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JOURNEE DES DOCTORANTS EN CHIMIE 2017
Vendredi, 10 novembre 2017
Programme et Résumés
Collège Doctoral Européen Campus de l’Esplanade
http://ed.chimie.unistra.fr/
AVANT-PROPOS
La Journée des doctorants en chimie en est à sa 11ème
édition. Pour les doctorants déjà engagés dans le cursus doctoral, cette journée leur permet d’exposer leurs travaux de recherche. Pour les doctorants de 1ère année, elle fait office de journée de rentrée et leur donne l’occasion :
- D’avoir un aperçu des recherches menées dans les laboratoires de chimie de l’Université de Strasbourg et du CNRS,
- De nouer des contacts avec les doctorants plus anciens, notamment ceux d’autres
équipes et d’autres campus,
- De poser toutes les questions concernant le déroulement de la formation doctorale en chimie ainsi que l’après-thèse.
Je tiens à remercier toutes les personnes qui ont accepté de présenter leurs travaux de recherche lors de cette journée ainsi que celles qui ont fait des Journées précédentes un succès. Mes remerciements vont tout particulièrement à Nathalie Kostmann pour sa contribution centrale dans l’organisation de la JDC 2017.
Jean-Serge REMY Directeur de l’EDSC
Communications orales
Amphithéâtre du CDE
Communications orales
Auditorium du CDE
8 h 00 - 8 h 50
8 h 50 - 9 h 00
9 h 00 - 10 h 00
10 h 00 - 10 h 30
10 h 30 - 10 h 50 1A STOECKEL Marc-Antoine 1B RUNSER Anne
10 h 50 - 11 h 10 2A ZAITCEVA Olesia 2B MARGUERITE Laure
11 h 10 - 11 h 30 3A WOJCIECHOWSKI Joanna 3B ESTEOULLE Lucie
11h30 - 11 h 50 4A SENJEAN Bruno 4B CHAZARIN Blandine
11 h 50 - 12 h 10 5A MAZOUIN Laurent 5B BOTZANOWSKI Thomas
12 h 10 - 12 h 30 6A JIMENEZ CALVO Pablo Isai 6B BOURGUET Maxime
12 h 30 - 14 h 00
Communications orales
Amphithéâtre du CDE
Communications orales
Auditorium du CDE
14 h 00 - 14 h 207A SARANTI KARAMESINI
Dionysia7B ALOISI Adriano
14 h 20 - 14 h 40 8A DJEMILI Ryan 8B TANG Shuang-Qi
14 h 40 - 15 h 00 9A CARVALHO Mary-Ambre 9B DE PINA CARDOSO Bernardo
15 h 00 - 15 h 20 10A CORSO Romain 10B PETIT Benoît
15 h 20 - 15 h 50 11A TUFENKJAN Elsa 11B BELTRAN Frédéric
15 h 50 - 16 h 10
16 h 10 - 16 h 30 12A VUKOVIC Vuk 12B SIRINDIL Fatih
16 h 30 - 16 h 50 13A COLARD-ITTE Jean-Rémy 13B DDUNGU John
16 h 50 - 17 h 10 14A BESSI Matteo 14B HLAVAC Matus
17 h 10 - 17 h 30 15A CAVALLO Gianni 15B EHKIRCH Anthony
17 h 30 - 17 h 50 16A BATISSE Chloé 16B RETE Cristian-Victor
Journée des Doctorants en Chimie 2017 - 10 novembre 2017
PROGRAMME
Pause - Boissons
OuvertureExposé de rentrée de Jean-Serge REMY, directeur de l'EDSC
Discussion avec les doctorants ; présence de Mme Lrhezzioui (Espace Avenir)
Pause - Boissons
Buffet - Jardin intérieur du Collège Doctoral Européen
(pour ceux qui se sont inscrits)
Conférence - Amphithéâtre du CDE
" Advancing synthetic chemistry in biological media "
Alain WAGNER
Présentation de la Société Chimique de France (SCF)Angélique SIMON-MASSERON
TITRES DES
COMMUNICATIONS ORALES
LISTE DES COMMUNICATIONS ORALES
AMPHITHEATRE, COLLEGE DOCTORAL EUROPEEN
(1A) Organo-metallic hybrid perovskite for oxygen sensing M.-A. Stoeckel, M. Gobbi, S. Bonacchi , F. Liscio, L. Ferlauto, E. Orgiu, P. Samorì Institut de Science et d’Ingénierie Supramoléculaires (I.S.I.S.), 8 allée Gaspard Monge, 67083 Strasbourg, France
(2A) New methods for the synthesis of coumarin and thiocoumarin from acetylene compounds catalyzed by plantinium or H-zeolite catalysts O. Zaitceva*, D. Ryabukhin**, B. Louis*, V. Bénéteau*, P. Pale*, A. Vasilyev** *Laboratoire de Synthèse, Réactivité Organiques et Catalyse, UMR 7177, Université de Strasbourg, Institut le Bel, 4 rue Blaise Pascal, 67000 Strasbourg, France **Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University, Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia
(3A) Light-driven synthesis of sub-nanometric metallic Ru catalysts on TiO2
Joanna Wojciechowskaa,b, Elisa Gitzhoferb, Nicolas Kellerb, Jacek Gramsa, Agnieszka M. Rupperta a Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, ul. Żeromskiego
116, 90-924, Łódź, Poland b Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé, CNRS/University of Strasbourg, 25 rue Becquerel, 67087 Strasbourg, France
(4A) Site-Occupation Embedding Theory Bruno Senjean1, Naoki Nakatani2, Masahisa Tsuchiizu3, Emmanuel Fromager1 1Laboratoire de Chimie Quantique, Institut de Chimie, CNRS / Université de Strasbourg,1 rue Blaise Pascal, F-67000 Strasbourg, France 2 Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan 3 Department of Physics, Nara Women’s University, Nara 630-8506, Japan
(5A) Green’s function-based density-functional theory for lattice Hamiltonians Laurent Mazouin, Emmanuel Fromager Laboratoire de Chimie quantique, Institut de Chimie, CNRS/Université de Strasbourg, 4 rue Blaise Pascal, Strasbourg, France
(6A) Synthesis, characterization and reactivity of photocatalytic Au-gC3N4 nanocomposites for Hydrogen production from water under solar-light P. Jiménez-Calvo1*, T. Cottineau1, V. Caps1, V. Keller1 1 ICPEES, Institut de Chimie et Procédés pour l’Energie, l’Environnement et la Santé, CNRS/Université de Strasbourg, UMR 7515 (CNRS), 25 rue Becquerel 67087 Strasbourg Cedex, France
(7A) Sequence-coded polymers and their use as molecular barcodes for materials labelling Denise Karamessini1, Benoit. E. Petit1, Michel Bouquey1, Laurence Charles2, Jean-François Lutz1*
1 Precision Macromolecular Chemistry, Institut Charles Sadron, CNRS UPR-22, 23 rue du Loess, 67034 Strasbourg Cedex 2, France, E-mail: [email protected] 2 Aix-Marseille Université – CNRS, UMR 7273, Institute of Radical Chemistry, 13397 Marseille Cedex 20, France
(8A) Mouvements moléculaires contrôlés dans des rotaxanes porphyriniques Ryan Djemili, Stéphanie Durot, Valérie Heitz Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnelles, Université de Strasbourg, Institut Le Bel, 4 rue Blaise Pascal, 67070 Strasbourg
(9A) Porphyrin assemblies on hopg M.-A. Carvalho, H. Dekkiche, L. Kamarzin, B. Vincent, R. Ruppert, M. Kanesato, Y. Kikkawa UMR 7177 CNRS-Institut de Chimie, Université de Strasbourg, rue Blaise Pascal, F-67000 STRASBOURG National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, TSUKUBA, Ibaraki 305-8562 (Japan)
(10A) Molecular tectonics: gas adsorption and chiral uptake of (L)- and (D)- tryptophan by homochiral porous coordination polymers Romain Corsob, Donata Asnaghia, Patrick Larpentb, Irene Bassanettia, Abdelaziz Jouaitib, Nathalie Kyritsakasb, Angiolina Comotti*a, Piero Sozzania and Mir Wais Hosseinib a Department of Materials Science, University of Milano Bicocco, via R. Cozzi 55, Milan, Italy b Laboratoire de Chimie de Coordination Organique (UMR-CNRS 7140, Université de Strasbourg, Institut Le Bel, 4 rue Blaise Pascal, 67000 Strasbourg, France
(11A) Molecular tectonics based on pyridine and terpyridine bearing nucleobases Elsa Tufenkjian, Veronique Bulach, Aziz Jouaiti, Nathalie Kyritsakas, Mir Wais Hosseini Laboratory of Molecular Tectonics, UMR UDS-CNRS 7140, Univeristy of Strasbourg, Institut Le Bel, F-67000, Strasbourg, France
(12A) Exploiting Higher Order Aggregation Phenomena in Brønsted Acid Catalysis Vuk D. Vuković, Edward Richmond, Eléna Wolf, Florent Noёl, Jing Yi, Pavle Kravljanac, Joseph Moran1 1 Institut de Science et d’Ingénierie Supramoléculaires - UMR 7006, Strasbourg, France
(13A) Rheological studies of contractile gels based on light-driven rotary molecular motors Jean-Rémy Colard-Itté1, Quan Li12, Dominique Collin3, Gad Fuks1, Emilie Moulin1, Giacomo Mariani4, Eric Buhler4, Nicolas Giuseppone1* 1 SAMS research group, Institut Charles Sadron, University of Strasbourg, CNRS, 23 rue du Loess, BP 84047, 67034, Strasbourg Cedex 2, France 2 Current address: Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, USA 3 SYCOMMOR research group, Institut Charles Sadron, University of Strasbourg, CNRS, 23 rue du Loess, BP 84047, 67034, Strasbourg Cedex 2, France 4 MSC research group, UMR 7057 CNRS, University Paris 7 Diderot, 75205 Paris Cedex 13, France
(14A) Development of stimuli-responsive polyamidoamine-based hydrogels Matteo Bessi, Dr. Simone Silvestrini, Prof. Luisa De Cola Laboratoire de Chimie et des Biomatériaux Supramoléculaires (ISIS) - Université de Strasbourg, 8 Allée Gaspard Monge, 67083 Strasbourg Cedex
(15A) Synthesis of monodisperse sequence encoded copolymers using fast orthogonal chemistry Gianni Cavallo1, Abdelaziz Al Ouahabi1, Laurence Oswald1, Laurence Charles2, Jean-François Lutz1 1 Precision Macromolecular Chemistry, Institut Charles Sadron, UPR-22 CNRS, BP 84047, 23 rue du Loess 67034 Strasbourg Cedex 2, France 2 Aix-Marseille Universitė, CNRS, Institute of Radical Chemistry UMR 7273, Marseille, France
(16A) Towards the enantioselective C(sp3) difluoromethylation Chloé Batisse, Armen Panossian, Gilles Hanquet, Frédéric R. Leroux Université de Strasbourg, CNRS, LCM UMR 7509, ECPM, 25 Rue Becquerel, 67087 Strasbourg, France
AUDITORIUM, COLLEGE DOCTORAL EUROPEEN
(1B) Luminescent lanthanide-loaded polymer nanoparticles as bright probes for cellular imaging Anne Runser1, Andreas Reisch1, Marcelina Cardoso Dos Santos2, Aline Nonat3, Loïc Charbonnière3, Andrey Klymchenko1, Niko Hildebrandt2 1 Laboratoire de Biophotonique et Pharmacologie, UMR 7213 CNRS, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch France 2 NanoBioPhotonics, Institut d’Electronique Fondamentale, Université Paris-Saclay, Université Paris-Sud, CNRS, Orsay, France 3 Laboratoire d’Ingénierie Moléculaire Appliquée à L’Analyse, IPHC, UMR 7178
(2B) Development of a pharmacophoric deconvolution method to accelerate the discovery of antiplasmodial molecules from Rhodophyta Laure Margueritte1, Mélanie Bourjot1, Petar Markov2, Guillaume Bret1, Marc-André Delsuc2, Didier Rognan1, Catherine Vonthron-Sénécheau1 1 Laboratoire d'Innovation Thérapeutique UMR CNRS 7200 et 2 Institut de Génétique et de Biologie
(3B) Fluorocarbon Conjugates: New Concept to Increase the Metabolic Stability of Peptides Targeting GPCRs Lucie Esteoulle
(4B) Compared effects of beta-hydroxybutyrate and bear serum on the proteome of human muscle cells Blandine Chazarin1, Stéphanie Chanon2, Guillemette GAuquelin-Koch3, Stéphane Blanc1, Etienne Lefai2, Fabrice Bertile1 1 CNRS, Université de Strasbourg, IPHC-Laboratoire de Spectrométrie de Masse BioOrganique, 67087 Strasbourg, France 2 Laboratoire CarMeN, INSERM U1060 / INRA 1397, Université de Lyon, 69921 OULLINS, France 3 Centre National d’études Spatiales, CNES, 75001 Paris, France
