This thesis deals with the copper-catalyzed substitution of allylic substrates. In the first part of this thesis, the synthesis of a series of metallocenethiolates is described. The thiolates were examined as ligands in the enantioselective copper(I)-catalyzed γ-substitution of allylic acetates. The second part describes a study on copper-catalyzed α-substitution of enantiomerically pure secondary allylic esters. It was observed that the degree of chirality transfer is strongly dependent on the reaction temperature. The loss of chiral information is consistent with an equilibration of the allylCu(III) intermediates prior to product formation, which is essential in order to realize a copper-catalyzed dynamic kinetic asymmetric transformation process. The third part describes a study on copper-catalyzed stereoselective α-substitution of enantiopure acyclic allylic esters. This method, when combined, with ruthenium and enzyme catalyzed dynamic kinetic resolution of allylic alcohols, provides a straightforward route to pharmaceutically important α-methyl carboxylic acids. The fourth part is a mechanistic study on the reaction of perfluoroallyl iodide with organocuprates. Experimental studies as well as theoretical calculations were used to explain the contrasting reactivity of perfluoroallyl iodide vs. allyl iodide in cuprate allylation reactions. In the fifth part, the development of a practical and useful method for the preparation of pentasubstituted acylferrocenes is presented.

This thesis deals with the impact of hydrogen bonding on the properties of phenols. The possibility for tyrosine to form hydrogen bonds to other amino acids has been found to be important for its function as an electron transfer mediator in a number of important redox enzymes. This study has focused on modeling the function of tyrosine in Photosystem II, a crucial enzyme in the photosynthetic pathway of green plants. Hydrogen bonds between phenol and amines in both inter- and intramolecular systems have been studied with quantum chemical calculations and also in some solid-state structures involving phenol and imidazole. Different phenols linked to amines have been synthesized and their possibilities of forming intra- and intermolecular hydrogen bonds have been studied as well as the thermodynamics and kinetics of the generation of phenoxyl radicals via oxidation reactions. Since carboxylates may in principle act as hydrogen bond acceptors in a manner similar to imidazole, proton coupled electron transfer has also been studied for a few phenols intramolecularly hydrogen bonded to carboxylates with the aim to elucidate the mechanism for oxidation. Electron transfer in a new linked phenol—ruthenium(II)trisbipyridine complex was studied as well. The knowledge is important for the ultimate goal of the project, which is to transform solar energy into a fuel by an artificial mimic of the natural photosynthetic apparatus

This project aims to investigate whether it is possible to detect consentrations down to 0,3 µg/L of oseltamirir in waste water by Quartz Crystal Microbalance. The risks linked to this contaminant could be not only environmental, scientists have found that infuence recistence can propagate due to contaminats of this kind. Cases similar to the bird- and swine-flu could occure if the drug spreads through animals and mutate.   Four systems of different character was synthesised. As a result it was found that MAA functional monomer systems probably was interfering with charges within it’s own nanowires. Reference systems could not detect 0,01 mg/mL and HEMA polymer surfaces was the only reliable system, pH of 5,1. Lowest limit of detection (LOD) was found in Molecular Imprinted Polymer nanowires (MIP Nw) at 0,01 mg/mL and could be scaled down to 0,1 mg/L with increased loop size (injection at 10x that of 0,01 mg/mL at about 500 µL and a halved flow rate.)   An alternative could be nano structuring such as ”polystyrene balls” that possibly could be able to achieve surfaces with even more binding sites needed to detect the lowest limit at 0,3 µg/L.

Coronaviruses have been responsible for several global disease outbreaks over the last 20 years, including the “Severe Acute Respiratory Syndrome” in 2002/2003, the “Middle East Respiratory Syndrome” in 2012, and the “Coronavirus Disease of 2019 (COVID19)”. These viruses are highly contagious and can cause multiple medical disorders upon contraction, such as common cold or lower respiratory infections. SARS-CoV-2, the newly emerged coronavirus variant of 2019, has been confirmed as the cause of the ongoing COVID19 pandemic, which infected over 167 million people worldwide and, by the end of May 2021, has a death toll of over 3 million people. Even though several SARS-CoV-2 vaccines have made it to the market, no proven options have yet been discovered for treating COVID19 infections. The aim of this project is, therefore, to improve the potency of two active SARS-CoV-2 main protease (Mpro) inhibitors (ML188 and X77) by performing a structure-activity-relationship study where two specific sites of the inhibitors are altered. The inhibition activity of these compounds is then tested on isolated SARS-CoV-2 Mpro. The four-component Ugi reaction was utilized to synthesize the ML188 and X77 analogs, which were purified by column chromatography before testing. During this project, six pure analogs were successfully synthesized and will be sent shortly for testing. Inhibitors with good activity against SARS-CoV-2 Mpro will be further tested for their antiviral activity in cell-based infection assays. The results obtained from this study will later be used to perform a second structure-activity-relationship study to further improve the potency of the two inhibitors by developing a 2nd generation library.

