The task of medicinal chemists in a drug discoveryproject is to synthesize/design analogues to the screening hits, simultaneouslyincreasing target potency and optimizing the pharmacological properties.  This requires a wide selection of moleculesto be synthesized, where both synthetic feasibility and price of startingmaterials are of great importance. In this work, a synthetic pathway from cheapand readily available starting materials to highly modifiable 2,4-disubstitutedpyrrolidines is demonstrated. Previously reported procedures to similarpyrrolidines use expensive catalysts, requires harsh conditions and requiresnon-commercially available starting materials. The suggested pathway herein has demonstrated great possibility forvariation in the 4-position, including fluoro, difluoro, nitrile and alcoholfunctional groups. There are several areas in which the synthesis can beimproved and expanded upon. Improvements can be made by optimizing thedescribed reaction conditions and further expansion of possible modificationsin both 2- and 4-position could be explored.

In recent years, medical treatments against respiratory tract infections (RTIs) based on trypsin from Atlantic cod targeting the surface proteins on viral particles have been approved. However, the stability and compatibility in the human body of human trypsin would be expected to be greater than that from cod. In this study, the process of producing human trypsin recombinantly in E. coli in a fed batch bioreactor was optimised using a Design of Experiment (DOE) method with four 2-level factors and two responses. The factors considered were temperature, carbon source, induction time point and feeding rate, and the two responses were yield and purity. The study was done in 8 consecutive runs in the bioreactor, with controlled changes made to the factors for each run. The responses were measured and analysed for significance and optimisation of factors. The optimal settings for the highest yield with a purity of at least 80% were found to be at 18 °C, glucose based feed at a restricting feed rate and induction at a low OD600. Only the induction time has a significant effect on purity, and no factor had a stand-alone significant effect on yield. These findings provide a baseline for further studies on purification and further production of trypsin recombinantly in E. coli at a larger industrial scale. The highest yield achieved was 7.9 g trypsin per litre media, almost 80 times higher than comparable methods using shake flasks. However, the sample with over 80% purity was 6.3 g trypsin per litre media.

No description available.

Metal–organic frameworks (MOFs) represent an important platform to immobilize and stabilize electroactive molecular catalysts due to their porosity, high surface area and well characterized three-dimensional structure. Most efforts in this area have been dedicated to the development of photocatalysts and traditional heterogeneous catalysts based on both precious and abundant transition metals. However, little work has been done to design nickel-based MOF electrocatalysts for organic synthesis. In this work we describe the synthesis of three linkers containing a bipyridine moiety, where two of the linkers are dicarboxylate extended linkers and one is a bispyrazole extended linker. The two dicarboxylate linkers are combined with zirconium clusters to build MOFs of the UiO-n family. The bispyrazole linker was used to synthesize copper-based MOFs. The developed MOFs function as support for the immobilization of nickel (II) species in isolated sites within the frameworks. Following this, the redox properties of these MOFs were studied by the means of electrochemistry. The structure of the organic linkers was confirmed by 1H NMR spectroscopy and mass spectrometry, and two of the linkers are new molecules never synthesized before. The synthesized MOFs were characterized by powder X-ray diffraction, where the MOFs of the UiO-n family showed small crystallite sizes. Similarly, the MOFs based on the bispyrazole linker showed low crystallinity. Metalation of the MOFs with a [Ni(phen)3]Cl2 complex was studied using UV-Vis spectroscopy and scanning electron microscopy, both techniques confirmed the immobilization of the nickel catalyst in the UiO-n MOFs. The electrochemical properties of the MOFs were studied using cyclic voltammetry. Both UiO-n MOFs showed a non-reversible event for the reduction of Ni(II) and the MOFs based on the bispyrazole linker showed a quasi-reversible event for the Cu(II)/Cu(I) couple.

