Photocatalytic Activation of Carboxylic Acids and Diol Derivatives

This thesis presents different methods for the photocatalytic activation of carboxylic acid and diol derivatives. Visible light-mediated cross-couplings or cleavage of these biomass-derived substrates have been achieved and mechanistic investigations are described. As carboxylic acids are abundant, non-toxic and inexpensive compounds with high structural diversity, they are ideal starting materials for modern, sustainable organic synthesis. Extrusion of CO₂ from different classes of carboxylic acids gives radical intermediates that react in various cross-coupling reactions. Chapter 1 summarizes recent developments in the field of photocatalytic decarboxylative reactions and compares different methods regarding scope, product yields, atom economy, reaction time and toxicity. Chapter 2 and Chapter 3 present the decarboxylative cross-coupling of natural carboxylic acids with a green light-mediated, environmentally friendly method. In both cases, amino acids, α-oxy acids and fatty acids from renewable resources are activated by esterification to N-(acyloxy)phthalimides. The decarboxylation takes place upon reductive quenching of the excited organic dye eosin Y to its radical anion by DIPEA and subsequent reduction of the N-(acyloxy)phthalimide. An alkyl radical is formed which can undergo C–C bond formation reactions. Chapter 2 describes the trapping of these alkyl radicals with electron-deficient alkenes. After cross-coupling, alkylated products without double-bonds are obtained. Although especially substrates with α-hetero atoms give good yields, even simple fatty acids are suitable, albeit giving lower yields. In Chapter 3, alkyl radicals which are formed upon decarboxylation react with acetylenic sulfones under elimination of a sulfonyl radical. Starting from easily available natural carboxylic acid derivatives, this method enables the synthesis of building blocks with an alkyne moiety which are important for organic synthesis. With this method, even complex starting materials like protected sugar acids, gemfibrozil or cholic acid can be alkynylated in good yields. Another important and abundant class of natural compounds are diols. Chapter 4 presents a photocatalytic method for the C–C bond cleavage of vicinal diols to aldehydes and ketones. This reaction proceeds via ligand-to-metal-charge-transfer (LMCT) with a cerium-catalyst and under irradiation with blue light. The scope includes aryl as well as alkyl substituted diols and the protocol for the valorization of diols is operationally simple as it works under air and at room temperature. The selective, visible light-induced fragmentation of 1,2-diol derivatives with one protected and one unprotected hydroxyl group is described in Chapter 5. The most abundant biomass-derived representatives of this class of compounds are lignin β-O-4 model compounds, a type of aromatic backbone diol derivative. Redox neutral cleavage of the β C(sp³)–O bond within one step is achieved with two different homogeneous photocatalysts, in the presence of a thiol co-catalyst and blue light. Different leaving groups are compatible with the system. With the metal-free catalyst 4CzIPN, the reaction proceeds under more robust conditions but is limited to benzylic diol derivatives. With [Ir(ppy)₂dtbpy]PF₆, the photoreactions have to be carried out under nitrogen atmosphere, but on the other side, even C–O cleavage of aliphatic diol derivatives is possible. A mechanistic pathway including reductive quenching of the excited photocatalyst and HAT of the α-hydrogen atom of the benzylic alcohol to the generated thiyl radical is postulated

Stochastic dynamics of virus capsid formation: direct versus hierarchical self-assembly

Background: In order to replicate within their cellular host, many viruses have developed self-assembly strategies for their capsids which are sufficiently robust as to be reconstituted in vitro. Mathematical models for virus self-assembly usually assume that the bonds leading to cluster formation have constant reactivity over the time course of assembly (direct assembly). In some cases, however, binding sites between the capsomers have been reported to be activated during the self-assembly process (hierarchical assembly). Results: In order to study possible advantages of such hierarchical schemes for icosahedral virus capsid assembly, we use Brownian dynamics simulations of a patchy particle model that allows us to switch binding sites on and off during assembly. For T1 viruses, we implement a hierarchical assembly scheme where inter-capsomer bonds become active only if a complete pentamer has been assembled. We find direct assembly to be favorable for reversible bonds allowing for repeated structural reorganizations, while hierarchical assembly is favorable for strong bonds with small dissociation rate, as this situation is less prone to kinetic trapping. However, at the same time it is more vulnerable to monomer starvation during the final phase. Increasing the number of initial monomers does have only a weak effect on these general features. The differences between the two assembly schemes become more pronounced for more complex virus geometries, as shown here for T3 viruses, which assemble through homogeneous pentamers and heterogeneous hexamers in the hierarchical scheme. In order to complement the simulations for this more complicated case, we introduce a master equation approach that agrees well with the simulation results. Conclusions: Our analysis shows for which molecular parameters hierarchical assembly schemes can outperform direct ones and suggests that viruses with high bond stability might prefer hierarchical assembly schemes. These insights increase our physical understanding of an essential biological process, with many interesting potential applications in medicine and materials science

The relationship between problematic smartphone use and psychopathology

Problemaatiline nutitelefoni kasutus (PNK) on liigne nutitelefoni kasutus, kus see avaldab mõju inimese vaimsele või füüsilisele tervisele. Varasemalt on uuritud PNK seoseid psühhopatoloogiatega ja õppeedukuse ning tööga. Käesolevas töös uuriti, kuidas on PNK seotud depressiooni ja üldistunud ärevushäire sümptomitega, vanuse, soo ja keskmise kasutusajaga. PNK-d mõõdeti lühendatud eestikeelse Nutitelefonisõltuvuse Küsimustikuga (E-SAPS18), emotsionaalse enesetunde mõõtmiseks kasutati Emotsionaalse Enesetunde Küsimustikku (EEK-2) ja nutitelefoni keskmine kasutusaeg ning nutitelefoni keskmine kasutuse sagedus olid enesekohaselt raporteeritud. PNK ja depressiivsuse skoori ning PNK ja üldistunud ärevushäire skoori vahel olid mõõdukad positiivsed seosed. PNK ja enesekohaselt raporteeritud nutitelefoni keskmise kasutusaja vahel oli keskmine positiivne seos. PNK ja vanuse vahel olulisi seoseid ei leitud. PNK ja sugu on omavahel oluliselt seotud. Antud uurimistöö aitab paremini mõista PNK-d ja selle seoseid vaimse tervisega

Prävention, Bewertung und Behandlung von Glaskörpertrübungen im Auge. Intraokulare Gesundheit

Die Datei "HH-PAG Mai 2013" ist eine umfangreiche Informationsquelle für Hilfesuchenden über "Prävention, Bewertung und Behandlung von Glaskörpertrübungen", erstellt von betroffenen Patienten für betroffene Patienten. Sie gewährt einen detaillierten Einblick in die Floaterproblematik und in den Krankheitswert der Störung. Die unterschiedlichen Typen und Ausprägungsstärke von Glaskörpertrübungen kommen zur Sprache. Auch auf die Ursachen wird eingegangen. Es wird vorgebracht welche Anforderungen der informierte Patient an eine sorgsame Diagnostik stellt und wie er sich die Aufklärung im Vorfeld einer Pars plana Vitrektomie als Behandlungsmöglichkeit wünscht. Auch dem Thema Prävention wird ein hoher Stellenwert beigemessen. Ein Forderungskatalog bezüglich der Qualität an einer guten augenärztlichen Versorgung rundet das Ganze ab. Mit dem Floaterscreening-Fragebogen wird dem Patienten ein Screeningtool für ein konstruktives Arzt-Patienten-Gespräch in die Hand gegeben. Ziel der Orientierungshilfe ist die Offenlegung eines Dilemmas in der Augenarztpraxis: „vermeintlich“ harmlose Glaskörpertrübungen kontra hoch invasive Vitrektomie als einzige Behandlungsmethode bei schweren Glaskörpertrübungen

Microstructured blood vessel surrogates reveal structural tropism of motile malaria parasites

Plasmodium sporozoites, the highly motile forms of the malaria parasite, are transmitted naturally by mosquitoes and traverse the skin to find, associate with, and enter blood capillaries. Research aimed at understanding how sporozoites select blood vessels is hampered by the lack of a suitable experimental system. Arrays of uniform cylindrical pillars can be used to study small cells moving in controlled environments. Here, an array system displaying a variety of pillars with different diameters and shapes is developed in order to investigate how Plasmodium sporozoites associate to the pillars as blood vessel surrogates. Investigating the association of sporozoites to pillars in arrays displaying pillars of different diameters reveals that the crescent-shaped parasites prefer to associate with and migrate around pillars with a similar curvature. This suggests that after transmission by a mosquito, malaria parasites may use a structural tropism to recognize blood capillaries in the dermis in order to gain access to the blood stream

Sleep in everyday life – relationship to mood and performance in young and older adults: a study protocol

Laboratory based sleep deprivation studies demonstrate that lack of sleep impairs well-being and performance ability, but suggest that these effects are mitigated in older adults. Yet, much less is known whether day-to-day variations of sleep have similar consequences in the context of everyday life. This project uses an intensive longitudinal design to investigate the occurrence of day-to-day variations in sleep and their impact on mood and performance in everyday life and to examine whether effects differ between young and older adults. We aim to include 160 young (18–30 years) and 160 older adults (55–75 years) to complete a 21-day experience sampling method (ESM) protocol. During the ESM period, participants are asked to fill in (i) a brief morning questionnaire, (ii) 8 short daytime questionnaires addressing momentary well-being, sleepiness, stress, and mind wandering, followed by a 1 min cognitive task and (iii) a brief evening questionnaire, all delivered via a mobile phone application. Sleep will be measured using self-reports (daily questions) and objectively with wrist actigraphy. The impact of adult age on mean levels and intraindividual variability of sleep will be analyzed using mixed-effects location scale models. The impact of sleep on daily cognitive performance will be analyzed using multilevel linear mixed models. The relationship of sleep to mean values and variability of positive and negative affect in young and older adults will be analyzed using mixed-effects location scale modeling. The overarching purpose of the project is improving the current knowledge on the occurrence of day-to-day variations in sleep and their relationship to performance as well as positive and negative affect in young and older adults

Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response

The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12 months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12 months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Positivity Effect and Working Memory Performance Remains Intact in Older Adults After Sleep Deprivation

Background: Older adults perform better in tasks which include positive stimuli, referred to as the positivity effect. However, recent research suggests that the positivity effect could be attenuated when additional challenges such as stress or cognitive demands are introduced. Moreover, it is well established that older adults are relatively resilient to many of the adverse effects of sleep deprivation. Our aim was to investigate if the positivity effect in older adults is affected by one night of total sleep deprivation using an emotional working memory task.Methods: A healthy sample of 48 older adults (60-72 years) was either sleep deprived for one night (n = 24) or had a normal night’s sleep (n = 24). They performed an emotional working memory n-back (n = 1 and 3) task containing positive, negative and neutral pictures.Results: Performance in terms of accuracy and reaction times was best for positive stimuli and worst for negative stimuli. This positivity effect was not altered by sleep deprivation. Results also showed that, despite significantly increased sleepiness, there was no effect of sleep deprivation on working memory performance. A working memory load × valence interaction on the reaction times revealed that the beneficial effect of positive stimuli was only present in the 1-back condition.Conclusion: While the positivity effect and general working memory abilities in older adults are intact after one night of sleep deprivation, increased cognitive demand attenuates the positivity effect on working memory speed