Chemistry Commons^™

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

The Spectral Features And Detectability Of Small, Cyclic Silicon Carbide Clusters, Christopher M. Sehring, C. Zachary Palmer, Brent R. Westbrook, Ryan C. Fortenberry

Faculty and Student Publications

Rovibrational spectral data for several tetra-atomic silicon carbide clusters (TASCCs) are computed in this work using a CCSD(T)-F12b/cc-pCVTZ-F12 quartic force field. Accurate theoretical spectroscopic data may facilitate the observation of TASCCs in the interstellar medium which may lead to a more complete understanding of how the smallest silicon carbide (SiC) solids are formed. Such processes are essential for understanding SiC dust grain formation. Due to SiC dust prevalence in the interstellar medium, this may also shed light on subsequent planetary formation. Rhomboidal Si2C2 is shown here to have a notably intense (247 km mol−1) anharmonic vibrational frequency at 988.1 cm−1 …

Efforts Towards The Asymmetric De Novo Synthesis Of Lanostanes And Euphanes, Htoo Tint Wai

Dartmouth College Ph.D Dissertations

Tetracyclic triterpenoids are ubiquitous in nature and biology, with members displaying a wide range of medically relevant properties and occupying rather distinct regions of chemical space. Members of this large class include well-known steroid hormones and sterols as well as structurally interesting subclasses such as lanostanes and euphanes, among others. Comprised of the tetracyclic skeleton with three stereodefined quaternary centers at ring-junction positions, lanostanes and euphanes present synthetic challenges that are different from those encountered in efforts targeting the structurally less complex steroid hormones. Lanostanes, in particular, stand as a historically important class of compounds as significant attention has been …

Probing Conformational Landscapes And Mechanisms Of Allosteric Communication In The Functional States Of The Abl Kinase Domain Using Multiscale Simulations And Network-Based Mutational Profiling Of Allosteric Residue Potentials, Keerthi Krishnan, Hao Tian, Peng Tao, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In the current study, multiscale simulation approaches and dynamic network methods are employed to examine the dynamic and energetic details of conformational landscapes and allosteric interactions in the ABL kinase domain that determine the kinase functions. Using a plethora of synergistic computational approaches, we elucidate how conformational transitions between the active and inactive ABL states can employ allosteric regulatory switches to modulate intramolecular communication networks between the ATP site, the substrate binding region, and the allosteric binding pocket. A perturbation-based network approach that implements mutational profiling of allosteric residue propensities and communications in the ABL states is proposed. Consistent with …

Pyridine Modifications Regulate The Electronics And Reactivity Of Fe–Pyridinophane Complexes, Magy A. Mekhail, Kristof Pota, Sugam Kharel, David M. Freire, Kayla N. Green

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

12-Membered pyridinophanes are the focus of many studies as biological mimics, chelators, and catalytic precursors. Therefore, the desire to tune the reactivity of pyridinophanes to better control the applications of derivative metal complexes has inspired many structure–activity relationship studies. However, the separation of structural versus electronic changes imparted by ligand modification has made these structure–activity relationship studies of transition metal catalysts challenging to define. In this work we show that 4-substitution of the pyridine ring in 12-membered tetra-aza pyridinophanes successfully provides a regulatory handle on the electronic properties of the metal center and, therefore, the catalytic C–C coupling activity of …

A Human Oral Fluid Assay For D- And L- Isomer Detection Of Amphetamine And Methamphetamine Using Liquid-Liquid Extraction, Brian Robbins, Rob E. Carpenter, Mary Long, Jacob Perry

Human Resource Development Faculty Publications and Presentations

Medical providers are increasingly confronted with clinical decision-making that involves (meth)amphetamines. And clinical laboratories need a sensitive, efficient assay for routine assessment of D- and L-isomers to determine the probable source of these potentially illicit analytes. This paper presents a validated method of D- and L-isomer detection in human oral fluid from an extract used for determination of a large oral fluid assay (63 analytes) on an older AB SCIEX 4000 instrument. Taken from the positive extract, D- and L-analytes were added. The method for extraction included addition of internal standard and a 2-step …

Wrack Lines Volume 22, Number 2, Fall-Winter 2022-2023, Nancy C. Balcom, Juliana Barrett, Judy Benson, Ben Crnic, Sto Len

Wrack Lines

With the theme, "Looking Ahead: People and Projects Shaping the Future," the Fall-Winter 2022-2023 leads with the first in what will be a series of articles about offshore wind development impacting Connecticut. That is followed by the inspiring story of how a dying forest was replanted for climate resilience. Next, a profile of longtime marine educator Tim Visel tells about his lasting impact on Connecticut schools and students. Lastly, the complex challenge of dealing with Contaminants of Emerging Concern is examined, with descriptions of how Sea Grant is involved and the particularly troublesome group of substances called PFAS.

Experimental Identification Of Aminomethanol (Nh2ch2oh)—The Key Intermediate In The Strecker Synthesis, Santosh K. Singh, Cheng Zhu, Jesse La Jeunesse, Ryan C. Fortenberry, Ralf I. Kaiser

Faculty and Student Publications

The Strecker Synthesis of (a)chiral α-amino acids from simple organic compounds, such as ammonia (NH3), aldehydes (RCHO), and hydrogen cyanide (HCN) has been recognized as a viable route to amino acids on primordial earth. However, preparation and isolation of the simplest hemiaminal intermediate – the aminomethanol (NH2CH2OH)– formed in the Strecker Synthesis to even the simplest amino acid glycine (H2NCH2COOH) has been elusive. Here, we report the identification of aminomethanol prepared in low-temperature methylamine (CH3NH2) – oxygen (O2) ices upon exposure to energetic electrons. Isomer-selective photoionization time-of-flight mass spectrometry (PI-ReTOF-MS) facilitated the gas phase detection of aminomethanol during the temperature …

Carbon Cycling And Critical Zone Dynamics In An Urbanized Karst Groundwater System, Amy Hourigan

Masters Theses & Specialist Projects

Increasing atmospheric CO₂ concentrations are correlated to rising global temperatures. Investigating the cumulative global carbon cycling processes is important to understand and quantify the global carbon cycle. By investigating basic geochemical parameters, EpCO₂, DIC, and δ¹³C_DIC, at four sites along Lost River Cave (LRC), in Bowling Green, Kentucky, concentrations, fluxes and sources of C dissolved in groundwater were determined. Urban karst groundwater systems, compared to more natural karst landscapes, typically exhibit widespread impervious, heat-absorbing surfaces, urban heat island effects, and increased anthropogenic groundwater inputs and localized CO₂ emissions. Carbonate hydrogeochemical …

Near-Infrared Dye-Glycogen Conjugates For Photodynamic And Photothermal Therapy, Farbod Shirinichi

Master's Theses

Near-Infrared (NIR) dyes are small organic molecules emerging as promising imaging agents and therapeutics for anticancer application. However, their small size inevitably resulted in several drawbacks, including low in vivo stability, inherent toxicity, and lack of targeting ability, which compromise their potential for clinical use. This project aims to address those issues by developing a novel “macromolecular” NIR dye. By covalently engineering the glycogen surface with indocyanine green (an FDA-approved NIR dye), we will create a series of glycogen-NIR dye conjugates with a size of 100-200 nm. In addition, this NIR dye is not stable in water for a long …

Senstive Enantiomeric Analysis Of N-Acyl Homoserine Lactones In Bacterial Matrices, Abiud E. Portillo

Chemistry & Biochemistry Dissertations - Archive

Communication between unicellular organism has long been studied with many facets yet to be discovered. A specific type of communication in gram-negative bacteria is quorum sensing (QS). N-acyl homoserine lactones (N-HLs) are the molecular signals in this process. At a critical concentration of N-HLs, all bacteria of the same population stop behaving like individuals and in a concerted manner induce a specific gene expression which ultimately benefits the entire population in major. This phenomenon has been coined with the term quorum sensing with the main signaling molecules dubbed L-N-acyl homoserine lactones (L-N-HL). Quorum sensing signaling pathways have their influence in …

A Continuously Renewed Copper Electrode For Constant-Potential Amperometry, Andrew T. Franklin

Chemistry & Biochemistry Theses - Archive

Pulsed amperometric detection (PAD) is a well-established technique used for the detection of electroactive compounds following Ion Chromatography (IC). Target analytes, such as carbohydrates and amino acids, typically have no suitable chromophores and are not detectable by suppressed conductivity following IC separation. While direct current (DC) amperometry is simpler, the formation of oxidation products quickly fouls the electrode surface; PAD removes these products extending electrode longevity for up to ~2 weeks of operation. To further extend electrode lifespans, a new strategy is introduced herein using DC amperometry on a sacrificial copper wire anode. The wire face continually dissolves under oxidative …

Turning Ligands On Their Side: Computational Investigation Into The Binding Of N2o And N2 In Transition Metal Complexes, Cole Donald