Uppsatsen undersöker hur virala TikTok-produkter påverkar köpbeslut hos unga kvinnor, särskilt med fokus på känslor av FOMO och reaktioner av impulsköp och ”överspendering”. Appen har lyckats etablera sig som en kraftfull aktör inom digital marknadsföring, där TikTok-användare influerar och inspirerar andra via videor, rekommendationer och kommentarer. I och med att analysera fenomen som FOMO, vill studien belysa hur TikTok kan påverka köpbeslut hos unga kvinnor i åldrarna 18-28 år. Både genom att se till impulsiva tendenser, men också risk för personliga överträdelser rent ekonomiskt i form av ”överspendering”. Fenomenet med virala produkter innebär att produkter blir eftertraktade på grund av användarinteraktioner och algoritmer. Därav skapas en organisk miljö av marknadsföring där produkter snabbt får spridning och stor uppmärksamhet. Tidigare forskning lyfter fram hur unga kvinnor tenderar att uppleva FOMO mer intensivt än män, vilket kan leda till ökade impulsiva inköp och högre skuldsättning. Känslor av FOMO är individuella, och grundar sig utifrån komplexa faktorer, som bland annat känslor baserade på självbild och sociala jämförelser. FOMO kan därmed bidra till påverkan av produktinnehåll och speglar därefter ungas reaktioner och konsumtionsbehov av virala produkter. Studiens forskningsmetod är kvalitativ och består av datainsamling från åtta semistrukturerade intervjuer. Metoden valdes för att få en djupare insikt i de känslor och drivkrafter som ligger bakom köpbesluten. Intervjuerna fokuserade på deltagarnas upplevelser av virala produkter, FOMO, impulsköp och ”överspendering”, i kombination med S-O-R modellen.  Resultaten visade att virala produkter på TikTok haft en påverkan på unga kvinnors köpbeslut. Samtliga av de intervjuade upplevde FOMO efter exponering av virala produkter, och att det till stor del baserades på egenskaper och intressen. Resultatet anger att det har lett till ett eller flera impulsköp, och i vissa fall till ”överspendering” på ett personligt plan.  Genom att belysa de samband, och i förknippning med S-O-R modellen, bidrar uppsatsen till en bättre förståelse av virala TikTok-produkters påverkan på köpbeslut hos unga kvinnor. Hur deras köpbeslut influeras av (stimuli) virala produkter, i vilken utsträckning de styrs av psykologiska effekter som FOMO (organism), och som konsekvens leder till handlingar av (respons) impulsköp och ”överspendering”. Studien erbjuder också etiska och moraliska insikter som kan vara användbara för företag och marknadsförare som riktar sig mot unga, och för dem som arbetar med att förebygga ekonomiska problem.

