Inherently chiral calix[4]arenes with planar chirality: two new entries to the family

The synthesis of two new inherently chiral calix[4]arenes (ICCs, 1 and 2), endowed with electron-rich concave surfaces, has been achieved through the desymmetrization of a lower rim distal-bridged oxacyclophane (OCP) macrocycle. The new highly emissive ICCs were resolved by chiral HPLC, and the enantiomeric nature of the isolated antipodes proved by electronic circular dichroism (CD). Using time-dependent density functional calculations of CD spectra, their absolute configurations were established. NMR studies with (S)-Pirkle's alcohol unequivocally showed that the host-guest interactions occur in the chiral pocket comprehending the calix-OCP exo cavities and the carbazole moieties.

Biomimetic sensors of molecularly-imprinted polymers for chlorpromazine determination

A new man-tailored biomimetic sensor for Chlorpromazine host-guest interactions and potentiometric transduction is presented. The artificial host was imprinted within methacrylic acid, 2-vinyl pyridine and 2-acrylamido-2-methyl-1-propanesulfonic acid based polymers. Molecularly imprinted particles were dispersed in 2-nitrophenyloctyl ether and entrapped in a poly(vinyl chloride) matrix. Slopes and detection limits ranged 51–67 mV/decade and 0.46–3.9 μg/mL, respectively, in steady state conditions. Sensors were independent from the pH of test solutions within 2.0–5.5. Good selectivity was observed towards oxytetracycline, doxytetracycline, ciprofloxacin, enrofloxacin, nalidixic acid, sulfadiazine, trimethoprim, glycine, hydroxylamine, cysteine and creatinine. Analytical features in flowing media were evaluated on a double-channel manifold, with a carrier solution of 5.0 × 10−2 mol/L phosphate buffer. Near-Nernstian response was observed over the concentration range 1.0 × 10−4 to 1.0 × 10−2 mol/L. Average slopes were about 48 mV/decade. The sensors were successfully applied to field monitoring of CPZ in fish samples, offering the advantages of simplicity, accuracy, automation feasibility and applicability to complex samples.

Biomimetic norfloxacin sensors made of molecularly-imprinted materials for potentiometric transduction

A biomimetic sensor for norfloxacin is presented that is based on host-guest interactions and potentiometric transduction. The artificial host was imprinted into polymers made from methacrylic acid and/or 2-vinyl pyridine. The resulting particles were entrapped in a plasticized poly(vinyl chloride) (PVC) matrix. The sensors exhibit near-Nernstian response in steady state evaluations, and detection limits range from 0.40 to 1.0 μg mL−1, respectively, and are independent of pH values at between 2 and 6, and 8 and 11, respectively. Good selectivity was observed over several potential interferents. In flowing media, the sensors exhibit fast response, a sensitivity of 68.2 mV per decade, a linear range from 79 μM to 2.5 mM, a detection limit of 20 μg mL−1, and a stable baseline. The sensors were successfully applied to field monitoring of norfloxacin in fish samples, biological samples, and pharmaceutical products.

Development of novel ionic liquids based on biological molecules

Ionic Liquids (ILs) belong to a class of compounds with unusual properties: very low vapour pressure; high chemical and thermal stability and the ability to dissolve a wide range of substances. A new field in research is evaluating the possibility to use natural chiral biomolecules for the preparation of chiral ionic liquids (CILs). This important challenge in synthetic chemistry can open new avenues of research in order to avoid some problems related with the intrinsic biodegradability and toxicity associated to conventional ILs. The research work developed aimed for the synthesis of CILs, their characterization and possible applications, based on biological moieties used either as chiral cations or anions, depending on the synthetic manipulation of the derivatives. Overall, a total of 28 organic salts, including CILs were synthesized: 9 based on L-cysteine derivatives, 12 based on L-proline, 3 based on nucleosides and 4 based on nucleotides. All these new CILs were completely characterized and their chemical and physical properties were evaluated. Some CILs based on L-cysteine have been applied for discrimination processes, including resolution of racemates and as a chiral catalyst for asymmetric Aldol condensation. L-proline derived CILs were also studied as chiral catalysts for Michael reaction. In parallel, the interactions of macrocyclic oligosugars called cyclodextrins (CDs) with several ILs were studied. It was possible to improve the solubility of CDs in water and serum. Additionally, fatty acids and steroids showed an increase in water solubility when ILs-CDs systems were used. The development of efficient and selective ILs-CDs systems is indispensable to expand the range of their applications in host-guest interactions, drug delivery systems or catalytic reactions. Novel salts derived from nucleobases were used in order to enhance the fluorescence in aqueous solution. Additionally, preliminary studies regarding ethyl lactate as an alternative solvent for asymmetric organocatalysis were performed.