Electronic Theses and Dissertations

Common greenhouse gas nitrous oxide (N₂O) is a thermodynamically potent and environmentally benign oxidant, making it a desirable target for metal center activation. Unfortunately, N₂O is a poor ligand for transition metals due to its weak sigma-donating and pi-accepting properties; as a result, few transition metal complexes capable of interacting with N₂O have been found. As the primary source of all nitrogen in organisms, abundant gas dinitrogen (N₂) is a crucially important tiny molecule and an essential part of daily existence. However, due to its inertness, it has limited practical uses in …

Unassisted Photoelectrochemical Solar-To-Hydrogen On Cubi2o4 Photocathodes Using Glycerol As A Sacrificial Oxidant, Caroline Eddy

Chemistry & Biochemistry Undergraduate Honors Theses

The need to decarbonize society has driven the development of alternative energy technologies. Solar panels are capable of generating electricity at large scale and at competitive costs to fossil fuels, such as coal or natural gas. However, they are only capable of generating electricity when the sun is out. It is therefore necessary to understand how to store that energy for on-demand use. It is also desirable that the storage be portable, lightweight, and compatible with transportation infrastructure like fossil fuels are. A very desirable chemical fuel is H₂ which can be produced simply by water electrolysis. Production of …

Designing Single Molecule Diode, Tinsae Alem

Longwood Senior Theses

The field of single molecule electronics is based on using single molecule devices to control current in electronic circuits. One area of interest is to reproduce the functionality of traditional components such as wires, switches, and diodes using single molecule junctions. We used computational chemistry to design diodes to investigate what molecular features affect their performance including using different donors, acceptors, and connectors. A comparison of the diode's performance was made by comparing the rectification ratio. About 50 diodes were designed and tested, with rectification ratios ranging from 1.0 to 5.8. The results indicate that multiple factors have a significant …

Veratrum Parviflorum Poisoning: Identification Of Steroidal Alkaloids In Patient Blood And Breast Milk, Jared T. Seale, Xinzhu Pu, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

Introduction

The Veratrum genus is composed of plants containing a diverse set of steroidal alkaloids. Veratrum plant material has been utilized for centuries as herbal medicines, however the alkaloids have such a low therapeutic index that they are not used in modern medicine. Here we report an incident of inadvertent ingestion of V. parviflorum by hikers in Georgia that allowed detection, and in several instances identification of alkaloids from the plant, and correlated their presence within patient blood and breast milk specimens.

Case history

Eight patients, three male and five female, presented in the spring of 2020 and 2021 with …

Elucidation Of Active Site And Mechanism Of Metal Catalysts Supported In Nu-1000, Hafeera Shabbir

All Dissertations

Advances in extraction of shale oil and gas has increased the production of geographically stranded natural gas (primarily consisting of methane (C1) and ethane (C2)) that is burned on site. A potential utilization strategy for shale gas is to convert it into fuel range hydrocarbons by catalytic dehydrogenation followed by oligomerization by direct efficient catalysts. This work focuses on understanding metal cation catalysts supported on metal-organic framework (MOF) NU-1000 that will actively and selectively do this transformation under mild reaction conditions, while remaining stable to deactivation (via metal agglomeration or sintering). I built computational models validated by experimental methods to …

Perfect Polar Alignment Of Parallel Beloamphiphile Monolayers: Synthesis, Characterization, And Crystal Architectures Of Unsymmetrical Phenoxy-Substituted Acetophenone Azines, Harmeet Bhoday, Michael Lewis, Steven P. Kelley, Rainer Glaser

Chemistry Faculty Research & Creative Works

It remains a great challenge to achieve polar order in organic molecular crystals because anti-parallel alignment of side-by-side molecules is intrinsically preferred. We have addressed this problem with a rational design that focuses on the polar stacking of parallel beloamphiphile monolayers (PBAMs) with strong lateral quadrupole-quadrupole attractions. We employ arene-arene interactions as lateral synthons. The first successes were achieved with unsymmetrical donor (X), acceptor (Y) substituted acetophenone azines which form polar PBAMs with double T-contacts between the azines. Near-perfect alignment was achieved with the methoxy series of (MeO, Y)-azines with Y=Cl, Br, I. Here, we report on the synthesis, the …

Characterization Of An Amine-Thiol Cosolvent System : Ethylenediamine And Mercaptoethanol, Fernanda Giongo Fernandes

Legacy Theses & Dissertations (2009 - 2024)

Since its introduction, the amine-thiol cosolvent system has been successfully utilized for the deposition of various thin-film devices, but its mechanism of action is still uncertain. Herein, we have attempted to dissect some of the chemical characteristics of amine-thiol cosolvents, with a special interest taken towards a mixture of ethylenediamine (en) and mercaptoethanol (ME). Conductivity was measured for multiple amine-thiol combinations at different ratios to determine extent of ionization in solution, with en-ME having one of the highest solution conductivities. Exposing the solution to air for several days was found to decrease the conductivity of en-ME, indicating the formation of …

