Rozprawy doktorskie na temat „Novel Magnetic Systems”

Wireless power transfer (WPT) technologies have become important for our everyday life. The most commonly used near-field WPT method is inductive coupling, which suffers from low efficiency and small range. The Strongly Coupled Magnetic Resonance (SCMR) method was developed recently, and it can be used to wirelessly transfer power with higher efficiency over a longer distance than the inductive coupling method. This dissertation develops new SCMR systems that have better performance compared to standard SCMR systems. Specifically, two new 3-D SCMR systems are designed to improve the angular misalignment sensitivity of WPT systems. Their power transfer efficiency for different angular misalignment positions are studied and analyzed. Prototypes are built for both systems and their performance is validated through measurement. Furthermore, new planar broadband conformal SCMR (CSCMR) systems are developed that maintain high efficiency while providing significantly larger bandwidth than standard CSCMR systems. Such broadband CSCMR systems are used here for the first time to simultaneously accomplish highly efficient wireless power transfer and high data rate communication through the same wireless link. These systems that combine wireless power and communication are expected to enable next-generation applications with battery-less and “power-hungry” sensors. Example applications include implantable and wearable sensors as well as embedded sensors for structural health monitoring.

Magnetic photocatalysts were synthesised by coating a magnetic core with a layer of photoactive titanium dioxide. This magnetic photocatalyst is for use in slurry-type reactors in which the catalyst can be easily recovered by the application of an external magnetic field. The first attempt at producing this magnetic photocatalyst involved the direct deposition of titanium dioxide onto the surface of magnetic iron oxide particles. The photoactivity of these Fe3O4/TiO2 was lower than that of single-phase TiO2 and was found to decrease with an increase in the heat treatment. These observations were explained in terms of an unfavourable heterojunction between the titanium dioxide and the iron oxide core. Fe ion diffusion from the iron oxide core into the titanium dioxide matrix upon heat treatment, leading to a highly doped TiO2 lattice, was also contributing to the observed low activities of these samples. These Fe3O4/TiO2 particles were found to be unstable, with photodissolution of the iron oxide phase being encountered. This photodissolution was dependent on the heat treatment applied, the greater the extent of the heat treatment, the lower the incidence of photodissolution. This was explained in terms of the stability of the iron oxide phases present, as well as the lower photoactivity of the titanium dioxide matrix. In fact, the observed photodissolution was found to be induced-photodissolution. That is, the photogenerated electrons in the titanium dioxide phase were being injected into the lower lying conduction band of the iron oxide core, leading to its reduction and then dissolution. Thus, the approach of directly depositing TiO2 onto the surface of a magnetic iron oxide core proved ineffective in producing a stable magnetic photocatalyst. The introduction of an intermediate passive SiO2 layer between the titanium dioxide phase and the iron oxide phase inhibited the direct electrical contact and hence prevented the photodissolution of the iron oxide phase. Improvements in the photoactivity were seen to be due to the inhibition of both the electronic and chemical interactions between the iron oxide and titanium dioxide phases. Preliminary optimisation experiments revealed that a thin SiO2 layer is sufficient for inhibiting the photodissolution. The thickness of the TiO2 coating was found not to have a significant effect on the photocatalytic performance of the coated particles. Finally, heat treating for 20 minutes at 450??C was sufficient for converting the titanium dioxide into a photoactive phase, longer heating times had no beneficial effect on the photoactivity.

This thesis presents the development of the first SQUID-based ac-magnetometer built in a dry dilution fridge. The possibility of expanding the frequency respond from tens of kHz of a commercial magnetometer to the bandwidth of muon-spin relaxation μSR (MHz), an indirect magnetic probe, which measures magnetic dynamics from the depolarisation of fundamental particles, is demonstrated. It opens a new scenario to investigate classical and quantum magnetic fluctuations by a direct probe in a range of frequencies that have an important role in exotic magnetic phases. Geometrical spin ices, frustrated magnets where magnetic excitations can be deconfined forming monopoles are good candidates to investigate. The study of magnetic fluctuations will help to understand the magnetic dynamics of these elementary excitations. Quantum spin liquids, frustrated systems without long-range order but with spins highly correlated that still fluctuate down to zero Kelvin are also interesting systems. The temperature dependence of their quantum fluctuations investigated by μSR have shown a dynamical plateau that might be corroborated by susceptibility measurements. The fabrication of the magnetometer has been combined with μSR investigations of the ground state of NbFe2 and CeRhIn5. The magnetic ground state of the ferromagnetic quantum critical point induced by growing around 1% Nbrich Nb1−yFe2+y is claimed to be reached in this kind of clean itinerant systems by a long–range spin density wave (SDW), although several attempts to identify the ground state by neutron scattering were unsuccessful. The μSR measurements prove that the ground state of the stoichiometric compound is governed by static and short-range correlations or by an incommensurate and helical SDW. The heavy fermion CeRhIn5 was investigated at ambient pressure due to the coexistence of antiferromagnetic and superconducting order in an intermediate region of pressures. The filamentary or bulk nature of the superconducting phase is still until debate and the onset of superconductivity at ambient pressure reported in some works may shed some light into the nature of the ground state. μSR and resistivity measurements were carried out to investigate the antiferromagnetic and helical phase without any signature of a superconducting transition.

The main focus of this thesis is the experimental muon-spin relaxation technique (μ+SR) and its application to study novel and unconventional magnetic behaviour. I present a range of experimental measurements which I supplement with theoretical calculations to remove the two main limitations inherent to μ+SR and thereby improve the understanding of the experimentally observed behaviour. Additionally, I investigate the potential effects of demagnetising fields on highfield μ+SR measurements. μ+SR employs positively charged muons as sensitive local magnetic probes but has the essential drawback that there is normally a lack of knowledge about where the muons implant in a given sample and the extent of subsequent local distortions. In some cases this nescience makes interpretation of μ+SR data very challenging and severely limits the conclusions that can be drawn. Two research projects presented in this thesis are centred around utilising ab initio structural calculations based on density functional theory in order to remove these two inherent limitations of μ+SR and gain insights into the stopping sites of the muons and their local environments. In the case of the Pr based pyrochlores Pr2B2O7 (B=Sn, Hf, Zr, Ir) I combine such ab initio computations of the muon sites with calculations of the crystalfield levels of the Pr3+ ions. I demonstrate that the non-Kramers doublet ground state of the Pr ions is split due to the presence of the muons and that this consequently results in a hyperfine enhancement of the Pr nuclear moments. By showing the theoretically calculated values of the ground state splittings to be in fair agreement with those obtained from fits to the experimental data, I demonstrate that the μ+SR measurements of Pr2B2O7 re ect muon induced effects rather than intrinsic behaviour. I subsequently investigate the conceptually very similar spin ices A2Ti2O7 (A= Dy, Ho) using the same methodology and confirm that in this case the muons act as passive probes. A second project presented in this thesis concerns the compound a-RuCl3, in which Ru ions form nearly perfect two-dimensional honeycomb layers. The experimental μ+SR data reveal two magnetic phase transitions, the origins of which I study by combining calculations of the potential muon sites with computations of the dipolar fields experienced by the muons at these sites for different magnetic structures. I show that the experimental observations are only fully explained through a temperature regime between the two measured transitions in which the Ru spins share significant correlations within the honeycomb layers but not between the separate layers. A final research aspect I present is a study of the potential effects of demagnetising fields in high field μ+SR measurements. I derive an analytical solution for the demagnetising tensor of a uniformly magnetised finite cylinder and use it to show that edge regions of a sample suffer the most from demagnetising effects. I subsequently discuss the resulting experimental signatures and methods to identify and reduce them.

Magnetic topological insulators (MTIs) are of considerable interest in developing novel spintronics and quantum computing applications. Under the topological protection by time-reversal Z2 invariant number, magnetic topological insulators are provided with robust electronic and magnetic properties against local perturbations. The quantum anomalous Hall effect (QAHE), which harbors dissipationless chiral edge states in MTIs, provides a competitive platform for future low-power consumption and high-speed spintronic devices. Although the present studies on both bulk and surface magnetic properties in MTIs have made significant progress, the in-depth understanding of the exchange couplings and the interaction between the two magnetization sources is far from completion. In addition, the optical control of the non-trivial properties in MTIs is important in achieving novel applications for ultrafast optoelectronics and optical spintronics. The goal of this dissertation is to understand and manipulate the dynamical spin coupling as well as the carrier relaxation dynamics in MTIs, using the static magneto-optical Kerr effect (MOKE) and the time-resolved magneto optical Kerr effect (TRMOKE) techniques. First, a pronounced spin-valve-like structure of dynamical magnetization is observed in Cr-(Bi,Sb)2Te3/CrSb bilayer heterostructure through the pump-modulated MOKE characterization. The characters of the soft and resilient ferromagnetic phases are distinguished in terms of the spin coupling between the dynamical surface and bulk ferromagnetism. The dynamical bulk ferromagnetic ordering is softened by a laser-induced heat effect on the lattice, while the dynamical surface magnetization is enhanced via the strengthening Dirac-hole-mediated exchange coupling. In addition, the pump-fluence-dependent measurement of the exchange-bias effect provides further evidence for the enhancement of MTI surface magnetization at the MTI/AFM interface. Lastly, we propose a theoretical model that includes the long-range p-d exchange coupling and a Dirac-hole-mediated exchange interaction and estimate the exchange coupling energies in the MTI/AFM bilayer structure. Second, ultralong carrier lifetimes (3~20 ns) of the optically pumped surface states are observed in Cr-(Bi,Sb)2Te3 MTI which corresponds to the slow radiative recombination within the gapped Dirac cone. The photoinjection dependency of radiative lifetimes suggests a strong Coulomb screening effect of electron-hole plasma on surface excitons. The experimental results are consistent with the theoretical simulation. On the other hand, the nonradiative nature of bulk electron relaxation is identified with a lifetime of ~1000 ps by photoinjection- and temperature- dependent reflectivity measurements. The finding of long-lived excited carriers in MTI improves the understanding of the general carrier dynamics in topological insulators-based materials.

