Digital Commons Network^™

Structural Insight Into The Mechanism Of Oxygen Activation And Substrate Selectivity Of Flavin-Dependent N-Hydroxylating Monooxygenases, Stefano Franceschini, Michael Fedkenheuer, Nancy J. Vogelaar, Howard H. Robinson, Pablo Sobrado, Andrea Mattevi

Chemistry Faculty Research & Creative Works

SidA from the human pathogen Aspergillus fumigatus catalyzes the generation of N5-hydroxyornithine in the biosynthesis of siderophores, a reaction essential for virulence. The crystal structures of SidA in complex with ornithine and lysine reveal the geometry of the interactions among flavin, NADP+, and the substrate amine group that underlie the hydroxylation reaction. The structural elucidation of the enzyme in complex with arginine provides insight into the role of electrostatics and hydrogen bonding in the mechanism of oxygen activation in this family of enzymes. © 2012 American Chemical Society.

Synthesis And Characterization Of Chain-End Functionalization Of Glycosaminoglycans, Nikola Paulic, Jacob J. Weingart

Undergraduate Research Posters 2012

This presentation reports the CSU Summer Undergraduate Research project, which is the synthesis and characterization of chain-end functionalized CS derivatives, which will be used to investigate various bio-orthogonal conjugation reactions in attempt to create a novel CS-rTM conjugate.

Derivatization Of Free Glycans For Glycan Sensor And Glyco-Functionalization Applications, Rhonda D. Jones

Undergraduate Research Posters 2012

Glycans, especially, cell surface glycans acting as receptors, are involved in a wide range of biological processes. Analysis of the cell surface glycans provides a basis for understanding the molecular mechanism of glycan-mediated biological process. The present method can be applied in derivatizing sugars from natural sources for glycan sensor and glyco-functionalization applications.

Aldehyde Bromination For Stilbenoid Syntheses, Dhanunjay N. Padal

Student Theses and Dissertations

This thesis will focus on being able to synthesize an alkyne from an aldehyde, forming a dibromoalkene as an intermediate. This alkyne then can be converted to a stilbenoid in the future on reaction with alkyl lithium. Combretastatin A-4 and resveratrol are the stilbenoids, which have biological significance. These compounds have therapeutic value and are extracted from plants or fruits for their production. The chemical synthesis for these compounds from an economic point of view is very important. The Corey-Fuchs reaction was used to synthesize the dibromoalkenes. Literature cites use of triphenylphosphine as a reactant, but triisopropyl phosphite was used …

Rnase L Controls Terminal Adipocyte Differentiation, Lipids Storage And Insulin Sensitivity Via Chop10 Mrna Regulation, O. Fabre, T. Salehzada, K. Lambert, Y. Boo Seok, Aimin Zhou, J. Mercier, C. Bisbal

Chemistry Faculty Publications

Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role of an endoribonuclease, endoribonuclease L (RNase L), using wild-type and RNase L-knockout mouse embryonic fibroblasts (RNase L^−/−-MEFs). Here, we identify C/EBP homologous protein 10 (CHOP10), a dominant negative member of the CCAAT/enhancer-binding protein family, as a specific RNase L target. We show that RNase L is associated with CHOP10 mRNA and regulates its stability. CHOP10 expression is conserved in RNase …

Development And Validation Of A Rapid Lc-Ms/Ms Method Fortthe Determination Of Jcc76, A Novel Antitumor Agent For Breast Cancer, In Rat Plasma And Its Application To A Pharmacokinetics Study, Xiaohan Cai, Bo Zhong, Bin Su, Songlin Xu, Baochuan Guo

Chemistry Faculty Publications

JCC76 is a novel nimesulide analog that selectively inhibits the human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cell proliferation and tumor progression. To support further pharmacological and toxicological studies of JCC76, a novel and rapid method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the quantification of the compound in rat plasma. A C18 column was used for chromatographic separation, and the mobile phase was aqueous ammonium formate (pH 3.7; 5 mm)–methanol (1:9, v/v) with an isocratic elution. With a simple liquid–liquid extraction procedure using the mixture of methyl …

Identification Of Selective Tubulin Inhibitors As Potential Anti-Trypanosomal Agents, Rati Lama, Ranjodh Sandhu, Bo Zhong, Bibo Li, Bin Su

