Dissertationen zum Thema „Coupling methodologies“

La present tesis doctoral està basada en el desenvolupament de noves metodologies de RMN per la mesura de constants d’acoblament homo- i heteronuclears en molècules petites. La tesi es presenta com a compendi de publicacions d’articles de recerca que han estat publicats en diferents revistes científiques. El punt de partida està basat en l’experiència i coneixement previ del nostre grup de recerca en aquest camp. S’ha pres com a referència principal l’experiment selHSQMBC, al qual s’hi han implementat noves funcions per tal de dissenyar un conjunt de noves metodologies capaces de resoldre els principals problemes que afecten aquest tipus de mesures. En la majoria de casos s’ha utilitzat la metodologia IPAP per tal d’aconseguir una mesura més exacte. A la vegada, el patró E.COSY, així com el concepte de espectroscòpia J-resolt, s’han implementat conjuntament amb la metodologia IPAP per tal d’obtenir una mesura simultània de diferents constants d’acoblament en un sol experiment de RMN. Tanmateix, també es descriuen nous avenços en la mesura de constants d’acoblament protó-carboni a un enllaç, així com constants d’acoblament protó-protó a dos enllaços en grups metilens diastereotòpics. Cada nou experiment s’analitza des d’un punt de vista metodològic alhora que s’avalua la seva aplicabilitat. La tesi s’ha dividit en cinc apartats. En el primer d’ells es fa una introducció general per situar el lector. Al segon capítol es descriuen els objectius principals. El tercer capítol, i més rellevant, conté les diferents publicacions presentades com a resultats i discussió. El quart capítol conté dos apèndixs diferents que no s’han pogut incloure com a publicacions degut a que encara es troben en preparació. Finalment, l’últim capítol conté les conclusions generals del treball.
The present doctoral thesis is focused on the development of modern NMR methodologies for the measurement of homo- and heteronuclear coupling constants in small molecules. The thesis is presented as a compendium of publications that have been published in different scientific journals as original research papers. The starting point was the previous experience and knowledge of our research group. Taking as a reference the selHSQMBC experiment, several new features have been implemented in order to design a complete set of different methodologies that allow us to overcome some of the most typical drawbacks regarding such measurements. In most of the cases the IPAP methodology is used to achieve an accurate measurement. A spin-state selective technique like the E.COSY pattern, as well as the concept of J-resolved spectroscopy, are implemented in conjunction with the IPAP methodology to obtain simultaneous measurement of several coupling constants in a single-shot NMR experiment. Moreover, advances in the measurement of one-bond proton-carbon and germinal proton-proton coupling constants in diastereotopic methylene groups are also presented. Each new experiment is theoretically discussed from a methodological point of view and an assessment on its application is also performed. The thesis is divided in five chapters. In the first one a general introduction is presented in order to situate the reader. In the second chapter main objectives of the thesis are described. The third section is the main chapter which collects all the publications presented as results and discussion. The fourth chapter contains two different appendixes with the results that could not be included as original research papers because they are still in preparation. Finally, last chapter contains general conclusions of the work.

This research focused on the synthesis of novel ogranoboron reagents in efforts to perform a variety of synthetic transformations, and additionally, the development of new methodologies to generate drug-like scaffolds. Initially, three novel tripod ligands were synthesized, and two were effectively chelated to boron to provide the desired organoborates. Such organoborates were employed in nucleophilic additions where they were found to be ineffective, whereas some activity was observed in Suzuki-Miyaura cross-coupling reactions. An additional project on organoboron compounds was conducted and focused on the development of organoboron frustrated Lewis pairs (FLPs) to facilitate the storage and transfer of hydrogen, nucleophilic addition reactions, and Claisen rearrangements. A new method for synthesizing a pyrrolidine diol unit was accomplished, and this intermediate was utilized to synthesize two FLPs. The reactivity of the FLPs with small molecules was assessed, and the pyrrolidine diol unit was subsequently evaluated for its ability to undergo a multicomponent reaction (MCR) to yield compounds possessing beneficial biological activity. Further research in this area was conducted, and a 5-aminoimidazole scaffold was synthesized employing a new MCR which is more efficient than previously reported methodologies. 5-Aminoimidazoles are frequently found in compounds which possess desirable biological activity, and this novel method was employed to generate a library of eleven 5-aminoimidazoles. Additionally, two post condensation modification reactions were developed. During initial studies, a side product was observed which was identified as a dihydrotriazine, which is another biologically appealing chemotype. Therefore, an enhanced method of synthesizing this product was developed, and a library of eleven dihydrotriazines was produced. In summary, novel organoboron reagents were synthesized, and their activity was evaluated. The pyrrolidine diol utilized to synthesize FLPs was applied towards an MCR. Furthermore, a novel MCR was developed for the synthesis of 5-aminoimidazoles, and an enhanced protocol for the synthesis of dihydrotriazines was found.

