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Author: Qing Wang Publisher: ISBN: Category : Nuclear magnetic resonance Languages : en Pages :
Book Description
Nuclear magnetic resonance (NMR) is a phenomenon that describes the microscopic environment of nuclear spins under the external magnetic field by applying radiofrequency waves at their corresponding nuclear Larmor frequency, and widely used in materials science, biochemistry, and medical imaging. It allows one to investigate molecular structural information and dipolar intramolecular interactions noninvasively. However, the majority of the nuclei are insensitive to NMR spectrometer and exhibit minute NMR signals due to their intrinsic weak nuclear magnetic moments. This low signal-to-noise issue has been mitigated by an approach called dynamic nuclear polarization (DNP) in which the high polarization of electron spins is transferred to the nuclei via microwave irradiation close to electron Larmor frequency at high magnetic field and low temperature. To harness this enhanced NMR signal for biomedical or chemical applications, the dissolution process is employed wherein the frozen polarized nuclei samples are rapidly dissolved into hyperpolarized liquids at physiological temperatures. Using this technology, the NMR signals of weak nuclei such as 13C and 89Y can be enhanced by several thousand-fold relative to their thermal equilibrium NMR signals. The bulk of this PhD dissertation entails a discussion of the details of DNP physics and applications of hyperpolarized low-gamma nuclei such as 13C-enriched organic compounds and 89Y-complexes that have chemical and biological relevance. Furthermore, this thesis also involves a discussion the construction of a homebuilt cryogen-free and variable-field DNP instrumentation. This DNP instrumentation is a major leap in the field of hyperpolarization since it does not require expensive liquid helium for DNP operation. As such, this instrumentation allowed us to measure, for the first time, the solid-state T1 relaxation times of 13C compounds at 1.8 K in the 0-9 T magnetic field range. The main finding of this measurement is that the 13C T1 relaxation times of carboxylates follow a power law dependence on magnetic field according to T1~B2-3 at cryogenic temperature. Meanwhile, the feasibility of hyperpolarized 89Y-EDTMP and 89Y-DTPMP as potential chemical shift-based NMR sensors for pH was studied. The results of this study show that hyperpolarized 89Y-EDTMP has a relatively wide chemical shift range of 16 ppm over pH 5-9 range with pKa close to neutral—a promising pH sensor for future in vivo applications. In addition, dissolution DNP also allows one to track the complexation of free Y3+ ion and ligand such as DOTA in realtime under certain buffered solution conditions, giving insight as a model for Gd3+ complexation with specific macrocyclic ligands. Furthermore, dissociation of 89Y-DTPA into free 89Y ion and DTPA ligand in the presence of Zn2+ in the solution has been monitored in real-time, providing a direct chemical reaction monitoring process for the complex. Additionally, the effect of 13C nuclear spin density of 13C DNP signal and T1 relaxation was also investigated. Finally, this thesis also includes a 13C/15N NMR investigation of alanine metabolism in glioblastoma cells. In summary, this PhD dissertation encompasses a discussion of the analytical power of hyperpolarized and conventional NMR spectroscopy in the investigation of chemical and biological systems.