Chemistry Faculty Publications

The potency of a series of sulfonamide tubulin inhibitors against the growth of Trypanosoma brucei (T. brucei), as well as human cancer and primary fibroblast cells were evaluated with the aim of determining whether compounds that selectively inhibit parasite proliferation could be identified. Several compounds showed excellent selectivity against T. brucei growth, and have the potential to be used for the treatment of Human African trypanosomiasis. A T. brucei tubulin protein homology model was built based on the crystal structure of the bovine tubulin. The colchicine-binding domain, which is also the binding site of the tested sulfonamide tubulin inhibitors, showed …

Structure To Function: Case Studies Of Hotdog-Fold Superfamily Thioesterases From Escherichia Coli, John A. Latham

Chemistry and Chemical Biology ETDs

My doctoral research primarily focuses on the Escherichia coli hotdog-fold thioesterases ydiI and ybgC. The ydiI gene is colocalized in the operon ydiHIJ. A substrate screen provided evidence that YdiI prefers aryl-CoA substrates and discriminated against the analogous aryl-ACP, unlike the paralog YbdB which works on 2,4-DHB-EntB in the enterobactin synthesis pathway. A bioinformatic approach showed that in some bacteria, ydiI is colocalized with genes from the menaquinone pathway. YdiI was shown to catalyze the hydrolysis of DHNA-CoA with physiological relevance (k_cat/K_M ~ 10⁵). Furthermore, the E. coli YdiI- strain was shown to …

Alkynal Involved Organocatalytic Reactions, Xinshuai Zhang

Chemistry and Chemical Biology ETDs

During the past twenty years, vast progress has been achieved in the field of organocatalysis. One of the fruitful areas is iminium catalysis using α, β-unsaturated aldehydes as essential reactants. Enals involved enantioselective reactions (including single-step reactions and cascade/tandem reactions) represent an enormous and fruitful research branch. In contrast, the protocols for the corresponding alkynals, even in single-step conjugate addition reactions, are extremely rare. Toward this end, my Ph. D. research work mainly focuses on the development of alkynal involved organocatalytic reactions and expands the scope of organocatalysis by uncovering new activation modes. Unlike enals, ynals with sp hybridized C≡C …

Synthesis And Catalytic Applications Of Platinum(Ii) And Palladium(Ii)-Pta And Dapta Complexes, Sitaram Acharya

Dissertations

The cage-like tertiary phosphine, 1,3,5-triaza-7-phosphaadamantane (PTA) has recently received interest because of its water-solubility, air-stability, non-ionic, non-surfactant, and basic nature. These properties can solubilize transition metal complexes in the aqueous phase. A related air-stable derivative, N,N’-diacetyl-1-3-5-triaza-7-phosphaadamantane (DAPTA) has greater water-solubility than PTA, however, its coordination chemistry has not been significantly explored. This study involved the synthesis and characterization of a series of novel air-stable and water-soluble four-coordinated dialkyl, dialkynyl, dihalo, and halo(alkyl) complexes of platinum and palladium bearing PTA and DAPTA ligands. The alkyl complexes of the type MX(R)P2 (M = Pt, Pd; X = Cl, Br, I; R = …

Nickel Catalyzed Homoallylation Reactions And Synthesis Of Potent Inhibitors Of Yoph, Mahesh Prasad Paudyal

Dissertations

Amphidinolides are cytotoxic natural products isolated from marine dinoflagellate Amphidinium species. Amphidinolides C, C2 and F are active against cancer cell lines. Homoallylation of aldehydes with isoprene and triethylborane catalyzed by Ni(acac)2 gave hydroxyalkenes in good yield with excellent regio- and stereoselectivity. Cross metathesis of the hydroxyalkenes with methyl acrylate using second-generation Grubbs catalyst and copper(I) iodide afforded α,β-unsaturated esters, which underwent cyclization in the presence of DBU to produce tetrahydrofurans with the correct relative configuration for the C1-C9 fragment of amphidinolides C, C2, and F. Homoallylation of chiral and achiral diene carboxylate esters and dienecarboxamides with various aldehydes were …

Immobilized Bis-Indenyl Ligands For Stable And Cost-Effective Metallocene Catalysts Of Hydrogenation And Polymerization Reactions, Thomas Max Simerly

Electronic Theses and Dissertations

Reactions of catalytic hydrogenations and polymerizations are widely used in industry for manufacture of fine chemicals, pharmaceuticals, and plastics. Homogeneous catalysts for the processes that have low stability and their separation is difficult. Therefore, the development of new highly active and stable catalysts for hydrogenations and polymerizations is a necessity. The objective of this research was the development of a strategy for immobilization of heterogeneous metallocene catalysts. First, a methodology of immobilization of bis-indenyl ligands on the surface of mesoporous silica gel was designed. Four bis-indenyl ligands containing functionalized tethers of various lengths with terminal alkene groups were synthesized. All …