(5B) Caractérisation d’anticorps immunoconjugués site spécifiques par spectrométrie de masse couplée à la mobilité ionique Thomas Botnawski1, Oscar Hernandez Alba1, Stéphane Erb1, Anthony Ehkirch1, David Rabuka2, Alain Beck3, Penelope Drake2, Sarah Cianferani1 1 Laboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CNRS, IPHC UMR 7178, 67000 Strasbourg, France 2 Catalent Biologics West, 5703 Hollis Street, Emeryville, California 94530, United States 3 Centre d’Immunologie Pierre-Fabre (CIPF), Saint-Julien-en-Genevois, France
(6B) Epitope characterization of anti-JAM-A antibodies using orthogonal mass spectrometry and surface plasmon resonance approaches Maxime Bourguet1, Guillaume Terral1, Thierry Champion2, François Debaene1, Olivier Colas2, Elsa Wagner-Rousset2, Nathalie Corvaia2, Alain Beck2, Sarah Cianférani1 1 Laboratoire de Spectrométrie de Masse BioOrganique(LSMBO), IPHC, DSA, CNRS UMR7178, UdS, Strasbourg, France - [email protected] 2 Centre d’Immunologie Pierre-Fabre (CIPF), Saint-Julien-en-Genevois, France
(7B) Foldamers based on adamantane Adriano Aloisia, Kasper K. Sørensenb, Niels J. Christensenb, Knud J. Jensenb, Alberto Biancoa a University of Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique, Strasbourg, France b University of Copenhagen, Department of Chemistry, Thoarvaldsensvej 40, 1871 Frederksberg (Denmark)
(8B) Synthesis of 6- or 7-membered N-O heterocycles and their applications in medicinal chemistry Shuang-Qi Tang, Martine Schmitt, Frédéric Bihel* Laboratoire d’Innovation Thérapeutique, UMR 7200
(9B) Insight to the structure of cationic CNHC,Calkyl-nickelacycles and study as azole C–H functionalization catalysts B. de P. Cardoso, S. Shahane, J.-M. Bernard-Schaaf, M. J. Chetcuti, V. Ritleng Université de Strasbourg, UMR 7509, 25 rue Becquerel, 67087 Strasbourg, France
(10B) Chemoselective Synthesis Of Readable Sequence-Coded Polyurethanes
Benoît Petit
(11B) Spirocyclization from keto-ynamides: toward the synthesis of azacycles Frédéric Beltrana, Indira Fabreb, Ilaria Cionfinib, Laurence Miescha* a Laboratoire de Chimie Organique Synthétique, Institut de Chimie, CNRS-UdS UMR 7177, 4, rue Blaise Pascal CS 90032, 67081 Strasbourg, France b Chimie ParisTech, PSL Research University, CNRS, Institut de Recherche de Chimie Paris (IRCP), 75005 Paris, France
(12B) Gold and palladium catalyzed cascade reactions towards the synthesis of natural products Fatih Sirindil1, Patrick Pale1, Aurélien Blanc1 1 Laboratoire de Synthèse, Réactivité Organique et Catalyse, Institut de Chimie, UMR 7177, Université de Strasbourg, 4 rue Blaise Pascal, 67070 Strasbourg, France
(13B) Synthesis and characterisation of silicon-based nanoparticles for multi-modal in vivo imaging applications John Ddungu†*, Luisa De Cola†* † Institut de Science et d’Ingénierie Supramoléculaires, Université de Strasbourg * Institute of Nanotechnology, Karlsruhe Institute of Technology (KIT), Germany
(14B) Synthesis and biological activity of predicted ALR2 inhibitors Matúš Hlaváčac, Lucia Kováčikováb, Gilles Hanquetc, Magdaléna Majekováb, Milan Štefekb, Andrej Boháčad* a Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, Mlynská dolina, 842 15, Bratislava, Slovakia, [email protected] bInstitute of Experimental Pharmacology and Toxicology, SAS, Dúbravská cesta 6, 841 04, Bratislava, Slovakia c Université de Strasbourg, Ecole Européenne de Chimie, Polyméres et Metériaux (ECPM), Laboratoire de Synthése et Catalyse (UMR CNRS 7509), 25 rue Becquerel, 67087 Strasbourg cedex 2, France d Biomagi, Ldt., Mamateyova 26, 851 04, Bratislava, Slovakia
(15B) An online four-dimensional HICxSEC-IMxMS methodology for in-depth characterization of antibody drug conjugates Anthony Ehkircha, Valentina D’Atrib, Florent Rouvièrec, Oscar Hernandez-Albaa, Alexandre Goyonb, Olivier Colasd, Morgan Sarrutc, Alain Beckd, Davy Guillarmeb, Sabine Heinischc, Sarah Cianférania a Laboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CRNS, IPHC UMR 7178, 67000 Strasbourg, France b School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU - Rue Michel-Servet, 1, 1206 Geneva – Switzerland c Univ Lyon, CNRS, Université Claude Bernard Lyon 1, Ens de Lyon, Institut des Sciences Analytiques, UMR 5280, 69100 VILLEURBANNE, France d Centre d’Immunologie Pierre-Fabre (CIPF), Saint-Julien-en-Genevois, France
(16B) Reversible Native Chemical Ligation : A Facile Method to Identify Peptide Ligands for Protein Targets Cristian-Victor Rețea, Manickasundaram Samiappana, Valentina Garavinia, Yves Ruffa, Stéphane Erbb, Jean-Marc Strubb, Sarah Cianferanib, Daniel Funeriua, Nicolas Giusepponea a SAMS Research Group, Institut Charles Sadron (CNRS), Université de Strasbourg – 23 rue du Loess, 67034 Strasbourg Cedex 2, France b Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Université de Strasbourg, Institut Pluridisciplinaire Hubert Curien (CNRS) – 23 rue du Loess, 67037 Strasbourg Cedex 2, France
RESUME DE LA CONFERENCE
Advancing synthetic chemistry in biological media
Alain WAGNER, Directeur de Recherche
Université de Strasbourg, Conception et Application de Molécules Bioactives (CAMB) – UMR 7199,
74 Route du Rhin, 67401 Illkirch Cedex
E-Mail : [email protected]
Our research focuses on the development of chemical reactions that are compatible with complex
biological media. They are qualified as bioorthogonal when they can take place in a complex biological
medium without distorting it, or as bio-specific when they touch only a precise part of it.
Taking advantage of imaging and bioanalytical methods, we have developed chemometric
methodologies to picture the bio-reactivity profile of bond-forming and bond-breaking chemical
reactions. By applying this methodology, we were able to characterize novel functional groups and
reagents that exhibit a precise activation profile and to uncover unexpected biospecificity.
Applications to bioconjugation, in vivo drug neutralization and chemoselective metabolomic
approaches will be presented.
RESUMES DES
COMMUNICATIONS ORALES
SESSION A
Organo-metallic hybrid perovskite for oxygen sensing
M.-A. Stoeckel, M. Gobbi, S. Bonacchi , F. Liscio, L. Ferlauto, E. Orgiu, P. Samorì
Institut de Science et d’Ingénierie Supramoléculaires (I.S.I.S.), 8 allée Gaspard Monge, 67083,
Strasbourg, France
CNR - IMM Sezione di Bologna Via P. Gobetti 101 40129 Bologna Italy
Since its popularisation due to a power conversion efficiency increasing at an unprecedented rate in
solar cells applications[1], organo-metallic hybrid perovskite materials are continually under
investigation to find new applications for low-cost and up-scalable devices production.
Devices based on methylammonium lead iodide (MAPbI3) already proved the capability of that
compound to be used as resistive sensor to ammonia or optical one for humidity[2,3]. It is also
reported that MAPbI3 can strongly interact with oxygen gas, leading to a peculiar increase of its
photoluminescence[4]. It has been suggested that Pb-O bond formation could be responsible for that
enhancement[5].
Using various electrical measurements, we present here the electrical characterization of MAPbI3 in
controlled atmospheres containing different quantities of oxygen. It was found that the electrical
resistance of the perovskite is strongly related to the gas composition of its environment.
That effect was attributed to a fully reversible vacancies passivation of the perovskite, leading to a
less trapped material. The two-terminal device exhibit strong oxygen sensitivity with fast response
time and high detection range.
Finally, MAPbI3 oxygen sensitivity was found to be highly related to the morphology adopted in the
thin film, through the deposition process used to prepare devices.[6]
[1] X. Li, D. Bi, C. Yi, J.-D. Décoppet, J. Luo, S. M. Zakeeruddin, A. Hagfeldt, M. Grätzel, Science 2016,
aaf8060.
[2] C. Bao, J. Yang, W. Zhu, X. Zhou, H. Gao, F. Li, G. Fu, T. Yu, Z. Zou, Chem Commun 2015, 51,
15426.
[3] L. Hu, G. Shao, T. Jiang, D. Li, X. Lv, H. Wang, X. Liu, H. Song, J. Tang, H. Liu, ACS Appl. Mater.
Interfaces 2015, 7, 25113.
[4] J. F. Galisteo-López, M. Anaya, M. E. Calvo, H. Míguez, J. Phys. Chem. Lett. 2015, 6, 2200.
[5] W. Kong, A. Rahimi-Iman, G. Bi, X. Dai, H. Wu, J. Phys. Chem. C 2016, 120, 7606.
[6] M.-A. Stoeckel, M. Gobbi, S. Bonacchi, F. Liscio, L. Ferlauto, E. Orgiu, P. Samorì, Adv. Mater. 2017,
29, DOI 10.1002/adma.201702469.
New methods for the synthesis of coumarin and thiocoumarin from acetylene
compounds catalyzed by platinum or H-zeolite catalysts
O. Zaitceva*, D. Ryabukhin**, B. Louis*, V. Bénéteau*, P. Pale*, A. Vasilyev**.
*Laboratoire de Synthèse, Réactivité Organiques et Catalyse, UMR 7177, Université de Strasbourg, Institut le Bel, 4 rue Blaise Pascal, 67000 Strasbourg, France. **Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University, Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia.
The first separation of coumarin was made in 1820, since then scientists extracted more than 1,400 natural
coumarins and came up with many ways to synthesize them. Coumarinic compounds are key fragments of a large
number of biologically active natural and synthetic compounds1. They found surprising properties with a large
number of anti-antibacterial2, antimalarial3, anticoagulation, antipsoriasis, anti-HIV4, antitumor agent5, cytotoxic6
(4-phenylfuranocoumarins), and also widely used as an intermediate product in organic synthesis7. Coumarins are
also used as ultraviolet absorbents8.
The main goal of our study relies on the development of new methods for preparing coumarin and
thiocoumarin derivatives 2 starting from acetylenic compounds 1.
Y zeolite USY zeolite
Vasilyev et al. have developed a
sophisticated platinum catalyst working together
with a silver co-catalyst. A nearly full conversion
of the acetylenic compounds could be achieved,
along with a good selectivity in corresponding
coumarins
Y zeolite - classical FAU Y zeolite synthesized by the method of the book:
H. Robson et al, Verified syntheses of zeolitic material, Elsevier, 2001
Zeolite USY CBV-720 produced by Zeolyst company
We tested a large number of different types of zeolites (mordenite, faujasite, beta, ferrierite and ZSM-5),
inorganic catalysts, superacids and several models of platinum catalysts, developed in the group of the professor A.
