Chemistry Commons^™

Myofilament Calcium Sensitivity: Consequences Of The Effective Concentration Of Troponin I, Jalal K. Siddiqui, Svetlana B. Tikunova, Shane D. Walton, Bin Liu, Meredith Meyer, Pieter P. De Tombe, Nathan Neilson, Peter M. Kekenes-Huskey, Hussam E. Salhi, Paul M.L. Janssen, Brandon J. Biesiadecki, Jonathan P. Davis

Chemistry Faculty Publications

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to …

Investigations Into The Effects Of Water Exchange And The Structure Of Lanthanide Chelates, Katherine Marie Payne

Dissertations and Theses

Lanthanide chelates are effective agents for improving contrast in MR images. Optimizing the relaxation of inner sphere water molecules is a common focus of research in this field. However, the efforts to design an optimal contrast agent have commonly over-looked the relationship of water position and water exchange kinetics. This work explores structural conformation, the impact of very fast water exchange kinetics on hydration, and differing tumbling rates for regioisomers of a number of lanthanide chelates. We have grown crystals of LnDOTMA and obtained structural data by X-ray diffraction that provide a picture of the chelate during water exchange and …

Ambient Ionization - Mass Spectrometry: Advances Toward Intrasurgical Cancer Detection, Alan Keith Jarmusch

Open Access Dissertations

My dissertation research has focused on the development of ambient ionization – mass spectrometry (MS) for clinical measurements, specifically intrasurgical cancer detection. The molecular differences between normal and cancerous tissue were detected via direct tissue analysis in vitro by touch spray ionization (TS) or by analyzing sectioned or smeared tissue using desorption electrospray ionization (DESI). The physical form of the tissue, e.g. in vitro sampling, sectioned, or smeared, was inconsequential in differentiating normal from cancerous tissue; however, the spectra acquired by TS and DESI differed due to differences in ionization processes. We envision that TS-MS and DESI-MS could impact diagnostic …

Relation Of Serum Estrogen Metabolites With Terminal Duct Lobular Unit Involution Among Women Undergoing Diagnostic Image-Guided Breast Biopsy., Hannah Oh, Zeina G Khodr, Mark E Sherman, Maya Palakal, Ruth M Pfeiffer, Laura Linville, Berta M Geller, Pamela M Vacek, Donald L Weaver, Rachael E Chicoine, Roni T Falk, Hisani N Horne, Daphne Papathomas, Deesha A Patel, Jackie Xiang, Xia Xu, Timothy Veenstra, Stephen M Hewitt, John A Shepherd, Louise A Brinton, Jonine D Figueroa, Gretchen L Gierach

Pharmaceutical Sciences Faculty Publications

Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with …

Design, Synthesis, And Evaluation Of Dasatinib-Amino Acid And Dasatinib-Fatty Acid Conjugates As Protein Tyrosine Kinase Inhibitors, Rakesh Tiwari, Alex Brown, Neda Sadeghiani, Amir Nasrolahi Shirazi, Jared Bolton, Amanda Tse, Gennady M. Verkhivker, Keykavous Parang, Gongqin Sun

Pharmacy Faculty Articles and Research

Derivatives of dasatinib were synthesized via esterification with 25 carboxylic acids including amino acids and fatty acids by extending the inhibitor to interact with more diverse sites and to improve specificity. Dasatinib-L-arginine derivative (Das-R, 7) was the most potent of the inhibitors tested with IC50 values of 4.4 nM, <0.25 nM, and <0.45 nM against Csk, Src, and Abl kinases, respectively. The highest selectivity ratio obtained in our study, 91.4 Csk/Src belonged to compound 18 (Das-C10) with an IC50 of 3.2 μM for Csk compared to 35 nM for Src. Furthermore, many compounds displayed increased selectivity toward Src, as compared with Abl. Compounds 15 (Das-E) and 13 (Das-C) demonstrated the largest gains (10.2 and 10.3 Abl/Src IC50 ratios). Das-R (IC50 = 2.06 μM) was significantly more potent than Das (IC50 = 26.3 μM) against Panc-1 cells while they both showed an IC50 < 51.2 pM against BV-173 and K562 cells. Molecular modeling and binding free energy simulations revealed a good agreement with the experimental results and rationalized differences in selectivity of the studied compounds. Integration of experimental and computational approaches in the design and biochemical screening of dasatinib derivatives facilitated rational engineering and diversification of dasatinib scaffold, providing useful insights into mechanisms of kinase selectivity.

