Chemicals and Drugs Commons^™

Modeling Sex-Specific Changes In Myocardial Fibrosis, Grace Martin

Chemical Engineering Undergraduate Honors Theses

Heart disease the leading cause of death for both men and women in the United States. Cardiac fibrosis, or accumulation of extracellular matrix proteins in the heart, can occur after a heart attack and increase the risk for further complications. Current treatments for heart disease do not include extracellular matrix regulators, partly due to the complicated signaling network responsible for the production of these proteins. By using a computational model of the signaling network in cardia fibroblasts, the relationship between particular molecules and downstream extracellular matrix production can be examined.

Biological sex is an important factor for cardiac health and …

The Purification And Thermal Stability Of The Peroxidase Enzyme In Cucurbita Moschata, Garen Hamner

Senior Honors Theses

Peroxidases are enzymes that catalyze the reduction of hydrogen peroxide to water while oxidizing organic substrates and are valuable in spheres like industrial and medical applications and histochemistry. Limitations still exist in the use of the well-studied horseradish peroxidase for certain activities due to limitations like poor thermal stability, thus the search for novel peroxidases that can overcome these limitations is an active area of research. Butternut squash peroxidase (Cucurbita moschata) (BSP) shows promise due to significant activity being found in the skin and apparent enhanced thermal stability, but an efficient purification scheme for it is lacking, as well as …

Why Your Clothes Could Be Killing You: The Detection Of Bpa In Clothing Using Fluorescence Spectrophotometry, Bella Bevel

Scholars Day Conference

Bisphenol-A, better known as BPA, is a carcinogenic compound found in many plastic-containing products due to its ability to add rigidity and strength to the plastic. However, BPA has been found in a wide variety of products not traditionally thought of as “plastic” including feminine hygiene products, printer receipts, and even clothing. Clothing containing a polyester/spandex blend, common in athletic wear, contains BPA, whereas traditional cotton clothing does not. Using flourospectroscopy, the presence of BPA in these types of clothing was confirmed, as well as measured over time. Strips of clothing containing polyester and spandex blends were submerged in a …

The Mental Health And Developmental Effects Of Bisphenol-A, Maryann Rettig

Scholars Day Conference

My directed study focuses on the mental health and developmental effects of bisphenol-A (BPA) on individuals in close contact with the chemical product. BPA is an organic chemical produced in large quantities that is used in the production of many polycarbonate plastics, feminine hygiene products, and epoxy resins that coat some metal food cans. Because of it being everywhere, BPA often leaches dermally and orally into the human body. The physical effects of BPA have been known and observed for years. However, its mental health effects specifically are not as commonly known. Therefore, in my directed study I would be …

Killing Cancer: Manipulating Hydrophobic Vanadium Complexes To Improve Anti-Cancer Activity, Levi Ausherman, Debbie C. Crans, Peter A. Lay, Maggi Braasch-Turi

SACAD: John Heinrichs Scholarly and Creative Activity Days

Hydrophobic vanadium complexes have recently shown improved anti-cancer activities compared to cisplatin. The hydrophobicity and anti-proliferative activity of [VO(Hshed)(dtb)] ([Hshed= N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethanediamine and dtb= 3,5-di(tert-butyl)catechol)]) have inspired the development of a library of hydrophobic vanadium complexes. Increasing the steric bulk of the catechol ligand has been shown to have a direct impact on hydrophobicity and anti-proliferative activities. Currently at Fort Hays State University, the Braasch-Turi group is synthesizing VO(HSHED)(dtb) to build up material to support the chemical analysis and biological assay performed by our collaborators at Colorado State University and the University of Sydney, Australia, respectively. In the future, we plan …

Accurate Characterization Of Binding Kinetics And Allosteric Mechanisms For The Hsp90 Chaperone Inhibitors Using Ai-Augmented Integrative Biophysical Studies, Chao Xu, Xianglei Zhang, Lianghao Zhao, Gennady M. Verkhivker, Fang Bai

Mathematics, Physics, and Computer Science Faculty Articles and Research

The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs in vivo, leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking. In this study, quantitative structure–kinetics relationship (QSKR) models were developed using 132 inhibitors targeting the ATP binding domain of heat shock protein 90α (HSP90α) to predict the dissociation rate …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Mechanistic Investigation Of C—C Bond Activation Of Phosphaalkynes With Pt(0) Complexes, Roberto M. Escobar, Abdurrahman C. Ateşin, Christian Müller, William D. Jones, Tülay Ateşin

