Chemistry Commons^™

The Dimerization Domain In Dape Enzymes Is Required For Catalysis, Boguslaw Nocek, Anna Starus, Magdalena Makowska-Grzyska, Blanca Gutierrez, Stephen Sanchez, Robert Jedrzejczak, Jamey C. Mack, Kenneth W. Olsen, Andrzej Joachimiak, Richard C. Holz

Chemistry: Faculty Publications and Other Works

The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Thereforedap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) convertsN-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role …

Parkinson Disease-Associated Mutation R1441h In Lrrk2 Prolongs The “Active State” Of Its Gtpase Domain, Jingling Liao, Chun-Xiang Wu, Christopher Burlak, Sheng Zhang, Dali Liu

Chemistry: Faculty Publications and Other Works

Mutation in leucine-rich-repeat kinase 2 (LRRK2) is a common cause of Parkinson disease (PD). A disease-causing point mutation R1441H/G/C in the GTPase domain of LRRK2 leads to overactivation of its kinase domain. However, the mechanism by which this mutation alters the normal function of its GTPase domain [Ras of complex proteins (Roc)] remains unclear. Here, we report the effects of R1441H mutation (Roc_R1441H) on the structure and activity of Roc. We show that Roc forms a stable monomeric conformation in solution that is catalytically active, thus demonstrating that LRRK2 is a bona fide self-contained GTPase. We further show …

Cellulose Acetate Replica Cleaning Study Of Genesis Non-Flight Sample 3cz00327, K.R. Kuhlman, Martina Schmeling, C.P. Gonzalez, J.H. Allton, D.S. Burnett

Chemistry: Faculty Publications and Other Works

Cellulose acetate replica cleaning of Genesis samples is validated using control sample 3CZ00327. Residues are removed using hot xylene and acetone.

Analysis Of Genesis Sample 60234 By Laboratory Total Reflection X-Ray Fluorescence Spectrometry And Synchrotron Grazing Incidence X-Ray Fluorescence, Martina Schmeling, E. Hwang, Y. Choi, P.J. Eng, J.E. Stubbs, I.V. Veryovkin

Chemistry: Faculty Publications and Other Works

Genesis sample 60234 was characterized by laboratory TXRF and synchrotron GI-XRF. Surface contaminants were identified as well as elements within the bulk.

Investigation Of Chicago Air Pollution And Meteorological Influence On Pollution Development: Physical Measurements And Multivariate Statistical Analyses, Katrina Lyn Binaku

Dissertations

The goal of this project was to evaluate air pollutants and meteorology in Chicago, Illinois during summers 2010, 2011, and 2012. Sixty-six collection days of air pollutant and meteorological data were completed at the Loyola University Chicago sampling station atop Mertz Hall. Trace gases, nitrogen oxides and ozone, as well as the water-soluble fraction of aerosol material were the air pollutants of focus in this study. Data analysis showed that chloride, nitrate, sulfate, and oxalate were the most frequently quantified water-soluble ions in aerosol samples, followed by acetate, formate, potassium, phosphate, calcium, and magnesium ions. Ionic ratios showed that stationary …

Polyaminocarboxylic Acids As Potential Candidates For Trivalent Actinide/Lanthanide Separations, Daniel Stephen Kissel

Dissertations

Nuclear energy, which has historically been considered an alternative energy solution in the United States, is regaining support as an efficient means of energy production. The viability of nuclear energy for the future, however, will remain suspect until issues involving the waste created are fully addressed in the next generation of advanced nuclear fuel cycles. The TALSPEAK process, developed at Oak Ridge National Laboratory, is a classic solvent extraction technique that employs a series of analytical separations in an effort to remove radioactive contaminants from spent nuclear fuel (SNF) and recover uranium in high purity. This separation utilizes a polyaminocarboxylic …

Investigating The Biochemical And Catalytic Properties Of Nitrile Hydratases, Salette Martinez

