DOCSLIB.ORG

Nitroxide-Mediated Polymerization

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Nitroxide-Mediated Polymerization Chapter 7 Nitroxide-Mediated Polymerization 7.1 Introduction Controlled radical polymerization (CRP) under radical initiation conditions belongs to priority areas in the development of the synthetic chemistry of polymers of the last years [1–16]. Nitroxide-mediated polymerization (NMP) was invented by Solomon [1, 13]. Since this discovery, nitroxide-mediated radical polymerization is a power- ful method to synthesize well-defined macromolecular architectures with precisely controlled topologies, compositions, microstructures, and functionalities [3–5]. The most common mechanisms for reversible activation in polymerization reactions are schematically illustrated in Scheme 7.1. Persistent radical effect (PRE) occurs when two radicals are generated at the same time, at the same rate, and one is more persistent than the other, the self-termination reactions are lowered, leading to an unusually high selectivity for the cross-coupling reaction [10]. The effect has been investigated for the preparation of macromolecules with a narrow molar mass distribution through radical polymerization. Nitroxide-mediated polymerization is widely applied in industrial polymer syn- theses as a method for production of large-tonnage polymers and is employed to manufacture new pigments, sealants, emulsion stabilizers, and block copolymers, etc., with a various set of properties. NMP has also paved an avenue for complex macromolecular architectures (statistical, block, graft) in the fields of nanoscience and nanotechnology [5, 9, 12] and references cited therein. A brief summary of NMP developments in both the patent and open literature during the period of the early Scheme 7.1 Mechanisms for reversible activation in polymerization reactions [6] © Springer Nature Switzerland AG 2020 161 G. I. Likhtenshtein, Nitroxides, Springer Series in Materials Science 292, https://doi.org/10.1007/978-3-030-34822-9_7 162 7 Nitroxide-Mediated Polymerization 1980–2000 was presented in [11]. Various important aspects in this area, such as syn- thesis of nitroxides and alkoxyamines, fundamentals to applications in materials sci- ence, kinetic aspects of NMP,recent developments in NMP,nitroxide-mediated poly- merization in dispersed media, NMP of methacrylic esters, complex macromolecular architectures prepared by NMP,surface-initiated NMP,from nanoporous materials to microelectronics, NMP under homogenous conditions, and NMP-derived materials for biomedical applications were presented and discussed in separate chapters of the book [12]. In this chapter, fundamentals and recent developments in the NMP area are briefly summarized and illustrated by particular examples. 7.2 Mechanism of the Nitroxide-Mediated Polymerization The basic idea of the NMP method (Scheme 7.1) is that the initiation of the “living” free polymerization (LEP) process occurs as a result of the dissociation of a special compound (A-S) into two radicals, active (AR·) and stable (SR·) ones. Persisted radical effect (PRE) can also occur for radicals generated from the decomposition of two different initiators affording the active radical and a persistent radical. The active radical involves into the polymer chain initiation and self-recombination reactions. The recombination of a stable radical is thermodynamically forbidden, and, in this case, it can only participate in reversible cross-recombinations with the partner radical (AR·) and with a polymer radical Rn·. The perfect candidates for the role of initiator of LFP were found to be alkoxyamines. These compounds cleave into transient alkyl and persistent aminoxyl radicals which then combine and regenerate the parent compounds. Simultaneously, the alkyl species self-terminate, and this causes a continuous buildup of excess aminoxyl. Hence, the back-reaction to the alkoxyamine (e.g., R1R2NOR) accel- erates, and the self-termination slows down in time. The cross-recombination of · · · macroradical (Rn ) with R1R2NO leads to a very low concentration of AR , limiting the self-termination reaction of the alkyl radical, and allowing the controlled growth of the macroradical. The first work on alkoxyamines R1R2NOR was reported by Jones and Major in 1927 [17]. The radical reactivity of these compounds was discovered by Kovtun et al. in 1974 [18].TheformationofR1R2NOR in