Carotenoids And Fatty Acids In Early Lactation: A Study Of A Peruvian Population, Vanesa Mendez

FIU Electronic Theses and Dissertations

Lipid soluble carotenoids are micronutrients present in human milk that serve as precursors of vitamin A and also play an important role protecting cells from damage arising from photooxidative processes and reactive oxygen species. Fatty acids comprise about 3-5% of human milk and are mainly present as triglycerides. They are a major energy source for the infant and are necessary to support cell growth required for normal development and maturation of critical organs. Transport of carotenoids into milk has been little studied and there has been no previous investigation of the relationship of carotenoid transport with that of individual fatty …

Novel Role Of Hypoxia In Ovarian Cancer Chemo Resistance Through Epigenetic Regulation Of Hif1Α, Noelle L. Cutter Ph.D., Tyler Walther Bsc, Liam Gallagher, Michael O'Sullivan, Benjamin Honigsfeld, Kim Doyle, Nevenka Dimitrova, Robert Lucito

Faculty Works: Biology, Chemistry, and Environmental Studies

Ovarian cancer is the fifth deadliest cancer in woman, and epithelial malignancies account for 90% of cases. Tumor recurrence after chemotherapy or radiation remains a major obstacle to successful ovarian cancer treatment. Despite the large number of studies, molecular events that govern the emergence of aggressive therapy-resistant cells after chemotherapy are poorly defined. Genetic modifications, such as copy number variation (CNV), play an important role in controlling the expression of genes that are involved in chemo resistance. We analyzed CNV data that is publically available through the Cancer Genome Atlas and others. Of particular interest was the transcription factor HIF1α …

Synthesis, Self-Assembly, And Immunological Activity Of Α-Galactose-Functionalized Dendron–Lipid Amphiphiles, John Trant, Namrata Jain, D. M. Mazzuca, J Trevor Mcintosh, Bo Fan, S M Mansour Haeryfar, Sebastien Lecommandoux, Elizabeth Gillies

Chemistry Publications

Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendron–lipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendron–lipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties. Self-assembly in …

Distribution, Quantification And Toxicity Of Cinnamaldehyde In Electronic Cigarette Refill Fluids And Aerosols, Rachel Z. Behar, Wentai Luo, Sabrina C. Lin, Yuhuan Wang, Jackelyn Valle, James F. Pankow, Prue Talbot

Chemistry Faculty Publications and Presentations

Objective The aim of this study was to evaluate the distribution, concentration and toxicity of cinnamaldehyde in electronic cigarette (e-cigarette) refill fluids and aerosols.

Methods The distribution and concentration of cinnamaldehyde were determined in 39 e-cigarette refill fluids plus 6 duplicates using gas chromatography and mass spectrometry (GC/MS). A cinnamaldehyde toxicity profile was established for embryonic and adult cells using a live cell imaging assay, immunocytochemistry, the comet assay and a recovery assay.

Results Twenty of the 39 refill fluids contained cinnamaldehyde at concentrations that are cytotoxic to human embryonic and lung cells in the MTT assay. Cinnamon Ceylon aerosol …

Microfilariae Of Brugia Malayi Inhibit The Mtor Pathway And Induce Autophagy In Human Dendritic Cells, Prakash Babu Narasimhan, Sasisekhar Bennuru, Zhaojing Meng, Rachel N Cotton, Kathleen R Elliott, Sundar Ganesan, Renee Mcdonald-Fleming, Timothy Veenstra, Thomas B Nutman, Roshanak Tolouei Semnani

Pharmaceutical Sciences Faculty Publications

Immune modulation is a hallmark of patent filarial infection, including suppression of antigen-presenting cell function and downmodulation of filarial antigen-specific T cell responses. The mammalian target of rapamycin (mTOR) signaling pathway has been implicated in immune regulation, not only by suppressing T cell responses but also by regulating autophagy (through mTOR sensing amino acid availability). Global proteomic analysis (liquid chromatography-tandem mass spectrometry) of microfilaria (mf)-exposed monocyte-derived dendritic cells (DC) indicated that multiple components of the mTOR signaling pathway, including mTOR, eIF4A, and eIF4E, are downregulated by mf, suggesting that mf target this pathway for immune modulation in DC. Utilizing Western …

Peroxiredoxin Catalysis At Atomic Resolution, Arden Perkins, Derek Parsonage, Kimberly J. Nelson, O. Maduka Ogba, Paul Ha-Yeon Cheong, Leslie B. Poole, P. Andrew Karplus

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases that guard cells against oxidative damage, are virulence factors for pathogens, and are involved in eukaryotic redox regulatory pathways. We have analyzed catalytically active crystals to capture atomic resolution snapshots of a PrxQ-subfamily enzyme (from Xanthomonas campestris) proceeding through thiolate, sulfenate, and sulfinate species. These analyses provide structures of unprecedented accuracy for seeding theoretical studies, and show novel conformational intermediates giving insight into the reaction pathway. Based on a highly non-standard geometry seen for the sulfenate intermediate, we infer that the sulfenate formation itself can strongly promote local unfolding of the active site to …

Alamethicin In Lipid Bilayers: Combined Use Of X-Ray Scattering And Md Simulations, Jianjun Pan, D. Peter Tieleman, John F. Nagle, Norbert Kučerka, Prof. Stephanie Tristram-Nagle Ph.D.

