Synthesis and investigation of boron phases at high pressures and temperatures
- Boron, discovered as an element in 1808 and produced in pure form in 1909, still remains one of the most complicated light elements full of surprises. Even the number of pure boron polymorphs is a subject of intensive discussions. It is proven the existence of α-, β- and γ-boron phases. Structural details of the most common boron phase (β-B) are still not fully revealed. For decades boron remained the last stable element in the periodic table, whose ground state was not determined. It has been a subject of a longstanding controversy, whether α-B or β-B is the thermodynamically stable phase at ambient pressure and temperature.
The existence of the α-tetragonal boron phase T-50 has been an open question since its first discovery. It was not clear if T-50 could be synthesized as a pure boron phase or its structure must be stabilized by the presence of carbon or nitrogen. Theorists claimed that T-50 could not exist at all because of its unstable electronic configuration.
We have developed a method of synthesis of single crystals of α-boron. They were crystallized from a boron-platinum melt at high pressures (6-11 GPa) and high temperatures (1450-1875 K). An average size of the as-grown isometric crystals was 60 μm to 80 μm in maximum dimension. The crystal structure is in good agreement with the literature data. Detailed investigation of single crystals of α-boron using Raman spectroscopy was performed under elevated pressures and temperatures. The behaviour of the Raman modes under pressure was studied both theoretically and experimentally. Single crystals of β-boron were grown at temperatures above 1550 K and pressures up to 11 GPa using the similar methodology like that worked out for synthesis of α-boron.
In a series of experiments above 8 GPa we synthesized single crystals of tetragonal δ-boron (also known in literature as α-tetragonal boron or T-50) and refined the crystal structure of this phase based on synchrotron X-ray diffraction data. The purity of δ-boron was confirmed by means of the microprobe analysis and the electron energy loss spectroscopy (EELS).
A new, so far unknown boron phase, ε-boron, was synthesized at pressures of 8-10 GPa and temperatures between 2000-2250 K. The microprobe analysis and EELS revealed that the samples were not contaminated. The crystal structure of the new phase was determined by means of single crystal X-ray diffraction. ε-boron crystallizes in a R-3m space group with the unit cell parameters a = 5.5940(7) Å and c = 12.0756(16) Å (in hexagonal setting). The unit cell contains 15 boron atoms. The structure can be presented by the network of B12 icosahedra with a group of three boron atoms in the inter-icosahedra space. This phase is isostructural to boron carbide B13C2 (if carbon atoms are substituted by boron ones). Measured hardness is ~60 GPa which places ε-boron in the family of superhard materials.
We have demonstrated that δ-boron and ε-boron are metastable polymorphs because (a) they were found only together with other stable boron phases (α-, β-, or γ-B), and (b) upon heating at high pressure, both δ-B and ε-B transform to β- or γ-B, if the PT conditions correspond to the fields of stability of the latter.
Summarising, in the course of the present work the high-pressure high-temperature synthesis of the five boron polymorphs was established as a reproducible, verifiable and well-documented process. Following the synthesis prescription one can grow single crystals of α-B, β-B, γ-B, δ-B, and ε-B phases. Based on results of numerous HPHT experiments, the phase boundaries between the stable boron phases (α-B, β-B, γ-B) were found. Thus, our serial exploration of the pressure-temperature field using the large volume press synthesis technique resulted in establishing the phase diagram of boron (showing also the PT fields of the appearance of its two metastable phases, δ-B and ε-B) in the pressure interval of 3 GPa to 18 GPa at temperatures between 1073 K and 2423 K. Based on our experimental data and linear extrapolation of the α/β phase boundary down to ambient pressure we could resolve a longstanding controversy on the ground state of boron in favour of the α-B phase.
Coarse-grained Modeling of Protein Dynamics using Elastic Network Models
- Dynamics is crucial for the functioning of biological macromolecules. Because of severe limitations in studying protein dynamics experimentally or with all-atom simulations, coarse-grained methods, especially elastic network models (ENMs), are frequently employed. In the last years, studies on various proteins showed that ENMs reliably reproduce experimental data, despite the simplified protein representation and the purely harmonic potential function. This work on two proteins with very different dynamical properties highlights the remarkable success of ENMs and shows which kind of questions can be answered using coarse-grained methods.
