Synthese, Untersuchung und Anwendung supramolekularer Wirte in der chemischen Sensorik

Während dieser Arbeit wurden verschiedene Bereiche der molekularen Erkennung untersucht und deren Anwendung in supramolekularer Sensorik evaluiert. Im ersten Teil der Arbeit wurden Molekularstruktur-Affinitäts-Beziehungen untersucht, indem Substrat-Affinitätsprofile für eine Reihe von supramolekularen Wirten auf Basis von Tetraphenylmethan und 9,9‘-Spirobifluoren sowie für Wirte basierend auf Resorcin[4]aren mit einer Auswahl an niedermolekularen Analyten gemessen wurden. Hieraus konnten neue Erkenntnisse für das Design und die Synthesestrategie von Affinitätsmaterialien zur Anwendung auf Quarzmikrowaagen gewonnen werden. In der Rigiditätsstudie mit Tetraphenylmethan- und 9,9‘-Spirobifluoren-basierten supra-molekularen Materialien konnte die Überlegenheit des starren Spirobifluoren-Gerüsts gezeigt werden. Hierbei konnte der mit Isosteviol-Derivaten funktionalisierte Spirobifluoren-Grundkörper formstabilere Bindungsstellen ausbilden und so den Gastmolekülen einen prononcierteren Wechselwirkungsraum zur Verfügung stellen. Die systematische Untersuchung der Resorcin[4]aren-basierten supramolekularen Wirte auf ihre Affinität führte zum besseren Verständnis des Einflusses der Hohlraumstruktur, der Zugänglichkeit, der Größe sowie der Art der supramolekularen Wechselwirkungen der Wirtsmoleküle. Hierbei konnte gezeigt werden, dass Resorcin[4]aren-Kavitanden mit definierten, tiefen Kavitäten überlegene supramolekulare Eigenschaften gegenüber weit-offenen und sogar oben verbrückten Resorcin[4]aren-basierten Strukturen aufweisen. Im letzten Teil dieser Arbeit konnte ein neues System zur Detektion, Separation und Lagerung des umweltschädlichen FCKWs Trichlorfluormethan erarbeitet werden. In der Studie wurden planare Bragg-Gitter-Sensoren mit per-Methyl-, per-Ethyl- und per-Allyl-substituierten Cyclo¬dextrinen als Affinitätsmaterialien auf gasförmiges Trichlorfluormethan sensibilisiert. Diese Art der Funktionalisierung hat sich als hocheffizient in der Anwendung erwiesen, da im Vergleich zu einem identischen, aber unbeschichteten Sensor eine bis zu 400-fach höhere Signalantwort erzielt werden konnte. Die vorgestellte Sensorvorrichtung weist eine Nachweis¬¬grenze von bis zu 5 ppm auf. Es konnte ebenfalls eine Abhängigkeit der Adsorptions¬kinetik von der Substituentenlänge gezeigt werden. Auf der einen Seite nehmen die Reaktionszeiten des Sensors mit zunehmender Länge der Substituenten des Affinitäts-materials ab. Auf der anderen Seite konnte eine höhere Sensitivität bei per-Methylierten Cyclodextrinen beobachtet werden. Auf diese Weise konnte ein Sensorsystem zur Trichlor-fluormethan-Detektion realisiert und untersucht werden. Besonders interessante Ergebnisse konnten in Verbindung des Trichlorfluormethans mit per-Methyliertem -Cyclodextrin festgestellt werden. Es konnte die Fähigkeit von Hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin nachgewiesen werden, selektiv einen sehr stabilen supra-molekularen Komplex mit Trichlorfluormethan auszubilden und so dauerhaft zu speichern. Die reversible Komplexierung führte zu einer hocheffizienten und stabilen Kristallisation im Verhältnis 4:1, welche sowohl kristallographisch, als auch thermogravimetrisch nachgewiesen wurde. Am Beispiel eines binären Gemisches aus Dichlormethan und Trichlorfluormethan konnte die außerordentliche Selektivität der Freon 11 Komplexierung innerhalb der Cyclodextrinkavität gezeigt werden. Darüber hinaus wurde die Anwendbarkeit von Hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin als Packungsmaterial für eine Festbett-adsorption demonstriert und somit die Herstellung von wirtschaftlichen, wiederverwend-baren und hoch nachhaltigen Filterelementen für gasförmiges Trichlorfluormethan ermöglicht. Des Weiteren konnte gezeigt werden, dass bei Anwendung dieses Cyclodextrins als Affinitätsschicht auf planaren Bragg-Gitter-Sensoren eine CFC-11-Konzentrationen über 35 Vol% zu einer sichtbaren spontanen Kristallisation der per-Me -Cyclodextrin-Affinitäts-schicht auf der Sensoroberfläche führte, sodass dieses Verhalten effektiv als Einwegsensor adaptiert werden kann und so zum Beispiel zur Überwachung von industriellen Produktions-anlagen oder Anlagen zur Kühlgeräteentsorgung eingesetzt werden kann, um die Umwelt vor der Exposition mit dem schädlichen Trichlorfluormethan zu schützen.During this work, different areas of molecular recognition were investigated and their application in supramolecular sensor technology was evaluated. The results could be summarized in three publications and a manuscript in revision in internationally recognized (peer-reviewed) scientific journals as well as a patent application. In the first part of the study, molecular structure affinity relationships were investigated by measuring substrate affinity profiles for a number of supramolecular hosts based on tetraphenylmethane and 9,9'-spirobifluoren as well as for hosts based on resorcin[4]aren with a selection of low molecular weight analytes. From this, new insights for the design and synthesis strategy of affinity materials for application on quartz microbalances were obtained. In the rigidity study with tetraphenylmethane and 9,9'-spirobifluorene-based supra-molecular materials, the superiority of the rigid spirobifluorenic scaffold was demonstrated. Here, the spirobifluorene base functionalized with isosteviol derivatives could form more stable binding sites and thus provide the guest molecules with a more pronounced interaction space. This was demonstrated by significantly higher affinities using quartz microbalance analysis. The systematic investigation of the affinity of resorcinol[4]arene based supramolecular hosts led to a better understanding of the influence of cavity structure, accessibility, size and type of supramolecular interactions of the host molecules. These results inevitably led to the conclusion that the interaction of these factors is of extraordinary importance for gravimetric sensing. It could be shown that resorcinol[4]arene-cavitands with defined, deep cavities have superior supramolecular properties compared to widely open and even top-bridged resorcinol[4]arene-based structures. Furthermore, it was demonstrated that interactions, such as halogen bridges, play only a minor role outside the cavity. Understanding the importance of interactions for supramolecular hosts with guest molecules used for quartz microbalance analysis is essential for an improved design of affinity materials for this sensor application. Based on the results presented in this paper, we expect the development of further, more powerful affinity materials that can be used in quartz microbalance analysis. In the last part of this work, a new system for the detection, separation and storage of the environmentally harmful CFC trichlorofluoromethane was developed. In the study, planar Bragg grating sensors with per-methyl-, per-ethyl- and per-allyl-substituted cyclodextrins as affinity materials were sensitized to gaseous trichlorofluoromethane. This type of functionalization has proven to be highly efficient in its application, since a signal response up to 400 times higher than that of an identical but uncoated sensor could be achieved. The sensor device presented here has a detection limit of up to 5 ppm. A dependence of the adsorption kinetics on the substituent length could also be shown. On the one hand, the reaction times of the sensor decrease with increasing length of the substituents of the affinity material. On the other hand, a higher sensitivity could be observed with per-methylated cyclodextrins. In this way, a sensor system for trichlorofluoromethane detection could be realized and investigated. Particularly interesting results were obtained in connection of trichlorofluoromethane with per-methylated cyclodextrin. The ability of hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin to selectively form a very stable supra-molecular complex with trichlorofluoromethane and thus store it permanently was demonstrated. The reversible complexation led to a highly efficient and stable crystallization in a ratio of 4:1, which was demonstrated both crystallographically and thermogravimetrically. Using the example of a binary mixture of dichloromethane and trichlorofluoromethane, the extraordinary selectivity of the Freon 11 complexation within the cyclodextrin cavity could be demonstrated. In addition, the applicability of hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin as a packing material for fixed bed adsorption was demonstrated, enabling the production of economical, reusable and highly sustainable filter elements for gaseous trichlorofluoromethane. Furthermore, it could be shown that when this cyclodextrin was applied as an affinity layer on planar Bragg grating sensors, CFC-11 concentrations above 35 vol% led to a visible spontaneous crystallization of the per-Me cyclodextrin affinity layer on the sensor surface, so that this behavior can be effectively adapted as a disposable sensor and thus be used, for example, for monitoring industrial production plants or refrigerator disposal plants in order to protect the environment from exposure to the harmful trichlorofluoromethane

