Programme des Journées Bibliographiques 2014 de l Ecole Doctorale de Chimie Moléculaire ED 406

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1 Programme des Journées Bibliographiques 2014 de l Ecole Doctorale de Chimie Moléculaire ED 406 Lundi 27 janvier 2014 (Amphithéâtre Langevin ESPCI ParisTech) 8h55 Ouverture - Mot d introduction (Pr Anna Proust) Modératrice : Dr Marine Desage- El Murr 9h00 10h00 10h15 10h30 Dr Manuel Alcarazo (Conférence plénière) - Cationic ligands: synthesis and applications Brendan Fallon - The use of organocatalytic cascade reactions for the synthesis of complex molecules Giorgio Caserta - Artificial hydrogenases for the reduction of protons in hydrogen Pause- café Modérateur : Dr Bastien Nay 11h00 11h15 11h30 11h45 12h00 Julien Escudero - Formation de liaisons C- N par fonctionnalisation de liaisons C- H catalysée par des complexes de métaux de transition Qirong Zhu - Nanotribological properties and wear studies of graphene Paul Marin - La catalyse tandem : définition et applications à la synthèse de polymères Pierre Quatremarre - Structures et applications des metallacrowns Pause déjeuner Modérateur : Dr Alejandro Perez Luna 14h00 14h15 14h30 14h45 Simon Guelen - Use of Lappert s stannylens and derivatives in Stille coupling reactions Julien Rossignol - Carbohydrates as vectors for gene delivery Sha Zhu - Recent progress on studies of morroniside from Cornus Officinalis Sieb et Zucc Marcelo Girardi - Chemically modified electrodes and their applications in electrocatalysis 15h00 Guillaume Boissonnat - Synthèse d hétérocycles par addition intramoléculaire de nucléophiles sur des allènes catalysée par les complexes d or 15h15 15h30 Xiaolei Zhu - PARP1 - A promising target and the development of PARP1- based candidates for anticancer intervention Pause café Modérateur : Pr Matthieu Sollogoub 16h00 Charlotte Grandclaudon - Halogénation énantiosélective d'insaturations carbonées: Accès à des hétérocycles fonctionnalisés 16h15 Dr Bernard Henrissat (Conférence plénière) Carbohydrates and their enzymes in the (meta)genomic era

2 Mardi 28 janvier 2014 (Amphithéâtre Langevin ESPCI ParisTech) Modérateur : Dr Andrei Corbu 9h00 10h00 10h15 10h30 Pr Stéphane Rigaut (Conférence plénière) - Molecular switches with organometallic carbon- rich complexes Baptiste Barré - Iridium- catalyzed asymmetric hydrogenation of Carbon- Carbon Double Bond Abdulghani Ismail - Nitric oxide: chemical reactivity, stocking forms, and delivery Pause- café Modérateur : Dr Tahar Ayad 11h00 11h15 11h30 11h45 12h00 Guillaume Ernouf - Fonctionnalisation de cyclopropanes par activation de liaisons C- H Hongxi Lei - Calix[4]arene- based fluorescent sensors Thomas Hostier - Formation de liaisons C Ar - S métallo- catalysée Jean Boulicault (Doc Up) Pause déjeuner Modérateur : Dr Cyril Ollivier 14h00 14h15 14h30 14h45 15h00 15h15 15h30 Mehdi Zaghouani - Le métabolisme de l éthanol Valentin Bochatay - Use of isocyanide in Organic Synthesis Jérémy Jacquet - Non- innocent Ligands: Concepts and Synthetic Applications Zhong Yi Mao - Total Syntheses of Aeruginosins Benjamin Laroche - Flow chemistry: concepts and recent applications in natural products synthesis Jérémy Scelle - Synthèse de polyrotaxanes par polymérisation de pseudo- rotaxanes Pause- café Modérateur : Dr Stellios Arseniyadis 16h00 17h00 Dr Igor Larrosa (Conférence plénière) - Au, Ag, and Pd in C- H activation: reactivity and selectivity control Mot de clôture

3 Manuel ALCARAZO Cationic Ligands: Synthesis and Applications Max-Planck-Institut für Kohlenforschung Cyclopropenylydene-stabilized [LR 2 P] +, [L 2 RP] 2+ and [L 3 P] 3+ cations have been synthesized for the first time by reaction between 1-chloro-2,3-bis(dialkylamino) cyclopropenium salts with different phosphorus sources. In addition, the structural characterization of such entities has been carried out. Consistent with the X-ray data, density functional calculations indicate that all these P- centered cations, despite of their moderate to high positive charges, still feature a non-bonding electron pair on the P atom (HOMO) and, depending of the total charge, a low-lying LUMO. These properties render [LR 2 P] + as strong σ-donor ligands while [L 2 RP] 2+ are moderate π-acceptors. Interestingly, [L 3 P] 3+ cations are still able to coordinate metal fragments displaying very poor σ-donor but excellent π-acceptor properties. 1 Figure. X-ray structure of [LPh 2 P] +, [L 2 PhP] 2+ and [L 3 P] 3+ cations respectively. H atoms and counter anions have been removed for clarity. Encouraged by their electronic properties we decided to test the potential of these compounds in catalysis and prepared a set of gold, rhodium and platinum complexes in which these salts were used as ligands. The practical utility of such coordination compounds in catalysis has been demonstrated in several mechanistically diverse transformations and will be presented. Additionally, taking advantage of the saline nature of our ligands, the recycling possibilities of the catalysts thereof derived have been also explored. Acknowledgments: Financial support for this work was provided by the Max Planck Gessellschaft, the Deutsche Forschung Gemeinschaft and the European Commission (ERC-Starting Grant to M.A.). References 1 (a) Petuškova, J.; Bruns, H.; Alcarazo, M. Angew. Chem. Int. Ed. 2011, 50, (b) Petuškova, J.; Patil, M.; Holle, H.; Lehmann, C.; Thiel, W.; Alcarazo, M. J. Am. Chem. Soc. 2012, 134, (c) Carreras, J.; Gopakumar, G.; Gu, L.; Gimeno, A.; Linowski, P.; Petuškova, J.; Thiel, W.; Alcarazo, M. J. Am. Chem. Soc (DOI : /ja411146x).