The allosteric enzyme aminoglycoside phosphotransferase(3')-IIIa (APH), which confers resistance against a broad range of aminoglycoside antibiotics to pathogenic bacteria, drastically changes its flexibility upon binding of substrates, but without changing its average conformation. In contrast, the homotrimeric vesicular stomatitis virus glycoprotein G (VSV-G), which triggers the pH-dependent fusion of viral and host membrane, undergoes a large structural rearrangement. A striking difference between the two proteins is their shape. VSV-G contains weakly constrained protein segments, the fusion loops, which can undergo large-scale motions at low energetic cost, whereas APH is not obviously arranged into different protein segments. Nevertheless, ENM calculations show that also APH consists of independently moving segments with correlated internal motion, so-called dynamic domains. The concept of dynamic domains can explain the differential effects of ligand binding on the dynamics of APH.
The first chapter of this thesis describes how experimental evidence for the importance of dynamics successively replaced the former idea of static proteins, and explains the dynamic basis of ligand binding, allostery and conformational changes. In the second chapter, theoretical methods for the analysis of protein dynamics are introduced, with emphasis on the ENM-based methods used in my studies. The studies are summarized in the third chapter. In the study on APH, I employ the Gaussian network model to analyze the ligand-dependent dynamics, the broad substrate specificity and the perturbation-sensitivity of the ligand binding sites. In a second study, ENM-based as well as all-atom molecular dynamics simulations are used to analyze the conformational change of VSV-G. Both approaches detect the fusion loops of VSV-G as most flexible parts of the protein, and thus as most likely starting point for the structural rearrangement, but only the all-atom model can generate deviations from the average structure at low pH. The last study describes the implementation and application of a dynamic domain assignment method, called CovarDom, which is based on covariances of residue fluctuations. Calculation of dynamic domains for a large protein set demonstrates the general applicability of CovarDom.
Endokrine Signale in der Kastendetermination der ursprünglichen Termite Mastotermes darwiniensis Froggatt (Isoptera: Mastotermitidae)
- Als „ecosystem engineers“ sind Termiten in subtropischen und tropischen Ökosystemen von wichtiger ökologischer Bedeutung. Gleichzeitig gelten einige Termitenarten als Bauholz- und Agrarschädlinge, die weltweit vorkommen und enorme Schäden anrichten können. Für die Entwicklung effizienter und umweltschonender Insektizide gegen Termiten dient besonders deren Kastendifferenzierung als Ansatzpunkt. Die Mechanismen der Kastendifferenzierung sind noch nicht vollständig aufgeklärt, das Juvenilhormon (JH) soll aber eine entscheidende Rolle spielen. Daher sollte in dieser Studie der Einfluss des Juvenilhormons auf die Kastendifferenzierung bei der basalen Termite Mastotermes darwiniensis untersucht werden. Die Regulation der JH-Biosynthese erfolgt über allatoregulierende Neuropeptide, von denen Allatostatin A (AST-A) das am weitesten verbreitete ist. Die Expression des AST-A Gens bei M. darwiniensis wurde daher ebenfalls analysiert.
Zunächst musste die Sequenz des AST-A Gens von M. darwiniensis und die Organisation des AST-A Prohormonvorläufers identifiziert werden. Das AST-A Gen kodiert einen Prohormonvorläufer mit 14 potentiellen Peptiden, die durch vier saure Spacerregionen zu Clustern zusammengefasst werden. Dabei weisen nicht alle Peptide die charakteristische C-terminale Sequenz Y/FXFGL/I/V-amid der AST-A Peptide auf. Trotzdem zeigt der AST-A Prohormonvorläufer von M. darwiniensis eine starke Ähnlichkeit zu dem ebenfalls in dieser Studie identifizierten AST-A Prohormonvorläufer der nahe verwandten Schabenart Cryptocercus darwini sowie zu den bekannten AST-A Prohormonvorläufern anderer Schaben und einer weiteren Termitenart. Die phylogenetische Analyse der Prohormonvorläufer und des AST-A Gens bestätigte die enge Verwandtschaft der Schaben und Termiten. Durch die zentrale Einordnung der Termiten innerhalb der Schaben konnte zudem die noch umstrittene Paraphylie der Blattaria bestätigt werden. Die Stammbäume, die aus AST-A Sequenzen von acht verschiedenen Insektenordnungen berechnet wurden, zeigten generell eine Übereinstimmung mit der anerkannten Phylogenie der Insekten. Eine unterschiedliche Topologie und teilweise geringe Bootstrap-Werte sprechen allerdings gegen die Eignung von AST-A für phylogenetische Analysen.
