As of today, synthetic cannabinoids are one of the biggest groups of new psychoactive substances.These substances can be used as substitutes for the psychoactive drug cannabis, avoiding the legalrestrictions on cannabis. Furthermore, a variety of synthetic cannabinoids are synthesized with eithersignificant or very minor structural differences, making the detection of said novel drugs hard to keepup with and is therefore of great importance to have standards which help in the identification of theintake of the parent synthetic cannabinoid. In this project, several metabolites ofsynthetic cannabinoids with indole/indazole cores with differentside chains was synthesized. The general strategy used in this project was to N-alkylate the desiredcore followed by amide coupling with L-tert-leucine methyl ester or L-Valine methyl esterhydrochloride which resulted in 8 potential synthetic cannabinoid metabolites.

Most patients diagnosed with cancer will receive systematic chemotherapy at some point during their illness, which almost always cause severe side effects for the patients such as, anemia, nausea and vomiting. The problems with today’s chemotherapy is not only that it cause severe side effects, but also that the cancer may develop resistance to the therapy, which is why the development of a new type of therapeutic agent is in dire need. The ubiquitin proteasome system (UPS) is a vital machinery for the cancer cells to maintain protein homeostasis, which also make them vulnerable to any disruption of this system. In recent years, a new technology has been developed that utilize the UPS by chemically bringing an E3 ubiquitin ligase into close proximity of a protein of choice and tagging the protein with ubiquitin for degradation. This technology is called proteolysis targeting chimera (PROTAC). In this project, we managed to theoretically develop a new type of cancer therapeutic agent, that utilize the PROTAC system together with the first-in-class proteasome regulatory subunit, POH1, inhibitor Capzimin as a warhead. By using Capzimin as a warhead it should be possible to polyubiquitinate POH1, and thus induce proteotoxic stress in the cancer cells to trigger apoptosis. This theoretically developed drug is therefore called Capzimin-PROTAC, which should be able to trigger apoptosis in cancer cells, and at the same time being relatively safe to normal healthy cells.

In today’s society many non-renewable and environmentally harming energy sources are used to facilitate people’s everyday energy demands. This causes ecosystems to break down, global temperatures to rise, pollution and many more critical long lasting problems. By replacing non-renewable energy sources and taking advantage of the 100% renewable energy source, light, these problems will diminish. This project has been in collaboration with a company called Epishine who develop indoor organic solar cell devices to be able to replace conventual battery driven electrical devices with solar power harvested from indoor light. Since there is no good existing contacting solution, for Epishine to be able to enter the market, a contact solution between their solar cell device and the electrical devices it will power has to be developed. This thesis focuses on developing, designing, testing and evaluating the performance of new contact solutions for encapsulated flexible organic printed solar cells with the feasibility, viability, scalability and durability in focus. This project was conducted by first performing a literature study, thereafter, establishing a baseline for future referencing of new contact solutions and the main part, developing new concepts and evaluating them. By using the design thinking method, an iterative process could take place, allowing for a constant flow of new ideas whilst testing concepts throughout the project. The baseline tests were successful and the hypothesis of organic materials degrading over time was confirmed. From the many sub-concepts and production methods for a new contacting solution, two concepts showed promising results and were merged into one main concept. Two devices were created with the new concept, one functional device and one showing the design. To conclude, the thesis resulted in a functional solar cell device with a new contact solution which shows great potential and a new production method which enables all organic printed electronics to be design and developed in a more compact and component dense design. This production method is beneficial to not only Epishine, but everywhere where printed electronics are used and need to be optimized due to restrictions such as space and weight. / I dagens samhälle används många icke-förnybara energikällor för att underlätta människans vardagliga behov men skadar samtidigt miljön. Detta leder till att hela ekosystem fallerar, den globala temperaturen stiger, giftiga ämnen släpps fria och flera kritiska, långvariga problem skapas. Genom att byta ut icke-förnybara energikällor och istället dra nytta av den 100 % förnybara energikällan, ljus, kommer dessa ovanstående problem att minska. Detta projekt har varit i samarbete med ett företag vid namn Epishine som utvecklar organiska solcellsenheter för inomhusbruk, för att kunna ersätta konventionella batteridrivna elektriska apparater med solenergi tillvaratagen av inomhusbelysning. I dagsläget finns det ingen bra kontaktlösning mellan solcellsenheten och den apparat den ska driva, vilket är ett av Epishines större problem i nuläget, som hindrar dem från att kunna slå igenom på marknaden. Denna avhandling fokuserar på att utveckla, designa, testa och utvärdera prestandan av nya kontaktlösningar för inkapslade flexibla organiska solceller. Projektet började med en litteraturstudie, därefter etablerades en ”baseline” för att kunna jämföra de nya kontaktlösningarna. Största delen av rapporten handlar om att utveckla och testa nya kontaktlösningar för att sedan utvärdera dem. Genom att använda ”Design thinking” processen, kunde en iterativ process äga rum, vilket möjliggjorde ett konstant flöde med nya idéer som genererades samtidigt som koncept och prototyper utvecklades och utvärderades. Resultaten av ”baseline”-testerna var framgångsrika och hypotesen om att de konduktiva egenskaperna av organiska material försämras med tiden bekräftades. Från alla delkoncept och potentiella produktionsmetoderna för en ny kontaktlösning visade två koncept lovande resultat och slogs därför samman till ett huvudkoncept. Två olika solcellsenheter skapades med den nya kontaktlösningen implementerad. En funktionell enhet skapades och en enhet som visar layouten och designen. Sammanfattningsvis resulterade avhandlingen i en funktionell solcellsenhet med en ny kontaktlösning som visar stor potential samt en ny produktionsmetod som gör att all organisk tryckt elektronik kan designas och tillverkas i en mer kompakt och komponenttät design. Denna produktionsmetod är en fördel inte bara för Epishine utan också överallt där tryckt elektronik används och behöver optimeras i form av utrymme och vikt.

