Author: Christopher Parish
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages :

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Book Description
Nuclear magnetic resonance (NMR) spectroscopy of nuclei with low magnetic moments such as 13C spins can be quite challenging and time-consuming. Dynamic nuclear polarization (DNP) via the dissolution method greatly alleviates this sensitivity problem by enhancing the NMR signals of these insensitive nuclei by several thousand-fold. Dissolution DNP thus allows 13C NMR tracking of cellular metabolism in living cells in real-time with superb sensitivity and high specificity. Herein, the bulk of my PhD dissertation work has been devoted to the elucidation and optimization of chemical physics of DNP technology in pursuit of attaining the highest NMR signal enhancements. One finding highlighted in this dissertation is the confirmation that the solidstate 13C DNP efficiency is affected by the isotopic location of the 13C label within the target molecule. Such can be explained via the thermal mixing model of DNP. Another major work in this dissertation is the investigation of the effects of 2H enrichment of the glassing solvents on the solid-state 13C spin-lattice T1 relaxation times of hyperpolarized 13C acetate. It is reported herein that glassing solvent deuteration elongates the 13C T1 relaxation times significantly, indicative of reduced intermolecular dipolar interaction of 13C spins with 2H spins compared to coupling with 1H spins. Next, this dissertation also encompasses two studies regarding the effect upon DNP of doping samples with mixtures of two different free radicals as opposed to doping them with one type of free radical. In one of the two studies, it was determined that a mixture of the wide EPR width 4-oxo-TEMPO and narrow EPR width trityl OX063 yields interesting 13C DNP results. There appears to be competing effects when the microwave irradiation frequency was set to the negative polarization peak of trityl OX063 which coincides with the positive polarization peak of 4-oxo-TEMPO. On the other hand, a mixture of both narrow EPR widths trityl and BDPA free radicals yields an additive effect. Finally, this dissertation also details the use of 13C NMR in the characterization of 13C-labelled amino acids and their application in investigating cancer cell metabolism. 13C-labeled amino acids are potential hyperpolarized 13C NMR spectroscopy and imaging (MRI) metabolic probes for cancer because a number of metabolic pathways that involve these biomolecules are abnormal in tumors. For instance, the enzyme branched chain amino acid transferase (BCAT), which catalyzes the conversion of branched chain amino acids (BCAA) to their ketoacid counterparts or vice versa, is overexpressed in several cancers. In this project, [1- 13C] L-leucine and [1- 13C] alpha-ketoisocaproate (KIC) were used to study the aberrant BCAT metabolic activity in glioblastoma. SfXL glioblastoma cells appear to preferentially convert 13CKIC to 13C leucine rather than vice versa. Western blot experiments confirmed that BCAT expression is higher in SfXL cells than in normal astrocytes. Overall, this dissertation details the chemical tuning methods in DNP that I have unraveled in pursuit of attaining the highest 13C NMR signal enhancements. These optimized DNP signals are crucial to the success of in vivo NMR or MRI studies, particularly in probing the hyperactive metabolism of cancer.

Author: Vladimir K. Michaelis
Publisher: John Wiley & Sons
ISBN: 1119441668
Category : Science
Languages : en
Pages : 920

