DOCSLIB.ORG

Polymeric Structures Containing Strained

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Polymeric Structures Containing Strained (19) TZZ _T (11) EP 2 879 665 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9/00 (2006.01) C08K 5/01 (2006.01) 29.03.2017 Bulletin 2017/13 C08G 63/78 (2006.01) C08G 69/16 (2006.01) C08G 69/48 (2006.01) D06M 13/322 (2006.01) (2006.01) (21) Application number: 13824926.3 D01F 6/68 (22) Date of filing: 31.07.2013 (86) International application number: PCT/US2013/052971 (87) International publication number: WO 2014/022535 (06.02.2014 Gazette 2014/06) (54) POLYMERIC STRUCTURES CONTAINING STRAINED CYCLOALKYNE FUNCTIONALITY FOR POST-FABRICATION AZIDEALKYNE CYCLOADDITION FUNCTIONALIZATION POLYMERSTRUKTUREN MIT GESPANNTER CYCLOALKYNFUNKTIONALITÄT FÜR AZIDALKYNCYCLOADDITIONSFUNKTIONALISIERUNG NACH DEM HERSTELLUNGSPROZESS STRUCTURES POLYMÉRIQUES CONTENANT UNE FONCTIONNALITÉ CYCLOALCYNE CONTRAINTE POUR UNE FONCTIONNALISATION PAR CYCLOADDITION D’AZIDE-ALCYNE POST-FABRICATION (84) Designated Contracting States: • EDA GUNGOR ET AL: "One-pot double click AL AT BE BG CH CY CZ DE DK EE ES FI FR GB reactions for the preparation of H-shaped GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO ABCDE-type quintopolymer", JOURNAL OF PL PT RO RS SE SI SK SM TR POLYMER SCIENCE PART A: POLYMER CHEMISTRY, vol. 47, no. 13, 27 May 2009 (30) Priority: 31.07.2012 US 201261677691 P (2009-05-27), pages 3409-3418, XP055246642, US ISSN: 0887-624X, DOI: 10.1002/pola.23421 (43) Date of publication of application: • JIANWEN XU ET AL: "A Versatile Monomer for 10.06.2015 Bulletin 2015/24 Preparing Well-Defined Functional Polycarbonates and Poly(ester-carbonates)", (73) Proprietor: The University of Akron MACROMOLECULES, vol. 44, no. 8, 26 April 2011 Akron, OH 44325 (US) (2011-04-26) , pages 2660-2667, XP055154042, ISSN: 0024-9297, DOI: 10.1021/ma200021m (72) Inventors: • GUO, JUN ET AL.: ’Surface Modification of • BECKER, Matthew L Polymeric Micelles by Strain, Promoted Akron Alkyne.Azide Cycloadditions.’ CHEMISTRY-A Ohio 44224 (US) EUROPEAN JOURNAL vol. 16, no. 45, 2010, • ZHENG, Jukuan pages 13360 - 13366, XP055182158 Akron • SUCH, GEORGINA K. ET AL.: ’Synthesis and Ohio 44314 (US) functionalization of nanoengineered materials using click chemistry.’ PROGRESS IN POLYMER (74) Representative: Tetzner, Michael et al SCIENCE vol. 37, no. 7, 2012, pages 1 - 19, TETZNER & PARTNER mbB XP055182159 Patent- und Rechtsanwälte • MBUA ET AL.: ’STRAIN-PROMOTED Van-Gogh-Strasse 3 ALKYNE-AZIDE CYCLOADDITIONS (SPAAC) 81479 München (DE) REVEAL NEW FEATURES OF GLYCOCONJUGATE BIOSYNTHESIS’ (56) References cited: CHEMBIOCHEM vol. 12, no. 12, 2011, pages 1911 US-A1- 2007 258 889 US-A1- 2012 172 575 - 1920, XP055182162 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 879 665 B1 Printed by Jouve, 75001 PARIS (FR) EP 2 879 665 B1 Description FIELD OF THE INVENTION 5 [0001] The present invention generally resides in the art of biocompatible polymeric structures. More particularly, the present invention relates to biocompatible polymeric structures bearing strained cycloalkyne functionality that survives the process of fabricating the polymeric structures. The cycloalkyne functionality can be beneficially employed in a post- fabrication functionalization through azidealkynecycloaddition. 10 BACKGROUND OF THE INVENTION [0002] For more than two decades, tremendous advances in regenerative medicine have provided hope that materials will offer solutions to organ and tissue shortages that occur worldwide. However, overcoming the remaining challenges will require many additional innovations, especially in materials that possess specific functionality that guide the regen- 15 erative processes. [0003] Nanofibrous scaffolds possessing mechanical properties, porous microstructure, and dimensional similarity to collagen fibers have been used to mimic the natural extracellular matrix (ECM) and are highly relevant for tissue engi- neering in a number of different applications. Polymeric nanofibers have been fabricated into a variety of constructs and scaffolds using melt- or electrospinning processes that are able to control size, morphology and alignment by varying 20 conditions including solvent, concentration, additives and electrode design. [0004] For regenerative medicine applications, the polymeric precursors used to fabricate the nanofiber-based scaf- folds