Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Cabotegravir Maintains Protective Efficacy In The Setting Of Bacterial Stis: A Secondary Analysis Of Hptn 083, Meredith E. Clement, Brett Hanscom, Daniel Haines, Jose A. Bazan, Nuntisa Chotirosniramit, Ryan Kofron, Sharon Mannheimer, Kenneth H. Mayer, Mayara Secco Torres Silva, Lydia Soto-Torres, Alex R. Rinehart, James F. Rooney, A Jennings, K Gomez-Feliciano, Marybeth Mccauley, Beatriz Grinsztejn, Raphael J. Landovitz, Et Al.

School of Medicine Faculty Publications

BACKGROUND: Sexually transmitted infections (STIs) have been shown to facilitate HIV transmission and acquisition. HPTN 083, a global clinical trial, demonstrated superiority of long-acting cabotegravir (CAB-LA) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention among transgender women and cisgender men who have sex with men. This analysis assessed whether CAB-LA maintained protective efficacy when bacterial STIs (syphilis, rectal/urethral gonorrhea and chlamydia) were present. METHODS: STI events per 100 person-years (PY) were calculated, including by subgroups (age, race/ethnicity, gender, education, treatment arm, drug use, alcohol use, region/country, condom usage, partner number, marital status, baseline STI). Association between baseline factors …

Effects Of Sex And Estrous Cycle On Extended-Access Oxycodone Self-Administration And Cue-Induced Drug Seeking Behavior, Bhumiben P Patel, Jessica A Loweth

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Increasing evidence indicates that sex is a factor that impacts the abuse liability and relapse vulnerability of prescription opioids like oxycodone. However, while women are more likely than men to be prescribed and to use these drugs, the impact of sex and ovarian hormones on prescription opioid use and relapse vulnerability remains unclear. Accurately assessing these measures is complicated by the fact that chronic opioid exposure can lower ovarian hormone levels and cause cycle irregularities.

METHODS: Adult male and female Sprague-Dawley rats self-administered oxycodone (0.1 mg/kg/infusion) under extended-access conditions (6 h/day, 10 days) followed by forced abstinence. Separate groups …

Hyperbaric Oxygen Therapy In The Atls/Acls Resuscitative Management Of Acutely Ill Or Severely Injured Patients With Severe Anemia: A Review, Keith W. Van Meter

School of Medicine Faculty Publications

For short periods, even without the presence of red blood cells, hyperbaric oxygen can safely allow plasma to meet the oxygen delivery requirements of a human at rest. By this means, hyperbaric oxygen, in special instances, may be used as a bridge to lessen blood transfusion requirements. Hyperbaric oxygen, applied intermittently, can readily avert oxygen toxicity while meeting the body's oxygen requirements. In acute injury or illness, accumulated oxygen debt is shadowed by adenosine triphosphate debt. Hyperbaric oxygen efficiently provides superior diffusion distances of oxygen in tissue compared to those provided by breathing normobaric oxygen. Intermittent application of hyperbaric oxygen …

Novel 3,6-Disubstituted Pyridazine Derivatives Targeting Jnk1 Pathway: Scaffold Hopping And Hybridization-Based Design, Synthesis, Molecular Modeling, In Vitro And In Vivo Anticancer Evaluation., Mai M. Shaalan, Essam Eldin A. Osman, Yasmeen M. Attia, Olfat A. Hammam, Riham F. George, Bassem H. Naguib

Pharmacy

A series of novel 3,6-disubstituted pyridazine derivatives was designed, synthesized, and biologically evaluated as preclinical anticancer candidates. Compound 9e exhibited the highest growth inhibition against most of the NCI-60 cancer cell lines. The in vivo anticancer activity of 9e was subsequently investigated at two dose levels using the Ehrlich ascites carcinoma solid tumor animal model where a reduction in the mean tumor volume allied with necrosis induction was reported, without any signs of toxicity in the treated groups. Interestingly, compound 9e was capable of downregulating c-jun N-terminal kinase-1 (JNK1) gene expression and curbing the protein levels of its phosphorylated form, …