On lions, impala, and bigraphs: modelling interactions in Ubiquitous Computing

As ubiquitous systems have moved out of the lab and into the world the need to think more systematically about how there are realised has grown. This talk will present intradisciplinary work I have been engaged in with other computing colleagues on how we might develop more formal models and understanding of ubiquitous computing systems. The formal modelling of computing systems has proved valuable in areas as diverse as reliability, security and robustness. However, the emergence of ubiquitous computing raises new challenges for formal modelling due to their contextual nature and dependence on unreliable sensing systems. In this work we undertook an exploration of modelling an example ubiquitous system called the Savannah game using the approach of bigraphical rewriting systems. This required an unusual intra-disciplinary dialogue between formal computing and human- computer interaction researchers to model systematically four perspectives on Savannah: computational, physical, human and technical. Each perspective in turn drew upon a range of different modelling traditions. For example, the human perspective built upon previous work on proxemics, which uses physical distance as a means to understand interaction. In this talk I hope to show how our model explains observed inconsistencies in Savannah and ex- tend it to resolve these. I will then reflect on the need for intradisciplinary work of this form and the importance of the bigraph diagrammatic form to support this form of engagement. Speaker Biography Tom Rodden Tom Rodden (rodden.info) is a Professor of Interactive Computing at the University of Nottingham. His research brings together a range of human and technical disciplines, technologies and techniques to tackle the human, social, ethical and technical challenges involved in ubiquitous computing and the increasing used of personal data. He leads the Mixed Reality Laboratory (www.mrl.nott.ac.uk) an interdisciplinary research facility that is home of a team of over 40 researchers. He founded and currently co-directs the Horizon Digital Economy Research Institute (www.horizon.ac.uk), a university wide interdisciplinary research centre focusing on ethical use of our growing digital footprint. He has previously directed the EPSRC Equator IRC (www.equator.ac.uk) a national interdisciplinary research collaboration exploring the place of digital interaction in our everyday world. He is a fellow of the British Computer Society and the ACM and was elected to the ACM SIGCHI Academy in 2009 (http://www.sigchi.org/about/awards/).

