Nuclear Quadrupole Double Resonance Spectroscopy: Studies of Hydrogen Bonding and Metal-Nitrogen Interactions

168 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1981.The past ten years have brought a renewed interest in nuclear quadrupole resonance (NQR) spectroscopy. This attention stems from the advent of double resonance methods capable of observing with high sensitivity the weak quadrupole resonances. Through double resonance NQR much new and useful information regarding the solid state electronic structure of light elements is now becoming known.The double resonance by level crossing (DRLC) technique of NQR detection is discussed with emphasis on its application of I = 1 nuclear spin systems. A description of NQR double resonance spectrometer of new design which is capable of performing DRLC is also included. This instrument, in favorable cases, is capable of generating NQR spectra on about 300 mg of sample.Applications of the DRLC technique to the study of nitrogen and deuterium electric field gradients in several chemical systems is presented. The ('14)N and ('2)H NQR spectra of anthranilic acid in its three polymorphic forms yield information that is explained in light of the extensive hydrogen bonding present in the solid material. ('14)N studies of divalent metal anthranilate complexes are also presented. The quadrupole resonance parameters are accounted for in terms of a modified Townes-Dailey model consistent with tetrahedral coordination about the amino-nitrogen center. Finally, the ('14)N NQR spectra of a series of square planar palladium diethylene-triamine compounds is presented. The NQR information is interpreted in light of hypothesis regarding the kinetic trans-effect.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Nuclear Quadrupole Double Resonance Spectroscopy: Studies of Hydrogen Bonding and Metal-Nitrogen Interactions

168 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1981.The past ten years have brought a renewed interest in nuclear quadrupole resonance (NQR) spectroscopy. This attention stems from the advent of double resonance methods capable of observing with high sensitivity the weak quadrupole resonances. Through double resonance NQR much new and useful information regarding the solid state electronic structure of light elements is now becoming known.The double resonance by level crossing (DRLC) technique of NQR detection is discussed with emphasis on its application of I = 1 nuclear spin systems. A description of NQR double resonance spectrometer of new design which is capable of performing DRLC is also included. This instrument, in favorable cases, is capable of generating NQR spectra on about 300 mg of sample.Applications of the DRLC technique to the study of nitrogen and deuterium electric field gradients in several chemical systems is presented. The ('14)N and ('2)H NQR spectra of anthranilic acid in its three polymorphic forms yield information that is explained in light of the extensive hydrogen bonding present in the solid material. ('14)N studies of divalent metal anthranilate complexes are also presented. The quadrupole resonance parameters are accounted for in terms of a modified Townes-Dailey model consistent with tetrahedral coordination about the amino-nitrogen center. Finally, the ('14)N NQR spectra of a series of square planar palladium diethylene-triamine compounds is presented. The NQR information is interpreted in light of hypothesis regarding the kinetic trans-effect.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide.

Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer