Chemistry Commons^™

Water-Mediated Carbon–Oxygen Hydrogen Bonding Facilitates S-Adenosylmethionine Recognition In The Reactivation Domain Of Cobalamin-Dependent Methionine Synthase, Robert J. Fick, Mary C. Clay, Lucas Vander Lee, Steve Scheiner, Hashim M. Al-Hashimi, Raymond C. Trievel

Chemistry and Biochemistry Faculty Publications

The C-terminal domain of cobalamin-dependent methionine synthase (MetH) has an essential role in catalyzing the reactivation of the enzyme following the oxidation of its cobalamin cofactor. This reactivation occurs through reductive methylation of the cobalamin using S-adenosylmethionine (AdoMet) as the methyl donor. Herein, we examine the molecular recognition of AdoMet by the MetH reactivation domain utilizing structural, biochemical, and computational approaches. Crystal structures of the Escherichia coli MetH reactivation domain in complex with AdoMet, the methyl transfer product S-adenosylhomocysteine (AdoHcy), and the AdoMet analogue inhibitor sinefungin illustrate that the ligands exhibit an analogous conformation within the solvent-exposed substrate binding cleft …

The Role Of Torsional Dynamics On Hole And Exciton Stabilization In Π‐Stacked Assemblies: Design Of Rigid Torsionomers Of A Cofacial Bifluorene, Denan Wang, Maxim Vadimovich Ivanov, Damian Kokkin, John Loman, Jin-Zhe Cai, Scott A. Reid, Rajendra Rathore

Chemistry Faculty Research and Publications

Exciton and charge delocalization across π‐stacked assemblies is of importance in biological systems and functional polymeric materials. To examine the requirements for exciton and hole stabilization, cofacial bifluorene (F2) torsionomers were designed, synthesized, and characterized: unhindered (model) ^MeF2, sterically hindered ^tBuF2, and cyclophane‐like ^CF2, where fluorenes are locked in a perfect sandwich orientation via two methylene linkers. This set of bichromophores with varied torsional rigidity and orbital overlap shows that exciton stabilization requires a perfect sandwich‐like arrangement, as seen by strong excimeric‐like emission only in ^CF2 and ^MeF2. …

The Preparation Of Palladium Complexes Of N-Pyrazolylpropanamide Derivatives, Tyler Palombo 5275714

Senior Honors Projects, 2010-2019

The reaction of 3,5-dimethylpyrazolyl-N-isopropylpropanamide (L1) with dichloro(1,5-cyclooctadiene)palladium(II) displaces cyclooctadiene forming Cl₂Pd(L1)₂. This complex has been characterized by NMR and IR spectroscopy, single crystal X-Ray diffraction, and elemental analysis. It is composed of a square planar Pd with trans L1 ligands attached through a pyrazolyl nitrogen and intramolecular hydrogen bonding between the amide and chloride. Similar reactions were carried out with 3,5-dimethylpyrazolylpropanamide (L2), pyrazolyl-N-isopropylpropanamide (L3), 3-(1H-benzotriazol-1-yl)-N,N-dimethylpropanamide (L4), 3-methylpyrazolylpropanamide (L5), 3-(1H-benzotriazol-1-yl)-2-methylpropanamide (L6), and N-pyrazolypropanamide (L7) presumably forming analogous complexes. This formulation for …

Mammalian Cell-Derived Vesicles For The Isolation Of Organelle Specific Transmembrane Proteins To Conduct Single Molecule Studies, Faruk H. Moonschi, Ashley M. Fox-Loe, Xu Fu, Christopher I. Richards

Chemistry Faculty Publications

Cell-derived vesicles facilitate the isolation of transmembrane proteins in their physiological membrane maintaining their structural and functional integrity. These vesicles can be generated from different cellular organelles producing, housing, or transporting the proteins. Combined with single molecule imaging, isolated organelle specific vesicles can be employed to study the trafficking and assembly of the embedded proteins. Here we present a method for organelle specific single molecule imaging via isolation of ER and plasma membrane vesicles from HEK293T cells by employing OptiPrep gradients and nitrogen cavitation. The isolation was validated through Western blotting, and the isolated vesicles were used to perform single …