4 Bernard HENRISSAT Carbohydrates and their enzymes in the (meta)genomic era Architecture et Fonction des Macromolécules Biologiques, CNRS, UMR 7257 Aix-Marseille Université, 163 Avenue de Luminy, Marseille cedex 9, France Carbohydrates are crucial for most organisms as carbon sources or as signaling molecules, but also for cell wall synthesis, host pathogen interactions, energy storage etc. We term carbohydrate-active enzymes (CAZymes) the enzymes that assemble and breakdown glycoconjugates, oligoaccharides and carbohydrate polymers. As such CAZymes find widespread applications in the food and feed, textile, medical and biotechnology sectors. Unlike most other classes of enzymes which carry limited informative power, the peculiarities of carbohydrate-active enzymes and of their substrates turn these enzymes into extremely powerful probes to examine and explain the lifestyle of living organisms. Over the last few years we have explored the CAZyme content of hundreds of genomes and dozens of metagenomes including the human gut microbiome. We will review how evolution shapes the CAZyme profile of individual organisms or microbial communities. Acknowledgments: My current research is supported by grants from ANR, IDEX Aix-Marseille, the European Commission (ERA-NET FP7) and the European Research Council.

5 Stéphane RIGAUT Molecular switches with organometallic carbon-rich complexes Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS Université de Rennes 1 stephane.rigaut@univ-rennes1.fr Carbon-rich ruthenium complexes have been involved in the building of original redox active molecular wires and junctions, owing to their excellent ability to promote a strong electronic coupling between the metal centers and the conjugated ligands. Combinations of such metal complexes with carefully chosen functional units also lead to original properties valuable to achieve functional materials that present effective switching behaviors. For example, the ruthenium(ii) carbon rich moiety is an efficient sensitizer to promote ytterbium luminescence, and further commutation of this near-ir emission is achieved by changing the oxidation state of this antenna. 1 Also, the perturbation of a dithienylethene (DTE) system with ruthenium moieties affords materials that gather efficient and suitable photo/electrochromism to achieve unique multifunctional switchable nanodevices. 2,3 References 1 Di Piazza, E.; Norel, L.; Costuas, K.; Bourdolle, A.; Maury, O.; Rigaut, S. J. Am. Chem. Soc. 2011, 133, Meng, F.; Hervault, Y.-M.; Norel, L.; Costuas, K.; Van Dyck, C.; Geskin, V.; Cornil, J.; Hoon Hng, H.; Rigaut, S.; Chen, X. Chem. Sci. 2012, 3, Meng, F.; Hervault, Y.-M.; Shao, Q.; Hu, B.; Norel, L.; Rigaut, S.; Chen, X. Nat. Commun (doi: /ncomms4023).

6 Igor LARROSA Au, Ag, and Pd in C-H activation: reactivity and selectivity control School of Biological and Chemical Sciences, Queen Mary University of London. Joseph Priestley Building. London, E1 4NS. United Kingdom The development of greener and more efficient synthetic methodologies is essential for organic chemistry to reach its full potential in its application to many applied and fundamental scientific problems. Direct C H arylation, where a readily available Ar-H is coupled with Ar-X, and oxidative double C H activation, where two different Ar-H are cross-coupled, have emerged in the last few years as promising alternatives to traditional cross-couplings. These approaches use nonprefuntionalized starting materials, thus eliminating several synthetic steps and the associated waste en route to the desired cross-coupling adducts. However, several challenges have to be resolved before this new approaches can be widely applied: 1) the development of mild reaction conditions with a broad scope, 2) the control of the regioselectivity of C H activation and, in the case of oxidative couplings 3) the control of the selectivity of homo- versus cross-coupling. In this talk I will present some of our group s approaches towards addressing these challenges. For some representative publications, see reference section. Acknowledgments: Igor Larrosa holds a European Research Council Starting Grant. Selected publications: 1 Ricci, P.; Krämer, K.; Cambeiro, X. C.; Larrosa, I. J. Am. Chem. Soc. 2013, 135, Cambeiro, X. C.; Boorman, T. C.; Lu, P.; Larrosa, I. Angew. Chem. Int. Ed. 2013, 52, (Hot Paper). 3 Cornella, J.; Righi, M.; Larrosa, I. Angew. Chem. Int. Ed. 2011, 50, Lu, P.; Boorman, T. C.; Slawin, A. M. Z.; Larrosa, I. J. Am. Chem. Soc. 2010, 132, Lebrasseur, N.; Larrosa, I. J. Am. Chem. Soc. 2008, 130, 2926.

