Heteroanionic hydrides offer great possibilities in the design of functional materials. For ternary rare earth hydride oxide REHO, several modifications were reported with indications for a significant phase width with respect to H and O of the cubic representatives. We obtained DyHO and ErHO as well as the thus far elusive LuHO from solid-state reactions of RE2O3 and REH3 or LuH3 with CaO and investigated their crystal structures by neutron and X-ray powder diffraction. While DyHO, ErHO, and LuHO adopted the cubic anion-ordered half-Heusler LiAlSi structure type (F4¯3m, a(DyHO) = 5.30945(10) Å, a(ErHO) = 5.24615(7) Å, a(LuHO) = 5.171591(13) Å), LuHO additionally formed the orthorhombic anti-LiMgN structure type (Pnma; LuHO: a = 7.3493(7) Å, b = 3.6747(4) Å, c = 5.1985(3) Å; LuDO: a = 7.3116(16) Å, b = 3.6492(8) Å, c = 5.2021(7) Å). A comparison of the cubic compounds’ lattice parameters enabled a significant distinction between REHO and REH1+2xO1−x (x < 0 or x > 0). Furthermore, a computational chemistry study revealed the formation of REHO compounds of the smallest rare earth elements to be disfavored in comparison to the sesquioxides, which is why they may only be obtained by mild synthesis conditions.

In clinical diagnostics and research, blood samples are one of the most frequently used materials. Nevertheless, exploring the chemical composition of human plasma and serum is challenging due to the highly dynamic influence of pre-analytical variation. A prominent example is the variability in pre-centrifugation delay (time-to-centrifugation; TTC). Quality indicators (QI) reflecting sample TTC are of utmost importance in assessing sample history and resulting sample quality, which is essential for accurate diagnostics and conclusive, reproducible research. In the present study, we subjected human blood to varying TTCs at room temperature prior to processing for plasma or serum preparation. Potential sample QIs were identified by Ultra high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) based metabolite profiling in samples from healthy volunteers (n = 10). Selected QIs were validated by a targeted MS/MS approach in two independent sets of samples from patients (n = 40 and n = 70). In serum, the hypoxanthine/guanosine (HG) and hypoxanthine/inosine (HI) ratios demonstrated high diagnostic performance (Sensitivity/Specificity > 80%) for the discrimination of samples with a TTC > 1 h. We identified several eicosanoids, such as 12-HETE, 15-(S)-HETE, 8-(S)-HETE, 12-oxo-HETE, (±)13-HODE and 12-(S)-HEPE as QIs for a pre-centrifugation delay > 2 h. 12-HETE, 12-oxo-HETE, 8-(S)-HETE, and 12-(S)-HEPE, and the HI- and HG-ratios could be validated in patient samples.

Nonalcoholic fatty liver disease (NAFLD) is among the leading causes of end-stage liver disease. The impaired hepatic lipid metabolism in NAFLD is exhibited by dysregulated PPARα and SREBP-1c signaling pathways, which are central transcription factors associated with lipid degradation and de novo lipogenesis. Despite the growing prevalence of this disease, current pharmacological treatment options are unsatisfactory. Genistein, a soy isoflavone, has beneficial effects on lipid metabolism and may be a candidate for NAFLD treatment. In an in vitro model of hepatic steatosis, primary human hepatocytes (PHHs) were incubated with free fatty acids (FFAs) and different doses of genistein. Lipid accumulation and the cytotoxic effects of FFAs and genistein treatment were evaluated by colorimetric and enzymatic assays. Changes in lipid homeostasis were examined by RT-qPCR and Western blot analyses. PPARα protein expression was induced in steatotic PHHs, accompanied by an increase in CPT1L and ACSL1 mRNA. Genistein treatment increased PPARα protein expression only in control PHHs, while CPTL1 and ACSL1 were unchanged and PPARα mRNA was reduced. In steatotic PHHs, genistein reversed the increase in activated SREBP-1c protein. The model realistically reflected the molecular changes in hepatic steatosis. Genistein suppressed the activation of SREBP-1c in steatotic hepatocytes, but the genistein-mediated effects on PPARα were abolished by high hepatic lipid levels.