Research Symposium

Carbon–carbon (C–C) bond activation has gained increased attention as a direct method for the synthesis of pharmaceuticals. Due to the thermodynamic stability and kinetic inaccessibility of the C–C bonds, however, activation of C–C bonds by homogeneous transition-metal catalysts under mild homogeneous conditions is still a challenge. Most of the systems in which the activation occurs either have aromatization or relief of ring strain as the primary driving force. The activation of unstrained C–C bonds of phosphaalkynes does not have this advantage. This study employs Density Functional Theory (DFT) calculations to elucidate Pt(0)-mediated C–CP bond activation mechanisms in phosphaalkynes. Investigating the …

Β-Sheets Mediate The Conformational Change And Allosteric Signal Transmission Between The Aslov2 Termini, Sian Xiao, Mayar Terek Ibrahim, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

Avena sativa phototropin 1 light-oxygen-voltage 2 domain (AsLOV2) is a model protein of Per-Arnt-Sim (PAS) superfamily, characterized by conformational changes in response to external environmental stimuli. This conformational change begins with the unfolding of the N-terminal A'α helix in the dark state followed by the unfolding of the C-terminal Jα helix. The light state is characterized by the unfolded termini and the subsequent modifications in hydrogen bond patterns. In this photoreceptor, β-sheets are identified as crucial components for mediating allosteric signal transmission between the two termini. Through combined experimental and computational investigations, the Hβ …

Purification And Isolation Of Α-Chloro-Β-Lactone Precursor Molecules, Matthew Ellis

ASPIRE 2024

This research investigates the synthesis of α-chloro-β-lactone molecules, focusing on the production, isolation, and purification of two precursor compounds from chloroacetic acid and substituted benzaldehydes. While multiple methods were explored, including EDC, DIC, and DCC catalysis, DCC proved to be most effective in producing higher yields. However, challenges in purification arose due to the formation of byproducts, particularly with DCC, prompting further investigation for efficient extraction and purification techniques. DCC, however, shows a promising route for α-chloro-β-lactone synthesis, despite purification complexities.

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

Cumulative Distribution Function And Spatially Resolved Surface-Enhanced Raman Spectroscopy For The Quantitative Analysis Of Emtricitabine, Jana Hrncirova, Marguerite R. Butler, Sucharita Dutta, Meredith R. Clark, John B. Cooper

Chemistry & Biochemistry Faculty Publications

Surface-enhanced Raman spectroscopy (SERS) has exceptional analytical sensitivity and selectivity. However, SERS irreproducibility presents an obstacle when using it for precise quantitative measurements. In this study, colloidal nanoparticles evaporated to dryness are used as a SERS active surface for the detection of the HIV drug emtricitabine (FTC; trade name Emtriva). Despite the irreproducibility of the SERS resulting from the stochastic process of evaporation, using a SERS scanning instrument, the SERS enhancement factors of spatially resolved spectra have a well-defined distribution of signals for a given analyte concentration. This distribution follows a power law function ranging from weak (very abundant signals) …

Combined Risk Based Inspection And Fault Tree Analysis For Repetitive 3-Phase Line Piping Leakage At West Java Offshore Topside Facility, Dona Yuliati, Akhmad Herman Yuwono, Datu Rizal Asral, Donanta Dhaneswara

Journal of Materials Exploration and Findings

Hydrocarbon releases might result in serious consequences in various aspects. In addition to the contribution to environmental pollution, repetitive leakages need high repair costs. This study aim is to minimize potential repetitive leakage for other typical 3-phase piping systems. We conducted the risk assessment by adopting Risk Based Inspection (RBI) API 581 to identify risk level, calculating piping lifetime, recommended inspection plan and mitigations. The most relevant root causes can be obtained through quantitative Fault Tree Analysis (FTA). Observation and investigation was taken from eight 3-phase piping systems that experienced repetitive leakages. It has been found that the risk level …

Nitrogen Gas Quenching Pressure Effect On Bs S155 Alloy Steel In Vacuum Furnace, Agus Mulyadi Hasanudin, Eddy Sumarno Siradj