Breast Tumour Initiating Cell Fate Is Regulated By Microenvironmental Cues From An Extracellular Matrix, Sharmistha Saha, Pang-Kuo Lo, Xinrui Duan, Hexin Chen, Qian Wang

Faculty Publications

Cancer stem cells, also known as tumour-initiating cells (TICs), are identified as highly tumorigenic population within tumours and hypothesized to be main regulators in tumour growth, metastasis and relapse. Evidence also suggests that a tumour microenvironment plays a critical role in the development and progression of cancer, by constantly modulating cell–matrix interactions. Scientists have tried to characterize and identify the TIC population but the actual combination of extracellular components in deciphering the fate of TICs has not been explored. The basic unanswered question is the phenotypic stability of this TIC population in a tissue extracellular matrix setting. The in vivo …

Gas Phase Characterization Of Supramolecules Using Cross-Sectional Areas By Fticr And Sustained Off-Resonance Irradiation Collision Induced Dissociation Techniques In A Fourier Transform Ion Cyclotron Resonance Mass Spectrometer, Fan Yang

Theses and Dissertations

In my dissertation, I use a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR-MS) to investigate supramolecules. Cross-sectional areas by Fourier transform ICR (CRAFTI), a novel technique for measurements of collision cross sections by FTICR, is demonstrated for the first time. The CRAFTI method measures the total "dephasing cross section" for removal of the ions from the coherent packet in the FTICR cell, including contributions not only from momentum transfer but also from reactive collisions including those leading to collisional dissociation. Experimental CRAFTI collision cross sections correlate linearly with theoretically computed results and with results obtained using ion mobility measurements. …

Mass Spectroscopic Identification And Quantification Of Protein Carbonyls, Zafer Ugur

Theses and Dissertations

It is well established that free radical mediated oxidative stress plays a critical role in aging and age-related diseases. Among the post-translational protein modifications, carbonylation has attracted a great deal of attention due to its irreversible and irreparable nature. Despite the fact that protein carbonylation is associated with a series of physiological and pathological processes, there are still issues to be clarified such as why certain proteins are more vulnerable to modification, what are the locations of the protein modifications, and how does the nature of the oxidant affect the preferred site of modification. In this study, we will seek …

Flow Valve Diagnostics For Label-Free, Quantitative Biomarker Detection: Device Fabrication, Surface Modification, And Testing, Danielle Scarlet Mansfield

Theses and Dissertations

Diseases are often diagnosed by detection of disease-specific biomarkers in fluid samples. However, many state-of-the-art detection methods require a lab with complex machinery, trained operators, and/or lengthy analysis time. In contrast, point-of-care (POC) devices are brought to the patient's location, they are easy to use, and results are obtained almost immediately. Many current POC devices are too difficult to be used without a skilled assistant, and although many are able to detect analytes above a threshold value, they give little or no quantitative information. This work presents the development of polymer-based microfluidic devices capable of sensing and quantifying biomarkers in …

Synthesis And Biological Evaluation Of Various Derivatives Of A Broad-Spectrum Anticancer Nucleoside, Jadd R. Shelton

Theses and Dissertations

Recently the Peterson lab discovered a promising anticancer adenosine derivative-- 2´,3´-bis-O-tert-butyldimethylsilyl-5´-deoxy-5´-[N-(methylcarbamoyl)amino]-N6-(N-phenylcarbamoyl)adenosine. This compound showed selective toxicity against human colon cancer cells in vitro with LC50's = 6--10 µM. It was hypothesized that the lead compound exerted its cytotoxic effects by interacting with a protein kinase. A systematic Structure Activity Relationship (SAR) was undertaken in an attempt to increase the kinase-binding affinity of the lead compound. Many regions of the lead compound were examined: the N6-phenyl urea moiety, the 5´-N-methyl urea group, the 2´,3´-bis-O-TBS groups, the nucleobase, and the ribose sugar. Results of these studies produced some promising new derivatives. In …

Studies Toward Tetrahydrofuran-Containing Natural Products: Total Synthesis Of Amphidinolide C And Oxylipids, Sudeshna Roy

Dissertations

Tetrahydrofurans (thf) and tetrahydropyrans (thp) are important structural motifs found in a broad array of biologically relevant natural products such as polyether antibiotics and acetogenins. Classic methods used for thf- or thp-ring synthesis have their own advantages and disadvantages which tend to be substrate specific. Therefore, development of new and efficient methods is imperative especially to address the issue of diastereoselectivity when attainment of both cis- and trans-2,5-thf (or 2,6-thp) is highly desirable. Herein, a strategy of cross-metathesis and Pd(0)-catalyzed cyclization, useful for obtaining both cis- and trans-2,5-disubstituted thf (or 2,6-disubstituted thp), will be discussed along with its application in …