John Copeland Nagle

We study fully hydrated bilayers of two di-monounsaturated phospholipids diC18:1PC (DOPC) and diC22:1PC with varying amounts of alamethicin (Alm). We combine the use of X-ray diffuse scattering and molecular dynamics simulations to determine the orientation of alamethicin in model lipids. Comparison of the experimental and simulated form factors shows that Alm helices are inserted transmembrane at high humidity and high concentrations, in agreement with earlier results. The X-ray scattering data and the MD simulations agree that membrane thickness changes very little up to 1/10 Alm/ DOPC. In contrast, the X-ray data indicate that the thicker diC22:1PC membrane thins with added …

Stability And Kinetics Of Dna Pseudoknots: Formation Of T∗A•T Base-Triplets And Their Targeting Reactions, Calliste Steffensmeier

Theses & Dissertations

Pseudoknots have been found to play important roles in the biology of RNA. These stem-loop motifs are considered to be very compact and the targeting of their loops with complementary strands is accompanied with lower favorable free energy terms. We used a combination of spectroscopic (UV, CD and fluorescence), calorimetric (DSC, PPC and ITC) and kinetic (SPR) techniques to investigate: 1) Local base-triplet formation in pseudoknots; 2) energetic contributions for the association of pseudoknots with their complementary strands; and 3) the kinetic rates as a function of targeting strand length.

We investigated a set of DNA pseudoknots with sequence: d(TCTCT …

Quef And Quef-Like: Diverse Chemistries In A Common Fold, Adriana Bon Ramos

Dissertations and Theses

The tunneling fold (T-Fold) superfamily is a small superfamily of enzymes found in organisms encompassing all kingdoms of life. Seven members have been identified thus far. Despite sharing a common three-dimensional structure these enzymes perform very diverse chemistries.

QueF is a bacterial NADPH-dependent oxidoreductase that catalyzes the reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ₀) to a primary amine (preQ₁) in the queuosine biosynthetic pathway. Previous work on this enzyme has revealed the mechanism of reaction but the cofactor binding residues remain unknown. The experiments discussed herein aim to elucidate the role of residues lysine 80, …

Developing Hyperpolarized Silicon Particles For In Vivo Mri Targeting Of Ovarian Cancer, Nicholas Whiting, Jingzhe Hu, Niki M. Zacharias, Ganesh L. R. Lokesh, David E. Volk, David G. Menter, Rajesha Rupaimoole, Rebecca Previs, Anil K. Sood, Pratip Bhattacharya

Nicholas Whiting

Inhibiting Androgen Receptor Nuclear Entry In Castration-Resistant Prostate Cancer, Julie A. Pollock, Suzanne E. Wardell, Alexander A. Parent, David B. Stagg, Stephanie J. Ellison, Holly M. Alley, Christina A. Chao, Scott A. Lawrence, James P. Stice, Ivan Spasojevic, Jennifer G. Baker, Sung Hoon Kim, Donald P. Mcdonnell, John A. Katzenellenbogen, John D. Norris

Chemistry Faculty Publications

Clinical resistance to the second-generation antiandrogen enzalutamide in castration resistant prostate cancer (CRPC), despite persistent androgen receptor (AR) activity in tumors, highlights the unmet medical need for next generation antagonists. We have identified and characterized tetra-aryl cyclobutanes (CBs) as a new class of competitive AR antagonists that exhibit a unique mechanism of action. These CBs are structurally distinct from current antiandrogens (hydroxyflutamide, bicalutamide, and enzalutamide), and inhibit AR-mediated gene expression, cell proliferation, and tumor growth in several models of CRPC. Conformational profiling revealed that CBs stabilize an AR conformation resembling an unliganded receptor. Using a variety of techniques, it was …

Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA and …

Countercurrent Chromatography Fractions Of Plant Extracts With Anti-Tuberculosis Activity, Douglas Armstrong, Nathan C. Krause, Drew Frey, J. Brent Friesen, Baojie Wan, Jordan Gunn, Scott Franzblau

Faculty Scholarship – Chemistry

Samples of numerous plant species were received from the southwestern part of the USA, from Richard Spjut, and plant samples were collected here in Illinois. All were extracted with typical solvents, giving crude residues, some of which were subjected to chromatographic methods. Some of the crude residues and some of the fractions were tested for anti-tuberculosis activity and/or antibacterial activity.

