Generation of Well-Defined Clickable Glycopolymers from Aqueous RAFT Polymerization of Isomaltulose-Derived Acrylamides OUAISS ABDELKADER, 1,2,3 SYLVIE MOEBS-SANCHEZ, 1,2 YVES QUENEAU, 1,2 JULIEN BERNARD, 3 ETIENNE FLEURY 3 1 INSA-Lyon, Institut de Chimie et de Biochimie Mole ´ culaires et Supramole ´ culaires, F-69621, Villeurbanne Cedex, France 2 ICBMS, UMR 5246; CNRS; Universite ´ de Lyon; Universite ´ Lyon 1; INSA-Lyon; CPE-Lyon; F-69621, Villeurbanne Cedex, France 3 Universite ´ de Lyon, INSA-Lyon, Universite ´ Claude Bernard Lyon 1, Inge ´ nierie des Mate ´ riaux Polyme ` res (UMR-CNRS 5223), F-69621, Villeurbanne Cedex, France Received 26 October 2010; accepted 2 December 2010 DOI: 10.1002/pola.24549 Published online 2 February 2011 in Wiley Online Library (wileyonlinelibrary.com). ABSTRACT: Original carbohydrate-based acrylamides bearing one azide group in C-2 or C-6 position namely, 2-[(2-deoxy-2-azido-a-D- mannopyranosyloxy)ethanamido]-ethyl acrylamide (II) and 2-[(6- deoxy-6-azido-a-D-glucopyranosyloxy)ethanamido]-ethyl acrylami- de (III), and their azide-free analogue, 2-[(a-D-glucopyranosyloxy)- ethanamido]-ethyl acrylamide (I), have been designed. Whereas the reversible addition fragmentation chain transfer (RAFT) pro- cess ensured the preparation of well-defined glycopolymers from I, the polymerization of monomers II and III proved to be challeng- ing at temperatures compatible with a thermally initiated radical process, due to the presumed concomitant 1,3-cycloaddition reac- tions between the azide and the acrylamide moieties. In contrast to III, for which no polymer could be obtained under any conditions, performing the RAFT polymerization of II at 30  C clearly favored the radical polymerization and conferred a controlled character to the process, affording well-defined azide-functionalized glycopoly- mers and block copolymers. The presence of numerous azide moieties was finally exploited to introduce carbohydrates onto the glycopolymer backbone through copper catalyzed azide-alkyne cycloaddition. V C 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 49: 1309–1318, 2011 KEYWORDS: azide; click chemistry; glycopolymer; isomaltulose; reversible addition fragmentation chain transfer polymerization INTRODUCTION As biomimetic counterparts of natural polysac- charides, glycopolymers have received much attention lately. Such synthetic polymers displaying saccharide moieties play a central role at the interface between polymer science and biology due to potential biocompatibility and enhanced carbohydrate-protein interactions benefitting from multivalency. 1 Applications of glyco- polymers include among others, therapeutics, 2 cell sensing, 3 tools for glycobiology as selectin antagonists, 4,5 model biomembranes, 6 targeted drug/gene delivery, 7,8 or synthetic biology. 9 A very large range of ‘‘living’’ and/or controlled polymerization techniques, that is, anionic, cationic, or ring-opening metathesis polymerization, cyanoxyl-mediated free-radical polymerization, nitroxide-mediated radical polymerization, transition-metal-cata- lyzed atom transfer radical polymerization or reversible addition fragmentation chain transfer (RAFT) polymerization, have been explored over the last decades to generate well-defined glycopolymers with different architectures. 10 Of particular inter- est is the versatile RAFT process, which operates efficiently with a wide range of monomers and enables the preparation of tailor made glycopolymers in water or protic solvents without recourse to protecting group chemistry. 11 RAFT polymerization has been particularly beneficial to the design of a broad array of glycoma- terials including linear homopolymers, 12 block copolymers, 13 polymer stars, 14 polymer brushes, 15 or glycoparticles 16 and con- sequently numerous bioapplications of RAFT-made glycopoly- mers have been reported in the last decade. 17 The recent advent of the ‘‘click chemistry’’ concept 18 that gathers robust, orthogonal and highly efficient chemical pathways, affording simple product isolation, have promoted the emergence of alternative successful routes to functional materials through the ligation of appropri- ately functionalized substrates onto reactive preformed polymer backbones. 19 Using an effective post-modification route enables to circumvent the poor availability of specific functional mono- mers, prevents a potential lack of orthogonality under poly- merization conditions, and generates effortlessly a library of diversely functionalized polymers. As a consequence a wide panel of well-defined glycomaterials has recently been elabo- rated by combining controlled polymerization techniques and ‘‘click’’ post-modifications involving copper catalyzed azide- alkyne cycloadditions (CuAAC), 20 thiol-ene reactions, 21 thiosu- gar/bromide and thiosugar/chloride reactions 22 or oxime, 23 and hydrazide chemistries. 24 Whereas a large variety of ‘‘clickable’’ polymer backbones have been described in the last decade, very few examples of Additional Supporting Information may be found in the online version of this article. Correspondence to: Y. Queneau (E-mail: yves.queneau@ insa-lyon.fr) or E. Fleury (E-mail: etienne.fleury@insa-lyon.fr) Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 49, 1309–1318 (2011) V C 2011 Wiley Periodicals, Inc. GLYCOPOLYMERS FROM RAFT POLYMERIZATION, ABDELKADER ET AL. 1309