Halogen and pnictogen bonding in host-guest chemistry

This thesis describes the synthesis and characterisation of acyclic and macrocyclic receptors containing halogen- and pnictogen bonding motifs for the study of sigma(σ)-hole interactions for anion recognition, as well as the stabilisation of reactive halonium species through macrocyclic ligands. Chapter 1 introduces supramolecular chemistry and the central concepts related to host-guest recognition and self-assembly. Different types of non-covalent interactions are discussed with a focus on sigma(σ)-hole interactions. Relevant literature examples related to anion recognition as well as interlocked host structures are furthermore presented. Chapter 2 presents the synthesis of a series of antimony(III) and bismuth(III) based pnictogen bonding acyclic receptors, which were studied to elucidate the strength and selectivity of pnictogen bonding based anion recognition. The synthesis and study of mixed pnictogen- and halogen bonding tripodal receptors as well as mono- and bis-stibanotriazole based receptors is furthermore discussed. Chapter 3 describes the synthesis of a series of halogen bonding lariat macrocycles incorporating ambidentate iodotriazole motifs into both the macrocycle and lariat arm. These were used to investigate anion and metal cation template directed synthetic routes for potential pseudo-[1]rotaxane assembly with the goal of constructing a functional [1]rotaxane capable of anion recognition through halogen bonding. Chapter 4 details the study of four different bis-pyridine-based macrocycles for the complexation and stabilisation of reactive halonium cations. To this end, the solid-state structures of bromonium complexes as well as their parent Ag(I) and electronically related d10 Au(I) complexes are presented together with solution phase halonium cation 1H NMR ligand exchange studies, which reveal evidence for a macrocyclic effect for halonium guest species. Chapter 5 presents a summary of the major conclusions from the research project and discusses future work. Chapter 6 contains synthetic details and full characterisation of all novel compounds, as well as further details regarding 1H NMR titration experiment protocols and single-crystal XRD experiments

Near-Complete Genome Sequence of Lötschberg Virus (Mononegavirales: Filoviridae) Identified in European Perch (Perca fluviatilis Linnaeus, 1758).

We obtained the near-complete genome sequence of a novel virus, Lötschberg virus (LTBV), from a European perch metatranscriptome. Genome organization and pairwise sequence comparison indicated that LTBV represents a tentative new species and genus of the mononegaviral family Filoviridae

PDE7A1 hydrolyzes cCMP

AbstractThe degradation and biological role of the cyclic pyrimidine nucleotide cCMP is largely elusive. We investigated nucleoside 3′,5′-cyclic monophosphate (cNMP) specificity of six different recombinant phosphodiesterases (PDEs) by using a highly-sensitive HPLC–MS/MS detection method. PDE7A1 was the only enzyme that hydrolyzed significant amounts of cCMP. Enzyme kinetic studies using purified GST-tagged truncated PDE7A1 revealed a cCMP KM value of 135±19μM. The Vmax for cCMP hydrolysis reached 745±27nmol/(minmg), which is about 6-fold higher than the corresponding velocity for adenosine 3′,5′-cyclic monophosphate (cAMP) degradation. In summary, PDE7A is a high-speed and low-affinity PDE for cCMP

How Will Hydroelectric Power Generation Develop under Climate Change Scenarios?

Climate change has a large impact on water resources and thus on hydropower. Hydroelectric power generation is closely linked to the regional hydrological situation of a watershed and reacts sensitively to changes in water quantity and seasonality. The development of hydroelectric power generation in the Upper Danube basin was modelled for two future decades, namely 2021-2030 and 2051-2060, using a special hydropower module coupled with the physically-based hydrological model PROMET. To cover a possible range of uncertainties, 16 climate scenarios were taken as meteorological drivers which were defined from different ensemble outputs of a stochastic climate generator, based on the IPCC-SRES-A1B emission scenario and four regional climate trends. Depending on the trends, the results show a slight to severe decline in hydroelectric power generation. Whilst the mean summer values indicate a decrease, the mean winter values display an increase. To show past and future regional differences within the Upper Danube basin, three hydropower plants at individual locations were selected. Inter-annual differences originate predominately from unequal contributions of the runoff compartments rain, snow-and ice-melt

