DOCSLIB.ORG

Synthesis of New Xanthene Derivatives

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Synthesis of New Xanthene Derivatives Synthesis of New Xanthene Derivatives Dissertation Zur Erlangung des Grades “Doktor der Naturwissenschaften” im Promotionsfach Pharmazie am Fachbereich Chemie, Pharmazie und Geowissenschaften der Johannes Gutenberg-Universität in Mainz Michaela Kotásková geboren in Skalica, Slowakei Mainz, 2012 II Vom Fachbereich Chemie, Pharmazie und Geowissenschaften der Johannes Gutenberg- Universität Mainz als Dissertation angenommen. D77 (Dissertation Johannes Gutenberg- Universität Mainz) III IV Hiermit erkläre ich eidesstattlich, dass ich die vorliegende Arbeit selbständig und unter Verwendung der angegebenen Quellen und Hilfsmittel angefertigt habe, sowie wörtliche oder inhaltliche Zitate als solche gekennzeichnet habe. Ich habe keinen anderen Promotionsversuch unternommen. Mainz, Mai 2012 Michaela Kotásková V VI VII VIII Michaela Kotásková, Magister (Corresponding to M. Sc.) Summary Title: Synthesis of New Xanthene Derivatives Xanthene dyes, including fluorescein, are a well-known class of fluorescent dyes, which have widespread applications in natural sciences. The synthesis of xanthene derivatives via acid catalyzed condensation of substituted phenols with phthalic anhydride, to afford the asymmetric derivatives, is well established. The high temperature, harsh reaction conditions and often low yields make this method less convenient. The synthesis of xanthene dyes by direct modification of the fluorophore moiety is a great option to circumvent the above mentioned drawbacks. Our new synthetic strategy for the preparation of novel asymmetric xanthene dyes via direct conversion of hydroxyl groups on 3'- and 6'-positions into leaving groups by mesylation is reported. It was discovered that 3',6'-di-mesylated fluorescein underwent a nucleophilic aromatic substitution with sulfur nucleophiles and afforded new asymmetric xanthene sulfides. The impact of substituents possessing an electron-withdrawing character such as chlorines and bromines was investigated with the aim to improve the aromatic substitution on the electron-rich fluorescein structure. It was observed that the incorporation of these groups did not considerably affect the substitution reaction and the yields were comparable with the unsubstituted fluorescein. This strategy provided novel fluorescent probes with the linker suitable to further modifications. The modifications of the linker delivered fluorescein derivatives that could be used as fluorescent labels in peptides, oligonucleotides and for cell imaging. The hydroxyl group on the linker was modified to achieve potent bioconjugate functionality such as azide. The new fluorescent azides were obtained in a 4-step synthesis, namely 2-(6-(2- azidoethylthio)-3-oxo-3H-xanthen-9-yl)benzoic acid with an overall yield of 13%, its 2',7'- dichloro derivative with an overall yield of 10% and its 2',4',5'-tribromo derivative with an overall yield of 1%, respectively. An asymmetric xanthene sulfide with an amino functionality placed on the aliphatic linker, namely 2-(6-((2-aminoethyl)thio)-3-oxo-3H-xanthen-9-yl)benzoic acid, was obtained in a 3- step synthesis with an overall yield of 33%. The impact of the substitution with sulfur nucleophiles on the 6'-position of the xanthene moiety on its fluorescent characteristics was investigated. In comparison with fluorescein new asymmetric xanthene sulfides afforded lower extinction coefficients and fluorescent quantum yields. On the other hand, the substitution with a sulfur nucleophile significantly improved the photostability of xanthene dyes. It was shown that after 10 hours of continuous excitation, the asymmetric sulfur-containing xanthene fluorophores exhibited 58-94% of their initial fluorescent intensities. This observation suggested that the novel dyes were 1-2 orders of magnitude more stable than fluorescein. The azido-modified xanthenes were “clicked” via Cu(I)-catalyzed azide-alkyne cycloaddition with an oligonucleotide, which contained the terminal alkyne residue. IX X Michaela Kotásková, Magister (Corresponding to M. Sc.) Zusammenfassung Titel: Synthesis of New Xanthene Derivatives Xanthen Farbstoffe, insbesondere Fluoreszein, sind sehr bekannt als Fluoreszenzfarbstoffe und haben eine Vielzahl von Anwendungen. Die Synthese von Xanthen Derivaten findet via eine säurekatalysierte Kondensation substituierter Phenole mit Phthalsäureanhydrid statt. Die hohen Temperaturen und extremen Bedingungen, unter denen diese Reaktion abläuft, führen oft zu schlechten Ausbeuten. Daher bietet eine direkte Modifikation der Fluorophore eine hervorragende Alternative. In dieser Doktorarbeit konnten neue Synthesewege zur Herstellung neuer asymmetrischer Xanthen Farbstoffe mittels direkter Überführung der Hydroxyl