7 Brendan FALLON The use of Organocatalytic cascade reactions for the synthesis of complex molecules Université Pierre et Marie Curie, Laboratoire de chimie organique Méthodes et Applications en Chimie Organique (MACO) UMR-CNRS 8232, case 229 4, Place Jussieu, PARIS 05 The variety of structures and level of complexity present in natural products has aroused the interest of organic chemists for years. Historically though, the synthesis of complex natural products reveals much of the limitations of current synthetic procedures i.e. the use of orthogonal protection strategy and single step transformations. Current developments in the domain of total synthesis are focused around the basic principle of biosynthesis namely cascade reactions. The obvious advantages of such domino cascades are at least two synthetic transformations are carried out in a single step, timely protection group manipulation and isolation/purification are reduced which increase synthetic efficiency and reduces operational costs. Herein is presented the current efforts towards organocatalytic cascade reactions as a new tool in total synthesis. 1,2,3 References 1 Enders, D.; Huttl, M.R.M.; Grondal, C.; Rabbe, G. Nature 2006, 44, Davis, H. M.; Sorensen, E. J. Chem. Soc. Rev. 2009, 38, Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem. Int. Ed. 2006, 45, 7134.

8 Giorgio CASERTA Artificial hydrogenases for the reduction of protons in hydrogen Laboratoire de Chimie des Processus Biologiques, Collège de France 11 place Marcelin Berthelot, Paris Figure.Examples of Biomimetic complexes (left), hybrid system with HydF (center), active site of [Fe-Fe] H 2 ase (right). The project aims at the development of catalysts for the production of H 2 by electrochemical or photoelectrochemical reduction of protons. This complex multielectronic process requires effective and cheap catalysts, rather with non noble metals. Numerous works concern the use of enzymes, the hydrogenases, which are the most active molecular catalysts for hydrogen production and uptake, based on Ni-Fe or Fe-Fe active sites, or on the development of bioinspired molecular catalysts. 1 Unfortunately, the first ones, very active, are difficult to produce and are characterized by a very high fragility, making their technological exploitation complex, whilst the second, more easily accessible, are generally much less effective and little stable in water. Hydrogenases of the [FeFe] type (HydA) are the most active H 2 producers. They contain a complex cofactor, the H-cluster, consisting of a simple cubane [4Fe-4S] cluster bound via cysteine to a unique [2Fe] subcluster in which two Fe atoms are coordinated by CO, CN - and a dithiolate bridge. 2 In the living cell, biosynthesis of the [2Fe] subcluster requires three Fe-S cluster-containing accessory proteins, HydE, HydG and HydF. The first two are radical S-adenosylmethionine (SAM) enzymes 3 while HydF is the scaffold for the [2Fe] subclaster assembly and transfers the cluster to the apo-hyda protein. 4 Notably, G. Berggren and coworkers (Figure 1) showed that an original synthetic mimic of the [2Fe] subcluster can be loaded onto HydF from Thermotoga maritima in vitro, mimicking the active site of hydrogenases. This artificially loaded HydF is able to transfer the di-iron complex to the apo form of [FeFe]-hydrogenase, HydA1, from Chlamydomonas reinhardtii, resulting in a fully active hydrogenase. 5 As a result, it is very likely that [FeFe]-hydrogenases from other microorganisms, overexpressed in their apo form, could also be activated through simple reaction with the artificially loaded HydF. To date, only a subset of HydA enzymes has been analyzed in biochemical and biophysical detail therefore we plan to isolate new apo-hydrogenases, apo-hyda, and new iron-sulfur proteins, HydF, from different species, as well as a whole series of site-directed mutants of these proteins, with the aim of finding the most active and stable enzymes.