The application of different analytical techniques is fundamental in forensic drug analysis. In the wake of the occurrence of large numbers of new psychoactive substances possessing similar chemical structures as already known ones, focus has been placed on applied criteria for their univocal identification. These criteria vary, obviously, depending on the applied technique and analytical approach. However, when two or more substances are proven to have similar analytical properties, these criteria no longer apply, which imply that complementary techniques have to be used in their differentiation. This work describes the synthesis of some structural analogues to synthetic cannabinoids and cathinones based on the evolving patterns in the illicit drug market. Six synthetic cannabinoids and six synthetic cathinones were synthesized, that, at the time for this study, were not as yet found in drug seizures. Further, a selection of their spectroscopic data is compared to those of already existing analogues; mainly isomers and homologues. The applied techniques were mass spectrometry (MS), Fourier transformed infrared (FTIR, gas phase) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. In total, 59 different compounds were analyzed with the  selected techniques. The results from comparison of spectroscopic data showed that isomeric substances may in some cases be difficult to unambiguously identify based only on their GC-MS EI spectra. On the other hand, GC-FTIR demonstrated more distinguishable spectra. The spectra for the homologous compounds showed however, that the GC-FTIR technique was less successful compared to GC-MS. Also a pronounced fragmentation pattern for some of the cathinones was found. In conclusion, this thesis highlights the importance of using complementary techniques for the univocal identification of synthetic cannabinoids and cathinones. By increasing the number of analogues investigated, the more may be learnt about the capabilities of different techniques for structural differentiations, and thereby providing important identification criteria leading to trustworthy forensic evidence.