Gruppen an 3'- und 6'- Position in Abgangsgruppen durch Mesylierung eingeführt werden. Des Weiteren konnte gezeigt werden, dass 3',6'-di-mesyliertes Fluoreszein eine nukleophile aromatischen Substitution mit Schwefel Nukleophilen eingeht, wobei neue asymmetrische Xanthen Sulfide erhalten wurden. Inwieweit elektronenziehende Substituenten, wie zum Beispiel Chlorid oder Bromid, die aromatische Substitution beeinflussen, wurde im Rahmen dieser Arbeit eingehend untersucht. Dabei wurde beobachtet, dass die Einführung dieser Gruppen keine signifikante Auswirkung auf die Substitutionsreaktion hat und die Ausbeuten vergleichbar waren mit der Reaktion an unsubstituiertem Fluoreszein. Um weitere Modifikationen einzuführen, wurden die Schwefel Nukleophile mit einem aliphatischen Linker verknüpft. Über diesen Linker wurden so Hydroxylgruppen eingeführt, die wiederum mit gängigen Biokonjugaten wie z.B. Aziden modifiziert wurden. Die Synthese eines neuen fluoreszenten Azids, 2-(6-(2-Azidoethylthio)-3-oxo-3H-xanthen-9- yl) Benzoesäure, konnte in nur 4 Stufen mit einer Gesamtausbeute von 13% realisiert werden. Auf dem gleichen Weg konnten das 2',7'-Dichloro- und 2',4',5'-Tribromo-Derivat in Ausbeuten von 10% und 1% gewonnen werden. In lediglich drei Stufen wurde ein asymmetrisches Xanthen Sulfid, welches als funktionelle Gruppe ein Amin am aliphatischen Linker trug, mit einer Gesamtausbeute von 33% synthetisiert: 2-(6-((2-Aminoethyl)thio)-3-oxo-3H-xanthen-9-yl) Benzoesäure. Der Einfluss der Substitution mit Schwefelnukleophilen in der 6'-Position von Xanthen auf das Fluoreszenzverhalten wurde eingehend untersucht und es konnte gezeigt werden, dass asymmetrische Xanthene, die Sulfide als funktionelle Gruppen tragen, einen niedrigeren Extinktionskoeffizent und eine niedrigere Quantenausbeute aufweisen als Fluoreszein selbst. Allerdings wiesen diese neuen modifizierten Xanthene eine erheblich bessere Photostabilität als herkömmliches Fluoreszein auf. Selbst nach kontinuierlicher Anregung über 10 Stunden waren noch 58-94% der ursprünglichen Floureszenz vorhanden. Diese Beobachtung führt zu der Fesstellung, dass die Stabilität dieser neuen Farbstoffe 1-2 Größenordnungen höher liegt als die des Fluoreszeins. Weiterhin konnten die mit einem Azid modifizierten Xanthene in einer „Click“ Reaktion durch eine Kupfer(I) katalysierte Azid-Alkin Cycloaddition mit einem Oligonukleotid umgesetzt werden, welches einen terminalen Alkinrest enthielt. XI XII ____________________________________________________________ Table of Contents Table of Contents 1 Introduction ........................................................................................................................ 1 1.1 Phenomena of Fluorescence ....................................................................................... 1 1.2 Classes of fluorescent Dyes ......................................................................................... 4 1.3 Xanthene Dyes ............................................................................................................. 6 1.3.1 Fluorescein .............................................................................................................. 7 1.3.2 Tokyo Green Dyes and their Derivatives ............................................................. 12 1.3.3 Rhodols and Rhodamines ..................................................................................... 13 1.4 Leuco Dyes ................................................................................................................. 17 1.5 Caged fluorescent Dyes ............................................................................................. 21 2 Objectives and Scope ....................................................................................................... 26 3 Results and Discussions ................................................................................................... 27 3.1 Overview .................................................................................................................... 27 3.2 Synthesis of Sulfonate Esters of Fluoresceins ......................................................... 27 3.2.1 Di-sulfonylation of Fluorescein ............................................................................ 27 3.2.2 Mono-sulfonylation of Fluorescein ...................................................................... 29 3.2.3 Sulfonylation of Derivatives of Fluorescein ......................................................... 30 3.3 Sulfonation of Fluorescein ........................................................................................ 32 3.3.1 Di-sulfonation of Fluorescein on 4',5'-Positions ................................................... 32 3.3.2 Mono-sulfonation of Fluorescein on 4'- or 5'-Position ........................................