Antioxidant and DPPH-Scavenging Activities of Compounds and Ethanolic Extract of the Leaf and Twigs of Caesalpinia bonduc L. Roxb.

Antioxidant effects of ethanolic extract of Caesalpinia bonduc and its isolated bioactive compounds were evaluated in vitro. The compounds included two new cassanediterpenes, 1α,7α-diacetoxy-5α,6β-dihydroxyl-cass-14(15)-epoxy-16,12-olide (1)and 12α-ethoxyl-1α,14β-diacetoxy-2α,5α-dihydroxyl cass-13(15)-en-16,12-olide(2); and others, bonducellin (3), 7,4’-dihydroxy-3,11-dehydrohomoisoflavanone (4), daucosterol (5), luteolin (6), quercetin-3-methyl ether (7) and kaempferol-3-O-α-L-rhamnopyranosyl-(1Ç2)-β-D-xylopyranoside (8). The antioxidant properties of the extract and compounds were assessed by the measurement of the total phenolic content, ascorbic acid content, total antioxidant capacity and 1-1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide radicals scavenging activities.Compounds 3, 6, 7 and ethanolic extract had DPPH scavenging activities with IC50 values of 186, 75, 17 and 102 μg/ml respectively when compared to vitamin C with 15 μg/ml. On the other hand, no significant results were obtained for hydrogen peroxide radical. In addition, compound 7 has the highest phenolic content of 0.81±0.01 mg/ml of gallic acid equivalent while compound 8 showed the highest total antioxidant capacity with 254.31±3.54 and 199.82±2.78 μg/ml gallic and ascorbic acid equivalent respectively. Compound 4 and ethanolic extract showed a high ascorbic acid content of 2.26±0.01 and 6.78±0.03 mg/ml respectively.The results obtained showed the antioxidant activity of the ethanolic extract of C. bonduc and deduced that this activity was mediated by its isolated bioactive compounds