recombination of corresponding radicals was also demonstrated. In NMP, the principle stages are [9]: (1) Initiation can be either performed in a bicomponent system or in a unimolecular initiation process. (2) The nitroxide can then cross-recombine with the propagating active chain to give a nitroxide- terminated radical as dormant species. (3) This macroalkoxyamine can undergo reversible C–ON bond homolysis at elevated reaction temperatures and releases the stable nitroxide radical as well as the active polymer chain. Detail schemes of the reaction mechanism in NMP and initiation mechanism of uni- and bimolecular initiators were presented in review [9]. The development of alkoxyamines as initia- tors permits controlled homopolymerization of acrylates and acrylamides. Data on 7.2 Mechanism of the Nitroxide-Mediated Polymerization 163 TEMPO derivatives, alkoxyamines including alkoxyamines bearing stereo centers, and light-sensitive alkoxyamines used in DNP were also described in the review. Steps involved in the TEMPO-mediated nitroxide-mediated polymerization are as follows: (1) The TEMPO/monomer adduct is formed with a source of radicals from a conventional initiator like benzoyl peroxide. (2) With an increase in temperature, the equilibrium is shifted to the addition of monomer, and the radical concentra- tion is controlled by the persistent radical effect. (3) Propagation continues and the growing polymer is capped by TEMPO and the cycle continues. The recent review [5] also provided information on the key components of NMP such as TEMPO derivatives used as nitroxides, alkoxyamines derivatives showing improved bond hydrolysis, alkoxyamines bearing stereo centers, nitroxides and alkoxyamines used for the polymerization (RDRP), of methyl methacrylate (MMA), and functional alkoxyamines. Spin traps are agents that are commonly used in electron spin resonance spec- troscopy (ESR) as a tool to convert transient radicals into a stable form. In polymer- izations, spin traps act as radical scavengers, and hence, mostly inhibit chain growth. Nitroxides and nitrons can be radical spin trap scavengers and used in ESR studies to quantify radical initiation [19–22]. A nitrone, for example, possesses higher affinity toward reacting with oxygen-centered radicals, acrylates, styrenic, and tertiary carbon-centered radicals [20, 21]. In enhanced spin capturing polymerization (ESCP), (macro)radical spin trapping by nitrons is in competition with conventional macroradical chain growth, leading to an effective chain length control of the polymerization, namely trapping macroradicals and shorting the resid- ual polymer chains. The trapped species constitutes a macronitroxide, which by itself is able to trap a further transient radical in a radical recombination event. Thus, the polymer product consists of a coupling product of two polymers, which is bridged by an alkoxyamine functionality in a typical example of the nitroxide-mediated polymerization, the preparation of ABA-type block copolymers via tandem enhanced spin capturing polymerization (ESCP) [23]. Midchain −1 alkoxyamine functional polystyrenes (Mn = 6200, 12,500, and 19,900 g mol ) were chain extended with styrene as well as tert-butyl acrylate at elevated tempera- ture NMP conditions (T = 110 °C), generating a tandem ESCP-NMP sequence. It 164 7 Nitroxide-Mediated Polymerization was found that the efficiency of the block copolymer formation process decreases with an increasing chain length of the ESCP precursor macromolecules. Photopolymerization reactions are recognized as powerful tool for modification of coatings, inks, photoresists, dual-cure systems, and others [24, 25]. Nitroxide- mediated photopolymerization (PNMP) is characterized by important advantages, e.g., thin films can be polymerized very rapidly by UV irradiation, and PNMP is an ecological alternative to thermal processes and is able to modify and pattern surfaces. During PNMP, the photolysis of an alkoxyamine bearing a chromophore, for example, leads to a reversible equilibrium between the alkoxyamine and the generated nitroxide and alkyl radicals, providing a controlled radical photopolymerization [26]. In the alkoxyamines with a closer proximity between the chromophore and the C–O bond, the homolysis of the alkoxyamine is facilitated due to an energy transfer from the chromophore (“antenna”) to the weak C–O bond. In work [27], the thermally driven polymerizations were