Physical Sciences and Mathematics Commons^™

High-Frequency Data Reveal Differential Dissolved And Suspended Solids Behavior From A Mixed Restored Prairie And Agricultural Catchment, Andrew Miller, Ashlee L. Dere, Tracy Coleman

Chemistry Faculty Publications

Quantifying temporal variability and fluxes within hydrologic catchments is critical to understanding the underlying chemical and physical processes leading to material transport. Measuring variability and fluxes requires sampling at time scales similar to the time scale of process occurrence. This demand has led to the development of automated sampling systems designed to sample at high frequencies, on the order of minutes. While widely deployed in a variety of systems, we installed two high-frequency sampling devices in a single drainage comprised of restored prairie and agricultural land uses in temperate Eastern Nebraska. The sampling systems determined flow rate, conductivity, and turbidity …

Aromatic Hydrazide Compounds That Inhibit The Growth Of Mycobacterium Tuberculosis, Ronald Bartzatt, Preeti Sule, Thushara Galbadage, Jeffrey D. Cirillo

Chemistry Faculty Publications

Aims: To demonstrate the efficacy of aromatic hydrazide compounds to inhibit growth of Mycobacterium tuberculosis.

Study Design: To synthesize tuberculostats and test their antibacterial activity in-vitro.

Place and Duration of Study: University of Nebraska, Durham Science Center, 6001 Dodge Street, Omaha NE 68182, and Texas A&M Health Science Center, Department of Microbial Pathogenesis and Immunology, 8447 State Hwy 47, Medical Research and Education Building, Room #3012, Bryan, TX 7780. From March 2019 to October 2019.

Methodology: Hydrazide functional groups were formed by covalently bonding hydrazine onto a carbonyl carbon that is a substituent of a single aromatic …

Molecular Modeling Studies On The Binding Mode Of The Pd-1/Pd-L1 Complex Inhibitors, Suliman Almahmoud, Haizhen A. Zhong

Chemistry Faculty Publications

The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) is an immune checkpoint (ICP) overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. To determine important residues for ligand binding, we applied molecular docking studies to PD-1/PD-L1 complex inhibitors against the PD-L1 protein. Our data revealed that the residues Tyr56, Asp122, and Lys124 play critical roles in ligand binding to the PD-L1 protein and they could be used to design ligands that are active against the PD-1/PD-L1 complex. The formation of H-bonds with Arg125 of the PD-L1 protein …

Assay Of Vitamin B6 (Pyridoxine Hydrochloride) Utilizing Isocratic Reversed Phase High Performance Liquid Chromatography, Ronald Bartzatt, Purnima Gajmer, Mai Han Cassandra Nguyen, Alexndra My-Hanh Tran

Chemistry Faculty Publications

Aims: To demonstrate an analysis for vitamin B6 from commercial aqueous nutritional drinks and solid tablets, utilizing isocratic conditions with high performance liquid chromatography (HPLC) and UV detection at 290 nm. Study Design: Vitamin B6 in the form of pyridoxine hydrochloride is assayed by HPLC from various samples. Place and Duration of Study: Department of Chemistry, Durham Science Center, University of Nebraska, Omaha Nebraska from May to August 2016. Methodology: Utilizing a reversed-phase C-18 column with eluent solvent (19% ethanol, 77% water, 4% acetic acid), the samples were prepared in sample solvent (19% ethanol, 81% distilled water). Detection of vitamin …

Conformational Studies Of Glucose Transporter 1 (Glut1) As An Anticancer Drug Target, Suliman Almahmoud, Xiaofang Wang, Jonathan L. Vennerstrom, Haizhen A. Zhong

Chemistry Faculty Publications

Glucose transporter 1 (GLUT1) is a facilitative glucose transporter overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. GLUT1 works through conformational switching from an outward-open (OOP) to an inward-open (IOP) conformation passing through an occluded conformation. It is critical to determine which conformation is preferred by bound ligands because the success of structure-based drug design depends on the appropriate starting conformation of the target protein. To find out the most favorable GLUT 1 conformation for ligand binding, we ran systemic molecular docking studies for different conformations of GLUT1 using known …