Dissertations

Chemical and pharmaceutical industries make extensive use of amide compounds for the manufacture of commodity chemicals (e.g., acrylamide) and drug intermediates (e.g., nicotinamide). Production of amide compounds is typically achieved by the hydration of nitrile compounds under acidic or basic conditions, high temperatures, and copper catalysts. However, the use of such chemical methods leads to the generation of unwanted by-products and toxic wastes, in addition to low product yields and high production costs. An alternative route for amide production is the use of a natural catalyst, for example nitrile hydratases (NHase, E.C. 4.2.1.84). NHase is a metalloenzyme that efficiently converts …

On The Origin Of Mode- And Bond-Selectivity In Vibrationally Mediated Reactions On Surfaces, Daniel Killelea, Arthur L. Utz

Chemistry: Faculty Publications and Other Works

The experimental observations of vibrational mode- and bond-selective chemistry at the gas–surface interface indicate that energy redistribution within the reaction complex is not statistical on the timescale of reaction. Such behavior is a key prerequisite for efforts to use selective vibrational excitation to control chemistry at the technologically important gas–surface interface. This paper outlines a framework for understanding the origin of non-statistical reactivity on surfaces. The model focuses on the kinetic competition between intramolecular vibrational energy redistribution (IVR) within the reaction complex, which in the long-time limit leads to statistical behavior, and quenching, scattering, or desorption processes that restrict the …

Spectroscopic Evidence Of Work Function Alterations Due To Photoswitchable Monolayers On Gold Surfaces, Matthew Alan Bartucci, Jan Florian, Jacob W. Ciszek

Chemistry: Faculty Publications and Other Works

Taking advantage of surfaces’ response to interfacial dipoles, a class of photochromophores (dihydroindolizine) is demonstrated to alter the work function of the underlying substrate (∼170 meV). This same molecule also provides spectroscopic signatures for correlating the change in molecular structure to the induced change in the surfaces’ electronic properties. Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) allows analysis of the characteristic dihydroindolizine C═C (1559 cm^–1) and pyridinium (1643 cm^–1) stretch as a function of photoexcitation. Structural assignments of this photochromophore are corroborated to density function theory calculations. Conformational changes in the monolayers appear in parallel with …

Statistical Analysis Of Aerosol Species, Trace Gases, And Meteorology In Chicago, Katrina Binaku, Timothy O'Brien, Martina Schmeling, Tinamarie Fosco

Chemistry: Faculty Publications and Other Works

Both canonical correlation analysis (CCA) and principal component analysis (PCA) were applied to atmospheric aerosol & trace gas concentrations and meteorological data collected in Chicago during the summer months of 2002, 2003, and 2004. Concentrations of ammonium, calcium, nitrate, sulfate, and oxalate particulate matter, as well as, meteorological parameters temperature, wind speed, wind direction, and humidity were subjected to CCA & PCA. Ozone and nitrogen oxide mixing ratios were also included in the data set. The purpose of statistical analysis was to determine the extent of existing linear relationship(s), or lack thereof, between meteorological parameters and pollutant concentrations in addition …

Unraveling The Activation Mechanism Of The Potato Tuber Adp-Glucose Pyrophosphorylase, Carlos M. Figueroa, Misty L. Kuhn, Christine A. Falaschetti, Ligin Solamen, Kenneth W. Olsen, Miguel Ballicora, Alberto A. Iglesias

Chemistry: Faculty Publications and Other Works

ADP-glucose pyrophosphorylase regulates the synthesis of glycogen in bacteria and of starch in plants. The enzyme from plants is mainly activated by 3-phosphoglycerate and is a heterotetramer comprising two small and two large subunits. Here, we found that two highly conserved residues are critical for triggering the activation of the potato tuber ADP-glucose pyrophosphorylase, as shown by site-directed mutagenesis. Mutations in the small subunit, which bears the catalytic function in this potato tuber form, had a more dramatic effect on disrupting the allosteric activation than those introduced in the large subunit, which is mainly modulatory. Our results strongly agree with …