Polyphenylendendrimere zur Gefahrstoffdetektion

Zusammenfassung: rnrn Die vorliegende Arbeit mit dem Thema „Polyphenylendendrimere zur Gefahrstoffdetektion“ ist hauptsächlich synthetisch orientiert und behandelt vor allem den Aufbau neuartiger innenfunktionalisierter Polyphenylendendrimer-Systeme durch die systematische Anwendung wiederholter Diels-Alder- bzw. Desilylierungs-Reaktionen. Diskutiert wird dabei die Synthese der dafür notwendigen Verzweigungsbausteine, die daraus hervorgehende Darstellung der verschiedenen Dendrimere sowie deren Charakterisierung. Als Referenz zu den monodispersen dendritischen Systemen werden parallel verschiedene hyperverzweigte Polymere mittels Diels-Alder-Reaktion bzw. Suzuki-Kupplung dargestellt und beide Makromolekül-Systeme im direkten Vergleich besprochen. Erstmals wird die Einbindung funktioneller Elemente, wie z.B. Triazol oder Pyren, synthetisch ermöglicht. Die dendritischen Systeme werden bis zur dritten Generation aufgebaut, im Fall des Ester-funktionalisierten Systems wird auch eine Darstellung der vierten Generation erreicht. Im Anschluss wird das supramolekulare Verhalten der erhaltenen dendritischen, wie auch polymeren Verbindungen mittels zweier unterschiedlicher Meßmethoden (QMB, ITC) gegenüber verschiedenen Lösungsmitteln und Gefahrstoffen untersucht. Dabei kann eine Diskrepanz im Einlagerungsverhalten der verschiedenen makromolekularen Strukturen gegenüber den verwendeten Gast-Molekülen beobachtet werden. Aufgrund der umfassenden systematischen Analyse aller getesteten Verbindungen wird ein tiefer greifendes Verständnis für die während des Einlagerungsprozesses verantwortlichen Wechselwirkungen aufgebaut. Dabei spielt die dreidimensionale Anordnung des dendritischen Gerüsts, resultierend aus der Polarität und dem sterischen Anspruch der eingebundenen funktionellen Gruppen eine entscheidende Rolle. Als Anwendungsbeispiel der dendritischen Strukturen wird die Verwendung eigens beschichteter Schwingquarze zur Detektion von Sprengstoffen, wie z. B. TATP, erläutert und eine daraus resultierende Steigerung der Sensibilität der Detektoren erklärt.rn

EPR spectroscopy as a tool for the elucidation of non-covalent structuring principles in complex soft matter

This thesis aims at connecting structural and functional changes of complex soft matter systems due to external stimuli with non-covalent molecular interaction profiles. It addresses the problem of elucidating non-covalent forces as structuring principle of mainly polymer-based systems in solution. The structuring principles of a wide variety of complex soft matter types are analyzed. In many cases this is done by exploring conformational changes upon the exertion of external stimuli. The central question throughout this thesis is how a certain non-covalent interaction profile leads to solution condition-dependent structuring of a polymeric system.rnTo answer this question, electron paramagnetic resonance (EPR) spectroscopy is chosen as the main experimental method for the investigation of the structure principles of polymers. With EPR one detects only the local surroundings or environments of molecules that carry an unpaired electron. Non-covalent forces are normally effective on length scales of a few nanometers and below. Thus, EPR is excellently suited for their investigations. It allows for detection of interactions on length scales ranging from approx. 0.1 nm up to 10 nm. However, restriction to only one experimental technique likely leads to only incomplete pictures of complex systems. Therefore, the presented studies are frequently augmented with further experimental and computational methods in order to yield more comprehensive descriptions of the systems chosen for investigation.rnElectrostatic correlation effects in non-covalent interaction profiles as structuring principles in colloid-like ionic clusters and DNA condensation are investigated first. Building on this it is shown how electrostatic structuring principles can be combined with hydrophobic ones, at the example of host-guest interactions in so-called dendronized polymers (denpols).rnSubsequently, the focus is shifted from electrostatics in dendronized polymers to thermoresponsive alkylene oxide-based materials, whose structuring principles are based on hydrogen bonds and counteracting hydrophobic interactions. The collapse mechanism in dependence of hydrophilic-hydrophobic balance and topology of these polymers is elucidated. Complementarily the temperature-dependent phase behavior of elastin-like polypeptides (ELPs) is investigated. ELPs are the first (and so far only) class of compounds that is shown to feature a first-order inverse phase transition on nanoscopic length scales.rnFinally, this thesis addresses complex biological systems, namely intrinsically disordered proteins (IDPs). It is shown that the conformational space of the IDPs Osteopontin (OPN), a cytokine involved in metastasis of several kinds of cancer, and BASP1 (brain acid soluble protein one), a protein associated with neurite outgrowth, is governed by a subtle interplay between electrostatic forces, hydrophobic interaction, system entropy and hydrogen bonds. Such, IDPs can even sample cooperatively folded structures, which have so far only been associated with globular proteins.