This thesis summarizes three novel and general reaction protocols for the synthesis of diaryliodonium salts. All protocols utilize mCPBA as oxidant and the acids used are either TfOH, to obtain triflate salts, or BF3•Et2O that gives the corresponding tetrafluoroborate salts in situ. Chapter two describes the reaction of various arenes and aryl iodides, delivering electron-rich and electron-deficient triflates in moderate to excellent yields. In chapter three, it is shown that the need of aryl iodides can be circumvented, as molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates. The final and fourth chapter describes the development of a sequential one-pot reaction from aryl iodides and boronic acids, delivering symmetric and unsymmetric, electron-rich and electron-deficient iodonium tetrafluoroborates in moderate to excellent yields. This protocol was developed to overcome mechanistic limitations existing in the protocols described in chapter two and three. The methodology described in this thesis is the most general, efficient and high-yielding existing up to date, making diaryliodonium salts easily available for various applications in synthesis.

Detta examensarbete beskriver optimering av ett katalytiskt protokoll för framställning av bisguaiacol F, ett ofarligt alternativ till bisphenol A. Lewissyrliga grupp IV metallkomplex med triflatligander användes som katalysatorer under milda betingelser och kinetisk analys användes för att underlätta optimeringen av reaktionsprotokollet för att öka utbyte och selektivitet för transformationen. Dessutom bidrog kinetiken med mekanistiska insikter och avslöjade att den nukleofila attacken starkt påverkar reaktionens selektivitet och utbyte. / This thesis describes the optimization of catalytic protocol for the formation of bisguaiacol F, a benign alternative to bisphenol A. Lewis acidic group IV metal complexes bearing triflate ligands were used as catalysts under mild conditions and kinetic analysis was used to aid optimization of the reaction protocol to increase the yield and selectivity of the transformation. In addition, the kinetics shed light on the operating mechanisms and revealed that competition of nucleophiles greatly impact selectivity and yield of the reaction.

Dynamic Combinatorial Chemistry (DCC) is a recently introduced supramolecular approach to generate dynamically interchanging libraries of compounds. These libraries are made of different building blocks that reversibly interact with one another and spontaneously assemble to encompass all possible combinations. If a target molecule, for instance a receptor is added to the system and one or more molecules show affinity to the target species, these compounds will, according to Le Châtelier´s principle, be amplified on the expense of the other non-bonding constituents. To date, only a handful of different systems and formats have been used. Hence, to further advance the technique, especially when biological systems are targeted, new reaction types and new screening methods are necessary. This thesis describes the development of reversible sulfur reactions, thiol/disulfide interchange and transthiolesterification (the latter being a new reaction type for DCC), as means of generating reversible covalent bond reactions. Two different types of target proteins are used, enzymes belonging to the hydrolase family and the plant lectin Concanavalin A. Furthermore, two new screening/analysis methods not previously used in DCC are also presented; the quartz crystal microbalance (QCM)-technique and catalytic self-screening. / QC 20101118

Den svenska vård-och omsorgsmarknaden har sedan dess avreglering för ca 20 år sedan utvecklats. Från att ha varit ett offentligt monopol har vi nu istället en starkt konkurrensutsatt marknad. Konkurrensfördelar som tillväxtstrategi kan nu vara avgörande för ett bolags framgång. Genom en närmast unik möjlighet att ta del av bolagsdata från ett av Sveriges största vård- och omsorgskoncerner har denna studie undersökt huruvida organiska eller oorganiska tillväxtstrategier lämpar sig bäst för vård- och omsorgsbolag som ämnar öka sin omsättning på ett kapitalmässigt effektivt sätt. Datat som tillhandahölls sträckte sig över fem år och innefattade 56 bolag. Studien genomfördes i form av två analyser. En kvantitativ regressionsanalys för att ta fram ett jämförelsetal motsvarande omsättning per krona spenderad i organiska investeringar och en delvis kvantitativ analys för att ta fram ett jämförelsetal motsvarande omsättning per krona spenderad i oorganiska investeringar. Analyserna visade sammanlagt att oorganiska tillväxtstrategier enligt datat är mer kapitalmässigt effektiva med avseende till omsättningstillväxt än organiska tillväxtstrategier. Studien tog dock bland annat inte hänsyn till potentiella synergieffekter från förvärv eller riskprofilen förknippad med de olika strategierna. Det framgick även från datat att investeringar i personal är positivt korrelerad med omsättningstillväxt, medan det inte gick att påvisa en korrelation mellan omsättningstillväxt och investeringar i IT eller generella investeringar. / The Swedish welfare industry has since its deregulation 20 years ago evolved. What was previously a publicly owned monopoly is now a competitive market. Competitive advantages such as growth strategies is now a key for a company’s success. Through an almost unique opportunity to use data from one of Sweden’s largest welfare groups this study has investigated whether organic or inorganic growth strategies is best suited for welfare companies looking to increase their total revenue in an, in terms of capital, effective way. The data provided spanned over five years and included data from 56 companies. The study was conducted as two separate analyses. A quantitative regression analysis was made to calculate a comparison number corresponding to revenue per SEK spent on organic investments. The second, in part quantitative analysis aimed to create a corresponding number for inorganic investments. The conclusion from the analyses was that according to the data, the inorganic growth strategies outperformed the organic growth strategies. The study did however not consider the potential synergy effects from acquisitions or the risk profile associated with the strategies. The study also revealed that according to the data investments in staff is positively correlated with revenue growth, but a correlation between revenue growth and both investments in IT and general investments could not be proven.