Large-Scale Structural Rearrangement Of A Serine Hydrolase From Francisella Tularensis Facilitates Catalysis, Ekaterina V. Filippova, Leigh A. Watson, Misty L. Kuhn, Brett Geissler, Daniel Becker

Chemistry: Faculty Publications and Other Works

Tularemia is a deadly, febrile disease caused by infection by the gram-negative bacterium, Francisella tularensis. Members of the ubiquitous serine hydrolase protein family are among current targets to treat diverse bacterial infections. Herein we present a structural and functional study of a novel bacterial carboxylesterase (FTT258) from F. tularensis, a homologue of human acyl protein thioesterase (hAPT1). The structure of FTT258 has been determined in multiple forms, and unexpectedly large conformational changes of a peripheral flexible loop occur in the presence of a mechanistic cyclobutanone ligand. The concomitant changes in this hydrophobic loop and the newly exposed hydrophobic substrate binding …

Functionalization Of Organic Semiconductor Crystals Via The Diels–Alder Reaction, Brittni A. Qualizza, Srividya Prasad, M. Paul Chiarelli, Jacob W. Ciszek

Chemistry: Faculty Publications and Other Works

A surface adlayer is generated on organic single crystals (tetracene and rubrene) using the site specific Diels–Alder reaction and a series of vapor phase dienophiles. X-ray photoelectron spectroscopy (XPS) confirms adsorption on the surfaces of tetracene and rubrene and mass spectrometry demonstrates the reaction’s applicability to a range of dienophiles.

Apparent Alkyl Transfer And Phenazine Formation Via An Aryne Intermediate, Daniel Becker, Andria M. Panagopoulos, Doug Steinman, Alexandra Goncharenko, Kyle Geary, Carlene Schleisman, Elizabeth Spaargaren, Matthias Zeller

Chemistry: Faculty Publications and Other Works

Treatment of chlorotriaryl derivatives 3a and 3d or fluorotriaryl derivatives 3b and 3e with potassium diisopropylamide afforded alkyl-shifted phenazine derivatives 5a/5b, rather than the expected 9-membered triazaorthocyclophane 2a. The phenazine derivatives were isolated in 78–98% yield depending on the halogen and alkyl group present. In the absence of the halogen (chloro or fluoro), the apparent alkyl shift proceeds more slowly and cannot proceed via the intermediacy of the aryne intermediate. Mechanistic possibilities include intramolecular nucleophilic attack on an aryne intermediate leading to a zwitterionic intermediate and alkyl transfer via a 5-endo-tet process, or via a Smiles rearrangement.

Rearrangement Of Cyclotriveratrylene (Ctv) Diketone: 9,10-Diarylanthracenes With Oled Applications, Samuel R. Sarsah, Marlon R. Lutz Jr., Matthias Zeller, David S. Crumrine, Daniel Becker

Chemistry: Faculty Publications and Other Works

Electroluminescent 9,10-diaryl anthracenes have been shown to be promising host and hole-transporting materials in organic electroluminescence due to their high thermal stability, electrochemical reversibility, and wide band gap useful for organic light-emitting diodes (OLEDs), especially blue OLEDs. Oxidation of cyclotriveratrylene (CTV) to the corresponding diketone and subsequent bromination resulted in an unexpected rearrangement to a highly functionalized 9-aryl-10-bromoanthracene derivative, which was employed in Suzuki couplings to synthesize a series of 9,10-diaryl compounds that are structural analogues of anthracene derivatives used in the preparation of OLEDs but are more highly functionalized, including electron-donating methoxy groups in addition to substitution by a …

The Ancestral Activation Promiscuity Of Adp-Glucose Pyrophosphorylases From Oxygenic Photosynthetic Organisms, Misty L. Kuhn, Carlos M. Figueroa, Alberto A. Iglesias, Miguel Ballicora

Chemistry: Faculty Publications and Other Works

Background

ADP-glucose pyrophosphorylase (ADP-Glc PPase) catalyzes the first committed step in the synthesis of glycogen in bacteria and starch in algae and plants. In oxygenic photosynthetic organisms, ADP-Glc PPase is mainly activated by 3-phosphoglycerate (3-PGA) and to a lesser extent by other metabolites. In this work, we analyzed the activation promiscuity of ADP-Glc PPase subunits from the cyanobacterium Anabaena PCC 7120, the green alga Ostreococcus tauri, and potato (Solanum tuberosum) tuber by comparing a specificity constant for 3-PGA, fructose-1,6-bisphosphate (FBP), fructose-6-phosphate, and glucose-6-phosphate.

Results

The 3-PGA specificity constant for the enzymes from Anabaena (homotetramer), O. tauri, …

Lysine Biosynthesis In Bacteria: A Metallodesuccinylase As A Potential Antimicrobial Target, Danuta M. Gillner, Daniel P. Becker Ph.D., Richard C. Holz

Chemistry: Faculty Publications and Other Works

In this review, we summarize the recent literature on dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor.

Investigating The Electrostatic Role Of A Critical Arginine For The Catalysis Of E. Coli Adp-Glucose Pyrophosphorylase, Angela Mahaffey, Saleh Aiyash, Miguel Ballicora, Ligin Solamen

Chemistry: Faculty Publications and Other Works

ADP-glucose pyrophosphorylase (ADP-Glc PPase) is the regulatory enzyme of the pathway for starch synthesis in plants and glycogen in mammals and enteric bacteria. It exists as a 200 kDa homotetramer (α4) in enteric bacteria, and as a heterotetramer (α2β2) in plants. In both in vivo and in vitro the substrates (Glucose 1-Phosphate; Glc-1P and Adenosine 5'-Triphosphate; ATP) are converted into a glucose donor ADP-Glucose and a pyrophosphate (PPi) via the ADP-Glc PPase enzyme. It has been noted that some residues are conserved in homotetrameric bacterial ADP-Glc PPases, but are not in some plant forms. One of them is …

The Rich Chemistry Of Cyclotriveratrylene (Ctv) And Ct-Inspired Reactions: Anthracenes With Organic Light-Emitting Diode (Oled) Applications And The Discovery Of Cascade Reactions, Samuel Sarsah

Dissertations

Cyclotriveratrylene (CTV) is a supramolecular scaffold with applications in host-guest chemistry, analytical detection, drug delivery and liquid crystals. We have discovered that CTV rearranges to a highly functionalized anthracene derivative that is ideal for the synthesis of 9,10-disubstituted anthracene derivatives that are useful for the construction of organic light-emitting diodes (OLEDs). Several diaryl anthracene derivatives have been synthesized and analyzed, and were found to have excellent electroluminescent properties, including one analog that exhibits an exceptionally high quantum yield. Red, green and blue are the primary colors needed for full color display, but blue fluorescence emitting organic compounds used in OLEDs …

Differentiation Of Surface Contaminants And Implanted Material On Genesis Solar Wind Samples Using Total Reflection X-Ray Fluorescence Spectometry And Grazing Incidence X-Ray Fluorescence, Martina Schmeling, Peter J. Eng, J.E. Stubbs, Y. Choi, Igor V. Veryovkin

Chemistry: Faculty Publications and Other Works

During the Genesis mission solar wind was implanted in collector materials for analysis by various instrumental methods. Unfortunately the space craft crash landed upon return to Earth shattering the collectors into small fragments and exposing them to desert soil and spacecraft debris. Thus only small fragments are available for analysis with each having different degrees of contamination present at and embedded within the surface. Cleaning procedures were developed and applied to remove the contamination. To aid in this process bench top total reflection X-ray fluorescence spectrometry (TXRF) was used to characterize a sample surface before and after various cleaning steps. …

Identification Of A Histidine Metal Ligand In The Arge-Encoded N-Acetyl-L-Ornithine Deacetylase From Escherichia Coli, Wade C. Mcgregor, Danuta M. Gillner, Sabina I. Swierczek, Dali Liu, Richard C. Holz