performed via the cleavage of the alkoxyamine functionality; whereas, the photochemically induced polymerizations were carried out either by nitroxide-mediated photopolymerization (NMP2) or by a mechanism, depending on the structure of the light-sensitive alkoxyamine employed. With each alkoxyamine, as initiators of thermally and photoinduced polymerizations, block copolymers were obtained, and the system was applied to the post-modification of polymer coatings for application in patterning and photografting. The photoradical polymerization of vinyl acetate was performed using 4- methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl as the mediator in the presence of bis(alkylphenyl)iodonium hexafluorophosphate (BAI) [28]. It was found that in this condition: (1) The polymerization proceeds by the living mechanism based on lin- ear
Load more

Recommended publications
  • Use of Mathematical Modeling and Other Biophysical Methods For
    USE OF MATHEMATICAL MODELING AND OTHER BIOPHYSICAL METHODS FOR INSIGHTS INTO IRON-RELATED PHENOMENA OF BIOLOGICAL SYSTEMS A Dissertation by JOSHUA D. WOFFORD Submitted to the Office of Graduate and Professional Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Chair of Committee, Paul A. Lindahl Committee Members, David P. Barondeau Simon W. North Vishal M. Gohil Head of Department, Simon W. North December 2018 Major Subject: Chemistry Copyright 2018 Joshua D. Wofford ABSTRACT Iron is a crucial nutrient in most living systems. It forms the active centers of many proteins that are critical for many cellular functions, either by themselves or as Fe-S clusters and hemes. However, Fe is potentially toxic to the cell in high concentrations and must be tightly regulated. There has been much work into understanding various pieces of Fe trafficking and regulation, but integrating all of this information into a coherent model has proven difficult. Past research has focused on different Fe species, including cytosolic labile Fe or mitochondrial Fe-S clusters, as being the main regulator of Fe trafficking in yeast. Our initial modeling efforts demonstrate that both cytosolic Fe and mitochondrial ISC assembly are required for proper regulation. More recent modeling efforts involved a more rigorous multi- tiered approach. Model simulations were optimized against experimental results involving respiring wild-type and Mrs3/4-deleted yeast. Simulations from both modeling studies suggest that mitochondria possess a “respiratory shield” that prevents a vicious cycle of nanoparticle formation, ISC loss, and subsequent loading of mitochondria with iron.
    [Show full text]
  • Electrochemical and Structural Characterization of Azotobacter Vinelandii Flavodoxin II
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Caltech Authors Electrochemical and structural characterization of Azotobacter vinelandii flavodoxin II Helen M. Segal,1 Thomas Spatzal,1 Michael G. Hill,2 Andrew K. Udit,2 and Douglas C. Rees 1* 1Division of Chemistry and Chemical Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125 2Division of Chemistry, Occidental College, Los Angeles, California 90041 Received 1 June 2017; Accepted 10 July 2017 DOI: 10.1002/pro.3236 Published online 14 July 2017 proteinscience.org Abstract: Azotobacter vinelandii flavodoxin II serves as a physiological reductant of nitrogenase, the enzyme system mediating biological nitrogen fixation. Wildtype A. vinelandii flavodoxin II was electrochemically and crystallographically characterized to better understand the molecular basis for this functional role. The redox properties were monitored on surfactant-modified basal plane graphite electrodes, with two distinct redox couples measured by cyclic voltammetry correspond- ing to reduction potentials of 2483 6 1 mV and 2187 6 9 mV (vs. NHE) in 50 mM potassium phos- phate, 150 mM NaCl, pH 7.5. These redox potentials were assigned as the semiquinone/ hydroquinone couple and the quinone/semiquinone couple, respectively. This study constitutes one of the first applications of surfactant-modified basal plane graphite electrodes to characterize the redox properties of a flavodoxin, thus providing a novel electrochemical method to study this class of protein. The X-ray crystal structure of the flavodoxin purified from A. vinelandii was solved at 1.17 A˚ resolution. With this structure, the native nitrogenase electron transfer proteins have all been structurally characterized.