The work reported in this Ph.D. thesis is focused on the use and immobilisation of enzymes to produce new materials, which are important for biotechnological applications. The use of enzymes in industrial sectors is continuously increasing. Enzymes offer many advantages over traditional chemical processes. The research work of this thesis can be divided into two parts. The first part is focused on the immobilisation of laccase and chitinase. The main object of enzymatic immobilisation is to enhance the economics of biocatalytic processes. Enzymatic immobilisation allows the reuse of enzymes for an extended period of time and enables easier separation of the catalyst from the product. Furthermore, immobilisation improves many properties of enzymes: performance in the organic solvents, pH tolerance and heat stability. The most widely used immobilisation method is the covalent binding of the enzyme to support. Different type of support can be chosen for enzymatic immobilisation. As the material can plays a crucial role in the immobilisation process and the properties of the produced catalytic system. In this thesis we have chosen two different supports: super paramagnetic nanoparticles for both the enzymes used and the chitosan beads as an alternative support for chitinase. Magnetic nanoparticles show interesting properties for enzymatic immobilisation, they can be obtained with small size, increasing the yield of enzymatic immobilisation and above all, the reaction products can be easily recovered applying an external magnetic field. Magnetic nanoparticles were prepared following the traditional method of co-precipitation of Fe2+ and Fe3+ ions. This immobilisation process was successfully used for chitinase, obtaining a high immobilisation yield and increasing enzymatic stability. Different was for laccase, which having a different catalytic mechanism a revision of the synthesis has been attempt. The use of the magnetic nanoparticles obtained with the traditional method hampered the detection of stable radical species formed during the catalytic mechanism as it happens for the oxidation product of 2,2'-azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS), the standard compound used to test the enzyme activity. Changing some synthetic parameters, the new magnetic nanoparticles were produced and characterized. In fact nanoparticles with a lower aggregation state and a smaller hydrodynamic diameter were obtained and tested without any interference with the ABTS substrate. Chitinase was also immobilised on chitosan beads/Macro-Spheres (CMS), as this support is completely atoxic and so most suitable for application in food industries.The presence of active amino groups in deacetylated GlcNAc units of chitosan also enables the binding of the linker (glutaraldehyde and genipin) and then of the enzyme. The goal of this part of the thesis was to attempt the immobilisation of Chitinase on different supports, MNPs and CMS, for the efficient production of COS. The second part of this thesis is focused on the use of enzymes to produce melanin pigments. Melanins have a variety of biological functions, including protection against UV radiation, free radical scavengers and metal ions chelators. Thanks to their properties, melanins found applications in several fields such as cosmetics, optoelectronics, food, and pharmacology. Eumelanin and Pheomelanin have been produced by oxidative enzymatic synthesis using laccase from Trametes versicolor and then characterized by the use of Multifrequency Continuos Wave (CW) and pulse Q-band EPR. Then, as soluble melanin pigments have important technological applications in different fields, like in optoelectonics, soluble pigments mimicking pyomelanin structure have been synthesized starting from Homogentisic Acid and Gentisic Acid monomers and spectroscopically characterized with their antioxidant activities determination.

Magnetic Resonance Imaging (MRI) is a widely used soft tissue imaging technique that has gained considerable success because of its sensitivity to several tissue parameters. However, commercially available whole-body imaging systems with large encircling radio frequency (RF) and gradient coils are less efficient when the goal is to obtain detailed, high-resolution images with high specificity and sensitivity from localized regions of the body such as the female breast. This research addresses these problems by proposing a new design in RF coil development for breast cancer screening in a conventional 1.5T MRI system. The new design provides two resonant receiving modes that operate in a quadrature configuration, and a region of interest (ROI) that closely conforms to the shape of the female breast. We adopted an optimum design strategy that combined the analytic Biot-Savart intergral equation with the Method of Moment formulation in the development of electromagnetic models and simulation tools. These models were used to analyze the magnetic field distribution and the spatial field coverage, as well as the magnetic field uniformity in the ROI. Results from our analysis were employed in the construction of a highly scalable prototype. The validation of our design strategy is confirmed by comparisons with the commercial Ansoft HFSS v8.5 finite element package.

Thesis (Ph.D)--Electrical and Computer Engineering, Georgia Institute of Technology, 2010.
Committee Chair: Tentzeris, Manos; Committee Member: DeJean, Gerald; Committee Member: Ingram, Mary; Committee Member: Kavadias, Stylianos; Committee Member: Laskar, Joy. Part of the SMARTech Electronic Thesis and Dissertation Collection.

The growing applications for IoT devices have caused an increase in the study of low power consuming circuit design to meet the requirement of devices to operate for various months without external power supply. Scaling down the conventional CMOS causes various complications to design due to CMOS properties, therefore various non-conventional CMOS design techniques are being proposed that overcome the limitations. This thesis focuses on some of those emerging and novel low power design technique namely Adiabatic logic and low power devices like Magnetic Tunnel Junction (MTJ) and Carbon Nanotube Field Effect transistor (CNFET). Circuits that are used for large computations (multipliers, encryption engines) that amount to maximum part of power consumption in a whole chip are designed using these novel low power techniques.

La presente tesis doctoral abarca la síntesis electroquímica y caracterización de las propiedades tanto físicas como fisicoquímicas de tres sistemas binarios diferentes, el cobalto-indio (Co-In), hierro-rodio (Fe-Rh) y hierro-fósforo (Fe-P). Se han llevado a cabo varias estrategias para miniaturizar estos sistemas tanto hacia la micro- como hacia la nanoescala. Se han sintetizado capas continuas de Co-In, sobre sustratos conductores de silicio recubiertos con capas semilla de titanio y oro, que muestran estructuras espacio-temporales (targets, anillos concéntricos y espirales de distinto tamaño). Los análisis de rayos X evidencian la formación de capas heterogéneas. La formación espontánea de este tipo de estructuras micrométricas durante la electrodeposición genera a su vez un patrón tanto topográfico como composicional que a su vez deriva en un patrón magnético. En cambio, al crecer el Co-In de forma confinada, en cavidades cilíndricas litografiadas de 50 µm de diámetro, se restringe el tipo de estructuras que conforman las espacio-temporales. Concretamente, en los microdiscos, sólo se generan de manera espontánea y únicamente a nivel composicional (es decir, prácticamente sin relieve topográfico) las estructuras que tienen forma de espiral. Como consecuencia, se ha revelado a través de técnicas avanzadas de caracterización de superficies, no sólo una modulación periódica del magnetismo, sino también de las propiedades eléctricas y mecánicas. También se ha llevado a cabo un estudio detallado de la sección de las capas de Co-In. El uso de técnicas de microscopia avanzadas ha revelado un crecimiento laminar que se expande a lo largo de todo el grosor de la capa (10 µm). Además, las variaciones composicionales locales de cada capa (175 nm de grosor aproximadamente) deja un patrón de franjas magnéticas. Por otro lado, se han depositado utilizando corriente continua nanopartículas bimetálicas de Fe-Rh con diferentes tamaños, relación Fe/Rh y grado de recubrimiento. El electrolito contenía Fe(III) para prevenir la formación de capas continuas. Las nanopartículas han quedado perfectamente adheridas al sustrato por lo que se pudieron emplear directamente como electrocatalizadores sin ningún proceso intermedio de inmovilización. Los análisis de espectroscopia de fotoelectrones emitidos por rayos X muestran que las nanopartículas son mayoritariamente metálicas. Dependiendo del contenido de hierro (15 at.\% ≤ Fe ≤ 36 at.\%), diámetro (20-80 nm) y grado de recubrimiento, las nanopartículas presentan una actividad catalítica diferente para la producción de hidrógeno en medio alcalino. Se han conseguido nanopartículas, fabricadas bajo condiciones de síntesis específicas, cuya actividad catalítica supera la de nanopartículas de Rh puro obtenidas a partir de un baño análogo. Finalmente, se han crecido por electrodeposición capas macroporosas altamente ordenadas de Fe-P en sustratos con litografía coloidal. Antes de la electrodeposición, se han depositado electroforéticamente esferas de poliestireno de 350 nm de diámetro que se ordenan sobre el sustrato. Para poder comparar resultados, también se han fabricado capas continuas de Fe-P. Tanto las capas continuas como las porosas presentan una relación Fe/P y un comportamiento magnético variable. Su actividad catalítica para las reacciones de evolución de hidrógeno y de oxígeno se ha investigado en medio alcalino.
This thesis dissertation covers the electrochemical synthesis and the characterization of the physical and physico-chemical properties of three different binary systems, namely cobalt-indium (Co-In), iron-rhodium (Fe-Rh) and iron-phosphorous (Fe-P). Several strategies toward systems miniaturization at micron- and nanoscales were pursued. Continuous thick Co-In films (25 at.\% ≤ Co ≤ 90 at.\%) featuring spatio-temporal patterns (targets, concentric rings and spirals of variable sizes) were prepared on flat, conductive Si/Ti/Au substrates. X-ray diffraction analyses evidenced the formation of highly heterogeneous coatings. The spontaneous formation of these micron-sized patterns during electrodeposition gave rise to topographical, compositional and, in turn, magnetic patterning. The confined growth of Co-In in lithographically patterned arrays of cylindrical holes of 50 µm in diameter imposed restrictions to the type of spatio-temporal motifs that could be formed. Specifically, only spiral-like patterns of purely compositional nature (with virtually no topographic features) were self-generated in the microdisks. As a result, not only a periodic modulation of the magnetic but also electric and mechanical properties was uncovered using advanced surface sensitive characterization techniques. A detailed assessment of the cross-sections of the continuous Co-In electrodeposits using electron microscopy techniques revealed a layer-by-layer growth mode spanning the whole deposit thickness (10 µm). The occurrence of local changes in composition within each layer (ca. 175 nm thick) also led to stripe-like magnetic patterning. Meanwhile, bimetallic Fe-Rh nanoparticles with different sizes, Fe/Rh ratios, and coverage degree were prepared by direct current electrodeposition from Fe(III) containing electrolyte solutions to prevent the formation of dense, continuous films. The nanoparticles were well-adhered to the substrate and could be directly tested as an electrocatalyst without the need for post-processing immobilization steps. The nanoparticles were mostly metallic as demonstrated by X-ray photoelectron spectroscopy analyses. Depending on the Fe content (15 at.\% ≤ Fe ≤ 36 at.\%), diameter (20-80 nm) and coverage, they showed dissimilar electrocatalytic activity towards hydrogen evolution reaction (HER) in alkaline media. Under specific synthetic conditions, the resulting nanoparticles outperformed pure Rh nanoparticles obtained from an analogous electrolytic solution. Finally, highly-ordered, macroporous Fe-P films were prepared by electrodeposition onto Si/Ti/Au substrates pre-patterned by colloidal templating. Prior to electrodeposition, polystyrene spheres of 350 nm in diameter were self-assembled on the substrate by electrophoresis. Fully dense Fe-P films were also electrodeposited for comparison purposes. Both dense and porous films showed tunable Fe/P ratios and magnetic behavior. The electrocatalytic activity towards HER and oxygen evolution reaction (OER) was investigated in alkaline media.

