Physical Sciences and Mathematics Commons^™

Process For The Preparation Of Citalopram Intermediate, Aslam A. Malik, Hasan Palandoken, Joy A. Stringer, Dershing Huang, Antonio Romero, Olivier Dapremont

Chemistry and Biochemistry

The present invention provides, inter alia, a novel process for the preparation of Citalopram, a known antidepressant.

The Role Of Phosducin-Like Protein And The Cytosolic Chaperonin Cct In G Beta Gamma Dimer Assembly, Ting Hu

Theses and Dissertations

Phosducin-like protein (PhLP), a G protein beta gamma subunit dimer binder and G protein signaling regulator, was suggested to regulate the activity of cytosolic chaperonin CCT by their high affinity interaction. In the present study, the three-dimensional structure of PhLP:CCT complex has been solved by cryoelectron microscopy. PhLP was found to bind only one of the chaperonin rings with both N- and C-terminal domains. It spans the central folding cavity of CCT and interacts with two opposite sides of the top apical region, inducing the constraining of the entry of the folding cavity. These findings support a putative role of …

Palladium-Imidazolium Carbene Catalyzed Heck Coupling Reactions And Synthesis Of A Novel Class Of Fluoroanthracenylmethyl Ptc Catalysts, Jiuqing Zhang

Theses and Dissertations

Palladium catalyzed Heck coupling with aryl and alkenyl halides has become a powerful means of carbon-carbon bond formation. This standard synthetic method has been developed to a high level of utility using various catalysts, conditions and substrates. Yet significant drawbacks remain, including poor reactivity, the need for high temperatures and base, limited substrate generality, and selectivity. Mixed products often suffer from olefin migration following insertion. N-Heterocyclic carbenes (NHC) have proven to be electron-rich donors which provide higher stability and reactivity than phosphines. In a previous paper reported by our research group the imidazolium-palladium carbene has proven to be highly efficient …

Performance Of Binary-Encounter-Bethe (Beb) Theory For Electron-Impact Ionization Cross Sections Of Molecules Containing Heavy Elements (Z > 10), Gregory E. Scott, Karl K. Irikura

Chemistry and Biochemistry

The binary-encounter-Bethe (BEB) theory developed by Kim and coworkers has been successful for computing electron-impact ionization cross sections of many molecules. However, some recent publications have stated that BEB theory performs poorly for molecules that contain heavier elements such as chlorine and sulfur. We have found that the BEB calculations in those publications were performed incorrectly. When performed correctly, BEB predictions are as good for heavy-element molecules as for light-element molecules. We recommended recently that an alternative, less-confusing procedure be used for molecules that contain heavier elements. The alternative procedure, based upon effective core potentials (ECPs), does not require explicit …

Total Syntheses Of (+)-Geldanamycin, (-)-Ragaglitazar, And (+)-Kurasoin A And Phase-Transfer-Catalyzed Asymmetric Alkylation, Erik J. Hicken

Theses and Dissertations

Geldanamycin possesses various biological activities as seen in the NCI 60 cell line panel (13 nM avg., 70 nM SKBr-3 cells). The predominant mode of action providing these unique results arises from the ability of geldanamycin (GA) to bind to the chaperone heat shock protein 90 (Hsp90). Despite its complicated functionality, the first total synthesis of GA was accomplished, which included two new reactions developed specifically to address the stereochemical features. The final step in the synthesis of GA was a demethylation-oxidation sequence to generate the desired para-quinone. This step could only be accomplished with HNO3/AcOH, producing GA in …

Specific Heat And Thermodynamic Properties Of Metallic Systems: Instrumentation And Analysis, Brian E. Lang

Theses and Dissertations

A small-scale adiabatic calorimeter has been constructed as part of a larger project to study nano-particles and to facilitate specific heat measurements on samples where it is difficult to obtain enough material to run on the current large-scale adiabatic apparatus. This calorimeter is designed to measure sample sizes of less than 0.8 cc over a temperature range from 13 K to 350 K. Specific heat results on copper, sapphire, and benzoic acid show the accuracy of the measurements to be better than ±0.4% for temperatures higher than 50 K. The reproducibility of these measurements is generally better than ±0.25%. Experimental …

Microcapsule Biosensors Based On Competitive Binding And Fluorescence Resonance Energy Transfer Assays, Swetha Chinnayelka