Journal of Materials Exploration and Findings

The production of metal and alloy products requires the use of heat treatment, when during the heat treatment process, quenching is a crucial step. The quenching medium can be anything from water, a salt bath, oil, air and gas. In a vacuum furnace, pressurized gas, most frequently nitrogen (N₂) gas, serves as one of the quenching mediums. One of the drawbacks of the quenching process is the distortion and dimensional change of the parts. This paper aims to investigate the influence of nitrogen gas quenching pressure on the distortion and dimensional change of aerospace actuator gear planet parts …

Variables Affecting The Extraction Of Antioxidants In Cold And Hot Brew Coffee: A Review, Brian Yust, Frank Wilkinson, Niny Rao

College of Life Sciences Faculty Papers

Coffee beans are a readily available, abundant source of antioxidants used worldwide. With the increasing interest in and consumption of coffee beverages globally, research into the production, preparation, and chemical profile of coffee has also increased in recent years. A wide range of variables such as roasting temperature, coffee grind size, brewing temperature, and brewing duration can have a significant impact on the extractable antioxidant content of coffee products. While there is no single standard method for measuring all of the antioxidants found in coffee, multiple methods which introduce the coffee product to a target molecule or reagent can be …

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Determining The Ideal Concentrations Of Ethanol And Propylene Glycol In Ethosomes For Transdermal Delivery Of Vitamin D3, Rebecca Conner

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Vitamin D₃ is an important chemical in the human body, however, many Americans have low levels of this vitamin. There are plenty of oral supplementations for Vitamin D₃ deficiency, but those of older age and busy schedules may struggle to meet the minimum requirement. A recently developed ethosomal transmembrane delivery system (Touitou, 2000), similar to liposomes but also containing ethanol, allows users to apply a gel dermally and have the desired drug or active ingredient reach the bloodstream faster. However, there is considerable variation in the concentration of ethanol and permeation enhancers used. Using an affordable method to …

Corrosion Of Implant Materials In The Human Body, Maedeh Barzmehri

Corrosion Research

This paper extensively examines the complex problem of implant corrosion occurring within the human body. The corrosion of implants gives rise to substantial challenges, encompassing compromised implant durability, patient safety concerns, and potential adverse impacts on the long-term functionality of the medical device. The study's primary objectives include offering a concise overview of the various corrosion mechanisms that impact a range of implant materials and outlining health complications linked to the byproducts of implant corrosion. Furthermore, it delves into a cost analysis specific to hip or knee revision arthroplasty, which has become a prevalent scenario in implant failure cases on …

Computational And Experimental Investigation Of Elemental Sulfur And Polysulfide, Jyoti Sharma

Dissertations

Petroleum processing results in the generation of significant quantities of elemental sulfur (S₈), leading to a surplus of sulfur worldwide. Despite its abundance and low cost, the use of sulfur in value-added organic compound synthesis is limited due to its unpredictable and misunderstood reactivity. This dissertation aims to address this issue by tackling it from two angles. Firstly, by utilizing Density Functional Theory (DFT) calculations, the reactivity of sulfur in the presence of nucleophiles is studied. This facilitates the identification of organic polysulfide intermediates that can be generated under different conditions, as well as the corresponding reactivity for …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Studying The Stability Of Collagen/Heparin Coatings To Be Used In Cell Therapy Applications, Gavin Mussino

Biological Sciences Undergraduate Honors Theses

This honors thesis aims to investigate the reusability and performance of cell coatings for cell therapy applications. Cell therapy, which involves the use of human cells to repair or replace damaged tissues, holds immense potential for medical advancements. However, ensuring the survival and functionality of transplanted cells remains a significant challenge. We focused on studying the effectiveness of coatings applied to cells for improved cell growth and viability. The research project involved the preparation of the coatings using a layer-by-layer method and the subsequent seeding of cells. The coated cells were then subjected to a series of experiments to assess …

Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …

Photodynamic Therapy Agents: The Power Of Mjöllnir To Eradicate Cancer, Sidney M. Hopper

Honors College Theses

After its discovery back in the 1900s, photosensitizers became a critical study for potential treatments and cures for medical issues, including cancer. It was discovered that porphyrins appeared to target and accumulate in proliferating cells, and to reach the cells, a certain wavelength of light with maximum absorbance associated with the porphyrin was necessary to achieve cell death. Photodynamic therapy involves making use of porphyrins or metalloporphyrins as activators when exposed to such light. When activated, these compounds generate reactive oxygen species (ROS), such as HO- or O2-, which can react with nucleic acids found in DNA and RNA. In …