This thesis presents novel radio frequency microelectromechanical (RF MEMS) circuits based on the three-dimensional (3-D) micromachined coplanar transmission lines whose geometry is re-configured by integrated microelectromechanical actuators. Two types of novel RF MEMS devices are proposed. The first is a concept of MEMS capacitors tuneable in multiple discrete and well-defined steps, implemented by in-plane moving of the ground side-walls of a 3-D micromachined coplanar waveguide transmission line. The MEMS actuators are completely embedded in the ground layer of the transmission line, and fabricated using a single-mask silicon-on-insulator (SOI) RF MEMS fabrication process. The resulting device achieves low insertion loss, a very high quality factor, high reliability, high linearity and high self actuation robustness. The second type introduces two novel concepts of area efficient, ultra-wideband, MEMS-reconfigurable coupled line directional couplers, whose coupling is tuned by mechanically changing the geometry of 3-D micromachined coupled transmission lines, utilizing integrated MEMS electrostatic actuators. The coupling is achieved by tuning both the ground and the signal line coupling, obtaining a large tuneable coupling ratio while maintaining an excellent impedance match, along with high isolation and a very high directivity over a very large bandwidth. This thesis also presents for the first time on RF nonlinearity analysis of complex multi-device RF MEMS circuits. Closed-form analytical formulas for the IIP3 of MEMS multi-device circuit concepts are derived. A nonlinearity analysis, based on these formulas and on  measured device parameters, is performed for different circuit concepts and compared to the simulation results of multi-device  conlinear electromechanical circuit models. The degradation of the overall circuit nonlinearity with increasing number of device stages is investigated. Design rules are presented so that the mechanical parameters and thus the IIP3 of the individual device stages can be optimized to achieve a highest overall IIP3 for the whole circuit.The thesis further investigates un-patterned ferromagnetic NiFe/AlN multilayer composites used as advanced magnetic core materials for on-chip inductances. The approach used is to increase the thickness of the ferromagnetic material without increasing its conductivity, by using multilayer NiFe and AlN sandwich structure. This suppresses the induced currents very effectively and at the same time increases the ferromagnetic resonance, which is by a factor of 7.1 higher than for homogeneous NiFe layers of same thickness. The so far highest permeability values above 1 GHz for on-chip integrated un-patterned NiFe layers were achieved.

QC 20140328

With the emergence of novel and more effective drug therapies, increased importance is being placed upon the methods by which these drugs are being delivered to the body. In conventional drug delivery systems, there is very little control over the release of drug. The effective concentration at the target site can be achieved by intermittent administration of grossly excessive doses, which, often results in constantly, unpredictable variations in plasma concentrations, with the risk of reaching levels below or above the therapeutic range leading to marked side effects. A plethora of formulation strategies mainly based on polymeric/lipid nanoparticles, are described in literature. Even though these systems are therapeutically advantageous in comparison to conventional systems, they remain insensitive to the changing metabolic states of the body although the symptoms of most metabolic diseases follow a rhythmic pattern.A more appropriate and effective approach of managing some of these conditions lies in the chronotherapy. This approach allows for pulsed or self-regulated drug delivery which is adjusted to the staging of biological rhythms, since the onset of certain diseases exhibits strong circadian temporal dependence. In order to reach the objective of mimicking the biophysical and biochemical processes of pathological states, many innovations in material design for drug delivery systems (DDS) that are able to release the therapeutic payload-on-demand were done to release the therapeutic agent only when it is required, according to the physiological need. The development of multidisciplinary research teams has brought huge advantages in the design, fabrication and utilization of such smart systems, especially in the pharmaceutical field. Interestingly, numerous smart polymeric materials exhibit a response to a specific stimulus. A step further, the elaboration of purpose-built monomers can give rise to compounds with tunable sensitivities or multi-stimuli responsiveness. These smart polymers demonstrate an active responsiveness to environmental (or external) signals and change their physicochemical properties as designed (e.g. conformation, solubility, shape, charge or size). As far as the stimuli are concerned, they consist of physical (e.g. temperature, ultrasound, light, electricity, magnetic or mechanical stress), chemical (e.g. pH, ionic strength) and biological signals (e.g. enzymes, biomolecules). Due to the intrapersonal variabilities which may make internal stimuli hazardous, externally controlled systems rely on externally applied stimuli that are produced by stimuli-generating devices, which results in pulsed drug delivery. This type of delivery may be rapid and allows a transient release of a determined amount of drug within a short period of time immediately after a pre-determined off-release period. A novel strategy for the formation of multi-stimuli responsive materials endowed with pH, magnetic and light sensitivity was achieved. The approach relied on the incorporation of magnetic tetrahalogenoferrate(III) anions along a polymeric backbone based on poly(2-(N,N-dimethylamino) ethyl meth-acrylate) (PDMAEMA). Starting from the same PDMAEMA, quaternized pending amine groups with various halide derivatives gave rise to magnetic materials after anion metathesis. Measuring the magnetic susceptibility of these materials exhibited that the magnetic susceptibility increased as the substituted group size decreased (become smaller) which was apparently related to the steric hindrance around the ionic pendants. Additionally, a good correlation between the magnetic susceptibility and ferric content was found. Additional experimental and theoretical Raman analyses allowed the determination of the nature of the magnetic species constituting the materials. This strategy further offers the opportunity to tailor the magnetic response through partial ammonium salt formation. In order to merge the magnetic properties of ferric-based materials with another stimuli-responsive functionality, random copolymers containing DMAEMA (D) with diazobenzene (A) unit were prepared. So, three copolymers PDA were synthesized (with targeted D/A ratios 4/6 (PDA4), 6/4 (PDA6) and 8/2 (PDA8)). Meanwhile, different degrees of amine quaternization (10, 50 and 100 %) were applied, which led to the following polymeric salts PDAX/Y where X = 4, 6, 8 (referring to the percentage of the DMAEMA unit) and Y = 10, 50 and 100 (referring to the percentage of quaternized amine groups). Finally, the aforementioned materials were converted into magnetic polymers by anion exchange. As a result, magnetic responses correlated well with amount of iron oxide in these compounds and the amount of ionic pending groups along the backbone. Moreover, the remaining tertiary amines conferred pH sensitivity to the polymers whereas the diazobenzene units ensured light responsiveness through the well-established trans-to-cis isomerization.In order to functionalize these materials in the pharmaceutical field, an intelligent delivery system was prepared. Firstly, an attempt to formulate riboflavin-5’-phosphate sodium (RPS) loaded on PDA8 microspheres was made using double emulsion evaporation method. Meanwhile, prednisolone (PRD) microspheres were prepared using s/o/w emulsion technique. Subsequently, coating systems of cochineal red tablets were developed. These tablets were coated with polymer solution (using each of three types of copolymers: PDA8, PDA6, and PDA4) until the desired percentage of the coating was achieved (10, 15, and 20 % w/w). The cumulative release profiles of cochineal red tablets coated with PDA8, PDA6, and PDA4 showed a pH-sensitive release behavior. The release in the neutral media (pH ≈ 7.0) was very slow (less than 3 % after one hour). Then, after changing the pH to 1.2, an increase in the release of cochineal was observed. Furthermore, the cumulative release of cochineal red was at the highest value for the PDA8 and the lowest for PDA4 depending on the percentage of PDMAEMA moieties. Moreover, by increasing the percentage of the coating from (10, 15 to 20 % w/w), the cumulative release of cochineal decreased. Therefore, the copolymer PDAX can be used for controlling the release of drug by changing the pH value.Finally, the cochineal tablets coated with PDA6 (10 %) showed features of light sensitivity. The release of cochineal red from coated tablets was only due to the switching in the conformational trans/cis isomerization of azobenzene moieties upon irradiation, which was confirmed by comparing the release of coated tablets with uncoated tablets upon irradiation.
Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie)
info:eu-repo/semantics/nonPublished

The subject of this thesis explores the development of magnetic hyperthermia technology at the preclinical stage. Magnetic hyperthermia uses magnetic nanoparticles as functionalisable agents, targeted to cancer sites. They can then be non-invasively activated by alternating magnetic fields to deliver lethal doses of heat to the cancer cells with minimal damage to healthy tissue. This work concentrates on several complex aspects concealed within the conceptual simplicity of magnetic hyperthermia. One key aspect lies in the design of the alternating magnetic field generator. Here, a novel device, the MACH system, that exceeds currently available AC magnetic field generators in performance, form factor and versatility is described and evaluated. Electronic characteristics for 5 different configurations, ranging from a solenoidal to a flat applicator, are presented. Furthermore, magnetic field distributions in and around the applicator coil were modeled for all real configurations and two hypothetical models. These models revealed that in certain configurations high magnetic field gradients exist, prompting careful positioning of samples in real experiments. Sixteen commercially available iron-oxide nanoparticles with potential as hyperthermia candidates were characterised using photon correlation spectroscopy, atomic emission spectroscopy, asymmetric field-flow fractionation, spectrophotometric iron trace analysis, calorimetric analysis and magnetometry. To compare the heating rates of nanoparticle samples, a new design rule parameter, the intrinsic loss parameter (ILP), was introduced to replace the status quo, the equipment-dependent specific absorption rate (SAR). The results highlight a magnetic crystal size dependence with ILP, and also imply that some commercial samples are approaching the best achievable results. Finally, the commercial potential of the MACH system is evaluated in light of new applications that exploit its unique, distinguishing features. Hyperthermia cancer treatment was concluded to have the greatest potential on the long run, with the adhesives and thermoset polymer industry being lucrative short-term targets.

Portland cements (PC) and blended PCs are the most commonly used binders in stabilisation/solidification (S/S) applications. However, such systems have found limited suitability with organic contaminants. Moreover, the high alkalinity associated with PC militates against the soil microbes and hence, hinders the natural attenuation of the organics. Furthermore, the production of PC is not only an extremely resource and energy intensive process but also has significant negative environmental impacts. Thus, with the aim of tackling the above issues, this research has been focused on firstly developing and applying a low-pH binder system for facilitating microbial activity in parallel to the S/S of heavy metals, and additionally on investigating the application of less environmentally damaging cement in S/S. These were addressed employing two novel binders; viz. low pH magnesia phosphate cements (MPCs) and reactive magnesia (MgO) cements respectively. This study was successful in formulating MPC mixes which not only developed low-pH ranges favourable to soil microbes but were also more effective in immobilising heavy metals than PC-based binders in an individual contamination scenario. Furthermore, the heavy metal stabilisation performance of the MPC mixes suffered negligible impact in the presence of organic contaminant.