Selective potassium chloride recognition, sensing, extraction, and transport using a chalcogen-bonding heteroditopic receptor

Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for applications in the field of molecular recognition. Recent studies have demonstrated ChB donor strength and potency to be remarkably sensitive to local electronic environments, including redox-switchable on/off anion binding and sensing capability. Influencing the unique electronic and geometric environment sensitivity of ChB interactions through simultaneous cobound metal cation recognition, herein, we present the first potassium chloride-selective heteroditopic ion-pair receptor. The direct conjugation of benzo-15-crown-5 ether (B15C5) appendages to Te centers in a bis-tellurotriazole framework facilitates alkali metal halide (MX) ion-pair binding through the formation of a cofacial intramolecular bis-B15C5 M+ (M+ = K+, Rb+, Cs+) sandwich complex and bidentate ChB···X- formation. Extensive quantitative 1H NMR ion-pair affinity titration experiments, solid-liquid and liquid-liquid extraction, and U-tube transport studies all demonstrate unprecedented KCl selectivity over all other group 1 metal chlorides. It is demonstrated that the origin of the receptor's ion-pair binding cooperativity and KCl selectivity arises from an electronic polarization of the ChB donors induced by the cobound alkali metal cation. Importantly, the magnitude of this switch on Te-centered electrophilicity, and therefore anion-binding affinity, is shown to correlate with the inherent Lewis acidity of the alkali metal cation. Extensive computational DFT investigations corroborated the experimental alkali metal cation-anion ion-pair binding observations for halides and oxoanions.publishe

The Advantages of Flexibility:The Role of Entropy in Crystal Structures Containing C-H···F Interactions

Molecular crystal structures are often interpreted in terms of strong, structure directing, intermolecular interactions, especially those with distinct geometric signatures such as H-bonds or π-stacking interactions. Other interactions can be overlooked, perhaps because they are weak or lack a characteristic geometry. We show that although the cumulative effect of weak interactions is significant, their deformability also leads to occupation of low energy vibrational energy levels, which provides an additional stabilizing entropic contribution. The entropies of five fluorobenzene derivatives have been calculated by periodic DFT calculations to assess the entropic influence of C-H···F interactions in stabilizing their crystal structures. Calculations reproduce inelastic neutron scattering data and experimental entropies from heat capacity measurements. C-H···F contacts are shown to have force constants which are around half of those of more familiar interactions such as hydrogen bonds, halogen bonds, and C-H···π interactions. This feature, in combination with the relatively high mass of F, means that the lowest energy vibrations in crystalline fluorobenzenes are dominated by C-H···F contributions. C-H···F contacts occur much more frequently than would be expected from their enthalpic contributions alone, but at 150 K, the stabilizing contribution of entropy provides, at −10 to −15 kJ mol-1, a similar level of stabilization to the N-H···N hydrogen bond in ammonia and O-H···O hydrogen bond in water.</p

Reliability of light microscopy and a computer-assisted replica measurement technique for evaluating the fit of dental copings