Vasilyev.We managed to achieve very good results and identify patterns. The results of the work will be presented
in the oral presentation at the conference.
1D. S. Ryabukhin, A.V. Vasilyev, Russian Chemical Reviews, 85(6), 637-665, (2016) 2 L. Verotta, Е. Lovaglio, G. Vidari, P.V. Finzi, M. G. Neri, A. Raimondi, S. Parapini,D. Taramelli, A. Riva,E. Bombardelli, Phytochemistry, 65, 2867–2879, (2004) 3 K. Kirandeep, J. Meenakshi, K. Tarandeep, J. Rahul, Bioorganic & Medicinal Chemistry, 17 (9), 3229-3256, (2009) 4 A. D Patil, A. J. Freyer, D. S. Eggleston, R. C. Haltiwanger, M. F. Bean, P. B. Taylor, M. J. Caranfa, A. L. Breen, H. R. Bartus, et al. Journal of Medicinal
Chemistry 36(26), 4131-4138, (1993) 5 R. D. H. Murray, Prog. Chem. Org. Nat. Prod., 58, 83 (1991) 6 D. Guilet, J.-J Helesbeux, D. Seraphin, T. Sevenet, P. Richomme, J. Bruneton, J. Nat. Prod., 64, 563–568, (2001) 7 M. E. Riveiro, N. De Kimpe, A. Moglioni, R. Vazquez, F. Monczor, C. Shayo, C. Davio, Curr. Med. Chem., 17, 1325 (2010). 8 A. M Asiri, Pigment & Resin Technology, 32(5), 326-330, (2003)
Two strategies
Heterogeneous catalysis over acidic zeolitesHomogeneous catalysis with Pt
complexes
Light-driven synthesis of sub-nanometric metallic Ru catalysts on TiO2
Joanna Wojciechowskaa,b
, Elisa Gitzhoferb, Nicolas Keller
b, Jacek Grams
a, and
Agnieszka M. Rupperta
a Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, ul.
Żeromskiego 116, 90-924, Łódź, Poland b Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé, CNRS/University of Strasbourg, 25
rue Becquerel, 67087 Strasbourg, France
Heterogeneous catalysis plays a crucial role in various industrial processes and
requires in most of the cases the design of tailored supported metal nanoparticles as catalysts.
In this frame, the implementation of sustainable preparation methods with fine control in
terms of size distribution is of high interest.
We focused on the synthesis of Ru/TiO2 catalysts that are promising heterogeneous
catalysts in several key-reactions involved in the catalytic conversion of biomass towards
biofuels, fuel additives or more generally biochemicals. We report on an elegant method for
synthesizing metallic Ru nanoparticles on a TiO2 support carrier. The strategy was to use the
redox photo-activity of TiO2 for developing a low-temperature one-step photo-assisted
synthesis method as a sustainable alternative to classical wet impregnation of the support,
with no use of thermal treatment and external hydrogen, or any chemical reductant.
Ru/TiO2 catalysts were successfully synthetized at room temperature under solar light
with sub-nanometric, sharp and finely tunable Ru particle
size distribution (Fig 1. e.g. with 1 wt.% of Ru) using both
Ru(acac)3 and RuCl3 metallic salt precursors in water or in
water/methanol solutions.
The presence of metallic Ru was proved by means
of Transmission Electron Microscopy (TEM) and X-ray
Photoelectron Spectroscopy (XPS). The reaction
parameters were optimized for both metallic Ru precursors
with no differences in terms of Ru particle size
distribution and of surface properties. However, the
apparent kinetic constant for the metallic Ru nanoparticle
synthesis were much lower in the case of Ru(acac)3 vs.
RuCl3 salt, so that Ru(acac)3 was not suitable for preparing
highly loaded catalysts.
Depending on the precursor salt used and on the
photoactivity of the host TiO2 supports, we will highlight
the similarities and the differences in terms of particle size
distribution, synthesis kinetic, surface properties as well as
reaction mechanisms, so that hypothesis relative to the
role of the photogenerated electrons and holes in the
synthesis of metallic Ru from the corresponding
precursors salts will be proposed.
Additionally, we evidenced that a fine monitoring of the metal Ru particle size was
possible via a controlled growth of Ru nanoclusters under irradiation, by tuning important
reaction parameters such as pH or by extending the duration of the irradiation.
The French Embassy in Poland is thanked for supporting the PhD work of J.W via a French Government Grant.
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10
20
30
40
50
60
Fre
qu
en
cy
, %
Particle diameter, nm
d = 0.6 nm
Fig. 1 TEM image of the Ru/TiO2 catalyst and
Ru particle size distribution
Journée des doctorants, Communication
Site-Occupation Embedding Theory
Bruno Senjean1, Naoki Nakatani2, Masahisa Tsuchiizu3, and Emmanuel Fromager1
1Laboratoire de Chimie Quantique, Institut de Chimie, CNRS / Université de Strasbourg,1 rue Blaise Pascal, F-67000Strasbourg, France
2 Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-Osawa,Hachioji, Tokyo 192-0397, Japan 3 Department of Physics, Nara Women’s University, Nara 630-8506, Japan
keywords : Density functional theory, electron correlation, Hubbard Hamiltonian.
Modelling strongly correlated systems is still challenging for both quantum chemical and conden-sed matter physics communities. Such systems are for instance transition metal oxides, which depictmetal-insulator transitions or have interesting properties such as high-Tc superconductivity in cu-prates. In those cases, mean-field approaches (Hückel, Hartree Fock) give a wrong description of theproperties of the system. One needs to go beyond the mean field approximation :
• On the one hand, post-Hartree Fock theories (called Wave Function Theory (WFT)) have beendeveloped and perform with a good accuracy, but they are computationally expensive.• On the other hand, Kohn-Sham Density Functional Theory (KS-DFT) is a computationally low costmethod with a relatively good accuracy. However, the approximations made for the density functionaloften fail to describe strongly correlated systems.
To make the best compromise between computa-tion cost and accuracy, the Site-Occupation Em-bedding Theory (SOET)1,2 has been proposed.The SOET is an in-principle exact embeddingtheory which relies on the mapping of the fully-interacting system onto an impurity-interactingone, in contrast to the standard KS-DFT wherethe mapping is done onto a noninteracting system.
t t
t t t t t t t t
t t
t
t t
t
t t
t t
t
t t t
t t t t t t t
t t
t t
t t t t t t t t
t t
t t
t
t t
t t
t
t t t
t t t t t t t
t
U
U
t t
t t t t t t t t
t
t t
t t
t
t t
t t
t
t t t
t t t t t t t
t t
t t
t t t t t t t t
t t
t t
t
t t
t t
t
t t t
t t t t t t t
t
t t
t t t t t t t t
t
t t
t t
t
t t
t t
t
t t t
t t t t t t t
t t
t t
t t t t t t t t
t t
t t
t
t t
t t
t
t t t
t t t t t t t
t
For a proof of concept, model Hamiltonians are used because of their simplicity combined withtheir physical richness. In this communication I will present the general context of the method andthe usefulness of model Hamiltonians, followed by the results obtained using impurity correlationenergies (functional of the density) based on those models.3
[1] E. Fromager, Mol. Phys., 2015, 113, 419.[2] B. Senjean, M. Tsuchiizu, V. Robert and E. Fromager, Mol.
Phys., 2017, 115, 48–62.[3] B. Senjean, N. Nakatani, M. Tsuchiizu and E. Fromager,
arXiv preprint arXiv :1710.03125, 2017.
!
Green’s function-based density-functional theory for lattice Hamiltonians
Laurent Mazouin and Emmanuel Fromager
Laboratoire de Chimie quantique, Institut de Chimie, CNRS/Université de Strasbourg,
4 rue Blaise Pascal, Strasbourg, France
For decades density-functional theory (DFT) has been the method of choice for treating
infinite systems such as molecules between electrodes, semi-conductors or graphene. The
success of DFT is due to the fact that, in theory, it is possible to recover the real electronic
density from a non-interacting reference system and incorporate all the effects of electron
repulsion into an effective local, potential. This approach transforms a many-body problem into
a one-body problem and reduces the computational cost considerably. However, all practical
calculations rely on approximations and perform poorly for strongly correlated materials.
In this work, we describe a more advanced form of DFT for lattice Hamiltonians, site-
occupation embedding theory (SOET)1,2,3
, which corrects the flaws of traditional DFT. The
methodology of SOET consists in including some electron repulsion effects into the reference
system by switching on the Coulomb repulsion on one site (embedded impurity) while the other
sites (bath) remain non-interacting. The impurity can in principle be treated exactly and the
effects of electron repulsion in the bath are included into the self-energy, a frequency-
dependent, non-local potential. This self-energy yields a new Green’s function that gives access
to the exact electronic density and a whole range of other properties of the system such as the
ground-state energy, the conductivity or the ionization potential. Unfortunately, the exact self-
energy of the bath is not known explicitly and calculating it numerically is computationally
very demanding. So, one of the major challenges in SOET consists in developing a density-
functional self-energy of the bath that leads to a hybrid DFT combined with Green’s functions.
In a first step, we present approximate self-energies which are based on second-order
perturbation theory (SOPT), GW4,5
and the T-matrix4,6
and illustrate the performance of these
methods by applying them to the two-site Hubbard model.
References
1. E. Fromager, Mol. Phys. 113, 419 (2015).
2. B. Senjean, M. Tsuchiizu, V. Robert, and E. Fromager, Mol. Phys. 115, 48 (2017).
3. B. Senjean, N. Nakatani, M. Tsuchiizu, and E. Fromager, ArXiv:1710.03125 (2017).
4. R.M. Martin, L. Reining, and D.M. Ceperley, Interacting Electrons (Cambridge University Press, 2016).
5. P. Romaniello, F. Bechstedt, and L. Reining, Phys. Rev. B, 85, 155131 (2012).
6. P. Romaniello, S. Guyot, and L. Reining, J. Chem. Phys., 131, 154111 (2009).
The different ways of connecting the non-interacting, the embedded impurity and the physical system through the
self-energy.
Synthesis, characterization and reactivity of photocatalytic Au-gC3N4
nanocomposites for Hydrogen production from water under solar-light P. Jiménez-Calvo
1*, T. Cottineau
1, V. Caps
1, V. Keller
1 1 ICPEES, Institut de Chimie et Procédés pour l’Energie, l’Environnement et la Santé, CNRS/Université de Strasbourg, UMR 7515 (CNRS), 25
rue Becquerel 67087 Strasbourg Cedex, France
Photocatalysis is an innovative and promising technology due to its facility to directly
harvest solar energy to induce chemical transformation and generate solar fuels that stored
the energy. Indeed, the water dissociation (water-splitting) highlighted by Fujishima and
Honda in a photoelectrocatalytic cell opened a promising way to produce hydrogen using
light energy1.
In our study, we will focus on photocatalytic graphitic carbon nitride (g-C3N4)
semiconductors synthesized in Air, H2, NH3, N2 and Argon atmospheres under continuous
flow and decorated with gold nanoparticles (Au NPs). g-C3N4 is obtained by thermal
polycondensation reaction using N2-rich precursors2. Gold nanoparticles were deposited
directly onto the g-C3N4 support by chemical reduction at room temperature3.
Even if the main characterizations revealed the fingerprints of g-C3N4, the use of different
synthesis atmospheres led to specific characteristics in terms of light absorption, stability,
structural, morphological and surface properties. After optimization of Au NPs deposition,
performances were evaluated
towards photocatalytic H2
production from water using very
low amount of sacrificial agent (1
vol.%). All the Au/g-C3N4
composites loaded with 0,3wt%
Au NPs achieved H2 production
under artificial solar-light
irradiation at room temperature.
The best photocatalytic activity
performance was found for g-C3N4
material synthesized under NH3
atmosphere which exhibited H2
formation rate of 324μmol*h-1
*g-
1. The structure-activity correlation
of the different g-C3N4
photocatalysts will be discussed
depending on the synthesis used.