The UK Committee on Radioactive Waste Management (CoRWM) recommended, in 2006, that geological disposal coupled with safe and secure interim storage should have been the way forward for the long-term management of the UK’s higher activity wastes. The design of the underground repository contemplates the presence of bentonite plugs to seal access galleries and deposition boreholes and hence the interaction between the clay-based backfill material and the underground water. Remote monitoring of the fluid saturation of the barrier, the waste canisters and of the surrounding subsurface Geological Disposal Facility environment assumes a relevant importance to guarantee the safety of the repository and to increase the confidence and the reliance of the communities living in areas potentially affected by the repository over time. This remote monitoring of the Engineered Barrier System represents a technical challenge due to the unsuitability of some of the traditional geotechnical techniques or to the intrinsic unreliability of many geophysical prospecting techniques in providing information about the evolution of the Thermo-Hydro-Mechanical-Chemical coupling of the system over long timescales up to and including post-closure evolution. In this project, I offer an initial approach to an innovative way of using mineral magnetism, and, in particular, I analyse the possible exploitation of corrosion-induced variations of the magnetic properties of several magnetic materials to monitor water saturation in the Engineered Barrier System and its evolution through time. Initially the reactivity of several natural and synthetic materials is tested under different “extreme” conditions to analyse the feasibility of the research concept and identify the materials more adapt to carry out the job. The effects that the corrosion of the magnetic materials has on the clay matrix is also analysed in detail throughout all the thesis work. The initial tests lead to the identification of specific transitions in the hysteretic behaviour of three of the initial candidates (Nd-Fe-B, AlNiCo and SmCo alloys). These three materials are subsequently tested under conditions closer to a real “evolved” Barrier System, where the groundwater interacts, with cementiferous grout producing hyperalkaline leachates. The final tests consider the temporal evolution (after 4, 8 and 12 months) of the magnetic properties of these materials in a dysoxic environment under imposed fluid-flow. The results show a clear change in the hysteretic properties of the three materials analysed and the feasibility of the monitoring of the Barrier fluid saturation in the short-term. Furthermore, the corrosion of the magnets, under the conditions applied, did not cause formation of non-swelling clays.

Micro- or nanometer sized magnetic particles (beads) currently have a vast range of life science applications in, for example, bioseparation techniques, cancer therapy, development of contrast agents and biosensing techniques. In the latter field, magnetic beads offer several unique advantages, including minimal background signals, physical and chemical stability and low manufacturing costs. Because of these properties, magnetic biosensing techniques are potential candidates for low-cost, easy-to-use molecular diagnostic devices. This doctoral thesis focuses mainly on the proof of principle and further development of a new magnetic biosensor platform for detection of DNA targets, a potential candidate for a new generation of low-cost, easy-to-use diagnostic devices: the Volume-Amplified Magnetic Nanobead Detection Assay (VAM-NDA). The VAM-NDA principle combines target recognition by padlock probe ligation followed by rolling circle amplification (RCA) of the reacted probes with changes in Brownian relaxation behaviour of magnetic nanobeads (typically ~100 nm in diameter) induced by a change in hydrodynamic bead volume. More specifically, the RCA products (coils, typically ~1 μm in diameter) are detected magnetically by adding magnetic beads tagged with detection probes complementary to part of the repeating RCA-coil sequence. Thus, depending on the target concentration, a certain quantity of beads binds to the coils by base-pair hybridisation (bead immobilisation), resulting in a dramatic bead volume increase, which is then detected by measuring the complex magnetisation spectrum. Use of a commercial SQUID magnetometer for measuring complex magnetisation resulted in a detection limit in the low pM range for DNA targets with excellent quantification accuracy. Simultaneous multiplexing was also evaluated. The stability and aging of typical commercial ferrofluids (suspensions of magnetic beads) were investigated by measuring the complex magnetisation of and interbead interactions in oligonucleotide-functionalised ferrofluids. In summary, the bead surface characteristics were found to have a strong impact on the measured dynamic magnetic properties.

L’insuffisance cardiaque est un problème de santé publique dans les pays développés, touchant 1 à 2% de la population générale, mais dont la prévalence atteint 10% après 70 ans. Les progrès thérapeutiques ont permis d’améliorer le pronostic des patients, notamment ceux ayant une altération de la fonction systolique ventriculaire gauche. Les troubles du rythme sont fréquents et nécessitent une pris en charge particulière au cours des situations d’insuffisance cardiaque. Cependant, il reste des questions non résolues : comment améliorer l’efficacité du traitement de l’insuffisance cardiaque à fonction systolique préservée, comment mieux sélectionner les patients pouvant bénéficier de la prévention primaire de la mort subite par un défibrillateur implantable, les patients âgés peuvent-ils bénéficier de la même prise en charge que les patients plus jeunes, et pour finir comment améliorer les résultats de l’ablation de fibrillation auriculaire dans les situations d’insuffisance cardiaque. Nous avons mis en place une étude prospective chez des patients présentant une dysfonction diastolique pour évaluer l’intérêt de l’algorithme de surveillance de l’apnée du sommeil disponible dans des stimulateurs cardiaques. En parallèle, nous avons analysé l’impact de l’évaluation par résonance magnétique des patients candidats à un défibrillateur sur la prédiction des évènements rythmiques, mais aussi le devenir des patients de plus de 75 ans appareillés avec un système de resynchronisation cardiaque. Enfin, nous nous sommes intéressés aux résultats d’un nouveau système de cartographie électroanatomique ultra-haute densité pour guider les procédures d’ablation de troubles du rythme supraventriculaires complexes chez des patients insuffisants cardiaques comparés à des patients contrôles
Heart failure is a major public health issue in developed countries, with a prevalence of 1-2% of global population, rising to 10% after 70 years of age. Therapeutic progresses have succeeded in improving patients’ prognosis, particularly in case of reduced left ventricular ejection fraction. Rhythm abnormalities are frequent, and need special consideration in case of heart failure. Meanwhile, there are still some gaps in the evidence: heart failure with preserved systolic function is complex and difficult to treat, primary prevention of sudden cardiac death is effective but there is a need to better select candidates, whether elderly patients should be treated as younger individuals, and finally how to improve outcomes of atrial fibrillation catheter ablation. Firstly, we have conducted a prospective study to evaluate the Sleep Apnea Monitoring algorithm provided in a novel pacemaker in patients with diastolic dysfunction. Besides, we analyzed whether magnetic resonance imaging could predict cardiac outcomes in patients with an implantable cardioverter defibrillator better than echocardiography. We also reported the outcomes of the cardiac resynchronization therapy in patients ≥75 years old compared to younger patients. Finally, we studied the results of a novel ultra-high density mapping system to guide ablation procedures of complex atrial arrhythmias in heart failure patients compared to controls