Das AST-A Gen wird bei M. darwiniensis überwiegend im Gehirn exprimiert. Eine geringere Expression konnte auch in verschiedenen Teilen des Darms nachgewiesen werden, wobei der Mitteldarm höhere Expressionsraten aufwies als der Vorder- und Hinterdarm. In den verschiedenen Entwicklungsstadien von M. darwiniensis zeigten sich ebenfalls Unterschiede bei der AST-A Expression, generell wiesen „adulte“ Stadien eine höhere Expression auf als juvenile Stadien.
Die Messung des Gehaltes von JH III und Ecdysteroiden bei den verschiedenen Entwicklungsstadien von M. darwiniensis erfolgte mittels HPLC-MS. Ein hoher JH III-Gehalt wurde bei Larven nachgewiesen, dieser lag über dem JH III-Gehalt der Nymphen derselben Altersgruppe. Der hohe JH III-Gehalt der mittleren Larven deutet auf die potentielle Entwicklung dieser Tiere zu Soldaten. Während der Entwicklung von Geschlechtstieren konnte nur ein geringer JH III-Gehalt gemessen werden. Dies galt sowohl für die Entwicklung von primären Geschlechtstieren aus Nymphen als auch für die Entwicklung sekundärer Geschlechtstiere aus Arbeitern. Der hohe JH III-Gehalt während der Soldatenentwicklung ebenso wie der niedrige JH III-Gehalt während der Geschlechtstierbildung stimmt mit dem Modell von Nijhout & Wheeler (1982) zum Einfluss von JH auf die Kastendifferenzierung bei Termiten überein. Dieses bezieht sich allerdings auf Termiten mit linearem Entwicklungsweg, während bei Termiten mit zweiästigem Entwicklungsweg – wie M. darwiniensis – bisher nur wenig zur Rolle von JH auf die Kastendifferenzierung bekannt war.
Es konnte ein signifikanter Zusammenhang zwischen dem JH III-Hämolymphtiter und der Expression des AST-A Gens im Gehirn bei M. darwiniensis nachgewiesen werden. Beide Parameter waren negativ miteinander korreliert, d. h. Entwicklungsstadien mit hohem JH III-Titer zeigten überwiegend geringe AST-A Expression und umgekehrt.
Zur weiterführenden Funktionsanalyse des AST-A Gens wurde zudem versucht, die Expression des AST-A Gens in Arbeitern von M. darwiniensis mittels RNA-Interferenz zu unterdrücken. Durch Injektion von doppelsträngiger RNA (dsRNA) abgeleitet vom AST-A Gen konnte die Expression um bis zu 92% reduziert werden. Die Reduktion war dabei in den verschiedenen Geweben unterschiedlich stark ausgeprägt. Es konnte keine vollständige Suppression der AST-A Expression erreicht werden. Drei Tage nach der Injektion von AST-A dsRNA konnte keine Auswirkung auf den JH III-Titer in der Hämolymphe der Tiere beobachtet werden.