NMR spectroscopy of paramagnetic solids provides detailed information about the local configuration and the chemical environment of the NMR observed center, as well as about the structural, magnetic and electronic properties of the coordianted paramagnetic centres. In the case of complex paramagnetic solids such as cathode materials for (rechargeable) batteries, NMR represents an invaluable tool to provide insight into the structural and electronic properties of the systems, which are at the base of the electrochemical performance of these materials. However, the paramagnetism makes the interpretation of the NMR data very challenging. This is primarily due to the interactions of the unpaired electrons with the NMR observed nucleus, and the interpretation of the NMR spectra often requires the aid of reliable theoretical and computational methods. Often the dominant interaction contributing to the measured isotropic shifts is the hyperfine interaction between the unpaired electrons and the observed nucleus, which results from the transfer of unpaired electrons from the paramagnetic centre(s) to the NMR observed site. In systems such as the ones studied here, in which the paramagnetic ions are a major constituent of the lattice, the multitide of different local environments results in a complex distribution of resonances. As in the case of the Li$_x$V$_6$O$_{13}$ cathode material, a methodical investigation of the configurational stability from first principles gives insight into the preferred site configurations. The combination of experimental $^7$Li NMR spectra and hyperfine shift DFT calculations of the so-found stable Li environments allows to unravel the complex lithiation mechanism of this material. In the other case of the LiTi$_x$Mn$_{2-x}$O$_4$ cathode materials, the $^7$Li hyperfine shifts calculated from first principles for a variety of Li environments are combined in a lattice model which allows to assign the isotropic regions of the experimental $^7$Li NMR spectra, helping to resolve the complex cation ordering as a function of Mn/Ti content in the series. For paramagnetic centres with an unquenched orbital component of the electron magnetic moment(s), the spin-orbit coupling effects also contribute to the paramagnetic NMR shift and shift anisotropy. A first principles model is derived, which describes how spin-orbit coupling and the single-ion $g$-tensor are defined and calculated in periodic paramagnetic solids, and how they can be coupled with the hyperfine interaction to model their effects on the NMR spectrum. The method is applied to a series of olivine-type LiTMPO$_4$ cathode materials (with TM = Mn, Fe, Co, and Ni) and the respective $^7$Li and $^{31}$P NMR spectra are simulated and compared with the experiments. The other paramagnetic effect considered in this thesis involves the bulk magnetic susceptibility (BMS), which is particularly important for paramagnetic single crystals and solids of complex shape. The BMS effect results from the discontinuity of the bulk susceptibility at the surface of the crystal, inducing a demagnetizing field throughout the sample which changes the measured NMR shift and shift anisotropy. A method to analytically calculate the demagnetising field and the BMS shift in crystals of different shapes is derived, and it is applied to a series of LiFePO$_4$ single crystals for which the $^7$Li NMR spectra are also measured experimentally. The study confirms that, particularly for $^7$Li NMR, the macroscopic shape-dependent BMS shift can indeed be a significant contribution to the measured resonances, determining the large variation in shift measured for the crystals of different shapes.

The advent and proliferation of planar technologies for power converters are driven in part by the overall trends in analog and digital electronics. These trends coupled with the demands for increasingly higher power quality and tighter regulations raise various design challenges. Because inductors and transformers constitute a rather large part of the overall converter volume, size and performance improvement of these structures can subsequently enhance the capability of power converters to meet these application-driven demands. Increasing the switching frequency has been the traditional approach in reducing converter size and improving performance. However, the increase in switching frequency leads to increased power loss density in windings and core, with subsequent increase in device temperature, parasitics and electromagnetic radiation. An accurate set of reduced-order modeling methodologies is presented in this work in order to predict the high-frequency behavior of inductors and transformers. Analytical frequency-dependent expressions to predict losses in planar, foil windings and cores are given. The losses in the core and windings raise the temperature of the structure. In order to ensure temperature limitation of the structure is not exceeded, 1-D thermal modeling is undertaken. Based on the losses and temperature limitation, a methodology to optimize performance of magnetics is outlined. Both numerical and analytical means are employed in the extraction of transformer parasitics and cross-coupling. The results are compared against experimental measurements and are found to be in good accord. A simple near-field electromagnetic shield design is presented in order to mitigate the amount of radiation. Due to inadequacy of existing winding technology in forming suitable planar windings for PCB application, an alternate winding scheme is proposed which relies on depositing windings directly onto the core.
Master of Science