This thesis presents results of novel methodologies applied to oriented systems. Both pure liquid crystalline materials as well as molecules oriented in liquid crystalline matrices have been studied. In particular this thesis presents investigations related to various aspects of NMR in liquid crystalline media, such as, assignment of resonances and the study of director dynamics of spinning liquid crystals in different phases and with different symmetry. Simplified methods for structure determination of solutes dissolved in liquid crystal solvents have been proposed. Diffusion ordered spectroscopy has been used to study a mixture of liquid crystals of opposite diamagnetic susceptibility at its coexistent phase. The methods presented represent novel techniques to characterize the liquid crystalline phase. NMR spectroscopy which has become a method of choice for understanding ordering mechanisms of mesogens requires a robust method for obtaining assignments of the NMR spectra of various nuclei that are found in the mesogens [1, 2]. It turns out that the spectra in the isotropic phase and in the nematic phase of a liquid crystal molecule are very different due to the presence of chemical shift anisotropy in the mesophase spectrum. There are a host of methodologies available for assigning spectra in the isotropic phase [3]. These methods however fail, when applied to the spectrum of the molecules in the mesophase due to the dominating role of strong anisotropic interactions, such as homonuclear couplings among protons. Problems arising while assigning spectral lines of liquid crystals in their nematic phase have been dealt with in chapter 2. To circumvent these problems, a property of the liquid crystal molecules under off-magic angle sample spinning can be utilized. It has been shown by Courtieu et al. [4] that the director/symmetry axis of a Δχ + ve liquid crystal aligns along the spinning axis for θ between 0 ° and θm, where θ is the angle between the spinning axis and the magnetic field and θm = 54.7° is the magic angle. It may be noted that the spectrum of θ = 0° spinning angle corresponds to the normal static spectrum, while the spectrum of θ = θm corresponds to the isotropic spectrum. In an earlier study, Teearr et al. [5] had recorded the 13C liquid crystal spectra as a function of very closely spaced θ values from 90° all the way up to 0°. From these plots of chemical shift versus the angle of spinning, it is possible to follow the trajectory of each 13C line from its position from θ = θm to θ = 0° and then match the spectrum in the isotropic phase (equivalently the magic angle sample spinning spectrum of the nematic phase) to the spectrum of the static sample in the nematic phase. However this method requires recording spectra at closely spaced angle intervals, so that one can unambiguously follow the trajectory of each of the lines without missing out any crossover of trajectories. However, this operation is time consuming. In this thesis we propose an alternate method, where we utilize the fact that the above trajectory has a very distinct relationship to the isotropic and anisotropic chemical shift and the problem of assignment does not require a continuous variation of angles, but just a few selected experiments should enable the assignment of the spectrum in the anisotropic phase. Thus the method of assignment has been made simpler and faster. It is shown that in addition to the assigned isotropic spectrum, only one other Off-magic angle spinning spectrum whose spinning angle θ is accurately known is necessary to obtain the complete assignment of the static spectrum. This procedure is non-trivial due to possibilities of errors in assignments arising out of inaccuracies in the knowledge of chemical shifts and the spinning angle. A computational procedure is proposed to take into account deviations arising out of non-ideal experimental conditions. A discussion regarding the details of the procedure and also situations where there can be ambiguities and how they can be resolved has been elaborated. The developed method has been demonstrated on a well known thermotropic liquid crystalline system, N-(4-ethoxybenzylidene)-4-n-butlyaniline [EBBA]. Since assignment of resonances in the nematic phase is a primary requirement for any further analysis regarding the ordering and deeper understanding of the role of various substituents in the mesogens we believe our novel prescription will be of immense use and utility. The third chapter presents the study of director dynamics in a lyotropic liquid crystal composed of Potassium laurate, 1-Decanol and D2O [6] under variable angle sample spinning using 2H NMR spectrum of D2O. A very interesting interplay of the magnetic orienting torque due to interaction of the liquid crystal director with the magnetic field and viscous torque arising from the viscosity of the sample on the director comes to fore. The relative magnitude of these torques has a direct bearing on the spectral pattern and line shapes observed, providing valuable insights into magnetohydrodynamics of the spinning liquid crystals. This study leads to even more interesting behavior for liquid crystals which deviate from uniaxial symmetry. This competition between magnetic and viscous torques has been quantitatively visualized by simulation of the 2H spectrum. It has been possible to visualize the observed spread in the director distribution arising out of viscous torque in terms of the energetics of the system under fast spinning. If the magnetic torque dominates over the viscous torque, then the equilibrium corresponds to the director orientation of δ = 0° where the energy is at its minimum. However the viscous and magnetic torques can become comparable as it may happen if the spinning angle is close to the magic angle or when the Δχ of the system is small. In those circumstances additional energy from the viscous torque causes the distribution of the director orientation to spread further away from δ = 0° for a positive Δχ liquid crystal. The trigonometric factor [P2(cosθ)∗P2(cosδ)] being proportional to the total energy of the system has been plotted against the spinning angle. The spectrum of the biaxial phase [7] as a function of the spinning angle shows more interesting director distribution. Here the patterns of the director distribution are observed on either side of the magic angle due to the presence of more than one director. The patterns observed also have information about the symmetry of the phase. This work provides insights into magnetohydrodynamics of spinning liquid crystals and can also be of relevance to samples of biological interest such as bicelles with protein oriented in them [8]. The fourth chapter deals with a novel characterization method relevant for the biaxial phase [9]. As an off shoot of the previous chapter, it effectively overcomes the disadvantages of the previous experimental methods which require simulation and line shape fitting to extract useful parameters. The chapter also presents the measurement of geometrical parameters of oriented solutes in phases exhibiting biaxial symmetry. The measured parameters show the effect of the onset of biaxiality as significant deviation in the value of the measured parameter. The utility of liquid crystalline media as solvents in high resolution NMR spectroscopy has been very rewarding since the pioneering work of Saupe and Englert [6]. The intramolecular interactions within solutes are only partially averaged. As a result one obtains a liquid like spectrum while at the same time very useful anisotropic interactions such as dipolar couplings, chemical shift anisotropies, quadrupolar couplings and anisotropic part spin-spin J couplings are extracted [10]. NMR spectra of molecules dissolved in thermotropic liquid crystals have long been used to obtain structural and orientational information. As the same time the complexity of the spectrum increases with the increase in the number of spins and the reduction in symmetry of the molecule, which can make the spectral analysis forbidding. Generally proton spectra have been used to obtain the geometry of the proton skeleton of the molecule and the information that includes dilute X nuclei such as 13C and 15N are available only from satellites which are buried in the intense proton spectrum. Different inequivalent dilute spins coupled to protons form different coupled spin systems in their natural abundance and appear as satellites in the proton spectra. Identification of transitions belonging to each of the spin system is essential to determine heteronuclear dipolar couplings, which is a formidable task. The fifth chapter deals with development of the techniques to obtain the complete structure of the dissolved molecules including nuclei other than protons in their natural abundance. The use of inverse experiments has been elaborated to overcome the problems of sensitivity and complexity for solute molecules having larger number of spins. In the present study using HSQC and HMQC experiments, we have selectively detected spectra of each inequivalent rare spin coupled to protons in pyrazine, pyrimidine and pyridazine dissolved in thermotropic Phase 4 and Phase 5 liquid crystal solvents. This way we could obtain enhancement in the intensity of satellites signals without the interference from the signals connected to the major isotopomers. Besides, we could resolve a complex spectrum into its sub-spectra corresponding to individual 13C and 15N isotopomers. This separation of the spectra corresponding to individual sub-spin systems makes analysis easy and helps analyze larger systems with higher number of spins and lower symmetry. Besides 1H-1H dipolar couplings, 13C-1H and 15N-1H dipolar couplings have been determined in natural abundance, thereby giving the complete dipolar coupling network between all the spins in the molecule. In this treatment pyrazine, pyrimidine and pyridazine have been used as examples of methodology developed. It is expected that the method will be of wider use for several other similar systems. Chapter six describes the diffusion ordered spectroscopic investigation [11] of a phase arising out of mixing together two liquid crystals having opposite signs of diamagnetic susceptibility anisotropy [12]. Towards this end we have used CH3CN as a probe molecule. The spectrum of CH3CN has with it the information about the parallel or perpendicular orientation of the phase. Such a mixture of liquid crystals have shown interesting behavior at the critical temperature where the two phases seem to coexist. It has been an interesting question to understand what exactly happens for the molecular orientation when the macroscopic anisotropy Δχ vanishes. Earlier Jokisaari et al. [13] have varied the temperature very finely taking due precautions to maintain homogeneity and stability of temperature to the tune of ±0.05K across the sample volume. Their observation of a powder pattern exactly in the critical temperature was interpreted as arising out of a distribution of directors equally oriented in all directions. In our experiments we have measured the diffusion coefficient of the probe molecule i.e. acetonitrile as we change the temperature of the system through the critical temperature. At the critical temperature we have a situation of being able to measure the parallel and perpendicular orientational diffusion coefficients simultaneously. The measurements show that the parallel component of the diffusion coefficient has reduced and the perpendicular component has increased in comparison to the trend in the immediate neighboring temperatures, thereby indicating that at the exact critical condition the liquid crystal mixture consists of an isotropic distribution of molecules. As a check to rule out any exchange of molecules in different domains of parallel and perpendicular orientations an EXSY experiment was conducted with a mixing time which was same as that of the diffusion delay in the DOSY experiment. The EXSY spectrum showed no exchange cross peaks between the two orientations, this confirms that the anisotropy of the diffusion vanishes at the critical temperature. Nematic liquid crystals exhibit a rich variety of phases and properties. NMR is a very powerful tool to study the various phases at the microscopic and molecular level. It has also turned out that some of these properties can be usefully utilized for investigation of both small and large molecules by NMR. Thus this thesis has attempted to expand several of the techniques already available for various applications and extend the utility of NMR for the study of partially ordered systems.