The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine meta-carborane, a water-soluble monosaccharide and a linking unit, namely glycine or ethylenediamine, for facile coupling with various tumor-selective biomolecules bearing a free amino or carboxylic acid group. In this work, coupling experiments with two selected biomolecules, a coumarin derivative and folic acid, were included. The task of every component in this approach was carefully chosen: the carborane moiety supplies ten boron atoms, which is a tenfold increase in boron content compared to the l-boronophenylalanine (l-BPA) presently used in BNCT; the sugar moiety compensates for the hydrophobic character of the carborane; the linking unit, depending on the chosen biomolecule, acts as the connection between the tumor-selective component and the boron-rich moiety; and the respective tumor-selective biomolecule provides the necessary selectivity. This approach makes it possible to develop a modular and feasible strategy for the synthesis of readily obtainable boron-rich agents with optimized properties for potential applications in BNCT.

Though numerous valuable compounds from red algae already experience high demand in medicine, nutrition, and different branches of industry, these organisms are still recognized as an underexploited resource. This study provides a comprehensive characterization of the chemical composition of 15 Arctic red algal species from the perspective of their practical relevance in medicine and the food industry. We show that several virtually unstudied species may be regarded as promising sources of different valuable metabolites and minerals. Thus, several filamentous ceramialean algae (Ceramium virgatum, Polysiphonia stricta, Savoiea arctica) had total protein content of 20–32% of dry weight, which is comparable to or higher than that of already commercially exploited species (Palmaria palmata, Porphyra sp.). Moreover, ceramialean algae contained high amounts of pigments, macronutrients, and ascorbic acid. Euthora cristata (Gigartinales) accumulated free essential amino acids, taurine, pantothenic acid, and floridoside. Thalli of P. palmata and C. virgatum contained the highest amounts of the nonproteinogenic amino acid β-alanine (9.1 and 3.2 μM g−1 DW, respectively). Several red algae tend to accumulate heavy metals; although this may limit their application in the food industry, it makes them promising candidates for phytoremediation or the use as bioindicators.

Although case studies in avoidant/restrictive food intake disorder (ARFID) indicate severe nutritional deficiencies in those with a highly limited amount or variety of food intake, systematic analyses on food intake in treatment-seeking children and adolescents with ARFID are lacking. Within this study, n = 20 patients with an interview-based diagnosis of ARFID (0–17 years) were included and compared to n = 20 healthy controls individually matched for age and sex. Children or parents completed three-day food diaries and a food list. Macronutrient, vitamin, and mineral supply was determined based on the percentage of their recommended intake. The results showed a significantly lower total energy and protein intake in ARFID versus controls, with trends for lower fat and carbohydrate intake. ARFID subtypes of limited amount versus variety of food intake significantly differed in macro-, but not micronutrient intake. Those with ARFID met only 20–30% of the recommended intake for most vitamins and minerals, with significantly lower intake relative to controls for vitamin B1, B2, C, K, zinc, iron, and potassium. Variety of food intake was significantly reduced in ARFID versus controls in all food groups except carbohydrates. This study demonstrated that ARFID goes along with reduced everyday life macro- and micronutrient intake, which may increase the risk for developmental and health problems. Future studies additionally assessing serum nutrient levels in a larger sample may further explore differences in food intake across diverse ARFID presentations.