Load more

Recommended publications
  • The Synthesis of Fluorescent 3, 6-Dihydroxyxanthones
    University of Wisconsin Milwaukee UWM Digital Commons Theses and Dissertations August 2016 The yS nthesis of Fluorescent 3, 6-dihydroxyxanthones: A Route to Substituted Fluoresceins Surajudeen Omolabake University of Wisconsin-Milwaukee Follow this and additional works at: https://dc.uwm.edu/etd Part of the Chemistry Commons Recommended Citation Omolabake, Surajudeen, "The yS nthesis of Fluorescent 3, 6-dihydroxyxanthones: A Route to Substituted Fluoresceins" (2016). Theses and Dissertations. 1299. https://dc.uwm.edu/etd/1299 This Thesis is brought to you for free and open access by UWM Digital Commons. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of UWM Digital Commons. For more information, please contact [email protected]. THE SYNTHESIS OF FLUORESCENT 3, 6-DIHYDROXYXANTHONES: A ROUTE TO SUBSTITUTED FLUORESCEINS by Surajudeen Omolabake A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science In Chemistry at University of Wisconsin-Milwaukee August 2016 ABSTRACT THE SYNTHESIS OF FLUORESCENT 3, 6-DIHYDROXYXANTHONES: A ROUTE TO SUBSTITUTED FLUORESCEIN by Surajudeen Omolabake University of Wisconsin-Milwaukee, 2016 Under the Supervision of Professor Alan W Schwabacher Xanthones belong to the family of compounds of the dibenzo-γ-pyrone framework. Naturally occurring xanthones have been reported to show a wide range of biological and medicinal activities including antifungal,19 antimalarial,20 antimicrobial,21 antiparasitic,22 anticancer,23 and inhibition of HIV activity in cells.24 Xanthones have also been used as a turn on fluorescent probe for metal ions,32 including use as pH indicators, metal ion sensors, in molecular biology, medicinal chemistry and in the construction of other dyes.
    [Show full text]
  • Benzyl-L-Threitol
    A Publication of Reliable Methods for the Preparation of Organic Compounds Working with Hazardous Chemicals The procedures in Organic Syntheses are intended for use only by persons with proper training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011; the full text can be accessed free of charge at http://www.nap.edu/catalog.php?record_id=12654). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices. In some articles in Organic Syntheses, chemical-specific hazards are highlighted in red “Caution Notes” within a procedure. It is important to recognize that the absence of a caution note does not imply that no significant hazards are associated with the chemicals involved in that procedure. Prior to performing a reaction, a thorough risk assessment should be carried out that includes a review of the potential hazards associated with each chemical and experimental operation on the scale that is planned for the procedure. Guidelines for carrying out a risk assessment and for analyzing the hazards associated with chemicals can be found in Chapter 4 of Prudent Practices. The procedures described in Organic Syntheses are provided as published and are conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
    [Show full text]
  • Use of Immunofluorescence and Viability Stains in Quality Control1
    Use of Immunofluorescence and Viability Stains in Quality Control1 M. J. CHILVER, J. HARRISON, and T. J. B. WEBB, Process Research Department, Allied Breweries Production Limited, Burton-on- Trent, Staffordshire, England DEM IBZ ABSTRACT has been the failure to differentiate live and dead cells. We have been studying the combined use of immunofluorescent and Immunofluorescence has been evaluated as a rapid quality control viability stains so that live and dead, culture and wild yeasts, can be technique for the detection of low levels of wild yeasts in culture yeast or differentiated on the same slide field. This paper details the results other brewery samples. Antisera have been prepared against antigenic groups A to F, pooled and absorbed with culture yeast. Using the indirect obtained when yeast samples are examined alternately with FITC- staining method and fluorescein isothiocyanate or rhodamine as exciting blue light wavelengths and rhodamine-exciting green light fluorochrome, levels as low as 10 wild yeasts per million cells can be detected and when incident fluorescent light is combined with transmitted in three hours. Combined immunofluorescence and viability staining allows white light to illuminate the specimen. the differentiation of live and dead, culture and wild yeast cells, on the same The potential use of fluorescein diacetate as a viability stain has slide by alternating the light sources. The preferred method uses fluorescein been established. Initial work by Rotman and Papermaster (22) isothiocyanate, excited by incident blue light, for wild yeast detection, was developed by Paton and Jones (21) and its use in brewery combined with methylene blue, viewed by transmitted light, for viability quality control has been described by Molzahn and Portno (19).