Nmr Studies Of Loaded Microspheres, Ming Huang, Sisi Chen, Rex E. Gerald Ii, Jie Huang, Klaus Woelk

Electrical and Computer Engineering Faculty Research & Creative Works

Porous-wall hollow glass microspheres (PWHGMs) are a novel form of glass materials that consist of 1-μm-thick porous silica shells, 20-100 μm in diameter, with a hollow cavity in the center. Utilizing the central cavity for material storage and the porous walls for controlled release is a unique combination that renders PWHGMs a superior vehicle for targeted drug delivery. In this study, NMR spectroscopy was used to characterize PWHGMs for the first time. A vacuum-based loading system was developed to load PWHGMs with various compounds followed by a washing procedure that uses solvents immiscible with the target material. Immiscible binary model …

Hydrodeoxygenation Of Pinyon-Juniper Catalytic Pyrolysis Oil Using Red Mud-Supported Nickel Catalysts, Hossein Jahromi, Foster Agblevor

Biological Engineering Faculty Publications

Red mud (RM) is an alkaline waste generated in the Bayer process of alumina production. In the present study red mud supported nickel catalysts (Ni/RM) were prepared at different concentrations of nickel (10, 20, 30, 40, 50, and 65 wt.%) and used to hydrodeoxygenate (HDO) pinyon-juniper (PJ) catalytic pyrolysis oil. Increasing the nickel content improved the activity of Ni/RM catalysts for HDO reactions. Maximum organic liquid yield (68.6%) was obtained when 40%Ni/RM was used. The upgraded oil had oxygen content of 1.35 wt.% and higher heating value of 45.77 MJ/kg compared to 24.88 wt.% and 28.41 MJ/kg, respectively, for the …

Sequential And Differential Interaction Of Assembly Factors During Nitrogenase Mofe Protein Maturation, Emilio Jimenez-Vicente, Zhi-Yong Yang, W. Keith Ray, Carlos Echavarri-Erasun, Valerie L. Cash, Luis M. Rubio, Lance C. Seefeldt, Dennis R. Dean

Chemistry and Biochemistry Faculty Publications

Nitrogenases reduce atmospheric nitrogen, yielding the basic inorganic molecule ammonia. The nitrogenase MoFe protein contains two cofactors, a [7Fe-9S-Mo-C-homocitrate] active-site species, designated FeMo-cofactor, and a [8Fe-7S] electron-transfer mediator called P-cluster. Both cofactors are essential for molybdenum-dependent nitrogenase catalysis in the nitrogen-fixing bacterium Azotobacter vinelandii. We show here that three proteins, NafH, NifW, and NifZ, copurify with MoFe protein produced by an A. vinelandii strain deficient in both FeMo-cofactor formation and P-cluster maturation. In contrast, two different proteins, NifY and NafY, copurified with MoFe protein deficient only in FeMo-cofactor formation. We refer to proteins associated with immature MoFe protein in …

Metallodithiolate Ligands For Reversing Metal Ion Induced Aggregation Of Beta Amyloid, Eleanor K. Adams, Marilyn Rampersad Mackiewicz

Student Research Symposium

Alzheimer’s Disease (AD) is the sixth leading cause of death in the United States with no known methods to cure, reverse or halt disease progression. The “metal hypothesis” states that Fe^II, Cu^II, Zn^II, and Al^II bind to truncated Aβ peptides and form soluble oligomers which deposit as senile plaques. These plaques play a crucial role in AD pathogenesis. For example, metallated-Aβ aggregates are hypothesized to disrupt membranes or generate a reactive oxygen species (ROS) through redox cycling in the presence of Cu^I/II or Fe^III/II and a reducing agent. ROS can lead …

Diagnostic Platform For Current Health Status Monitoring, Albert S. Benight, Megan M. Koslen, Matthew W. Eskew

Student Research Symposium

Our approach is based on physical measurements of blood plasma and exploits the plethora of information contained in the human plasma proteome, as a reporter of human health status. The assay involves collection and analysis ofthermograms of plasma from human blood measured by differential scanning calorimetry (DSC).