Three-dimensional (3D) printing has an important role for fabrication of degradable scaffoldsfor soft tissue regeneration. Among the 3D printing techniques, photopolymerization-based 3Dprinting is one of fastest growing, offering environmental benefits and high precision of 3Dobjects. In this approach, photocurable macromonomers/monomers are cross-linked layer bylayer in the presence of photoinitiators under visible or UV light to fabricate 3D designedobjects. However, a limited biomedical material selection has prevented it from spreading overclinical application. Furthermore, poly(ε-caprolactone), a common degradable polymer usedfor 3D printing, shows not satisfactory physical properties for soft tissue regeneration. Thedearth of materials with proper properties raises the need for novel degradable materials,which should be not only compatible for photopolymerization-based 3D printing but alsosuitable for soft and gel-like scaffold fabrication. Here, the aim was to design photocurable macromonomers consisting of oligo(ε-caprolactoneran-p-dioxanone), oCLDX, with acrylate chain-end groups. A metal-free synthetic strategy wasdeveloped for the bulk ring-opening of ε-caprolactone (CL) and p-dioxanone (DX) at roomtemperature using diphenyl phosphate (DPP) as organocatalyst and multifunctional initiators. The oligomers had low dispersity (<1.2) and targeted molecular weight around 2000 g mol-1.The random sequence and the control over chain growth of oCLDXs were confirmed byreactivity ratios using 1D and 2D NMR analysis. Kinetics study of co-oligomerizationdemonstrated that within DPP-catalysed reaction, DX possessed higher reactivity than CL andthe ring-opening co-oligomerization followed an activated monomer mechanism (AMM). Thetopology of the co-oligomers could also be varied by using different alcohol initiators. The co-oligomers possessed lower degree of crystallinity than homopolymers of DX or CL and,depending on the composition, they were liquid at room temperature. The lower melting pointand gel-like appearance make them good candidates for photopolymerization-based 3Dprinting. The suitability toward photopolymerization was proven for the ethylene glycol-initiatedco-oligomer containing 30 mol% of DX. The cross-linked gels were soft but brittle and showedgood water uptake capacity. / Tredimensionell (3D)-utskrift har en viktig roll vid tillverkning av nedbrytbara matriser förregenerering av mjukvävnad. Bland 3D-utskriftteknikerna är fotopolymerisationsbaserad 3Dutskriften av de snabbast växande, och erbjuder miljöfördelar och hög precision hos 3Dobjekten.För att tillverka 3D-designade objekt med denna teknik är fotohärdandemakromonomerer/ monomerer tvärbundna lager på lager i närvaro av fotoinitiatorer och synligteller UV-ljus. Emellertid har ett begränsat urval av biomedicinska material hindrat tekniken frånatt spridas till kliniska applikationer. Vidare har poly(ε-kaprolakton), en vanlig nedbrytbarpolymer som används för 3D-utskrift, inte tillfredsställande fysikaliska egenskaper förregenerering av mjukvävnad. Bristen på material med rätt egenskaper ökar behovet av nyanedbrytbara material, som inte bara ska vara kompatibla för fotopolymerisationsbaserad 3Dutskriftutan också lämplig för mjuk och gelliknande matristillverkning.Här var syftet att designa fotohärdande makromonomerer bestående av oligo(ε-kaprolaktonsam-p-dioxanon), oCLDX, med akrylatkedjeändgrupper. En metallfri syntetisk strategiutvecklades för bulkringöppning av ε-kaprolakton (CL) och p-dioxanon (DX) vidrumstemperatur genom att använda difenylfosfat (DPP) som organisk katalysator ochmultifunktionella initiatorer. Oligomererna hade den förutbestämda molekylvikten, omkring2000 g mol-1, och en låg dispersitet (<1,2). Den slumpmässiga sekvensen och kontrollen avkedjans tillväxt, till oCLDX, bekräftades genom reaktivitetsförhållanden med hjälp av 1D och2D NMR-analys. Kinetikstudie av samoligomeriseringen visade att med DPP-katalyseradreaktion hade DX högre reaktivitet än CL och att den ringöppnande samoligomeriseringenföljde en aktiverad monomermekanism (AMM). Topologin hos samoligomererna kunde ocksåvarieras genom att använda olika alkoholinitiatorer. Samoligomererna hade lägre grad av kristallinitet än homopolymerer av DX eller CL ochberoende på kompositionen var de flytande vid rumstemperatur. Den lägre smältpunkten ochgelliknande utseendet gör dem till bra kandidater för fotopolymerisationsbaserad 3D-utskrift. Lämpligheten för fotopolymerisation bevisades för den etylenglykolinitierade samoligomerensom innehöll 30 mol% DX. De tvärbundna gelerna var mjuka men spröda och uppvisade godvattenupptagningskapacitet.