    [Show full text]
  • DAPI (4',6-Diamidino-2-Phenylindole, Dihydrochloride) for Nucleic Acid Staining
    DAPI (4',6-Diamidino-2-Phenylindole, Dihydrochloride) for nucleic acid staining Catalog number: AR1176-10 Boster’s DAPI solution is a fluorescent dye with higher efficiency for immunofluorescence microscopy. This package insert must be read in its entirety before using this product. For research use only. Not for use in diagnostic procedures. BOSTER BIOLOGICAL TECHNOLOGY 3942 B Valley Ave, Pleasanton, CA 94566 Phone: 888-466-3604 Fax: 925-215-2184 Email:[email protected] Web: www.bosterbio.com DAPI (4',6-Diamidino-2-Phenylindole, Dihydrochloride) for nucleic acid staining Catalog Number: AR1176-10 Product Overview Material DAPI dihydrochloride (MW = 350.3) Form Liquid Size 10 mL(100 assys) Concentration 1μg/ml 8 mM sodium phosphate, 2 mM potassium phosphate, 140 mM sodium chloride, 10 Buffer mM potassium chloride; pH 7.4. Storage Upon receipt store at -20°C, protect from light. Stability When stored as directed, product should be stable for one year. Molecular formula C16H15N5 • 2 HCL Excitation: DAPI 340nm Emission: DAPI 488nm Excitation: DAPI-DNA complexes 360nm Emission: DAPI-DNA complexes 460nm Thermofisher (Product No. 62247); Thermofisher (Product No. 62248); Millipore Equivalent Sigma (Product No. D9542) BOSTER BIOLOGICAL TECHNOLOGY 3942 B Valley Ave, Pleasanton, CA 94566 Phone: 888-466-3604 Fax: 925-215-2184 Email:[email protected] Web: www.bosterbio.com Notes: Type of DAPI Molecular formula Molecular weight Catalog Number DAPI dihydrochloride C16H15N5 • 2 HCL 350.25 AR1176-10 DAPI dilactate C16H15N5 • 2 C3H6O3 457.48 N/A Introduction DAPI (4',6-diamidino-2-phenylindole) is a fluorescent dye which can bind DNA strands robustly, the fluorescence being detected by fluorescence microscope.
    [Show full text]
  • Fluorescein) Injection 10% 2
    NEW ZEALAND DATA SHEET 1. PRODUCT NAME FLUORESCITETM (fluorescein) Injection 10% 2. QUALITATIVE AND QUANTITATIVE COMPOSITION FluoresciteTM injection 10% contains 100 mg/mL fluorescein (equivalent to 113.2 mg/mL fluorescein sodium). 3. PHARMACEUTICAL FORM Solution, sterile pyrogen-free injection. Unpreserved with a pH of 8.0 to 9.8. 4. CLINICAL PARTICULARS 4.1. Therapeutic indications Indicated in diagnostic fluorescein angiography or angioscopy of the fundus and of the iris vasculature. 4.2. Dose and method of administration The usual adult dose is the contents of one FluoresciteTM injection 10% vial (5 mL of 10% solution) via intravenous administration. For children, the dose is calculated on the basis of 8 mg/kg of body weight. Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration. Do not mix or dilute with other solutions or drugs. Flush intravenous cannulae before and after drugs are injected to avoid physical incompatibility reactions. Product is for single use in one patient only. Discard any residue. Contains no antimicrobial agent. Inject the contents of the vial rapidly into the antecubital vein after taking precautions to avoid extravasation. A syringe filled with FluoresciteTM injection 10% is attached to transparent tubing and a 23 gauge butterfly needle for injection. Insert the needle and draw the patient's blood to the hub of the syringe so that a small air bubble separates the patient's blood in the tubing from the FluoresciteTM injection 10%. With the room lights on, slowly inject the blood back into the vein while watching the skin over the needle tip.