Organic Gunshot Residue : Detection, Identification, And Characterization For Forensic Purposes, Shelby R. Khandasammy

Legacy Theses & Dissertations (2009 - 2024)

The major focus of this thesis was to explore methods for the detection, identification, and characterization of organic gunshot residues (OGSRs) for forensic purposes using various spectroscopic techniques. There are four major projects detailed in this thesis. The first project details the development of a novel-two step method for the detection and identification of organic gunshot residues using fluorescence spectroscopy for detection and Raman spectroscopy as a confirmatory step. The second chapter builds upon the study conducted in the first chapter by applying the novel-two step method covered in the first chapter to OGSRs directly fired into cloth substrates. This …

Soil From Footwear Is A Newly Rediscovered Type Of Forensic Evidence Due To The Application Of Modern Analytical Techniques : A Review, Rhilynn Haley Ogilvie

Legacy Theses & Dissertations (2009 - 2024)

Traces of soil discovered on a footwear were historically among the first types of evidence used by crime scene investigators. This type of evidence has been rediscovered recently due to the application of powerful analytical techniques providing quantitative characteristics of the soil (bio)chemical composition. Advanced statistical analysis of the quantitative data further improves the probative value of the soil evidence. The article overview main aspects of the emerging techniques for the forensic soil analysis and the factors that challenge data interpretation including mixing, contamination, and composition complexity. Overcoming these issues is crucial for utilizing soil analysis for forensic purposes.

Turning Density Functional Theory Calculations Into Molecular Mechanics Simulations : Establishing The Fluctuating Density Model For Rna Nucleobases, Christopher A. Myers

Legacy Theses & Dissertations (2009 - 2024)

Molecular mechanics (MD) simulations and density functional theory (DFT) have been the backbone of computational chemistry for decades. Due to its accuracy and computational feasibility, DFT has become the go-to method for theoretically predicting interaction energies, polarizability, and other electronic properties of small molecules at the quantum mechanical level. Although less fundamental than DFT, molecular mechanics (MM) algorithms have been just as influential in the fields of biology and chemistry, owing their success to the ability to compute measurable, macroscopic quantities for systems with tens of thousands to hundreds of thousands of atoms at a time. Nevertheless, MD simulations would …

Molecular Dynamics Simulations Of The Adenylate Kinase Enzyme And Its Mutant States, Beata Izabella Dulko Smith

Chemistry & Biochemistry Dissertations - Archive

Adenylate kinase (AK) is a small, monomeric enzyme present across all domains of life. It is responsible for maintaining homeostasis of an intracellular adenylate pool and catalyzes a reversible transfer of the phosphoryl group from NTP (nucleoside triphosphate) to NMP producing two NDP molecules. While most known isoforms take ATP as phosphate donor, AK3 present in mitochondrial matrix employs GTP. Crystallographic investigations revealed that the basis for its selectivity for GTP over ATP came from an additional hydrogen bond between guanosine’s O6 and backbone nitrogen of threonine is responsible for recognition of GTP. Molecular dynamics (MD) simulations have demonstrated that …

Development Of Colorimetric And Fluorescent Antibiotic Biosensors And Synthesis Of Drug-Related Biomimetic Molecules For Calcium Carbonate Polymorph Control And Stabilization, Shan Hazoor

Chemistry & Biochemistry Dissertations - Archive

Polydiacetylene (PDA) polymers are conjugated macromolecules with desirable sensing properties. The presence of alternate double and triple bonds (en-yne subunits) generates electron delocalization in the PDA backbone, yielding a characteristic blue color, which changes to red upon environmental perturbations to the conjugated backbone structure. In chapter 1 PDA polymers containing a functional monomer 10,12- pentacosadiynoic acid-vancomycin conjugate (PCDA-Van) were prepared. Syntheses of different monomers containing different polar head groups were carried out to investigate a compatible monomer with PCDA-van stability. Gram-positive bacterial cell wall sequencing oligopeptides (OP) D-Ala-D-Ala and L-Lys-D-Ala-D-Ala were synthesized as a model for bacterial sensing. The PCDA-Van …

Probing Short-Range Structural Distortion Of Stereochemically Active Lone Pairs In Extended Solid-State Materials, Uyen Phuong Dang

