Sensitivity enhancement in NMR by using parahydrogen induced polarization

Enhancing the sensitivity of nuclear magnetic resonance measurements via hyperpolarization techniques like parahydrogen induced polarization (PHIP) is of high interest for spectroscopic investigations. Parahydrogen induced polarization is a chemical method, which makes use of the correlation between nuclear spins in parahydrogen to create hyperpolarized molecules. The key feature of this technique is the pairwise and simultaneous transfer of the two hydrogen atoms of parahydrogen to a double or triple bond resulting in a population of the Zeeman energy levels different from the Boltzmann equation. The obtained hyperpolarization results in antiphase peaks in the NMR spectrum with high intensities. Due to these strong NMR signals, this method finds arnlot of applications in chemistry e.g. the characterization of short-lived reaction intermediates. Also in medicine it opens up the possibility to boost the sensitivity of medical diagnostics via magnetic labeling of active contrast agents. Thus, further examination and optimization of the PHIP technique is of significant importance in order to achieve the highest possible sensitivity gain.rnrnIn this work, different aspects concerning PHIP were studied with respect to its chemical and spectroscopic background. The first part of this work mainly focused on optimizing the PHIP technique by investigating different catalyst systems and developing new setups for the parahydrogenation. Further examinations facilitated the transfer of the generated polarization from the protons to heteronuclei like 13C. The second part of this thesis examined the possibility to transfer these results to different biologically active compounds to enable their later application in medical diagnostics. Onerngroup of interesting substances is represented by metabolites or neurotransmitters in mammalian cells. Other interesting substances are clinically relevant drugs like a barbituric acid derivative or antidepressant drugs like citalopram which were investigated with regard to their applicability for the PHIP technique and the possibility to achievernpolarization transfer to 13C nuclei. The last investigated substrate is a polymerizable monomer whose polymer was used as a blood plasma expander for trauma victims after the first half of the 20th century. In this case, the utility of the monomer for the PHIP technique as a basis for later investigations of a polymerization reaction using hyperpolarized monomers was examined.rnrnHence, this thesis covers the optimization of the PHIP technology, hereby combining different fields of research like chemical and spectroscopical aspects, and transfers the results to applications of real biologally acitve compounds.

Alpha, Omega end group functionalization of RAFT polymers based on pentafluorophenyl esters and methane thiosulfonates

While polymers with different functional groups along the backbone have intensively been investigated, there is still a challenge in orthogonal functionalization of the end groups. Such well-defined systems are interesting for the preparation of multiblock (co) polymers or polymer networks, for bio-conjugation or as model systems for examining the end group separation of isolated polymer chains. rnHere, Reversible Addition Fragmentation Chain Transfer (RAFT) polymerization was employed as method to investigate improved techniques for an a, w end group functionalization. RAFT produces polymers terminated in an R group and a dithioester-Z group, where R and Z stem from a suitable chain transfer agent (CTA). rnFor alpha end group functionalization, a CTA with an activated pentafluorophenyl (PFP) ester R group was designed and used for the polymerization of various methacrylate monomers, N-isopropylacrylamide and styrene yielding polymers with a PFP ester as a end group. This allowed the introduction of inert propyl amides, of light responsive diazo compounds, of the dyes NBD, Texas Red, or Oregon Green, of the hormone thyroxin and allowed the formation of multiblocks or peptide conjugates. rnFor w end group functionalization, problems of other techniques were overcome through an aminolysis of the dithioester in the presence of a functional methane thiosulfonate (MTS), yielding functional disulfides. These disulfides were stable under ambient conditions and could be cleaved on demand. Using MTS chemistry, terminal methyl disulfides (enabling self-assembly on planar gold surfaces and ligand substitution on gold and semiconductor nanoparticles), butynyl disulfide end groups (allowing the “clicking” of the polymers onto azide functionalized surfaces and the selective removal through reduction), the bio-target biotin, and the fluorescent dye Texas Red were introduced into polymers. rnThe alpha PFP amidation could be performed under mild conditions, without substantial loss of DTE. This way, a step-wise synthesis produced polymers with two functional end groups in very high yields. rnAs examples, polymers with an anchor group for both gold nanoparticles (AuNP) and CdSe / ZnS semi-conductor nanoparticles (QD) and with a fluorescent dye end group were synthesized. They allowed a NP decoration and enabled an energy transfer from QD to dye or from dye to AuNP. Water-soluble polymers were prepared with two different bio-target end groups, each capable of selectively recognizing and binding a certain protein. The immobilization of protein-polymer-protein layers on planar gold surfaces was monitored by surface plasmon resonance.Introducing two different fluorescent dye end groups enabled an energy transfer between the end groups of isolated polymer chains and created the possibility to monitor the behavior of single polymer chains during a chain collapse. rnThe versatility of the synthetic technique is very promising for applications beyond this work.