Expanding And Testing A Computational Method For Predicting The Ground State Reduction Potentials Of Organic Molecules On The Basis Of Empirical Correlation To Experiment, Eugene J. Lynch, Amy L. Speelman, Bryce A. Curry, Charles S. Murillo, Jason G. Gillmore

Faculty Publications

A method for predicting the ground state reduction potentials of organic molecules on the basis of the correlation of computed energy differences between the starting S-0 and one-electron-reduced D-0 species with experimental reduction potentials in acetonitrile has been expanded to cover 3.5 V of potential range and 74 compounds across 6 broad families of molecules. Utilizing the conductor-like polarizable continuum model of implicit solvent allows a global correlation that is computationally efficient and has improved accuracy, with r(2) > 0.98 in all cases and root mean square deviation errors of(mean absolute deviationsmV) for either B3LYP/6-311+G(d,p) or B3LYP//6-31G(d) with an appropriate choice …

Water Quality In Restored Wetlands And The Valparaiso Chain Of Lakes Watershed, Diandra Obermeyer, John Stewart

Symposium on Research and Creative Expression (SORCE)

Over the past decade, The Great Marsh has been undergoing a restoration process. In conjunction with the National Park Service and LAC, Valparaiso has taken an active role in monitoring the restoration effort. Previously, 18 different sites entering, within, and exiting The Great Marsh had been established. Over the past few years, 16 water quality parameters were monitored at those sites. These parameters included total and reactive phosphorus testing, temperature, chloride, nitrate, and dissolved oxygen levels. Previously the data has shown a decrease in all values from entering to exiting the marsh. This decrease indicates that the wetland has been …

Surface Functionalized Water-Dispersible Magnetite Nanoparticles: Preparation, Characterization And The Studies Of Their Bioapplications, Haiou Qu

LSU New Orleans Theses and Dissertations

Iron oxide magnetic nanoparticle synthesis and their surface functionalization hold a crucial position in the design and fabrication of functional materials for a variety of biomedical applications. Non-uniform nanoparticles with poor crystallinity, prepared by conventional methods, have only limited value in biological areas. Large scale synthesis methods that are able to produce high quality, mono-dispersed iron oxide nanoparticles using low cost and environment friendly chemicals are highly desirable. Following synthesis, appropriate surface functionalization is necessary to direct the dispersibility of nanoparticles in aqueous solution in order to provide them with acceptable colloidal stability against the ion strength and many biomolecules …

Quantification And In Vitro Analysis Of Nanolipoproteins (Nlps) Containing Adjuvants, Purna Venkataraman, Craig Blanchette, Nicholas O. Fischer

STAR Program Research Presentations

Nanolipoprotein particles (NLPs) self-assemble into nanoscale structures that can be used as vaccines or drug delivery agents. Due to the nature of the NLPs, a variety of immune stimulating compounds or adjuvants can be readily incorporated into NLPs: a characteristic difficult to engineer into most other nanoscale platforms. In light of this, a method for quantifying the amount adjuvant actually incorporated into NLPs is a question of high importance. Through the use of reverse phase High-Performance Liquid Chromatography (HPLC) and an Evaporative Light Scattering Detector (ELSD), standard curves can be constructed by analyzing mixtures of NLP components of known concentration, …

Photochemical Oxidation Studies Of Porphyrin Ruthenium Complexes, Eric Vanover

Masters Theses & Specialist Projects

In nature, transition metal containing enzymes display many biologically important, attractive and efficient catalytic oxidation reactions. Many transition metal catalysts have been designed to mimic the predominant oxidation catalysts in nature, namely, the cytochrome P450 enzymes. Ruthenium porphyrin complexes have been the center of this research and have successfully been utilized, as catalysts, in major oxidation reactions, such as the hydroxylation of alkanes. The present work focuses on photocatalytic studies of aerobic oxidation reactions with well characterized ruthenium porphyrin complexes.

The photocatalytic studies of aerobic oxidation reactions of hydrocarbons The photocatalytic studies of aerobic oxidation reactions of hydrocarbons catalyzed by …

Sillica Nanoporous Materials Adsorption And Release Study, Gang Wang

Chemistry - Dissertations

The lower efficiency of the current common ways of delivering drugs to humans like oral administration and injection make it necessary to find more efficient delivery systems. In this regard, a class of nanostructured materials called mesoporous silicates such as MCM-41, SBA-15 has attracted the attention of many scientists as drug delivery vehicles for their outstanding features like high surface area, high porosity, well-ordered, tunable nanometer pores and "non-cytotoxic" properties.