Abstract The aim of this in vitro study was to assess the reliability of two measurement systems for evaluating the marginal and internal fit of dental copings. Material and Methods: Sixteen CAD/CAM titanium copings were produced for a prepared maxillary canine. To modify the CAD surface model using different parameters (data density; enlargement in different directions), varying fit was created. Five light-body silicone replicas representing the gap between the canine and the coping were made for each coping and for each measurement method: (1) light microscopy measurements (LMMs); and (2) computer-assisted measurements (CASMs) using an optical digitizing system. Two investigators independently measured the marginal and internal fit using both methods. The inter-rater reliability [intraclass correlation coefficient (ICC)] and agreement [Bland-Altman (bias) analyses]: mean of the differences (bias) between two measurements [the closer to zero the mean (bias) is, the higher the agreement between the two measurements] were calculated for several measurement points (marginal-distal, marginal-buccal, axial-buccal, incisal). For the LMM technique, one investigator repeated the measurements to determine repeatability (intra-rater reliability and agreement). Results: For inter-rater reliability, the ICC was 0.848-0.998 for LMMs and 0.945-0.999 for CASMs, depending on the measurement point. Bland-Altman bias was −15.7 to 3.5 μm for LMMs and −3.0 to 1.9 μm for CASMs. For LMMs, the marginal-distal and marginal-buccal measurement points showed the lowest ICC (0.848/0.978) and the highest bias (-15.7 μm/-7.6 μm). With the intra-rater reliability and agreement (repeatability) for LMMs, the ICC was 0.970-0.998 and bias was −1.3 to 2.3 μm. Conclusion: LMMs showed lower interrater reliability and agreement at the marginal measurement points than CASMs, which indicates a more subjective influence with LMMs at these measurement points. The values, however, were still clinically acceptable. LMMs showed very high intra-rater reliability and agreement for all measurement points, indicating high repeatability

Accuracy of intraoral and extraoral digital data acquisition for dental restorations

The computer-aided design (CAD) and computer-aided manufacturing (CAM) process chain for dental restorations starts with taking an impression of the clinical situation. For this purpose, either extraoral digitization of gypsum models or intraoral digitization can be used. Despite the increasing use of dental digitizing systems, there are only few studies on their accuracy. Objective This study compared the accuracy of various intraoral and extraoral digitizing systems for dental CAD/CAM technology. Material and Methods An experimental setup for three-dimensional analysis based on 2 prepared ceramic master dies and their corresponding virtual CAD-models was used to assess the accuracy of 10 extraoral and 4 intraoral optical non-contact dental digitizing systems. Depending on the clinical procedure, 10 optical measurements of either 10 duplicate gypsum dies (extraoral digitizing) or directly of the ceramic master dies (intraoral digitizing) were made and compared with the corresponding CAD-models. Results The digitizing systems showed differences in accuracy. However, all topical systems were well within the benchmark of ±20 µm. These results apply to single tooth measurements. Conclusions Study results are limited, since only single teeth were used for comparison. The different preparations represent various angles and steep and parallel opposing tooth surfaces (incisors). For most digitizing systems, the latter are generally the most difficult to capture. Using CAD/CAM technologies, the preparation angles should not be too steep to reduce digitizing errors. Older systems might be limited to a certain height or taper of the prepared tooth, whereas newer systems (extraoral as well as intraoral digitization) do not have these limitations

DELIKAT – Fachdialoge Deliberative Demokratie: Analyse Partizipativer Verfahren für den Transformationsprozess