Trälim utgör en stor del av alla lim globalt och är avgörande för skapandet av träkompositmaterial, som många industrier och produkter är beroende av. Bland de vanligaste trälimmen använder flera formaldehyd som en väsentlig komponent i deras polymera struktur. Medan formaldehyd är ett allmänt använt, billigt och pålitligt material, är det också giftigt och har generellt ursprung från petroleumkällor. Ett ersättningsmaterial med di- eller polyaldehydisk funktionalitet av grönt ursprung är därför önskvärt för framtida trälimkemi. En potentiell lösning involverar att oxidera polysackarider såsom stärkelse och dextrin för att funktionalisera de upprepande glukosenheterna med aldehyder, ketoner och karboxylsyror. Här visas att Fenton-liknande förhållanden, med väteperoxid som oxidationsmedel och järn som katalysator, kan användas för att utföra reaktionen effektivt under atmosfäriska förhållanden, vilket producerar minimala biprodukter såsom vätgas, vatten och järnkomplex. Betydande funktionalisering observerades i en lågmolekylviktsfraktion som frigörs från polysackariden vid oxidation, en fraktion som traditionellt förloras under upparbetning via centrifugering. Detta arbete antyder att retention av denna lågmolekylviktsfraktion i produktblandningen kan förbättra framtida limegenskaper vid låg grad av oxidation i material med hög polymerisationsgrad, även om kvarhållande av depolymeriserade fraktioner från material med lägre polymeriseringsgrad, såsom dextrin, kanske inte ger de önskade polyaldehydiska produkterna i tillräckliga koncentrationer. Kvarhållandet av lågmolekylviktsfraktionen antyder också att stora mängder oxidationsmedel och katalysator bör undvikas, eftersom högre oxidationsgrad kan resultera i oönskade monofunktionella molekyler på grund av hög depolymerisation. / Wood adhesives comprise a large part of all adhesives globally and are essential in creation of wood composite materials, which many industries and products are entirely reliant on. Amongst the most common wood adhesives, several utilize formaldehyde as an essential component of their polymeric structure. While formaldehyde is a widely used, cheap and reliable material, it is also toxic, and generally derived from petroleum sources. A replacement with di- or poly-aldehydic functionality of green origin is therefore desirable for future wood adhesive chemistry. One potential solution involves oxidizing polysaccharides such as starch and dextrin, to functionalize the repeating glucose units with aldehydes, ketones, and carboxylic acids. Herein, it is demonstrated that Fenton-type conditions, using hydrogen peroxide as oxidant and iron as catalyst, can be used to perform the reaction efficiently in atmospheric conditions, producing minimal byproducts such as hydrogen gas, water, and iron complexes. Significant functionalization was observed in a small molecular weight fraction released from the polysaccharide upon oxidation, a fraction which is traditionally lost during workup via centrifugation. This work suggests that retention of this small molecular weight fraction in the product mixture may enhance future adhesive properties at low degrees of oxidation in materials with high degrees of polymerization, though retention of depolymerized fractions of lower chain length materials such as dextrin may not provide the targeted poly-aldehydic products in sufficient concentrations. The retention of the small molecular weight fraction also suggests that large amounts of oxidant and catalyst should be avoided, as higher degree of oxidation may result in undesired mono-functional molecules due to higher degrees depolymerization.

New strategies are needed to counter the growing problem of bacterial resistance to antibiotics. One such strategy is to design compounds that target bacterial virulence, which could work separately or in concert with conventional bacteriostatic or bactericidal antibiotics. Pilicides are a class of compounds based on a ring-fused 2-pyridone scaffold that target bacterial virulence by blocking the chaperone/usher pathway in E. coli and thereby inhibit the assembly of pili. This thesis describes the design, synthesis, and biological evaluation of compounds based on the pilicide scaffold with the goal of improving the pilicides and expanding their utility. Synthetic pathways have been developed to enable the introduction of substituents at the C-2 position of the pilicide scaffold. Biological evaluation of these compounds demonstrated that some C-2 substituents give rise to significant increases in potency. X-ray crystallography was used to elucidate the structural basis of this improved biological activity. Furthermore, improved methods for the preparation of oxygen-analogues and C-7 substituted derivatives of the pilicide scaffold have been developed. These new methods were used in combination with existing strategies to decorate the pilicide scaffold as part of a multivariate design approach to improve the pilicides and generate structure activity relationships (SARs). Fluorescent pilicides were prepared using a strategy where selected substituents were replaced with fluorophores having similar physicochemical properties as the original substituents. Many of the synthesized fluorescent compounds displayed potent pilicide activities and can thus be used to study the complex interactions between pilicide and bacteria. For example, when E. coli was treated with fluorescent pilicides, it was found that the compounds were not uniformly distributed throughout the bacterial population, suggesting that the compounds are primarily associated to bacteria with specific properties. Finally, by studying compounds designed to inhibit the aggregation of Aβ, it was found that some compounds based on the pilicide scaffold inhibit the formation of the functional bacterial amyloid fibers known as curli; these compounds are referred to as 'curlicides'. Some of the curlicides also prevent the formation of pili and thus exhibit dual pilicide-curlicide activity. The potential utility of such 'dual-action' compounds was highlighted by a study of one of the more potent dual pilicide-curlicides in a murine UTI model were the compound was found to significantly attenuate virulence in vivo.