Allopurinol: Clinical Considerations In The Development And Treatment Of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, And Other Associated Drug Reactions, Kathryn M. Dillman, Alison M. Hawkins, Amanda R. Ragland, Grace C. Wester, Driskell R. Greene, Giustino Varrassi, Peyton Moore, Raju Behara, Shahab Ahmadzadeh, Harish Siddaiah, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Allopurinol lowers urate production through the inhibition of xanthine oxidase. It is oxidatively hydroxylated to oxypurinol and is the most prescribed medication for gout treatment. Although it has a beneficial effect in the treatment of this common disease, like many medications, it is also known for having numerous adverse effects. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), diseases that exist on a spectrum, are two of the most dangerous adverse effects associated with allopurinol use. These immune-mediated disease processes involve almost every organ system. They are essential to recognize as early as possible, as they could potentially be deadly, …

Effects Of Dexmedetomidine As An Adjunct To General Anesthesia On Postoperative Pain And Opioid Consumption In Major Abdominal Surgery, Ahmad H. Elrefahy

Rowan-Virtua Research Day

This review examines the impact of dexmedetomidine, an alpha-2 adrenergic receptor agonist, on postoperative pain and opioid consumption in major abdominal surgery. Dexmedetomidine, known for its sedative, analgesic, and opioid-sparing properties, is increasingly used as an adjunct to anesthesia. Analyzing existing literature, the review found that dexmedetomidine administration alongside general anesthesia significantly improves postoperative pain management and reduces opioid consumption. Patients receiving dexmedetomidine reported decreased postoperative pain ratings and required fewer opioids during the recovery phase. Additionally, intraoperative dexmedetomidine use correlated with reduced postoperative pain severity and increased patient satisfaction compared to control groups. However, potential side effects such as …

Odevixibat: A Novel Bile Salt Inhibitor Treatment For Pruritus In Progressive Familial Intrahepatic Cholestasis, Farrah E. Flattmann, Farhan S. Mohiuddin, Anjuni Singh, Anamika Tandon, Stewart J. Lockett, Jon D. Hirsch, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Chronic pruritus is defined as an itch lasting greater than six weeks. It can manifest from a wide variety of etiologies, as many different substances can act as pruritogens, such as steroids, histamine, progesterone, endogenous opioids, and serotonin. In the setting of cholestatic liver disease, increased bile acids play a major role in chronic pruritus. The itching in cholestatic liver disease is worsened in intensity at night and localized frequently to the palms, soles, knees, and other pressure sites. It can be hard to manage, affecting the quality of sleep and causing irritability, poor attention, and, in some cases, depression. …

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 …

Etiology Of Drug-Induced Edema: A Review Of Dihydropyridine, Thiazolidinedione, And Other Medications Causing Edema, Evan S. Sinnathamby, Bretton T. Urban, Robert A. Clark, Logan T. Roberts, Audrey J. De Witt, Danielle M. Wenger, Aya Mouhaffel, Olga Willett, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi

School of Medicine Faculty Publications

Edema is an accumulation of fluid in the body's tissues that affects millions of Americans yearly. It can affect multiple body parts, for example, the brain or eyes, but often occurs in the periphery, including the feet and legs. Medications, such as dihydropyridine and thiazolidinediones (TZDs), can be the etiology of edema. Edema can develop in association with problems in the vasculature or lymphatic flow. In recent years, a better understanding of these drug-induced mechanisms has been appreciated. Specifically, dihydropyridines can increase hydrostatic pressure and cause selective pre-capillary vessel vasodilation. TZDs can cause edema through increased vascular permeability and increased …

Doxazosin Immediate Release As A Novel Treatment For Nightmares In Posttraumatic Stress Disorder., Danyaal Khan, Christie Richardson, Martin Forsberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Nightmares and flashbacks are common debilitating symptoms of posttraumatic stress disorder (PTSD) that can disrupt daily functioning. Prazosin, an alpha-1 adrenergic antagonist, has been commonly used off-label for the treatment of these intrusion symptoms, although its short half-life makes it so that often multiple doses are needed. Doxazosin, another alpha-1 antagonist, is starting to be investigated in the treatment of PTSD-related nightmares due to its lesser side effect profile and longer half-life. In our case series, we present three cases of patients with PTSD-related nightmares who were successfully treated with doxazosin following a relapse of symptoms after discontinuation of prazosin …

Design, Synthesis, And Anti-Mcf-7 Activity Of New Thieno[2,3-D]Pyrimidinone Derivatives As Potential Breast Cancer Treatment, Bassem H. Naguib, Amgad Albohy, Mostafa A. Abdelaziz, Hanan H. Kadry