Dynamic charge densities of amino acids and proteins
Prathapa Siriyara Jagannatha
- This PhD thesis deals with the notion of dynamic electron density and describes the effect of temperature on the electron density distribution by analyzing both static and dynamic densities of crystals. The dynamic electron densities have been successfully computed by inverse Fourier transform of accurately computed structure factors from the structure model by employing the method of fast Fourier transform (FFT). Static and dynamic electron densities corresponding to independent atom models (IAM), structure models based on high-order refinement of the IAM (IAM-HO), invariom (INV) models and multipole (MP) models have been constructed for several molecular crystals. Based on all four structure models, the static and dynamic electron densities have been calculated and compared using the low-temperature (T ≈ 20 K) high-resolution data sets of α-glycine, D,L-serine, L-alanine and L-alanyl-L-tyrosyl-L-alanine (Ala-Tyr-Ala) as well as the protein Crambin (T = 100 K). By using a multi-temperature data set of D,L-serine, the effect of temperature on electron densities have been analyzed. Density values near atomic maxima are found to be much smaller in dynamic than in static electron densities due to the thermal smearing in dynamic densities. The electron densities at bond critical points (BCPs) of covalent bonds obtained from dynamic electron densities possess slightly smaller values in comparison to the static densities. However, rather larger differences have been observed for Laplacians. The discrepancy increases with increasing polarity of the bond and with increasing temperature. Nevertheless, at temperatures below 100 K, topological properties at BCPs of dynamic electron densities provide at least a semi-quantitative estimate of the topological properties of static electron densities. In contrast to covalent bonds, electron densities at BCPs of hydrogen bonds possess slightly larger values in dynamic electron densities compared to static densities.
In case of the protein Crambin, it has been found that the ADPs of Crambin at 100 K are larger or equal to ADPs of D, L-serine at 298 K. In corresponding dynamic densities, bonding features have been found to be attenuated due to the masking effects of large ADPs. As a result, the topological properties obtained from dynamic densities of Crambin at 100 K appear to be similar with the topological properties of small molecules at room temperature.
Calculations using the maximum entropy method (MEM) have been undertaken with all four types of dynamic model densities, mentioned above, as prior densities. Electron density analysis by the MEM has been performed for all small molecules studied in this thesis. It is shown that MEM density maps show a tendency to converge to a density map that is independent of choice of prior. Apart from the MP model as prior, it has been found that a good characterization of chemical bonds, at least in organic molecules, can be obtained by the MEM using the IAM-HO or the INV dynamic model densities as prior, while the IAM dynamic model density as prior leads to slightly inferior MEM densities. It will become especially important for the intended application to large systems (for example proteins) where the free refinement of MP model is not possible.
Functional Triblock Terpolymers for Multicompartment Micelle and Janus Particle Synthesis
- This thesis describes the synthesis of ABC triblock terpolymers with functional moieties via living anionic polymerization, followed by Janus particle (JP) and multicompartment micelle (MCM) synthesis from the as prepared triblock terpolymers.
A synthesis method that can accomplish the tasks of the preparation of spherical as well as non-spherical JPs that are well-defined and in the nanometer size range is based on converting self-assembled triblock terpolymer bulk structures via selective cross-linking of the middle block. Until now such soft JPs were prepared mainly from polystyrene-block-polybutadiene-block-poly(methyl methacrylate) and polystyrene-block-polybutadiene-block-poly(tert-butyl methacrylate). However, these polymers do not offer many possibilities of chemical alterations and stimuli-responsive elements.
Therefore, potential new functional monomers for the use in JP synthesis from triblock terpolymer bulk structures were identified and their anionic polymerization examined, p-tert-butoxystyrene (tS) and 4-(dimethylaminomethyl)styrene (DMAMS). Polymers with low polydispersity indices could be prepared from both monomers in tetrahydrofuran (THF) with sec-butyllithium (sec-BuLi) as initiator.
Poly(p-tert-butoxystyrene) (PtS) was hydrolyzed to poly(p-hydroxystyrene) (PHS) which is water-soluble at high pH values, opening the possibility to prepare water-soluble JPs. The pH-responsive behavior of poly(4-(dimethylaminomethyl)styrene) could be confirmed and for the first time an LCST behavior was documented with cloudpoints of 59.3 °C at pH 7 and 28.5 °C at pH 8.
PtS was then used in the preparation of two triblock terpolymers, poly(tert-butoxystyrene)-block-polybutadiene-block-poly(tert-butyl methacrylate) (tSBT) and poly(tert-butoxystyrene)-block-polybutadiene-block-poly(2-(dimethylamino)ethyl methacrylate) (tSBD). tSBT exhibited a lamella-cylinder (lc) bulk morphology with polybutadiene (PB) spheres surrounded by alternating lamellae of PtS and poly(tert-butyl methacrylate) (PtBMA). However, the bulk structure of tSBD consisted of a symmetrical lamella-lamella pattern that is not suitable for JP synthesis.