This thesis presents results of novel methodologies applied to oriented systems. Both pure liquid crystalline materials as well as molecules oriented in liquid crystalline matrices have been studied. In particular this thesis presents investigations related to various aspects of NMR in liquid crystalline media, such as, assignment of resonances and the study of director dynamics of spinning liquid crystals in different phases and with different symmetry. Simplified methods for structure determination of solutes dissolved in liquid crystal solvents have been proposed. Diffusion ordered spectroscopy has been used to study a mixture of liquid crystals of opposite diamagnetic susceptibility at its coexistent phase. The methods presented represent novel techniques to characterize the liquid crystalline phase. NMR spectroscopy which has become a method of choice for understanding ordering mechanisms of mesogens requires a robust method for obtaining assignments of the NMR spectra of various nuclei that are found in the mesogens [1, 2]. It turns out that the spectra in the isotropic phase and in the nematic phase of a liquid crystal molecule are very different due to the presence of chemical shift anisotropy in the mesophase spectrum. There are a host of methodologies available for assigning spectra in the isotropic phase [3]. These methods however fail, when applied to the spectrum of the molecules in the mesophase due to the dominating role of strong anisotropic interactions, such as homonuclear couplings among protons. Problems arising while assigning spectral lines of liquid crystals in their nematic phase have been dealt with in chapter 2. To circumvent these problems, a property of the liquid crystal molecules under off-magic angle sample spinning can be utilized. It has been shown by Courtieu et al. [4] that the director/symmetry axis of a Δχ + ve liquid crystal aligns along the spinning axis for θ between 0 ° and θm, where θ is the angle between the spinning axis and the magnetic field and θm = 54.7° is the magic angle. It may be noted that the spectrum of θ = 0° spinning angle corresponds to the normal static spectrum, while the spectrum of θ = θm corresponds to the isotropic spectrum. In an earlier study, Teearr et al. [5] had recorded the 13C liquid crystal spectra as a function of very closely spaced θ values from 90° all the way up to 0°. From these plots of chemical shift versus the angle of spinning, it is possible to follow the trajectory of each 13C line from its position from θ = θm to θ = 0° and then match the spectrum in the isotropic phase (equivalently the magic angle sample spinning spectrum of the nematic phase) to the spectrum of the static sample in the nematic phase. However this method requires recording spectra at closely spaced angle intervals, so that one can unambiguously follow the trajectory of each of the lines without missing out any crossover of trajectories. However, this operation is time consuming. In this thesis we propose an alternate method, where we utilize the fact that the above trajectory has a very distinct relationship to the isotropic and anisotropic chemical shift and the problem of assignment does not require a continuous variation of angles, but just a few selected experiments should enable the assignment of the spectrum in the anisotropic phase. Thus the method of assignment has been made simpler and faster. It is shown that in addition to the assigned isotropic spectrum, only one other Off-magic angle spinning spectrum whose spinning angle θ is accurately known is necessary to obtain the complete assignment of the static spectrum. This procedure is non-trivial due to possibilities of errors in assignments arising out of inaccuracies in the knowledge of chemical shifts and the spinning angle. A computational procedure is proposed to take into account deviations arising out of non-ideal experimental conditions. A discussion regarding the details of the procedure and also situations where there can be ambiguities and how they can be resolved has been elaborated. The developed method has been demonstrated on a well known thermotropic liquid crystalline system, N-(4-ethoxybenzylidene)-4-n-butlyaniline [EBBA]. Since assignment of resonances in the nematic phase is a primary requirement for any further analysis regarding the ordering and deeper understanding of the role of various substituents in the mesogens we believe our novel prescription will be of immense use and utility. The third chapter presents the study of director dynamics in a lyotropic liquid crystal composed of Potassium laurate, 1-Decanol and D2O [6] under variable angle sample spinning using 2H NMR spectrum of D2O. A very interesting interplay of the magnetic orienting torque due to interaction of the liquid crystal director with the magnetic field and viscous torque arising from the viscosity of the sample on the director comes to fore. The relative magnitude of these torques has a direct bearing on the spectral pattern and line shapes observed, providing valuable insights into magnetohydrodynamics of the spinning liquid crystals. This study leads to even more interesting behavior for liquid crystals which deviate from uniaxial symmetry. This competition between magnetic and viscous torques has been quantitatively visualized by simulation of the 2H spectrum. It has been possible to visualize the observed spread in the director distribution arising out of viscous torque in terms of the energetics of the system under fast spinning. If the magnetic torque dominates over the viscous torque, then the equilibrium corresponds to the director orientation of δ = 0° where the energy is at its minimum. However the viscous and magnetic torques can become comparable as it may happen if the spinning angle is close to the magic angle or when the Δχ of the system is small. In those circumstances additional energy from the viscous torque causes the distribution of the director orientation to spread further away from δ = 0° for a positive Δχ liquid crystal. The trigonometric factor [P2(cosθ)∗P2(cosδ)] being proportional to the total energy of the system has been plotted against the spinning angle. The spectrum of the biaxial phase [7] as a function of the spinning angle shows more interesting director distribution. Here the patterns of the director distribution are observed on either side of the magic angle due to the presence of more than one director. The patterns observed also have information about the symmetry of the phase. This work provides insights into magnetohydrodynamics of spinning liquid crystals and can also be of relevance to samples of biological interest such as bicelles with protein oriented in them [8]. The fourth chapter deals with a novel characterization method relevant for the biaxial phase [9]. As an off shoot of the previous chapter, it effectively overcomes the disadvantages of the previous experimental methods which require simulation and line shape fitting to extract useful parameters. The chapter also presents the measurement of geometrical parameters of oriented solutes in phases exhibiting biaxial symmetry. The measured parameters show the effect of the onset of biaxiality as significant deviation in the value of the measured parameter. The utility of liquid crystalline media as solvents in high resolution NMR spectroscopy has been very rewarding since the pioneering work of Saupe and Englert [6]. The intramolecular interactions within solutes are only partially averaged. As a result one obtains a liquid like spectrum while at the same time very useful anisotropic interactions such as dipolar couplings, chemical shift anisotropies, quadrupolar couplings and anisotropic part spin-spin J couplings are extracted [10]. NMR spectra of molecules dissolved in thermotropic liquid crystals have long been used to obtain structural and orientational information. As the same time the complexity of the spectrum increases with the increase in the number of spins and the reduction in symmetry of the molecule, which can make the spectral analysis forbidding. Generally proton spectra have been used to obtain the geometry of the proton skeleton of the molecule and the information that includes dilute X nuclei such as 13C and 15N are available only from satellites which are buried in the intense proton spectrum. Different inequivalent dilute spins coupled to protons form different coupled spin systems in their natural abundance and appear as satellites in the proton spectra. Identification of transitions belonging to each of the spin system is essential to determine heteronuclear dipolar couplings, which is a formidable task. The fifth chapter deals with development of the techniques to obtain the complete structure of the dissolved molecules including nuclei other than protons in their natural abundance. The use of inverse experiments has been elaborated to overcome the problems of sensitivity and complexity for solute molecules having larger number of spins. In the present study using HSQC and HMQC experiments, we have selectively detected spectra of each inequivalent rare spin coupled to protons in pyrazine, pyrimidine and pyridazine dissolved in thermotropic Phase 4 and Phase 5 liquid crystal solvents. This way we could obtain enhancement in the intensity of satellites signals without the interference from the signals connected to the major isotopomers. Besides, we could resolve a complex spectrum into its sub-spectra corresponding to individual 13C and 15N isotopomers. This separation of the spectra corresponding to individual sub-spin systems makes analysis easy and helps analyze larger systems with higher number of spins and lower symmetry. Besides 1H-1H dipolar couplings, 13C-1H and 15N-1H dipolar couplings have been determined in natural abundance, thereby giving the complete dipolar coupling network between all the spins in the molecule. In this treatment pyrazine, pyrimidine and pyridazine have been used as examples of methodology developed. It is expected that the method will be of wider use for several other similar systems. Chapter six describes the diffusion ordered spectroscopic investigation [11] of a phase arising out of mixing together two liquid crystals having opposite signs of diamagnetic susceptibility anisotropy [12]. Towards this end we have used CH3CN as a probe molecule. The spectrum of CH3CN has with it the information about the parallel or perpendicular orientation of the phase. Such a mixture of liquid crystals have shown interesting behavior at the critical temperature where the two phases seem to coexist. It has been an interesting question to understand what exactly happens for the molecular orientation when the macroscopic anisotropy Δχ vanishes. Earlier Jokisaari et al. [13] have varied the temperature very finely taking due precautions to maintain homogeneity and stability of temperature to the tune of ±0.05K across the sample volume. Their observation of a powder pattern exactly in the critical temperature was interpreted as arising out of a distribution of directors equally oriented in all directions. In our experiments we have measured the diffusion coefficient of the probe molecule i.e. acetonitrile as we change the temperature of the system through the critical temperature. At the critical temperature we have a situation of being able to measure the parallel and perpendicular orientational diffusion coefficients simultaneously. The measurements show that the parallel component of the diffusion coefficient has reduced and the perpendicular component has increased in comparison to the trend in the immediate neighboring temperatures, thereby indicating that at the exact critical condition the liquid crystal mixture consists of an isotropic distribution of molecules. As a check to rule out any exchange of molecules in different domains of parallel and perpendicular orientations an EXSY experiment was conducted with a mixing time which was same as that of the diffusion delay in the DOSY experiment. The EXSY spectrum showed no exchange cross peaks between the two orientations, this confirms that the anisotropy of the diffusion vanishes at the critical temperature. Nematic liquid crystals exhibit a rich variety of phases and properties. NMR is a very powerful tool to study the various phases at the microscopic and molecular level. It has also turned out that some of these properties can be usefully utilized for investigation of both small and large molecules by NMR. Thus this thesis has attempted to expand several of the techniques already available for various applications and extend the utility of NMR for the study of partially ordered systems.

碩士
國立成功大學
電機工程學系
87
Electromagnetic levitation system makes use of magnetic force to resist gravity so that the iron ball can be suspended on the air without any mechanical contact. A magnetic levitation system is one of the famous mechatronic systems. Implementation of a classical magnetic levitation control system should include a set of electromagnetic coil, an iron ball, a set of position sensor, a driver, and a designed controller. This thesis, however, brings up a novel concept exploiting two electromagnetic coils to control position of the ball. In this thesis, a mathematic model of magnetic levitation system is examined first. Secondly, we design a fuzzy controller and a fuzzy sliding-mode controller for this system and compare their performances by computer simulations. Furthermore, we design and set up the overall system including the frame, the electromagnetic coil, the electrical circuits of the sensor, driver and controller. The physical experiments are realized by two approaches. One is to use the analog phase lead controller. The other one is to exploit the hybrid controllers, which are accomplished by an analog controller and a digital fuzzy sliding-mode controller. All these experimental result are recorded on the videotape and demonstrate the validity of the proposed architecture.

碩士
南台科技大學
機械工程系
93
The requirements of high speed and high accuracy become more demanding in the trend of industry development. Positioning systems of high accuracy and great tracking performance, such as X-Y stages in wafer transportation, play an important role therewith. Such a system can be realized by a magnetic levitation (maglev) stage, driven by voice coil motors (VCM). The magnetic levitation endows it with the contact-free characteristics, which makes it suitable in clean room and vacuum operation. Nevertheless, the controller used must be robust enough in the presence of uncertainties. Therefore, we first build a model of a dual-axis maglev system, for which we design a suitable controller to meet the requirements of high tracking performance. Both backstepping method and sliding mode control are used for comparison. Finally, direct adaptive control laws are implemented into either controller to ensure sufficient robustness to parameter variation. Convergence is guaranteed since every controller is derived using the Lyapunov stability theorem. The MATLAB simulation demonstrates that the dual-axis maglev system settles very fast with negligible errors for arbitrary trapezoidal trajectories using any of the proposed adaptive controllers.

碩士
雲林科技大學
電機工程系碩士班
96
The requirements of high speed and high accuracy demand become the recent trend in industry development. Therefore, servo position systems of high accuracy and excellent tracking performance play important roles. The magnetic ball suspension system uses the magnetic force to maintain the magnetic ball suspension in the air. It avoids the contact friction for the machine elements. However, the system is a nonlinear and open loop unstable system. In classical control, the controller is designed by using the operating point linearization method. It is suitable in the small region of operating point and sensitive to the parameter variations and external disturbances. In this thesis, we first build a model of a magnetic ball suspension system. In controller part, the backstepping controller and sliding mode controller are proposed. The fuzzy law and neural network estimators are designed to estimate the bounds of uncertainties and the stability of fuzzy and neural network algorithm are approved by Lyapunov stability theory. Finally, we employ the experiments to validate the proposed controller for estimating boundary of uncertainties, eliminating steady state error and tracking the position commands.

碩士
國立成功大學
奈米科技暨微系統工程研究所
97
Formation of emulsion droplets is crucial for a variety of industrial and scientific applications. This study presents a new microfluidic emulsion system capable of generating tunable and uniform-sized droplets and subsequently deflecting these droplets at various inclination angles using a combination of flow-focusing and moving-wall structures. A pneumatic air chamber was used to activate the moving-wall structures, located nearby the outlet of the flow-focusing microchannels, such that the sheath flows can be locally accelerated. The flow-focusing microchannel forced the continuous phase and disperse phase fluids to pass through a narrow orifice. With this approach, the size of the droplets can be fine-tuned and sorted without adjusting the syringe pumps. One can control the shear force by adjust the sheath flows velocities. Thus, the droplets size can be easily controlled by the moving-wall structure without changing the flow rate of a syringe pump. Experimental data showed that droplets with diameters ranging from 31.4 to 146.2 μm with a variation of less than 5.39% can be generated. Besides, by using different operation modes, droplets can be sorted upwards or backwards with an inclination angle ranging from 0° to 53.5°. Meanwhile, the droplet diameters and the inclination angle can be adjusted at the same time. By using a similar droplet-based platform, magnetic alginate particles was also produced and collected successfully. A two-stage process, using a flow focusing method to generate magnetic alginate droplets in n-hexadecane, and then dripped them into the cross-linking buffer for solidification, was reported. The magnetic alginate droplets with diameters ranging from 56.4 to 102.4 μm were generated. The development of this microfluidic emulsion platform for generation of magnetic alginate droplets may be promising for applications in pharmaceuticals, cosmetics and food industries.