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Book Description
Addresses Dynamic Nuclear Polarization (DNP) as a technique for sensitivity-enhancement in solid-state NMR spectroscopy This comprehensive handbook is a compendium of the current state-of-the art of high field Dynamic Nuclear Polarization—from long-proven, early developments, up to today’s hot topics. It covers all the relevant subjects that have made a direct or indirect contribution toward advancing this field, and focuses on topics such as: the theory behind the effects seen within DNP; instrumentation required for carrying out DNP; and specific applications of DNP including protein monitoring, catalysis, nanoparticles, biological and clinical studies. Development and application of techniques that have indirectly contributed to advancing MAS DNP NMR, such as DNP experiments on static solids within microwave resonant structures, and high-field EPR, are also examined. Handbook of High Field Dynamic Nuclear Polarization is presented in three sections—Theoretical Aspects, DNP Development (instrumentation / radical / sample), and DNP NMR Applications. The first section offers chapters on; solid and cross effect DNP; thermal mixing; Overhauser; and dissolution DNP. The second looks at: microwave technology, gyrotron, and IOE; homebuilt and commercial DNP spectrometers; and glassing vs. solvent-free DNP. The final section provides information on; amyloid, membrane, and nanocrystalline proteins; metals, and surface enhanced DNP; pharmaceuticals; nanoparticles; and much more. Covers one of the biggest developing fields in magnetic resonance Relevant to students, academics, and industry within the physical, materials, medical, and biochemical sciences An excellent starting point and point-of-reference for researchers in the field Edited by a widely respected team with contributions from key researchers in the NMR community Part of the eMagRes Handbook Series Handbook of High Field Dynamic Nuclear Polarization is an ideal reference for all researchers and graduate students involved in this complex, interdisciplinary field. About eMagRes Handbooks eMagRes publishes a wide range of online articles on all aspects of magnetic resonance in physics, chemistry, biology and medicine. The existence of this large number of articles, written by experts in various fields, is enabling the publication of a series of eMagRes Handbooks on specific areas of NMR and MRI. The chapters of each of these handbooks will comprise a carefully chosen selection of eMagRes articles. In consultation with the eMagRes Editorial Board, the eMagRes Handbooks are coherently planned in advance by specially-selected Editors, and new articles are written to give appropriate complete coverage. The handbooks are intended to be of value and interest to research students, postdoctoral fellows and other researchers learning about the scientific area in question and undertaking relevant experiments, whether in academia or industry. Have the content of this Handbook and the complete content of eMagRes at your fingertips! Visit: www.wileyonlinelibrary.com/ref/eMagRes

Author: Björn Dollmann
Publisher: Sudwestdeutscher Verlag Fur Hochschulschriften AG
ISBN: 9783838125602
Category :
Languages : en
Pages : 192

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Book Description
Nuclear magnetic resonance (NMR) is a versatile technique relying on spin-bearing nuclei. Since its discovery more than 60 years ago, NMR and related techniques have become indispensable tools with innumerable applications in physics, chemistry, biology and medicine. One of the main obstacles in NMR is its notorious lack of sensitivity, which is due to the minuscule energy splitting of the nuclear spins at room temperature. Appropriately, the inherent low polarization allows for a theoretical sensitivity enhancement of more than 10,000. The NMR signal enhancement of protons which can be achieved by means of Dynamic Nuclear Polarization (DNP) is approximately 660. In this book, different hardware aspects and polarizing agents for DNP were studied. The results show the potential of DNP, especially at a magnetic field of B=0.35 T, when it comes to the polarization of nuclei with a very low magnetogyric ratio which should result in many new applications. These presented components and designs could be the foundation to open up the application of a mobile DNP polarizer for medical applications.

Author: Ivano Bertini
Publisher: Elsevier
ISBN: 0444634487
Category : Science
Languages : en
Pages : 510

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Book Description
NMR of Paramagnetic Molecules: Applications to Metallobiomolecules and Models, Second Edition is a self-contained, comprehensive reference for chemists, physicists, and life scientists whose research involves analyzing paramagnetic compounds. Since the previous edition of this book was published, there have been many advancements in the field of paramagnetic NMR spectroscopy. This completely updated and expanded edition contains the latest fundamental theory and methods for mastery of this analytical technique. Users will learn how to interpret the NMR spectra of paramagnetic molecules, improve experimental techniques, and strengthen their understanding of the underlying theory and applications. - Reflects all advances in the field in a completely updated new edition - Presents new material on self-orientation residual dipolar couplings, solid state NMR, dynamic nuclear polarization, and paramagnetic restraints for structure calculations - Includes information relevant to paramagnetic molecules, metallobiomolecules, paramagnetic compounds, and paramagnetic NMR spectroscopy - Presents specific examples of paramagnetic inorganic species and experimental techniques for structure characterization

Author: Lars T. Kuhn
Publisher: Springer
ISBN: 364239728X
Category : Science
Languages : en
Pages : 311

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Book Description
Elucidating Organic Reaction Mechanisms using photo-CIDNP Spectroscopy, by Martin Goez. Parahydrogen Induced Polarization by Homogeneous Catalysis: Theory and Applications, by Kerstin Münnemann et al. Improving NMR and MRI Sensitivity with Parahydrogen, by R. Mewis & Simon Duckett. The Solid-state Photo-CIDNP Effect, by Jörg Matysik et al. Parahydrogen-induced Polarization in Heterogeneous Catalytic Processes, by Igor Koptyug et al. Dynamic Nuclear Polarization Enhanced NMR Spectroscopy, by U. Akbey & H. Oschkinat. Photo-CIDNP NMR Spectroscopy of Amino Acids and Proteins, by Lars T. Kuhn.