Doctoral Dissertations

Fluorescent sensing systems offer the potential for minimally invasive monitoring with implantable devices, but they require carrier technologies that provide suitable immobilization, accessibility, and biocompatibility while maintaining adequate response characteristics. Towards the development of this goal, a general design of a biosensor with the capability of detecting different metabolites was investigated. The approach is based on the encapsulation of a competitive binding assay in microcapsules and monitoring the changes in fluorescence resonance energy transfer (FRET) in the presence of analyte. To experimentally demonstrate this type of sensing system, glucose was chosen as the model target analyte. The design, fabrication, and …

A Facile Synthesis Of (Tert-Alkoxy)Amines, Hasan Palandoken, Chris M. Bocian, Michelle R. Mccombs, Michael H. Nantz

Chemistry and Biochemistry

Tertiary alcohols react with stoichiometric BF₃·Et₂O and N-hydroxyphthalimide to yield N-alkoxyphthalimides. Subsequent hydrazinolyses afford the title compounds.

Polymer Microchips For Capillary Electrophoresis And Electric Field Gradient Focusing Of Biomolecules, Ryan Thomas Kelly

Theses and Dissertations

Polymeric materials have seen increasing use as microfluidic device substrates due to their low cost and the simplicity of templated fabrication procedures. I showed that poly(methyl methacrylate) (PMMA) microdevices could be enclosed in a boiling water bath, which allowed the seal to form more quickly than in conventional approaches, and enabled microchannels to remain hydrated throughout the bonding process. Microchip capillary electrophoresis (µ-CE) devices were fabricated using water-based enclosure, and a mixture of fluorescently labeled amino acids was separated in 30 s in these microchips. To create more robust capillary electrophoresis (CE) microdevices with improved separation performance, phase-changing sacrificial materials …

Structure Elucidation Of Bioactive Compounds Isolated From Endophytes Of Alstonia Scholaris And Acmena Graveolens, Nicholas James Hundley

Theses and Dissertations

Alstonia scholaris is an evergreen tree native to Southeast Asia and Australia. It is commonly used as a medicinal plant throughout these regions. In the present study, an endophyte of the genus Xylaria was isolated from a stem of Alstonia scholaris, its mycelia and exudate extracted, and the extract assayed for growth inhibition of HeLa cancer cells in vitro. Several known compounds were isolated and identified based on NMR, infrared, and mass spectral data. The compounds identified are 19,20-epoxycytochalasin C; 19,20epoxycytochalasin D; and xylobovide. Two other compounds, fusaric acid and dehydrofusaric acid, were discovered in an endophyte of the Hypocreales …

An Acyl Radical Cascade Model For The Total Synthesis Of Lyconadin A, Seth W. Grant

Theses and Dissertations

Lyconadin A (1) is a structurally unique Lycopodium alkaloid with antitumor properties, isolated from the club moss Lycopodium complanatum. We are developing a synthetic route to 1 based on a novel 7-exo-trig/6-exo-trig acyl radical cascade cyclization. The synthesis of model acyl radical cascade precursor 23 will be presented. Key features of this synthesis include the suppression of competing elimination during the alkylation of a hindered phenethyl bromide and the use of a lactone as a precursor to a compound bearing two differentially protected primary alcohols. An account of our studies on the model acyl radical cascade cyclization (23 to 24 …

Effect Of Melatonin And Dopamine In Site Specific Phosphorylation Of Phosducin In Intact Retina, Arinzechukwu Okere Nkemdirim

Theses and Dissertations

Phosducin (Pdc) is a 28 kDa binding partner for the G protein beta gamma subunit dimer (G-beta-gamma) found abundantly in the photoreceptor cells of the retina and pineal gland. In the retina, light-dependent changes in cAMP and Ca2+ control the phosphorylation of Pdc at serine 73 and 54, respectively, which in turn controls the binding of Pdc to G protein beta gamma subunit dimer . G protein beta gamma subunit dimer binding has been proposed to facilitate light-driven transport of G protein beta gamma subunit dimer from the site of phototransduction in the outer segment of the photoreceptor cell to …

Post-Translational Regulation Of Adipose Differentiation-Related Protein By The Ubiquitin/Proteasome Pathway, John Tansey

Chemistry Faculty Scholarship

Adipose differentiation-related protein (ADRP) is localized to lipid droplets in most mammalian cells. ADRP, proposed to regulate
fatty acid mobilization and lipid droplet formation, is linked to lipid accumulation in foam cells of human atherosclerotic
lesions. In this report, we show that ADRP protein accumulates in Chinese hamster ovary fibroblastic cells cultured in the
presence of oleic acid but is destabilized when fatty acid sources are removed from culture serum. The latter effect was blocked
by the proteasome inhibitor MG132, whereas inhibitors of other proteolytic processes were ineffective. Pulse-chase experiments
confirmed that ADRP degradation is inhibited by MG132. Conditions that …