Structural Identification And Kinetic Analysis Of The In Vitro Products Formed By Reaction Of Bisphenol A‑3,4-Quinone With N‑Acetylcysteine And Glutathione, Douglas E. Stack, John A. Conrad, Bejan Mahmud

Chemistry Faculty Publications

Bisphenol A (BPA) has received considerable attention as an endocrine disrupting chemical and a possible substrate for genotoxic metabolites. BPA metabolism leads to formation of electrophilic o-quinones cable of binding to DNA and other endogenous nucleophiles. We have structurally identified the products resulting from the reaction of bisphenol A-3,4-quinone (BPAQ) with N-acetylcysteine (NAC) and glutathione (GSH). The major and minor isomers are both the result of 1,6-conjugate addition and are produced almost instantly in high yield. Reactions using 1.3 equiv of GSH showed the presence of a bis-glutathionyl adduct which was not observed using higher GSH concentration relative to BPAQ. …

Prediction Of Novel Anti-Ebola Virus Compounds Utilizing Artificial Neural Network (Ann), Ronald Bartzatt

Chemistry Faculty Publications

Artificial Neural Network (ANN) analysis is shown to predict the molecular properties of new anti-EBOLA compounds following training/learning by use of 60 previously known and studied drugs. Following training/learning by applying properties of 60 known drugs the TIBERIUS ANN system can efficiently predict the molecular properties of comparable new drugs. Molecular weight (MW) is an important and dominant property of perspective drugs considered for clinical trials. TIBERIUS ANN was able to predict comparable values of MW for drugs following training cycles. One-way ANOVA, F and T tests indicate that actual and predicted MW have the same means (P=.99). Passing-Bablok regression …

Neurological Impact Of Zinc Excess And Deficiency In Vivo, Ronald Bartzatt

Chemistry Faculty Publications

Zinc is an essential mineral that can cause pathological effects whether in excess or deficiency. Zinc is a component for over 250 enzymes and is required for cell growth, cell division, and cell function. Zinc is found in muscle and bones, with the prostrate, liver, skin, and kidney having detectable levels of zinc. However, zinc present in excess or deficiency can cause significant pathology in patients that include deleterious effects neurologically. Zinc in excess in vivo can cause focal neuronal pathology, while zinc deficiency can bring about mental lethargy, neuropsychiatric disorders, and reduced nerve conduction. Zinc is assimilated within the …

Pyrimethamine Based Anti-Protozoan Agents From Isostere And Heuristic Structure-Similarity Search, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To generate new medicaments for control and treatment of the parasitic protozoan Toxoplasma gondii.

Study Design: Structure similarity search and isostere search was conducted over a broad range of structure categories. Correlation and highest similarity scores were implemented to select the best drug candidates.

Place and Duration of Study: University of Nebraska, Department of Chemistry, Durham Science Center, 6001 Dodge Street, Omaha Nebraska 68182, from June 2016 to February 2017.

Methodology: Utilizing pyrimethamine as the parent compound, a broad range of similar structures and isosteres were found by applying search methods. The compounds having the highest correlation and …

Design, Synthesis And Biological Evaluation Of Novel Hedgehog Inhibitors For Treating Pancreatic Cancer, Vinod Kumar, Amit Kumar Chaudhary, Yuxiang Dong, Haizhen Zhong, Goutam Mondal, Feng Lin, Virender Kumar, Ram I. Mahato

Chemistry Faculty Publications

Hedgehog (Hh) pathway is involved in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) maintenance resulting in tumor progression. GDC-0449, an inhibitor of Hh pathway component smoothened (Smo) has shown promise in the treatment of various cancers including pancreatic cancer. However, the emergence of resistance during GDC-0449 treatment with numerous side effects limits its use. Therefore, here we report the design, synthesis and evaluation of novel GDC-0449 analogs using N-[3-(2-pyridinyl) phenyl] benzamide scaffold. Cell-based screening followed by molecular simulation revealed 2-chloro-N1-[4-chloro-3-(2-pyridinyl)phenyl]-N4,N4-bis(2-pyridinylmethyl)-1,4- benzenedicarboxamide (MDB5) as most potent analog, binding with an extra interactions in seventransmembrane (7-TM) domain of Smo due to …