9 The new apo-hydrogenases will be activated, through 2-HydF (2 is referred to the synthetic inorganic complex with the azadithiolate bridge) or new analogues, to transform them into artificial hydrogenases, using the knowledge described by Berggren and coworkers. These new hybrid systems will be characterized at the structural level and we will evaluate their catalytic performances. Additionally, J. Esselborn et al. showed that it is possible to produce artificial hydrogenases even through spontaneous integration of [FeFe] synthetic mimic, containing an azadithiolate bridge, into algal apo-hyda1. 6 Accordingly, we aim to optimize and synthesize a variety of diiron complexes, trying to mimic the active site of hydrogenases, searching the [2Fe] complex endowed with the best catalytic performances. These new complexes will be incorporated into the proteins HydF and HydA with the aim to understand how the protein matrix is able to modulate the catalytic activity, in particular through site-directed mutagenesis of the subcluster binding site. This approach may lead to artificial hydrogenases such as x-hydf (x are referred to the synthetic inorganic complexes), as well as to modified hydrogenases such as x-hyda. Furthermore, the ability to reconstitute apo-hydrogenases even in the absence of maturation factors now allows to explore a large variety of HydA sequences, from different species or derived from directed mutagenesis, with the aim of finding the most active and stable enzymes for exploitation in biotechnological processes of H 2 production. Acknowledgments: This work is supported by the Collège de France Fondation. Professor M. Fontecave is kindly acknowledged for giving me the opportunity to work with him as a PhD student. Commisariat à l Energie Atomique et aux Energies Alternatives is gratefully acknowledged. References 1 Tard, C.; Pickett, C. J. Chem. Rev. 2009, 109, Peters, J.W. Lanzilotta, W. N.; Lemon, B. J.; Seefeldt, L. C. Science 1998, 282, Kuchenreuther, J. M.; Myers, W. K.; Stich, T. A.; George, S. J.; NejatyJahromy, Y.; Swartz, J. R.; Britt, R. D. Science 2013, 342, Mulder, D. W.; Boyd, E. S.; Sarma, R.; Lange, R. K.; Endrizzi, J. A.; Broderick, J. B.; Peters, J. W. Nature 2010, 465, Berggren, G.; Adamska, A.; Lambertz, C.; Simmons, T. R.; Esselborn, J.; Atta, M.; Gambarelli, S.; Mouesca, J.-M.; Reijerse, E.; Lubitz, W.; Happe, T.; Artero, V.; Fontecave, M. Nature 2013, 499, Esselborn, J.; Lambertz, C.; Adamska-Venkatesh, A.; Simmons, T.; Berggren, G.; Noth, J.; Siebel, J.; Hemschemeier, A.; Artero, V.; Reijerse, E.; Fontecave, M.; Lubitz, W.; Happe, T. Nat. Chem. Biol. 2013, 9, 607.

10 Julien ESCUDERO Formation de Liaisons C-N par Fonctionnalisation de Liaisons C-H Catalysée par des Complexes de Métaux de Transition Pr Janine COSSY, Pr Véronique BELLOSTA Laboratoire de chimie organique de l ESPCI 10, rue Vauquelin PARIS Julien.escudero@espci.fr La fonctionnalisation de liaisons carbone-hydrogène est devenue un outil puissant en chimie organique et constitue un domaine d intense recherche. 1 La plupart des composés biologiquement actifs contiennent un ou plusieurs atomes d azote. La formation directe de liaisons C-N à partir de liaisons C-H est donc un défi particulièrement intéressant. 2 Différentes méthodes de formation de liaisons C-N à partir de liaisons C-H à l aide de métaux de transition seront présentées. Un grand nombre de réactions impliquant l addition oxydante d un métal comme le palladium ou le rhodium dans une liaison C-H ont été mises au point. 3,4 D autres métaux tels que le cuivre, le ruthénium ou l or ont également été utilisés. 5,6,7 L argent, le fer et le zinc ont également montré de bonnes propriétés catalytiques pour la formation de liaisons C-N à partir de liaisons C-H mais par un autre mécanisme faisant intervenir des complexes métalliques de transfert de nitrène. 8,9,10 Les différentes réactions et leurs mécanismes seront discutés et des applications synthétiques seront présentées. Références 1 (a) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem. Int. Ed. 2012, 51, (b) Godula, K.; Sames, D. Science 2006, 446, 67. (c) Labinger, J. A.; Bercaw, J. E.; Nature 2002, 417, 507. (d) Jun, C.; Moon, C. W.; Lee, D. Chem., Eur. J. 2002, 8, (a) Collet, F.; Dodd, R. H.; Dauban, P. Chem. Comm. 2009, 45, (b) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, (c) Thansandote, P.; Lautens, M. Chem., Eur. J. 2009, 15, (d) Stokes, B. J.; Driver, T. G. Eur. J. Org. Chem. 2011, 22, (a) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2011, 110, (b) Bacalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107, Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, (a) Hamada, T.; Ye, X.; Sthal, S. S.; J. Am. Chem. Soc. 2008, 130, 833. (b) Wang, Q.; Schreiber, S. T. Org. Lett. 2009, 11, (c) Monguchi, D.; Fujiwara, T.; Furukawa, H.; Mori, A. Org. Lett. 2009, 11, (a) Hu, J.; Chen, S.; Sun, Y.; Yang, J.; Rao, Y. Org. Lett. 2012, 14, (b) Louillat, M.; Patureau, F. W. Org. Lett. 2013, 15, Li, Z.; Capretto, D. A.; Rahaman, R. O.; He, C. J. Am. Chem. Soc. 2007, 129, Li, Z.; Capretto, D. A.; Rahaman, R.; He, C. Angew. Chem. Int. Ed. 2007, 46, Wang, Z.; Zhang, Y.; Fu, H.; Jiang, Y.; Zhao, Y. Org. Lett. 2008, 10, Kalita, B.; Lamar, A. A.; Nicholas, K. M. Chem. Comm. 2008, 44, 4291.

