Medicinal-Pharmaceutical Chemistry Commons^™

Role Of Water On The Rotational Dynamics Of The Organic Methylammonium Cation: A First Principles Analysis, Ross D. Hoehn, Joseph S. Francisco, Sabre Kais, Ali Kachmar

Department of Chemistry: Faculty Publications

Understanding the degradation mechanisms of lead-halide perovskites (CH₃NH₃PbI₃) under exposure to liquid/aerosol water is an essential problem within the photovoltaic community. Herein we investigate both the static and the dynamic properties of the methylammonuim cation (MA) as it coordinates with invading water molecules (MA.(H₂O)_n, n = 1, 2, 3, 4) using both stationary state quantum mechanics and first principle molecular dynamics simulations. Various solvation structures of MA were characterized by their stabilization energies, dipoles, and Maximally-Localized Wannier Function (MLWF) centers. Calculation – and analysis – of vibrational shifts in the …

Indole Reverses Intrinsic Antibiotic Resistance By Activating A Novel Dual-Function Importer, Yan Wang, Tian Tian, Jingjing Zhang, Xin Jin, Huan Yue, Xiao-Hua Zhang, Liangcheng Du, Fan Bai

Department of Chemistry: Faculty Publications

Bacterial antibiotic resistance modulation by small signaling molecules is an emerging mechanism that has been increasingly reported in recent years. Several studies indicate that indole, an interkingdom signaling molecule, increases bacterial antibiotic resistance. However, the mechanism through which indole reduces antibiotic resistance is largely unknown. In this study, we demonstrated a novel mechanism for indole-mediated reversal of intrinsic antibiotic resistance in Lysobacter. This reversal was facilitated by a novel BtuD-associated dual-function importer that can transfer both vitamin B₁₂ and antibiotics. Indole stimulated btuD overexpression and promoted efficient absorption of extracellular vitamin B₁₂; meanwhile, the weak selectivity …

High Initial Reversible Capacity And Long Life Of Ternary Sno2‑Co‑Carbon Nanocomposite Anodes For Lithium‑Ion Batteries, Pan Deng, Jing Yang, Shengyang Li, Tian-E Fan, Hong-Hui Wu, Yun Mou, Hui Huang, Qiaobao Zhang, Dong-Liang Peng, Baihua Qu

Department of Chemistry: Faculty Publications

The two major limitations in the application of SnO₂ for lithium-ion battery (LIB) anodes are the large volume variations of SnO₂ during repeated lithiation/delithiation processes and a large irreversible capacity loss during the first cycle, which can lead to a rapid capacity fade and unsatisfactory initial Coulombic efficiency (ICE). To overcome these limitations, we developed composites of ultrafine SnO₂ nanoparticles and in situ formed Co(CoSn) nanocrystals embedded in an N-doped carbon matrix using a Co-based metal–organic framework (ZIF-67). The formed Co additives and structural advantages of the carbon-confined SnO₂/ Co nanocomposite effectively inhibited Sn coarsening …

Spheroid-3d And Monolayer-2d Intestinal Electrochemical Biosensor For Toxicity/Viability Testing: Applications In Drug Screening, Food Safety, And Environmental Pollutant Analysis, Evangelia Flampouri, Shahzad Imar, Kieran O'Connell, Baljit Singh

Articles

The rise of three-dimensional cell culture systems that provide in vivo-like environments for pharmaco-toxicological models has prompted the need for simple and robust viability assays suitable for complex cell architectural structures. This study addresses that challenge with the development of an in vitro enzyme based electrochemical sensor for viability/cytotoxicity assessment of two-dimensional (2D) monolayer and three-dimensional (3D) spheroid culture formats. The biosensor measures the cell viability/toxicity via electrochemical monitoring of the enzymatic activity of nonspecific esterases of viable cells, through the hydrolysis of 1-naphthyl acetate to 1-naphthol. The proposed sensor demonstrated strong correlation (r = 0.979) with viable …

A Comparison Of The Efficacy Of Newly-Synthesized Antimicrobial Polymers And A Preview Into Their Interaction With The Bacterial Cell Membrane., Kailey Christman

Williams Honors College, Honors Research Projects

Antibiotic-resistant bacteria present an obstacle for physicians and researchers. Over 35,000 people die annually in the U.S. from antibiotic-resistant infections each year. New antibiotics are being developed and studied, and natural products are screened to find potential new antibiotics. In this study, four polymer antibiotics with polyester backbones and peptide functional groups were studied with Escherichia coli and Staphylococcus aureus to determine the polymers’ efficacies on the different bacteria and compare the polymers to each other. Timed fluorescence microscopy experiments were performed to determine how long it takes the antibiotics to compromise the membrane integrity of fluorescently-labelled E. coli. …

Highly Stable And Efficient All-Inorganic Lead-Free Perovskite Solar Cells With Native-Oxide Passivation, Min Chen, Ming-Gang Ju, Hector F. Garces, Alexander D. Carl, Luis K. Ono, Zafer Hawash, Yi Zhang, Tianyi Shen, Yabing Qi, Ronald L. Grimm, Domenico Pacifici, Xiao Cheng Zeng, Yuanyuan Zhou, Nitin P. Padture