Pharmacy

Breast cancer is one of the top leading causes of death and the most aggressive type of cancer in women. Resistance to chemotherapy is one of the challenges associated with the development of strategies for the treatment of breast cancer. One way to overcome this issue is to design new agents that target breast cancer cell lines such as MCF-7. In this study, a new series of S-alkylated thieno[2,3-d]pyrimidin-4-ones bearing carboxamide or ketonic scaffolds was synthesized and screened for their cytotoxicity against MCF-7 breast cell lines. Among synthesized candidates, 6d exhibited more potent cytotoxicity against MCF-7 cell lines with IC50 …

Continuous Flow As A Process Intensification Tool For The Preparation Of Pharmaceutically Relevant N-Heterocycles, John W. Tomlin Jr

Theses and Dissertations

Continuous flow as a process intensification tool for the preparation of pharmaceutically relevant N-heterocycles

John W. Tomlin

Thesis Defense: 17 January 2024

Committee: B. Frank Gupton, Ph.D. (Advisor), Suzanne M. Ruder, Ph.D. (Chair), Heather R. Lucas, Ph.D., James K. Ferri, Ph.D., Matthew C.T. Hartman, Ph.D.

A dissertation submitted in partial fulfillment of the requirements of Doctor of Philosophy at Virginia Commonwealth University

© 2024 John W. Tomlin Jr All Rights Reserved

Abstract

Essential medicines must be produced in large quantities to accommodate large global demand. The preparation of these active pharmaceutical ingredients (API) must therefore strive to be both cost-effective …

Advancing Small Molecule Therapies For Myotonic Dystrophy Type 1, Sawyer M. Hicks

Electronic Theses & Dissertations (2024 - present)

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expression of expanded CUG (CUG^exp) repeat RNA from the myotonic dystrophy protein kinase (DMPK) gene. This CUG^exp repeat RNA’s gain-of-function mechanism leads to the sequestration of muscleblind-like (MBNL) proteins, resulting in widespread alternative splicing dysregulation across tissues. Despite significant research, there are currently no approved therapeutics targeting the underlying causes of DM1. This dissertation explores the development and optimization of a novel class of small molecules, Modified Polycyclic Compounds (MPCs), designed to address splicing dysregulation in DM1. MPCs were designed from previously published …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

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 …

Folate Deficiency Modifies The Risk Of Cin3+ Associated With Dna Methylation Levels: A Nested Case–Control Study From The Ascus-Col Trial, María C. Agudelo, Samuel Agudelo, Attila Lorincz, Arianis Tatiana Ramírez, Kelly Melisa Castañeda, Isabel Garcés-Palacio, Arnold H. Zea, Chandrika Piyathilake, Gloria Ines Sanchez

School of Medicine Faculty Publications

Purpose: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case–control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations. Methods: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 …

Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle

School of Graduate Studies Faculty Publications

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …

In Vitro Evaluation Of Phthalimide Derivatives Against Cancer Cell Lines, Crystel A. Sierra Rivera, Muhammad Kashif, Lenci Karina Vazquez Jimenez, Gildardo Rivera Sanchez, Alfredo Juarez Saldivar, Alma Delia Paz Gonzalez, Alejandro Zugasti Cruz

Research Symposium

Los cánceres de pulmón, próstata e hígado se encuentran entre los más prevalentes en los hombres. El cáncer de mama, de cuello uterino y de tiroides se encuentran entre los más prevalentes en mujeres (OMS, 2019). El tratamiento del cáncer generalmente incluye quimioterapia y radioterapia; sin embargo, los medicamentos contra el cáncer disponibles tienen una selectividad baja y causan efectos adversos graves, como nefrotoxicidad, neurotoxicidad y mielosupresión (Matsuo et al., 2010). Por tanto, el diseño y desarrollo de compuestos como nuevos agentes anticancerígenos frente a los tipos de cáncer de mayor incidencia son de vital importancia en el campo de …

Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero

School of Medicine Faculty Publications

Purpose: Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by Plod2-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)β1. Methods: Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b …

Growing Use Of Xylazine As An Adulterant In Opioids And Its Effects, Oluwapelumi Oluwo

Rowan-Virtua Research Day

Xylazine, according to the National Institutes of Health (NIH), is a non-opioid tranquilizer used in veterinary medicine. Although this drug has not been approved for human use, it can be linked to an increase in opioid overdose deaths due to its role as an adulterant in drugs like fentanyl.

Xylazine was detected in drugs involved in 41% of all opioid-involved unintentional deaths and in 44% of all unintentional overdose deaths with fentanyl involved in the year of 2021 in Philadelphia.