11 Qirong ZHU Nanotribological properties and wear studies of graphene a Institut Parisien de Chimie Moléculaire, Université Pierre et Marie Curie 4 Place Jussieu, Paris cedex 5, France b DSM/DRECAM/SPSCI, CEA-Saclay, Gif-Sur-Yvette Cedex, F-91191, France qirong.zhu@etu.upmc.fr, Qirong.ZHU@cea.fr Figure. Friction versus load for graphene films with different layers Since graphene was discovered by Geim s and co-workers in 2004, it has been attracting so many scientists from different research areas to explore its characteristics and potential applications. 1 The ultra-low friction of graphene and multilayer graphene will make them as good candidates for nanoscale data storage devices, nanocomposites, and nanoelectromechanical systems (NEMS). 2 Therefore, the understanding of the thin film s adhesion, friction, wear properties and the interaction forces with contact surfaces would be particularly crucial. However, the different preparing methods make this kind of materials own the diverse fictional characteristics. Also, the substrate plays a very important role in the friction measurements. Sometimes, the same thin films deposited on different substrates even have completely opposite frictional results. 2,3,4 In my experiments, in addition to the frictionai properties, I find that different layers graphene exhibit quite different wear resistance. Références 1 Novoselov, K. S.; Geim, A. K.; Morozov, S.; Jiang, D.; Zhang, Y.; Dubonos, S. V.; Grigorieva, I. V.; Firsov, A. A. Science 2004, 306(5969), Lee, C.; Li, Q.; Kalb, W.; Liu, X.-Z.; Berger, H.; Carpick, R. W.; Hone, J. Science 2010, 328, Filleter, T.; McChesney, J.; Bostwick, A.; Rotenberg, E.; Emtsev, K. V.; Seyller, Th.; Horn, K.; Bennewitz, R. Phys. Rev. Lett. 2009, 102(8), Kim, K. S.; Lee, H. J.; Lee, C.; Lee, S. K.; Jane, H.; Ahn, J. H.; Kim, J. H.; Lee, H. J. ACS Nano 2011, 5, 5107.

12 Paul MARIN La catalyse tandem : définition et applications à la synthèse de polymères Laboratoire Charles Friedel Equipe Chimie Organométallique et Catalyse de Polymérisation 11 rue Pierre et Marie Curie75231 PARIS cedex 5 paul.marin@chimie-paristech.fr Au cours de ces vingt dernières années, un intérêt croissant a été apporté au développement de processus «one pot», présentant plusieurs réactions (catalytiques ou non) mais ne nécessitant qu une seule étape de traitement. 1 Economiques en atomes et permettant la mise en jeu d intermédiaires peu stables, difficiles voire impossibles à isoler, ces procédés ont évolués conjointement aux réactions catalysées par des métaux de transition. 2 En s inspirant des systèmes multienzymatiques complexes présents dans la nature, la catalyse tandem, définie comme un processus au cours duquel interviennent deux (ou plus) cycles catalytiques distincts s appliquant séquentiellement (Figure), a permis à la fois la synthèse de petites molécules et de polymères. 3 Figure. Représentation schématique de la catalyse tandem 4 Au cours de cette présentation seront exposées les différentes classes de la catalyse tandem, leurs avantages et inconvénients respectifs 5 ainsi que plusieurs exemples d application de la catalyse tandem à la synthèse de polymères. 6 Acknowledgments : Pr. Christophe THOMAS, Dr. Carine ROBERT Références 1 Tietze, L. F.; Chem. Rev. 1996, 96, Poli, G.; Giambastiani, G.; Heumann, A. Tetrahedron 2000, 56, Wasilke, J.-C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C. Chem. Rev. 2005, 105, Shindoh, N.; Takemoto, Y.; Takasu, K. Chem. Eur. J. 2009, 15, Fogg, D. E.; dos Santos, E. N. Coord. Chem. Rev. 2004, 248, Robert, C.; Thomas, C. M. Chem. Soc. Rev. 2013, 42, 9392.

13 Pierre QUATREMARE Structures et applications des «Metallacrowns» Equipe Chimie Supramoléculaire, Institut Parisien de Chimie Moléculaire Université Pierre et Marie Curie 4 place Jussieu, Bat F 74 4eme ETG case 42 pierre.quatremare@upmc.fr Figure. Structure cristallographique du metallacrown 30-MC Mn III Les metallacrowns sont considérés comme étant les analogues inorganiques des éthers couronnes. De la même manière que dans ces derniers, on retrouve dans les metallacrowns une structure cyclique où le motif de répétition est généralement de la forme -[M-N-O] n -. Depuis l apparition de cette nouvelle catégorie de métallo-macrocyles, une importante variété de composés a été synthétisée, permettant ainsi d obtenir des structures possédant des topologies et des tailles diverses. En effet, les premières molécules reportées n avaient un cycle qui n était composé au maximum que de 15 atomes. 2 Par la suite, des macrocycles constituer de 60 atomes ont pu être formés. 3 On observe donc l existence d une très grande versatilité de structure pour ce type de système. De plus, les metallacrowns ont également été étudié pour tenter de développer de nouvelles propriétés ou bien d améliorer certaines déjà existantes sur d autres macrocycles, comme par exemple leur capacités à être des agents de reconnaissance spécifique pour certains anions ou cations. 4 D autre part, ces molécules possèdent certaines fonctions intéressantes, comme par exemple dans le domaine de la catalyse, de l imagerie médicale, en tant qu agent antibactérien ou encore de molécule aimant. 4 Acknowledgments: Dr. V. Marvaud, Équipe SUPRA IPCM Références 1 Liu, S.; Lin, S.; Lin, B.; Lin, C.; Huang, J. Angew. Chem. Int. Ed. 2001, 40, a) Pecoraro, V. L. Inorg. Chim. Acta, 1989, 155, b) Lah, M.S.; Pecoraro, V. L. J. Am. Chem. Soc. 1989, 111, Moon, D.; Lee, K.; John, R. P.; Kim, G. H.; Suh, B. J.; Lah, M. S. Inorg. Chem. 2006, 45, Mezei, G.; Zaleski, C. M.; Pecoraro, V. L. Chem. Rev. 2007, 107,

