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A Moessbauer study of relaxation and phase transitions in some magnetic systemsChadwick, J. January 1988 (has links)
No description available.
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Magnetic Relaxation Dynamics and Processes in Mono- and Dinuclear Lanthanide Single-Molecule MagnetsHarriman, Katie Lois Marie 16 July 2021 (has links)
Single-molecule magnets (SMMs) have been lauded for their application in next generation devices for their enhanced information storage capabilities, increased processing speeds, and increased storage densities compared to bulk magnets. However, the success of SMMs in such applications and their technological readiness is hindered by their operation temperatures and memory lifetimes. SMMs are molecular species that possess a bistable ground state and magnetic anisotropy, which together result in an energy barrier to the reorientation of the magnetic moment. The magnetic memory response relies on its ability to retain magnetization in the absence of an external field. To this end, lanthanide ions with their large inherent magnetic anisotropy combined with well-defined crystal field microstates are attractive candidates for eliciting higher operation temperatures and lifetimes. This dissertation focuses on the use of lanthanide ions in the development of high barrier SMMs with a close emphasis on the magnetic anisotropy and crystal field manipulation through geometry, design, and modification.
In the pursuit of lanthanide (Ln)-based SMMs, two cyclooctatetraenyl (COT2-) complexes of the non-Kramers ion, TmIII, [TmIII(η8-COT)I(THF)2] and [K(18-C-6)(THF)2][TmIII(η8-COT)2], were isolated. As an ion that possess an integer angular momentum projection (J = 6), it was vital that a highly symmetric local environment was utilized to observe field-induced slow magnetic relaxation. The static and dynamic properties of TmIII(η8-COT)I(THF)2] and [K(18-C-6)(THF)2][TmIII(η8-COT)2] were characterized revealing Ueff of 7.93 K and 53.3 K, respectively. More importantly, the effect of increased symmetry was observed on the rate of quantum tunneling of the magnetization (QTM), where the rate was two orders of magnitude faster in the heteroleptic complex. This emphasized the importance of local symmetry for non-Kramers ions and contributed to the rare class of TmIII SMMs.
Due to the prevalent role of QTM in Ln-based SMMs, a common strategy is to induce magnetic communication between Ln ions to overcome its detrimental effects. To this end, bridging units should be sufficiently small enough to bring the Ln ions close in proximity, yet the surrounding environment of the metal center should still promote uniaxial magnetic anisotropy. We compared the effect of ancillary ligands on the magnetic properties of two dinuclear DyIII compounds with the same {μ-Cl}2 core bridge. The complexes [DyIII{N(SiMe3)2}2(μ-Cl)(THF)]2 and [DyIII(η8-COT)(μ-Cl)(THF)]2 were characterized with static and dynamic magnetic measurements. The well-matched ligand field of the silyl amide ligands with the DyIII ion, precluded the observation of zero field tunneling. While both complexes are characterized by antiferromagnetic coupling, it is evident that peripheral ligands also play a vital role in determining the performance of multinuclear SMMs.
Magnetic coupling between 4f centers is classically weak; however, the use of ligands with diffuse electron clouds may penetrate the shielded 4f orbitals to effectively promote communication. One such ligand that had not previously been investigated for its ability to couple the magnetic moment of Ln ions was the trianionic cycloheptatrienyl. Utilizing Ln silyl amides, in situ deprotonation afforded the dinuclear complexes [KLnIII2(η7-C7H7){N(SiMe3)2}4] (Ln = GdIII, DyIII, ErIII). The static and dynamic magnetic characterization revealed rare and highly sought-after ferromagnetic coupling in a Ln-based system. The ancillary silyl amide ligands were a necessity for the isolation of these dinuclear species yet did not provide a synergistic ligand field for the Ln ions when combined with the cycloheptatrienyl bridge, ultimately preventing the observation of slow relaxation in some of the variants studied.