Metallorganische Gerüstverbindungen (MOFs) sind hochporöse Materialien, welche aus Metallionen oder –clustern und sogenannten organischen Linkern bestehen. Aufgrund ihres modularen Aufbaus lassen sich gewünschte Eigenschaften der Materialien relativ leicht konstruieren und somit für Anwendungen hoch spezialisierte Materialien generieren. Neben klassischen Anwendungen poröser Materialen wie Gasspeicherung, Gastrennung und Katalyse kommen sie auch für speziellere Anwendungsgebiete in Sensoren oder als Wirkstoffträger für Medikamente in Frage. Insbesondere das flexible Verhalten einiger MOFs unter physikalischen oder chemischen Stimuli schafft dabei interessante Möglichkeiten. Flexible MOFs verändern zum Beispiel unter Einwirkung von Druck oder Gasen ihre Kristallstruktur, sodass bei Adsorptionsprozessen variables Verhalten auftreten kann. Einer der MOFs, welcher derartiges Verhalten aufweist ist DUT-13 (Dresden University of Technology Material Nummer 13). Dieser MOF hat eine offenporige (op) Phase, welche bei der Adsorption von Gasen wie Stickstoff, Methan und CO2 zu einer geschlossenen (cp) Phase kontrahiert. Eine weitere Drucksteigerung beim Adsorptionsprozess öffnet das Porensystem wieder. Diese Art der Flexibilität wird als breathing bezeichnet. Ein anderer MOF der diese Art von Flexibilität aufweist, ist DUT-49. Im Gegensatz zu DUT 13 zeigt dieser MOF allerdings zusätzlich das kontraintuitive Phänomen der negativen Gasadsorption (NGA). Bei dieser wird während des Adsorptionsprozesses in einem bestimmten Druckbereich bei der Phasentransformation von der op zur cp Phase Gas desorbiert, da in der op Phase zu diesem Zeitpunkt bereits mehr Gas adsorbiert ist, als in die cp Phase hineinpasst. Wichtig für das Auftreten dieses Phänomens ist also die Metastabilität der teilweise beladenen op Phase. Diese kann durch Faktoren wie Kristallitgröße, Temperatur, Adsorptiv, Metall im MOF und Porengröße beeinflusst werden. Da das Phänomen bisher nur in DUT-49 und isoretikulären Strukturen (Strukturen gleicher Netzwerktopologie) aufgetreten ist, soll das Phänomen im Rahmen dieser Arbeit auf andere Netzwerktopologien übertragen werden. Da der Flexibilitätsmechanismus in DUT-49 auf dem Verbiegen des Linkers beruht und dessen Eigenschaften somit großen Einfluss auf die Phasentransformation haben, wurde mit der näheren Untersuchung eines MOFs mit sehr ähnlichem Linker, DUT-13, begonnen. In dieser Arbeit wird die bisher unbekannte cp Phase von DUT-13 und der zugrundeliegende Flexibilitätsmechanismus des Netzwerkes aufgeklärt. Außerdem wird der Einfluss der Temperatur auf das Adsorptionsverhalten von DUT-13 geprüft. Zusätzlich wird durch die Synthese einer isoretikulären Serie von DUT-13-analogen MOFs der Einfluss der Porengröße auf die Flexibilität des Netzwerkes untersucht. So wird unter Anderem der hochflexible neue MOF DUT-190 hergestellt, welcher über den gesamten Temperaturbereich von Siedepunkt bis zum kritischen Punkt bei der Methanadsorption flexibles Verhalten zeigt. Außerdem wird an diesem neuen MOF der Einfluss des Metalls auf die Flexibilität untersucht, indem ein postsynthetischer Metallaustausch durchgeführt wird. Da die synthetisierten Linker der isoretikulären Reihe zu hohe Flexibilität in den MOFs induziert haben, wurden außerdem Linker hergestellt, welche die beiden äußeren Phenylringe am Linker durch eine Ethyleneinheit verbrücken. Auf Basis der so entstandenen Linker wurden weitere neue MOFs synthetisiert, welche das seltene Motiv von Siebenringen in MOFs einführen. Einer der so erhaltenen MOFs, DUT-193, weist dabei eine bisher unbekannte neue Netzwerktopologie auf. DUT 193 zeigt zudem hohe Porosität und rigides Verhalten. Um das Verständnis für die Anforderungen an den Linker zur Erzeugung von NGA zu erweitern, wurden abschließend einige Tests zum postsynthetischen Linkeraustausch an DUT-13 und DUT-49 durchgeführt, um den rigideren DUT-49-Linker in DUT-13 einzubauen und umgekehrt.:Danksagung I Inhaltsverzeichnis III Abkürzungsverzeichnis VI Theoretischer Teil 1 1 Motivation 1 2 Stand der Forschung 3 2.1 Was sind Metallorganische Gerüstverbindungen? 3 2.2 Isoretikuläre Chemie und Netzwerktopologien 4 2.3 MOF-Synthese und Aktivierung 8 2.3.1 Konventionelle Synthesen 8 2.3.2 Postsynthetischer Linkeraustausch 9 2.3.3 Postsynthetischer Metallaustausch 10 2.3.4 Aktivierung von MOFs 11 2.4 Röntgendiffraktometrie 12 2.5 Adsorption 16 2.6 Strukturelle Flexibilität in MOFs 22 Experimenteller Teil 28 3 Generelle Angaben 28 3.1 Chemikalien 28 3.2 Methoden 30 3.2.1 Methoden zur Charakterisierung der organischen Verbindungen 30 3.2.2 Methoden zur Handhabung und Charakterisierung synthetisierter MOFs 31 4 Synthesen.. 37 4.1 Linkersynthesen 37 4.1.1 Synthese des Linkers H4ndtb (Naphthalen-2,6-diamin-tetrabenzoesäure) 37 4.1.2 Synthese des Linkers H4benztb (Benzidintetrabenzoesäure) 38 4.1.3 Route 1 zur Synthese des Linkers H4benztpb (Benzidin-tetra-(p-phenylbenzoesäure)) 39 4.1.4 Route 2 zur Synthese des Linkers H4benztpb 40 4.1.5 Synthese des Linkers H4tpdatb (p-Terphenyldiamin-tetrabenzoesäure) 42 4.1.6 Synthese des Linkers H4BBCDC (9,9'-([1,1'-Biphenyl]-4,4'-diyl)bis(9H-carbazole-3,6-dicarbonsäure)) 44 4.1.7 Synthese der Linker H4TBBDDADC (5,5'-(3,3',5,5'-Tetramethyl-[1,1'-biphenyl]-4,4'-diyl)bis(10,11-dihydro-5H-dibenzo[b,f]azepin-2,8-dicarbonsäure)) und H4BBDDADC (5,5'-([1,1'-Biphenyl]-4,4'-diyl)bis(10,11-dihydro-5H-dibenzo[b,f]azepin-2,8-dicarbonsäure)) 45 4.1.8 Synthesen weiterer Linker und Linkervorstufen 51 4.2 MOF-Synthesen 53 4.2.1 Basierend auf H4ndtb 53 4.2.2 Basierend auf H4benztb 54 4.2.3 Basierend auf H4tpdatb 54 4.2.4 Basierend auf H4benztpb 55 4.2.5 Basierend auf H4BBCDC 56 4.2.6 Basierend auf den Azepinlinkern H2DDADC, H4TBBDDADC und H4BBDDADC 56 5 Ergebnisse und Diskussion 58 5.1 DUT-13 (Zn4O(benztb)3/2) 58 5.1.1 Charakterisierung von DUT-13cp und dem Mechanismus der Phasentransformation 58 5.1.2 Methanadsorption bei unterschiedlichen Temperaturen 60 5.2 H4tpdatb basierte MOFs DUT-180 und DUT-190 61 5.2.1 DUT-180 (Zn2(tpdatb)(H2O)2) 62 5.2.2 DUT-190 (Zn4O(tpdatb)3/2) 64 5.2.3 Metallaustausch an DUT-190(Zn) 70 5.3 H4ndtb und H4benztpb basierte MOFs (DUT-181 und DUT-191 bzw. DUT-182 und DUT-192) 76 5.3.1 DUT-181 und DUT-191 basierend auf Zink und H4ndtb 77 5.3.2 DUT-182 und DUT-192 basierend auf Zink und H4benztpb 78 5.4 Azepinlinker basierte MOFs DUT-183, DUT-184, DUT-193 und DUT-194 81 5.4.1 DUT-193 (Zn4O(TBBDDADC)3/2) 84 5.4.2 DUT-184 (Zn2(BBDDADC)(NMP)2) 87 5.4.3 DUT-194 89 5.4.4 DUT-183 (Zn4O(DDADC)3) 90 5.5 DUT-13 und DUT-49 mit gemischten Linkern 91 6 Zusammenfassung und Ausblick 97 Literaturverzeichnis 101 Anhang 106 Kristallstrukturdaten 106 Abbildungen der Analytik zum Experimentalteil 108 NMR-Spektren: 111 ATR-IR-Spektren: 131 Ergänzende Abbildungen zur Auswertung 135

Networks of crosslinked keratin filaments are abundant in epithelial cells and tissues, providing resilience against mechanical forces and ensuring cellular integrity. Although studies of in vitro models of reconstituted keratin networks have revealed important mechanical aspects, the mechanical properties of crosslinked keratin structures remain poorly understood. Here, we exploited the power of electron beam irradiation (EBI) to crosslink in vitro networks of soft epithelial keratins 8 and 18 (k8–k18) filaments with different irradiation doses (30 kGy, 50 kGy, 80 kGy, 100 kGy, and 150 kGy). We combined bulk shear rheology with confocal microscopy to investigate the impact of crosslinking on the mechanical and structural properties of the resultant keratin gels. We found that irradiated keratin gels display higher linear elastic modulus than the unirradiated, entangled networks at all doses tested. However, at the high doses (80 kGy, 100 kGy, and 150 kGy), we observed a remarkable drop in the elastic modulus compared to 50 kGy. Intriguingly, the irradiation drastically changed the behavior for large, nonlinear deformations. While untreated keratin networks displayed a strong strain stiffening, increasing irradiation doses shifted the system to a strain softening behavior. In agreement with the rheological behavior in the linear regime, the confocal microscopy images revealed fully isotropic networks with high percolation in 30 kGy and 50 kGy-treated keratin samples, while irradiation with 100 kGy induced the formation of thick bundles and clusters. Our results demonstrate the impact of permanent crosslinking on k8–k18 mechanics and provide new insights into the potential contribution of intracellular covalent crosslinking to the loss of mechanical resilience in some human keratin diseases. These insights will also provide inspiration for the synthesis of new keratin-based biomaterials.