Chemistry & Biochemistry Dissertations - Archive

The structural and electronic effects of the lone pairs play an important role in magnetic, photocatalytic, and semiconducting behaviors of materials. Investigating the role of stereochemically active ns2 lone pairs derived from p-block cations in solid-state materials is important to phenomena associated with polarizable bonding, e.g., ferroelectricity. The effect of lone pairs in ferroelectric polarization has been studied on the lead metaniobate in which the covalency between Pb and O stabilizes the in-plane polarization which leads to orthorhombic symmetry. PbTiO3 has been widely studied for ferroelectric polarization associated with the off-centering of Ti in TiO6 due to the characteristic 6s2 …

Intelligent Fluorescence Image Analysis Of Giant Unilamellar Vesicles Using Convolutional Neural Network, Il Hyung Lee, Sam Passaro, Selin Ozturk, Juan Ureña, Weitian Wang

Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works

Background: Fluorescence image analysis in biochemical science often involves the complex tasks of identifying samples for analysis and calculating the desired information from the intensity traces. Analyzing giant unilamellar vesicles (GUVs) is one of these tasks. Researchers need to identify many vesicles to statistically analyze the degree of molecular interaction or state of molecular organization on the membranes. This analysis is complicated, requiring a careful manual examination by researchers, so automating the analysis can significantly aid in improving its efficiency and reliability. Results: We developed a convolutional neural network (CNN) assisted intelligent analysis routine based on the whole 3D z-stack …

Rational Design Of Precisely Tailored Electrocatalysts For Efficient And Durable Electrocatalytic Devices, Mohmed Sanad Noufal

Open Access Theses & Dissertations

Due to their superior conversion efficiency, high power density, and green nature, sustainable energy technologies such as Fuel cells and Zinc-air batteries, once installed to produce green hydrogen fuel as well as energy storage devices, are expected to play an essential role in reducing the environmental effect of human transportation by replacing fossil fuels. However, the current bottleneck for the low-temperature polymer membrane fuel cells that dominate the fuel cell vehicle market is the sluggish kinetics of the oxygen reduction reaction (ORR) at the cathode. The slow ORR kinetics significantly reduce the efficiency of chemical-electrical energy conversion. Similarly, hydrogen production …

Rapid Detection Of Recurrent Non-Muscle Invasive Bladder Cancer In Urine Using Atr-Ftir Technology, Abdullah I. El-Falouji, Dalia M. Sabri, Naira M. Lofti, Doaa M. Medany, Samar A. Mohamed, Mai Alaa-Eldin, Amr Mounir Selim, Asmaa A. El Leithy, Haitham F. Kalil, Ahmed El-Tobgy, Ahmed Mohamed

Chemistry Faculty Publications

Non-muscle Invasive Bladder Cancer (NMIBC) accounts for 80% of all bladder cancers. Although it is mostly low-grade tumors, its high recurrence rate necessitates three-times-monthly follow-ups and cystoscopy examinations to detect and prevent its progression. A rapid liquid biopsy-based assay is needed to improve detection and reduce complications from invasive cystoscopy. Here, we present a rapid spectroscopic method to detect the recurrence of NMIBC in urine. Urine samples from previously-diagnosed NMIBC patients (n = 62) were collected during their follow-up visits before cystoscopy examination. Cystoscopy results were recorded (41 cancer-free and 21 recurrence) and attenuated total refraction Fourier transform infrared (ATR-FTIR) …

Photoproducts And Transformations Of Organic Pollutants In Aquatic Environments, Elizabeth Whisenhant

LSU New Orleans Theses and Dissertations

The degradation of petroleum-derived organic pollutants in aquatic systems occurs through lengthened exposure to UV and visible light. In this thesis, organic pollutants include crude oil, refined fuels, and plastic particles or films. The photo-oxidation of these pollutants are monitored over natural waters. To characterize the molecular signatures of photo-oxidized petroleum, bench-scale spills of refined fuels and crude oil were irradiated over Alaskan waters. A 4-component fluorescence PARAFAC model revealed a unique feature associated with photo-oxidized refined fuel unlike traditional “microbial”- or “terrestrial-like” components. In contrast, crude oil photolytically decomposed into humic-like components and oxidized aliphatics. FT-ICR MS data corroborated …

Synthesis And Electrochemical Characterization Of Alkali Metal Borides As Redox Active Anion Frameworks, Michael R. Shabetai

LSU New Orleans Theses and Dissertations

Redox activity in intercalation cathodes is commonly attributed to changes in oxidation states of transition metal ions. Recently, a growing body of evidence revealed that the redox activity of oxygen contributes to the capacity of some known cathodes. We focused on designing an oxygen free intercalation cathode with redox-active anions. In order to overcome the entropic driving force for the decomposition of a charged redox active anion cathode, we looked for chemistries with solid (no gases) possible decomposition products. Additionally, the involvement of anions in a network of covalent bonds with shared electrons was considered as a possible way for …