In this dissertation, comparative investigations of the adsorption capacity and drug release properties of these materials whose surfaces were functionalized with judiciously chosen organic groups via either post-grafting or co-condensation …

Department Of Chemistry News, Fall 2012, Illinois State University, Department Of Chemistry

Chem Letter

Newsletter of the Illinois State University Department of Chemistry

Understanding The Molecular Determinants Of Substrate And Inhibitor Specificities In The Carbapenemase Kpc-2: Exploring The Roles Of Arg220 And Glu276

Chemistry Faculty Publications

β-Lactamases are important antibiotic resistance determinants expressed by bacteria. By studying the mechanistic properties of β-lactamases, we can identify opportunities to circumvent resistance through the design of novel inhibitors. Comparative amino acid sequence analysis of class A β-lactamases reveals that many enzymes possess a localized positively charged residue (e.g., R220, R244, or R276) that is critical for interactions with β-lactams and β-lactamase inhibitors. To better understand the contribution of these residues to the catalytic process, we explored the roles of R220 and E276 in KPC-2, a class A β-lactamase that inactivates carbapenems and β-lactamase inhibitors. Our study reveals that substitutions …

Long-Range Ordered Carbon Clusters: A Crystalline Material With Amorphous Building Blocks, Lin Wang, Bingbing Liu, Hui Li, Wenge Yang, Yang Ding, Stanislav V. Sinogeikin, Yue Meng, Zhenxian Liu, Xiao Cheng Zeng, Wendy L. Mao

Xiao Cheng Zeng Publications

Solid-state materials can be categorized by their structures into crystalline (having periodic translation symmetry), amorphous (no periodic and orientational symmetry), and quasi-crystalline (having orientational but not periodic translation symmetry) phases. Hybridization of crystalline and amorphous structures at the atomic level has not been experimentally observed. We report the discovery of a long-range ordered material constructed from units of amorphous carbon clusters that was synthesized by compressing solvated fullerenes. Using x-ray diffraction, Raman spectroscopy, and quantum molecular dynamics simulation, we observed that, although carbon-60 cages were crushed and became amorphous, the solvent molecules remained intact, playing a crucial role in maintaining …

Synthesis Of 1,1-Dialkyhydrazines And Their Hydroxyl Radical Degradation In Aqueous Environments, Benjamin F. Strong

Masters Theses

Determination of hydroxyl radical rate constants are essential to ensure adequate degradation of contaminants in wastewater. Hydrazines are an important class of organic contaminants and are the focus of this research. Ten 1,1-dialkylhydrazines are synthesized by the zinc reduction of the corresponding N-nitrosamines. Their hydroxyl radical rate constants are determined using the linear accelerator at the Notre Dame Radiation Laboratory at pH 4, 7, and 10.

Their rate constants are found to depend on the protonation state of the molecule. At pH 4 the molecules are fully protonated and hydrogen atom abstraction is favored from the alkyl chains. At …

Synthesis And Applications Of Novel Silver Nanoparticle Structures, Kyle Dukes

All Theses

ABSTRACT
The field of nanotechnology is rapidly expanding across disciplines as each new development is realized. New exciting technologies are being driven by advances in the application of nanotechnology; including biochemical, optical, and semiconductors research. This thesis will focus on the use of silver nanoparticles as optical labels on cells, methods of forming different small structures of silver nanoparticles, as well as the use of silver nanoparticles in the development of a photovoltaic cell.
Silver nanoparticles have been modified with self-assembled monolayers of hydroxyl-terminated long chain thiols and encapsulated with a silica shell. The resulting core-shell nanoparticles were used as …

Experimental And Theoretical Studies In Nuclear Magnetic Resonance, John D. Persons

Department of Chemistry: Dissertations, Theses, and Student Research

Nuclear Magnetic Resonance (NMR) has proven to be an excellent tool to probe the structure of molecules by gaining insight into nuclear interactions. Used in conjunction with theoretical calculations, NMR has the potential to elucidate these nuclear interactions and how they affect structure, bonding and dynamics on a molecular scale. The first two projects presented herein study the peroxide explosive hexamethylene triperoxide diamine (HMTD). In the first project, we use the characteristics of the solid-state NMR lineshape to determine the ¹⁴N quadrupole coupling constant (C_Q). The second project uses multi-dimensional solution-state NMR and chiral shift reagents …