Comparative Analysis Of Antihistamines And Nonsteroidal Anti-Inflammatory Drugs (Nsaids): Properties, Structure And Prediction Of New Potential Drugs, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To determine the molecular properties of common antihistamines and non-steroidal antiinflammatory agents (NSAIDs). To identify interrelationships among these two groups of drugs utilizing pattern recognition methods and statistical analysis.

Study Design: After determination of molecular properties, values thereof are examined using pattern recognition methods and other numerical analysis for underlying relationships and similarities.

Place and Duration of Study: Durham Science Center, University of Nebraska, Omaha, Nebraska from September 2016 to January 2017.

Methodology: Thirty compounds were identified as antihistamines and 27 compounds identified as NSAIDs. Properties such as Log P, molecular weight, polar surface area, etc. are determined. Molecular …

Crystal Structure Of Li3ga(Bo3)2, Robert W. Smith, Darien Holman, Eric M. Villa

Chemistry Faculty Publications

The crystal structure of trilithium gallium bis(orthoborate), Li3Ga(BO3)2, is isotypic with Li3Al(BO3)2 in a triclinic cell in space-group type P1. The three Li and the unique Ga atom are coordinated by four O atoms each in tetrahedra, and the two B atoms are coordinated by three O atoms in orthoborate triangles. Chains with composition [Ga2(BO3)4] 6 extend along the a axis. The Li atoms interleave these chains in tetrahedral interstices. A comparison is made between the structure model of the title compound and that of a previously reported model for a compound with the same composition [Abdullaev & Mamedov (1972). …

Relative Properties And Relative Potency Of Various Hydrazide Compounds That Inhibit Growth Of Mycobacterium Tuberculosis, Ronald Bartzatt

Chemistry Faculty Publications

The molecular properties of compounds expressing growth inhibition of Mycobacterium tuberculosis are determined and examined for underlying relationships by pattern recognition methods. Pattern recognition methods such as hierarchical cluster analysis will show relationships between compounds. Descriptive statistical analysis of molecular properties reveal commonality among bacteriostatic compounds. Outliers within any category of descriptor is identified by Grubb’s test. Potency of growth inhibition measured as MIC (minimum inhibitory concentration) after in vitro evaluation will be compared and analyzed. Structure moieties and their effect on activity is identified. All compounds analyzed showed substantial growth inhibition of Mycobacterium tuberculosis, having MIC values ranging from …

Potency And Properties Of Hydrazide Compounds That Inhibit The Growth Of Mycobacterium Tuberculosis, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To examine the properties of hydrazide compounds shown to inhibit Mycobacterium tuberculosis. To identify properties that affect efficiency of bacterial inhibition.

Study Design: Utilizing data from previous studies of compounds that inhibit Mycobacterium tuberculosis, then statistical and pattern recognition methods are applied to identify interrelationships.

Place and Duration of Study: Department of Chemistry, Durham Science Center, University of Nebraska at Omaha, from January 2016 to July 2016.

Methodology: Interrelationships of pharmacological properties were identified by use of various pattern recognition techniques, such as hierarchical cluster analysis and path analysis. Molecular properties and descriptors for all compounds were …

Nmr Analysis Of T‐Butyl‐Catalyzed Deuterium Exchange At Unactivated Arene Localities, Douglas E. Stack, Rachel Eastman

Chemistry Faculty Publications

Regioselective labelling of arene rings via electrophilic exchange is often dictated by the electronic environment caused by substituents present on the aromatic system. Previously, we observed the presence of a t‐butyl group, either covalently bond or added as an external reagent, could impart deuterium exchange to the unactivated, C1‐position of estrone. Here, we provide nuclear magnetic resonance analysis of this exchange in a solvent system composed of 50:50 trifluoroacetic acid and D2O with either 2‐t‐butylestrone or estrone in the presence of t‐butyl alcohol has shed insights into the mechanism of this t‐butyl‐catalyzed exchange. Fast exchange of the t‐butyl group concurrent …

Properties And Drug-Likeness Of Compounds That Inhibit Ebola Virus Disease (Evd), Ronald Bartzatt

Chemistry Faculty Publications

Aims: To present the molecular structures of compounds that has been shown to inhibit the proliferation of Ebola virus. To elucidate the molecular properties of these virus inhibiting compounds.