From tSBT bulk material, three different types of non-spherical JPs could be obtained. Photo-cross-linking of the lamella-cylinder (lc)-morphology by co-casting a radical photo-initiator and UV exposure resulted in the expected Janus cylinders. When the bulk material was first swollen in acetonitrile and cross-linked by cold vulcanization, Janus sheets were obtained. Swelling in acetonitrile/decane emulsion lead to a new type of JPs, Janus ribbons. In both cases a phase transition had occurred; in case of the Janus sheets a thin PB layer had formed between the original PB cylinders, resulting in an undulated-lamella morphology. For the formation of Janus ribbons a connecting PB phase had formed in every second interspace along the major axis of the cylinders. Casting a tSBT film from tert-butanol, a non-solvent for PB, also enabled the synthesis of spherical JPs. This way, the importance and versatile application of swelling agents and cross-linking methods for the preparation of JPs from bulk structures was demonstrated. The obtained Janus cylinders were hydrolyzed to have one PHS and one poly(methacrylic acid) (PMAA) hemicylinder, resulting in water-soluble particles.
Further, solution structures of tSBD and tSBT triblock terpolymers were investigated. In water, tSBD formed core-corona micelles that exhibited pH-responsive and LCST behavior due to the responsive poly(2-(dimethylamino)ethyl methacrylate) corona. Employing the novel method of directed hierarchical self-assembly, “football” MCMs were obtained from tSBD whereas tSBT formed “clover” structures. Cross-linking of the B block in such MCMs and their subsequent dissolution in a solvent for all three blocks can be used to prepare spherical JPs. However, as tSBD MCMs existed in water, no sufficient cross-linking method could be found to cross-link the organic PB phase within the aqueous solution. For tSBT MCMs in ethanol the standard approach of adding a photo-initiator to the MCM solution followed by UV exposure was successfully employed and spherical JPs were obtained. These were again hydrolyzed to acquire water-soluble JPs. Apart from some isolated single Janus spheres, cryogenic transmission electron microscopy mainly revealed the formation of “clover” and “hamburger” oligomers possibly due to the slightly better solubility of PMAA. Here, the applicability of the concept of directed hierarchical self-assembly to create MCMs was demonstrated for two different triblock terpolymers and the corresponding method of solution-based JP synthesis was successfully conducted for tSBT.
Dynamic Self-Assembly of Magnetic Colloidal Particles
Dynamic self-assembly represent one of the most powerful tools in Nature to spontaneously organize a system on a hierarchy of different scales.
Most of the processes at the nano/micro scale occur at very low Reynold’s number where inertia can be neglected. Creeping flow magnetic systems can be characterized by the Mason number.
The Mason number measures the ratio between the viscous and the magnetic torque and is the main parameter governing the behavior of paramagnetic colloids investigated in this thesis.
The work presented in this thesis explores new dynamic regimes of colloidal dynamics which occur when suddenly switching to high Mason numbers.
In a static magnetic field the equilibrium structure of paramagnetic colloids are chains. At high Mason number in a rotating magnetic field the time averaged equilibrium conformation is a two dimensional cluster.
By switching from a static to a rotating magnetic external field, we cause a transient dynamics from a static to the dynamic equilibrium state.
The first question addressed in this thesis is: what is the physics that determines the transient folding pathway from one to the other equilibrium state?
Dynamic magnetic fields were used by others to propel top down DNA-linked chains of paramagnetic colloids in a liquid.
The second question asked is whether we can dynamically self-assemble swimmers taking a fully bottom up approach?
The third question is: is it possible to assemble more complex dynamic patterns that lead to motion of the swimmers governed by more collective coupled hydrodynamics that goes beyond slender body theory of the linked chains?
This thesis answers the three questions and contributes to the understanding of colloidal dynamics and self-assembly in dynamic magnetic fields in the regime of high Mason numbers.
We explore two aspects of the dynamic self-assembly i.e. the transient kinetics between two dynamic self-assembled equilibria and the dynamically self-assembled propulsion of magnetic swimmers beyond slender body hydrodynamics.