Case Series: Continued Remission Of Ptsd Symptoms After Discontinuation Of Prazosin, Christie Richardson, Jonathan Yuh, Jing Su, Martin Forsberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Post-traumatic stress disorder is a debilitating chronic illness that affects 6 out of 100 adults after a severe trauma. The alpha-adrenergic antagonist prazosin, which is prescribed off-label for flashbacks and nightmares due to trauma, is often continued indefinitely due to reports of symptoms returning upon discontinuation. There is no standard guidance for a trial of discontinuation of prazosin due to intolerance or side effects. In this case series, three patients are started on prazosin leading to remission of trauma-related symptoms, and symptoms continue to remit after treatment for an average of about 2 years followed by discontinuation of the medication. …

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, …

Triazole Compounds – Potentials In The Treatment Of Cystic Fibrosis, Maggie Taylor

Undergraduate Research Conference

Cystic Fibrosis (CF) is a genetic disease that affects the respiratory and digestive system and is most common among Caucasians of Northern European origin. CF is caused by mutations in a membrane protein CFTR (Cystic Fibrosis Transmembrane-conductance Regulator). This mutation impairs the membrane protein’s chloride ion channel function. One of the most common CFTR mutations is the DF508 mutation that affects over 70% of CF cases. Our research has shown that the DF508-CFTR mutation can be partially reversed by physical and chemical means [Heda & Marino, BBRC, 271:659-664, 2000]. In cell lines expressing DF508-CFTR, synthetic anion carriers have shown to …

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

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 …

Prazosin Dosed 3 Times A Day To Treat Flashbacks Related To Ptsd: A Case Report, Christie Richardson, Alexander Swartz, Martin Forsberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Prazosin is an alpha-1 adrenergic receptor antagonist widely known by mental health providers for its off-label use for nightmares in patients with PTSD. Prazosin is lipophilic and crosses the blood-brain barrier to antagonize alpha-1 receptors in the central nervous system, potentially reducing autonomic arousal caused by PTSD. There have been numerous case reports describing the reduction of nightmares and daytime flashbacks due to PTSD with prazosin dosed at night and during the day, respectively. This case report illustrates the resolution of flashbacks related to chronic PTSD with prazosin dosed 3 times a day. As the half-life of prazosin is only …

Treating Trichotillomania With Olanzapine, Christopher Lee

Rowan-Virtua Research Day

Trichotillomania (TTM) is characterized by repetitive pulling of one’s hair leading to hair loss and problems in social, occupational, or other important areas of functioning. Often individuals with TTM try to decrease or stop hair pulling, however are often unsuccessful without treatment. Community prevalence studies suggest that TTM is a common disorder with point prevalence estimate of 0.5% to 2.0% and with significant psychological comorbidity. Of note, people with TTM are often embarrassed about their condition, so epidemiology data may be underestimated compared to the true prevalence of this condition. The female to male ratio for this condition is 4:1. …

Antibacterial Activity, Structure-Activity Relationships, And Scale-Up Reaction Of 1,3,4-Oxadiazoles, Olivia Marie Smith

Undergraduate Honors Thesis Projects

Oxadiazoles are compounds in the field of organic chemistry that have been gathering interest in the medicinal chemistry and microbiology communities for their biological properties, which range from anti-inflammatory agents, to chemotherapy drugs, to antibiotics. The synthesis of oxadiazoles can be difficult due to the expensive and complex nature of the techniques used as well as the volatile reagents and elevated temperatures that are often required in organic synthesis. The Grote lab has recently developed a new method for the synthesis of 1,3,4-oxadiazoles under mild conditions. The goals of this thesis were thus twofold: to develop a viable scale-up procedure …

Synthesis Of Selenotryptophan For Protein Elucidation, James P. Reiselman

[Archive] Belmont University Research Symposium (BURS)

Through complex intermolecular and intramolecular forces, proteins conformationally change to form complex 3-d geometry that carries out biochemical processes and mapping their structures is becoming a field of interest in the biological community. Techniques for modeling protein’s structure typically follow the path of X-ray crystallography, which has an intrinsic phase problem that can make reading the electron density map they produce very difficult. This can be mitigated by appending a heavy-atom containing amino acid analogue into a crystal sample of the protein being studied. A selenium containing tryptophan analogue will be synthesized to be appended into proteins as a chemical …