References 1
A. Fujishima, K. Honda, Nature 238, 1972, 37 2
Y. Wang, X. Wang and M. Antonietti, Angew. Chem., Int. Ed., 2012, 51, 68–89.
3 V. Caps et al, Catalysis Today, 235, 2014, 90-97
Sequence-coded polymers and their use as molecular barcodes for
materials labelling
Denise Karamessini1, Benoit. E. Petit1, Michel Bouquey1, Laurence Charles2, Jean-François Lutz1*
1Precision Macromolecular Chemistry, Institut Charles Sadron, CNRS UPR-22, 23 rue du Loess, 67034 Strasbourg
Cedex 2, France, E-mail: [email protected].
2 Aix-Marseil le Université – CNRS, UMR 7273, Institute of Radical Chemistry, 13397 Marseille Cedex 20, France
Anti-counterfeit technologies have become very important during the last decades, for example in the
domains of food and pharmaceutical packaging, paper currency, luxury products and high-value
artworks. These technologies require novel techniques for tracing commercial products that are
extremely difficult to be copied but very efficient for discriminating original products from fraud ones. In
this context, sequence-coded polymer barcodes have recently been proposed as an interesting new
option. In the present work, digitally-encoded polyurethanes, synthesized by orthogonal solid-phase
synthesis, were tested as molecular barcodes. The inclusion of these sequence-coded labels into
commodity plastics,such as polystyrene films, photopolymerized 3D methacrylate prints and intraocular
implants, was studied and their extraction was investigated by mass spectrometry and NMR. In all cases,
the labels were efficiently extracted from the plastic materials and their coded sequences were easily
deciphered by tandem mass spectrometry. These results indicate that sequence-coded polyurethane
tags represent a promising class of polymers for product labeling and traceability.
References
1. J.-F. Lutz, M. Ouchi, D. R. Liu, M. Sawamoto, Science 2013, 341,
2. H. Colquhoun, J.-F. Lutz, Nat. Chem. 2014, 6, 455.
3 H. Mutlu, J.-F. Lutz, Angew. Chem., Int. Ed. 2014, 53, 13010.
4 U. S. Gunay, B. E. Petit, D. Karamessini, A. Al Ouahabi, J.-A. Amalian, C. Chendo, M. Bouquey, D. Gigmes, L.
Charles, J.-F. Lutz, Chem 2016, 1, 114-126.
5 D. Karamessini, B. E. Petit,Michel Bouquey,L. Charles, J.-F. Lutz, Adv. Funct. Mater2017, 27, 1604595
Mouvements moléculaires contrôlés dans des rotaxanes
porphyriniques
Djemili Ryan
Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnelles
Université de Strasbourg, Institut Le Bel, 4 rue Blaise Pascal, 67070 Strasbourg
Directrice de thèse : Pr. Valérie Heitz
Co-encadrante : Dr. Stéphanie Durot
Les molécules imbriquées mécaniquement (MIM) sont des assemblages de plusieurs sous-unités covalentes liées entre
elles non pas par des liaisons covalentes, mais par l’incapacité qu’ont ces sous-unités à se désentrelacer. Il existe deux
grands archétypes de MIM : les caténanes et les rotaxanes.1 Les rotaxanes sont composés, dans leur forme la plus
simple appelée [2]rotaxane, d’un axe linaire passant à travers un macrocycle et terminé par des bouchons volumineux
destinés à éviter le désenfilage.
La synthèse et l’étude des MIM, au départ considérées comme une curiosité ésotérique, ont connu depuis trois
décennies un essor considérable et ce, grâce à l’utilisation des MIM dans de nombreuses applications.2
L’objectif fixé est de synthétiser un [2]rotaxane dont l’anneau traditionnel sera remplacé par une cage moléculaire
synthétisée au laboratoire (Figure 1).3
Figure 1 : Schéma du [2]rotaxane.
Les cages moléculaires sont des architectures possédant une structure creuse. Un nouveau microenvironnement
chimique dont les propriétés diffèrent de celles de la solution est ainsi créé.4,5
L’originalité du rotaxane envisagé réside en l’utilisation d’une cage possédant une taille de cavité variable.
Dans cette optique, la recherche de molécules invitées encapsulées à l’intérieur de la cavité de la cage et la synthèse
des différents éléments composant le [2]rotaxane seront présentés.
Références
(1) J. F. Stoddart, Chem. Soc. Rev., 2009, 38, 1802.
(2) J. E. M. Lewis, M. Galli, S. M. Goldup, Chem. Commun., 2017, 53, 298.
(3) L. Schoepff, L. Kocher, S. Durot, V. Heitz, J. Org. Chem., 2017, 82, 5845.
(4) J. Kang, J. Rebek, Jr., Nature, 1997, 385, 50.
(5) Yoshizawa, M.; Tamura, M.; Fujita, M., Science, 2006, 312, 251.
(6) L. Kocher, S. Durot, V. Heitz, Chem. Commun., 2015, 51, 13181.
PORPHYRIN ASSEMBLIES ON HOPG
M.-A. CARVALHO, H. DEKKICHE, L. KARMAZIN, B. VINCENT, R. RUPPERT,
M. KANESATO, Y. KIKKAWA
UMR 7177 CNRS-Institut de Chimie, Université de Strasbourg, rue Blaise Pascal, F-67000 STRASBOURG National Institute
of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, TSUKUBA,
Ibaraki 305-8562 (Japan)
Porphyrins are extensively studied due to their exceptional electronic and optical properties.
Porphyrins bearing alkyl or alkoxy chains can be well organised on surfaces using Van der Waals
interactions,1 hydrogen bonds
2 or coordination bonds.
For example, coordination bonds have been used to
assemble porphyrins possessing two or more external coordination sites leading to wires or nanosheets.3
However, these wires do not present particular electronic properties because the external coordination
sites used prevented electronic interactions between the porphyrins.
Our group has designed various dimers and oligomers of porphyrins linked by metal ions through
external coordination sites.4 Strong electronic interactions between the subunits were demonstrated by
electronic spectroscopy, electrochemistry, energy transfer studies and DFT calculations.5 Adding alkyl or
alkoxy chains to our porphyrin dimers allowed their ordered assembly at the solid/liquid interface on
HOPG, as visualized by STM. Using an unusual method, transition metal-linked porphyrin oligomers
were obtained on HOPG by adding a metal cation to well-organized hydrogen bonded assemblies of
porphyrins bearing two external coordination sites. Electronic delocalization along these self-assembled
wires is expected, as demonstrated for dimers and finite oligomers in solution.
Porphyrin dimer and STM image of a dimer on HOPG.
1 J.Otsuki , E. Nagamine , T. Kondo , Iwasaki K., M. Asakawa , K. Miyake. J. Am. Chem. Soc. 2005, 127, 10400.
2 R. Sakamoto, K. Takada, T. Pal, H. Maeda, T. Kambe, H. Nishihara, Chem. Comm., 2017, 53, 5781.
3 M. E. Garah, N. Marets, M. Mauro, A. Aliprandi, S. Bonacchi, L. D. Cola, A. Ciesielski, V. Bulach, M. W. Hosseini, P.
Samori, J. Am. Chem. Soc., 2015, 137, 8450.
4 S. Richeter, C. Jeandon, J.-P. Gisselbrecht , R. Ruppert, H. J. Callot H. J. Am. Chem. Soc. 2002, 124, 6168-6179.
5 H. Dekkiche , A. Buisson, A. Langlois, P.-L. Karsenti, L. Ruhlmann, R. Ruppert, P. Harvey. Chem. Eur. J. 2016, 22, 10484.
N
N
N
N
Ni
X
NH
Ar
Ar
Ar N
N
N
N
Ni
X
HN
Ar
Ar
Ar
Pd
Ar =
Ar =
t-Bu
t-Bu
OC12H25
X = O, S
Spherical
cavity
Molecular tectonics: gas adsorption and chiral uptake of (L)- and (D)- tryptophan by homochiral
porous coordination polymers
Romain Corsob, Donata Asnaghi
a, Patrick Larpent
b, Irene Bassanetti
a, Abdelaziz Jouaiti
b, Nathalie Kyritsakas
b,
Angiolina Comotti*a, Piero Sozzani
a and Mir Wais Hosseini
b
a Department of Materials Science
University of Milano Bicocco, via R. Cozzi 55, Milan, Italy b Laboratoire de Chimie de Coordination Organique (UMR-CNRS 7140)
Université de Strasbourg, Institut Le Bel, 4 tue Blaise Pascal, 67000 Strasbourg, France
Since several years, the interest in coordination networks or metal-organic frameworks (MOFs)
increases due to their structural features (dimension, geometry, topology) and their properties.1,2
These
porous coordination networks are composed of organic tectons and metallic nodes. The design, formation
and description of such periodic architectures may be explored by the approach called Molecular Tectonic.3-5
Combinations of a series of enantiomerically pure organic tectons bearing four carboxylate moieties
(figure 1) with Zn(II) or Cu(II) cations lead to the formation of isostructural chiral porous crystals. The
crystalline materials have been characterized by X-ray diffraction on single crystals as well as by powder X-
ray diffraction.
Fig.1: Different tectons used
In all cases studied, the X-Ray diffraction investigations revealed their isostructural nature. The
porous crystals (figure 2) display two types of cavities differing by their volumes, one spherical (small
cavity) and the other of the ovaloid type (larger cavity).
Fig.2: DRX structure of the networks
Gas sorption of N2 and CO2 propensity of the porous crystalline materials was investigated by BET.
Uptake of (L)- and (D)-tryptophan in pores was also studied and a preference for (L)-tryptophan by RR-
alkyl-MoF has been observed.6
References
1. Chem. Rev. 2012, 112, MOFs special issue.
2. Chem. Soc. Rev. 2014, 43, themed issue on MOFs.
3. Mann, S. Nature 1993, 365, 499−505.
4. Simard, M.; Su, D.; Wuest, J. D., J. Am. Chem. Soc. 1991, 113, 4696−4698.
5. Hosseini, M. W. Acc. Chem. Res. 2005, 38, 313-323
6. Asnaghi, D.; Corso, R.; Larpent, P.; Bassanetti, I.; Jouaiti, A. ; Kyritsakas, N. ; Comotti, A. ; Sozzani, P,.
Hosseini, M. W., Chem. Comm., 2017, 53, 5740-5743
Ovaloïd cavity
Molecular tectonics based on pyridine and terpyridine bearing
nucleobases
Elsa Tufenkjian, Veronique Bulach, Aziz Jouaiti, Nathalie Kyritsakas, Mir Wais Hosseini Laboratory of Molecular Tectonics, UMR UDS-CNRS 7140, Univeristy of Strasbourg, Institut Le Bel, F-
67000, Strasbourg, France
Molecular tectonics is a domain of supramolecular chemistry dealing with the formation of one, two and
three-dimensional periodic architectures. These periodic architectures or Molecular Networks result from
self-assembly processes of building blocks referred to as tectons. Tectons offer complementary interaction
sites leading to a recognition pattern via specific interactions.(1) Coordination and H-bonds are among the
most widely used interactions in molecular tectonics due to their directionality that should in principle
allow a certain prediction of the topology of the final assembly. Coordination bonds take place between
organic tectons bearing coordinating sites and a metal center generating coordination networks.(2) H-
bonds, although less energetic, is directional and can thus be used as a secondary recognition site. (3) Our
interest is to use both types of intermolecular interactions for the design of tectons bearing both
coordination and hydrogen bond donor/acceptor sites. One of the most used Hydrogen bonding pattern
of the Watson-Crick type is based on complementary nucleobases (NBs).(4) Our aim is to connect
coordinating site such as pyridine or terpyridine to NBs and to use these tectons to build H-bonded
coordination networks of various topology in the presence of metal cations. During this talk, we will
present the synthesis of a library of new tectons based on pyridine or terpyridine moiety and nucleobases
as well as the generation of H-bonded coordination networks. (Figure 1)
Figure 1: Coordination networks obtained upon combining a thymine-terpyridine based tecton with Cd(NO3)2 (left) and
Cu(CH3OO)2(right)
(1) (a) J.M. Lehn, Pure Appl. Chem., 1978, 365,499, (b) S. Mann, Nature, 1993, 365, 499-505, (c) M. W. Hosseini, Chem. Comm., 2005, 5825.
(2) (a) B.F. Abrahams, B. F. Hoskins, R. Robson, J. Am. Chem. Soc., 1991, 113, 3606, (b) M. W. Hosseini, Acc. Chem. Res., 2005, 38, 313-323.