This doctoral thesis documents my research on novel devices and systems for terahertz (THz) spectroscopy and imaging. The research is particularly focused on the manipulation of THz radiation, including subwavelength concentration and low-loss wave guiding. One of the major obstacles for THz imaging is the poor spatial resolution due to the diffraction of the long-wavelength light source. To break this restriction, we build a THz near-field microscopy system by combining apertureless near-field scanning optical microscopy (ANSOM) with terahertz time-domain spectroscopy (THz-TDS). The experimental result indicates a sub-wavelength spatial resolution of about 10 micron. Abnormal frequency response of the ANSOM probe tip is observed, and a dipole antenna model is developed to explain the bandwidth reduction of the detected THz pulses. We also observe and characterize the THz wave propagation on the near-field probe in ANSOM. These studies not only demonstrate the feasibility of ANSOM in the THz frequency range, but also provide fundamental insights into the near-field microscopy in general, such as the broadband compatibility, the propagation effects and the antenna effects. Motivated by our study of the propagation effects in THz ANSOM, we characterize the guided mode of THz pulses on a bare metal wire by directly measuring the spatial profile of electric field of the mode, and find that the wire structure can be used to guide THz waves with outstanding performance. This new broadband THz waveguide exhibits very small dispersion, extremely low attenuation and remarkable structural simplicity. These features make it especially suitable for use in THz sensing and imaging systems. The first THz endoscope is demonstrated based on metal wire waveguides. To improve the input coupling efficiency of such waveguides, we develop a photoconductive antenna with radial symmetry which can generate radially polarized THz radiation matching the waveguide mode. Through THz-TDS measurements and theoretical calculations, we study the dispersion relation of the surface waves on metal wires, which indicates the increasing importance of skin effects for surface waves in the THz frequency range.

Carbohydrates are ubiquitous and important biomolecules. Initially thought to be dull, energy storing moieties, the importance of carbohydrates and their conjugates, glycoproteins and glycopilids, in cellular communication and various related processes has been well established. Carbohydrate recognition events are involved in the progression of various diseases, as the binding of pathogens to the host cells is carbohydrate mediated. Also the malfunctioning of carbohydrate processing enzymes has been implicated in life-threatening diseases. Thus there is tremendous interest in the design of molecules which can mimic the carbohydrates and provide insights into the mechanisms of action of carbohydrate processing enzymes. Such designer glycomimics possess several advantages over the parent molecules. In this regard the synthesis of small molecules based on the polyhydroxylated cyclohexane framework has gained vital importance. Some of the efforts of several research groups actively working on the design and synthesis of glycomimics have culminated in therapeutics and resulted in the development of many synthetic routes to polyoxygenated cyclohexanoids emanating from either the chiral pool or from aromatics and other non-carbohydrate sources. Nevertheless, the design of a general and variable strategy to access these cyclohexitols is essential. Our quest for a general and more versatile strategy for accessing several of the polyoxygenated cyclohexanoids led to the development of a new norbornyl based approach. The important feature of our approach involves extraction of the inherent cyclohexanoid from the norbornyl scaffold. The present thesis entitled “Norbornyl system revisited: Exploring a versatile building block for the syntheses of natural products and analogues” delineates our synthetic endeavors. The thesis is represented in two parts “Part 1: Synthesis of polyoxygenated cyclohexanoids and azepanes” is subdivided into Introduction, Results and Discussion, Summary, Experimental, Spectra and References sections and describes our synthetic efforts towards various polyoxygenated cyclohexanoids and azepanes. Introduction deals briefly about the importance of glycomimics and synthetic approaches from the literature towards these polyhydroxylated cyclohexanoids. Our findings constitute the Results and Discussion section wherein we delineate the synthesis of a versatile cyclohexanoid building block through a Grob like Wharton fragmentation on an suitably crafted norbornyl scaffold. The synthetic utililty and versatility of this building block are explored in subsections titled Carbasugars, Cyclitols, Gabosines, Aminocyclitols and Azepanes. The synthesis of several polyhydroxylated cyclohexanoid natural products and analogues is discussed. “Part 2: Synthetic studies towards the novel diterpenoid rameswaralide” deals with the elaboration of the versatile norbornyl building block towards the synthesis of a novel 5-7-6 fused diterpenoid rameswaralide. This part is again divided into Introduction, Results and Discussion, Summary, Experimental, Spectra and References sections. The Introduction briefs the relevance and importance of total synthesis of natural products, with a mention of terpenoids. The structure and biological significance of rameswaralide and related molecules is discussed. In the Results and Discussion our synthetic studies towards rameswaralide are delineated. Restructuring the norbornyl framework to a 5,5 fused all cis Corey lactone and its further amplification through ring closing metathesis and Diels-Alder protocols are described.

Carbohydrates are ubiquitous and important biomolecules. Initially thought to be dull, energy storing moieties, the importance of carbohydrates and their conjugates, glycoproteins and glycopilids, in cellular communication and various related processes has been well established. Carbohydrate recognition events are involved in the progression of various diseases, as the binding of pathogens to the host cells is carbohydrate mediated. Also the malfunctioning of carbohydrate processing enzymes has been implicated in life-threatening diseases. Thus there is tremendous interest in the design of molecules which can mimic the carbohydrates and provide insights into the mechanisms of action of carbohydrate processing enzymes. Such designer glycomimics possess several advantages over the parent molecules. In this regard the synthesis of small molecules based on the polyhydroxylated cyclohexane framework has gained vital importance. Some of the efforts of several research groups actively working on the design and synthesis of glycomimics have culminated in therapeutics and resulted in the development of many synthetic routes to polyoxygenated cyclohexanoids emanating from either the chiral pool or from aromatics and other non-carbohydrate sources. Nevertheless, the design of a general and variable strategy to access these cyclohexitols is essential. Our quest for a general and more versatile strategy for accessing several of the polyoxygenated cyclohexanoids led to the development of a new norbornyl based approach. The important feature of our approach involves extraction of the inherent cyclohexanoid from the norbornyl scaffold. The present thesis entitled “Norbornyl system revisited: Exploring a versatile building block for the syntheses of natural products and analogues” delineates our synthetic endeavors. The thesis is represented in two parts “Part 1: Synthesis of polyoxygenated cyclohexanoids and azepanes” is subdivided into Introduction, Results and Discussion, Summary, Experimental, Spectra and References sections and describes our synthetic efforts towards various polyoxygenated cyclohexanoids and azepanes. Introduction deals briefly about the importance of glycomimics and synthetic approaches from the literature towards these polyhydroxylated cyclohexanoids. Our findings constitute the Results and Discussion section wherein we delineate the synthesis of a versatile cyclohexanoid building block through a Grob like Wharton fragmentation on an suitably crafted norbornyl scaffold. The synthetic utililty and versatility of this building block are explored in subsections titled Carbasugars, Cyclitols, Gabosines, Aminocyclitols and Azepanes. The synthesis of several polyhydroxylated cyclohexanoid natural products and analogues is discussed. “Part 2: Synthetic studies towards the novel diterpenoid rameswaralide” deals with the elaboration of the versatile norbornyl building block towards the synthesis of a novel 5-7-6 fused diterpenoid rameswaralide. This part is again divided into Introduction, Results and Discussion, Summary, Experimental, Spectra and References sections. The Introduction briefs the relevance and importance of total synthesis of natural products, with a mention of terpenoids. The structure and biological significance of rameswaralide and related molecules is discussed. In the Results and Discussion our synthetic studies towards rameswaralide are delineated. Restructuring the norbornyl framework to a 5,5 fused all cis Corey lactone and its further amplification through ring closing metathesis and Diels-Alder protocols are described.