Cette thèse porte sur la caractérisation, la modélisation et l'analyse des phénomènes de «Pulling» et de «Pushing» dans les systèmes de boucles à verrouillage de phase (PLL), utilisant une approche globale où les effets de couplages électromagnétiques aux différents niveaux d'intégration (niveau puce, niveau assemblage, niveau report sur PCB) sont pris en compte de manière distribuée. L'approche de modélisation adopte une méthodologie hybride où l'analyse des couplages électromagnétiques combinée à des schémas équivalents large-bande (compatibles avec les modèles de composants actifs disponibles dans les librairies) est couplée à des représentations comportementales dynamiques. Les représentations comportementales développées permettent de capturer des effets de non-linéarités tant au niveau composant (caractéristique non-linéaire des Varicap en fonction des tensions de contrôle) qu'au niveau block de fonction (gain KVCO non uniforme de l'oscillateur contrôlé en tension (VCO) en fonction de la fréquence).Cette méthodologie hybride permet l'évaluation d'effets compétitifs résultant de phénomènes de «pulling» et de «Pushing» au niveau de la puce (influence de la PLL, effets de l'amplificateur de puissance, intégrité des alimentations ou distribution des références de masse, etc.) , et des distorsions induites par des éléments extérieurs à la puce (exemple de composants sur PCB : Filtre SAW, capacités de découplages, réseaux d'adaptation).L'approche proposée est utilisée pour l'étude et la conception de deux types de circuits développés par NXP-semi-conducteurs pour des applications liées à la sécurité automobile (PLL fonctionnant aux alentours de 1.736GHz) et à la réception satellitaire (PLL de faible consommation fonctionnant à 9.75/10.6 GHz pour les circuits LNB).Les résultats de modélisation obtenus sont validés par corrélations avec les données expérimentales et par comparaison avec les résultats obtenus de différents outils (ADS Harmonic- Balance/Transient de Agilent, Spectre de Cadence
This thesis work focuses on characterization, modeling and analysis of «Pulling» and «Pushing» phenomena in Phase Locked Loops (PLL) based on a global approach where distributed effects of electromagnetic couplings at different integration levels (chip-level, assembly-level, board or PCB-level) are taken into account. The modeling approach adopts a hybrid methodology where the analysis of electromagnetic couplings combined with broadband equivalent circuit synthesis (compatible with library models of active components) is coupled with dynamic behavioral representations. The derived behavioral representations properly capture the effects of nonlinearities both at component scale (non-linear characteristic of varicap as function of control voltages) and at function block level (non-uniform gain KVCO of VCO circuits depending on frequency).The hybrid methodology renders possible the assessment of competitive effects resulting from «Pulling» and «Pushing» phenomena at chip level (influence of the PLL, effects of the power amplifier, power integrity, or ground reference distribution, etc..), and the distortions induced by components external to the chip at package and board levels (such as components on PCB: SAW filters, decoupling capacitors, matching networks).The proposed approach is used for the study and design of two types of circuits developed by NXP- Semiconductors, for applications related to automotive security and immobilization (an RF low power transceiver Integrated Circuit (PLL running around 1.763GHz), and to satellite receiver (PLL operating at low power for LNB circuits working at 9.75/10.6 GHz).The obtained modeling results are validated by correlation with experimental data and by comparison with different time-domain and frequency-domain simulation tools results (ADS-Harmonic Balance, ADS-Shooting solutions, Cadence-Spectre)

A major focus of the Leighton group has been the development of efficient, scalable and step-economical reactions towards our goal of expanding the structural variants of medicinally relevant non-aromatic polyketide natural products. Over the last few years the Leighton group has developed a novel mode of strained-silane Lewis acid activation with the use of weakly-coordinating anionic catalysts. Hyper-coordinate silicates with unprecedented levels of reactivity have facilitated previously unattainable late stage complex fragment couplings. A novel method of chiral anion catalyzed nucleophilic addition to α- and β-diketones has been explored. Finally, an operationally straightforward, efficient and direct β-ketoaldehyde allylation methodology will be discussed.