Chemistry: Faculty Publications and Other Works

The H355A, H355K, H80A, and H80K mutant enzymes of the argE-encoded N-acetyl-L-ornithine deacetylase (ArgE) from Escherichia coli were prepared, however, only the H355A enzyme was found to be soluble. Kinetic analysis of the Co(II)-loaded H355A exhibited activity levels that were 380-fold less than Co(II)-loaded WT ArgE. Electronic absorption spectra of Co(II)-loaded H355A-ArgE indicate that the bound Co(II) ion resides in a distorted, five-coordinate environment and Isothermal Titration Calorimetry (ITC) data for Zn(II) binding to the H355A enzyme provided a dissociation constant (K_d) of 39 μM. A three-dimensional homology model of ArgE was generated using the …

Functionalization Of Organic Semiconductor Crystals Via The Diels-Alder Reaction, Brittni A. Qualizza, Srividya Prasad, M. Paul Chiarelli, Jacob W. Ciszek

Chemistry: Faculty Publications and Other Works

A surface adlayer is generated on organic single crystals (tetracene and rubrene) using the site specific Diels–Alder reaction and a series of vapor phase dienophiles. X-ray photoelectron spectroscopy (XPS) confirms adsorption on the surfaces of tetracene and rubrene and mass spectrometry demonstrates the reaction’s applicability to a range of dienophiles.

Synthesis, Crystal Structure, And Rearrangements Of Ortho-Cyclophane Cyclotetraveratrylene (Cttv) Tetraketone, Marlon R. Lutz Jr., Matthias Zeller, Samuel R.S. Sarsah, Artur Filipowicz, Hailey Wouters, Daniel Becker

Chemistry: Faculty Publications and Other Works

Oxidation of cyclotetraveratrylene (CTTV) with potassium permanganate in pyridine under reflux gave tetraketone (the [14]ketonand) 3 which exists as a previously unobserved barrel conformation with S4symmetry in the crystal structure, although the more familiar ‘boat’ conformer was shown by semi-empirical AM1 calculations to be 3.03 kcal/mol lower in energy. In addition to CTTV tetraketone 3, an isomeric bis-spirolactone 4 was isolated from the basic oxidation conditions, analogous to the product of trans-annular attack and rearrangement observed with oxidation of cyclotriveratrylene, whereas in acid at elevated temperatures, tetraketone 3 underwent a very efficient rearrangement and decarboxylation to afford the highly symmetric …

Analysis Of Illicit Drugs, Their Metabolites And Other Micropollutants In Water By Liquid Chromatography Tandem Mass Spectrometry, Deepika P. Panawennage

Dissertations

The goal of this project is to develop liquid chromatography tandem mass spectrometry (LC/MS/MS) methods for the analysis of different, novel micropollutants in waste water and natural water. Micropollutants are compounds that can exert adverse environmental and human health effects at low concentrations. Most of these compounds include personal care products and pharmaceuticals, such as antibiotics and controlled substances. In the first part of this study, we focused in the analysis of illicit drugs and drug metabolites because these analyses have the potential to serve as markers of drug abuse. We have detected over sixteen different illicit drugs and their …

Spectroelectrochemical Studies Of The Reductive Intermediates Of Anthraquinone-2,6-Disulfonate In Aqueous Media, Anna Weiss

Dissertations

Reactive intermediates in the reduction of anthraquinone-2,6-disulfonate (AQDS) by dithionite combine to form a transient dimer which has shown to give rise to a series of charge transfer bands in the visible range (600-750 nm). Additional wavelengths associated with these intermediate species have been observed at wavelengths 402, 444 and 510 nm. These transient intermediates are generated as dithionite decomposition products re-oxidize AQDS. Evidence of the dimer was also found in experiments in which reduction of AQDS was achieved electrochemically by the use of a potentiostat. This implies three things: 1. dithionite is not required for dimerization of reactive intermediates; …