Author: Qing Wang Publisher: ISBN: Category : Nuclear magnetic resonance Languages : en Pages :
Book Description
Nuclear magnetic resonance (NMR) is a phenomenon that describes the microscopic environment of nuclear spins under the external magnetic field by applying radiofrequency waves at their corresponding nuclear Larmor frequency, and widely used in materials science, biochemistry, and medical imaging. It allows one to investigate molecular structural information and dipolar intramolecular interactions noninvasively. However, the majority of the nuclei are insensitive to NMR spectrometer and exhibit minute NMR signals due to their intrinsic weak nuclear magnetic moments. This low signal-to-noise issue has been mitigated by an approach called dynamic nuclear polarization (DNP) in which the high polarization of electron spins is transferred to the nuclei via microwave irradiation close to electron Larmor frequency at high magnetic field and low temperature. To harness this enhanced NMR signal for biomedical or chemical applications, the dissolution process is employed wherein the frozen polarized nuclei samples are rapidly dissolved into hyperpolarized liquids at physiological temperatures. Using this technology, the NMR signals of weak nuclei such as 13C and 89Y can be enhanced by several thousand-fold relative to their thermal equilibrium NMR signals. The bulk of this PhD dissertation entails a discussion of the details of DNP physics and applications of hyperpolarized low-gamma nuclei such as 13C-enriched organic compounds and 89Y-complexes that have chemical and biological relevance. Furthermore, this thesis also involves a discussion the construction of a homebuilt cryogen-free and variable-field DNP instrumentation. This DNP instrumentation is a major leap in the field of hyperpolarization since it does not require expensive liquid helium for DNP operation. As such, this instrumentation allowed us to measure, for the first time, the solid-state T1 relaxation times of 13C compounds at 1.8 K in the 0-9 T magnetic field range. The main finding of this measurement is that the 13C T1 relaxation times of carboxylates follow a power law dependence on magnetic field according to T1~B2-3 at cryogenic temperature. Meanwhile, the feasibility of hyperpolarized 89Y-EDTMP and 89Y-DTPMP as potential chemical shift-based NMR sensors for pH was studied. The results of this study show that hyperpolarized 89Y-EDTMP has a relatively wide chemical shift range of 16 ppm over pH 5-9 range with pKa close to neutral—a promising pH sensor for future in vivo applications. In addition, dissolution DNP also allows one to track the complexation of free Y3+ ion and ligand such as DOTA in realtime under certain buffered solution conditions, giving insight as a model for Gd3+ complexation with specific macrocyclic ligands. Furthermore, dissociation of 89Y-DTPA into free 89Y ion and DTPA ligand in the presence of Zn2+ in the solution has been monitored in real-time, providing a direct chemical reaction monitoring process for the complex. Additionally, the effect of 13C nuclear spin density of 13C DNP signal and T1 relaxation was also investigated. Finally, this thesis also includes a 13C/15N NMR investigation of alanine metabolism in glioblastoma cells. In summary, this PhD dissertation encompasses a discussion of the analytical power of hyperpolarized and conventional NMR spectroscopy in the investigation of chemical and biological systems.
Author: Youngbok Lee Publisher: ISBN: Category : Languages : en Pages :
Book Description
Nuclear magnetic resonance (NMR) spectroscopy is one of the most important analytical tools for organic and biological chemistry. It provides not only detailed information on the structure of small molecules and macromolecules, but also on molecular interactions. Because of the inherent low sensitivity of NMR, a long signal averaging time or a high spin concentration is often required. A variety of methods have been explored to improve the sensitivity of NMR. Especially, large signal gains can be obtained by hyperpolarization of the nuclear spins. NMR signals of hyperpolarized samples are enhanced by several orders of magnitude. Dissolution Dynamic Nuclear Polarization (D-DNP) is a versatile technique capable of polarizing many different nuclei in the solid state, and subsequently providing a hyperpolarized liquid sample following a dissolution step. The resulting signal enhancement has made it possible to obtain detailed information in research fields as varied as metabolic imaging or enzyme catalysis. This dissertation aims to extend the applicability of D-DNP into new areas of chemistry, which involve the characterization of interactions and reactions involving large molecules. In a first project, fluorine hyperpolarization is exploited to investigate protein-ligand interactions. The enhancement of 19F signal allows for the detection of submicromolar concentrations of fluorinated ligands in the strong-, intermediate-, and weak-binding regimes. Several NMR parameters are utilized to observe ligand binding to the macromolecule, and to determine dissociation constants. In a second project, competitive binding of ligands to the same binding pocket on a protein is investigated. Here, polarization flows from a first ligand hyperpolarized on protons to the protein, and then to the second ligand. The buildup in function of time of the signals due to this relayed nuclear Overhauser effect contains structural information on the binding epitope. In a third project, the aim is to directly detect a larger molecule, a polymer, which has been synthesized starting from hyperpolarized monomers. Using DNP, single scan observation of 13C, a common nucleus with large chemical shift dispersion, is possible. Time resolved 13C NMR spectroscopy in combination with kinetic models permits the description of polymerization reaction of the living anionic polymerization of styrene. In summary, several approaches have been investigated for utilizing a large hyperpolarization initially produced on small molecules, for the benefit of characterizing properties of macromolecules. These developments extend the capabilities of D-DNP and demonstrate the potential for leading to new applications in fields as diverse as drug discovery and polymer science. The electronic version of this dissertation is accessible from http://hdl.handle.net/1969.1/149344