(3) (a) M. Simard, D. Su, J. D. Wuest, J. Am. Chem. SOC. 1991, 113, 4696-4698, (b) K. Fujimoto et al.,Materials Science and Engineering,
2007, 27,142-147, (c) Sargsyan, A. A. Schatz, J. Kubella, M. Balaz, Chem. Commun, 2013, 49, 1020-1022.
(4) a) J. D. Watson, F.H. C. Crick, Nature, 1953, 171, 737-738, (b) W. Saenger,principles of Nucleic Acid Structures, Springer-Verlag, New
York,1983, (c) J. L. Sessler, C.M. Lawrence, J. Jayawickramarajah, Chem. Soc. Rev.2007, 36, 314-325.
Exploiting Higher Order Aggregation Phenomena in Brønsted Acid Catalysis
Vuk D. Vuković, Edward Richmond, Eléna Wolf, Florent Noёl, Jing Yi, Pavle Kravljanac, Joseph Moran1
1Institut de Science et d’Ingénierie Supramoléculaires - UMR 7006, Strasbourg, France
Email: [email protected] and [email protected]
Abstract
The catalytic activation of alcohols towards dehydrative bond formation in the absence of pre-activation
has become a major research interest over the past two decades.[1,2,3]
In this communication, the
importance of aggregation in Brønsted acid catalyzed Friedel-Crafts reactions of highly electronically
deactivated primary benzylic alcohols is presented.[4]
A similar approach is described regarding the
activation of propargylic alcohols as a new route to selectively access CF3-substituted allenes and indenes
from the same starting compounds. Finally, we discuss catalytic Friedel-Crafts reactions of unactivated
and donor-acceptor cyclopropanes.
Figure 1. Chemical transformations achieved thanks to Brønsted acid induced aggregation in 1,1,1,3,3,3-
hexafluoroisopropanol (HFIP)
Acknowledgments
V. D. V. thanks the French Government for a PhD scholarship.
References
[1] For a recent review, see: Dryzhakov, M.; Richmond, E.; Moran, J. Synthesis 2016, 935.
[2] Constable D. et al. Green Chem. 2007, 9, 411.
[3] For selected recent examples, see: (a) Zheng H., Ghanbari S., Nakamura S., Hall D. G. Angew. Chem.
Int. Ed. 2012, 51, 6187; (b) Mo X., Yakiwchuk J., Danserau J., McCubbin J. A., Hall D. G. J. Am. Chem.
Soc. 2015, 137, 9694; (c) Dryzhakov, M.; Hellal, M.; Wolf, E.; Falk, F.; Moran, J. J. Am. Chem. Soc.
2015, 137, 9555.
[4] Vuković, V. D.; Richmond, E.; Wolf, E.; Moran, J. Angew. Chem. Int. Ed. 2017, 56, 3085.
Rheological studies of contractile gels based on
light-driven rotary molecular motors.
Jean-Rémy Colard-Itté1, Quan Li1,2, Dominique Collin3, Gad Fuks1, Emilie Moulin1, Giacomo
Mariani4, Eric Buhler4, Nicolas Giuseppone1*
1SAMS research group, Institut Charles Sadron, University of Strasbourg, CNRS, 23 rue du Loess, BP 84047,
67034, Strasbourg Cedex 2, France. 2Current address: Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, USA
3SYCOMMOR research group, Institut Charles Sadron, University of Strasbourg, CNRS, 23 rue du Loess, BP
84047, 67034, Strasbourg Cedex 2, France.
4MSC research group, UMR 7057 CNRS, University Paris 7 Diderot, 75205 Paris Cedex 13, France.
*E-mail address: [email protected]
The ability to create out-of-equilibrium collective molecular movements and to transfer them
up to a macroscopic scale is of particular interest to access a firmly new generation of active
materials. Recently, we have integrated rotary molecular motors as reticulation nodes in
polymer networks.1 By designing chemical connections with proper topologies, and upon light
activation, the rotation of the motors results in the winding of the polymer chains at the local
scale, and in the contraction of the material at higher length scales. The overall process produces
an effective mechanical work by converting light energy into elastic energy within polymer
entanglements. We have also shown that, by using additional molecular elements (e.g.
modulators), one can release the stored energy and reset the system to its expanded state which
can thus function as a muscle-like material driven out-of-equilibrium at all scales.2 We now
wish to present the first rheological and neutron scattering studies performed on these active
materials. We will describe shearing experiments achieved with a piezo-rheometer on two
different sets of gels. In the first set, we varied the length of the polymer chains between the
motors; and in the second set, we varied the polymer molar concentration for a given molecular
weight. For each set, the shear modulus of the gel was measured before and after light
irradiation. The experimental results show that the ratio of the modulus is directly correlated to
the ratio of volume before and after actuation of the material. In addition, the material presents
a maximum of efficiency for a given polymer mass concentration, which allows the prediction
of optimal systems based on their critical overlap concentration. Neutron scattering studies also
reveal the major importance of inhomogeneities in the macroscopic contraction process.
1- Li, Q., Fuks, G., Moulin, E., Maaloum, M., Rawiso, M., Kulic, I., Foy, J. T., Giuseppone N., Nature
Nanotech. 2015, 10, 161-165.
2- Foy, J. T., Li, Q., Goujon, A., Colard-Itté, J.-R., Fuks, G., Moulin, E., Schiffmann, O., Dattler, D.,
Funeriu, D. P., Giuseppone, N., Nature Nanotech. 2017, 12, 540-545.
[1] M.C. Koetting et al. Mater Sci Eng R Rep 2015, 93, 1–49
[2] F. Fiorini et al. Small 2016, 12, 4881–4893
[3] W. T. Tan et al. Electroanalysis 2008, 20, 2447–2453
Development of stimuli-responsive polyamidoamine-based hydrogels
Matteo Bessi, Dr. Simone Silvestrini, Prof. Luisa De Cola
Laboratoire de Chimie et des Biomatériaux Supramoléculaires
ISIS - Université de Strasbourg
8 Allée Gaspard Monge, 67083 Strasbourg Cedex
Hydrogels are hydrophilic, cross-linked molecular structures capable of storing huge
amounts of water and are considered promising systems for the development of new hybrid
materials. Stimuli-responsive hydrogels have unique features, in that their chemical and
mechanical properties can be tuned through external stimuli such as changes in temperature, pH
or irradiation with light. This has made them popular in the material science community and they
are being proposed for the development of sensors, drug delivery systems, and prostheses.[1]
Our group has recently reported the formulation of a biocompatible, non-stimuli-
responsive hydrogel. The polyamidoamine backbone shown in the figure, is formed without the
need for initiators through aza-Michael condensation of methylene-bis-acrylamide (MBA) and g-
aminobutyric acid (GABA), with pentaethylenehexamine (PEHA) serving as a cross-linker.
Interestingly, this hydrogel is able to release small molecules and allows cells proliferations.[2]
Figure 1: Synthesis scheme of the polyamidoamine hydrogel (left); Reaction scheme for the oxidation of methionine with C60-
hydrogel under light exposure (right).[3]
In this presentation, the preparation of new stimuli-responsive hydrogels will be outlined
starting from the general molecular structure described above, by substituting one or more of its
constituents. The new monomers designed to this end bear both the functional groups necessary
to the polymerization of the polyamidoamine chains and structures that can (i) generate singlet
oxygen upon light irradiation, (ii) disrupting or changing the wettability of the polymer matrix by
getting oxidized or (iii) allow for the transport of an electrical signal through the hydrogel.
Synthesis of monodisperse sequence encoded copolymers using fast orthogonal chemistry
Gianni Cavallo1, Abdelaziz Al Ouahabi
1, Laurence Oswald
1, Laurence Charles
2, Jean-François
Lutz1
1 Precision Macromolecular Chemistry, Institut Charles Sadron, UPR-22 CNRS, BP 84047, 23 rue du Loess 67034 Strasbourg Cedex 2, France,
2 Aix-Marseille Universitė, CNRS, Institute of Radical Chemistry UMR 7273, Marseille, France
Information containing polymers constitute a new class of molecules that enables data storage at the molecular
level.1 These linear macromolecules are built up using two comonomers, representing bit 0 and 1 respectively, thus
allowing binary coding. Several strategies for the efficient synthesis of information containing polymers have been
developed by J.-F. Lutz and coworkers2. For instance, polymers synthesized by phosphoramidite protocols
3 as well
as the new class of poly(alkoxy amine amide)s4 show interesting features. Here we present a new strategy for the
iterative synthesis of information-containing polymers based on two chemoselective steps, namely the
phosphoramidite coupling and a radical-radical coupling. This orthogonal strategy does not employ protecting
groups and utilizes two different types of building blocks: a spacer which contain nitroxide and hydroxy functions
and a coded monomer, defining the bits (0 and 1), that exhibit phosphoramidite and alkyl bromide functional
groups. Moreover, the encoded sequences can be easily analyzed by tandem mass spectrometry. Hence,
sequence-coded poly(alkoxyamine phosphodiester)s represent a promising new class of information containing
macromolecules
References
1. Jean-François Lutz, Jean-Marie Lehn, E.W. Meijer and Krzysztof Matyjaszewski, Nat. Rev. Mat. 24, 16024 (2016)
2. Jean-François Lutz, Macromolecules, 48, 4759-4767 (2015)
3. Abdelaziz Al Ouahabi, Laurence Charles, and Jean-François Lutz, J. Am. Chem. Soc. 137, 5629-5635 (2015) 4. Raj Kumar Roy, Anna Meszynska, Chloė Laure, Laurence Charles, Claire Verchin & Jean-François Lutz, Nat. Commun.6:7237 (2015)
Towards the enantioselective C(sp3) difluoromethylation
Chloé BATISSE, Armen PANOSSIAN, Gilles HANQUET and Frédéric R. LEROUX
Université de Strasbourg, CNRS, LCM UMR 7509, ECPM, 25 Rue Becquerel, 67087 Strasbourg, France.
e-mail: [email protected], [email protected], [email protected]
Despite being largely absent from natural products and biological processes, fluorine plays an increasingly important role in numerous areas of our daily life. Decades of chemical research have shown that the fluorine atom and the fluorine-containing motifs profoundly impact the structure, reactivity and function of organic and inorganic molecules.1 Fluorine containing compounds are nowadays synthesized in pharmaceutical, agrochemical, polymer and electronic researches on a routine basis. A logical consequence of these highly desirable properties is that more than 200 pharmaceuticals and 155 agrochemicals (among the 920 registered) containing at least one fluorine atom are currently on the market, which accounts for approximately 25% of the bioactive compounds.2 The presence of fluorine atoms or fluoroalkyl groups in bioactive molecules can indeed deeply modify their physical, chemical and biological properties.3 For instance, it can enhance their metabolic stability, lipophilicity, bioavailability and membrane permeability as well as modify their acidity or basicity. In contrast to the enantioselective trifluoromethylation, the enantioselective introduction of a difluoromethyl group is in its infancy.4 We wish here to describe a new way to access enantioenriched difluoromethylated molecules using a chiral inductor. This inductor can perform central-to-central chirality transfer and can therefore lead to building-blocks of high added value.
Scheme: Strategy to access highly enantioenriched difluoromethylated alcohols
References 1. (a) J. P. Bégué, D. Bonnet-Delpon, Bioorganic and Medicinal Chemistry of Fluorine; John Wiley & Sons, Inc.: Hoboken, 2008; (b) Fluorine In Medicinal Chemistry And Chemical Biology (Ed.: I.Ojima), John Wiley & Sons Ltd., 2009. 2. Wang, J.; Sanchez-Rosello, M.; Acena, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A. and Liu, H
Chem. Rev. 2014, 114, 2432-2506. 3. (a) K. L. Kirk, J. Fluorine Chem. 2006, 127, 1013-1029; (b) K. Müller, C. Faeh, F. Diederich, Science 2007, 317, 1881; (c) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37, 320-330. 4. (a) Shibata, N.; Mizuta, S.; Kawai, H. Tetrahedron: Asymmetry 2008, 19, 2633-2644; (b) C. Ni, F. Wang, J. Hu, Beilstein J. Org. Chem. 2008, 4, 21.