Crystal Structure Of Bacillus Subtilis Gabr, An Autorepressor And Transcriptional Activator Of Gabt, Raji Edayathumangalam, Rui Wu, Roman Garcia, Yuguang Wang, Wei Wang

Chemistry: Faculty Publications and Other Works

Bacillus subtilis GabR is a transcription factor that regulates gamma-aminobutyric acid (GABA) metabolism. GabR is a member of the understudied MocR/GabR subfamily of the GntR family of transcription regulators. A typical MocR/GabR-type regulator is a chimeric protein containing a short N-terminal helix-turn-helix DNA-binding domain and a long C-terminal pyridoxal 5′-phosphate (PLP)-binding putative aminotransferase domain. In the presence of PLP and GABA, GabR activates the gabTD operon, which allows the bacterium to use GABA as nitrogen and carbon sources. GabR binds to its own promoter and represses gabRtranscription in the absence of GABA. Here, we report two crystal structures of …

Parallel Text Immersion, Daniel P. Becker Ph.D.

Chemistry: Faculty Publications and Other Works

A new method of teaching foreign languages to beginning, intermediate, and advancing foreign language students is proposed involving reading out loud passages, chapters, and entire works of literature that are familiar to the student through required pre-reading in the students’ mother tongue. Testing is proposed to evaluate the success of the method.

Conformational And Thermodynamic Properties Modulate The Nulceotide Excision Repair Of 2-Aminofluorene And 2-Acetylaminofluorene Dg Adducts In The Nari Sequence, Vipin Jain, Benjamin Hilton, Satyakam Patnaik, Yue Zou, M. Paul Chiarelli, Bongsup P. Cho

Chemistry: Faculty Publications and Other Works

Nucleotide excision repair (NER) is a major repair pathway that recognizes and corrects various lesions in cellular DNA. We hypothesize that damage recognition is an initial step in NER that senses conformational anomalies in the DNA caused by lesions. We prepared three DNA duplexes containing the carcinogen adduct N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-acetylaminofluorene (FAAF) at G(1), G(2) or G(3) of NarI sequence (5'-CCG(1)G(2)CG(3)CC-3'). Our (19)F-NMR/ICD results showed that FAAF at G(1) and G(3) prefer syn S- and W-conformers, whereas anti B-conformer was predominant for G(2). We found that the repair of FAAF occurs in a conformation-specific manner, i.e. the highly S/W-conformeric G(3) and -G(1) …

Evaluation Of The Performance Of Non-Covalent Molecular Mechanical Models For Zn2+ And Mg2+ Metal Ions, Maria Magdalena Kamm

Master's Theses

Computer simulations using molecular dynamics (MD) on classical molecular mechanical

(MM) interatomic potentials can provide valuable information and quantitative

predictions about these systems. In MD calculations binding free energies of ions to

host molecules can be studied if correct ion solvation free energies in aqueous solution

are obtained. However, no MM models exist that parametrize various Zn2+ and

transition metals consistently and consider both structural and thermodynamic data

simultaneously.

The first part of our work focused on MD free energy perturbation (FEP) simulations

to derive MM interaction parameters for Zn2+ and Mg2+ ions in aqueous

solution. To obtain these parameters …

Direct Patterning Of A Cyclotriveratrylene Derivative For Directed Self-Assembly Of C60, Zachary R. Osner, Dorjderem Nyamjav, Richard C. Holz, Daniel P. Becker

Chemistry: Faculty Publications and Other Works

A novel apex-modified cyclotriveratrylene (CTV) derivative with an attached thiolane-containing lipoic acid linker was directly patterned onto gold substrates via dip-pen nanolithography (DPN). The addition of a dithiolane-containing linker to the apex of CTV provides a molecule that can adhere to a gold surface with its bowl-shaped cavity directed away from the surface, thereby providing a surface-bound CTV host that can be used for the directed assembly of guest molecules. Subsequent exposure of these CTV microarrays to C60 in toluene resulted in the directed assembly of predesigned, spatially controlled, high-density microarrays of C60. The molecular recognition capabilities of this CTV …