    [Show full text]
  • Ribonucleotide Reductase Subunit M2B Deficiency Leads To
    Am J Transl Res 2018;10(11):3635-3649 www.ajtr.org /ISSN:1943-8141/AJTR0084684 Original Article Ribonucleotide reductase subunit M2B deficiency leads to mitochondrial permeability transition pore opening and is associated with aggressive clinicopathologic manifestations of breast cancer Lijun Xue1*, Xiyong Liu2,6*, Qinchuan Wang3,4, Charlie Q Liu3, Yunru Chen3, Wei Jia5, Ronhong Hsie6, Yifan Chen8, Frank Luh2,6, Shu Zheng7, Yun Yen2,6,8 1Department of Pathology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA; 2Sino-American Cancer Foundation, California Cancer Institute, Temple, CA 91780, USA; 3Department of Molecular Pharmacology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA; 4Surgical Oncology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; 5Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA; 6TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan, ROC; 7Cancer Institute, Zhejiang University, Hangzhou 310009, Zhejiang, China; 8PhD Program of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan, ROC. *Co-first authors. Received August 27, 2018; Accepted October 19, 2018; Epub November 15, 2018; Published November 30, 2018 Abstract: Ribonucleotide reductase small subunit M2B (RRM2B) plays an essential role in maintaining mitochon- drial homeostasis. Mitochondrial permeability transition pore (MPTP) is a key regulator of mitochondrial homeo- stasis. MPTP contributes to cell death and is crucial in cancer progression. RRM2B’s relation to MPTP is not well known, and the role of RRM2B in cancer progression is controversial. Here, our aim was to study the role of RRM2B in regulating MPTP and the association between RRM2B and clinicopathological manifestations in breast cancer.
    [Show full text]
  • Mitochondrial Hepatopathies Etiology and Genetics the Hepatocyte Mitochondrion Can Function Both As a Cause and As a Target of Liver Injury
    Mitochondrial Hepatopathies Etiology and Genetics The hepatocyte mitochondrion can function both as a cause and as a target of liver injury. Most mitochondrial hepatopathies involve defects in the mitochondrial respiratory chain enzyme complexes (Figure 1). Resultant dysfunction of mitochondria yields deficient oxidative phosphorylation (OXPHOS), increased generation of reactive oxygen species (ROS), accumulation of hepatocyte lipid, impairment of other metabolic pathways and activation of both apoptotic and necrotic pathways of cellular death. Figure 1: Since the mitochondria are under dual control of nuclear DNA and mitochondrial DNA (mtDNA), mutations in genes of both classes have been associated with inherited mitochondrial myopathies, encephalopathies, and hepatopathies. Autosomal nuclear gene defects affect a variety of mitochondrial processes such as protein assembly, mtDNA synthesis and replication (e.g., deoxyguanosine kinase [dGUOK]) and DNA polymerase gamma [POLG]), and transport of nucleotides or metals. MPV17 (function unknown) and RRM2B (encoding the cytosolic p53-inducible ribonucleotide reductase small subunit) are two genes recently identified as also causing mtDNA depletion syndrome and liver failure, as has TWINKLE, TRMU, and SUCLG1. Most children with mitochondrial hepatopathies have identified or presumed mutations in these nuclear genes, rather than mtDNA genes. A classification of primary mitochondrial hepatopathies involving energy metabolism is presented in Table 1. Drug interference with mtDNA replication is now recognized as a cause of acquired mtDNA depletion that can result in liver failure, lactic acidosis, and myopathy in human immunodeficiency virus infected patients and, previously, in hepatitis B virus patients treated with nucleoside reverse transcriptase inhibitors. Current estimates suggest a minimum prevalence of all mitochondrial diseases of 11.5 cases per 100,000 individuals, or 1 in 8500 of the general population.