In a general way, bioactive natural products are dealt with very well by Liang & Fang. More specifically, the southwestern part of the United States has a large variety of indigenous plants many of which have not been investigated for …

Analysis Of The Intricacies Of Substrate Recognition Of High Mobility Group Proteins And Aminoacyl-Trna Synthetases Using Non-Cognate Substrates, Douglas Van Iverson Ii

Dissertations

The studies presented in section 1 (Chapters I-IV) focus on the design and development of nucleic acid four-way junctions (4WJs) to target a member of the high mobility group (HMG) proteins, the proinflammatory cytokine high mobility group box 1 protein (HMGB1). In the present study, hybrid PNA-DNA 4WJs based on a model DNA 4WJ were constructed to improve the thermal stability of 4WJs while maintaining strong binding affinity toward HMGB1. An electrophoretic mobility shift assay (EMSA) was used to examine the binding affinity of an isolated DNA binding domain of HMGB1, the HMGB1 b-box (HMGB1b), toward a set of PNA-DNA …

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …

Abstract 2934: Gsk3Β Modulates Chemoresistance In Epithelial Ovarian Cancer, Noelle L. Cutter Ph.D., Naeha Pathak

Faculty Works: Biology, Chemistry, and Environmental Studies

Introduction: Epithelial ovarian cancer is one of the most common gynecological malignancies and the fifth most frequent cause of cancer death in women, affecting over 22,000 women annually. Nearly 15,500 affected women die from this disease annually, and chemoresistance from the commonly prescribed platinum-based drug, carboplatin, is a major contributor to this mortality. Previous studies have identified genes with CpG islands that are methylated and transcriptionally silenced in resistant epithelial ovarian cancer patients. One of these genes is GSK3β, an important regulator of apoptosis and cell growth in the Wnt pathway. Thus, understanding the role of GSK3β suppression in chemoresistance …

Conformational Dynamics And Stability Associated With Magnesium Or Calcium Binding To Dream In The Regulation Of Interactions Between Dream And Dna Or Presenilins, Khoa Ngoc Pham

FIU Electronic Theses and Dissertations

Downstream regulatory element antagonist modulator (DREAM) is involved in various interactions with targets both inside and outside of the nucleus. In the cytoplasm, DREAM interacts with the C-terminal fragments of presenilins to facilitate the production of β-amyloid plaques in Alzheimer’s disease. In the nucleus, Ca²⁺ free DREAM directly binds to specific downstream regulatory elements of prodynorphin/c-fos gene to repress the gene transcription in pain modulation. These interactions are regulated by Ca²⁺ and/or Mg²⁺ association at the EF-hands in DREAM. Therefore, understanding the conformational dynamics and stability associated with Ca²⁺ and/or Mg²⁺ binding to DREAM …

Using Wastewater-Based Epidemiology To Estimate Drug Consumption—Statistical Analyses And Data Presentation, Caleb J. Banta-Green, Alex J. Brewer, Christoph Ort, Dennis R. Helsel, Jason R. Williams, Jennifer A. Field

All Faculty Scholarship for the College of the Sciences

Aim

Analysis of wastewater samples can be used to assess population drug use, but reporting and statistical issues have limited the utility of the approach for epidemiology due to analytical results that are below the limit of quantification or detection. Unobserved or non-quantifiable—censored—data are common and likely to persist as the methodology is applied to more municipalities and a broader array of substances. We demonstrate the use of censored data techniques and account for measurement errors to explore distributions and annual estimates of the daily mean level of drugs excreted per capita.

Measurements

Daily 24-hour composite wastewater samples for 56 …

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S Mhashilkar, Sai L Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R Palli, H. Lee Woodcock Iii, Thomas R Unnasch

Chemistry Faculty Publications

BACKGROUND: A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

METHODOLOGY/ PRINCIPAL FINDINGS: Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. …

Screening The Low Molecular Weight Fraction Of Human Serum Using Atr-Ir Spectroscopy, Franck Bonnier, Matthew J. Baker, Hugh Byrne

Articles

Vibrational spectroscopic techniques can detect small variations in molecular content, linked with disease, showing promise for screening and early diagnosis. Biological fluids, particularly blood serum, are potentially valuable for diagnosis purposes. The so-called Low Molecular Weight Fraction (LMWF) contains the associated peptidome and metabolome and has been identified as potentially the most relevant molecular population for disease-associated biomarker research. Although vibrational spectroscopy can deliver a specific chemical fingerprint of the samples, the High Molecular Weight Fraction (HMWF), composed of the most abundant serum proteins, strongly dominates the response and ultimately makes the detection of minor spectral variations a challenging task. …