I rotaxaner följs förflyttningen av makrocykeln vanligtvis med 1H-NMR spektroskopi. Målet med detta projekt är i stället att utveckla ett system som möjliggör att förflyttningen av makrocykeln kan observeras med hjälp av luminiscerande lantanid emission. Detta bör vara ett kraftfullt verktyg, då luminiscerande emission skulle möjliggöra att makrocykelns position längs med tråden kan avläsas direkt med blotta ögat. För att lantanid-baserade system ska kunna luminiscera krävs det att en aktiverande antennmolekyl finns i närheten av lantaniden. I detta projekt placerades en lantanidligand i den ena stoppande änden av en [2]rotaxan och en antennmolekyl sattes på den trådade makrocykeln. En förändring av pH:t medför att makrocykeln förflyttas närmre till lantanidliganden, vilket i sin tur medför att antennen aktiverar lantaniden och den luminiscerande emissionen startar. Baserat på styrkan av luminiscensen bör man då kunna avgöra makrocykelns position i rotaxanen. I framtiden hoppas vi kunna använda detta visualiseringsverktyg för att kunna börja använda rotaxaner som biosensorer för medicinsk diagnostik. / In rotaxanes, the movement of the macrocycle is usually tracked using 1H-NMR spectroscopy. The goal of this project is to instead develop systems so one can follow the macrocycle movement through luminescent lanthanide emission. This should be a powerful tool, as luminescence emission would allow for a direct visual readout of the macrocycle position along the thread with the naked eye. To allow luminescence in lanthanide-based systems, a sensitizing antenna molecule needs to be present in close proximity to the lanthanide. In this project, a lanthanide ligand was placed at the stoppered end of a [2]rotaxane, and a sensitizing antenna was attached to the threaded macrocycle. A change in pH induces the macrocycle to move closer to the lanthanide stopper, which causes the antenna to sensitize the lanthanide and start the luminescence emission. Based on the strength of the luminescence, one should then be able to determine the location of the macrocycle in the rotaxane. We hope to use this visual readout tool to eventually turn rotaxanes into useful point-of-care biosensors for medical diagnostics.