Plasma thermograms arise from the temperature-induced denaturation profile of proteins within blood plasma measured by DSC. This insightful measurement thereby provides a snapshot of the current state of the human plasma proteome which directly informs on overall systemic health. Such measurements have been shown to be highly accurate and sensitive indicators of health …

Structure Of Frequency-Interacting Rna Helicase From Neurospora Crassa Reveals High Flexibility In A Domain Critical For Circadian Rhythm And Rna Surveillance, Yalemi Morales, Keith J. Olsen, Jacqueline M. Bulcher, Sean J. Johnson

Chemistry and Biochemistry Faculty Publications

The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact. In contrast with the earlier FRH structures, a new crystal form of FRH …

Structural Characterization Of The P1+ Intermediate State Of The P-Cluster Of Nitrogenase, Stephen M. Keable, Oleg A. Zadvornyy, Lewis E. Johnson, Bojana Ginovska, Andrew J. Rasmussen, Karamatullah Danyal, Brian J. Eilers, Gregory A. Prussia, Axl X. Levan, Simone Raugei, Lance C. Seefeldt, John W. Peters

Chemistry and Biochemistry Faculty Publications

Nitrogenase is the enzyme that reduces atmospheric dinitrogen (N₂) to ammonia (NH₃) in biological systems. It catalyzes a series of single-electron transfers from the donor iron protein (Fe protein) to the molybdenum–iron protein (MoFe protein) that contains the iron–molybdenum cofactor (FeMo-co) sites where N₂ is reduced to NH₃. The P-cluster in the MoFe protein functions in nitrogenase catalysis as an intermediate electron carrier between the external electron donor, the Fe protein, and the FeMo-co sites of the MoFe protein. Previous work has revealed that the P-cluster undergoes redox-dependent structural changes and that the …

Small-Angle X-Ray Scattering In Amorphous Silicon: A Computational Study, Durga Paudel, Raymond Atta-Fynn, David A. Drabold, Stephen R. Elliott, Parthapratim Biswas

Faculty Publications

We present a computational study of small-angle x-ray scattering (SAXS) in amorphous silicon (α-Si) with particular emphasis on the morphology and microstructure of voids. The relationship between the scattering intensity in SAXS and the three-dimensional structure of nanoscale inhomogeneities or voids is addressed by generating large high-quality (α-Si networks with 0.1%–0.3% volume concentration of voids, as observed in experiments using SAXS and positron annihilation spectroscopy. A systematic study of the variation of the scattering intensity in the small-angle scattering region with the size, shape, number density, and the spatial distribution of the voids in the networks is presented. Our results …

Dissecting Structure-Encoded Determinants Of Allosteric Cross-Talk Between Post-Translational Modification Sites In The Hsp90 Chaperones, Gabrielle Stetz, Amanda Tse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Post-translational modifications (PTMs) represent an important regulatory instrument that modulates structure, dynamics and function of proteins. The large number of PTM sites in the Hsp90 proteins that are scattered throughout different domains indicated that synchronization of multiple PTMs through a combinatorial code can be invoked as an important mechanism to orchestrate diverse chaperone functions and recognize multiple client proteins. In this study, we have combined structural and coevolutionary analysis with molecular simulations and perturbation response scanning analysis of the Hsp90 structures to characterize functional role of PTM sites in allosteric regulation. The results reveal a small group of conserved PTMs …

Photoinduced Interfacial Charge Separation Dynamics In Zeolitic Imidazolate Framework, Brian Pattengale, Jier Huang

Chemistry Faculty Research and Publications

Owing to their porous structure and tunable framework, zeolitic imidazolate frameworks (ZIFs) have garnered considerable attention as promising photocatalytic materials. However, little is known regarding their photophysical properties. In this work, we report the photoinduced charge separation dynamics in a ZIF-67 thin film through interfacial electron transfer (ET) to methylene blue (MB⁺) via ultrafast transient absorption spectroscopy. We show that the ET process occurs through two distinct pathways, including an ultrafast (<200 fs) process from the [Co^II(mim)₂] units located on the surface of ZIF-67 film that are directly in contact with MB⁺ and a relatively slower ET process …

Functional And Biochemical Characterization Of Dib1'S Role In Pre-Messenger Rna Splicing, Christian C. Schreib, Emily K. Bowman, Cody A. Hernandez, Amber L. Lucas, Camile H. S. Potts, Corina Maeder