Utilizing Ultra-Performance Chromatography High-Resolution Mass Spectrometry To Investigate Fatty Acid Mediated Antibiotic Tolerance, Brittni Woodall

Doctoral Dissertations

The lipid membrane is the first component necessary to sustain life. To maintain homeostasis, segregate cellular machinery, provide protection from the environment, and reproduce, an organism must establish a boundary in which the processes can occur. Throughout the last two decades, research has propelled our knowledge of lipid membranes much beyond original hypotheses. Once thought of to be static and uniform, the understanding of the lipid membrane has evolved to encompass a structure that is responsive, unique, and intricately constructed by the organism itself. By chance or by choice, organisms adapt the lipid membrane according to the environment for which …

Design And Synthesis Of Peripherally Selective Endocannabinoid Enzyme Inhibitors For Ocular Indications, Kezia Reji Thomas

Senior Honors Theses

Peripherally selective compounds have been found to stimulate endocannabinoid receptor activity, which has been observed to have positive physiological effects such as ocular wound healing and inflammation control. The activation of the cannabinoid 1 receptor via binding of the endogenous ligands, anandamide and 2-arachidonoylglycerol, has been indicated to elicit these effects. Both ligands are controlled by two hydrolase enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which can be targeted for therapeutic inhibition. Sulfonamide derivatives of JZL195 containing carbamate functionalities in the southern region of the inhibitor compounds were produced using novel carbamate exchange reactions. Polar functionalities were …

Coarse-Grained Molecular Simulations And Ensemble-Based Mutational Profiling Of Protein Stability In The Different Functional Forms Of The Sars-Cov-2 Spike Trimers: Balancing Stability And Adaptability In Ba.1, Ba.2 And Ba.2.75 Variants, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, and allosteric modulation. In this study, we embarked on a systematic comparative analysis of the conformational dynamics, electrostatics, protein stability, and allostery in the different functional states of spike trimers for BA.1, BA.2, and BA.2.75 variants. Using efficient and accurate coarse-grained simulations and atomistic reconstruction of the ensembles, we examined the conformational dynamics of the spike trimers that agree with the recent functional studies, suggesting that BA.2.75 trimers are the most stable …

Synthesis And Characterization Of Some Disubstituted Cyclopentadienyl Rhenium Complexes As Potential Candidates In Semiconductive Materials, Chloe Vernon

Senior Honors Theses

Since 2000, when the Nobel Prize in Chemistry as awarded for conductive polymer research few studies have been performed concerning the conductive capabilities of discrete organometallic compounds. For this project, organometallic compounds were formed specifically with a transition metal included in the structure. Through oxidation and reduction reactions, the variation in the electrical conductivity could allow for an analysis of whether this unique structure would allow for tunability. The goal of this research was to begin with aromatic substituted fulvenes and perform various multistep synthesis processes, utilizing thallium salt intermediates, to produce several disubstituted cyclopentadienyl rhenium complexes. In this project, …

Potential Of Biduri Fiber (Calotropis Gigantea) As Material For Oil Spill Absorbent, Anne Sukmawati, Wulan Septiani

Journal of Materials Exploration and Findings

Biduri fiber (Calotropis gigantea) is a natural hollow fiber with hydrophobic and oleophilic properties potentially used as oil spilled sorbent from seawater. This study aims to determine the absorption capacity and efficiency of the Biduri fiber and membrane to fuel oil. Measurement of oil absorption to seawater was carried out at various fiber weights (0.5-1.5 g), fiber composition (50-95%), contact time (10-90 minutes), temperature (30 and 50°C), and compared with commercial products. The results showed that the fiber weight variation of 0.5-1.5 g has an average absorption efficiency of 96.67%, and the highest absorption was obtained in a weight of …

Cultivating Health, Not Wealth In The United States' Healthcare System: Comprehensive Revisions For The Orphan Drug Act Of 1983, Kayla Smith

Regis University Student Publications (comprehensive collection)

This thesis explores the way in which the Orphan Drug Act of 1983, originally instituted in response to a lack of treatments for rare diseases in the United States of America, has failed to achieve its initial objectives in the 40 years since its implementation. In evaluating various successful examples of government subsidization programs designed to intervene in private industry, this thesis composes the criterion required for funding-based legislation which maximize market outcomes while minimizing tax-payer burden. An analysis of the synthetic organic chemistry industry – and a case study into the production of a particular orphan treatment for a …