Abstracts of 51st EASD Annual Meeting

Background and aims: Presence and frequency of beta cell (BC) dysfunction(BCD) and insulin resistance (IR) in patients with newly diagnosedtype 2 diabetes mellitus (NDT2D) are imperfectly known, becauseprevious studies used small cohorts and/or only surrogate indexes of BCfunction and IR.We sought to assess BC function and IR with state-of-artmethods in the VNDS.Materials and methods: In 712 GADA-negative, drug naïve, consecutiveItalian NDT2D patients we assessed: 1. standard parameters; 2. insulinsensitivity (IS) by the euglycaemic insulin clamp); 3. BC functionby state-of-art modeling of prolonged (5 hours) OGTT-derived glucose/C-peptide curves. Thresholds for BCD and IR were the 25th percentilesof BC function and IS assessed with the same methods of the VNDS inItalian subjects with normal glucose regulation of the GENFIEV (n=340)and GISIR (n=386) studies, respectively.Results: In the VNDS, 89.8% [95% C.I.: 87.6 - 92.0%] and87.8% [85.4 - 90.2] patients had BCD and IR, respectively. Patientswith only one defect were 19.7% [16.8 - 22.6]. IsolatedBCD and isolated IR were present in 10.9% [8.6 - 13.2] and8.9% [6.8 - 11.0] patients, respectively. Coexistence of BCDand IR was observed in 78.9% [75.9 - 81.9] of the patients.1.4% [0.5 - 2.3] of the patients had no detectable alterations inBC function and IS. Patients (19.7%) with only one metabolicdefect had lower BMI, fasting glucose, HbA1c, triglycerides andBC function, and higher HDL-cholesterol and IS than patientswith both BCD and IR (p<0.01 or less after Bonferroni’scorrection).Conclusion: In conclusion, in NDT2DM patients: 1. at least 75.9% haveboth BCD and IR; 2. At least 87.6% and 85.4% have BCD and IR,respectively; 3. At least 16.8% have only one defect and a significantlydifferent (milder) metabolic phenotype compared to patients with bothdefects. These findings may be relevant to therapeutic strategies centeredon the metabolic phenotype of the patient.Clinical Trial Registration Number: NCT00879801; NCT01526720Supported by: University of Veron

A Systematic Review and Meta-Analysis of the Incidence of Injury in Professional Female Soccer

The epidemiology of injury in male professional football is well documented and has been used as a basis to monitor injury trends and implement injury prevention strategies. There are no systematic reviews that have investigated injury incidence in women’s professional football. Therefore, the extent of injury burden in women’s professional football remains unknown. PURPOSE: The primary aim of this study was to calculate an overall incidence rate of injury in senior female professional soccer. The secondary aims were to provide an incidence rate for training and match play. METHODS: PubMed, Discover, EBSCO, Embase and ScienceDirect electronic databases were searched from inception to September 2018. Two reviewers independently assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology statement using a 22-item STROBE checklist. Seven prospective studies (n=1137 professional players) were combined in a pooled analysis of injury incidence using a mixed effects model. Heterogeneity was evaluated using the Cochrane Q statistic and I2. RESULTS: The epidemiological incidence proportion over one season was 0.62 (95% CI 0.59 - 0.64). Mean total incidence of injury was 3.15 (95% CI 1.54 - 4.75) injuries per 1000 hours. The mean incidence of injury during match play was 10.72 (95% CI 9.11 - 12.33) and during training was 2.21 (95% CI 0.96 - 3.45). Data analysis found a significant level of heterogeneity (total Incidence, X2 = 16.57 P < 0.05; I2 = 63.8%) and during subsequent sub group analyses in those studies reviewed (match incidence, X2 = 76.4 (d.f. = 7), P <0.05; I2 = 90.8%, training incidence, X2 = 16.97 (d.f. = 7), P < 0.05; I2 = 58.8%). Appraisal of the study methodologies revealed inconsistency in the use of injury terminology, data collection procedures and calculation of exposure by researchers. Such inconsistencies likely contribute to the large variance in the incidence and prevalence of injury reported. CONCLUSIONS: The estimated risk of sustaining at least one injury over one football season is 62%. Continued reporting of heterogeneous results in population samples limits meaningful comparison of studies. Standardising the criteria used to attribute injury and activity coupled with more accurate methods of calculating exposure will overcome such limitations