    [Show full text]
  • Arsenic Hexoxide Has Differential Effects on Cell Proliferation And
    www.nature.com/scientificreports OPEN Arsenic hexoxide has diferential efects on cell proliferation and genome‑wide gene expression in human primary mammary epithelial and MCF7 cells Donguk Kim1,7, Na Yeon Park2,7, Keunsoo Kang3, Stuart K. Calderwood4, Dong‑Hyung Cho2, Ill Ju Bae5* & Heeyoun Bunch1,6* Arsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer efects in humans. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA‑sequencing and bioinformatics analyses, diferentially expressed genes in signifcantly afected biological pathways in these cell types were validated by real‑time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly diferential efects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without afecting the growth of HUMEC in a dose‑dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are signifcantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6‑treated MCF7 cells.
    [Show full text]
  • A Ferrous-Triapine Complex Mediates Formation of Reactive Oxygen Species That Inactivate Human Ribonucleotide Reductase
    586 A Ferrous-triapine complex mediates formation of reactive oxygen species that inactivate human ribonucleotide reductase Jimin Shao,1,2 Bingsen Zhou,1 Angel J. Di Bilio,3 cytotoxicity assays. These results indicate that Triapine- Lijun Zhu,1,2 Tieli Wang,1 Christina Qi,1 induced inhibition of ribonucleotide reductase is caused by Jennifer Shih,1 and Yun Yen1 ROS. We suggest that ROS may ultimately be responsible for the pharmacologic effects of Triapine in vivo. [Mol 1Department of Medical Oncology and Therapeutic Research, Cancer Ther 2006;5(3):586–92] City of Hope National Medical Center, Duarte, California; 2Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of Introduction 3 China; Department of Chemistry, California Institute of Ribonucleotide reductases catalyze the reduction of Technology, Pasadena, California ribonucleotides to deoxyribonucleotides, which are re- quired for DNA replication and repair (1, 2). Human Abstract ribonucleotide reductase is a protein tetramer featuring Ribonucleotide reductase plays a central role in cell two identical large (hRRM1) and two identical small proliferation by supplying deoxyribonucleotide precursors (hRRM2 or p53R2) subunits. hRRM1 harbors the sub- for DNA synthesis and repair. The holoenzyme is a protein strate-catalytic and allosteric regulation sites. The small tetramer that features two large (hRRM1) and two small subunit contains an oxygen-linked diferric cluster and a (hRRM2 or p53R2) subunits. The small subunit contains a stable tyrosyl radical that are needed for function (Fig. 1A; refs. 1–4). p53R2 is a newly identified p53-inducible di-iron cluster/tyrosyl radical cofactor that is essential for f enzyme activity.
    [Show full text]
  • TRACE: Tennessee Research and Creative Exchange
    University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 8-2009 Structure-Function Studies of the Large Subunit of Ribonucleotide Reductase from Homo sapiens and Saccharomyces cerevisiae James Wesley Fairman University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Biochemistry, Biophysics, and Structural Biology Commons Recommended Citation Fairman, James Wesley, "Structure-Function Studies of the Large Subunit of Ribonucleotide Reductase from Homo sapiens and Saccharomyces cerevisiae. " PhD diss., University of Tennessee, 2009. https://trace.tennessee.edu/utk_graddiss/49 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by James Wesley Fairman entitled "Structure- Function Studies of the Large Subunit of Ribonucleotide Reductase from Homo sapiens and Saccharomyces cerevisiae." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Biochemistry and Cellular and Molecular Biology. Chris G. Dealwis,
    [Show full text]
  • RRM2B-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Renal Tubulopathy
    RRM2B-related mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy Description RRM2B-related mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy (RRM2B-MDS) is a severe condition that begins in infancy and affects multiple body systems. It is associated with brain dysfunction combined with muscle weakness (encephalomyopathy). Many affected individuals also have a kidney dysfunction known as renal tubulopathy. Infants with RRM2B-MDS have weak muscle tone (hypotonia) and a failure to grow or gain weight at the expected rate (failure to thrive). Many have a smaller-than-normal head size (microcephaly). Due to muscle weakness, affected infants typically have difficulty controlling head movement and may have delayed development of other motor skills, such as rolling over or sitting. Weakness of the muscles used for breathing leads to serious breathing difficulties and can result in life-threatening respiratory failure. Most affected infants have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can also be life-threatening. Some individuals with RRM2B-MDS have a digestion problem known as gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently. This disorder may lead to swallowing difficulties, vomiting, and diarrhea and can contribute to a failure to thrive. Less commonly, individuals with RRM2B-MDS develop seizures or hearing loss that is caused by nerve damage in the inner ear (sensorineural hearing loss). Because of the severity of the signs and symptoms, people with RRM2B-MDS usually live only into early childhood. Frequency RRM2B-MDS is a rare condition; the exact prevalence is unknown.