Author: Kalevi Pihlaja Publisher: VCH Publishers ISBN: Category : Science Languages : en Pages : 408
Book Description
A review of recent research on strategies and applications of the C-13 chemical shift, a method for determining configuration of organic compounds. Introduces C-13 NMR spectroscopy, and describes conditions for collecting the FID, for data handling, and for obtaining a well- resolved C-13 NMR spectrum, as well as various substituent effect correlations, their derivations, and the origin of the effects. Also discusses the use of multidimensional NMR methods. For organic, physical, and natural products chemists. Includes bandw diagrams. Annotation copyright by Book News, Inc., Portland, OR
Author: C. Richard Publisher: Springer ISBN: 9783642657955 Category : Science Languages : en Pages : 0
Book Description
Anomalous electron-spin state populations in the Electron Paramagnetic Re sonance (EPR) spectra of radicals formed during radio lysis experiments were observed in 1963 by FESSENDEN and SCHULER [170a]. This phenomenon did not receive much attention at the time. In 1967, BARGON, FISCHER, and JOHNSEN [5] and independently WARD and LAWLER [7,8] reported a similar phenomenon for Nuclear Magnetic Resonance (NMR) spectra taken during radical reactions: emission or enhanced absorption, or both. The earliest attempts to explain this new NMR phenomenon treated these effects in a way similar to that of Dynamic Nuclear Polarization (DNP) or the Overhauser effect. Although the polarization has a completely different origin, DNP gave its name to this effect: Chemically Induced Dynamic Nuclear Polariza tion (CIDNP). [The name Chemically Induced Dynamic Electron Polarization (CIDEP) was introduced later by analogy with CIDNP]. After the initial publica tions, all the new data demonstrated that the first theory could not be correct. In 1969, a new theory was proposed by CLOSS [18] and independently by KAPTEIN and OOSTERHOFF [23] and called the radical-pair theory. This mechanism was proposed to account for the observations of polarization in both NMR and EPR. The radical-pair theory is based on weak interactions in a pair of radicals: the strength of interaction between the electronic states of the radicals depends in particular on the nuclear-spin states.
Author: Peter James Niedbalski Publisher: ISBN: Category : Carbon Languages : en Pages :
Book Description
Nuclear magnetic resonance (NMR) is a technique that probes the microscopic environment of molecules by investigating the interaction between nuclear magnetic moments and the magnetic field in which they reside. Nuclear magnetic moments, however, are very weak, causing the Boltzmann polarization of nuclei and hence the NMR signal to be very small. This may be resolved through the use of dynamic nuclear polarization (DNP), a process by which high electron polarization is transferred to nuclei through microwave irradiation near the electron resonance. In this work, primary focus is given to dissolution DNP in which nuclei are highly polarized at cryogenic temperature and then rapidly dissolved with a superheated solvent. This process results in a liquid sample whose NMR signal is enhanced many thousand-fold over thermal equilibrium. While applications of this technique are abundant, there are many unanswered questions surrounding the underlying physics and methods of optimization of the DNP process. In this work, some of these open questions are investigated through development of instrumentation and exploration of DNP free radicals. In particular, the construction of two high magnetic field DNP polarizers are discussed, one of which is the first of a new generation of cryogen-free polarizers. Furthermore, the water soluble DNP free radicals TEMPO and trityl are thoroughly investigated with a specific emphasis on the addition of paramagnetic ion complexes. Over the course of these experiments, several paramagnetic agents were tested for the first time and proven to be effective to a similar degree as the field standard gadolinium. Additionally, the link between shortened electronic T1 and improved DNP efficiency was con firmed through the study of transition metal complex dopants to DNP. A number of supporting experiments are also discussed, including Earth's field NMR and classification of free radicals by UV-Vis spectrophotometry and electron paramagnetic resonance. Finally, several basic molecular imaging applications of dissolution DNP are presented highlighting one of the many possible uses of hyperpolarized 13C NMR spectroscopy. Ultimately, this dissertation presents and discusses a number of novel methods by which 13C dynamic nuclear polarization may be optimized, paving the way for further study into the physics and applications of this technique.