Department of Chemistry: Faculty Publications

There has been an urgent need to eliminate toxic lead from the prevailing halide perovskite solar cells (PSCs), but the current lead-free PSCs are still plagued with the critical issues of low efficiency and poor stability. This is primarily due to their inadequate photovoltaic properties and chemical stability. Herein we demonstrate the use of the lead-free, allinorganic cesium tin-germanium triiodide (CsSn_0.5Ge_0.5I₃) solid-solution perovskite as the light absorber in PSCs, delivering promising efficiency of up to 7.11%. More importantly, these PSCs show very high stability, with less than 10% decay in efficiency after 500 h …

Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, Mckenzie K. Lehman, Vinai C. Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey

Department of Chemistry: Faculty Publications

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH₃ and CO₂ from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes …

An Enzymology And Inhibition Study Of A Camp-Dependent Protein Kinase Linked To Acth-Independent Cushing's Syndrome, Nicole Luzi

Theses and Dissertations

Cyclic-AMP dependent protein kinase (PKA) is a key intracellular signal transduction kinase that is modulated by G_s- and G_i-coupled GPCRs. Under normal physiological conditions, PKA exists as an inactive holoenzyme made up of two catalytic subunits and two regulatory subunits. Upon cAMP binding to the regulatory subunits, the catalytic subunits (PKACa) are released to perform various downstream phosphorylation events. However, aberrant PKA activation can cause various diseases including Cushing’s Syndrome, which is an endocrine disorder caused by the overproduction of cortisol by the hypothalamus-pituitary-adrenal hormone system. This disorder can be caused by pituitary adenomas that release …

Machine Learning Enabled Prediction Of Mechanical Properties Of Tungsten Disulfide Monolayer, Xinyu Wang, Dan Han, Yang Hong, Haiyi Sun, Jingzhi Zhang, Jingchao Zhang

Department of Chemistry: Faculty Publications

One of two-dimensional transition metal dichalcogenide materials, tungsten disulfide (WS₂), has aroused much research interest, and its mechanical properties play an important role in a practical application. Here the mechanical properties of h-WS₂ and t-WS₂ monolayers in the armchair and zigzag directions are evaluated by utilizing the molecular dynamics (MD) simulations and machine learning (ML) technique. We mainly focus on the effects of chirality, system size, temperature, strain rate, and random vacancy defect on mechanical properties, including fracture strain, fracture strength, and Young’s modulus. We find that the mechanical properties of h-WS₂ surpass those of …

Insights Into Gemcitabine Resistance And The Potential For Therapeutic Monitoring, Teklab Gebregiworgis, Fatema Bhinderwala, Vinee Purohit, Nina V. Chaika, Pankaj K. Singh, Robert Powers

Department of Chemistry: Faculty Publications

Introduction—Gemcitabine is an important component of pancreatic cancer clinical management. Unfortunately, acquired gemcitabine resistance is widespread and there are limitations to predicting and monitoring therapeutic outcomes.

Objective—To investigate the potential of metabolomics to differentiate pancreatic cancer cells that develops resistance or respond to gemcitabine treatment.

Results—We applied 1D ¹H and 2D ¹H-¹³C HSQC NMR methods to profile the metabolic signature of pancreatic cancer cells. ¹³C₆-glucose labeling identified thirty key metabolites uniquely altered between wild-type and gemcitabine-resistant cells upon gemcitabine treatment. Gemcitabine resistance was observed to reprogram glucose metabolism and to enhance the pyrimidine …

Detailed Characterization Of The Solution Kinetics And Thermodynamics Of Biotin, Biocytin And Haba Binding To Avidin And Streptavidin, Roberto F. Delgadillo, Timothy C. Mueser, Kathia Zaleta-Rivera, Katie A. Carnes, Jose Gonzalez-Valdez, Lawrence J. Parkhurst

Department of Chemistry: Faculty Publications

The high affinity (K_D ~ 10⁻¹⁵ M) of biotin for avidin and streptavidin is the essential component in a multitude of bioassays with many experiments using biotin modifications to invoke coupling. Equilibration times suggested for these assays assume that the association rate constant (kon) is approximately diffusion limited (10⁹ M^-1s^-1) but recent single molecule and surface binding studies indicate that they are slower than expected (10⁵ to 10⁷ M^-1s^-1). In this study, we asked whether these reactions in solution are diffusion controlled, which reaction model and thermodynamic …

Robert J. Lefkowitz And Discovery Of The G-Protein-Coupled Receptor Family, Clarence Lee

Natural Sciences Student Research Presentations

This poster for the Natural Sciences Poster Session at Parkland College features Dr. Robert J. Lefkowitz, 2012 Nobel Prize in Chemistry winner (with Brian Kobilka) for their research on G-protein-coupled receptors, proteins in the plasma membrane that allow for the transmission of information through the membrane and into the cell. This research was to impact the development of medications that target these receptors, such as SSRIs.

Therapeutic Delivery Technology And Its Economic Impact, Paul E. Savas Jr.