should be both biocompatible and biodegradable. Many biodegradable and biocompatible polymers such as pol- yglycolic acid (PGA), poly(lactic acid) (PLA), poly(lactide-co-glycotide) (PLGA) and poly(ε-caprolactone) (PCL) have been widely investigated as fiber and nanofiber precursor materials. Although these degradable polymers meet several 25 of the basic requirements for tissue engineering applications, bioactive molecules to guide cellular behavior and preserve cell phenotype are required for optimal performance. Specific functionalities that could guide or direct specific biological function need to be incorporated efficiently. There are generally two methods available for biomolecule functionalization: physical adsorption and chemical bonding. While physical adsorption risks the loss of biomolecules over time, chemical conjugation usually requires multi-step processing, and purification both of which often included harsh conditions. 30 [0005] Additionally, the derivitization of nanofibers often requires multiple procedures, including plasma treatment, wet chemical methods, surface graft polymerization, and co-electrospinning of surface active agents with polymers. Each of these modifications is time and resource intensive to optimize and may lead to immune specific reactions and biocompatibility problems. [0006] A new method that enables efficient, orthogonal and bio-system friendly functionalization is preferred. Copper- 35 catalysed click chemistry has been used for efficient functionalization of polymers. However, the side effect of copper ions leads to biocompatibility problems. Recently, the discovery of strain-promoted azide alkyne cycloaddition has pro- vided a robust chemical method for the efficient conjugation of biomolecules. This method has been widely used in bioimaging and bioconjugation. The present invention makes beneficial use of this click chemistry and provides guidance for the creation of fibrous scaffolds and their post fabrication biofunctionalization through such azide alkyne cycloaddition 40 chemistry. [0007] Peptides, growth factors and carbohydrates have each been covalently tethered to the surfaces of synthetic and naturally-derived polymers to stimulate specific cell functions. Concerns about the bioavailability, specificity and activity of the tethered species persist. Recent studies show that the desired biological response can be obtained with the appropriate tether. A number of synthetic degradable polymers, including poly(lactic acid) are presently utilized 45 clinically; but, cellular systems do not readily interact directly with synthetic polymers through normal integrin mediated assemblies. Tyr-Ile-Gly-Ser-Arg (YIGSR), a bio-active peptide derived from laminin, was shown to promote cell attach- ment and laminin receptor binding. Graf, J.; Ogle, R. C.; Robey, F. A.; Sasaki, M.; Martin, G. R.; Yamada, Y.; Kleinman, H. K. Biochemistry 1987, 26, 6896-6900. YIGSR-functionalized matrices have showed similar or superior cellular effects to Ile-Lys-Val-Ala-Val (IKVAV) peptide, a more commonly studied laminin-derived peptide and laminin-coated matrices. 50 The art could benefit from incorporating YIGSR into nanofibers matrices to promote the directed differentiation of em- bryonic stem cells into neurons. However, the precise, regiospecific functionalization of degradable polymers with bio- logical motifs capable of directing cellular function has been so complicated with regard to solvents, catalysts, residuals and processing methods, that they have been deemed translationally irrelevant. The recent evolution of click chemistry as a method to functionalize polymers and materials has enabled the derivatization of both natural and synthetic polymers 55 in ways that were not previously possible. [0008] Jun Guo et al.: "Surface Modification of Polymeric Micelles by Strain.Promoted Alkyne-Azide Cycloadditions", Chemistra - A European Journal, 16 (45), 2010, 13360-13366 describes a method of forming a biocompatible polymer, the method comprising the formation of poly(ethylene oxide) and poly(ε-caprolactone) functionalized with strained cy- 2 EP 2 879 665 B1 cloalkyne, wherein the strained cycloalkyne remains on the biocompatible polymer, which forms micelles that are then modified with azido-containing probes. [0009] Ngalle Eric Mbua et al.: "Strain-Promoted Alkyne-Azide Cycloadditions (SPAAC) Reveal New Features of Glycoconjugate Biosynthesis", ChemBioChem, 12 (12), 2011, 1912-1921 discloses a method for preparing 4-dibenzo- 5 cyclooctynol. SUMMARY OF THE INVENTION [0010] A first embodiment of this invention provides a method of creating biocompatible polymeric structures comprising 10 the steps of: preparing a biocompatible polymer including a strained cycloalkyne end group by polymerizing monomers through a ring-opening polymerization employing a ROP initiator having a strained cycloalkyne;