The thesis therefore aims at achieving magnetic control over the assembly of complex dynamic colloidal structures.
"The New Chemistry" - Sustainable Catalysis with Alcohols
- Subject of the thesis are new iridium complexes stabilized by anionic P,N- or P,N,P-ligands. These complexes were used in homogeneous catalysis. Furthermore, mechanistic studies were performed to provide an insight into the catalytic cycles. Synthesis protocols for a multitude of different product classes have been developed.
The iridium complex 1, stabilized by a neutral P,N-ligand, reacts under basic conditions with 2-aminopyridines. By elimination of dipyridylamine the new catalyst species 2a was formed, which is more stable than catalyst 1.
Based on this finding eight new anionic P,N-ligands and the resulting iridium complexes were synthesized.
After optimization of the reaction conditions (solvent, base, temperature and catalyst loading) these catalysts were used in BH (borrowing hydrogen)/HA (hydrogen autotransfer) reactions. The selective monoalkylation of anilines with primary alcohols was investigated. In comparative experiments the superiority of the new class of catalysts versus the original catalyst 1 was clearly shown. Under mild reaction conditions (70 °C) the selectivity profile with respect to the monoalkylation has been preserved.
The catalytic protocol was subsequently extended to the alkylation of aromatic diamines. Therefore various diaminobenzenes were used as substrates. Also Dapsone®, an important drug in treatment of leprosy could be used as starting material. We succeeded in both symmetric and unsymmetric monoalkylations of diamines. Due to the selectivity profile of the catalyst regarding aromatic amines, also unprotected amino alcohols could be used as alkylating reagents.
By the use of tridentate P,N,P-ligands, a novel class of more stable catalysts compared to complexes 2a-9a, could be developed. Due to sealing the synthesis reactor with a semipermeable membrane, the retransfer of the “borrowed” hydrogen could be prevented and H2 is released. Dehydrogenation and condensation steps are now possible instead of BH/HA. By reacting secondary alcohols with β-amino alcohols, pyrroles were accessible.
After adapting the synthesis protocol to this new class of products the tolerance of functional groups was tested. Diversely functionalized alcohols were used. Under mild reaction conditions (90 °C) and very low catalyst loadings (down to 0.03 mol% iridium), a large number of novel pyrroles was accessible. Using this protocol 21 differently substituted α,α-pyrroles, 12 bicyclic pyrroles, symmetrically as well as non-symmetrically substituted oligopyrroles and three β-aminopyrroles were synthesized. The catalyst resting state was identified by NMR experiments and X-ray structure analysis to be an iridium trihydride. This trihydride is formed under catalytic conditions, by treatment of the pre-catalyst with alcohols or in hydrogen atmosphere.
In the final part of the work, a catalytic pyridine synthesis was developed. In this so far unknown heterocycle synthesis up to four different substituents could be introduced within a single reaction step. 2,6-, 2,5-, 2,4- and 2,3-substituted pyridines were synthesized selectively by using variously substituted primary or secondary alcohols and γ-amino alcohols. Furthermore, both the synthesis of bicyclic pyridines as well as the synthesis of pyridines that bear chiral substituents is possible.
On Efficient Solution Methods for Mixed-Integer Nonlinear and Mixed-Integer Quadratic Optimization Problems
- In this thesis we focus on solution methods for convex mixed-integer nonlinear
optimization problems (MINLP). As one main result, we propose a new algorithm
guaranteeing global optimality for convex MINLPs under standard
assumptions. The new algorithm called MIQP-supported outer approximation
(MIQPSOA) incorporates the successive solution of convex mixed-integer
quadratic programs (MIQP) in a linear outer approximation framework. An extensive
numerical competitive study based on several different MINLP solvers shows,
that a first implementation of the new method performs well in terms of both
the reliability and the efficiency. Since the new method is designed to solve simulation-based optimization problems arising in practical engineering applications, the main performance criterion is the number of function evaluations required to solve a problem.
Furthermore, the test results indicate, that the integration of mixed-integer search steps, resulting from the solution of convex MIQPs, significantly improves the reliability and the efficiency compared to well-known linear outer approximation methods.