    [Show full text]
  • Cell Viability Measurement
    Cell Viability Measurement • Viability is a measure of the metabolic state of a cell population which is indicative of the potential for growth • Most common method: membrane integrity – Trypan blue exclusion: leaky membrane allows blue dye to get into cells – Good: capable for manual microscopy – Issues: operator dependent • Cellometer solution: use software algorism – Reduce operator dependency – Reduce calculation error – Speed up counting – Better management of data Nexcelom.com Online Resources [email protected] | 978.327.5340 Cellometer® Simply Counted Trypan Blue Viability for Cell Lines: Exclusion Assay H9 LCL M19 Raw K562 T cell Cellometer has been used for more than 300 cell lines Nexcelom.com Online Resources [email protected] | 978.327.5340 Cellometer® Simply Counted Fluorescence Based Cell Viability Methods • Membrane integrity – DNA binding dye with permeability dependency – AO (acridine Orange): permeable for live and dead cells – PI (propidium iodide), EB (Ethidium bromide), 7-AAD: not permeable for live cells – Others: SYTO ® 13, SYTO 24 ®, SYTO® 14 • Enzymatic activity – Non fluorescent esterases diffuse into cells – Live cells with strong enzymatic activity produce fluorescent products – Live cells retain fluorescent products – Examples: • Calcein-AM to calcein • Fluorescein diacetate (FDA)to fluorescein • Simultaneous detection of both live and dead cell populations for cell lines – Combination of the above with duo-fluorescence detection for each cell sample Nexcelom.com Online Resources [email protected] | 978.327.5340 Cellometer® Simply Counted References [1] S. A. Altman, L. Randers, and G. Rao, "Comparison of Trypan Blue-Dye Exclusion and Fluorometric Assays for Mammalian-Cell Viability Determinations," Biotechnology Progress, vol. 9, pp. 671-674, Nov-Dec 1993.
    [Show full text]
  • Bio-Based Chemicals from Renewable Biomass for Integrated Biorefineries
    energies Review Bio-Based Chemicals from Renewable Biomass for Integrated Biorefineries Kirtika Kohli 1 , Ravindra Prajapati 2 and Brajendra K. Sharma 1,* 1 Prairie Research Institute—Illinois Sustainable Technology Center, University of Illinois, Urbana Champaign, IL 61820, USA; [email protected] 2 Conversions & Catalysis Division, CSIR-Indian Institute of Petroleum, Dehradun, Uttarakhand 248005, India; [email protected] * Correspondence: [email protected] Received: 10 December 2018; Accepted: 4 January 2019; Published: 13 January 2019 Abstract: The production of chemicals from biomass, a renewable feedstock, is highly desirable in replacing petrochemicals to make biorefineries more economical. The best approach to compete with fossil-based refineries is the upgradation of biomass in integrated biorefineries. The integrated biorefineries employed various biomass feedstocks and conversion technologies to produce biofuels and bio-based chemicals. Bio-based chemicals can help to replace a large fraction of industrial chemicals and materials from fossil resources. Biomass-derived chemicals, such as 5-hydroxymethylfurfural (5-HMF), levulinic acid, furfurals, sugar alcohols, lactic acid, succinic acid, and phenols, are considered platform chemicals. These platform chemicals can be further used for the production of a variety of important chemicals on an industrial scale. However, current industrial production relies on relatively old and inefficient strategies and low production yields, which have decreased their competitiveness with fossil-based alternatives. The aim of the presented review is to provide a survey of past and current strategies used to achieve a sustainable conversion of biomass to platform chemicals. This review provides an overview of the chemicals obtained, based on the major components of lignocellulosic biomass, sugars, and lignin.