Author: Qing Wang
Publisher:
ISBN:
Category : Nuclear magnetic resonance
Languages : en
Pages :

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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: The Nuclear Magnetic Resonance Society of Japan
Publisher: Springer
ISBN: 9811059667
Category : Science
Languages : en
Pages : 634

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Book Description
This book describes the advanced developments in methodology and applications of NMR spectroscopy to life science and materials science. Experts who are leaders in the development of new methods and applications of life and material sciences have contributed an exciting range of topics that cover recent advances in structural determination of biological and material molecules, dynamic aspects of biological and material molecules, and development of novel NMR techniques, including resolution and sensitivity enhancement. First, this book particularly emphasizes the experimental details for new researchers to use NMR spectroscopy and pick up the potentials of NMR spectroscopy. Second, the book is designed for those who are involved in either developing the technique or expanding the NMR application fields by applying them to specific samples. Third, the Nuclear Magnetic Resonance Society of Japan has organized this book not only for NMR members of Japan but also for readers worldwide who are interested in using NMR spectroscopy extensively.

Author: Eul Hyun Suh
Publisher: Academic Press
ISBN: 0323918433
Category : Science
Languages : en
Pages : 266

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Book Description
The Chemistry of Hyperpolarized Magnetic Resonance Probes, Volume Seven focuses on the chemical aspects of hyperpolarized NMR/MRI technology, with synthesis and characterizations of labeled compounds discussed from a practical point-of-view. A brief overview of the various hyperpolarization techniques are given, with the optimization of hyperpolarization conditions and the determination of critical parameters such as polarization level and T1 relaxation values described. A practical guide on the in vivo applications of hyperpolarized compounds in small animals is also included. - Helps readers understand the structural features that determine the properties of HP-probes, such as chemical shift and relaxation times - Aids readers in selecting stable isotope labeled probes for hyperpolarized NMR/MRI applications - Teachers readers how to use the most appropriate synthetic methodology for the labeled probes - Covers how to find the most suitable polarization technique (DNP, PHIP etc.) for the probe

Author: Olivier Ouari
Publisher: Royal Society of Chemistry
ISBN: 1788019660
Category : Science
Languages : en
Pages : 611

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Book Description
Nitroxides are versatile small organic molecules possessing a stabilised free radical. With their unpaired electron spin they display a unique reactivity towards various environmental factors, enabling a diverse range of applications. They have uses as synthetic tools, such as catalysts or building blocks; imaging agents and probes in biomedicine and materials science; for medicinal antioxidant applications; and in energy storage. Polynitroxides (polymers bearing pendant nitroxide sidechains) have been used in organic radical batteries, oxidation catalysts and in exchange reactions for constructing complex architectures. Chapters in this book cover the synthesis of nitroxides, EPR studies and magnetic resonance applications, physiochemical studies, and applications including in batteries, imaging and organic synthesis. With contributions from leaders in the field, Nitroxides will be of interest to graduate students and researchers across chemistry, physics, biology and materials science.

Author: Harald Günther
Publisher: John Wiley & Sons
ISBN: 3527674772
Category : Science
Languages : en
Pages : 842

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Book Description
Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful and widely used techniques in chemical research for investigating structures and dynamics of molecules. Advanced methods can even be utilized for structure determinations of biopolymers, for example proteins or nucleic acids. NMR is also used in medicine for magnetic resonance imaging (MRI). The method is based on spectral lines of different atomic nuclei that are excited when a strong magnetic field and a radiofrequency transmitter are applied. The method is very sensitive to the features of molecular structure because also the neighboring atoms influence the signals from individual nuclei and this is important for determining the 3D-structure of molecules. This new edition of the popular classic has a clear style and a highly practical, mostly non-mathematical approach. Many examples are taken from organic and organometallic chemistry, making this book an invaluable guide to undergraduate and graduate students of organic chemistry, biochemistry, spectroscopy or physical chemistry, and to researchers using this well-established and extremely important technique. Problems and solutions are included.