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Rapid Reversible Borane To Boryl Hydride Exchange By Metal Shuttling On The Carborane Cluster Surface, Bennett J. Eleazer, Mark D. Smith, Alexey A. Popov, Dmitry V. Peryshkov

Faculty Publications

In this work, we introduce a novel concept of a borane group vicinal to a metal boryl bond acting as a supporting hemilabile ligand in exohedrally metalated three-dimensional carborane clusters. The (POBOP)Ru(Cl)(PPh3) pincer complex (POBOP ¼ 1,7-OP(i-Pr)2-m-2-carboranyl) features extreme distortion of the two-center-two-electron Ru–B bond due to the presence of a strong three-centertwo-electron B–H/Ru vicinal interaction. Replacement of the chloride ligand with a hydride afforded the (POBOP)Ru(H)(PPh3) pincer complex, which possesses B–Ru, B–H/Ru, and Ru–H bonds. This complex was found to exhibit a rapid exchange between hydrogen atoms of the borane and the terminal hydride through metal center shuttling between …

Stereochemical Preference Toward Oncotarget: Design Synthesis And In Vitro Anticancer Evaluation Of Diastereomeric B-Lactams, Fabian Olazarán-Santibáñez, Debasish Bandyopadhyay, Pilar Carranza-Rosales, Gildardo Rivera, Isias Balderas-Rentería

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Purpose: In the battle against cancer discovery of new and novel chemotherapeutic agent demands extreme obligation. Development of anticancer compounds with higher potency and reduced side-effects is timely and challenging.

Experimental Design: A small series of fourteen diastereomeric β-lactams (seven pairs) were synthesized through multi-step process exploring [2+2] ketene-imine cycloaddition as the key step. Comparative stereochemical preferences were studied through computational docking and validated by in vitro evaluation. β-tubulin was considered as possible molecular target and in vitro anticancer evaluation was conducted against SiHa, B16F10, K562 and Chang cell lines. Caspase-3 activation assay and hematoxylin/eosin staining of the cells were …

Preferential Binding Effects On Protein Structure And Dynamics Revealed By Coarse-Grained Monte Carlo Simulation, Ras B. Pandey, D.L. Jacobs, Barry L. Farmer

Faculty Publications

The effect of preferential binding of solute molecules within an aqueous solution on the structure and dynamics of the histone H3.1 protein is examined by a coarse-grained Monte Carlo simulation. The knowledge-based residue-residue and hydropathy-index-based residue-solvent interactions are used as input to analyze a number of local and global physical quantities as a function of the residue-solvent interaction strength (f). Results from simulations that treat the aqueous solution as a homogeneous effective solvent medium are compared to when positional fluctuations of the solute molecules are explicitly considered. While the radius of gyration (R_g) of the …

Development Of Luminescent Quantum Dot-Enabled Nano- And Microplatforms For Multiplex Detection Of Biomarkers, Kristen S. Williams

LSU New Orleans Theses and Dissertations

Luminescent semiconductor quantum dots (QDs) are extensively researched for use in biological applications. They have unique optical and physical properties that make them excellent candidates to replace conventional organic dyes for cellular labeling, multiplexing, nucleic acid detection, and as generalized probes. The primary focus of this dissertation was to utilize quantum dots for improvement in immunoassays. Specifically, atherosclerosis biomarkers were detected simultaneously in an effort to demonstrate advances in early detection diagnostics.

Quantum dot-antibody bioconjugates were prepared by encapsulation into mesoporous silica and functionalized with thiol and amine groups to enable bioconjugation. Functionalization of the mesoporous silica quantum dot composites …

Studies Directed Towards The Iridium Catalyzed Synthesis Of New Carbon-Nitrogen Bonds., Maria Lindsay

LSU New Orleans Theses and Dissertations

Amines are ubiquitous in nature and serve a variety of functions in living organisms. Because of this fact amines are of great biological and pharmaceutical interest. The iridium catalyst (pentamethylcyclopentadienyl) iridium dichloride dimer ([Cp*IrCl₂]₂) has been used in a number of ways to synthesize new carbon-nitrogen bonds. These studies were directed toward the development of a method for the iridium catalyzed N-alkylation of alpha-amino acid esters as well as the development of a strategy for synthesis of the natural product 275A.

We have optimized a method for the N-alkylation for alpha-amino acid esters. Using this …

Cancer Cell Spheroids Are A Better Screen For The Photodynamic Efficiency Of Glycosylated Photosensitizers, Patrícia M. R. Pereira, Naxhije Berisha, N.V.S. Dinesh K. Bhupathiraju, Rosa Fernandes, João P.C. Tomé, Charles Michael Drain

Publications and Research

Environmental remediation requires ion-selective polymers that operate under a wide range of solution conditions. In one example, removal of trivalent and divalent metal ions from waste streams resulting from mining operations before they enter the environment requires treatment at acidic pH. The monoethyl ester phosphate ligands developed in this report operate from acidic solutions. They have been prepared on polystyrene-bound ethylene glycol, glycerol, and pentaerythritol, and it is found that intraligand hydrogen bonding affects their metal ion affinities. The affinity for a set of trivalent (Fe(III), Al(III), La(III), and Lu(III)) and divalent (Pb(II), Cd(II), Cu(II), and Zn(II)) ions is greater …

Mass Spectrometry-Based Structural Analysis Of Photosynthetic Protein Assemblies, Yue Lu

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation focuses on using mass spectrometry-based techniques to study photosynthetic protein assemblies. Photosynthesis is a process that converts light energy into chemical energy, the basis of most life on Earth. The two most crucial protein machineries involved in this process are reaction center and light harvesting complexes. They are usually giant protein complexes with different numbers of co-factors. In a more expanded sense, photosynthesis is not just about the utilization of solar energy, the regulation of light energy is also essential as excess light energy is detrimental to photosynthesis organisms. Again, protein assemblies play an indispensable role in this …

Tissue Damage Quantification In Alzheimer's Disease Brain Via Magnetic Resonance Gradient Echo Plural Contrast Imaging (Gepci), Yue Zhao

Arts & Sciences Graduate Student Theses and Dissertations

Alzheimer’s disease (AD) affected approximately 48 million people worldwide in 2015. Its devastating consequences have stimulated an intense search for AD prevention and treatment. Clinically, AD is characterized by memory deficits and progressive cognitive impairment, leading to dementia. Over the past two to three decades, researchers have found that amyloidbeta (Aβ) plaques and neurofibrillary tau tangles occur during a long pre-symptomatic period (preclinical stage) before the onset of clinical symptoms. As a result, identification of the preclinical stage is essential for the initiation of prevention trials in asymptomatic individuals. Currently, Positron Emission Tomography (PET) imaging with injected 11C or 18F …

Mapping Analyte-Signal Relations In Lc-Ms Based Untargeted Metabolomics, Nathaniel Guy Mahieu

Arts & Sciences Graduate Student Theses and Dissertations

The goal of untargeted metabolomics is to profile metabolism by measuring as many metabolites as possible. A major advantage of the untargeted approach is the detection of unexpected or unknown metabolites. These metabolites have chemical structures, metabolic pathways, or cellular functions that have not been previously described. Hence, they represent exciting opportunities to advance our understanding of biology. This beneficial approach, however, also adds considerable complexity to the analysis of metabolomics data - an individual signal cannot be readily identified as a unique metabolite. As such, a major challenge faced by the untargeted metabolomic workflow is extracting the analyte content …

Study Of Selectivity In Extraction, Separation, And Detection On Drugs Using Gas Chromatography, Anumeha P. Muthal

Seton Hall University Dissertations and Theses (ETDs)

The selectivity of a method is defined by its ability to determine a particular analyte without interference in a complex mixture. Selectivity in gas chromatography (GC) can be obtained at different points in the analysis including the sample preparation, sample introduction, separation on column and detection. In GC, the first dimension of selectivity can be obtained in sample preparation; the second dimension in chromatographic separation and the third dimension in detection. This research focuses on the relationships between selectivity in these different dimensions, studied using some non-steroidal anti-inflammatory drugs, glucocorticoids, fatty acid methyl esters and polycyclic aromatic hydrocarbons. Recent methodologies …

Understanding The Dynamic Process Of Dissolution Using In-Situ Ft-Ir Spectroscopy, Vrushali M. Bhawtankar

Seton Hall University Dissertations and Theses (ETDs)

Dissolution studies provide valuable and critical drug release information (in vitro) that are important for quality control drug development. Using in-situ FT-IR spectroscopy methods has been developed for analyzing and monitoring dissolutions of pharmaceutical APIs. The accuracy of this technique was found to be ± 3% relative to HPLC and UV/Vis Spectroscopy. A dynamic analysis of the dissolution and subsequent hydrolysis of aspirin has been determined by in-situ FT-IR. This technique allows real-time analysis of the behavior of aspirin under simulated physiological conditions (pH 1.2, 4.5, 6.8) as aspirin (1205 cm^-1) and salicylic acid (1388 cm^-1) …