Senior Honors Theses

Therapeutic delivery technology is a current area of high interest in both university and industrial settings. These technologies are being developed in order to deliver therapeutic agents, such as genes, proteins, and drugs, to patients more efficiently. Nanoscale delivery vehicles have proven to be useful for these applications; these vehicles may either be naturally produced or chemically synthesized. The physical properties of these nanomaterials must be characterized correctly using instrumentation that evaluates their size, morphology, and potential for agglomeration. These technologies represent a high-growth economic area that fosters entrepreneurship and innovation. Because of this innovative spirit, research and economic interest …

Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber

Theses and Dissertations--Pharmacy

Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …

Transactivation Of Human Endogenous Retroviruses By Tumor Viruses And Their Functions In Virus-Associated Malignancies., Jungang Chen, Maryam Foroozesh, Zhiqiang Qin

Faculty and Staff Publications

Human endogenous retroviruses (HERVs), viral-associated sequences, are normal components of the human genome and account for 8–9% of our genome. These original provirus sequences can be transactivated to produce functional products. Several reactivated HERVs have been implicated in cancers and autoimmune diseases. An emerging body of literature supports a potential role of reactivated HERVs in viral diseases, in particular viral-associated neoplasms. Demystifying studies on the mechanism(s) of HERV reactivation could provide a new framework for the development of treatment and prevention strategies targeting virus-associated tumors. Although available data suggest that coinfection by other viruses, such as Kaposi’s Sarcoma-associated herpesvirus (KSHV) …

Xflow: An Algorithm For Extracting Ion Chromatograms, Mathew M. Gutierrez, Rob Smith

Graduate Student Theses, Dissertations, & Professional Papers

Abstract: Mass spectrometry is a fundamental tool for modern proteomics. The increasing availability of mass spectrometry data paired with the increasing sensitivity and fidelity of the instruments necessitates new and more potent analytical methods. To that end, we have created and present XFlow, a feature detection algorithm for extracting ion chromatograms from MS1 LC-MS data. XFlow is a parameter-free procedurally agnostic feature detection algorithm that utilizes the latent properties of ion chromatograms to resolve them from the surrounding noise present in MS1 data. XFlow is designed to function on either profile or centroided data across different resolutions and instruments. This …

Antitumor Properties Of Imidazolium Salts, Jenna Frantz

Williams Honors College, Honors Research Projects

This is the final write-up for an honors research project for the University of Akron Williams Honors College. Synthesis of novel imidazolium salts was conducted. Following synthesis of imidazolium salts, the stability of the compound was tested at 37°C over a 72-hour period to give preliminary information about drug stability in vivo. 2D NMR was also conducted to confirm the structure of TPP-1. The student wrote an experimental protocol for the use of C57BL/6 mice and performed the online CITI training by the IRB to prepare to work with animals in a study of the antitumor properties of imidazolium salts …

Synthesis Of Oligodeoxynucleotides Containing Sensitive Electrophiles, Shahien Shahsavari

Dissertations, Master's Theses and Master's Reports

Oligodeoxynucleotides (ODNs) containing electrophilic groups are useful in many studies including antisense drug development and DNA/protein interaction. Due to the use of strong nucleophiles for cleavage and deprotection, traditional ODN synthesis methods are not suitable for their preparation. To solve this problem, a new ODN synthesis technology using the 1,3- dithiane-2-yl-methoxycarbonyl (Dmoc) function as protecting groups and linker has been developed. Furthermore, Dmoc-derivatives were developed to demonstrate the feasibility of the technology. The Dmoc and Dmoc derivative functions are stable under all ODN synthesis conditions using the phosphoramidite chemistry. Upon oxidation of the sulfides in them, because of the drastically …

The Inductive Effect In Organic Chemistry, Charles A. Kingsbury

Department of Chemistry: Faculty Publications

The subtle difference between the successive polarization model and the flow of electrons through sigma bonds is explored, as well as the alternating charge model of Pople and the pervasive field model. The present paper is concerned with the ability of alkyl groups to serve as sigma inductive electron donors.

Electrocaloric Effect In Ferroelectric Ceramics With Point Defects, Ming Wu, Qingshan Zhu, Jianting Li, Dongsheng Song, Honghui Wu, Mengyao Guo, Jinghui Gao, Yang Bai, Yujun Feng, Stephen J. Pennycoock, Xiaojie Lou

Department of Chemistry: Faculty Publications

The electrocaloric effect has drawn much attention due to its potential application in cooling devices. A negative electrocaloric effect is predicted to be induced in defect-doped ferroelectrics by computational results [A. Grunebohm and T. Nishimatsu, Phys. Rev. B 93, 134101 (2016) and Ma et al., Phys. Rev. B 94, 094113 (2016)], but it need to be confirmed by experimental results. In this work, we prepared a 1mol. % Mn-doped Pb(Zr_0.2,Ti_0.8)O₃ ceramics (Pb((Zr_0.2,Ti_0.8)_0.99,Mn_0.01)O₃), and the electrocaloric effect of the defect-containing ferroelectric ceramics has …