After reviewing available solution techniques for convex MINLP problems, we present the algorithmic set-up as well as the convergence proof of MIQPSOA. As pointed out in this dissertation, MIQPSOA is a first step towards a convergent MINLP solution method, that solely relies on the successive solution of convex MIQPs as proposed by Exler and Schittkowski. Finally, we present an extensive numerical test case study considering different solution methods for convex MINLPs.
The second part of this thesis deals with efficient solution techniques for
convex mixed-integer quadratic programs, that arise as subproblems during the
solution of MINLPs by MIQP-based algorithms, such as MIQPSOA. First, we
briefly review latest developments in state-of-the-art mixed-integer linear
(MILP) solvers, since we want to develop a MIQP solver that incorporates the most successful components of MILP solvers. As we focus on branch-and-bound methods, one main component is an efficient and robust sub-solver for continuous quadratic programs, which is able to perform warmstarts. On the other hand, cutting planes have led to a tremendous speed-up of mixed-integer linear solvers during the last 20 years. As a consequence, we extend an efficient construction method for disjunctive cutting planes, such that it can be applied for MIQPs.
Extensive numerical tests show, that the performance of a branch-and-bound solver can be significantly increased by exploiting warmstarts. Furthermore, it turns out, that in a majority of the test cases, where disjunctive cutting planes exist, the calculation times are reduced up to a factor of more than 5. Nevertheless there are also instances, where the presents of disjunctive cutting planes significantly slows down the performance. Due to the efficient cut generation method developed within this thesis, the generation of cutting planes has almost no influence on the calculation time, if no disjunctive cuts exist, which is the case in about 45 \% of all test instances. As a consequence, the application of cutting planes for MIQPs needs further attention and especially a dynamic cut management might be very profitable. Finally, we compare the performance of our branch-and-cut solver MIQL with the solver SCIP, which is one of the state-of-the-art MILP solvers, that can also solve MIQPs. These tests indicate, that MIQL outperforms SCIP on hard MIQP instances, while SCIP is faster for simpler test cases.
RNA interference with allatoregulating neuropeptide genes affecting circadian rhythm, development, mating and reproduction of Spodoptera frugiperda (Lepidoptera: Noctuidae)
Intisar Taha Elhag Hassanien
- Juvenile hormones (JHs) have juvenoid functions but also act as a true gonadotropin in the Lepidoptera. JHs are released by the corpora allata (CA) into the hemolymph, which are under allatotropic and allatostatic neuropeptide control as well as under somatic and environmental stimulus.
Two types of allatostatins (Spofr-AS type Manse-AS and Spofr-AS type A or FGLamides) and two allatotropins (Spofr-AT 1 or Manse-AT and Spofr-AT 2) were identified and cloned from Spodoptera frugiperda. Their functions were already investigated in our laboratory. Most of these peptides are pleiotropic in function but their specific roles in the various developmental stages of S. frugiperda are still unclear.
My work mainly emphasizes on the AT 1 gene function on JH and ecdysteroid titers in the hemolymph of larvae and adults as well as on females’ and males’ reproductive tissues and on the daily egg rate of the females. Studies were carried out by knockdown of the AT 1 gene using RNA interference. My results show a significant role of this neuropeptide on the circadian rhythm of prepupal commitment and metamorphosis, but also on the profile of egg laying and the number of deposited eggs. In general, Spofr-AT 1 acts as a true allatotropin in larvae and adults, but its functions may be substituted, at least in part, by Spofr-AT 2.
Silencing of Spofr-AT 1 and AS type A genes in males supported either allatotropic or allatostatic actions on the accessory glands (AGs) of the males, but had no effect on the JH transferred to the female bursa copulatrix (BC) during mating, nor on the fertility of the females.