Synthesis Of Pyranobenzopyrans, Sumiea B. Eltayeb

Seton Hall University Dissertations and Theses (ETDs)

Carbohydrates and their derivatives are involved in a wide array of biological processes and are crucial for the survival of living entities. As a result, sugar-based compounds have become attractive scaffolds for drug design. In addition, pyranobenzopyran derivatives have shown promise in the treatment of numerous health conditions such as anticoagulants, antifungal, and anti-inflammatory agents. They have also shown important properties as antibiotics anti-AIDS agents) and antitumor drugs. The main point of our research was to determine and develop a synthetic method for the preparation of pyranobenzopyrans and carbohydrate fused heterocyclic compounds. This was accomplished via a [4+2] cycloaddition reaction …

Surface Mutation Thr34his Facilitates Purification Of Haemophilus Influenza Carbonic Anhydrase Via Metal Affinity Chromatography, Caroline Foley, Dr. Kathleen Cornely

Chemistry & Biochemistry Student Scholarship

In order to pursue Haemophilus influenza carbonic anhydrase (HICA) as a potential drug target, easy and efficient purification methods must be developed. While immobilized metal affinity chromatography (IMAC) may be used, complications with polyhistidine tags is a concern. Inspired by the endogenous metal affinity of Escherichia coli β-carbonic anhydrase (ECCA), we suggest that the generation of histidine clusters on HICA’s surface will facilitate its purification by metal affinity chromatography without the potential interference of His-tags. Here we investigate the Thr34His mutation as a method to generate metal affinity in HICA. Since Thr34His is located only 5.3 Å away from His32, …

Adsorption And Wetting In Model Mesoporous Silicas And In Complex Metal Oxide Catalysts, Karthik Jayaraman

Seton Hall University Dissertations and Theses (ETDs)

The surface of most metal oxides is covered by hydroxyl groups which influence many surface phenomena such as adsorption and wetting, catalysis and surface reactions. Surface chemistry of silica is a subject of exhaustive studies owing to a wide variety of practical applications of silica. In Chapter 1, a brief review of classification, synthesis and characterization of silica is provided. The hydroxylation of silica surface i.e the number of hydroxyl (-OH) groups on the surface is of utmost importance for its practical applications. In Chapter 2, a brief introduction to surface hydration of silica is provided followed by the gas …

High-Resolution Three-Dimensional Nmr Structure Of The Kras Proto-Oncogene Promoter Reveals Key Features Of A G-Quadruplex Involved In Transcriptional Regulation, A. Kerkour, J. Marquevielle, S. Ivashchenko, Liliya A. Yatsunyk, J.-L. Mergny, G. F. Salgado

Chemistry & Biochemistry Faculty Works

Non-canonical base pairing within guanine-rich DNA and RNA sequences can produce G-quartets, whose stacking leads to the formation of a G-quadruplex (G4). G4s can coexist with canonical duplex DNA in the human genome and have been suggested to suppress gene transcription, and much attention has therefore focused on studying G4s in promotor regions of disease-related genes. For example, the human KRAS proto-oncogene contains a nuclease-hypersensitive element located upstream of the major transcription start site. The KRAS nuclease-hypersensitive element (NHE) region contains a G-rich element (22RT; 5′-AGGGCGGTGTGGGAATAGGGAA-3′) and encompasses a Myc-associated zinc finger-binding site that regulates KRAS transcription. The NEH region …

In The Tristate Area Consisting Of Kansas, Missouri, And Oklahoma, A Local And State Level Comparison Of High School Chemistry Prerequisites, High School Chemistry Instructor Preparation, And The Readiness Of A High School Student For College Chemistry, Greg Howard

Electronic Theses & Dissertations

The purpose of this thesis is to create an awareness among secondary and post-secondary instructors as to the student’s preparation in high school Chemistry I and the student’s readiness for General Chemistry I in college for a tristate area consisting of Kansas, Missouri, and Oklahoma. Student preparation in this research included chemistry I course prerequisites, high school chemistry teacher qualifications including preparation, and student exposure to rigorous science and math course patterns in high school as these relate to college readiness.