    [Show full text]
  • Genomic Evidence of Reactive Oxygen Species Elevation in Papillary Thyroid Carcinoma with Hashimoto Thyroiditis
    Endocrine Journal 2015, 62 (10), 857-877 Original Genomic evidence of reactive oxygen species elevation in papillary thyroid carcinoma with Hashimoto thyroiditis Jin Wook Yi1), 2), Ji Yeon Park1), Ji-Youn Sung1), 3), Sang Hyuk Kwak1), 4), Jihan Yu1), 5), Ji Hyun Chang1), 6), Jo-Heon Kim1), 7), Sang Yun Ha1), 8), Eun Kyung Paik1), 9), Woo Seung Lee1), Su-Jin Kim2), Kyu Eun Lee2)* and Ju Han Kim1)* 1) Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Korea 2) Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea 3) Department of Pathology, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Korea 4) Kwak Clinic, Okcheon-gun, Chungbuk, Korea 5) Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, Uijeongbu, Korea 6) Department of Radiation Oncology, Seoul St. Mary’s Hospital, Seoul, Korea 7) Department of Pathology, Chonnam National University Hospital, Kwang-Ju, Korea 8) Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 9) Department of Radiation Oncology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea Abstract. Elevated levels of reactive oxygen species (ROS) have been proposed as a risk factor for the development of papillary thyroid carcinoma (PTC) in patients with Hashimoto thyroiditis (HT). However, it has yet to be proven that the total levels of ROS are sufficiently increased to contribute to carcinogenesis. We hypothesized that if the ROS levels were increased in HT, ROS-related genes would also be differently expressed in PTC with HT. To find differentially expressed genes (DEGs) we analyzed data from the Cancer Genomic Atlas, gene expression data from RNA sequencing: 33 from normal thyroid tissue, 232 from PTC without HT, and 60 from PTC with HT.
    [Show full text]
  • A Mathematical Model of Iron Import and Trafficking in Wild-Type and Mrs3/4ΔΔ Yeast Cells Joshua D
    Wofford and Lindahl BMC Systems Biology (2019) 13:23 https://doi.org/10.1186/s12918-019-0702-2 RESEARCH ARTICLE Open Access A mathematical model of iron import and trafficking in wild-type and Mrs3/4ΔΔ yeast cells Joshua D. Wofford1 and Paul A. Lindahl1,2* Abstract Background: Iron plays crucial roles in the metabolism of eukaryotic cells. Much iron is trafficked into mitochondria where it is used for iron-sulfur cluster assembly and heme biosynthesis. A yeast strain in which Mrs3/4, the high- affinity iron importers on the mitochondrial inner membrane, are deleted exhibits a slow-growth phenotype when grown under iron-deficient conditions. However, these cells grow at WT rates under iron-sufficient conditions. The object of this study was to develop a mathematical model that could explain this recovery on the molecular level. Results: A multi-tiered strategy was used to solve an ordinary-differential-equations-based mathematical model of iron import, trafficking, and regulation in growing Saccharomyces cerevisiae cells. At the simplest level of modeling, all iron in the cell was presumed to be a single species and the cell was considered to be a single homogeneous volume. Optimized parameters associated with the rate of iron import and the rate of dilution due to cell growth were determined. At the next level of complexity, the cell was divided into three regions, including cytosol, mitochondria, and vacuoles, each of which was presumed to contain a single form of iron. Optimized parameters associated with import into these regions were determined. At the final level of complexity, nine components were assumed within the same three cellular regions.