RESUMES DES
COMMUNICATIONS ORALES
SESSION B
Luminescent lanthanide-loaded polymer nanoparticles as bright probes for
cellular imaging
Anne Runser1, Andreas Reisch1, Marcelina Cardoso Dos Santos2, Aline Nonat3, Loïc
Charbonnière3, Andrey Klymchenko1 and Niko Hildebrandt2.
1 Laboratoire de Biophotonique et Pharmacologie, UMR 7213 CNRS, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch France
2 NanoBioPhotonics, Institut d’Electronique Fondamentale, Université Paris-Saclay, Université Paris-Sud, CNRS, Orsay, France
3 Laboratoire d’Ingénierie Moléculaire Appliquée à L’Analyse, IPHC, UMR 7178 CNRS, Université de Strasbourg, 25 rue Becquerel, 67000 Strasbourg France
E-mail: [email protected]
Lanthanides have emerged over the last years as attractive probes for bioimaging.[1] Indeed the exceptionally long lifetime of lanthanides as well as their large Stokes shift can be used to overcome autofluorescence and light scattering issues in biological samples. However, they are strongly limited by their low extinction coefficients providing a limited brightness. Nevertheless, a superior brightness might be achieved by loading a large quantity of the emitters inside polymer nanoparticles (NPs).[2]
Here, we propose an approach to design bright luminescent probes by encapsulating a lanthanide complex inside a polymer matrix. We previously described a charge-controlled nanoprecipitation for making ultrasmall polymer NPs allowing an efficient encapsulation of high amounts of hydrophobic fluorescent dyes.[3,4] Using this approach, we assembled three series of poly(methyl methacrylate) (PMMA) based NPs with different sizes (10, 20 and 30 nm) encapsulating up to 40 wt% of an Eu complex (AMN-106). The resulting NPs were characterized with respect to their size, absorbance and luminescence properties. These lanthanide-loaded polymer NPs showed quantum yields up to 40% even at the highest loadings corresponding to more than 200 luminescent complexes per particle. These NPs are readily internalized by cells and show excellent stability and brightness for cellular imaging.
Funding: Agence National de Recherche JC/JC grant “supertrack” ANR-16-CE09-0007 and European Research Council (ERC) Consolidator Grant BrightSens 648528.
Acknowledgement: We thank Christine Ruhlmann for help with electron microscopy.
References:
[1] Sy, M.; Nonat, A.; Hildebrandt, N.; Charbonnière, L.J, Chem. Commun. 52, (2016), 5080-5095. [2] Reisch, A.; Klymchenko, A.S. Small 12, 15 (2016), 1968-1992. [3] Reisch, A.; Runser, A.; Arntz, Y.; Mély, Y.; Klymchenko, A.S. ACS Nano 9, 5 (2015), 5104-5116. [4] A. Reisch, P. Didier, L. Richert, S. Oncul, Y. Arntz, Y. Mély, A.S. Klymchenko, Nat Commun. 2014, 9, 4089.
Development of a pharmacophoric deconvolution method to accelerate the discovery of antiplasmodial molecules from Rhodophyta
Laure Margueritte1, Mélanie Bourjot
1, Petar Markov
2, Guillaume Bret
1, Marc-André Delsuc
2, Didier
Rognan1, Catherine Vonthron-Sénécheau
1
1 Laboratoire d'Innovation Thérapeutique UMR CNRS 7200 et
2 Institut de Génétique et de Biologie
Moléculaire et Cellulaire, INSERM U596, UMR CNRS 7104, Université de Strasbourg, Illkirch,
In natural-product research, the bioassay-guided isolation is usually used to find new bioactive
compounds. However, this strategy is time-consuming, onerous and sometimes leads to well-known
molecules1. We are developing a new method based on the Differential Analysis 2D-NMR Spectra
(DANS) and the use of the hyphenated method HPLC-SPE-NMR to solve these inconveniences2. This
method aims to do accelerate the discovery process of new bioactive products from complex natural
extracts. The DANS step enables us to detect a chemical fingerprint through the specific peaks
detection of the bioactive molecule. This step is computerizing by a software development called
Plasmodesma. This software is a tool for 2D-NMR data processing such as data bucketing. Other
processing stages are in writing for spectral cleaning and the differential analysis. In this way, we have
obtained the chemical fingerprint of bio-active molecules from algal extracts enriched with artemisinin
or chloroquine, two known anti-malarial compounds. This analytical strategy will indeed be used to
identify new anti-malarial molecules with an original mechanism of action from active red algae
extracts. Previously, it was shown that red algae are a source of anti-plasmodial products
3. The
parasite Plasmodium possesses a relict organelle, the apicoplast, which is a plastid from a secondary
endosymbiosis of a red alga4. Because of this particular evolutionary past, we hypothesized that red
algae molecules could interfere with apicoplastic biosynthesis pathways in Plasmodium and inhibit its
development.
[1] A.L. Harvey, R. Edrada-Ebel, R.J. Quinn, Nat. Rev. Drug. Discov. 2015, 14(2), 111–129
[2] M. Bourjot, L. Margueritte, P. Markov, F. Nardella, J. B. Galle, B. Schaeffer, J. M. P. Viéville, G. Bret, M-A. Delsuc, D.
Rognan, C. Vonthron-Sénécheau, Planta Med., 2016, 81, S1-S381.
[3] C. Vonthron-Sénécheau, M. Kaiser, I. Devambez, A. Vastel, I. Mussio, A. M. Rusig, Mar. Drugs 2011, 9, 922–933
[4] N. M. Fast, J. C. Kissinger, D.S. Roos, P.J. Keeling, Mol. Biol. Evol. 2001, 18, 418–426
[5] S. A. Ralph, G. G. van Dooren, R. F. Waller, M. J. Crawford, M. J. Fraunholz, B. J. Foth, C. J. Tonkin, D. S. Roos, G. I.
McFadden, Nat. Rev. Microbiol. 2004, 2, 203–216
Fluorocarbon Conjugates: New Concept to Increase the Metabolic
Stability of Peptides Targeting GPCRs
Over the past decade, peptides have shown an increasing interest for therapeutic applications. To
date, 60 therapeutic peptides have been already approved by the FDA, 140 are currently under
evaluation in clinical trials and 500 are in preclinical development1. In general, peptides are selective
and efficacious signaling molecules that bind to specific cell surface receptors, such as G protein-
coupled receptors (GPCRs). However, peptides are often not directly suitable for use as convenient
therapeutics because they have intrinsic weaknesses, including poor chemical and physical stability,
and a short in vivo half-life due to rapid enzymatic degradation2, 3
.
To enhance the metabolic stability of GPCR peptide ligands, we propose an unprecedented strategy
based on the grafting of fluorocarbon chains (F-chains) onto peptides of potential therapeutic
interest. The idea was to induce a self-organization of the fluoropeptide in aqueous solution resulting
in the subsequent protection of the native peptide from enzymatic degradation. To demonstrate the
efficacy of our approach the apelin peptide, a neuro-vasoactive peptide which presents a short
plasma half-life, was selected as model4, 5
. Different F-chains were then grafted onto apelin following
a solid-phase approach. The human plasma stability of the resulting fluoropeptides was carefully
investigated.
To gain insight into the mechanism leading to the increase of human plasma stability, original
fluorescent probes were designed and synthesized enabling the studies of the physicochemical and
plasma binding properties of fluoropeptides. Finally, the optimized construct was evaluated in
normotensive rat model highlighting the efficacy of our approach to greatly improve the in vivo
stability of apelin peptide. All together, these promising results should open the route to a
convenient, safe and general approach to greatly increase the metabolic stability of numerous native
peptides for their in vivo use as pharmacological tools and/or therapeutic agents.
1 Fosgerau, K.; Hoffmann. Drug Discovery Today 2015, 20, 122-128.
2 Hallberg, M. Med Res Rev 2015, 35, 464-519.
3 Vlieghe, P.; Lisowski, V.; Martinez, J.; Khrestchatisky, M. Drug Discovery Today 2010, 15, 40-56.
4 Tatemoto, K.; Hosoya, M.; Habata, Y.; Fujii, R.; Kakegawa, T.; Zou, M. X.; Kawamata, Y.; Fukusumi, S.; Hinuma, S.; Kitada, C.; Kurokawa, T.;
Onda, H.; Fujino, M. Biochem. Biophys. Res. Commun. 1998, 251, 471-6.
5 O'Carroll, A. M.; Lolait, S. J.; Harris, L. E.; Pope, G. R. J. Endocrinol. 2013, 219, 13-35.
Compared effects of beta-hydroxybutyrate and bear serum on the proteome of human muscle cells
Blandine Chazarin1, Stéphanie Chanon2, Guillemette GAuquelin-Koch3, Stéphane Blanc1, Etienne
Lefai2 and Fabrice Bertile1
1 CNRS, Université de Strasbourg, IPHC-Laboratoire de Spectrométrie de Masse BioOrganique, 67087
Strasbourg, France 2 Laboratoire CarMeN, INSERM U1060 / INRA 1397, Université de Lyon, 69921 OULLINS, France 3 Centre National d’études Spatiales, CNES, 75001 Paris, France
We recently showed that winter bear serum triggers changes in cultivated human myotubes that
mimics a hibernation-like state. The identification of the active components in the bear serum would
pave the way for innovative solutions to fight human muscle atrophy, one of the main deleterious
characteristics of human ageing and physical inactivity. Βeta-hydroxybutyrate (betaOH) could be a
good candidate as its concentration is markedly increased in winter bear serum and betaOH-
supplemented diets have positive effects on human muscle mass preservation. Hence, human
myotubes were incubated with either FCS or bear serum in the presence of various betaOH
concentrations (N=4/condition). After extraction, proteins were separated on SDS-PAGE gels (4
bands) and tryspin-digested. Tryptic peptides were analyzed using a quantitative label-free-based
method on a nanoUPLC-system (nanoAcquity, Waters) coupled to a Q-Exactive Plus (Thermo) before
data analysis using MaxQuant (Swissprot Homo sapiens database). Quality controls (spiked iRT
peptides and repeated analysis of a same sample pool) indicated very good reproducibility of
retention times (median CV of 0.71%) and quantitative data (median CV of 20.2%). 3780 proteins
(FDR 1%) were quantified, of which a hundredth exhibited a differential abundance across groups
(ANOVA+Tukey tests, p<0.05). As expected, the bear serum induced the main effects, in line with a
decreased protein turnover in human myotubes and possibly reflecting a pro-inflammatory status of
muscle cells. The effects of betaOH, which may favor protein synthesis, were more marked when
added in FCS, but remained limited. These data suggest that the known beneficial effects of betaOH
on muscle mass preservation could be indirect, and that they could be masked by the already potent
impact of the bear serum on human muscle cell protein balance.
Demande de communication orale
Caractérisation d’anticorps immunoconjugués site spécifiques par spectrométrie de masse couplée à la mobilité ionique
Thomas BOTZANOWSKI1, Oscar HERNANDEZ ALBA1, Stéphane ERB1, Anthony
EHKIRCH1, David RABUKA2, Alain BECK3, Penelope DRAKE2, Sarah CIANFERANI1
1Laboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CNRS, IPHC UMR
7178, 67000 Strasbourg, France
2Catalent Biologics West, 5703 Hollis Street, Emeryville, California 94530, United States
3Centre d’Immunologie Pierre-Fabre (CIPF), Saint-Julien-en-Genevois, France
Les anticorps monoclonaux immunoconjugués (Antibody Drug Conjugates, ADCs)
constituent une nouvelle génération de protéines thérapeutiques pour traiter de nombreuses
maladies, dont les cancers. Ce sont des molécules tripartites constituées d’un agent
cytotoxique (drogue) lié de manière covalente à un anticorps monoclonal (mAb) via un linker.