Study Design: The molecular properties of virus inhibiting compounds are elucidated and compiled. Pattern recognition methods and statistical analysis are applied to determine optimal properties of this group of compounds.

Place and Duration of Study: Chemistry Department, Durham Science Center, University of Nebraska, Omaha NE. between December 2015 and February 2016.

Methodology: A total of 60 compounds were identified as inhibiting the virus Ebola. The molecular properties such as Log P, …

Four Compounds Suppressing Growth Of Mycobacterium Tuberculosis, Ronald Bartzatt, Preeti Sule, Woojung Kim, Jeffrey D. Cirillo

Chemistry Faculty Publications

Aims: To demonstrate the efficacy of several small molecular weight compounds having hydrazide groups, for inhibiting the growth of Mycobacterium tuberculosis. To show these same compounds have favorable drug-likeness properties.

Study Design: To synthesize tuberculostats and test their antibacterial activity in-vitro.

Place and Duration of Study: University of Nebraska, Durham Science Center, 6001 Dodge Street, Omaha NE 68182, and Texas A&M Health Science Center, Department of Microbial Pathogenesis and Immunology, 8447 State Hwy 47, Medical Research and Education Building, Room #3012, Bryan, TX 7780. From January 2015 to June 2015.

Methodology: Hydrazide groups were formed by covalently bonding hydrazine …

Acridine Orange Staining Of Virus Infected Host Cells To Monitor Proliferation Of Viral Infection, Ronald Bartzatt

Chemistry Faculty Publications

Acridine orange staining is a methodology for nucleic acid selective metachromatic staining that is useful for following cell cycle determination. The interaction of acridine orange with target molecules (i.e. DNA and RNA) is by intercalation or electrostatic attraction, respectively. This work presents methodology and results of a cell staining that utilizes acridine orange fluoresence. It is possible to visualize under dark field ultraviolet microscope the actual viral infected host cells. The color production is stark and easily selected. This method appears to be versatile for a number of various cell types in tissue culture, including human lymphocytes. This methodology is …

Identifying The Tautomeric Form Of A Deoxyguanosine-Estrogen Quinone Intermediate, Douglas E. Stack

Chemistry Faculty Publications

Mechanistic insights into the reaction of an estrogen o-quinone with deoxyguanosine has been further investigated using high level density functional calculations in addition to the use of 4-hyroxycatecholestrone (4-OHE1) regioselectivity labeled with deuterium at the C1-position. Calculations using the M06-2X functional with large basis sets indicate the tautomeric form of an estrogen-DNA adduct present when glycosidic bonds cleavage occurs is comprised of an aromatic A ring structure. This tautomeric form was further verified by use of deuterium labelling of the catechol precursor use to form the estrogen o-quinone. Regioselective deuterium labelling at the C1-position of the estrogen A ring allows …

Block Design-Based Asynchronous Neighbor Discovery Protocol For Wireless Sensor Networks, Sangil Choi, Wooksik Lee, Teukseob Song, Jong-Hoon Youn

Chemistry Faculty Publications

Neighbor discovery is a significant research topic in wireless sensor networks. After wireless sensor devices are deployed in specific areas, they attempt to determine neighbors within their communication range. This paper proposes a new Block design-based Asynchronous Neighbor Discovery protocol for sensor networks called BAND. We borrow the concept of combinatorial block designs for neighbor discovery. First, we summarize a practical challenge and difficulty of using the original block designs. To address this challenge, we create a new block generation technique for neighbor discovery schedules and provide a mathematical proof of the proposed concept. A key aspect of the proposed …