Pseudo-linear complexes, those molecules with strong axial donors have shown immense promise in the design of highly efficient SMMs. Our work has shown that amides are effective in directing the anisotropy of the Ln ions, thus the removal of the central organometallic bridge from the previous compounds would effectively create a highly anisotropic complex. This was achieved in our study of a formally five-coordinate complex of a ferrocene diamide ligated DyIII ion, [(NNTBS)DyIIII(THF)2]. The static and dynamic magnetic properties were characterized, yielding Ueff = 771 K with open magnetization hysteresis loops at zero-field, due in part to the axial disposition of the nitrogen atoms of the diamide ligand. Computational analysis of the parent compound and its fragments was completed. Our results indicated that the presence of equatorially coordinated solvent molecules such as THF, influence the axiality in the crystal field microstates more significantly than the coordinated halide.
The removal of coordinated solvent such as THF, is imperative to improve the performance of DyIII SMMs. By way of a bulky bisanilide ligand that precludes the approach of solvent to the metal center, combined with a large bite angle, [K(DME)n][LArDyIII(X)2], a formally four coordinate complex, was investigated. In contrast to the complex of the ferrocene diamide ligand, retention of the magnetic moment was not observed at zero-field, despite the fact that the slow relaxation dynamics occurred over a greater temperature range for which Ueff = 1278-1334 K. In addition, variants of the bound halide (X = Cl, I) were examined for their effect on the static and dynamic magnetic properties, revealing zero field relaxation times that were on average 5.6x longer for the heavier congener.
The collective results of the findings presented herein are being utilized to synthesize new low-coordinate Ln-based SMMs. Combining divalent and redox chemistries with bulky amido ligands will ideally elicit even larger energy barriers to spin reversal and higher blocking temperatures, supporting the push towards Ln-based SMMs with increased technological readiness.
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Estudo de propriedades petrofísicas de rochas sedimentares por Ressonância Magnética Nuclear / Petrophysical properties study of sedimentary rocks by Nuclear Magnetic ResonanceSouza, André Alves de 28 May 2012 (has links)
A Ressonância Magnética Nuclear (RMN) é uma das técnicas mais versáteis de investigação científica experimental, com destaque para o estudo da dinâmica, estrutura e conformação de materiais. Em particular, sua utilização na ciência do petróleo é uma de suas primeiras aplicações rotineiras. Metodologias desenvolvidas especificamente para atender esta comunidade científica mostraram-se desde cedo muito úteis, sendo o estudo da interação rocha/fluido uma de suas vertentes mais bem sucedidas. Desde então, importantes propriedades petrofísicas de reservatórios de óleo e gás têm sido determinadas e entendidas, tanto em laboratório quanto in-situ, nas próprias formações geológicas que armazenam esses fluidos. Entre estas propriedades, a permeabilidade, porosidade e molhabilidade de um reservatório figuram dentre as mais importantes informações estimadas. Com essa finalidade, a determinação e correlação dos possíveis efeitos que a interação rocha/fluido pode causar nos fenômenos de relaxação magnética e difusão molecular, tais como influência da susceptibilidade magnética e geometria do espaço poroso, foram estudados em onze rochas sedimentares retiradas de afloramentos, que possuem propriedades petrofísicas similares àquelas apresentadas por rochas reservatório de petróleo. Os resultados mostraram que os tipos de interação rocha/fluido, detectáveis pelos experimentos de RMN, são por sua vez influenciados pelas características geométricas e estruturais do meio poroso, sendo possível obter essas informações pelos resultados de RMN. Assim, este trabalho teve como objetivo principal estudar e estabelecer essas correlações, afim de se obter informações petrofísicas com maior acurácia e abrangência. Em particular, o estudo da razão T1/T2, que é a razão entre os tempos de relaxação longitudinal e transversal, típicos parâmetros envolvidos numa medida de RMN, mostrou ser um parâmetro útil no estabelecimento destas correlações. Ainda, diferentes metodologias para se medir estes e outros parâmetros de RMN foram estudadas e propostas, cuja interpretação conjunta mostrou ser fundamental para o entendimento dessas correlações. A permeabilidade das rochas, importante parâmetro que define as propriedades de transporte de fluidos dentro da matriz porosa, foi estimada aplicando-se essas metodologias propostas, mostrando excelentes resultados. Através do uso da técnica de RMN em estado-estacionário, esses resultados podem ser estendidos para a escala de well-logging, fato que aumenta consideravelmente a importância desses resultados. Uma vez consolidadas as medidas in-situ, as metodologias propostas deverão auxiliar a indústria de exploração e produção de petróleo a otimizar seus métodos e estratégias de produção, reduzindo seus custos e aumentando a vida útil de seus reservatórios. / The Nuclear Magnetic Resonance (NMR) technique is one of the most versatile techniques for scientific research, specially for the study of dynamics, structure and conformational of materials. In particular, its application in oil science is one of its first routine applications. Methodologies developed specifically to match this scientific community proved to be very useful, and the study of rock/fluid interactions is one of its most successful cases. Since then, important petrophysical properties of oil and gas reservoirs have been determined and understood both in the laboratory and inside the geological formations that store those fluids. Among these properties, the permeability, porosity and wettability of a reservoir formation are the most important information to be estimated. For this purpose, the determination and correlation of possible rock/fluid interaction effects that cause alterations on magnetic relaxation phenomena and molecular diffusion, such as the influence of the magnetic susceptibility and geometry of the porous space, were studied in eleven sedimentary rock cores taken from outcrops, since they have the same petrophysical properties presented by oil reservoir rocks. The results obtained confirmed that the types of rock/fluid interactions, detectable by the NMR experiments, are for instance influenced by the porous media geometry and structure, being possible so to obtain such information using those NMR results. Thus, the main goal of this work was the study and establishment of these correlations, in order to obtain petrophysical information with greater accuracy and comprehensiveness. In particular, the study of the T1/T2 ratio, which is the ratio of longitudinal and transverse relaxation times, common parameters strongly involved in a typical NMR measurement, was found to be useful in establishing those correlations. Moreover, different methodologies to measure this and other NMR parameters were studied and proposed, whose joint interpretation proved to be fundamental for the success of these correlations. The permeability of the rocks, an important parameter that controls the fluid transport properties inside the porous matrix, was estimated using the proposed methodologies, showing excellent results. Appling the steady-state NMR technique, those results could be extended to the well-logging scale, which could improve considerably the importance of that results. Once confirmed in measurements in-situ, the proposed methodologies will be able to help the production and exploration industry to optimize their production methods and strategies, thereby reducing production costs and increasing the reservoir lifetimes.
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Cálculo da contribuição de impurezas magnéticas à relaxação nuclear em metais / Magnetic-impurity contribution to the nuclear magnetic relaxation in metalsCohen, Abraham Moyses 08 November 1982 (has links)
As técnicas do grupo de renormalização, desenvolvidas originalmente por Wilson para o problema Kondo, são aplicadas, pela primeira vez, ao problema de relaxação de spins nucleares em ligas magnéticas diluídas. Desenvolve-se um formalismo para calcular o tempo de relaxação longitudinal T1 válido para todas as faixas de temperatura 0 < KBT < D, onde D é a largura da banda. Em particular, para T=0 deriva-se uma expressão analítica para T1; para distâncias R, entre o núcleo e a impureza, muito grandes comparadas com o inverso do momento de Fermi kF o resultado recai na expressão obtida por Korringa para o tempo de relaxação de spins nucleares em metais puros. Diminuindo-se kFR, T1 aumenta, tornando-se infinito no limite kF R→ 0. Desenvolve-se um método numérico para o cálculo do tempo de relaxação a temperaturas finitas. Para estimar a precisão desse método, calcula-se T1 no limite T 𔾴 0; o resultado desse cálculo concorda muito bem com a expressão analítica obtida anteriormente. O resultado de T1 para T1 no limite T → 0 concorda com aquele obtido recentemente por Roshen e Saam, que analisaram este problema usando a teoria de líquido de Fermi de Nozieres apenas no limite kF R→ ∞. Apontam-se as deficiências no tratamento desses autores para o caso de kFR finito, onde seus resultados discordam daqueles aqui derivados / The renormalization group techniques developed by Wilson for the Kondo problem are applied, for the first time, to the calculation of nuclear spin relaxation rates in dilute magnetic alloys. A procedure that calculates the longitudinal relaxation time T1 is derived; for distances R between the impurity and the nucleus large compared to the inverse Fermi momentum kF, the result is identical to Korringa\'s expression for the nuclear spin relaxation rate in the pure For smaller kFR, T1 increases and become infinite as kF R→ 0. A numerical approach, capable of calculating T1 at finite temperatures, is presented and tested by calculating T1 for T → 0; the numerical results are in excellent agreement with the analytical expression discussed above. Only for kF R→ ∞ do the results for T1 at T=0 agree with those found by Roshen and Saam, who recently analysed this problem in the light of Nozieres\'s Fermi liquid theory. The reasons for the discrepancy for finite KFR are discussed
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Cálculo da contribuição de impurezas magnéticas à relaxação nuclear em metais / Magnetic-impurity contribution to the nuclear magnetic relaxation in metalsAbraham Moyses Cohen 08 November 1982 (has links)
As técnicas do grupo de renormalização, desenvolvidas originalmente por Wilson para o problema Kondo, são aplicadas, pela primeira vez, ao problema de relaxação de spins nucleares em ligas magnéticas diluídas. Desenvolve-se um formalismo para calcular o tempo de relaxação longitudinal T1 válido para todas as faixas de temperatura 0 < KBT < D, onde D é a largura da banda. Em particular, para T=0 deriva-se uma expressão analítica para T1; para distâncias R, entre o núcleo e a impureza, muito grandes comparadas com o inverso do momento de Fermi kF o resultado recai na expressão obtida por Korringa para o tempo de relaxação de spins nucleares em metais puros. Diminuindo-se kFR, T1 aumenta, tornando-se infinito no limite kF R→ 0. Desenvolve-se um método numérico para o cálculo do tempo de relaxação a temperaturas finitas. Para estimar a precisão desse método, calcula-se T1 no limite T 𔾴 0; o resultado desse cálculo concorda muito bem com a expressão analítica obtida anteriormente. O resultado de T1 para T1 no limite T → 0 concorda com aquele obtido recentemente por Roshen e Saam, que analisaram este problema usando a teoria de líquido de Fermi de Nozieres apenas no limite kF R→ ∞. Apontam-se as deficiências no tratamento desses autores para o caso de kFR finito, onde seus resultados discordam daqueles aqui derivados / The renormalization group techniques developed by Wilson for the Kondo problem are applied, for the first time, to the calculation of nuclear spin relaxation rates in dilute magnetic alloys. A procedure that calculates the longitudinal relaxation time T1 is derived; for distances R between the impurity and the nucleus large compared to the inverse Fermi momentum kF, the result is identical to Korringa\'s expression for the nuclear spin relaxation rate in the pure For smaller kFR, T1 increases and become infinite as kF R→ 0. A numerical approach, capable of calculating T1 at finite temperatures, is presented and tested by calculating T1 for T → 0; the numerical results are in excellent agreement with the analytical expression discussed above. Only for kF R→ ∞ do the results for T1 at T=0 agree with those found by Roshen and Saam, who recently analysed this problem in the light of Nozieres\'s Fermi liquid theory. The reasons for the discrepancy for finite KFR are discussed
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Água e carboidratos : aspectos macroscópicos e moleculares de suas interações / Water and carbohydrates : macroscopic and molecular aspects of their interactionsCardoso, Marcus Vinicíus Cangussu, 1981- 20 August 2018 (has links)
Orientadores: Edvaldo Sabadini, Munir Salomão Skaf / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-20T16:17:25Z (GMT). No. of bitstreams: 1
Cardoso_MarcusViniciusCangussu_D.pdf: 5363072 bytes, checksum: 77f8ee9c80c8ce3514b001281dfddae6 (MD5)
Previous issue date: 2012 / Resumo: Soluções aquosas de mono, di, oligo, e polissacarídeos foram estudas nos níveis macroscópico e molecular, empregando-se enfoques termodinâmicos e espectroscópicos. A influência da intensidade da ligação de hidrogênio sobre a solubilidade dos carboidratos (lineares e cíclicos) mostrou-se fortemente dependente de suas solubilidades. Quanto menos solúvel o carboidrato, maior é o efeito da substituição isotópica do solvente (H2O por D2O). Este efeito sugere que carboidratos menos solúveis (e maiores) perturbam mais fortemente a estruturação das moléculas de água. Devido ao efeito cooperativo da transição coil-helix da k-carragena, o efeito isotópico sobre a gelificação é bastante intensificado. Segundo um perspectiva mais molecular, as taxas de troca protônicas, kb, entre os prótons da água e os grupos OH dos carboidratos dependem da natureza do açúcar, sendo os maiores valores observados para a forma linear, seguida pela forma piranosidea e por último pela forma furanosidea. Já as transferências de magnetização entre as populações de prótons da água e dos grupos CH-carboidratos são moduladas pelos movimentos moleculares e intermediadas pelas trocas protônicas com os grupos OH. Propõe-se que os prótons das moléculas de água interagem preferencialmente com os prótons OH e negligenciavelmente com os prótons CH. Estudos de relaxação H mostraram-se ricos para o estudo de processos moleculares de agregação micelar dos n-alquil-glicosídeos sendo possível demonstrar experimentalmente que a agregação leva a indisponibilização das hidroxilas ao interagirem com as moléculas de água / Abstract: Aqueous solutions of mono, di, oligo, and polysaccharides were studied on the macroscopic and molecular standpoints through thermodynamic and spectroscopic approaches. The effect of hydrogen-bonding strength on the solubility of a series of (linear and cyclic) saccharides showed to be strongly dependent of the solubility of the carbohydrate. As lower is the solubility of the carbohydrate, greater will be the deuterium isotopic effect of the solvent (H2O for D2O) on the carbohydrate solubilities. These results suggest that low soluble carbohydrates (and larger ones) perturb more strongly the water structure. Owing to the cooperativity of the coil-helix transition, the deuterium isotope effect on the gelling of k-carrageenan is intensified leading to stronger gels and double-helices more stable in D2O. Looking deeper onto a molecular perspective and based on spin-spin nuclear magnetic relaxation, the proton exchange rates, kb, between water and OH-carbohydrate, are dependent of the nature of the saccharide. The kb values are higher for linear than for pyranoside form, and the slowest value is found for fructofuranoside form. The transferring of magnetization between proton pools of water and CH-carbohydrates are modulated by molecular motions and intermediated by proton exchanging process between water and OH-carbohydrate protons. H NMR relaxation experiments of exchangeable protons provide to be rich in probing the micelar aggregation of n-alkyl-glucosides. It was possible to demonstrate experimentally that the aggregation of the surfactant molecules provoke a drastic reduction on the interactions between water and OH-saccharide head groups / Doutorado / Físico-Química / Doutor em Ciências
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Local Dynamics Of Polymers In Solution Monitored By 13c NMR Relaxation : Studies On Poly (2-Vinylpyridine) And Poly (Isobutylmethacrylate)Ravindranathan, Sapna 09 1900 (has links) (PDF)
No description available.