Les chimies de couplage les plus classiquement utilisées ciblent les lysines ou cystéines,
engendrant ainsi une hétérogénéité de greffage au niveau de l’ADC. Afin de mieux contrôler
l’homogénéité des sites de fixation de la drogue sur le mAb, de nouvelles stratégies de
couplage chimique pour cibler spécifiquement certaines positions de l’anticorps et maîtriser
le nombre de molécules cytotoxiques greffées ont été développées. Ces nouvelles chimies
de couplage ont récemment permis de faire émerger une troisième génération d’anticorps
appelée site specific. Dans cette présentation, nous montrons l’intérêt de la mobilité ionique
couplée à la spectrométrie de masse native (IM-MS) pour la caractérisation d’un anticorps de
troisième génération site-spécifique. Dans un premier temps, l’intégrité de l’ADC ainsi que le
profil de greffage et le nombre de moyen de drogues greffées ont été déterminés par MS
native, permettant ainsi d’évaluer l’hétérogénéité de greffage et de valider l’efficacité de la.
nouvelle chimie de couplage utilisée. D’autre part, les expériences de mobilité ionique ont
permis de mesurer les sections efficaces de collision (CCS) du mAb non conjugué et de son
immunoconjugué associé. Pour la première fois, des expériences Collision Induced
Unfolding ont été réalisées sur un ADC et mettent en évidence des profils de déploiement
(unfolding) différents pour le mAb et l’ADC. L’ensemble des résultats obtenus est comparé
aux précédentes études réalisées sur deux anticorps immunoconjugués de référence à
lysine (T-DM1) et à cystéine (Brentuximab Vedotin). Cette étude démontre l’intérêt des
approches de spectrométrie de masse en conditions natives pour la caractérisation de
protéines thérapeutiques de dernière génération.
Etudiant : Maxime Bourguet (3A)
Abstract pour demande de communication orale lors de la JDD du 10/11/2017
---------------------------------------------------------------------------------------------
Epitope characterization of anti-JAM-A antibodies using orthogonal
mass spectrometry and surface plasmon resonance approaches
Maxime Bourguet1, Guillaume Terral1 , Thierry Champion2, François Debaene1, Olivier Colas2,
Elsa Wagner-Rousset2, Nathalie Corvaia2,Alain Beck2and Sarah Cianférani1
(1)Laboratoire de Spectrométrie de Masse BioOrganique(LSMBO), IPHC, DSA, CNRS UMR7178, UdS,
Strasbourg, France - [email protected]
(2) Centre d’Immunologie Pierre-Fabre (CIPF), Saint-Julien-en-Genevois, France - alain.beck@pierre-
fabre.com
Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein expressed
by endothelial and epithelial cells and associated with cancer progression. We present here
the extensive characterization of immune complexes involving JAM-A antigen and three
monoclonal antibodies (mAbs), including hz6F4-2, a humanized version of anti-tumoral 6F4
mAb identified by a functional and proteomic approach in our laboratory. A specific workflow
that combines orthogonal approaches has been designed to determine binding
stoichiometries along with JAM-A epitope mapping determination at high resolution for these
three mAbs. Native mass spectrometry experiments revealed different binding
stoichiometries and affinities, with two molecules of JAM-A being able to bind to hz6F4-2 and
F11 Fab, while only one JAMA was bound to J10.4. Surface plasmon resonance indirect
competitive binding assays suggested epitopes located in close proximity for hz6F4-2 and F11.
Finally, hydrogen-deuterium exchange mass spectrometry was used to precisely identify
epitopes for all mAbs. The results obtained by orthogonal biophysical approaches showed a
clear correlation between the determined epitopes and JAM-A binding characteristics,
allowing the basis for molecular recognition of JAM-A by hz6F4-2 to be definitively established
for the first time. Taken together, our results highlight the power of MS-based structural
approaches for epitope mapping and mAb conformational characterization.
Foldamers based on adamantane
Adriano Aloisi,a Kasper K. Sørensen,
b Niels J. Christensen,
b Knud J. Jensen,
b Alberto
Biancoa!
aUniversity of Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire,
Immunopathologie et Chimie Thérapeutique, Strasbourg, France
bUniversity of Copenhagen, Department of Chemistry, Thoarvaldsensvej 40, 1871
Frederksberg (Denmark)
Adamantane is a hydrocarbon with the formula C10H16. This cycloalkane (four connected
cyclohexane rings arranged in the “armchair” configuration) was first identified from a
sample of petroleum in 1933. Today this molecule is generated in large quantities by thermal
cracking from crude oils and is very cheap. It is highly reactive compared to other
hydrocarbons and it is characterised by a rigid structure. Moreover, the hydrophobicity
combined with the well-define 3D conformation provide to adamantane derivatives
favourable biological properties (i.e. antiviral, anticancer, against neurodegenerative
diseases).
We have decided to use these properties together with the possibility of controlled
multifunctionalisation to obtain a γ-amino acid based on adamantane, which can be use in
solid-phase peptide synthesis (SPPS) to build new foldamers. We designed short peptide
sequences incorporating the adamantane amino acid, together with glycine and L- or D-
tyrosine. We previously observed by computer simulation that L- or D-tyrosine combined
with the well-defined structure of adamantane can induced a chirality in the secondary
structure of the peptides.
We first developed a multistep synthesis to prepare a non-natural amino acid based on
adamantane with two protected carboxylic groups (esterification), one free carboxylic
groupand a protected amine for the solid-phase peptide synthesis. Then we optimised a SPPS
protocol, by mixing Boc and Fmoc strategy, without affecting the stability of the resin, the
linkers and the protecting groups on the adamantane moiety. We build our sequences using
microwave heating to avoid the low nucleophilicty of the amine on adamantane. We also
developed a cleavage method to obtain the desire peptide without removing the protecting
group of the carboxylic functions on adamantane. Then, an appropriate hydrolysis strategy
allowed us to obtain fully-protected and fully-unprotected peptides. The peptides have been
characterised by HPLC and mass spectrometry. Circular dichroism allowed to elucidate the
conformation. In conclusion, adamantane characteristics offer the possibility to an ease
functionalisation to obtain a γ-amino acid which can be used in solid-phase peptide synthesis
to build foldamers.
JOURNEE DES DOCTORANTS EN CHIMIE 2017 – Université de Strasbourg
Insight to the structure of cationic CNHC,Calkyl-nickelacycles and study as azole C–H functionalization catalysts
B. de P. Cardoso, S. Shahane, J.-M. Bernard-Schaaf, M. J. Chetcuti, V. Ritleng
Université de Strasbourg, UMR 7509, 25 rue Becquerel, 67087 Strasbourg, France
The low toxicity, low cost and high abundance of nickel, as well as its intrinsic fascinating
reactivity[1] prompt chemists to pay more and more attention to this metal, and nickel N-
heterocyclic carbene (NHC) complexes are becoming an important class of pre-
catalysts.[2]
Noteworthy is the application of nickel catalysts in the functionalization of C–H bonds that
has experienced an explosion in the last few years.[3] A motif of high performing N,N or
P,P bidentate chelates was a clear opportunity to replace for chelating bidentate NHC
ligands. With this in mind, we recently reported the complex [(MeCN)nNi{Mes-NHC-
(CH2)2CH(CN)}]PF6 bearing a chelating CNHC,Calkyl scaffold and labile MeCN ligands.[4]
CN
N
N Ni
CN
N
N NiY
N+ I
Y
N
[Ni] (5 mol%)
LiOtBu (2 equiv.)
1,4-Dioxane
(0.12 M),140 °C, 36 h, Ar
or
N
N
N R
Y = O, SSquare planar T-shaped
Figure 1. The cation [(MeCN)nNi{Mes-NHC-(CH2)2CH(CN)}]+ at the crux of the structural puzzle – 1 or 2 MeCN ligands (left); Catalytic C–H bond functionalization of benzothiazole with iodobenzene (right).
However, the initial report left open the precise formula and structure of the nickel
complex; 2 MeCN ligands: a common square planar structure, or 1 MeCN ligand: possibly
a rare 14-electron trivalent Ni(II) species[5] (Figure 1, left). Improvement of the synthetic
methodology, extensive spectroscopic studies, and DFT calculations allowed us to better
determine the actual structure of this class of cationic nickel complexes. Transporting of
the chelation strategy to this C,C system proved to be successful in the coupling of azoles
and iodoarenes, for which a brief scope and mechanistic studies were explored (Figure 2,
right).
[1] S. Z. Tasker, E. A. Standley, T. F. Jamison, Nature, 2014, 509, 299; V. P. Ananikov, ACS Catal., 2015,5, 1964 [2] V. Ritleng, M. Henrion, M. J. Chetcuti, ACS Catal., 2016, 6, 890; M. Henrion, V. Ritleng, M. J. Chetcuti, ACS Catal., 2015, 5, 1283 [3] G. Pototschnig, N. Maulide, M. Schnürch, Chem. - A Eur. J. 2017,23, 9206; J. Yamaguchi, K. Muto, K. Itami, Top. Curr. Chem. 2016, 374, 55; J. Yamaguchi, K. Muto, K. Itami, European J. Org. Chem. 2013, 19 [4] M. Henrion, A. M. Oertel, V. Ritleng, M. J. Chetcuti, Chem. Commun. 2013, 49, 6424 [5] S. Pelties, R. Wolf, Organometallics, 2016, 35, 2722; C. A. Laskowski, G. L Hillhouse, J. Am. Chem. Soc., 2008, 130, 13846.
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Polyurethanes constitute a class of plastic materials used on a large scale by industry for a wide
range of applications. However, they usually have a non-uniform primary structure, as they are
produced by step-growth polymerisation. Here we report a facile protective-group-free approach to
prepare sequence-defined polyurethanes. This method relies on the use of two chemoselective steps.
In a first step, a hydroxy group was reacted with N,N’- disuccinimidyl carbonate to afford an active
carbonate. In a second step, this carbonate was reacted with an amino alcohol to afford selectively a
hydroxyl-functional carbamate. The iterative repetition of these two steps on a Wang resin modified
with a hydroxy carboxylic acid linker led to the synthesis of a sequence-defined polyurethane.
Different sequence-coded polymers have been synthetized using two different amino alcohols,
defined as 0 and 1 bit. Thanks to the carboxylic function from the linker cleavage and the selective
fragmentation of the C-O carbamate bound, the sequence of this new type of polymers can be easily
read by tandem mass spectrometry in negative mode.
Spirocyclization from keto-ynamides: toward the synthesis of azacycles
Frédéric BELTRAN a, Indira FABRE b, Ilaria CIOFINI b, Laurence MIESCH a,*
a Laboratoire de Chimie Organique Synthétique, Institut de Chimie, CNRS-UdS UMR 7177,
4, rue Blaise Pascal CS 90032, 67081 Strasbourg, France
b Chimie ParisTech, PSL Research University, CNRS, Institut de Recherche
de Chimie Paris (IRCP), 75005 Paris, France
[email protected] ; [email protected]
http://www-chimie.u-strasbg.fr/~lcos/
The chemistry of acetylenic ω-keto-esters is an important topic of research in our laboratory.
As one example, we have found that keto-2-alkynoates react in the presence of a catalytic amount of
silver triflimidate to lead to spirocyclic compounds.1 The fact that a wide range of natural products
possess at least one nitrogen-containing heterocycle in their structure led us to study ynamides as an
entry to these important ring systems. Recently, our group has focused on the reactivity of keto-
ynamides toward silver salts, leading to the formation of bridged enamides.2
In this context, we have undertaken a study of the reactivity of keto-ynamides for the formation
of nitrogen-containing spirocyclic compounds. These spirocyclic systems, incorporating azacyclic
substructures, are prominent in natural Aspidosperma type alkaloids and furthermore represent a
synthetic challenge. Using chemistry developed in our laboratory, good yields of spirocyclic
compounds are observed in reactions between alkynyl bromides and indanone or indolone type keto-
sulfonamides in the presence of an excess of cesium carbonate.3 The spirocyclization reaction
presented herein tolerates many acetylenic substituents and cycloalkanones. The obtained spiro-
enamides are generated with high E selectivity about the double bond. This reaction could therefore
be applied to the synthesis of natural products such as Jerantinine E.4
1 Schäfer, C.; Miesch, M.; Miesch, L., Chem. Eur. J. 2012, 18, 8028. 2 Heinrich, C.; Fabre, I.; Miesch, L. Angew. Chem. Int. Ed. 2016, 55, 5170–5174. 3 Beltran, F.; Fabre, I.; Ciofini, I; Miesch, L. Org. Lett. 2017, DOI: 10.1021/acs.orglett.7b02216.4 Frei, R.; Staedler, D.; Raja, A.; Franke, R.; Sasse, F.; Gerber-Lemaire, S.; Waser, J. Angew. Chem. Int. Ed. Engl.