The Clearance Of Protein-Bound Solutes By Hemofiltration And Hemodiafiltration, Timothy W. Meyer, Jason L. Walther, Maria Enrica Pagtalunan, Andres W. Martinez, Ali Torkamani, Patrick D. Fong, Natalie S. Recht, Channing R. Robertson, Thomas H. Hostetter

Chemistry and Biochemistry

Background. Hemofiltration in the form of continuous venovenous hemofiltration (CVVH) is increasingly used to treat acute renal failure. Compared to hemodialysis, hemofiltration provides high clearances for large solutes but its effect on protein-bound solutes has been largely ignored.

Methods. Standard clinical systems were used to remove test solutes from a reservoir containing artificial plasma. Clearances of the protein-bound solutes phenol red (C_PR) and indican (C_IN) were compared to clearances of urea (C_UREA) during hemofiltration and hemodiafiltration. A mathematical model was developed to predict clearances from values for plasma flow Q_p, …

Fluorescent Photoinduced Electron Transfer (Pet) Cation Sensors Derived From Natural Products, Kenny Loo

Theses, Dissertations and Culminating Projects

Two new second generation fluorescent switches that are based on the chromophore-spacer-receptor architecture are reported in this thesis. The fluorescence modulation of these switches is a result of quenching or initiating photoinduced electron transfer (PET) between the chromophore and the receptors due to cation binding. These two molecules utilize an alkaloid, anabasine, as the proton receptor, and function as fluorescent off-on-off switches with decreasing pH. One of these molecules also utilizes a coumarin as the chromophore, making it the first rationally designed fluorescent PET system based on natural products. Further studies of two well-known first generation fluorescent switches to achieve …

A Modified Poisson–Boltzmann Analysis Of The Capacitance Behavior Of The Electric Double Layer At Low Temperatures, Douglas Henderson, L. B. Bhuiyan, C. W. Outhwaite

Faculty Publications

The modified Poisson–Boltzmann theory is used to analyze the anomalous behavior of the electric double layer capacitance for small surface charge at low temperatures and densities. Good agreement is found with simulation and recent density-functional theory results. Negative adsorption is also found in line with theory and simulation. An unsatisfactory feature is the relatively poor structure in this region due to the inherent approximations in the theory. This feature is unimportant in relation to the capacitance results but has implications when calculating adsorption properties.

Hard-Sphere Radial Distribution Function Again, Andrij Trokhymchuk, Douglas Henderson, Ivo Nezbeda, Jan Jirsak

Faculty Publications

A theoretically based closed-form analytical equation for the radial distribution function, g(r), of a fluid of hard spheres is presented and used to obtain an accurate analytic representation. The method makes use of an analytic expression for the short- and long-range behaviors of g(r), both obtained from the Percus-Yevick equation, in combination with the thermodynamic consistency constraint. Physical arguments then leave only three parameters in the equation of g(r) that are to be solved numerically, whereas all remaining ones are taken from the analytical solution of the Percus-Yevick equation.

Angiotensin Ii-Mediated Regulation Of The Human Angiotensin Ii Type 1 Receptor Gene, Xylophone Vijai Aasee Victor

Theses and Dissertations

The physiological responses of angiotensin II (Ang II) are mediated across the cell membrane through the angiotensin II type 1 receptor (AT1R), a heptahelical membrane protein coupled to trimeric G-proteins on the cytosolic side. AT1R on binding its ligand, Ang II, leads to downregulation of cell-surface receptor and also its mRNA. We have investigated whether the 3'- and 5'-untranslated regions of the human AT1R mRNA mediate the degradation of hAT1R mRNA by post-transcriptional mechanisms in human adrenocortical carcinoma cell line (H295R cells). Protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate (PMA), showed that the downregulation of hAT1R mRNA is mediated by the …

Development Of A Model For The Kinetics And Mechanism Of Nitrogenase, Phillip E. Wilson

Theses and Dissertations

Nitrogenase has a central role in the global nitrogen cycle as the enzyme that catalyzes the reduction of atmospheric N2 to NH3. Fixed nitrogen is generally limiting in the environment and in agriculture, so nitrogenase has received much attention as an alternative to nitrogen fertilizers. Characterizing the mechanism of nitrogenase is the goal of this work. The molybdenum nitrogenase enzyme system is comprised of the MoFe protein and the Fe protein. Interactions between these proteins and nucleotides are crucial to catalysis. An important approach to characterize these interactions is to correlate the kinetics of nitrogenase catalysis to a mechanism based …

An Analysis Of The Chemical Processes In The Smoke Plume From A Savanna Fire, Jorg Trentmann, Robert J. Yokelson, Peter V. Hobbs, Tanja Winterrath, Ted J. Christian, Meinrat O. Andreae, Sherri A. Mason

Chemistry and Biochemistry Faculty Publications

[1] Photochemistry in young plumes from vegetation fires significantly transforms the initial fire emissions within the first hour after the emissions are injected into the atmosphere. Here we present an investigation of field measurements obtained in a smoke plume from a prescribed savanna fire during the SAFARI 2000 field experiment using a detailed photochemical box-dilution model. The dilution used in the model simulations was constrained by measurements of chemically passive tracers (e.g., CO) near and downwind of the fire. The emissions of the dominant carbonaceous compounds, including oxygenated ones, were taken into account. The field measurements revealed significant production of …

Preparation, Structural Characterization, And Dynamic Properties Investigation Of Permalloy Antidot Arrays, Andriy Vovk, Leszek M. Malkinski, Scott L. Whittenburg, Charles O'Connor, Jin-Seung Jung, Suk-Hong Min

Chemistry and Biochemistry Faculty Publications

Regular nanosized structures are considered to be promising materials for magnetic information storage media with high density of information. Recently attention was paid to static and dynamic magnetic properties arising from dimensional confinement in such nanostructures. Here we present an investigation of permalloy antidot arrays of different thicknesses. Thin permalloyfilms of thickness ranging from were deposited on nanoporous membranes with a pore size of . It was found that additional ferromagnetic resonance peaks appear for film thicknesses below , while films with larger thicknesses show resonanceproperties similar to continuous films. A comparison between the filmsdeposited onto Si wafers and porous …

Biomolecule Detection Via Target Mediated Nanoparticle Aggregation And Dielectrophoretic Impedance Measurement, Philip J. Costanzo, Enzhu Liang, Timothy E. Patten, Scott D. Collins, Rosemary L. Smith

Chemistry and Biochemistry

A new biosensing system is described that is based on the aggregation of nanoparticles by a target biological molecule and dielectrophoretic impedance measurement of these aggregates. The aggregation process was verified within a microchannel via fluorescence microscopy, demonstrating that this process can be used in a real time sensor application. Positive dielectrophoresis is employed to capture the nanoparticle aggregates at the edge of thin film electrodes, where their presence is detected either by optical imaging via fluorescence microscopy or by measuring the change in electrical impedance between adjacent electrodes. The electrical detection mechanism demonstrates the potential for this method as …

Alterations In Uterine And Placental Sodium Pump Abundance May Contribute To The Onset Of Mouse Labor, Carlos Jacob Vance

Theses and Dissertations

Objective: Reductions in sodium pump (SP) abundance can give rise to increases in contractile force in uterine and vascular smooth muscle as well as an increased secretion in secretory cells, including potentially those of the placenta. To determine whether the mouse might serve as a model for human pregnancy in terms of the SP and to determine whether changes in SP abundance anticipate or follow labor, we studied pregnant mice over the final trimester of their pregnancy.

Study Design: C57Bl6 dams (n=46) were bred and studied during their pregnancy. Animals (n=4) were sacrificed at specific gestational time points. Other mice …

Ion Transmission In The First Vacuum Stage Of An Inductively Coupled Plasma Mass Spectrometer, Jeffrey Harris Macedone

Theses and Dissertations

The inductively coupled plasma mass spectrometer (ICP-MS) is the instrument of choice for trace and ultra-trace elemental analysis. However, the ICP-MS suffers from matrix effects. Matrix effects occur when instrument response varies as the composition of the sample matrix is changed. Matrix effects, or non-spectroscopic interferences, limit the accuracy of routine analysis. Identification of the sources of matrix effects provide a basis for reducing or eliminating them. As inaccuracies in the ICP-MS are more severe than those in the ICP atomic emission spectrometer, the problem may be due, at least in part, to the vacuum interface used to couple the …

Clean, High-Yield Preparation Of S,S- And R,S- Amino Acid Isosteres, Aslam A. Malik, Todd E. Clement, Hasan Palandoken, James Robinson Iii, Joy A. Stringer

Chemistry and Biochemistry

The present invention provides compounds and methods that can be used to convert the intermediate halomethyl ketones (HMKs), e.g., chloromethyl ketones, to the corresponding S,S- and R,S-diastereomers. More particularly, the present invention provides: (1) reduction methods; (2) inversion methods; and (3) methods involving the epoxidation of alkenes. Using the various methods of the present invention, the R,S-epoxide and the intermediary compounds can be prepared reliably, in high yields and in high purity.