Data was gathered from a local cohort group consisting of high schools in Southeast Kansas (SEK), Southwest Missouri (SWM), …

Facile Synthesis And Characterization Of Graphene Nanoribbons/Polypyrrole Nanocomposite, Johara A. Al Dream

Electronic Theses & Dissertations

Carbon is present in various forms such as coal, carbon nanotubes, graphene, diamond etc. Among various forms, carbon nanotubes and graphene have attracted considerable research attention due to their high thermal stability, high mechanical strength and electrical conduction. These properties largely depend on synthesis procedure. In this work, we synthesized graphene nanoribbons using carbon nanotubes for nanocomposites with polypyrrole. Chemical oxidation was used to unzip the carbon nanotubes. These graphene nanoribbons were used to fabricate nanocomposites with polypyrrole for energy storage applications. The synthesized nanocomposites were structurally and electrochemically characterized.

The structural characterization was performed using X-ray diffraction, FT-IR, SEM, …

One-Pot Syntheses And Characterizations Of “Click-Able” Polyester Polymers For Potential Biomedical Applications, James F. Beach Ii

Electronic Theses & Dissertations

In this study, a synthetic polyester polymer was designed using polyethylene glycol, sorbitol, glutaric acid and 4-pentynoic acid as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by Novozyme-435, an enzyme suitable for polyesterification of biocompatible compounds. The progress of the reaction was monitored with respect to time and vacuum exposure, with samples being subjected to standard characterization protocols. Polymers with high molecular weight and water solubility were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to cancer cells. This was achieved by employing a solvent diffusion method, wherein the polymer …

Molecularly Targeted Nanomedicine: Role Of Hsp90 Inhibitor And Sophorolipids In The Treatment Of Lung Cancer, Shuguftha Naz Ms

Electronic Theses & Dissertations

Lactonic sophorolipids (LSL) are a class of enzymatically modified glycolipids known to have HDAC inhibition activity and anticancer properties. Ganetespib (GT), an Hsp90 inhibitor, is known for its superior antitumor activity in several K-RAS mutant Non-Small-Cell Lung Cancer (NSCLC) cells. In this study, a new anti-oxidant nanoplatform is formulated using the combination of these two drugs, LSL and GT, in order to target both HDAC inhibition and Hsp90 signaling pathways in NSCLC. Nanoceria (NC) is an excellent redox platform will be specifically used to supplement the therapeutic potency of these drugs in the effective treatment of NSCLC. We hypothesized that …

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 …

The Study Of Zirconium Hydroxide And Zirconium (Iv) Metal-Organic Frameworks As Reactive Substrates For The Decomposition Of Chemical Warfare Agents, James W. Kollar

Master of Science in Chemical Sciences Theses

Nerve agents have been described by the Center for Disease Control and Prevention to be the most toxic and rapidly acting of chemical warfare agents. The present study investigates the efficacy of zirconium hydroxide, Zr(OH)₄, and Zr(IV) Metal-Organic Frameworks (MOFs) in the uptake and decomposition of the gas phase nerve agent simulant dimethyl methylphosphonate, DMMP. This investigation was carried out using two different methods: 1) with the use of Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) to examine the surface reaction between DMMP and the solid; and 2) using a flow reactor system that monitored gas phase reaction …

A Perspective On How To Improve Undergraduate Research Education In The Physical Sciences At Usc, Michael Caleb Bagley

Senior Theses

My years at the University of South Carolina have been some of the most challenging and edifying periods of my life. I have been blessed by having a great professional and chemistry mentor in Dr. John L. Ferry who has helped me engage in scientific research in a meaningful way. As I watched other chemistry students, in particular, struggle with understanding what research really was and even how to understand the results and methodologies of it I felt that this was a huge issue that could be rather simply fixed. I have been privileged to apply for and receive a …

Discovery Of A Diaminopyrimidine Flt3 Inhibitor Active Against Acute Myeloid Leukemia, Jamie A. Jarusiewicz, Jae Yoon Jeon, Michele C. Connelly, Yizhe Chen, Lei Yang, Sharyn D. Baker, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

Profiling of the kinase-binding capabilities of an aminopyrimidine analogue detected in a cellular screen of the St. Jude small-molecule collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure–activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological profiling demonstrated that compound 5e shows characteristics suitable for further preclinical development.

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 …

Synthesis Of Α, Β-Substituted Alkenylphosphonates From Α-Phosphonovinyl Triflates: I) Palladium Catalyzed Suzuki-Miyaura Cross-Coupling With Aryl Boronic Acids Ii) Palladium Catalyzed Reduction, Ronald Laryea Mensah

Master of Science in Chemical Sciences Theses

Alkenylphosphonates (vinylphosphonates) are important targets for R & D because they have interesting chemical, biological and pharmacological properties. Vinylphosphonates are used in synthesis, polymer applications, and have demonstrated potential as anticancer and antimicrobial agents.