Das Projekt erfasst und bewertet die Potenziale existierender Partizipationsformate für die Transformation des politischen Systems zu einer kooperativen und deliberativen Demokratie. Angestrebt wird kein Alternativentwurf zu einer repräsentativen Demokratie, sondern Empfehlungen für eine Ergänzung dieser Regierungsform durch kooperative und deliberative Elemente, die der gesellschaftlichen Forderung nach einem „Mehr an Beteiligung“ Rechnung tragen. Den Hintergrund für die theoretische Reflexion bildet die normative Annahme, dass die Öffentlichkeit nicht nur an Wahlprozessen beteiligt sein soll, sondern auch an der Entscheidungsvorbereitung und der Abwägung von kollektiv verbindlichen Handlungsoptionen, von deren Konsequenzen sie in ihrem Lebensumfeld betroffen sein werden. Anhand der Ergebnisse des Projektes ergeben sich Anknüpfungspunkte für zukünftige Vorhaben auf zwei Ebenen. Die Partizipationsmatrix bietet auf der Verfahrensebene gute Möglichkeiten zur Kombination und Rekombination einzelner Verfahren wie auch Verfahrensbestandteile. Die Politikempfehlungen zeigen weitergehend konkrete Wege für die Umsetzung einer neuen Partizipationskultur durch Politik und Verwaltung im Sinne eines neuen Mainstreamings von Partizipation. Diese sprechen sich im Kern dafür aus, mehr Beteiligung zu wagen, ja, eine „Kultur der Beteiligung“ zu etablieren. Diese ist jedoch an Voraussetzungen gebunden, die ebenso aufgeführt werden. Der institutionelle Unterbau einer solchen Beteiligungskultur wird letztlich in einem Mainstreaming von Partizipation auf allen Ebenen von Politik und Verwaltung lokalisiert.The project detects and evaluates the potential of existing participation formats to transform the political system into a cooperative and deliberative democracy. The aim is to develop recommendations for the integration of cooperative and deliberative elements into representative democracy, rather than to develop an alternative model. These new elements take societal demands for increased involvement into account. The normative assumption that the public should not only be involved in elections but also in the preparation of collectively binding decisions and in the assignment of trade-offs between various political options serves as the basis for the theoretical reflection. The results of this project have significant implications for future projects on two levels. On the procedural level, the participation matrix offers opportunities for combining and recombining individual procedures and procedural elements. On the substantive level, the political recommendations offer structural advise on how to realise a new participation culture through politics and administration. This can also be described as a “mainstreaming” of participation. The recommendations promote attempts at increased participation and the establishment of a “culture of participation”. This, however, is bound to certain conditions, which are also listed and explained. Ultimately, the institutional foundation of such a participation culture is localised in a serious attempt to implement mainstreaming of participation on all levels of politics and administration

心房ナトリウム利尿ペプチドは、ミネラルコルチコイド受容体活性を抑制して心筋リモデリングを予防する

BACKGROUND:The endocrine balance between atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system is critical for the maintenance of arterial blood pressure and volume homeostasis. This study investigated whether a cardiac imbalance between ANP and aldosterone, toward increased mineralocorticoid receptor (MR) signaling, contributes to adverse left ventricular remodeling in response to pressure overload.METHODS AND RESULTS:We used the MR-selective antagonist eplerenone to test the role of MRs in mediating pressure overload-induced dilatative cardiomyopathy of mice with abolished local, cardiac ANP activity. In response to 21 days of transverse aortic constriction, mice with cardiomyocyte-restricted inactivation (knockout) of the ANP receptor (guanylyl cyclase [GC]-A) or the downstream cGMP-dependent protein kinase I developed enhanced left ventricular hypertrophy and fibrosis together with contractile dysfunction. Treatment with eplerenone (100 mg/kg/d) attenuated left ventricular hypertrophy and fully prevented fibrosis, dilatation, and failure. Transverse aortic constriction induced the cardiac expression of profibrotic connective tissue growth factor and attenuated the expression of SERCA2a (sarcoplasmic reticulum Ca(2+)-ATPase) in knockout mice, but not in controls. These genotype-dependent molecular changes were similarly prevented by eplerenone. ANP attenuated the aldosterone-induced nuclear translocation of MRs via GC-A/cGMP-dependent protein kinase I in transfected HEK 293 (human embryonic kidney) cells. Coimmunoprecipitation and fluorescence resonance energy transfer experiments demonstrated that a population of MRs were membrane associated in close interaction with GC-A and cGMP-dependent protein kinase I and, moreover, that aldosterone caused a conformational change of this membrane MR/GC-A protein complex which was prevented by ANP.CONCLUSIONS:ANP counter-regulates cardiac MR activation in hypertensive heart disease. An imbalance in cardiac ANP/GC-A (inhibition) and aldosterone/MR signaling (augmentation) favors adverse cardiac remodeling in chronic pressure overload.博士（医学）・甲第630号・平成27年3月16日© 2014 American Heart Association, Inc