A minor enantiomer recycling one-pot process usingω-functionalized prochiral aldehydes as starting materials and two reinforcing catalysts has been reported. The desired aldehyde for these process studies was 5-bromo-1-pentanal. In a two-phase solvent system, enzyme-catalyzed hydrolysis of the minor enantiomer regenerates continuously the prochiral starting material and Lewis acid catalysed addition of acetyl cyanide provides the O-acetylated cyanohydrins. The minor enantiomer recycling process has been studied and improved for 5-bromo-1-pentanal to receive high enantiomeric excess and yield of the expected O-acetylated cyanohydrin.

The development of an inexpensive, portable, stable, sensitive and selective biosensor for detection of odorants is a daunting task. Here, we hypothesized the development of a detector layer composed of the protein groups; the olfactory receptors (ORs) and the odorant binding proteins (OBPs), known to bind odorants in animal sensing. We report the design of 13 OR gene-vector constructs, and their subsequent transformation into Escherichia (E.) coli (BL21 (DE3)-STAR-pLysS) strain. Moreover, we report the expression of several ORs into an in vitro wheat germ extract using three separate detergent mixes for protein solubilization.   In addition, we describe the design of an odorant binding protein from the Aenopheles gambiae mosquito PEST strain (OBP-PEST) gene-vector construct under an IPTG (Isopropyl β-D-1-thiogalactopyranoside) inducible promoter. OBP-PEST was heterologously expressed in E.coli with an 8 amino acid long sequence (WSPQFEK) attached C-terminally, via a thrombin cleavage site and a flexible linker (GSSG). The WSPQFEK sequence, commonly referred to as a Strep-tag, enabled subsequent affinity chromatography purification of the protein, via binding to an engineered Streptavidin equivalent. Surprisingly, the OBP-PEST was found to contain a signal sequence leading to its truncation and secretion when expressed in E.coli.   Biophysical analyses were established using Circular Dichroism (CD) for the analysis of two lipocalins: Beta-lactoglobulin (BLG) and OBP-PEST. We studied the solubility, refoldability and the conformational transitions of BLG, as a result of change in solvent, pH and temperature. The secondary structure of OBP-PEST and its thermal stability was investigated.   In conclusion, this thesis work has enabled biophysical analyses of OBP-PEST and future analogs of interest to the development of a stable protein detector layer. Although further experiments are needed to fully characterize the biophysical properties, and to find odorant substrates of OBP-PEST, it was found to be a suitable alternative to ORs in a biosensor detector layer application. More importantly, an inherent OBP-PEST signal sequence was found to mediate protein secretion when expressed heterologously in E.coli. To the best of our knowledge this is the first lipocalin discovered to be secreted upon heterologous expression in E.coli.   We hypothesize that this signal peptide could be used as a means for targeted secretion and, hence, efficient protein purification.

The potential antimalarial and anticancer effect of molecules containing 1,10-phenanthroline skeleton has been suspected on several previous studies. It is why the goal of this project is to synthesize novel 1,10-phenanthrolines and cyclic analogs. The originality of this project is the synthesis way of these novel compounds. Indeed, these structures will be obtained through an original redox approach developed in the SMITH laboratory using the tetrakis(dimethylamino)ethylene (TDAE) reagent.      The TDAE is an electron rich organic molecule which is an effective reducing agent capable of generating an anion from halogenated derivatives under mild conditions via a single electron transfer (SET). From the different substrate we will work with, the TDAE will generate an anion which will be additioned on the 1,10-phenanthroline-5,6-dione. These different substrates will be aromatic and heterocyclic nitro-benzylic, and quinonic derivates as well as bromodifluoromethyl heteroarylated substrates. A one pot two step (reduction, dehydration) reaction will be done on these addition products, in order to obtain a cyclised product.        It is the first time we try these reactions on these kind on molecules, it is why this project needs a lot of optimization and that the yield obtained are medium or equal to zero. However, we observed that the addition reaction with TDAE worked with 4 substrates out of 6. We tried the cyclisation reaction on only one addition product and we think that after some improvement of the reaction conditions and the work-up, we will be able to obtain the product with a good yield. / Tidigare studier har indikerat att molekyler med 1,10-phenanthrolineskelett har en skyddande effekt mot malaria och cancer. Syftet med detta projekt är att syntetisera nya 1,10-phenanthrolinar och cykliska analoger. Framställningsmetoden som användes i denna studie har inte undersökts tidigare.    Föreningen skapades genom en originalmetod utnyttjande en redoxreaktion med hjälp av en TDAE-reagens. TDAE är en elektronrik organisk molekyl och fungerar som en effektiv reduktionsagent. Med hjälp av en enelektronöverföring (SET) kan en anjon framställas under milda förhållanden utifrån halogena derivat. Anjonen tillförs 1,10-phenanthroline-5,6-dione. De olika substraten är heteroaromatiska nitro-benzyliska och quinoniska derivat, samt bromodifluorometylheteroarylerade. Cykliska produkter erhölls genom en tvåstegsreaktion (reduktion, dehydratisering) genomförd i ett enda reaktionskärl.   Med detta projekt har dessa reaktioner för första gången testats på den här typen av molekyler. Det krävs mer optimering eftersom utbytena var låga till medelhöga. Utav sex möjliga substrat fungerade additionsreaktionen med TDAE med fyra stycken. I detta försök testades dock endast en cyklisk reaktion på additionsprodukten. Med ytterligare förbättringar av reaktionsvillkor och upparbetningar förväntas man kunna producera önskad produkt i gott utbyte.