Chemical modification of smectite clays

Today, speciality use organoclays are being developed for an increasingly large number of specific applications. Many of these, including use in cosmetics, polishes, greases and paints, require that the material be free from abrasive impurities so that the product retains a smooth `feel'. The traditional `wet' method preparation of organoclays inherently removes abrasives naturally present in the parent mineral clay, but it is time-consuming and expensive. The primary objective of this thesis was to explore the alternative `dry' method (which is both quicker and cheaper but which provides no refining of the parent clay) as a process, and to examine the nature of the organoclays produced, for the production of a wide range of commercially usable organophilic clays in a facile way. Natural Wyoming bentonite contains two quite different types of silicate surface (that of the clay mineral montmorillonite and that of a quartz impurity) that may interact with the cationic surfactant added in the `dry' process production of organoclays. However, it is oil shale, and not the quartz, that is chiefly responsible for the abrasive nature of the material, although air refinement in combination with the controlled milling of the bentonite as a pretreatment may offer a route to its removal. Ion exchange of Wyoming bentonite with a long chain quaternary ammonium salt using the `dry' process affords a partially exchanged, 69-78%, organoclay, with a monolayer formation of ammonium ions in the interlayer. Excess ion pairs are sorbed on the silicate surfaces of both the clay mineral and the quartz impurity phases. Such surface sorption is enhanced by the presence of very finely divided, super paramagnetic, Fe2O3 or Fe(O)(OH) contaminating the surfaces of the major mineral components. The sorbed material is labile to washing, and induces a measurable shielding of the 29Si nuclei in both clay and quartz phases in the MAS NMR experiment, due to an anisotropic magnetic susceptibility effect. XRD data for humidified samples reveal the interlamellar regions to be strongly hydrophobic, with the by-product sodium chloride being expelled to the external surfaces. Many organic cations will exchange onto a clay. The tetracationic cyclophane, and multipurpose receptor, cyclobis(paraquat-p-phenylene) undergoes ion exchange onto Wyoming bentonite to form a pillared clay with a very regular gallery height. The major plane of the cyclophane is normal to the silicate surfaces, thus allowing the cavity to remain available for complexation. A series of group VI substituted o-dimethoxybenzenes were introduced, and shown to participate in host/guest interactions with the cyclophane. Evidence is given which suggests that the binding of the host structure to a clay substrate offers advantages, not only of transportability and usability but of stability, to the charge-transfer complex which may prove useful in a variety of commercial applications. The fundamental relationship between particle size, cation exchange capacity and chemical composition of clays was also examined. For Wyoming bentonite the extent of isomorphous substitution increases with decreasing particle size, causing the CEC to similarly increase, although the isomorphous substitution site: edge site ratio remains invarient throughout the particle size range studied.

Concentration dependence of sodium permeation and sodium ion interactions in the cyclic AMP-gated channels of mammalian olfactory receptor neurons

The dependence of currents through the cyclic nucleotide-gated (CNG) channels of mammalian olfactory receptor neurons (ORNs) on the concentration of NaCl was studied in excised inside-out patches from their dendritic knobs using the patch-clamp technique. With a saturating concentration (100 mu M) of adenosine 3', 5'-cyclic monophosphate (cAMP), the changes in the reversal potential of macroscopic currents were studied at NaCl concentrations from 25 to 300 mM. In symmetrical NaCl solutions without the addition of divalent cations, the current-voltage relations were almost linear, reversing close to O mV. When the external NaCl concentration was maintained at 150 mM and the internal concentrations were varied, the reversal potentials of the cAMP-activated currents closely followed the Na+ equilibrium potential indicating that P-Cl/P-Na approximate to 0. However, at low external NaCl concentrations (less than or equal to 100 mM) there was some significant chloride permeability. Our results further indicated that Na+ currents through these channels: (i) did not obey the independence principle; (ii) showed saturation kinetics with K(m)s in the range of 100-150 mM and (iii) displayed a lack of voltage dependence of conductance in asymmetric solutions that suggested that ion-binding sites were situated midway along the channel. Together, these characteristics indicate that the permeation properties of the olfactory CNG channels are significantly different from those of photoreceptor CNG channels.