Rheology of arrested colloids : a parameter study using novel experimental methods

The steadily increasing diversity of colloidal systems demands for new theoretical approaches and a cautious experimental characterization. Here we present a combined rheological and microscopical study of colloids in their arrested state whereas we did not aim for a generalized treatise but rather focused on a few model colloids, liquid crystal based colloidal suspensions and sedimented colloidal films. We laid special emphasis on the understanding of the mutual influence of dominant interaction mechanisms, structural characteristics and the particle properties on the mechanical behavior of the colloid. The application of novel combinations of experimental techniques played an important role in these studies. Beside of piezo-rheometry we employed nanoindentation experiments and associated standardized analysis procedures. These rheometric methods were complemented by real space images using confocal microscopy. The flexibility of the home-made setup allowed for a combination of both techniques and thereby for a simultaneous rheological and three-dimensional structural analysis on a single particle level. Though, the limits of confocal microscopy are not reached by now. We show how hollow and optically anisotropic particles can be utilized to quantify contact forces and rotational motions for individual particles. In future such data can contribute to a better understanding of particle reorganization processes, such as the liquidation of colloidal gels and glasses under shear.

Untersuchungen von Aerosolpartikeln und Wolkenresidualpartikeln mittels Einzelpartikel-Massenspektrometrie und optischen Methoden

Atmosphärische Partikel beeinflussen das Klima durch Prozesse wie Streuung, Reflexion und Absorption. Zusätzlich fungiert ein Teil der Aerosolpartikel als Wolkenkondensationskeime (CCN), die sich auf die optischen Eigenschaften sowie die Rückstreukraft der Wolken und folglich den Strahlungshaushalt auswirken. Ob ein Aerosolpartikel Eigenschaften eines Wolkenkondensationskeims aufweist, ist vor allem von der Partikelgröße sowie der chemischen Zusammensetzung abhängig. Daher wurde die Methode der Einzelpartikel-Laserablations-Massenspektrometrie angewandt, die eine größenaufgelöste chemische Analyse von Einzelpartikeln erlaubt und zum Verständnis der ablaufenden multiphasenchemischen Prozesse innerhalb der Wolke beitragen soll.rnIm Rahmen dieser Arbeit wurde zur Charakterisierung von atmosphärischem Aerosol sowie von Wolkenresidualpartikel das Einzelpartikel-Massenspektrometer ALABAMA (Aircraft-based Laser Ablation Aerosol Mass Spectrometer) verwendet. Zusätzlich wurde zur Analyse der Partikelgröße sowie der Anzahlkonzentration ein optischer Partikelzähler betrieben. rnZur Bestimmung einer geeigneten Auswertemethode, die die Einzelpartikelmassenspektren automatisch in Gruppen ähnlich aussehender Spektren sortieren soll, wurden die beiden Algorithmen k-means und fuzzy c-means auf ihrer Richtigkeit überprüft. Es stellte sich heraus, dass beide Algorithmen keine fehlerfreien Ergebnisse lieferten, was u.a. von den Startbedingungen abhängig ist. Der fuzzy c-means lieferte jedoch zuverlässigere Ergebnisse. Darüber hinaus wurden die Massenspektren anhand auftretender charakteristischer chemischer Merkmale (Nitrat, Sulfat, Metalle) analysiert.rnIm Herbst 2010 fand die Feldkampagne HCCT (Hill Cap Cloud Thuringia) im Thüringer Wald statt, bei der die Veränderung von Aerosolpartikeln beim Passieren einer orographischen Wolke sowie ablaufende Prozesse innerhalb der Wolke untersucht wurden. Ein Vergleich der chemischen Zusammensetzung von Hintergrundaerosol und Wolkenresidualpartikeln zeigte, dass die relativen Anteile von Massenspektren der Partikeltypen Ruß und Amine für Wolkenresidualpartikel erhöht waren. Dies lässt sich durch eine gute CCN-Aktivität der intern gemischten Rußpartikel mit Nitrat und Sulfat bzw. auf einen begünstigten Übergang der Aminverbindungen aus der Gas- in die Partikelphase bei hohen relativen Luftfeuchten und tiefen Temperaturen erklären. Darüber hinaus stellte sich heraus, dass bereits mehr als 99% der Partikel des Hintergrundaerosols intern mit Nitrat und/oder Sulfat gemischt waren. Eine detaillierte Analyse des Mischungszustands der Aerosolpartikel zeigte, dass sich sowohl der Nitratgehalt als auch der Sulfatgehalt der Partikel beim Passieren der Wolke erhöhte. rn