    [Show full text]
  • Sugar Alcohols a Sugar Alcohol Is a Kind of Alcohol Prepared from Sugars
    Sweeteners, Good, Bad, or Something even Worse. (Part 8) These are Low calorie sweeteners - not non-calorie sweeteners Sugar Alcohols A sugar alcohol is a kind of alcohol prepared from sugars. These organic compounds are a class of polyols, also called polyhydric alcohol, polyalcohol, or glycitol. They are white, water-soluble solids that occur naturally and are used widely in the food industry as thickeners and sweeteners. In commercial foodstuffs, sugar alcohols are commonly used in place of table sugar (sucrose), often in combination with high intensity artificial sweeteners to counter the low sweetness of the sugar alcohols. Unlike sugars, sugar alcohols do not contribute to the formation of tooth cavities. Common Sugar Alcohols Arabitol, Erythritol, Ethylene glycol, Fucitol, Galactitol, Glycerol, Hydrogenated Starch – Hydrolysate (HSH), Iditol, Inositol, Isomalt, Lactitol, Maltitol, Maltotetraitol, Maltotriitol, Mannitol, Methanol, Polyglycitol, Polydextrose, Ribitol, Sorbitol, Threitol, Volemitol, Xylitol, Of these, xylitol is perhaps the most popular due to its similarity to sucrose in visual appearance and sweetness. Sugar alcohols do not contribute to tooth decay. However, consumption of sugar alcohols does affect blood sugar levels, although less than that of "regular" sugar (sucrose). Sugar alcohols may also cause bloating and diarrhea when consumed in excessive amounts. Erythritol Also labeled as: Sugar alcohol Zerose ZSweet Erythritol is a sugar alcohol (or polyol) that has been approved for use as a food additive in the United States and throughout much of the world. It was discovered in 1848 by British chemist John Stenhouse. It occurs naturally in some fruits and fermented foods. At the industrial level, it is produced from glucose by fermentation with a yeast, Moniliella pollinis.
    [Show full text]
  • Analysis of Dye Mixtures Thin-Layer Chromatography SCIENTIFIC
    Analysis of Dye Mixtures Thin-Layer Chromatography SCIENTIFIC Introduction Thin-layer chromatography (TLC) is a valuable analytical technique for separating and analyzing organic compounds. In dye analysis, for example, TLC is used to identify dyes in fabrics or fibers (forensics) and to determine the composition of natural dyes in plants and animals. In this demonstration, thin layer chromatography will be used to separate mixtures of dyes. Concepts • Chromatography • Physical properties Materials Authentic dye samples (eosin Y, fluorescein, methylene blue, and safranin), 0.25 g each Chromatography solvent (acetone), 80 mL Thin layer chromatography sheet (silica gel on plastic backing), 20 cm × 20 cm Beakers, 100-mL, 4 Graduated cylinder, 50-mL Beakers, 400-mL, 4 Metric ruler Beral type pipets, 4 Pencil Microtip pipets, 16 Reaction plate, 24-well Ethyl alcohol, 50 mL Scissors Filter paper Watch glasses, large, or Petri dish covers Safety Precautions Acetone and ethyl alcohol are flammable organic solvents and a dangerous fire risk—keep away from flames, sparks, and other sources of ignition. Work with acetone in a well-ventilated lab only. Wear chemical splash goggles, chemical-resistant gloves, and chemical- resistant apron. Please review current Material Safety Data Sheets for additional safety, handling, and disposal information. Preparation 1. Prepare 0.5% solutions of each dye—dissolve 0.25 g of the dye in 50 mL of water 5 cm (fluorescein, methylene blue, and safranin) or ethyl alcohol (eosin Y). 2. Add about 1 mL of each dye solution to separate wells in a 24-well reaction plate. In other wells, combine 0.5 mL of two or more dyes to prepare dye mixtures.