Synthesis of Group (lV) Transition Metal Complexes and their Applications as Catalysts for Ethylene Polymerization
- The aim of the project included the synthesis and characterization of new group (IV) metal complexes and their applications as catalysts in homogeneous ethylene polymerization reactions. For this purpose, different types of organic compounds and their group (IV) metal complexes were synthesized and tested for ethylene polymerization after activation with MAO. The first part of this work describes the synthesis of symmetric and asymmetric metallocene dichloride complexes bearing bulky alkoxy substituents on indenyl moieties and the investigation of their potential as ethylene polymerization catalysts. Indenyl compounds bearing bulky alkoxy substituents can be prepared by refluxing phenol or naphthol derivatives with w-bromo-1-indenylalkanes and potassium carbonate in the presence of catalytic amounts of 18-crown-6 in acetone. They can be prepared in better yields by the reaction of w-bromo-1-phenoxyalkanes with indenyl lithium. Symmetric metallocene dichloride complexes were synthesized by deprotonating the alkoxy substituted indenyl compounds with n-butyllithium followed by the reaction with metal tetrachlorides. Asymmetric metallocene dichloride complexes were synthesized by deprotonating alkoxy substituted indenyl compounds with n-butyllithium followed by the reaction with indenyl zirconium trichloride. The second part of this work deals with the synthesis of bis (indenyl) zirconium dichloride complexes bearing bulky 9-methyl fluorenyl substituents. 9-Methyl fluorenyl substituted indenyl compounds can be synthesized by the reaction of w-bromo-1-indenylalkanes with the lithium salt of 9-methyl fluorene. The reaction of zirconium tetrachloride with the lithium salts of the substituted indenyl compounds afford the bis (indenyl) zirconium dichloride complexes in good yields. Asymmetric chelating diamide complexes of titanium and zirconium were also synthesized and tested for ethylene polymerization as a part of the project. Reaction of the desired aniline with an appropriate dibromoalkane compound affords the N-substituted bromoalkyl aniline derivative which can react with tertiary butyl amine to yield the desired asymmetric diamine compound. Deprotonation of the diamine compounds with n-butyllithium followed by the reaction with titanium tetrachloride or zirconium tetrachloride yields the desired chelating diamide complexes. Titanium and zirconium complexes with a Schiff base derivative of 2-(2-aminophenyl)benzothiazole were also synthesized. The reaction of 2-(2-aminophenyl)benzothiazole with benzaldehyde yields its Schiff base derivative which can react with titanium tetrachloride or zirconium tetrachloride to afford the desired complexes. The above mentioned complexes were used for homogeneous ethylene polymerization after activation with MAO (M:Al = 1:2000). The alkoxy substituted metallocene catalysts showed good to moderate activities which depend on the length of the bridging alkylidene chain between alkoxy group and indenyl ligand of the zirconocene dichloride complex as well as the steric bulk of the alkoxy substituent. The activity maximum (27467 kg PE/mol cat. h) was found for a chain length of four carbon atoms. Further increase or decrease in the chain length resulted in a decrease of activity. The decrease of steric bulk at the phenoxy group also resulted in a decrease of activity. The 9-methyl fluorenyl substituted metallocene catalysts showed good activities towards ethylene polymerization. The catalyst with butylidene bridge between 9-methyl fluorenyl group and indenyl ligand showed the maximum activity (15786 kg PE/mol cat. h). The activated asymmetric chelating diamide complexes of titanium and zirconium (M:Al = 1:1000) showed low activities. The complex bearing bulky isopropyl groups at the aniline moiety showed the highest activity (263 kg PE/mol cat. h). The activity decreased by decreasing the steric bulk at the aniline moiety. Titanium and zirconium complexes of the Schiff base derivative of 2-(2-aminophenyl) benzothiazole also showed low activities (432 and 276 kg PE/mol cat. h) after activation with MAO (M:Al = 1:2000). A possible reason for the low activity could be the coordination of the sulphur atom to the active species. The symmetric alkoxy substituted metallocene catalysts produced polyethylenes of lower melting points, melting enthalpies, crystallinities and viscosity average molecular weights (112.9 J/mol, 126 °C, 0.39 and 270000 g/mol than their asymmetric analogues (155.3 J/mol, 137.2 °C, 0.54 and 420000 g/mol). The polyethylenes produced by 9-methyl fluorenyl substituted metallocene catalysts are of medium melting points, melting enthalpies and crystallinities (142 J/mol, 129.3 °C and 0.49). The polyethylenes produced by the asymmetric chelating diamide catalysts have medium melting points but low melting enthalpies and crystallinities (137.8 J/mol, 116.5 °C and 0.44).