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Estudo de propriedades petrofísicas de rochas sedimentares por Ressonância Magnética Nuclear / Petrophysical properties study of sedimentary rocks by Nuclear Magnetic ResonanceAndré Alves de Souza 28 May 2012 (has links)
A Ressonância Magnética Nuclear (RMN) é uma das técnicas mais versáteis de investigação científica experimental, com destaque para o estudo da dinâmica, estrutura e conformação de materiais. Em particular, sua utilização na ciência do petróleo é uma de suas primeiras aplicações rotineiras. Metodologias desenvolvidas especificamente para atender esta comunidade científica mostraram-se desde cedo muito úteis, sendo o estudo da interação rocha/fluido uma de suas vertentes mais bem sucedidas. Desde então, importantes propriedades petrofísicas de reservatórios de óleo e gás têm sido determinadas e entendidas, tanto em laboratório quanto in-situ, nas próprias formações geológicas que armazenam esses fluidos. Entre estas propriedades, a permeabilidade, porosidade e molhabilidade de um reservatório figuram dentre as mais importantes informações estimadas. Com essa finalidade, a determinação e correlação dos possíveis efeitos que a interação rocha/fluido pode causar nos fenômenos de relaxação magnética e difusão molecular, tais como influência da susceptibilidade magnética e geometria do espaço poroso, foram estudados em onze rochas sedimentares retiradas de afloramentos, que possuem propriedades petrofísicas similares àquelas apresentadas por rochas reservatório de petróleo. Os resultados mostraram que os tipos de interação rocha/fluido, detectáveis pelos experimentos de RMN, são por sua vez influenciados pelas características geométricas e estruturais do meio poroso, sendo possível obter essas informações pelos resultados de RMN. Assim, este trabalho teve como objetivo principal estudar e estabelecer essas correlações, afim de se obter informações petrofísicas com maior acurácia e abrangência. Em particular, o estudo da razão T1/T2, que é a razão entre os tempos de relaxação longitudinal e transversal, típicos parâmetros envolvidos numa medida de RMN, mostrou ser um parâmetro útil no estabelecimento destas correlações. Ainda, diferentes metodologias para se medir estes e outros parâmetros de RMN foram estudadas e propostas, cuja interpretação conjunta mostrou ser fundamental para o entendimento dessas correlações. A permeabilidade das rochas, importante parâmetro que define as propriedades de transporte de fluidos dentro da matriz porosa, foi estimada aplicando-se essas metodologias propostas, mostrando excelentes resultados. Através do uso da técnica de RMN em estado-estacionário, esses resultados podem ser estendidos para a escala de well-logging, fato que aumenta consideravelmente a importância desses resultados. Uma vez consolidadas as medidas in-situ, as metodologias propostas deverão auxiliar a indústria de exploração e produção de petróleo a otimizar seus métodos e estratégias de produção, reduzindo seus custos e aumentando a vida útil de seus reservatórios. / The Nuclear Magnetic Resonance (NMR) technique is one of the most versatile techniques for scientific research, specially for the study of dynamics, structure and conformational of materials. In particular, its application in oil science is one of its first routine applications. Methodologies developed specifically to match this scientific community proved to be very useful, and the study of rock/fluid interactions is one of its most successful cases. Since then, important petrophysical properties of oil and gas reservoirs have been determined and understood both in the laboratory and inside the geological formations that store those fluids. Among these properties, the permeability, porosity and wettability of a reservoir formation are the most important information to be estimated. For this purpose, the determination and correlation of possible rock/fluid interaction effects that cause alterations on magnetic relaxation phenomena and molecular diffusion, such as the influence of the magnetic susceptibility and geometry of the porous space, were studied in eleven sedimentary rock cores taken from outcrops, since they have the same petrophysical properties presented by oil reservoir rocks. The results obtained confirmed that the types of rock/fluid interactions, detectable by the NMR experiments, are for instance influenced by the porous media geometry and structure, being possible so to obtain such information using those NMR results. Thus, the main goal of this work was the study and establishment of these correlations, in order to obtain petrophysical information with greater accuracy and comprehensiveness. In particular, the study of the T1/T2 ratio, which is the ratio of longitudinal and transverse relaxation times, common parameters strongly involved in a typical NMR measurement, was found to be useful in establishing those correlations. Moreover, different methodologies to measure this and other NMR parameters were studied and proposed, whose joint interpretation proved to be fundamental for the success of these correlations. The permeability of the rocks, an important parameter that controls the fluid transport properties inside the porous matrix, was estimated using the proposed methodologies, showing excellent results. Appling the steady-state NMR technique, those results could be extended to the well-logging scale, which could improve considerably the importance of that results. Once confirmed in measurements in-situ, the proposed methodologies will be able to help the production and exploration industry to optimize their production methods and strategies, thereby reducing production costs and increasing the reservoir lifetimes.