Chemistry Faculty Research

The spliceosome is a dynamic macromolecular machine that undergoes a series of conformational rearrangements as it transitions between the several states required for accurate splicing. The transition from the B to Bact is a key part of spliceosome assembly and is defined by the departure of several proteins, including essential U5 component Dib1. Recent structural studies suggest that Dib1 has a role in preventing premature spliceosome activation, as it is positioned adjacent to the U6 snRNA ACAGAGA and the U5 loop I, but its mechanism is unknown. Our data indicate that Dib1 is a robust protein that tolerates incorporation of …

Molecular Dynamics Simulations Of Apo And Holo Forms Of Fatty Acid Binding Protein 5 And Cellular Retinoic Acid Binding Protein Ii Reveal Highly Mobile Protein, Retinoic Acid Ligand, And Water Molecules, Nathanael H. Hunter, Blair C. Bakula, Chrystal D. Bruce

2018 Faculty Bibliography

Structural and dynamic properties from a series of 300 ns molecular dynamics, MD, simulations of two intracellular lipid binding proteins, iLBPs, (Fatty Acid Binding Protein 5, FABP5, and Cellular Retinoic Acid Binding Protein II, CRABP-II) in both the apo form and when bound with retinoic acid reveal a high degree of protein and ligand flexibility. The ratio of FABP5 to CRABP-II in a cell may determine whether it undergoes natural apoptosis or unrestricted cell growth in the presence of retinoic acid. As a result, FABP5 is a promising target for cancer therapy. The MD simulations presented here reveal distinct differences …

Discovery Of A Novel Inhibitory Compound Produced By The Soil Bacterium Rhodococcus Sp. Mtm3w5.2, Patrick South

Undergraduate Honors Theses

Due to increases in antibiotic resistance stemming from the overuse of commercial antibiotics, the need to discover novel antibacterial compounds is becoming more urgent. A species of Rhodococcus, MTM3W5.2, has been discovered and was found to produce a metabolite with inhibitory activity against closely related species. The aim of this study is to elucidate the structure of the inhibitory metabolite by isolating and purifying it; then characterizing it using spectroscopic techniques. The compound was isolated from MTM3W5.2 RM broth cultures using n-butanol extraction, which yielded an active crude extract. The crude extract was then subjected to fractionation using a Sephedex …

Approaches Toward The Total Synthesis Of Oroidin Alkaloids:Nagelamide A, C And Ageliferin, Apsara Herath

Chemistry & Biochemistry Dissertations - Archive

Nagelamides and ageliferin are oroidin-derived alkaloids which have gained the attention of the scientific community, because of their significant biological activity as well as the unprecedented structural diversity. Our work is directed toward the development of synthetic methods for the construction of oroidin dimers. Accordingly, this dissertation is composed of two sections; the chapter one provides an overview of the oroidin alkaloids with a particular focus on the nagelamide family and the third chapter describes synthetic studies towards ageliferin. The first part of chapter two focuses on the Palladium-catalyzed Stille cross-coupling reaction for the construction of the main dimeric scaffolds …

Decreased Brood-Size Of Starvation-Induced Postdauer Adults Is Inherited Transgenerationally Via Hrde-1, Ibnul Rafi

Renée Crown University Honors Thesis Projects - All

Environmental stress experienced in utero or in early life has profound effects on the behavior and physiology of an adult animal. Interestingly, genome-wide association studies in humans have shown that early-life stress not only affects the exposed individual, but also their future generations. However, the molecular mechanisms of how early-life stress can impact physiology transgenerationally in the absence of the original stress are not well understood. To study the mechanisms and consequences of environmental stress on adult phenotypes, we utilize the life cycle of the model organism Caenorhabditis elegans. In favorable conditions, the life cycle of C. elegans includes 5 …

3,5-Bis(3,5-Bis(Trifluoromethyl)Phenyl)Pyrazolyl Complexes Of Coinage Metals, Jaspreet Singh Lakhi