    [Show full text]
  • Ribonucleotide Reductase: In-Vitro S- Glutathionylation of R2 and P53r2 Subunits of Mammalian Class I Ribonucleotide Reductase Protein
    Ribonucleotide Reductase: In-vitro S- glutathionylation of R2 and p53R2 Subunits of Mammalian Class I Ribonucleotide Reductase Protein Ajanta Chatterji Amity University Kolkata Arne Holmgren Karolinska Institutet RAJIB SENGUPTA ( [email protected] ) Amity University https://orcid.org/0000-0002-9665-8784 Short Report Keywords: Ribonucleotide reductases (RNR), S-glutathionylation, DNA, antiviral drugs Posted Date: August 24th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-823076/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/10 Abstract Ribonucleotide reductases (RNR) catalyze the rate-limiting step in DNA synthesis during the S-phase of the cell cycle. Its constant activity in order to maintain dNTP homeostasis is a fascinating area of research and an attractive candidate for cancer research and antiviral drugs. Redox modication such as S-glutathionylation of the R1 subunit of mammalian RNR protein has been presumed to regulate the activity of RNR during catalytic cycles. Herein, we report S-glutathionylation of the R2 subunit. We have also shown Grx1 system can eciently deglutathionylate the S-glutathionylated R2 subunit. Additionally, our data also showed for the very rst time S-glutathionylation of mammalian p53R2 subunit that regulates DNA synthesis outside S-phase during DNA damage and repair. Taken together, these data will open new avenues for future research relating to exact physiological signicance, target thiols, and/or overall RNR activity due to S-glutathionylation of R2 and p53R2 subunits and provide valuable insights for effective treatment regimes. 1. Introduction: Ribonucleotide reductase (RNR) is an essential enzyme that catalyzes the rate-limiting step in the conversion of ribonucleotides (rNTP) to concomitant deoxyribonucleotides (dNTP) during de novo DNA synthesis [1, 2].
    [Show full text]
  • Discovery of Industrially Relevant Oxidoreductases
    DISCOVERY OF INDUSTRIALLY RELEVANT OXIDOREDUCTASES Thesis Submitted for the Degree of Master of Science by Kezia Rajan, B.Sc. Supervised by Dr. Ciaran Fagan School of Biotechnology Dublin City University Ireland Dr. Andrew Dowd MBio Monaghan Ireland January 2020 Declaration I hereby certify that this material, which I now submit for assessment on the programme of study leading to the award of Master of Science, is entirely my own work, and that I have exercised reasonable care to ensure that the work is original, and does not to the best of my knowledge breach any law of copyright, and has not been taken from the work of others save and to the extent that such work has been cited and acknowledged within the text of my work. Signed: ID No.: 17212904 Kezia Rajan Date: 03rd January 2020 Acknowledgements I would like to thank the following: God, for sending me angels in the form of wonderful human beings over the last two years to help me with any- and everything related to my project. Dr. Ciaran Fagan and Dr. Andrew Dowd, for guiding me and always going out of their way to help me. Thank you for your patience, your advice, and thank you for constantly believing in me. I feel extremely privileged to have gotten an opportunity to work alongside both of you. Everything I’ve learnt and the passion for research that this project has sparked in me, I owe it all to you both. Although I know that words will never be enough to express my gratitude, I still want to say a huge thank you from the bottom of my heart.
    [Show full text]