The research work reported in this thesis is focused on the chiral analysis, quantification of enantiomeric composition, assignment of absolute configuration of molecules with chosen functional groups. The weak intra-molecular hydrogen bonding interactions are detected by exploiting several multinuclear and multi-dimensional techniques. Pulse sequences have been designed to manipulate the spin dynamics to derive specific information from the complex NMR spectra encountered in diverse situations. Broadly, the thesis can be classified in to three sections. The section I containing two chapters reports the introduction of new chiral auxiliaries and protocols developed for enantiomeric discrimination, measurement of enantiomeric contents, assignment of absolute configuration for molecules possessing specific functional groups using chiral solvating and derivatizing agents. The section II, reports NMR experimental evidence for the observation of the rare type of intramolecular hydrogen bonds involving organic fluorine in biologically important organic molecules, that are corroborated by extensive DFT based theoretical calculations. The section II also discusses the H/D exchange mechanism as a tool for quantification of HB strengths in organic building blocks. The section III reports the two different novel NMR methodologies designed for deriving information on the scalar interaction strengths in an orchestrated manner. The designed sequences are able to completely eradicate the axial peaks, prevents the evolution of unwanted couplings and also yields ultrahigh resolution in the direct dimension, permitting the accurate measurement of scalar couplings for a particular spin. The brief summary about each chapter is given below. Chapter 1 provides a general introduction to one and two dimensional NMR spectroscopy. The pedagogical approach has been followed to discuss the conceptual understanding of spin physics and the NMR spectral parameters. The basic introduction to chirality, existing approaches in the literature for discrimination of enantiomers and the assignment of absolute configuration of molecules with chosen functional groups and their limitations are briefly discussed. The brief introduction to hydrogen bond, experimental methods to obtain the qualitative information about the strengths of hydrogen bonds, and the theoretical approaches employed in the thesis to corroborate the NMR experimental findings have been provided. The mechanism of H/D exchange, the utilization of exchange rates to derive strengths of intra-molecular hydrogen bond in small molecules have also been discussed. This chapter builds the bridge for the rest of the chapters. Each of these topics are discussed at length in the corresponding chapters. Part I: NMR Chiral Analysis: Novel Protocols Chapter 2 discusses a simple mix and shake method for testing the enantiopurity of primary, secondary and tertiary chiral amines and their derivatives, amino alcohols. The protocol involves the in-situ formation of chiral ammonium borate salt from a mixture of C2 symmetric chiral BINOL, trialkoxyborane and chiral amines. The proposed concept has been convincingly demonstrated for the visualization of enantiomers of a large number of chiral and pro-chiral amines and amino alcohols. The protocol also permits the precise measurement of enantiomeric composition. The significant advantage of the protocol is that it can be performed directly in the NMR tube, without any physical purification. The structure of the borate complex responsible for the enantiodifferentiation of amines has also been established by employing multinuclear NMR techniques and DFT calculations. From DOSY and 11B NMR experiments it has been ascertained that there are only two possible complexes or entities which are responsible for differentiating enantiomers. From the combined utility of DFT calculations and the 11B NMR chemical shifts, the structure of the borate complex has been determined to be an amine-coordinated complex with the N atom of the amine. Chapter 3 discusses a simple chiral derivatizing protocol involving the coupling of 2-formylphenylboronic acid and an optically pure [1,1-binaphthalene]-2,2-diamine for the rapid and accurate determination of the enantiopurity of hydroxy acids and their derivatives, possessing one or two optically active centers. It is established that this protocol is not only rapid method for discrimination of enantiomers but also highly effective for assigning the absolute configuration of various chiral hydroxy acids and their derivatives. The developed protocol involves the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and 2-formylphenylboronic acid with (S)-[1,1-binaphthalene]-2,2-diamine as chiral derivatizing agents. The absence of aliphatic peaks from the derivatizing agent, large chemical shift separation between the discriminated peaks of diastereomers, and the systematic change in the direction of displacement of peaks for an enantiomer in a particular diastereomeric complex, permitted the unambiguous assignment of absolute configuration. Part II : Rare Type of Intramolecular Hydrogen Bonding In chapter 4 The rare occurrence of intramolecular hydrogen bonds of the type N–H˖˖˖F–C, in the derivatives of imides and hydrazides in a low polarity solvent, is convincingly established by employing multi-dimensional and multinuclear solution state NMR experiments. The observation of 1hJFH, 2hJFN, and 2hJFF of significant strengths, where the spin polarization is transmitted through space among the interacting NMR active nuclei, provided strong and conclusive evidence for the existence of intra-molecular hydrogen bonds. Solvent induced perturbations and the variable temperature NMR experiments unambiguously supported the presence of intramolecular hydrogen bond. The two dimensional HOESY and 15N–1H HSQC experiments reveals the existence of multiple conformers in some of the investigated molecules. The 1H DOSY experimental results discarded any possibility of self or cross-dimerization of the molecules. The results of DFT based calculations, viz., Quantum Theory of Atoms In Molecules (QTAIM) and Non Covalent Interaction (NCI), are in close agreement with the NMR experimental findings. In chapter 5 the rates of hydrogen/deuterium (H/D) exchange determined by 1H NMR spectra have been utilized to derive the strength of hydrogen bonds and to monitor the electronic effects in the site-specific halogen substituted benzamides and anilines. The theoretical fitting of the time dependent variation in the integral areas of 1H NMR resonances to the first order decay function permitted the determination of H/D exchange rate constants (k) and their precise half-lives (t1/2) with high degree of reproducibility. The comparative study also permitted the determination of relative strengths of hydrogen bonds and the contribution from electronic effects on the H/D exchange rates. Part III: Novel NMR Methodologies for the Precise Measurement of 1H-1H Couplings Chapter 6 describes two novel NMR methodologies developed for the precise measurement of 1H-1H couplings. Poor chemical shift dispersion and the pairwise interaction among the entire coupled network of protons results in the severely complex and overcrowded one dimensional 1H NMR spectra, hampering both the resonance assignments and the accurate determination of nJHH. The available two-dimensional selective refocusing (SERF) based experiments suffer from the evolution of magnetization from uncoupled protons as intense uninformative axial peaks. This creates ambiguity in the identification of peaks belonging to the coupled partners of a selectively excited proton, hindering the extraction of their interaction strengths. This challenge has been circumvented by designing two novel experimental technique, cited as “Clean-G-SERF” and “PS-Clean-G-SERF”. The Clean-G-SERF technique completely eradicates the axial peaks and suppresses the evolution of unwanted couplings while retaining only the couplings to the selectively excited proton. The method permits the accurate determination of spin-spin couplings even from a complex proton NMR spectrum in an orchestrated manner. The PS-Clean-G-SERF technique has been designed for the complete elimination of axial peaks and undesired couplings, with a blend of ultra-high resolution achieved by real time broad band homonuclear decoupling has been discussed in this chapter. The spin dynamics involved in both these pulse sequences have been discussed. The diverse applications of both these novel experiments have been demonstrated.

The research work reported in this thesis is focused on the chiral analysis, quantification of enantiomeric composition, assignment of absolute configuration of molecules with chosen functional groups. The weak intra-molecular hydrogen bonding interactions are detected by exploiting several multinuclear and multi-dimensional techniques. Pulse sequences have been designed to manipulate the spin dynamics to derive specific information from the complex NMR spectra encountered in diverse situations. Broadly, the thesis can be classified in to three sections. The section I containing two chapters reports the introduction of new chiral auxiliaries and protocols developed for enantiomeric discrimination, measurement of enantiomeric contents, assignment of absolute configuration for molecules possessing specific functional groups using chiral solvating and derivatizing agents. The section II, reports NMR experimental evidence for the observation of the rare type of intramolecular hydrogen bonds involving organic fluorine in biologically important organic molecules, that are corroborated by extensive DFT based theoretical calculations. The section II also discusses the H/D exchange mechanism as a tool for quantification of HB strengths in organic building blocks. The section III reports the two different novel NMR methodologies designed for deriving information on the scalar interaction strengths in an orchestrated manner. The designed sequences are able to completely eradicate the axial peaks, prevents the evolution of unwanted couplings and also yields ultrahigh resolution in the direct dimension, permitting the accurate measurement of scalar couplings for a particular spin. The brief summary about each chapter is given below. Chapter 1 provides a general introduction to one and two dimensional NMR spectroscopy. The pedagogical approach has been followed to discuss the conceptual understanding of spin physics and the NMR spectral parameters. The basic introduction to chirality, existing approaches in the literature for discrimination of enantiomers and the assignment of absolute configuration of molecules with chosen functional groups and their limitations are briefly discussed. The brief introduction to hydrogen bond, experimental methods to obtain the qualitative information about the strengths of hydrogen bonds, and the theoretical approaches employed in the thesis to corroborate the NMR experimental findings have been provided. The mechanism of H/D exchange, the utilization of exchange rates to derive strengths of intra-molecular hydrogen bond in small molecules have also been discussed. This chapter builds the bridge for the rest of the chapters. Each of these topics are discussed at length in the corresponding chapters. Part I: NMR Chiral Analysis: Novel Protocols Chapter 2 discusses a simple mix and shake method for testing the enantiopurity of primary, secondary and tertiary chiral amines and their derivatives, amino alcohols. The protocol involves the in-situ formation of chiral ammonium borate salt from a mixture of C2 symmetric chiral BINOL, trialkoxyborane and chiral amines. The proposed concept has been convincingly demonstrated for the visualization of enantiomers of a large number of chiral and pro-chiral amines and amino alcohols. The protocol also permits the precise measurement of enantiomeric composition. The significant advantage of the protocol is that it can be performed directly in the NMR tube, without any physical purification. The structure of the borate complex responsible for the enantiodifferentiation of amines has also been established by employing multinuclear NMR techniques and DFT calculations. From DOSY and 11B NMR experiments it has been ascertained that there are only two possible complexes or entities which are responsible for differentiating enantiomers. From the combined utility of DFT calculations and the 11B NMR chemical shifts, the structure of the borate complex has been determined to be an amine-coordinated complex with the N atom of the amine. Chapter 3 discusses a simple chiral derivatizing protocol involving the coupling of 2-formylphenylboronic acid and an optically pure [1,1-binaphthalene]-2,2-diamine for the rapid and accurate determination of the enantiopurity of hydroxy acids and their derivatives, possessing one or two optically active centers. It is established that this protocol is not only rapid method for discrimination of enantiomers but also highly effective for assigning the absolute configuration of various chiral hydroxy acids and their derivatives. The developed protocol involves the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and 2-formylphenylboronic acid with (S)-[1,1-binaphthalene]-2,2-diamine as chiral derivatizing agents. The absence of aliphatic peaks from the derivatizing agent, large chemical shift separation between the discriminated peaks of diastereomers, and the systematic change in the direction of displacement of peaks for an enantiomer in a particular diastereomeric complex, permitted the unambiguous assignment of absolute configuration. Part II : Rare Type of Intramolecular Hydrogen Bonding In chapter 4 The rare occurrence of intramolecular hydrogen bonds of the type N–H˖˖˖F–C, in the derivatives of imides and hydrazides in a low polarity solvent, is convincingly established by employing multi-dimensional and multinuclear solution state NMR experiments. The observation of 1hJFH, 2hJFN, and 2hJFF of significant strengths, where the spin polarization is transmitted through space among the interacting NMR active nuclei, provided strong and conclusive evidence for the existence of intra-molecular hydrogen bonds. Solvent induced perturbations and the variable temperature NMR experiments unambiguously supported the presence of intramolecular hydrogen bond. The two dimensional HOESY and 15N–1H HSQC experiments reveals the existence of multiple conformers in some of the investigated molecules. The 1H DOSY experimental results discarded any possibility of self or cross-dimerization of the molecules. The results of DFT based calculations, viz., Quantum Theory of Atoms In Molecules (QTAIM) and Non Covalent Interaction (NCI), are in close agreement with the NMR experimental findings. In chapter 5 the rates of hydrogen/deuterium (H/D) exchange determined by 1H NMR spectra have been utilized to derive the strength of hydrogen bonds and to monitor the electronic effects in the site-specific halogen substituted benzamides and anilines. The theoretical fitting of the time dependent variation in the integral areas of 1H NMR resonances to the first order decay function permitted the determination of H/D exchange rate constants (k) and their precise half-lives (t1/2) with high degree of reproducibility. The comparative study also permitted the determination of relative strengths of hydrogen bonds and the contribution from electronic effects on the H/D exchange rates. Part III: Novel NMR Methodologies for the Precise Measurement of 1H-1H Couplings Chapter 6 describes two novel NMR methodologies developed for the precise measurement of 1H-1H couplings. Poor chemical shift dispersion and the pairwise interaction among the entire coupled network of protons results in the severely complex and overcrowded one dimensional 1H NMR spectra, hampering both the resonance assignments and the accurate determination of nJHH. The available two-dimensional selective refocusing (SERF) based experiments suffer from the evolution of magnetization from uncoupled protons as intense uninformative axial peaks. This creates ambiguity in the identification of peaks belonging to the coupled partners of a selectively excited proton, hindering the extraction of their interaction strengths. This challenge has been circumvented by designing two novel experimental technique, cited as “Clean-G-SERF” and “PS-Clean-G-SERF”. The Clean-G-SERF technique completely eradicates the axial peaks and suppresses the evolution of unwanted couplings while retaining only the couplings to the selectively excited proton. The method permits the accurate determination of spin-spin couplings even from a complex proton NMR spectrum in an orchestrated manner. The PS-Clean-G-SERF technique has been designed for the complete elimination of axial peaks and undesired couplings, with a blend of ultra-high resolution achieved by real time broad band homonuclear decoupling has been discussed in this chapter. The spin dynamics involved in both these pulse sequences have been discussed. The diverse applications of both these novel experiments have been demonstrated.