Two series of new mononuclear ruthenium complexes with hydrophobic or hydrophilic ligands [Ru(bda)L2] and [Ru(pdc)L3] (H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid; H2pdc = 2,6-pyridinedicarboxylic acid; L = pyridyl ligands) were synthesized and their electrochemical properties and catalytic activity toward water oxidation were examined. It was revealed that the hydrophobic ligands introduced to [Ru(bda)L2 ] improved the catalytic performance, ahnost twofold TON and TOF values were achieved compared to the [Ru(bda)] catalyst with hydrophilic ligands. The cyclic voltammogram of [Ru(bda)L2] exhibited marginal difference between the catalysts with hydrophobic ligands and hydrophilic ones, implying that the hydrophobic ligands promoted the catalytic activity by :lacilitating formation of a reaction intermediate dimer.

Lignin is the most abundant source of naturally occurring aromatic compounds but has mainly been considered as waste material or energy source in the pulp and paper industry. However, due to the drive to find new material applications derived from renewable resources, there are extensive research activities aiming to develop new routes to utilize this source toward novel polymer materials. In this project, cinnamyl alcohol was used as a benchmark substrate in determining the most favorable reaction conditions for the optimal dehydrative etherification of allylic alcohols. The optimal reaction conditions determined for cinnamyl alcohol aimed to be applied to the etherification of the structurally similar, lignin-derived coniferyl alcohol to produce a bio-based allylic ether of relevance for biomaterial applications. However, due to the COVID-19 pandemic, the investigation of the etherification of coniferyl alcohol could not be conducted and the project had to be limited to the synthesis of 2-phenylethyl cinnamyl ether. Thus, this project serves as a pre-study for the sustainable etherification of lignin-derived allylic alcohols of relevance for biomaterials. The optimal reaction conditions for the synthesis of 2-phenylethyl cinnamyl ether was concluded to be 0.25 M cinnamyl alcohol and 1.00 M 2-phenylethanol as initial concentration of the reactants, 0.02 M Zr(Cp)2(OTf)2 ∙ THF as initial concentration of the catalyst, benzotrifluoride as solvent, a reaction mixture temperature of 60 °C, and a reaction time of four hours. Using optimized reaction conditions, coniferyl alcohol, a lignin-derived allylic alcohol, could in further research be evaluated as a sustainably sourced allylating agent with potential for biomaterial purposes.

The need for a safe and sustainable chemical industry has called for the development of emerging technologies with improved environmental performance. In this study, an emerging electrochemical hydrogenation process over Ni foam is being developed at the laboratory scale with an expectation of less environmental impacts than a conventional palladium on carbon hydrogenation process. To understand better the potential environmental performance of the process at the matured scale, a prospective life cycle assessment was conducted to identify environmental hotspots for early process improvement. There is no standardised method for prospective life cycle assessment, hence a methodological recommendation in conducting a prospective LCA was proposed through a literature review.  The proposed methodology consists of three steps which are a pre-inventory stage, an inventory stage, and a post-inventory stage. These steps have been connected to the ISO 14044 standard methodology for conducting an LCA where the pre-inventory stage relates to the goal and scope definition, the inventory stage to inventory analysis, and the post-inventory connected to both the inventory analysis, impact assessment, and interpretation stages of the ISO methodology. The proposed methodology was applied to the electrochemical hydrogenation process over nickel foam cathode where a three-case scenario (lab, worst- and best-case scenarios) was investigated to identify hotspots for early process improvement. The theoretical upscaled process had a better environmental performance compared to the lab process. The identified hotspots in the upscaled process (worst-case) include electricity process, evaporation process, and solvent recycling process for ecotoxicity (freshwater), human toxicity (cancer), human toxicity (non-cancer), climate change and resource use (minerals and metals) impact categories. The best-case scenario had its identified hotspots in the electricity process, solvent recycling process, and distillation process. This shows the importance of circularity, recycling, and lean manufacturing to the pillars of sustainability. Reducing resource consumption per unit product while increasing the recycling efficiency of process waste will be imperative towards ensuring a green chemical industry. Based on the results, a reduction of electricity demand for the process, utilisation of an alternative less energy-consuming processes, or cleaner energy sourcing could further improve the potential environmental performance of the process. Based on the quality of the data used, it is recommended that the outcome of the study be cautiously interpreted.