Les objectifs de cette thèse portent sur l’élaboration de nouveaux matériaux réticulés réversibles et sur la compréhension de leurs propriétés mécaniques. Pour atteindre ces objectifs, nous avons exploité deux stratégies : la réaction de Diels-Alder (DA) à partir de copolymères parfaitement définis dotés de motifs furanes et la remarquable réactivité des azlactones vis-à-vis des amines. Les copolymères ont été synthétisés par polymérisation radicalaire contrôlée afin d’obtenir des copolymères parfaitement définis fonctionnalisés en chaine latérale. Différents copolymères réticulés ont été préparés via la réaction de DA et caractérisés en termes de température de transition vitreuse et de taux de gonflement. L’étude de leurs propriétés thermiques et viscoélastiques a mis en évidence une influence de la réticulation. Dans un second temps, les propriétés telles que leur réversibilité et leur comportement mécanique ont été étudiées. Nous avons défini l’existence d’une relation entre les mécanismes de plasticité et l’évolution structurale induite. Concernant les copolymères à base d’azlactones, nous avons montré que la nouvelle plateforme polymère était facilement modifiable par une grande variété d’amines primaires permettant d’élaborer de nouveaux matériaux avec des propriétés intéressantes (fluorescent, électroactif…). Les polymères fonctionnalisés ainsi obtenus ont été caractérisés par diverses techniques d’analyses qui ont permis de traduire le caractère quantitatif de la réaction. Enfin, des matériaux réticulés ont également été élaborés par la réaction des motifs azlactones avec un composé diamine. / The main objectives of this work were the elaborate new reversible crosslinked materials and to get a better understanding of their physical and mechanical properties. Two strategies have been investigated to prepare such materials. The first one consisted in applying to well-defined furan functionalized side-chain copolymers the Diels-Alder (DA) / retroDiels-Alder reactions. The second approach was based on the high reactivity of azlactone units embedding in well-defined copolymer chains toward primary amines. The controlled radical polymerization has been exploited in order to provide an effective way for the control synthesis of the well-defined side-chain functionalized copolymers. Then, various crosslinked materials have been prepared using the DA reaction and characterized to determine their glass transition temperature and their swelling ratio. The study of their thermal and viscoelastic properties highlighted the deep impact of the crosslinking. Then, their reversible and mechanical behaviors were investigated and we observed a correlation between the plastic deformation mechanisms and the induced structural evolution. Concerning the azlactone based copolymer, we have shown that this new polymeric platform could be efficiently modified by various primary amines, affording new materials with interesting properties (fluorescence, electroactive,…). The ring-opening reactions of azlactone functionalized copolymers were fully characterized proving the quantitative character of this reaction. Endly, crosslinked materials have been also elaborated by treating the azlactone copolymer with a diamino component.

Ce travail de thèse porte sur la synthèse de (co)polymères thermosensibles présentant une fonctionnalité azlactone par polymérisation radicalaire contrôlée RAFT pour l’ancrage de biomolécules. Trois stratégies différentes ont été étudiées. La première stratégie a consisté en la synthèse d’un nouvel agent de transfert permettant d’obtenir des polymères thermosensibles à fonctionnalité azlactone en position . La seconde approche a permis d’introduire la fonctionnalité azlactone en position ω de copolymères thermosensibles via la combinaison de la polymérisation RAFT et de l’addition de Michaël « thiol-ène ». La dernière stratégie a conduit à des copolymères thermosensibles à fonctionnalité azlactone en position latérale par copolymérisation RAFT de la 2-vinyl-4,4-diméthylazlactone avec d’autres monomères. Enfin, la réactivité de ces copolymères thermosensibles pour l’ancrage d’une protéine modèle (lysozyme) a été mise en évidence. / The synthesis of well-defined azlactone-functionalized thermoresponsive copolymers was performed using the RAFT polymerization and their interaction with primary amines and proteins was studied. Three different strategies have been developed. The first strategy was based on the synthesis of a novel azlactone-functionalized chain transfer agent which was used to target well defined  azlactone-functionalized thermoresponsive polymers. In the second approach, ω-azlactone-terminated thermoresponsive copolymers were prepared by a combination of RAFT polymerization and “thiol ene” Michaël’s addition. In the last strategy, RAFT copolymerization of 2-vinyl-4,4 dimethylazlactone with other monomers has been performed to target well-defined azlactone functionalized copolymers. Finally, the reactivity of such reactive thermoresponsive copolymers was successfully demonstrated by bioconjugation with a model protein (lysozyme).