Load more

Recommended publications
  • Stabilization of Anti-Aromatic and Strained Five-Membered Rings with A
    ARTICLES PUBLISHED ONLINE: 23 JUNE 2013 | DOI: 10.1038/NCHEM.1690 Stabilization of anti-aromatic and strained five-membered rings with a transition metal Congqing Zhu1, Shunhua Li1,MingLuo1, Xiaoxi Zhou1, Yufen Niu1, Minglian Lin2, Jun Zhu1,2*, Zexing Cao1,2,XinLu1,2, Tingbin Wen1, Zhaoxiong Xie1,Paulv.R.Schleyer3 and Haiping Xia1* Anti-aromatic compounds, as well as small cyclic alkynes or carbynes, are particularly challenging synthetic goals. The combination of their destabilizing features hinders attempts to prepare molecules such as pentalyne, an 8p-electron anti- aromatic bicycle with extremely high ring strain. Here we describe the facile synthesis of osmapentalyne derivatives that are thermally viable, despite containing the smallest angles observed so far at a carbyne carbon. The compounds are characterized using X-ray crystallography, and their computed energies and magnetic properties reveal aromatic character. Hence, the incorporation of the osmium centre not only reduces the ring strain of the parent pentalyne, but also converts its Hu¨ckel anti-aromaticity into Craig-type Mo¨bius aromaticity in the metallapentalynes. The concept of aromaticity is thus extended to five-membered rings containing a metal–carbon triple bond. Moreover, these metal–aromatic compounds exhibit unusual optical effects such as near-infrared photoluminescence with particularly large Stokes shifts, long lifetimes and aggregation enhancement. romaticity is a fascinating topic that has long interested Results and discussion both experimentalists and theoreticians because of its ever- Synthesis, characterization and reactivity of osmapentalynes. Aincreasing diversity1–5. The Hu¨ckel aromaticity rule6 applies Treatment of complex 1 (ref. 32) with methyl propiolate to cyclic circuits of 4n þ 2 mobile electrons, but Mo¨bius topologies (HC;CCOOCH3) at room temperature produced osmapentalyne favour 4n delocalized electron counts7–10.
    [Show full text]
  • Cycloalkanes, Cycloalkenes, and Cycloalkynes
    CYCLOALKANES, CYCLOALKENES, AND CYCLOALKYNES any important hydrocarbons, known as cycloalkanes, contain rings of carbon atoms linked together by single bonds. The simple cycloalkanes of formula (CH,), make up a particularly important homologous series in which the chemical properties change in a much more dramatic way with increasing n than do those of the acyclic hydrocarbons CH,(CH,),,-,H. The cyclo- alkanes with small rings (n = 3-6) are of special interest in exhibiting chemical properties intermediate between those of alkanes and alkenes. In this chapter we will show how this behavior can be explained in terms of angle strain and steric hindrance, concepts that have been introduced previously and will be used with increasing frequency as we proceed further. We also discuss the conformations of cycloalkanes, especially cyclo- hexane, in detail because of their importance to the chemistry of many kinds of naturally occurring organic compounds. Some attention also will be paid to polycyclic compounds, substances with more than one ring, and to cyclo- alkenes and cycloalkynes. 12-1 NOMENCLATURE AND PHYSICAL PROPERTIES OF CYCLOALKANES The IUPAC system for naming cycloalkanes and cycloalkenes was presented in some detail in Sections 3-2 and 3-3, and you may wish to review that ma- terial before proceeding further. Additional procedures are required for naming 446 12 Cycloalkanes, Cycloalkenes, and Cycloalkynes Table 12-1 Physical Properties of Alkanes and Cycloalkanes Density, Compounds Bp, "C Mp, "C diO,g ml-' propane cyclopropane butane cyclobutane pentane cyclopentane hexane cyclohexane heptane cycloheptane octane cyclooctane nonane cyclononane "At -40". bUnder pressure. polycyclic compounds, which have rings with common carbons, and these will be discussed later in this chapter.
    [Show full text]
  • Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides
    Top Curr Chem (Z) (2016) 374:16 DOI 10.1007/s41061-016-0016-4 REVIEW Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides 1 1 Jan Dommerholt • Floris P. J. T. Rutjes • Floris L. van Delft2 Received: 24 November 2015 / Accepted: 17 February 2016 / Published online: 22 March 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract A nearly forgotten reaction discovered more than 60 years ago—the cycloaddition of a cyclic alkyne and an organic azide, leading to an aromatic triazole—enjoys a remarkable popularity. Originally discovered out of pure chemical curiosity, and dusted off early this century as an efficient and clean bio- conjugation tool, the usefulness of cyclooctyne–azide cycloaddition is now adopted in a wide range of fields of chemical science and beyond. Its ease of operation, broad solvent compatibility, 100 % atom efficiency, and the high stability of the resulting triazole product, just to name a few aspects, have catapulted this so-called strain-promoted azide–alkyne cycloaddition (SPAAC) right into the top-shelf of the toolbox of chemical biologists, material scientists, biotechnologists, medicinal chemists, and more. In this chapter, a brief historic overview of cycloalkynes is provided first, along with the main synthetic strategies to prepare cycloalkynes and their chemical reactivities. Core aspects of the strain-promoted reaction of cycloalkynes with azides are covered, as well as tools to achieve further reaction acceleration by means of modulation of cycloalkyne structure, nature of azide, and choice of solvent. Keywords Strain-promoted cycloaddition Á Cyclooctyne Á BCN Á DIBAC Á Azide This article is part of the Topical Collection ‘‘Cycloadditions in Bioorthogonal Chemistry’’; edited by Milan Vrabel, Thomas Carell & Floris P.
    [Show full text]
  • WO 2013/089962 Al 20 June 2013 (20.06.2013) W P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/089962 Al 20 June 2013 (20.06.2013) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every B01J 31/04 (2006.01) B01J 31/18 (2006.01) kind of national protection available): AE, AG, AL, AM, B01J 31/14 (2006.01) B01J 31/22 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 12/065285 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 15 November 2012 (15.1 1.2012) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 13/323,328 12 December 201 1 (12. 12.201 1) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): CHEV¬ GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, RON PHILLIPS CHEMICAL COMPANY LP UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, [US/US]; 10001 Six Pines Drive, The Woodlands, Texas TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 77380 (US).
    [Show full text]
  • Highly Accelerated Inverse Electron-Demand Cycloaddition of Electron-Deficient Azides with Aliphatic Cyclooctynes
    ARTICLE Received 22 Jul 2014 | Accepted 25 Sep 2014 | Published 10 Nov 2014 DOI: 10.1038/ncomms6378 Highly accelerated inverse electron-demand cycloaddition of electron-deficient azides with aliphatic cyclooctynes Jan Dommerholt1, Olivia van Rooijen2, Annika Borrmann1,Ce´lia Fonseca Guerra2, F. Matthias Bickelhaupt1,2 & Floris L. van Delft1 Strain-promoted azide–alkyne cycloaddition (SPAAC) as a conjugation tool has found broad application in material sciences, chemical biology and even in vivo use. However, despite tremendous effort, SPAAC remains fairly slow (0.2–0.5 M À 1 s À 1) and efforts to increase reaction rates by tailoring of cyclooctyne structure have suffered from a poor trade-off between cyclooctyne reactivity and stability. We here wish to report tremendous acceleration of strain-promoted cycloaddition of an aliphatic cyclooctyne (bicyclo[6.1.0]non-4-yne, BCN) with electron-deficient aryl azides, with reaction rate constants reaching 2.0–2.9 M À 1 s À 1. A remarkable difference in rate constants of aliphatic cyclooctynes versus benzoannulated cyclooctynes is noted, enabling a next level of orthogonality by a judicious choice of azide– cyclooctyne combinations, which is inter alia applied in one-pot three-component protein labelling. The pivotal role of azide electronegativity is explained by density-functional theory calculations and electronic-structure analyses, which indicates an inverse electron-demand mechanism is operative with an aliphatic cyclooctyne. 1 Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands. 2 Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
    [Show full text]
  • Rapid Calculation of the Number of Π-Bonds, Σ-Bonds, Single and Triple Bonds in Aliphatic Unsaturated Open Chain and Cycloalkynes
    World Journal of Chemical Education, 2014, Vol. 2, No. 1, 1-3 Available online at http://pubs.sciepub.com/wjce/2/1/1 © Science and Education Publishing DOI:10.12691/wjce-2-1-1 Rapid Calculation of the Number of π-bonds, σ-bonds, Single and Triple Bonds in Aliphatic Unsaturated Open Chain and Cycloalkynes Arijit Das1,*, Suman Adhikari1, Debapriya Pal2, Bijaya Paul3, R. Sanjeev4, V. Jagannadham5 1Department of Chemistry, Govt. Degree College, Dharmanagar, Tripura(N), India 2Department of Science, Netaji Vidyapith Institute, Unakoti, Tripura, India 3Department of Chemistry, Tripura University, Suryamaninagar, Tripura(W), India 4Department of Chemistry, Avanthi Degree and PG College, Hyderabad, India 5Department of Chemistry, Osmania University, Hyderabad, India *Corresponding author: [email protected] Received September 20, 2013; Revised December 15, 2013; Accepted December 30, 2013 Abstract Prediction of number of π-bonds, σ-bonds, single and triple bonds of aliphatic unsaturated open chain and cycloalkynes is a vitally important tool for students of chemistry at undergraduate and graduate level for solving different kinds of problems regarding different chemical reactions. In this manuscript, we try to present a simple and innovative method for easy calculation of number of π-bonds, σ-bonds, single and triple bonds with the help of completely 8 (eight) new formulae. Keywords: open chain and cycloalkynes, π and σ-bond, triple and single bond, number of carbon, hydrogen atoms Cite This Article: Arijit Das, Suman Adhikari, Debapriya Pal, Bijaya Paul, R. Sanjeev, and V. Jagannadham, “Rapid Calculation of the Number of π-bonds, σ-bonds, Single and Triple Bonds in Aliphatic Unsaturated Open Chain and Cycloalkynes.” World Journal of Chemical Education 2, no.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0068738A1 BERTOZZ Et Al
    US 20090068738A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0068738A1 BERTOZZ et al. (43) Pub. Date: Mar. 12, 2009 (54) COMPOSITIONS AND METHODS FOR Related U.S. Application Data MODIFICATION OF BOMOLECULES (63) Continuation-in-part of application No. 1 1/264,463, filed on Oct. 31, 2005. (75) Inventors: CAROLYN RUTH BERTOZZI, (60) Provisional application No. 60/624.202, filed on Nov. BERKELEY, CA (US); 1, 2004. NICHOLAS J. AGARD, BERKELEY, CA (US); Publication Classification JENNIFER A. PRESCHER, (51) Int. Cl. BERKELEY, CA (US): JEREMY CI2N 5/06 (2006.01) MICHAEL BASKIN, C07D 495/04 (2006.01) BERKELEY, CA (US); ELLEN CD7C 65/26 (2006.01) MAYSLETTEN, BERKELEY, CA C7H I/00 (2006.01) (US) (52) U.S. Cl. ...................... 435/375: 548/304.1; 540/480; 562/473; 536/55.3 Correspondence Address: (57) ABSTRACT BOZICEVIC, FIELD & FRANCIS LLP The present invention provides modified cycloalkyne com 1900 UNIVERSITY AVENUE, SUITE 200 pounds; and method of use of Such compounds in modifying EAST PALOALTO, CA 94.303 (US) biomolecules. The present invention features a cycloaddition reaction that can be carried out under physiological condi (73) Assignee: THE REGENTS OF THE tions. In general, the invention involves reacting a modified UNIVERSITY OF cycloalkyne with an azide moiety on a target biomolecule, CALIFORNLA, Oakland, CA (US) generating a covalently modified biomolecule. The selectiv ity of the reaction and its compatibility with aqueous envi ronments provide for its application in Vivo (e.g., on the cell (21) Appl. No.: 12/049,034 Surface or intracellularly) and in vitro (e.g., synthesis of pep tides and other polymers, production of modified (e.g., (22) Filed: Mar.
    [Show full text]
  • IUPAC Nomenclature Rule for Alkyne
    IUPAC nomenclature Rule for Alkyne (1) Select the longest carbon chain containing a triple bond (2) The numbering of the carbon chain is in such a way that the carbon attached to the triple bond should get the lowest possible number (3) The numbering of the triple bond carbon should be mentioned in the nomenclature (4) All other rules of substituents are the same as alkanes and alkenes ethyne 1-propyne 5-methyl-2-hexyne Nomenclature of cycloalkynes: Nomenclature is according to the suffix = cycloalkyne 4-methyl cyclopentyne cyclohexyne 3-methyl cyclobutyne IUPAC nomenclature Rule for Compounds containing both double and triple bonds (1) If the organic compound contains both double and triple bond, then select the longest carbon chain in such a way that the sum of the carbons attached to the double and triple bond should get the lowest possible number. 1-hexene-3-yne 1 + 3 = 4 (Correct numbering - small sum total) 3 + 5 = 8 (Incorrect numbering - large sum total) (2) Nomenclature is always according to the alkene followed by alkyne i.e. Prefix = alkene, Suffix = alkyne (3) If the sum of the carbons attached to double and triple bond is the same (for both LHS to RHS and RHS to LHS), then select the longest carbon chain in such a way that carbon attached to the double bond should get the lowest possible number 1-butene-3-yne 1 + 3 = 4 (Correct numbering - small sum total) 1 + 3 = 4 (Correct numbering - small sum total) (4) Numbering from LHS to RHS is correct because double bond carbon gets the lower possible number .
    [Show full text]
  • Certified by
    Estimation Method for the Thermochemical Properties of Polycyclic Aromatic Molecules by Joanna Yu Bachelor of Science in Engineering, Escola Politcnica-USP, Sao Paulo, Brazil, 2001 Submitted to the Department of Chemical Engineering in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemical Engineering Practice at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY September 2004 © Massachusetts Institute of Technology 2004. All rights reserved. Author. · epartment of Chemical Engineering September 1, 2004 Certifiedbyby ............... .............. ,f.\.. ................................... (U)William H. Green, Jr. Texaco-Mangelsdorf Associate Professor Thesis Supervisor Acceptedby............ ................... ..... Daniel Blankschtein Professor of Chemical Engineering Chairman, Committee for Graduate Students MASSACHUSETTS INSTTUTE OF TECHNOLOGY F SEP 12 2005 _ 11"C4,1~e- LIBRARIES Estimation Method for the Thermochemical Properties of Polycyclic Aromatic Molecules by Joanna Yu Bachel)or of Science in Engineering, Escola Polit6cnica-USP, So Paulo, Brazil, 2001 Submitted to tle Departmenlt of Chemical Engineering on September 1, 2004, in partial fulfillment of the requiremlents for tle degree of Doctor of Philosophy in Chemical Engineering Practice Abstract Polycy( lic aromatic molecules, icluding polycyclic aromatic hydrocarbons (PAHs) have attracted c(onsiderable attention in the Ipast few decades. They are formed dur- ing the incomipliete combustion of hydrocarbon fuels and are precursors of soot. Some PAHs are known carcilnogens, and control of their emissions is an important issue. These nlolecules uarefound in Ilany materials, including coal, fuel oils, lubricants, andl carton )l lack. They are also ilmpi)licatedi tle formation of fullerenes, one of the Ilost. chemi(( ally versatile class of molecules known. Clearly, models that p)rovide predic- tive cap:,ability for their formation and growth are highly d(esiral)le.
    [Show full text]
  • Mechanisms of Metal-Mediated Cyclizations
    Mechanisms of Metal-Mediated Cyclizations by Benjamin Peter Warner Submitted to the Department of Chemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Organic Chemistry at the Massachusetts Institute of Technology February 1995 © Massachusetts Institute of Technology, 1995 All Rights Reserved Signature of Author.., .... ..,. ....................... ................................................................ Department of Chemistry February 1, 1995 Certified by ........................... I....................... Stephen L. Buchwald Thesis Supervisor Accepted by.............................................v..................................................................... Dietmar Seyferth Chair, Departmental Committee on Graduate Students Sciencx- This doctoral thesis has been examined by a committee of the Department of Chemistry as follows: Professor Gregory C. Fu.............................. .... ........................................................... Chair Professor Stephen L. Buchwald .................. ;................... Thesis Supervisor Professor Christopher C. Cummins.................. ................. .. ...............................; 2 Mechanisms of Metal-Mediated Cyclizations by Benjamin Peter Warner Submitted to the Department of Chemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Organic Chemistry at the Massachusetts Institute of Technology Abstract A complex of zirconocene with two rq2-alkynyl ligands is described. This
    [Show full text]
  • Versatile Naphthalimide Tetrazines for Fluorogenic Bioorthogonal Labelling† Cite This: DOI: 10.1039/D1cb00128k Ab Ab Cd E Marcus E
    RSC Chemical Biology View Article Online PAPER View Journal Versatile naphthalimide tetrazines for fluorogenic bioorthogonal labelling† Cite this: DOI: 10.1039/d1cb00128k ab ab cd e Marcus E. Graziotto, Liam D. Adair, Amandeep Kaur, Pauline Ve´rite´, Sarah R. Ball,c Margaret Sunde, cd Denis Jacquemin e and Elizabeth J. New *abd Fluorescent probes for biological imaging have revealed much about the functions of biomolecules in health and disease. Fluorogenic probes, which are fluorescent only upon a bioorthogonal reaction with a specific partner, are particularly advantageous as they ensure that fluorescent signals observed in biological imaging arise solely from the intended target. In this work, we report the first series of naphthalimide tetrazines for bioorthogonal fluorogenic labelling. We establish that all of these compounds can be used for imaging through photophysical, analytical and biological studies. The best candidate was Np6mTz, where the tetrazine ring is appended to the naphthalimide at its 6-position via a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. phenyl linker in a meta configuration. Taking our synthetic scaffold, we generated two targeted variants, LysoNpTz and MitoNpTz, which successfully localized within the lysosomes and mitochondria Received 10th June 2021, respectively, without the requirement of genetic modification. In addition, the naphthalimide tetrazine Accepted 24th June 2021 system was used for the no-wash imaging of insulin amyloid fibrils in vitro, providing a new method that DOI: 10.1039/d1cb00128k can monitor their growth kinetics and morphology. Since our synthetic approach is simple and modular, these new naphthalimide tetrazines provide a novel scaffold for a range of bioorthogonal tetrazine- rsc.li/rsc-chembio based imaging agents for selective staining and sensing of biomolecules.
    [Show full text]
  • Max-Planck-Institut Für Kohlenforschung Report for The
    Max-Planck-Institut für Kohlenforschung Report for the Period of January 2002 – December 2004 Printed May 2005 Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm-Platz 1 45470 Mülheim an der Ruhr, Germany Tel. +49 208 3 06 1 Fax +49 208 3 06 29 80 http://www.mpi-muelheim.mpg.de Managing Director Professor Dr. Ferdi Schüth Director of the Department of Synthetic Organic Chemistry Professor Dr. Manfred T. Reetz Tel. +49 208 3 06 20 00 Fax +49 208 3 06 29 85 E-mail: [email protected] Director of the Department of Homogeneous Catalysis NN Director of the Department of Heterogeneous Catalysis Professor Dr. Ferdi Schüth Tel. +49 208 3 06 23 73 Fax +49 208 3 06 29 95 E-mail: [email protected] Director of the Department of Organometallic Chemistry Professor Dr. Alois Fürstner Tel. +49 208 3 06 23 42 Fax +49 208 3 06 29 94 E-mail: [email protected] Director of the Department of Theory Professor Dr. Walter Thiel Tel. +49 208 3 06 21 50 Fax +49 208 3 06 29 96 E-mail: [email protected] External Scientific Members of the Max-Planck-Institut für Kohlenforschung Professor Dr. Alois Haas Medonstrasse 17 14532 Kleinmachnow Germany Professor Dr. Jack Halpern University of Chicago Department of Chemistry 5735 South Ellis Avenue Chicago, Illinois 60637 USA Professor Dr. Walter Leitner Lehrstuhl für Technische Chemie und Petrolchemie Institut für Technische und Makromolekulare Chemie Rheinisch-Westfälische Technische Hochschule Aachen Worringer Weg 1 52074 Aachen Germany Member of the Scientific Council of the Max Planck Society, Section of Chemistry, Physics and Technology Professor Dr.
    [Show full text]