Dipolar couplings are one of the major source of structural information. Due to their dependence on the distance between the nuclei and the angle of orientation of the dipolar vector with respect to the magnetic field, they provide significant insight into the geometry and topology of molecules. As the dipolar interactions are in general present in the solid phase of the compounds, solid state NMR experiments have gained significant popularity and is widely used. Separated Local Field NMR spectroscopy based on cross-polarization technique has been used to measure the heteronuclear dipolar couplings in solid state. However, the technique undergoes many experimental challenges and requires further development. This thesis is concerned mainly with the development of techniques to measure the dipolar couplings accurately in oriented molecules. In this regard, a method for fast data acquisition is also proposed. The first chapter briefly introduces the basics of NMR spectroscopy, methodologies applied for obtaining a high resolution NMR spectrum in the solid state. An introduction to liquid crystals is presented and the nature of NMR interaction in the liquid crystalline phases is described. In chapter-2, a new pulse scheme has been proposed that includes the X-nucleus polarization in the SLF experiments and is shown to provide better sensitivity and resolution. A quantitative analysis with simulation and experimental results are also presented. In chapter-3, the performance of various homonuclear decoupling pulse schemes incorporated into SLF experiments tested on oriented systems are compared. The proposed pulse schemes are shown to provide high resolution spectrum with accurate dipolar coupling measurement for natural abundant samples and for uniformly labeled compounds as well. Theoretical description with simulation and experimental results shown here are found to provide optimum results under several technical complications seen with respect to the conventional methods used for SLF experiments. Chapter-4, an attempt is made to reconstruct 2D J-resolved and 2D- SLF spectra from several 1D experimental data. This is achieved with the help of projection reconstruction method and is shown to provide high resolution 2D spectrum with saving of experimental time by an order of two. Chapter-5, high resolution spectra from SLF experiments under phase alternating pulses and using amplitude and time averaged nutation techniques are shown for accurate dipolar coupling measurement with a dramatic reduction in rf power. This is important as the use of low rf power leads to low sample heating and can be applied suitably for the study of liquid crystals and salty biomolecules. Chapter-6, attempts are made to characterize two novel thiophene based liquid crystals using both solution and solid state NMR spectroscopy. C-H dipolar couplings measured from SLF experiments are mainly used to find the order parameters and geometry of the molecules.

Dipolar couplings are one of the major source of structural information. Due to their dependence on the distance between the nuclei and the angle of orientation of the dipolar vector with respect to the magnetic field, they provide significant insight into the geometry and topology of molecules. As the dipolar interactions are in general present in the solid phase of the compounds, solid state NMR experiments have gained significant popularity and is widely used. Separated Local Field NMR spectroscopy based on cross-polarization technique has been used to measure the heteronuclear dipolar couplings in solid state. However, the technique undergoes many experimental challenges and requires further development. This thesis is concerned mainly with the development of techniques to measure the dipolar couplings accurately in oriented molecules. In this regard, a method for fast data acquisition is also proposed. The first chapter briefly introduces the basics of NMR spectroscopy, methodologies applied for obtaining a high resolution NMR spectrum in the solid state. An introduction to liquid crystals is presented and the nature of NMR interaction in the liquid crystalline phases is described. In chapter-2, a new pulse scheme has been proposed that includes the X-nucleus polarization in the SLF experiments and is shown to provide better sensitivity and resolution. A quantitative analysis with simulation and experimental results are also presented. In chapter-3, the performance of various homonuclear decoupling pulse schemes incorporated into SLF experiments tested on oriented systems are compared. The proposed pulse schemes are shown to provide high resolution spectrum with accurate dipolar coupling measurement for natural abundant samples and for uniformly labeled compounds as well. Theoretical description with simulation and experimental results shown here are found to provide optimum results under several technical complications seen with respect to the conventional methods used for SLF experiments. Chapter-4, an attempt is made to reconstruct 2D J-resolved and 2D- SLF spectra from several 1D experimental data. This is achieved with the help of projection reconstruction method and is shown to provide high resolution 2D spectrum with saving of experimental time by an order of two. Chapter-5, high resolution spectra from SLF experiments under phase alternating pulses and using amplitude and time averaged nutation techniques are shown for accurate dipolar coupling measurement with a dramatic reduction in rf power. This is important as the use of low rf power leads to low sample heating and can be applied suitably for the study of liquid crystals and salty biomolecules. Chapter-6, attempts are made to characterize two novel thiophene based liquid crystals using both solution and solid state NMR spectroscopy. C-H dipolar couplings measured from SLF experiments are mainly used to find the order parameters and geometry of the molecules.