2013, 52, 13373–13376.
GOLD AND PALLADIUM CATALYZED CASCADE REACTIONS
TOWARDS THE SYNTHESIS OF NATURAL PRODUCTS
Fatih SIRINDIL,1 Patrick PALE
1 and Aurélien BLANC
1
1Laboratoire de Synthèse, Réactivité Organique et Catalyse, Institut de Chimie, UMR 7177,
Université de Strasbourg, 4 rue Blaise Pascal, 67070 Strasbourg, France.
Natural products have mostly an heterocyclic scaffold and retain particular attention from organic
chemists due to their biological activity and also their utility to provide an attractive platform to
establish the usefulness of novel synthetic pathways. Palladium catalyzed reactions and more
recently reactions involving gold catalyst are wide used to this aim given that, those metals offers
an abundance of possibilities of carbon-carbon and carbon-heteroatom bond formations [1]
.
Figure 1: Palladium catalyzed sulfonyl migration and cross-coupling reactions
We recently developed new methods using gold (I) and palladium (II) catalysts to obtain fused N-
heterocyclic compounds 2 from ynone substituted N-sulfonyl substrates 1 (Figure 1). The
unprecedented 1,5 migration of sulfonyl group from nitrogen to oxygen is occurring during the
cyclization catalyzed by gold (I) and also with palladium (II) [2]
. The palladium catalyzed tandem
1,5 migration – cross coupling reactions leads to bicyclic heterocycle 3. The resulting pyrrole,
dihydropyrrolizidine and indolizidine scaffolds 3 are founds in biologically active natural products
and especially antitumor alkaloids [3]
. The developed catalytic pathways are currently employed
for the total synthesis of rhazinal family natural products.
[1] Tsuji, Jiro (2004), Palladium Reagents and Catalysts New Perspectives for the 21st Century.
England : John Wiley & Sons Ltd
[2] Miaskiewicz, S. ; Gaillard, B. ; Kern, N. ; Weibel. J. M. ; Pale, P. ; Blanc, A. ; Angew. Chem.,
Int. Ed. 2016, 55, 1 [3] Bowie, A. L. ; Trauner, Jr. ; Trauner, D. J. Org. Chem. 2009, 74, 1581
Cross-CouplingRearrangement
Sulfonyl migration
1 2 3
RN
SO2Ar
O
R1 N
ArO2SO
R
R1 N
Ar
R
R1
Palladium
orGold Palladium
NR
HN
OR= CHO ; Rhazinal
R= CH2OH; Kopsiyunnanine C3
R= CH2OMe; Kopsiyunnanine C1
R= CH2OEt; Kopsiyunnanine C2
Synthesis and characterisation of silicon-based nanoparticles for multi-modal
in vivo imaging applications.
John Ddungu†* and Luisa De Cola†*
†Institut de Science et d’Ingénierie Supramoléculaires, Université de Strasbourg
*Institute of Nanotechnology, Karlsruhe Institute of Technology (KIT), Germany
Nanoparticles have received growing attention over the past decades due to their potential as
effective nanoprobes in bio-imaging.[1] Within this field, those based on semiconductor materials,
such as II-VI or III-V quantum dots, in addition to carbon based quantum dots, have shown great
promise. This is due to their strong photophysical properties, high electro- and chemical stability, as
well as the ability to functionalise a single nanoparticle structure with multiple molecular or
macromolecular species. Through this, it is possible to image the engineered nanoparticles with
different diagnostic techniques simultaneously.[2]
The application of silicon-based nanoparticles (SiNPs) in particular has gained much research interest.
The ability to synthesise SiNPs of ultra-small sizes through wet chemistry techniques, their ease of
functionalisation, low toxicity and biodegradation over time makes them an ideal choice for multi-
modal nanoprobes for in vivo imaging applications.[3]
Challenges remain in the full charaterisation of prepared SiNPs and their multi-modal in vivo
performance must still be further explored. Our approach involves the use of SiNPs functionalized
with various moieties on the surface for in vitro and eventually in vivo applications. The synthesised
nanoparticles are characterised using a variety of techniques before and after functionalisation, with
the aim of developing a number of highly defined systems that can be applied to multi-modal
imaging of cancerous tumors in different parts of the body.
References:
[1] M. Montalti, A. Cantelli and G. Battistelli, Chem. Soc. Rev., 2015,44, 4853-4921
[2] J. Key and J. F. Leary, Int J Nanomedicine., 2014, 9, 711–726.
[3] L. Ruizendaal, S. Bhattacharjee, K. Pournazari, M. Rosso-Vasic, L. H. J. de Haan, G. M. Alink, A. T. M. Marcelis
and H. Zuilhof, Nanotoxicology., 2009, 3, 339–347
Schematic summary of the different multimodal SiNP systems currently being studied
Synthesis and biological activity of predicted ALR2 inhibitors
Matúš Hlaváč, a,c
Lucia Kováčiková, b
Gilles Hanquet, c
Magdaléna Majeková, b
Milan Štefek, b
and Andrej Boháč a,d,*
a Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in
Bratislava, Ilkovičova 6, Mlynská dolina, 842 15, Bratislava, Slovakia,
bInstitute of Experimental Pharmacology and Toxicology, SAS, Dúbravská cesta 6, 841 04,
Bratislava, Slovakia
c Université de Strasbourg, Ecole Européenne de Chimie, Polyméres et Metériaux (ECPM),
Laboratoire de Synthése et Catalyse (UMR CNRS 7509), 25 rue Becquerel, 67087 Strasbourg
cedex 2, France
d
Biomagi, Ldt., Mamateyova 26, 851 04, Bratislava, Slovakia
Inhibition of an aldose reductase (ALR2), the first enzyme of a polyol pathway, is a promising
approach in the treatment of diabetic complications. Most of ALR2 inhibitors contain
carboxylic group, which interacts to an anion binding pocket in an active site of ALR2. In a
recent study1 of carboxymethylated thioxotriazinoindoles, CMTI (cemtirestat) was identified
as a powerful ALR2 inhibitor possessing a good selectivity and drug-like properties. Based on
the structure drug design, several potential analogues of CMTI were proposed. Among them,
compound 1 (OCMTI, IC50 = 42 nM) showed almost 3-fold higher inhibitory activity than
CMTI in an in vitro ALR2 enzymatic assay and 8-fold higher selectivity relative to ALR1
(IC50 = >100 µM). Based on these results we can conclude, that isosteric replacement of
sulphur with oxygen plays an important role in the inhibition of ALR2 and its selectivity.
Figure 1. The structures of CMTI, its oxygen analogue derivatives 1-4 and obtained ALR2 inhibitory activities.
1Stefek, M., Soltesova Prnova, M., Majekova, M., Rechlin, C., Heine, A., Klebe, G.: Identification of novel
aldose reductase inhibitors based on carboxymethylated mercaptotriazinoindole scaffold. J. Med. Chem., 2015;
58(6): 2649-57.
An online four-dimensional HICxSEC-IMxMS methodology for in-
depth characterization of antibody drug conjugates
Anthony Ehkircha, Valentina D’Atrib, Florent Rouvièrec, Oscar Hernandez-Albaa,
Alexandre Goyonb, Olivier Colasd, Morgan Sarrutc, Alain Beckd, Davy Guillarmeb,
Sabine Heinischc, Sarah Cianférania
a Laboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CRNS, IPHC UMR 7178,
67000 Strasbourg, France b School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU - Rue Michel-Servet, 1,
1206 Geneva – Switzerland c Univ Lyon, CNRS, Université Claude Bernard Lyon 1, Ens de Lyon, Institut des Sciences Analytiques, UMR
5280, 69100 VILLEURBANNE, France d Centre d’Immunologie Pierre-Fabre (CIPF), Saint-Julien-en-Genevois, France
Antibody Drug Conjugates (ADCs) are tripartite molecules consisting of a monoclonal
antibody (mAb) onto which highly cytotoxic small molecules are conjugated by
cleavable or non-cleavable linkers. They show better efficiency than canonical
unconjugated mAbs, due to the synergic effect of mAb specificity for its target and the
efficacy of the highly cytotoxic drug.1
There are currently two main techniques allowing the analytical characterization of
cysteine linked antibody drug conjugates under non denaturing conditions, namely
hydrophobic interaction chromatography (HIC) and native high resolution mass
spectrometry.
HIC is a chromatographic technique allowing the evaluation of drug load profile and
calculation of average drug to antibody ratio (DAR).2,3 High resolution mass
spectrometry (MS) offers a wealth of information on the biochemical and biophysical
properties of ADCs, thanks to accurate mass measurement.4 On-line coupling of both
techniques can potentially be of great interest, but the presence of large amounts of
non-volatile salts in HIC mobile phases make them non compatible with MS.
Here, we present an innovative multidimensional analytical approach combining
comprehensive on-line two dimensional chromatography (HICxSEC) to ion mobility
and mass spectrometry (IM-MS) for performing analytical characterization of ADCs
under non-denaturing conditions. Online hyphenation of non-denaturing 2D
chromatography to 2D IM-MS enabled comprehensive and streamlined
characterization of both native and stressed ADC samples.
1. Ornes, S. Proc. Natl. Acad. Sci. 2013, 110, 13695–13695
2. Rodriguez-Aller, M.; Guillarme, D.; Beck, A.; Fekete, S. J. Pharm. Biomed. Anal. 2016, 118, 393–403.
3. Cusumano, A.; Guillarme, D.; Beck, A.; Fekete, S. J. Pharm. Biomed. Anal. 2016, 121, 161–173.
4. Debaene, F.; Bœuf, A.; Wagner-Rousset, E.; Colas, O.; Ayoub, D.; Corvaïa, N.; Van Dorsselaer, A.;
Beck, A.; Cianférani, S. Anal. Chem. 2014, 86, 10674–10683.
Reversible Native Chemical Ligation :
A Facile Method to Identify Peptide Ligands for Protein Targets
Cristian-Victor Rețe,a Manickasundaram Samiappan,a Valentina Garavini,a Yves Ruff,a
Stéphane Erb,b Jean-Marc Strub,b Sarah Cianferani,b Daniel Funeriu,a Nicolas Giusepponea
a SAMS Research Group, Institut Charles Sadron (CNRS), Université de Strasbourg – 23 rue du Loess, 67034 Strasbourg Cedex 2, France b Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Université de Strasbourg, Institut Pluridisciplinaire Hubert Curien (CNRS) – 23 rue du Loess, 67037 Strasbourg Cedex 2, France
The collection of dynamic combinatorial techniques that can be used to discover
ligands/inhibitors (ranging from organic to biomolecular fragments) for biological targets has
expanded substantially in the past decade.1 Each of these approaches allows various protein
targets to be addressed. The proper use of these techniques can lead to advances in biological
understanding, new protein-drug conjugates and targeted medical imaging agents.
Figure 1. Schematic representation of the concept behind the generation of dynamic combinatorial
peptide libraries under the selection pressure of a protein receptor
The dynamic exchange reactions in the current toolkit (e.g. disulphide bond exchange, imine
bond exchange, etc.) vary widely in their inherent biocompatibility and functional group
compatibility. We have considered of particular interest the use of newly adapted native
chemical ligation (NCL) methodologies2,3 for the generation of dynamic combinatorial libraries
(DCLs) in the presence of protein receptors. Herein we report the development of reversible
NCL for the selection of Affibody® ligands for the Fc region of immunoglobulin G from a
peptide DCL (Figure 1).
1 Mondal, M.; Hirsch, A. K. H. Chem. Soc. Rev. 2015, 44, 2455-2488. 2 Ruff, Y.; Garavini, V.; Giuseppone, N. J. Am. Chem. Soc. 2014, 136, 6333–6339. 3 Ollivier, N.; Blanpain, A.; Boll, E.; Raibaut, L.; Drobecq, H.; Melnyk, O. Org. Lett. 2014, 16, 4032-4035.