The purpose of this doctoral thesis is to investigate and develop catalytic processes mediated by iridium(III) complexes. By understanding the mechanisms, the weaknesses of the designed catalysts can be identified and be overcome in the following generation. The thesis is composed of two general sections dedicated to the synthesis and applications of homogeneous catalysts and to the preparation of heterogeneous catalysts based on metal-organic frameworks (MOFs). After a general introduction (Chapter 1), the first part of the thesis (Chapters 2-4, and Appendix 1) covers the use of several homogeneous bifunctional [Cp*Ir(III)] catalysts in a variety of chemical transformations, as well as mechanistic studies. Chapter 2 summarizes the studies on the N-alkylation of anilines with benzyl alcohols catalyzed by bifunctional Ir(III) complexes. Mechanistic investigations when the reactions were catalyzed by Ir(III) complexes with a hydroxy-functionalized N-heterocyclic carbene (NHC) ligand are discussed, followed by the design of a new generation of catalysts. The chapter finishes presenting the improved catalytic performance of these new complexes.    A family of these NHC-iridium complexes was evaluated in the acceptorless dehydrogenation of alcohols, as shown in Chapter 3. The beneficial effect of a co-solvent was investigated too. Under these base-free conditions, a wide scope of alcohols was efficiently dehydrogenated in excellent yields. The unexpected higher activity of the hydroxy-containing bifunctional NHC-Ir(III) catalysts, in comparison to that of the amino-functionalized one, was investigated experimentally. In the fourth chapter, the catalytic process presented in Chapter 3 was further explored on 1,4- and 1,5-diols, which were transformed into their corresponding tetrahydrofurans and dihydropyrans, respectively. Mechanistic investigations are also discussed. In the second part of the thesis (Chapter 5), a Cp*Ir(III) complex was immobilized into a MOF. The heterogenization of the metal complex was achieved efficiently, reaching high ratios of functionalization. However, a change in the topology of the MOF was observed. In this chapter, the use of advanced characterization techniques such as X-ray absorption spectroscopy (XAS) and pair distribution function (PDF) analyses enabled to study a phase transformation in these materials. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Submitted.</p>

Conducting polymers entered the research field in late 70´s and efforts aimed at achieving printed electronics started a decade later. This thesis treats printable organic electrochemical transistors (OECT). Some conjugated polymers can be switched between a high conducting and a low conducting state in an electrochemical cell. In this thesis, the work carried out using poly(3,4-ethylenedioxythiophene) (PEDOT) as the active material in an electrochemical transistor is reported. The electrochemical transistors, presented, can be designed into a bi-stable and dynamic mode of operation. These transistors operates at voltages below 2V and current on/off ratios are typically 5000, but 105 have been reached. The transistor device can be built up from all-organic materials using common printing techniques such as with screen-printing. The bi-stable transistor can be combined with an electrochromic (EC) display cell to form a smart pixel circuit. Combining several of these smart pixels yield an actively addressed cross-point matrix display. From this an all-organic active matrix display printable on paper has been achieved. The OECT, combined with a resistor network was successfully used in inverter and logic circuits. One important feature of these organic electrochemical devices is that both ions and electrons are used as the charge (signal) carriers. This is of particular interest and importance for chemical sensors. By combining a proton-conducting electrolyte (Nafion®) that changes its conductivity upon exposure to humidity, a simple OECT humidity sensor was achieved. This proves the use of this OECT as the ion-to-electron transducer.

This thesis deals with different optimization problems encountered in organic synthesis. The use of response surface, sequential simplex and PLS techniques, for simultanious optimization of yield and suppression of side reactions is investigated. This is illustrated by an example of enamine synthesis, were a side reaction was a serious problem. The problem of efficient screening to find suitable catalysts and solvents in new reactions is also investigated. Here, the use of principal properties as selection criterion, is demonstrated with a new process for the silylation of a,ß-unsaturated ketones. The extension of the new method to bis silylation of 1,2- and 1,3-diketones is demonstrated. The total synthesis of (±)-geosmin is investigated by an approach aimed to reduce the number of necessary steps involved. The suggested strategy, is to find compatible solvents through several transformations in the sequence to accomplish one-pot multistep reactions. In this context an improved method for the preparation of 1,10-dimethyl-l(9)-octalone-2 was established. Comparison with previously reported total syntheses of (±)-geosmin was done. / digitalisering@umu