Potential Antineoplastic Structural Variations Of Uracil Mustard (Uramustine) Retaining Cytotoxic Activity And Drug-Likeness Suitable For Oral Administration, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To present 12 new variants of uracil mustard having drug-like properties and cytotoxic functional group, by utilizing uracil mustard (uramustine) as a lead compound. Utilize rigorous substructure and similarity of a molecular scaffold to determine drug like variants. Physicochemical properties determined indicate the variants have favorable drug-likeness.

Study Design: Conduct molecular database search utilizing features of substructure and similarity based upon uracil mustard. Place and Duration of Study: Department of Chemistry, Medicinal Chemistry Study Section, University of Nebraska at Omaha, Omaha Nebraska between January 2015 to March 2015.

Methodology: Uracil mustard consists of the pyrimidine derivative uracil, …

Design Of Cox-1 Inhibitors Utilizing Class I Isosteres, Class Ii Isosteres, And Nonclassical Bioisosteres For Substituent Substitution On Proved Parent Structures, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To identify isosteres and bioisosteres suitable for substitution on the molecular scaffold of meclofenamic acid and tolfenamic acid. The compounds will be studied to determine drug-likeness and other properties.
Study Design: Isosteres and bioisosteres were selected and emplaced on the scaffold of meclofenamic acid and tolfenamic acid to ascertain drug-likeness outcome. Drug candidates were selected based on favorable drug-likeness.
Place and Duration of Study: Chemistry Department, University of Nebraska at Omaha, Omaha Nebraska from March 2015 to May 2015.
Methodology: Two non-steroidal anti-inflammatory drugs, meclofenamic acid and tolfenamic acid, are selected based on versatile isosteres and bioisosteres substitution. Placement …

Measuring The Alkylation Kinetics And Drug Likeness Of Four Candidate Antineoplastic Compounds, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To synthesize small molecule alkylating compounds and analyze the kinetics of the alkylation in aqueous solution. Determine molecular properties and the drug likeness of these four compounds as potential antineoplastic agents and apply statistical analysis to identify interrelationships of properties.

Study Design: Four compounds were synthesized, characterized, and studied for alkylation capability. The alkylation kinetics were elucidated, as well as drug likeness properties. The interrelationships of properties were examined by statistical methodology.

Place and Duration of Study: Department of Chemistry, Durham Science Center, University of Nebraska at Omaha, Omaha NE, from May 2015 to June 2015.

Methodology: Four compounds …

Drug Analogs Of Cox-2 Selective Inhibitors Lumiracoxib And Valdecoxib Derived From In Silico Search And Optimization, Ronald Bartzatt

Chemistry Faculty Publications

The medicinal activity of COX-2 inhibitors are sufficiently beneficial to urge the search for new drug designs. This study presents 16 analogs of lumiracoxib and 10 analogs to valdecoxib having properties suitable as COX-2 inhibitors. For lumiracoxib analogs the mean Log P, polar surface area, and formula weight are 3.00, 70.46 A2, and 276.60, respectively. For valdecoxib analogs the mean Log P, polar surface area, and formula weight are 3.65, 68.46 A2, and 322.32, respectively. Grubb’s test analysis of seven properties for seven known COX-2 selective inhibitors and those of 26 analog compounds indicated no outliers. The unpaired t-test compared …

Detection And Assay Of Riboflavin (Vitamin B2) Utilizing Uv/Vis Spectrophotometer And Citric Acid Buffer, Ronald Bartzatt, Michelle Lee Follis

Chemistry Faculty Publications

Aims: Riboflavin is a B vitamin that is required for a wide variety of cellular processes. The absorbance spectrum of riboflavin was determined at different pH utilizing several buffers. The buffer at pH demonstrating table absorbance peaks with high numerical values of molar absorptivity is followed by accurate and sensitive assay of riboflavin by spectrophotometer. Study Design: The absorbance spectrum of riboflavin is determined in an aqueous buffer at various pH values. After identifying the absorbance peaks providing maximal molar absorptivity the assay of riboflavin in the identical buffer was undertaken. Place and Duration of Study: Department of Chemistry, Durham …