Chemistry & Biochemistry Theses - Archive

Pyrazoles are an important class of five membered heterocyclic compounds consisting of two nitrogen atoms. Pyrazolate anions serve as useful ligands in coordination chemistry. When fluorinated substituents are attached to this ligand they provide favorable properties such as volatility, thermal and oxidative stability. Trinuclear pyrazolate complexes of monovalent coinage metals (i.e., Cu(I), Ag(I), and Au(I)) represent an important class of compounds with interesting structures and fascinating properties. Little has been done in adding sterically hindered substituents onto the pyrazole ring. This thesis includes the introduction of heavily fluorinated bulky aryl substituents such as 3,5-(CF3)2Ph- at the 3- and 5- position …

Supercharging And Multiple Reaction Monitoring Optimization Of High Molecular Weight Intact Proteins Using Triple Quadrupole Mass Spectrometry, Durga Devi Khanal

Chemistry & Biochemistry Theses - Archive

Various supercharging agents, such as meta-nitrobenzyl alcohol, dimethyl sulfoxide, trifluoroethanol (TFE), and sulfolane were tested in different concentrations to study the effects of supercharging agents on the charge distributions of the high molecular weight intact proteins. The data were analyzed by triple quadrupole mass spectrometry. For most of the proteins, m-NBA and TFE worked more effectively than other supercharging agents, both to shift the charge state and increase intensity. The settings of different instrumental parameters were also studied. Both increases in source temperature and flow rate had a negative impact on average charge state observed. The goal of this work …

Lithium And The Foreseeable Future, Paolo Vargas

Mechanical Engineering Undergraduate Honors Theses

This paper aims to clarify the uncertainties regarding worldwide lithium resource availability in the years to come. Previous studies made on the subject are presented with some ambiguity and this work intends to fill the gaps. The information and data presented throughout this script with respect to global lithium resources and reserves are mostly based on data released by the United States Geological Survey (USGS). Lithium resource availability in the future is a point of paramount significance primarily for the automotive, portable electronics, and the power generation industry. Since, a change of supply would ultimately affect the price of lithium, …

Imide Arylation With Aryl(Tmp)Iodonium Tosylates, Souradeep Basu, Alexander H. Sandtorv, David R. Stuart

Chemistry Faculty Publications and Presentations

Herein, we describe the synthesis of N-aryl phthalimides by metal-free coupling of potassium phthalimide with unsymmetrical aryl(TMP)iodonium tosylate salts. The aryl transfer from the iodonium moiety occurs under electronic control with the electronrich trimethoxyphenyl group acting as a competent dummy ligand. The yields of N-aryl phthalimides are moderate to high and the coupling reaction is compatible with electron-deficient and sterically encumbered aryl groups.

Spectroscopic And Mechanistic Investigation Of The Enzyme Mercaptopropionic Acid Dioxygenase (Mdo), The Role Of The Conserved Outer-Sphere 'Catalytic Triad' In Directing Promiscuous Substrate-Specificity, Sinjinee Sardar

Chemistry & Biochemistry Dissertations - Archive

Mercaptopropionate dioxygenase (MDO) from Aztobacter Vinelandii is a non-heme mononuclear iron enzyme that catalyzes the oxygen dependent conversion of 3-mercaptopropionic acid (3mpa) to produce 3-sulfinopropinioic acid (3spa). Nearly, all thiol dioxygenases have a conserved ‘catalytic triad’ within the active site, consisting of three outer Fe-coordination sphere residues S155, H157 and Y159. With the notable exception of mammalian cysteamine (2-aminoethanethiol) dioxygenase (ADO), this ‘catalytic triad’ is universally conserved across phylogenic domains. X-ray crystallographic studies clearly show a hydrogen bond network connecting the ‘catalytic triad’ to the mononuclear iron site; however, its influence on substrate specificity and catalytic efficiency is poorly understood. …

Development Of New Useful Methods For Aldehyde Synthesis And Its Application In Synthesis, He Huang

Chemistry and Chemical Biology ETDs

Development of sustainable synthetic technologies for molecular construction is an important but formidably challenging task in modern organic synthesis. Aldehyde synthesis represents a long-standing interest in synthesis because of the synthetic utility. Classic methods for aldehyde synthesis have the drawbacks of the use of harsh reaction conditions, poor atom-economy and multi-step operation, and production of stoichiometric amount of chemical wastes. The state-of-the-art strategies employ transition metal complexes as catalysts to promote formylation reactions. The concerns of catalyst cost, operation complexity and poor functional group tolerance demands more efficient synthetic technologies. My Ph.D. study focuses on design of conceptually novel catalytic …