Author: Sean Michael Bowen Publisher: ISBN: Category : Languages : en Pages :
Book Description
Nuclear magnetic resonance (NMR) yields remarkably detailed structural information about virtually any molecule. However, its application to non-equilibrium systems is hampered by a lack of sensitivity. To increase the amount of signal that can be obtained from a NMR experiment, various hyperpolarization schemes have been previously introduced. One such technique is dynamic nuclear polarization (DNP), which can enhance NMR sensitivity by several orders of magnitude. The work detailed here focuses on the development of methods utilizing DNP to study non-equilibrium systems such as chemical and biochemical reactions in real-time. To work with hyperpolarized samples, we have designed and constructed a rapid injection and mixing system. This system allows samples to be transported between superconducting magnets used for polarization and for NMR spectroscopy in less than two seconds. Rapid transport is essential for successful use of samples with short spin-lattice relaxation times. For the study of reactions under non-equilibrium conditions, the system provides the additional capability for samples to be mixed with a second, unpolarized reagent. A chromogenic trypsin catalyzed ester hydrolysis reaction was used to validate the DNP-NMR technique as a tool for kinetic analysis. It is shown that the DNP-NMR method agrees with the conventional UV method within the uncertainty of the measurement. Hyperpolarization in this modality presents both challenges and opportunities, each of which motivate the development of new NMR techniques. In addition to the determination of kinetics, DNP-NMR is amenable to mechanistic analysis of a reaction. We have developed a technique based on selective inversion of spin-polarization, which allows for mapping of atoms between reactant and product of a reaction. This scheme was applied to a Grignard reaction, demonstrating applicability to organic reactions. Signal averaging, as it is applied for conventional multi-dimensional correlation spectroscopy cannot always be applied easily when using hyperpolarized sample. For the rapid measurement of heteronuclear correlation spectra, we have developed a technique utilizing the differential scaling of scalar coupling under off-resonance irradiation. Although DNP-NMR yields spectra of outstanding quality even with small quantities of sample, peak intensities are not quantitative. It is nevertheless possible to compare peak multiplets obtained from fractionally isotope labeled samples. Using biosynthetically labeled lipids from E. Coli cells, we showed that the resulting labeling patterns reflect their biosynthetic pathways. As a final case-study employing several of these newly developed methods, the uronate isomerase catalyzed isomerization of glucuronate into fructuronate was studied. The ability to follow the reaction in real-time while directly observing all anomeric forms of the reactant and product permits the independent determination of kinetics for each anomeric form of substrate and product. This study revealed the anomeric specificity of the enzyme.
Author: Qing Wang
Author: Qing Wang
Author: Youngbok Lee
Author: Kalevi Pihlaja
Author: C. Richard
Author: Eberhard Breitmaier
Author: Raymond John Abraham
Author: Peter James Niedbalski
Author: F. W. Wehrli
Author: Sean Michael Bowen
Author: Wolfgang Bremser