A Randomized Controlled Study To Evaluate The Effect Of Bexarotene On Amyloid-Β And Apolipoprotein E Metabolism In Healthy Subjects, Kaushik Ghosal, Michael Haag, Philip B Verghese, Tim West, Timothy Veenstra, Joel B Braunstein, Randall J Bateman, David M Holtzman, Gary E Landreth

Pharmaceutical Sciences Faculty Publications

INTRODUCTION: We conducted a phase Ib proof of mechanism trial to determine whether bexarotene (Targretin) increases central nervous system (CNS) apolipoprotein E (apoE) levels and alters Aβ metabolism in normal healthy individuals with the

METHODS: We used stable isotope labeling kinetics (SILK-ApoE and SILK-Aβ) to measure the effect of bexarotene on the turnover rate of apoE and Aβ peptides and stable isotope spike absolute quantitation (SISAQ) to quantitate their concentrations in the cerebrospinal fluid (CSF). Normal subjects were treated for 3 days with bexarotene (n = 3 women, 3 men, average 32 years old) or placebo (n = 6 women, …

2016-01-A3dsrinp-Csc-Sta-Cmb-522-Bps-542, Raymond Pulver, Neal Buxton, Xiaodong Wang, John Lucci, Jean Yves Hervé, Lenore Martin

Bioinformatics Software Design Projects

Cholesterol is carried and transported through bloodstream by lipoproteins. There are two types of lipoproteins: low density lipoprotein, or LDL, and high density lipoprotein, or HDL. LDL cholesterol is considered “bad” cholesterol because it can form plaque and hard deposit leading to arteries clog and make them less flexible. Heart attack or stroke will happen if the hard deposit blocks a narrowed artery. HDL cholesterol helps to remove LDL from the artery back to the liver.

Traditionally, particle counts of LDL and HDL plays an important role to understanding and prediction of heart disease risk. But recently research suggested that …

The Synthesis Of 1,3-Difluoro-2-Methyl-4-Phenylbenzene From A One-Pot Reaction Of Difluorocarbene And 1-Phenyl-2-Methylcyclobutene, Ruth Felicitas Menger

Senior Honors Projects, 2010-2019

Previous studies show that 1,2-disubstituted cyclobutenes can be used in reaction with difluorocarbene to produce 1,3-difluorobenzenes. A pathway to the synthesis of these types of compounds is of interest due to their presence in fluoroquinolone antibacterials, resins, and insecticides. The synthesis is unique because the fluorine atoms from the difluorocarbene are not adjacent to each other when the ring expands to a benzene ring. This study focuses on the reaction of difluorocarbene with 1-phenyl-2-methylcyclobutene, which was synthesized in one-pot in 4 steps starting from 1-phenyl-1-propyne and zirconocene dichloride.

Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying

Honors Thesis

The Zn(II) metal ion has been shown to interact with Islet Amyloid Polypeptide (IAPP), a protein implicated in the progression of Type II Diabetes Mellitus, in such a way as to prevent the protein from aggregating into toxic fibers. We set out to find whether other metal ions might similarly prevent IAPP aggregation. Using Thioflavin T (ThT) spectroscopic assays, which measure fluorescence of ThT upon binding to aggregated IAPP, we observed a decrease in aggregation when incubated with Zn(II), Cu(II), Ni(II), and Sn(II). Atomic Force Microscopy (AFM), which can visualize fibril formation, revealed that the metals were not inhibiting IAPP …

Innovative Synthesis Of Diltiazem/Clentiazem Analogs, Emelyn Magtanong

Journal of Interdisciplinary Undergraduate Research

Cardiovascular disease defines disorders of the heart and blood vessels, and is the number one cause of death in America. Diltiazem and clentiazem are common calcium channel blockers incorporated into drugs used to treat various cardiovascular diseases. Methods to synthesize 5-[2-(dimethylamino)ethyl]-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one, an analog of the core of diltiazem and clentiazem, using cost-efficient starting materials allows for affordable treatment and increased availability to affected individuals. N-(N,N-dimethylethanamine)-4-aminophenol can be oxidized to form a quineoneimine, which can be further reacted with 3-mercaptopropionic acid via Michael addition. Subsequent addition of a coupling reagent, N,N'-dicyclocarbodiimide (DCC),¹ produces 5-[2-(dimethylamino)ethyl]-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one, analogous to the core …