The amount of boron accumulated in tumor tissue plays an important role regarding the success of the boron neutron capture therapy (BNCT). In this article, we report a modular system, combining readily available starting materials, like glycine, 1,3,5-triazine and the well-known 9-mercapto-1,7-dicarba-closo-dodecaborane(12), as well as alpha-d-galactopyranose for increased hydrophilicity, with a novel boron-rich tris-meta-carboranyl thiol.

The herbal preparation coffee charcoal is produced by over-roasting and milling green dried Coffea arabica L. seeds, and has a long-standing tradition in the treatment of inflammatory and gastrointestinal disorders. Its therapeutic properties are commonly attributed to adsorptive and astringent effects. This insufficiently explains its mode of action, especially when used in the treatment of inflammatory diseases in lower dosages. Our investigations aimed to identify bioactive secondary plant metabolites affecting cytokine-signaling. Thus, a phytochemical analysis of coffee charcoal extract was conducted using HPLC and LC/MS. Trigonelline, neochlorogenic acid, chlorogenic acid, caffeine, cryptochlorogenic acid, feruloylquinic acid isomers, and a caffeoylquinolacton were identified in the extract. Subsequently, the effects of coffee charcoal extract, chlorogenic acid isomers, their metabolite caffeic acid, caffeine, and trigonelline on cytokine (TNF, IL-6, MCP-1) release from LPS-challenged human THP-1 macrophages were examined to evaluate anti-inflammatory activity. Coffee charcoal showed concentration-dependent mild-to-medium inhibitory effects. The chlorogenic acid isomers and caffeic acid inhibited the TNF release, with cryptochlorogenic acid exerting the most distinct effects, as well as decreasing the release of IL-6 and MCP-1. In addition, scanning electron microscopic images provided an impression of the particle constitution, indicating a larger particle size and less structured surface of coffee charcoal in comparison to activated charcoal. In conclusion, our findings underline that beyond adsorptive effects, coffee charcoal exhibits pharmacological properties, which derive from a spectrum of secondary plant metabolites and support the therapeutic use in inflammatory diseases. Chlorogenic acids, particularly cryptochlorogenic acid, appear as pivotal bioactive compounds.