14 Simon GUELEN Use of Lappert s stannylens and derivatives in Stille coupling reactions Université Pierre et Marie Curie, Laboratoire de chimie organique Méthodes et Applications en Chimie Organique (MACO) UMR-CNRS 8232, case 229 4, Place Jussieu, PARIS 05 simon.guelen@upmc.fr The creation of carbon-carbon bonds using organotin reagents and a transition-metal catalyst has been widely developed for the last 10 years. The most popular method remains by far the palladium-catalyzed reaction, also named Stille coupling. 1 However, preparation of organostannane precursors is not always straightforward. They are toxic and the removal of tin reagents is quite difficult. With the aim of promoting the chemistry of nontoxic and easily removable tin reagents, the group of Fouquet has focused on the direct synthesis of new monoallyltins 2,3 prepared from Lappert s stannylene 1. 4,5 Acknowledgment: Labex Michem References: 1 Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, Herve, A.; Rodriguez, A. L.; Fouquet, E. J. Org. Chem.2005, 70, Fouquet, E.; Pereyre, M.; Rodriguez, A. L. J. Org. Chem. 1997, 62, Davidson, P. J.; Lappert, M. F. J. C. S. Chem. Comm. 1973, Harris, D. H.; Lappert, M. F. J. C. S. Chem. Comm. 1974, 895.

15 Julien ROSSIGNOL Carbohydrates as Vectors for Gene Delivery IPCM Equipe GOBS Université Pierre et Marie Curie (UPMC) 4 place Jussieu, Paris Cedex 05, Bâtiment F/74 julien.rossignol@upmc.fr Gene delivery is one of the lead strategies that are currently investigated to provide new treatments for several diseases. 1 One of the key points in this strategy is to carry the genetic material (DNA, RNA or irna) to dysfunctional cells. In order to do so, encapsulation is necessary to protect it from nucleases. 2 Several approaches can be used, using various polymer types. Among them, carbohydrate-based polymers present interesting properties such as biocompatibility and biodegradability. 3,4 As an example, cyclodextrin-based polymers have already been used to successfully transfect cells with sirna. 5 Réferences: 1 Cavazzana-Calvo, M. Science 2000, 80, 288, Niven, R.; Pearlman, R.; Wedeking, T.; Mackeigan, J.; Noker, P.; Simpson-Herren, L.; Smith, J. G. J. Pharm. Sci. 1998, 87, Borchard, G. Adv. Drug Deliv. Rev. 2001, 52, Azzam, T.; Eliyahu, H.; Shapira, L.; Linial, M.; Barenholz, Y.; Domb, A. J. J. Med. Chem. 2002, 45, Davis, M. E. Mol. Pharm. 2009, 6, 659.

16 Sha ZHU Recent progress on studies of morroniside from Cornus Officinalis Sieb. et Zucc. Supervisors: Dr.Yongmin ZHANG, Pr. Matthieu Sollogoub GOBS, Institut Parisien de Chimie Moléculaire, CNRS UMR place Jussieu, Paris, France emyzhusha@gmail.com Modern researches 1 show that the total iridoid glycosides are the main active part in Cornus Officinalis Sieb. et Zucc.(Fructus Corni). This herb is used clinically for the treatment of various health problems in China, such as spontaneous perspiration, night sweating, spermatorrhea, enuresis, vertigo, tinnitus, and impotence. 2 Morroniside, the most aboundant iridoid glycoside of this herb, showed interesting biological activities 3 of anti-inflammatory, hepatoprotection, inhibition of melanogenesis and immunosuppression, especially the effective function of neuroprotection, antidiabetic and the complication. 4,5 H COOCH3 HO O O HO H O O HO HO OH Morroniside Current researches reveal that morroniside is an efficient neuroprotective and antioxidant agent. Whereas the coefficient partition of oil/water of morroniside indicates this hydrophilic compound is not profitable to tissue absorption. The shorter metabolism half life suggests some defects in the structure. 6 Moreover, morroniside is effective in protecting brain cells and improving brain hypoxia tolerance in mice in a dose-effect relationship, but it is weak in crossing blood-brain barrier due to high water-solubility, so systemic studies modification are significant. Some structure modifications at C-7 position were developed which demonstrate a better performance of the modified morroniside in anti-inflammatory. 7,8 Acknowledgments: The China Scholarship Council is gratefully acknowledged for financial support. References: 1 Yokozawa, T.; Kang, K. S.; Park, C. H.; Noh, J. S.; Yamabe, N.; Shibahara, N.; Tanaka, T. Drug Discov. Ther. 2010, 4, China Pharmacopoeia Committee (ed). Pharmacopoeia of the People s Republic of China 2009, 1, Yasuhiko, N.; Junko, E.; Tomihisa, O.; Journal Cosmetic Science 2007, 58, Wang, W.; Xu, J.; Li, L.; Wang, P.; Ji, X.; Ai, H.; Zhang, L.; LI, L. Brain Res. Bull. 2010, 83, Park, C. H.; Tanaka, T.; Kim, J. H.; Cho, E. J.; Park, J. C.; Shibahara, N.; Yokozawa, T. Toxicology 2011, 290, Chen, H. L.; Jiang, B.; Li, Y. C. Chinese J. Med. Chem. 2011, 21, Takeda, Y.; Tanigawa, N.; Sunghwa, F.; Ninomiya, M.; Hagiwara, M.; Matsushita, K.; Koketsu, M. Bioorg. Med. Chem. Lett. 2010, 20, Sunghwa, F.; Sakurai, H.; Saiki, I.; Koketsu, M. Chem. Pharm.Bull. 2009, 57, 112.