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Development of Multifunctional Nanoparticles: From Synthesis to Theranostic ApplicationsOzkaya Ahmadov, Tevhide 03 June 2016 (has links)
No description available.
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Assessment Of Molecular Interactions Via Magnetic Relaxation: A Quest For Inhibitors Of The Anthrax ToxinSantiesteban, Oscar 01 January 2012 (has links)
Anthrax is severe disease caused by the gram-positive Bacillus anthracis that can affect humans with deadly consequences. The disease propagates via the release of bacterial spores that can be naturally found in animals or can be weaponized and intentionally released into the atmosphere in a terrorist attack. Once inhaled, the spores become activated and the anthrax bacterium starts to reproduce and damage healthy macrophages by the release of the anthrax toxin. The anthrax toxin is composed of three virulent factors: (i) anthrax protective antigen (APA), (ii) anthrax lethal factor (ALF), and (iii) anthrax edema factor (AEF) that work in harmony to effectuate the lethality associated with the disease. Out of the two internalized factors, ALF has been identified to play a critical role in cell death. Studies in animals have shown that mice infected with an anthrax strain lacking ALF survive the infection whereas when ALF is present the survivability of the mice is eliminated. Although the current therapy for anthrax is antibiotic treatment, modern medicine faces some critical limitations when combating infections. Antibiotics have proven very efficient in eliminating the bacterial infection but they lack the ability to destroy or inhibit the toxins released by the bacteria. This is a significant problem since ALF can remain active in the body for days after the infection is eliminated with no way of inhibiting its destructive effects. The use of inhibitors of ALF is an attractive method to treat the pathogenesis of anthrax infections. Over the last decade several inhibitors of the enzymatic activity of ALF have been identified. In order to identify inhibitors of ALF a variety of screening approaches such as library screenings, Mass Spectroscopy- based screenings and scaffold-based NMR screening have been used. Results from these iv screening have yielded mainly small molecules that can inhibit ALF in low micromolar to nanomolar concentrations. Yet, although valuable, these results have very little significance with regards to treating ALF in a real-life scenario since pharmaceutical companies are not willing to invest in further developing these inhibitors. Furthermore, the low incidence of inhalation anthrax, the lack of a market for an ALF inhibitor, and the expenses associated with the approval process of the FDA, have hindered the motivation of pharmaceutical companies to pursuit these kind of drugs. Therefore we have screened a small-molecule library of FDA approved drugs and common molecules in order to identify currently approved FDA drugs that can also inhibit ALF (Chapter III). The screening revealed that five molecules: sulindac, fusaric acid, naproxen, ketoprofen and ibuprofen bound to either ALF or APA with sulindac binding both. Additionally, we have developed a nanoparticle-based screening method that assesses molecular interactions by magnetic relaxation changes (Chapter II). Using this assay, we were able to accurately measure the dissociation constants of different interactions between several ligands and macromolecules. Moreover, we have used computational docking studies to predict the binding site of the identified molecules on the ALF or APA (Chapter IV). These studies predicted that two molecules sulindac and fusaric acid could be potential inhibitors of ALF since they bind at the enzymatic pocket. As a result, we tested the inhibitory potential of these molecules as well as that of the metabolic derivatives of sulindac (Chapter V). Results from these studies provided conclusive evidence that fusaric acid and sulindac were both strong inhibitors of ALF. Furthermore, the metabolic derivatives of sulindac, sulindac sulfide and sulindac sulfone v also inhibited ALF. Overall, taking together these results we have discovered the alternate use of a currently used drug for the treatment of ALF pathogenesis.
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