    [Show full text]
  • The Generation and Reactivity of Organozinc Carbenoids
    The Generation and Reactivity of Organozinc Carbenoids A Thesis Presented by Caroline Joy Nutley In Partial Fulfilment of the Requirements for the Award of the Degree DOCTOR OF PHILOSOPHY of the UNIVERSITY OF LONDON Christopher Ingold Laboratories Department of Chemistry University College London London WCIH OAJ September 1995 ProQuest Number: 10016731 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10016731 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Through doubting we come to questioning and through questioning we come to the truth. Peter Abelard, Paris, 1122 Abstract This thesis concerns an investigation into the generation and reactivity of organozinc carbenoids, from both a practical and mechanistic standpoint, using the reductive deoxygenation of carbonyl compounds with zinc and a silicon electrophile. The first introductory chapter is a review of organozinc carbenoids in synthesis. The second chapter opens with an overview of the development of the reductive deoxygenation of carbonyl compounds with zinc and a silicon electrophile since its inception in 1973. The factors influencing the generation of the zinc carbenoid are then investigated using a control reaction, and discussed.
    [Show full text]
  • A Simple Synthesis of 2-Keto-3-Deoxy-D-Erythro-Hexonic
    A simple synthesis of 2-keto-3-deoxy-D-erythro-hexonic acid isopropyl ester, a key sugar for the bacterial population living under metallic stress Claire Grison, Brice-Loïc Renard, Claude Grison To cite this version: Claire Grison, Brice-Loïc Renard, Claude Grison. A simple synthesis of 2-keto-3-deoxy-D-erythro- hexonic acid isopropyl ester, a key sugar for the bacterial population living under metallic stress. Bioorganic Chemistry, Elsevier, 2014, 52, pp.50-55. 10.1016/j.bioorg.2013.11.006. hal-03149058 HAL Id: hal-03149058 https://hal.archives-ouvertes.fr/hal-03149058 Submitted on 15 Mar 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. A simple synthesis of 2-keto-3-deoxy-D-erythro-hexonic acid isopropyl ester, a key sugar for the bacterial population living under metallic stress ⇑ Claire M. Grison a, , Brice-Loïc Renard b, Claude Grison b a ICMMO UMR 8182, Equipe Synthèse Organique & Méthodologie, Université Paris Sud, Bât. 420, 15 rue Georges Clémenceau, 91405 Orsay cedex, France b CEFE UMR 5175, Campus CNRS, 1919 route de Mende, 34293 Montpellier cedex 5, France abstract 2-Keto-3-deoxy-D-erythro-hexonic acid (KDG) is the key intermediate metabolite of the Entner Doudoroff (ED) pathway.
    [Show full text]
  • Evaluation of Fundamental Characteristics of D-Threitol As
    Evaluation of fundamental characteristics of D-Threitol as phase change material at high temperature On Line Number 790 Hideto Hidaka,1 Masanori Yamazaki,1 Masayoshi Yabe,1 Hiroyuki Kakiuchi,1 Erwin P. Ona,2 Yoshihiro Kojima3 and Hitoki Matsuda2 1 Mitsubishi Chemical Group Science and Technology Research Center, Toho-Cho 1, Yokkaichi, Mie 540-8530, Japan, [email protected] 2 Department of Chemical Engineering, Nagoya University, Furo-Cho, Chikusa, Aichi 464-8630, Japan 3 Research Center for Advanced Waste and Emission Management, Nagoya University, Furo-Cho, Chikusa, Aichi 464-8630, Japan ABSTRACT This study focused on polyalcohols as phase change material, which stores a large amount of latent heat at high temperature. D-Threitol, which is an isomer of meso-Erythritol, was studied to obtain its phase change characteristics by means of DSC analysis and a lab-scale heating and cooling apparatus. Usability of D-Threitol as phase change material was evaluated by comparison with other polyalocohols. It was found that D-Threitol started to melt at around 90 degrees C with a relatively large latent heat of 225 kJ/kg. On the other hand, D-Threitol started solidification when the temperature was cooled between at 40 degrees C and 46 degrees C, indicated by a rapid rise to 89 degrees C in a lab-scale heating and cooling apparatus. It was then considered that D-Threitol was applicable as an environmental-friendly PCM for a hot water supply. KEYWORDS Phase change materials, Polyalcohols, Threitol INTRODUCTION Latent heat storage by Phase Change Materials (PCMs) has the advantage to store and release a relatively large quantity of heat in a constant narrow temperature range during phase change.
    [Show full text]