17 Marcelo GIRARDI Chemically modified electrodes and their applications in electrocatalysis Pr. Anna PROUST, Dr. Sébastien BLANCHARD Institut Parisien de Chimie Moléculaire, Equipe POM Université Pierre et Marie Curie (UPMC) 4 place Jussieu, Paris Cedex 05, Bâtiment F/74 marcelo.girardi@upmc.fr Electrochemical catalysis, also coined electrocatalysis, is a particular field of catalysis where an electrode is used as a chemical interface to supply reducing or oxidizing equivalents in order to perform a catalytic redox reaction (for example the reduction of H + to H 2 ). Early studies in this field have shown the influence of the electrode surface/material in the outcome, kinetics, of these reactions. However, the conducting nature of the electrode severely limits the repertoire of available surfaces, and thus in many cases limits strongly the selectivity and efficiency of the catalysis. This has led as early as the mid 70's to the development of Chemically Modified Electrodes (CME), in which the electrode surface has been modified through interactions with electrochemically reactive molecular materials. 1,2 Principle of Electrocatalysis 2 Reduction of CO 2 on a protein-based modified electrode 3 Immobilization of synthetic molecules on electrodes surfaces can indeed improve the electrocatalysis efficiency by controlling the reaction sites, while making the oxydoreduction mechanisms much more predictable. By this mean, it is possible to tune the selectivity and specificity of the reaction, to increase its rate and even to reduce the overvoltage, synonymous with energy loss, required for the activation step. In return, one should also take care of the electrochemical stability of the modified surface. In this presentation, we will mainly focus on the attachment of the electrocatalysts and more specifically to the related interactions with the surfaces. 4 An example of CME employing biochemical tools will be presented to illustrate its application in electrocatalysis. 3 References: 1 Murray, R. W. Techniques of chemistry 1992, (Molecular Design of Electrode) 22, 1. 2 Benson, E. E.; Kubiak, C. P.; Sathrum, A. J.; Smieja, J. M. Chem. Soc. Rev. 2009, 38, Armstrong, F.A.; Ragsdale, S. W. J. Am. Chem. Soc 2007, 129, Salaita, G. N.; Hubbard, A. T. Techniques of chemistry 1992, (Molecular Design of Electrode) 22, 49.

18 Guillaume BOISSONNAT Synthèse d hétérocycles par addition intramoléculaire de nucléophiles sur des allènes catalysée par les complexes d or ESPCI Paristech, Laboratoire de Chimie Organique, 10 rue Vauquelin, Paris Cedex 5 guillaume.boissonnat@gmail.com La catalyse homogène par les complexes d or(i) et d or(iii) a connu un essor considérable ces dix dernières années. Ces catalyseurs électrophiles p-acides activent de manière particulièrement efficace les liaisons carbone-carbone insaturées et permettent ainsi l addition de divers nucléophiles. 1,2 Lorsque les allènes A sont utilisés comme substrats, l addition intramoléculaire de nucléophiles oxygénés, azotés voire soufrés, catalysée par des complexes d or(i) ou d or(iii), peut conduire à quatre types d hétérocycles B E possédant une double liaison exocyclique ou endocyclique et un hétéroatome en position vinylique ou allylique. 3 n * X R 1 [Au] n R 2 R 1 n X H A X H X H [Au] R 1 R 1 R R 2 R 2 * 2 R 1 H * X R 2 n X n X n B C D E R 1 R 2 (X = O, N, S) exo endo exo endo n R 1 R 2 Les principaux résultats relatifs au contrôle de la régiosélectivité de la cyclisation, selon substrat ou le catalyseur, le transfert de la chiralité axiale de l allène aux hétérocycles B, D et E, ainsi que le développement de versions énantiosélectives seront présentés. 4 Références: 1 (a) Hashmi, A. S. K.; Toste, F. D. in Modern Gold-Catalysed Synthesis, Wiley-VCH, Weinheim, (b) Toste, D.; Michelet, V. in Gold Catalysis: An Homogeneous Approach, Imperial College Press, London, (a) Fürstner, A.; Davies, P. W. Angew. Chem. Int. Ed. 2007, 46, (b) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, (c) Rudolph, M.; Hashmi, S. K. Chem. Commun. 2011, 47, (d) Corma, A.; Leyva-Perez, A.; Sabater, M. J. Chem. Rev. 2011, 111, (a) Muzart, J. Tetrahedron 2008, 64, (b) Winter, C.; Krause, N. Chem. Rev. 2011, 111, (a) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Quian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128, (b) Gockel, B.; Krause, N. Org. Lett. 2006, 8, (c) Piera, J.; Krumlinde, P.; Strübing, D.; Bäckvall, J.-E. Org. Lett. 2007, 9, (d) Higginbotham, M. C. M.; Bebbington, M. P. Chem. Commun. 2012, 48, (e) Cox, N.; Uehling, M. R.; Haelsig, K. T.; Lalic, G. Angew. Chem. Int. Ed. 2013, 52, 4878.