Synthesis And Characterization Of Biodiesel Fuels From Furfuryl Alcohol And Spent Coffee Grounds, Amanda Raley

Electronic Theses and Dissertations

ABSTRACT

Biodiesel can be synthesized using several different triacylglycerides, alcohols, and catalysts. In this study, fatty acid methyl esters (FAMEs) and fatty acid ethyl esters (FAEEs) were produced from their respective alcohols and coffee oil, using either a basic (K₂CO₃) catalyst or an acidic catalyst (H₂SO₄). Fatty acid furfuryl esters (FAFurEs) were produced using commercially-purchased cooking oils (canola, olive, corn, sunflower, and peanut) with furfuryl alcohol, a basic (K₂CO₃) catalyst, a co-solvent (THF), and an ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate). All samples were produced using either conventional heating methods …

Elucidation Of Substrate Binding To Photolyase From Sulfolobus Solfataricus Using Isothermal Titration Calorimetry, Amanda Rose Kuerzi

Theses, Dissertations and Culminating Projects

DNA photolyase is a DNA repair enzyme commonly found across the kingdom of life. Binding studies for the hyperthermophilic photolyase derived from Sulfolobus solfataricus (SsPL) may serve to illuminate how DNA photolyase can adapt over a large temperature range. In the first section of this study, the thermodynamics of substrate binding for SsPL in a choline chloride buffer were determined using isothermal titration calorimetry. Using the Counter-Ion Condensation Concept as a model, ionic strength studies were performed to separate the binding interactions into electrostatic, and nonelectrostatic components. The electrostatic interactions do not appear to make a significant contribution to the …

Genetically Engineered Peptides For Light Harvesting And Folding Kinetics Studies, Aileen M. Eagleton

Chemistry

The preparation and characterization of β-sheet forming polypeptides for use in light harvesting applications is described. The Higashiya genetic cassette strategy (HGCS) was employed in order to make DNA libraries of repetitive DNA sequences. These DNA libraries contained gene cassettes coding for proteins designed to fold into the desired secondary motif. The conditions required for peptide expression, folding and formation of micron length fibrils was determined for the purpose of photophysical characterization, such as fluorescence lifetimes and acceptor dye quantum yields. Of special interest was the investigation of an “antenna effect” under FRET illumination, the intensity of acceptor dye emission …

Forensic Identification Of Condom Lubricants By Advanced Statistical Analysis Processing Of Direct Analysis In Real Time Mass Spectrometric Data – Towards Development Of A Condom Residue Database For Forensic Science Practitioners, Allix M. Coon

Chemistry

The ability to identify condom derived trace evidence is gaining importance because of the increasing frequency with which perpetrators of sexual assault use condoms in order to avoid leaving behind incriminating DNA evidence that might link them to the crime. Although DNA remains the gold standard for sexual assault evidence, other forms of trace evidence are needed in its absence. When condoms are used, the lubricants associated with them are the trace evidence. For the lubricant residue to be useful in a forensics context, a database of chemical signatures of lubricants against which acquired evidence can be screened is required, …

Evaluation Of The Biocompatibility And Micromechanical Properties Of Experimental Dental Adhesives, Hoda Moussa

Forensic Science Theses

The purpose of this study was to investigate the biocompatibility and micromechanical properties of newly synthesized antibacterial monomer and cross-linker functional surfactants into a commercially available dental adhesive (Single Bond, 3M ESPE, Saint Paul, MN, USA) at three concentrations (0.05, 0.1, 0.25 mg/mg). All groups were analyzed by evaluation of micro-tensile bond strength, ultimate tensile strength, cell viability, antibacterial properties, and surface micro-hardness. Scanning electron microscopy (SEM) was used for interfacial characterization.

Human extracted molars were used as a substrate for bonding adhesives for the micro-tensile bond strength (MTBS) and scanning electron microscopy (SEM) studies. Twenty resin-dentin beams (0.9 ± …