Vinyl triflates are useful in organic synthesis and are referred to as pseudo-halides because they react in a manner similar to halides. Vinyl triflates have a broad range of synthetic utility because they undergo nucleophilic substitutions and transition metal-mediated reactions. There is a growing interest in using α-phosphonovinyl pseudo-halides in transition metal-mediated cross-coupling reactions as a means to synthesize α, β-substituted alkenylphosphonates. Over the past three …

Analysis Of Structural Stability Of Human Prosecretory Mitogenic Lacritin By Circular Dichroism, Anna P. Desmarais, Casey Q. Ramirez Cortes

Senior Honors Projects, 2010-2019

Purpose: Lacritin is a human tear glycoprotein that has high thermal stability. When cleaved, lacritin has antimicrobial activity resulting from the C-terminus amphipathic alpha helical region. The alpha helices contain three salt bridges; ionic bonds between neighboring oppositely charged amino acids. The purpose of this research was to investigate the hypothesis that the salt bridges within the alpha helices contribute to the high thermal stability.

Methods: To determine the role of salt bridges in the thermal stability of lacritin, point mutants were prepared for each salt bridge by site directed mutagenesis that replaced the oppositely charged amino acids with serine. …

Synthesis Of Oxidative Metabolites Of Di(2-Ethylhexyl) Phthalate, Kelly Mcdaniel

Departmental Honors & Graduate Capstone Projects

Di(2-ethylhexyl) phthalate (DEHP) is a chiral persistent organic pollutant that is used as a plasticizer in polyvinyl chloride (PVC). Humans are exposed to DEHP through inhalation, ingestion, and intravenous exposure; it has shown toxicity as an endocrine disrupter and carcinogen. In the body, DEHP is broken down into mono(2-ethylhexyl) phthalate (MEHP), which is subsequently oxidized in various locations on the ethylhexyl chain. Since previous studies of DEHP have ignored chirality, the purpose of this research is to synthesize enantiomerically pure oxidative metabolites of DEHP. One of the oxidative metabolites of DEHP, 2cx-MMHP, was produced by a malonic ester synthesis followed …

Development Of Neurotensin-Based Radiopharmaceuticals For Neurotensin-Receptor-1-Positive Tumors Targeting, Yinnong Jia

Theses & Dissertations

The neurotensin receptor 1 (NTR1) is overexpressed in many cancers, due to its role as a growth pathway. These NTR1-positive cancers include pancreatic, colon, prostate and breast cancers. In the radiopharmaceutical field, the overexpression of NTR1 in cancer has prompted the development of NTR1-targeted diagnostics and therapeutics. The neurotensin (NT) peptide exhibits low nanomolar affinity for NTR1 and has been the paradigm for NTR1-targeted agents. Since the 1980’s, radiolabeled NT analogs have been developed and evaluated for targeting NTR1-positive cancers. Since native NT is rapidly degraded in vivo by a variety of peptidases, a tremendous amount of effort has been …

Paper Microzone Plates As Analytical Tools For Studying Enzyme Stability: A Case Study On The Stabilization Of Horseradish Peroxidase Using Trehalose And Su-8 Epoxy Novolac Resin, Kirsten A. Ganaja, Cory Chaplan, Jingyi Zhang, Nathaniel W. Martinez, Andres W. Martinez

Chemistry and Biochemistry

Paper microzone plates in combination with a noncontact liquid handling robot were demonstrated as tools for studying the stability of enzymes stored on paper. The effect of trehalose and SU-8 epoxy novolac resin (SU-8) on the stability of horseradish peroxidase (HRP) was studied in both a short-term experiment, where the activity of various concentrations of HRP dried on paper were measured after 1 h, and a long-term experiment, where the activity of a single concentration of HRP dried and stored on paper was monitored for 61 days. SU-8 was found to stabilize HRP up to 35 times more than trehalose …

Development Of New Routes For The Synthesis Of Carbaporphyrins And Carbachlorins, Navneet Sahota

Theses and Dissertations

Carbaporphyrins and carbachlorins are porphyrin analogs in which one of the nitrogens is replaced with a carbon atom within a porphyrin-like cavity. These systems form stable organometallic derivatives and exhibit unusual chemical reactivity. In the monocarbaporphyrinoids such as benzocarbaporphyrins, one of the pyrrole rings is replaced by an indene unit. Although syntheses of monocarbaporphyrins with fused rings have been widely investigated over the past 20 years, a few examples of carbaporphyrins without fused rings have been reported in the literature.

In this thesis, two projects were conducted to further explore carbaporphyrin and carbachlorin chemistry. The first project utilized a ‘3+1’ …