Novel Tuberculostatic Agents Suitable For Treatment Of Mycobacterium Tuberculosis Infections Of The Central Nervous System, Ronald Bartzatt, Preeti Sule, Suat L.G. Cirillo, Jeffrey D. Cirillo

Chemistry Faculty Publications

Aims: To demonstrate the efficacy of five small molecule compounds for inhibiting the growth of Mycobacterium tuberculosis. To present evidence that these compounds will penetrate into the central nervous system.

Study Design: Five small molecule compounds bearing a hydrazide group were synthesized utilizing microwave excitation. These compounds were then placed into tissue culture with Mycobacterium tuberculosis at various concentrations for evaluation of bacterial growth inhibition.

Place and Duration of Study: The compounds to be tested were prepared at the University of Nebraska Chemistry Department August 2013. The evaluation of antibacterial activity was determined at the Texas A&M Health Science …

Lomustine Analogous Drug Structures For Intervention Of Brain And Spinal Cord Tumors: The Benefit Of In Silico Substructure Search And Analysis, Ronald Bartzatt

Chemistry Faculty Publications

Lomustine is a nitrosourea anticancer agent shown to be effective for treatment of childhood medulloblastoma. In silico substructure searches produced 17 novel nitrosourea agents analogous to lumustine and retaining activity for DNA alkylation and cytotoxic activity. The mean values for Log P, polar surface area, formula weight, number of oxygens & nitrogens, and rotatable bonds were 2.524, 62.89 Anstroms2, 232.8, 5, and 2, respectively. All 17 agents have formula weight less than 450 and Log P less than 5, two criteria preferred for blood-brain barrier penetration.These agents have a polar surface area less than 90 Angstroms2. Each show zero violations …

Test Selection On Extended Finite State Machines With Provable Guarantees, Bo Guo, Mahadevan Subramaniam

Chemistry Faculty Publications

Building high confidence regression test suites to validate new system versions is a challenging problem. A model- based approach to build a regression test suite from a given test suite is described. The generated test suite includes every test that will traverse a change performed to produce the new version, and consists of only such tests to reduce the testing costs. Finite state machines extended with typed variables (EFSMs) are used to model systems and system changes are mapped to EFSM transition changes adding/deleting/replacing EFSM transitions and states. Tests are a sequence of input and expected output messages with concrete …

Experimental Determination Of Pka Values By Use Of Nmr Chemical Shifts, Revisited, Alan D. Gift

Chemistry Faculty Publications

This laboratory experiment, using proton NMR spectroscopy to determine the dissociation constant for heterocyclic bases, has been modified from a previously described experiment. A solution of a substituted pyridine is prepared using deuterium oxide (D2O) as the solvent. The pH of the solution is adjusted and proton NMR spectra are collected for a variety of pH values. The chemical shifts of the peaks in the NMR spectrum change depending on the degree of protonation of the pyridine ring. Analysis of the spectral data is used to calculate the dissociation constant of the substituted pyridine. This experiment is suitable for a …

Evolutionary History And Phylodynamics Of Influenza A And B Neuraminidase (Na) Genes Inferred From Large-Scale Sequence Analyses, Haizhen Zhong

Chemistry Faculty Publications

Background: Influenza neuraminidase (NA) is an important surface glycoprotein and plays a vital role in viral replication and drug development. The NA is found in influenza A and B viruses, with nine subtypes classified in influenza A. The complete knowledge of influenza NA evolutionary history and phylodynamics, although critical for the prevention and control of influenza epidemics and pandemics, remains lacking.

Methodology/Principal findings: Evolutionary and phylogenetic analyses of influenza NA sequences using Maximum Likelihood and Bayesian MCMC methods demonstrated that the divergence of influenza viruses into types A and B occurred earlier than the divergence of influenza A …