Temperature Dependence Of The Double Layer Capacitance For The Restricted Primitive Model Of An Electrolyte Solution From A Density Functional Approach, Douglas Henderson, J. Reszko-Zygmunt, Stefan Sokolowski, Dezso Boda

Faculty Publications

We apply a different version of the density functional theory, given by Pizio, Patrykiejew, and Sokolowski [J. Chem. Phys. 121, 11957 (2004)], for a nonuniform restricted primitive model of an electrolyte solution to evaluate the temperature dependence of the capacitance of an electric double layer. We show that this theory is capable of reproducing the computer simulation data at a quantitative level. In particular, the reversal of the temperature dependence of the capacitance at low temperatures is predicted. This phenomenon has been difficult to predict from theory. Further, this theory also leads to an accurate description of the double layer …

Preparation Of 2s,3s-N-Isobutyl-N-(2-Hydroxy-3-Amino-4-Phenylbutyl)-P-Nitrobenzenesulfonylamide Hydrochloride And Other Derivatives Of 2-Hydroxy-1,3-Diamines, Aslam A. Malik, Hasan Palandoken, Joy A. Stringer, Roland P. Carlson, John Leach, Thomas G. Archibald, Robert G. Miotke

Chemistry and Biochemistry

The present invention provides a new process for the preparation of 2S,3S-N-isobutyl-N-(2-hydroxy-3-amino-4phenylbutyl)- p-nitrobenzenesulfonylamide hydrochloride, wherein this compound is prepared directly from the chloromethylalcohol. Importantly, the process of the present invention results in higher yields of 2S,3S-N-isobutyl-N-(2hydroxy -3 -amino -4-phenylbutyl) -pnitrobenzenesulfonylamide hydrochloride without sacrificing its purity. The processes of the present invention can be used to prepare not only the 2S,3S-derivative, but also the 2R,3S-, 2S,2R- and the 2R,3R-derivatives.

Removal Of P-Cresol Sulfate By Hemodialysis, Andres W. Martinez, Natalie S. Recht, Thomas H. Hostetter, Timothy W. Meyer

Chemistry and Biochemistry

Protein-bound solutes are poorly cleared by dialysis. Among the most extensively studied of these solutes is p-cresol, which has been shown to be toxic in vitro. This study examined the form in which p-cresol circulates and quantified its removal by hemodialysis. HPLC analysis of plasma from hemodialysis patients contained a peak whose mobility corresponded to synthetic p-cresol sulfate (PCS) but no detectable unconjugated p-cresol. Treatment with sulfatase resulted in recovery of this peak as p-cresol, confirming its identity. Subsequent studies compared the removal of PCS and another protein-bound solute, indican, to the removal of urea during clinical hemodialysis treatments. …

Ethan's Land Use Photos, Colby Environmental Assessment Team, Colby College, Problems In Environmental Science Course (Biology 493), Colby College

Colby College Watershed Study: China Lake (2005, 1989)

No abstract provided.

Reduced Macrophage Apoptosis Is Associated With Accelerated Atherosclerosis In Low-Denstiy Lipoprotein Receptor-Null Mice, Michael Sinensky, J. Liu, D. P. Thweke, Y. R. Su, M. F. Linton, S. Fazio

Faculty Publications, Biological Sciences

Objective— The majority of apoptotic cells in atherosclerotic lesions are macrophages. However, the pathogenic role of macrophage apoptosis in the development of atherosclerosis remains unclear. Elevated expression of Bax, one of the pivotal proapoptotic proteins of the Bcl-2 family, has been found in human atherosclerotic plaques. Activation of Bax also occurs in free cholesterol-loaded and oxysterol-treated mouse macrophages. In this study, we examined the effect of Bax deficiency in bone marrow-derived leukocytes on the development of atherosclerosis in low-density lipoprotein receptor-null (LDLR−/−) mice. Methods and Results— Fourteen 8-week-old male LDLR−/− mice were lethally irradiated and reconstituted with either wild-type (WT) …