound’s local electrophilicity was introduced. Together with the surface electrostatic potential, the new property predicts and rationalizes regioselectivity and trends of molecular reactions, and interactions on metal and oxide nanoparticles and extended surfaces. Detailed atomistic understanding of chemical processes is a prerequisite for the efficient development of chemistry. We therefore envisage that the results of this thesis will find widespread use in areas such as heterogeneous catalysis, drug discovery, and nanotechnology. / Den kemiska bindningen – en hörnsten inom naturvetenskapen och oumbärlig för allt liv – är det centrala temat i den här avhandlingen. Både grundläggande och tillämpade aspekter behandlas. Detta inkluderar utvecklingen av nya beräkningsmetoder för förståelse och karaktärisering av kemiska interaktioner. Dessutom behandlas korrosion av kopparbaserade material. Det sistnämnda är motiverat av förslaget att använda koppar som inkapslingsmaterial för hanteringen av kärnavfall i Sverige. Kvantkemiska beräkningsmetoder enligt state-of-the-art har använts för att studera kemi på atomnivå, detta i nära sammabete med experimentella grupper. Initialt studerades oxidation av kopparnanopartiklar under syrgasfria och vattenrika förhållanden. Detta för att bättre kartlägga koppar-vattensystemets termodynamik. Av samma orsak detaljstuderades även gränsskiktet mellan vatten och kuprit med fokus på dess kemiska sammansättning och reaktivitet. Resultaten har jämförts med metanols och vätesulfids kemiska beteende på ytan av kuprit. En övergripande målsättningen under arbetet med att utveckla nya beräkningsbaserade analysverktyg för kemiska bindningar har varit att överbrygga gapet mellan molekylär- och materialkemi. Därför presenteras teoretiska aspekter samt tillämpningar från både ett molekylärt samt ett fast-fas perspektiv. En ny deskriptor för karaktärisering av föreningars lokala elektrofilicitet har introducerats – den lokala elektronadditionsenergin. Tillsammans med den elektrostatiska potentialen uppvisar den nya deskriptorn förmåga att förutsäga samt förklara regioselektivitet och trender för molekylära reaktioner, och för interaktioner på metal- och oxidbaserade nanopartiklar och ytor. En detaljerad förståelse av kemiska processer på atomnivå är en nödvändighet för ett effektivt utvecklande av kemivetenskapen. Vi förutspår därför att resultaten från den här avhandlingen kommer att få omfattande användning inom områden som heterogen katalys, läkemedelsdesign och nanoteknologi. / <p>QC 20170829</p>

Ultra-high performance liquid chromatography (UHPLC) provides a considerable increase in throughput compared to HPLC and a reduced solvent consumption. The implementation of UHPLC in pharmaceutical analysis, e.g. quality control, has accelerated in recent years and there is currently a mix of HPLC and UHPLC instrumentation within pharmaceutical companies. There are, however, technical and regulatory challenges converting a HPLC method to UHPLC making it difficult to take full advantage of UHPLC in regulatory-focused applications like quality control in pharmaceutical production. Using chromatographic modelling and fundamental theory, this thesis investigated method conversion between HPLC and UHPLC. It reports on the influence of temperature gradients due to viscous heating, pressure effects and stationary phase properties on the separation performance. It also presents a regulatory concept for less regulatory interaction for minor changes to approved methods to support efficient life cycle management. The higher pressure in UHPLC gave a retention increase of up to 40% as compared to conventional HPLC while viscous heating, instead, reduced retention and the net result was very solute dependent. Selectivity shifts were observed even between solutes with similar structure when switching between HPLC and UHPLC and an experimental method to predict such selectivity shifts was therefore developed. The peak shape was negatively affected by the increase in pressure for some solutes since secondary interactions between the solute and the stationary phase increased with pressure. With the upcoming ICH Q12 guideline, it will be possible for the industry to convert existing methods to UHPLC in a more flexible way using the deeper understanding and the regulatory concept presented here as a case example. / Ultra-high performance liquid chromatography (UHPLC) provides a considerable increase in throughput compared to conventional HPLC and a reduced solvent consumption. The implementation of UHPLC in pharmaceutical analysis has accelerated in recent years and currently both instruments are used. There are, however, technical and regulatory challenges converting a HPLC method to UHPLC making it difficult to take full advantage of UHPLC in regulatory-focused applications like quality control in pharmaceutical production. In UHPLC, the column is packed with smaller particles than in HPLC resulting in higher pressure and viscous heating. Both the higher pressure and the higher temperature may cause changes in retention and selectivity making method conversion unpredictable. Using chromatographic modelling and fundamental theory, this thesis investigates method conversion between HPLC and UHPLC. It reports on the influence of temperature gradients due to viscous heating, pressure effects and stationary phase properties on the separation performance. It also presents a regulatory concept for less regulatory interaction for minor changes to approved quality control methods and how predicable method conversion is achieved by improved understanding.