Effects of oxide promoters on metal dispersion and metal-support interactions in Ni catalysts supported on activated carbon

Various oxide-promoted Ni catalysts supported on activated carbon were prepared, and the effect of promoters on the surface structure and properties of Ni catalysts was studied. Physical adsorption (Na adsorption), thermogravimetric analysis (TGA), temperature-programmed desorption (TPD), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were used to characterize the catalysts. It is found that nickel is fairly uniformly distributed in the pores of the carbon support. Addition of promoters produces a more homogeneous distribution of nickel ion in carbon. However, distributions of promoters in the pores are varying. Addition of promoters increases the dispersion of nickel in carbon. Promoters also change the interaction between the carbon and Ni, resulting in significantly different behaviors of catalysts under various environments. CaO and MgO promoters improve the reactivity of nickel catalysts with O-2 but retard the interaction between nickel oxide and carbon. La2O3 shows some inhibiting effect on the interactions between nickel oxide and oxygen as well as carbon.

Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study

Risk factors for melanoma include environmental (particularly ultraviolet exposure) and genetic factors. In rare families, susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK4, with more common, less penetrant genes also postulated. A further, potent risk factor for melanoma is the presence of large numbers of melanocytic nevi so that genes controlling nevus phenotype could be such melanoma susceptibility genes. A large Australian study involving twins aged 12 y of predominantly U.K. ancestry showed strong evidence for genetic influence on nevus number and density. We carried out essentially the same study in the U.K. to gain insight into gene-environment interactions for nevi. One hundred and three monozygous (MZ) and 118 dizygous (DZ) twin pairs aged 10-18 y were examined in Yorkshire and Surrey, U.K. Nevus counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p = 0.009) and higher in Australia (110.4) than in the U.K. (79.2, adjusted to age 12 y, p < 0.0001), and nevus densities were higher on sun-exposed sites (92 per m(2)) than sun-protected sites (58 per m(2)) (p < 0.0001). Correlations in sex and age adjusted nevus density were higher in MZ pairs (0.94, 95% CI 0.92-0.96) than in DZ pairs (0.61, 95%CI 0.49-0.72), were notably similar to those of the Australian study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability (65% in the U.K., 68% in Australia). We conclude that emergence of nevi in adolescents is under strong genetic control, whereas environmental exposures affect the mean number of nevi.

Monetary and fiscal policies interactions in a monetary union with country-size asymmetry

Within a country-size asymmetric monetary union, idiosyncratic shocks and national fiscal stabilization policies cause asymmetric cross-border effects. These effects are a source of strategic interactions between noncoordinated fiscal and monetary policies: on the one hand, due to larger externalities imposed on the union, large countries face less incentives to develop free-riding fiscal policies; on the other hand, a larger strategic position vis-à-vis the central bank incentives the use of fiscal policy to, deliberately, influence monetary policy. Additionally, the existence of non-distortionary government financing may also shape policy interactions. As a result, optimal policy regimes may diverge not only across the union members, but also between the latter and the monetary union. In a two-country micro-founded New-Keynesian model for a monetary union, we consider two fiscal policy scenarios: (i) lump-sum taxes are raised to fully finance the government budget and (ii) lump-sum taxes do not ensure balanced budgets in each period; therefore, fiscal and monetary policies are expected to impinge on debt sustainability. For several degrees of country-size asymmetry, we compute optimal discretionary and dynamic non-cooperative policy games and compare their stabilization performance using a union-wide welfare measure. We also assess whether these outcomes could be improved, for the monetary union, through institutional policy arrangements. We find that, in the presence of government indebtedness, monetary policy optimally deviates from macroeconomic to debt stabilization. We also find that policy cooperation is always welfare increasing for the monetary union as a whole; however, indebted large countries may strongly oppose to this arrangement in favour of fiscal leadership. In this case, delegation of monetary policy to a conservative central bank proves to be fruitful to improve the union’s welfare.

Protease-activated receptor 2 and [alpha]-crystallin : interactions and functional implications

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2010