19 Xiaolei ZHU PARP1 a promising target and the development of PARP1-based candidates for anticancer intervention Institut Parisien de Chimie Moléculaire (CNRS UMR 7201) Glycochimie Organique Biologique et Supramoléculaire Bât F, 2ème étage 4place Jussieu. C. 181, Paris, France xl.zhu@hotmail.com PARP1 inhibition, increasing chemosensitization and conferring independent antiproliferation against defective homologous recombination cells, has provided a unique opportunity. Poly(ADPribose) polymerase 1 (PARP1), a best established target for the treatment of oncology attributed to its intimate role in DNA repair. Up to date, intensified medicinal chemistry efforts have led to the discovery of 12 PARP1 inhibitors that have been advanced into clinical trial. These candidates are classified into three categories based on the chemical structure, including lactam type, pseudo ring type and untypical PARP1 inhibitors, for a sequential overview of them. In particular, the development of some candidates will be highlighted to direct the future exploration of PARP1 inhibitors. 1,2 Binding mode of PARP1 inhibitors interaction with NI site References: 1 Riffell, J. L.; Lord, C. J.; Ashworth, A. Nat. Rev. Drug Discov. 2012, 11, Ferraris, D. V. J. Med. Chem. 2010, 53, 4561.

20 Charlotte GRANDCLAUDON Halogénation énantiosélective d'insaturations carbonées: Accès à des hétérocycles fonctionnalisés Institut de Recherche de Chimie de Paris, Chimie Paristech 11 Rue Pierre et Marie Curie PARIS Cedex 05 Les réactions d'halocyclisations sont connues depuis longtemps en chimie organique, la première iodolactonisation ayant été décrite en 1904 par Bougault. 1 Reposant sur l'attaque nucléophile d'hétéroatomes (N,O) sur des insaturations carbonées (alcènes, allènes, alcynes) activées par un halogène, ces réactions permettent d'accéder à des hétérocycles variés tels que des lactones, des éthers ou des amines cycliques. Ces réactions présentent de nombreuses applications en synthèse, qui exploitent les possibilités de fonctionnalisation offertes par la présence de l'atome d'halogène. En dépit de leur historique et leur importance, les versions énantiosélectives de ces halocyclisations n'ont été développées que très récemment. 2 C'est principalement le design de nouveaux organocatalyseurs chiraux tels que les acides phosphoriques, 3 les dérivés d'alcaloïdes de type quinine 4 ou encore les urées 5 qui ont permis d'accéder à de très hautes valeurs d'excès énantiomériques sur ces réactions (Type I). Les transformations asymétriques catalysées par des complexes chiraux de métaux de transition ont été en revanche bien moins développées (Type II). 6 Figure: Différents types d'activation électrophiles des insaturations carbonées Dans ce cadre, nous présenterons les avancées récentes concernant les versions énantiosélectives des halocyclisations en nous intéressant particulièrement aux transformations organocatalysées. References: 1 Bougault, M. J. R. Acad. Sci. 1904, 139, Castellanos, A.; Fletcher, S. P. Chem. Eur. J. 2011, 17, (a) Denmark, S. E.; Burk, M. T. Org. Lett. 2012, 14, 256. (b) Xie, W.; Jiang, G.; Liu, H.; Hu, J.; Pan, X.; Zhang, H.; Wan, X.; Lai, Y.; Ma, D. Angew. Chem. Int. Ed. 2013, 52, (in press) 4 a) Zhou, L.; Tan, C. K.; Jiang, X.; Chen, F.; Yeung, Y.-Y. J. Am. Chem. Soc. 2010, 132, (b) Jaganathan, A.; Garzan, A.; Whitehead, D. C.; Staples, R. J.; Borhan, B. Angew. Chem. Int. Ed. 2011, 50, Tungen, J. E.; Nolsøe, J. M. J.; Hansen, T. V. Org. Lett. 2012, 14, Miles, D. H.; Veguillas, M.; Toste, F. D. Chem. Sci. 2013, 4, 3427.