4, 4'-Dihydroxybenzophenone-2, 4-dinitrophenylhydrazone (A-007) has recently completed a phase-I clinical trial, and objective responses were seen in advanced breast cancer, lung cancer, ovarian cancer, melanoma, skin cancer and non-Hodgkin's lymphoma. Despite the promising results in the clinical trials, the major disadvantage to using A-007 as a broad-scale therapeutic is its poor water solubility. To make use of this promising anticancer drug either orally or intravenously, the short-term obstacle must be to overcome the limited solubility of A-007 in water. There are several approaches to overcome this obstacle. The first approach is to make hydrolysable prodrugs of A-007. The second approach is to make an A-007 complex with a water soluble host, such as cyclodextrin. We used a combination of these two previously described methods, i.e. transforming A-007 into a more water soluble prodrugs and then further increasing the prodrug water solubility by making their cyclodextrin inclusion complexes. Our syntheses and spectroscopic explorations of A-007 prodrugs are presented in this dissertation. Tetramic acid (2, 4 pyrrolidine-2, 4-dione ring system) containing compounds have been found to display a remarkable diversity of biological activities and have attracted the interest of medicinal and synthetic chemists. Magnesidin (1-acetyl-3-octanoyl-5-ethylidene tetramic acid) has strong antimicrobial activity against bacteria that cause gingivitis and dental plaque. Current efforts toward the synthesis of Magnesidin are discussed along with the plans for the completion of synthesis.

La nanomédecine, appliquée en particulier au traitement du cancer, suscite depuis une quinzaine d’années un intérêt grandissant, développant des stratégies innovantes pour le ciblage spécifique de tissues malades. De nouveaux progrès en la matière sont encore à venir, mais nécessitent de nouveaux matériaux offrant une grande flexibilité en termes de synthèse, ainsi que la possibilité de fonctionnalités et de propriétés physicochimiques variées ; avantages tous présentés par l’utilisation des techniques de polymérisation radicalaire contrôlée (CRP). Ces techniques de polymérisation ont déjà démontré leur fort potentiel à travers différents systèmes nanoparticulaires à base de prodrogues de polymère, mais aucun d’entre eux ne s’avère dégradable ce qui pourrait empêcher à l’avenir leur utilisation et leur développement.Anticipant les besoins, ce projet a eu pour but la synthèse de polymères PEGylés dégradables par la technique de polymérisation contrôlée par les nitroxydes (NMP), travail très en amont de l’habituel procédé d’élaboration d’un nouveau nanomédicament. Pour ce faire, la NMP du méthacrylate de méthyl éther oligo(éthylène glycol) (MeOEGMA) a été combinée à la polymérisation radicalaire par ouverte de cycle (rROP) des acétals de cétène cyclique (CKAs), connus comme précurseurs de fonctions esters.Parmi trois CKAs étudiés, le 2-méthylène-4-phényl-1,3-dioxolane (MPDL) a montré une capacité unique à copolymériser avec les dérivés de méthacrylates, grâce à sa structure ouverte de type « styrènique » permettant son utilisation en NMP. A travers une étude approfondie des propriétés de contrôle et de caractère vivant de ces copolymères, le MPDL s’est également révélé être le premier comonomère de contrôle des méthacrylates à être dégradable. Un lien direct entre dégradabilité et quantité de MPDL insérée a été démontré, permettant jusqu’à l’hydrolyse complète des matériaux. Ces copolymères n’ont montré aucune cytotoxicité, et ce sur trois types de cellules différents (fibroblastes, cellules endothéliales et macrophages), et une étude similaire sur la toxicité de leurs produits de dégradation a permis d’aboutir à la même conclusion, soulignant la possible biocompatibilité de ces nouveaux matériaux qui, si confirmée, permettrait leur utilisation pour des applications biomédicales.Parallèlement, un second projet portant sur la mise au point d’une nouvelle alcoxyamine à base du nitroxide SG1 et présentant une fonction azlactone, baptisée AzSG1, a été développé pour la synthèse de polymères fonctionnalisables par NMP. Utilisant l’alcoxyamine AzSG1 comme amorceur, les NMPs du styrène, de l’acrylate de n-butyle et du méthacrylate de méthyle ont été réalisées avec succès, ainsi que le couplage quantitatif de la benzylamine comme preuve de concept de la possible fonctionnalisation. Dans un avenir proche, utiliser cet amorceur fonctionnalisable pour la synthèse de copolymères à base de MeOEGMA et de MPDL pourrait ainsi permettre l’élaboration de copolymères PEGylés, dégradables et fonctionnalisables par NMP, pour des applications dans le domaine de la bioconjugaison et du drug delivery. / Nanomedicine, especially for cancer treatment, has attracted much interest over the last fifteen years, developing innovative strategies for targeting diseased tissues. Further improvements of these approaches will require advanced new materials affording versatility, functionalities and specific physico-chemical properties, all advantages offered by the controlled radical polymerization (CRP) techniques. These radical polymerizations already showed their great potential through various efficient anticancer polymer nanocarriers but all lacking of degradability, which may hinder any actual developments.Anticipating the needs, this project focused on the synthesis of degradable PEG-based polymers by nitroxide-mediated polymerization (NMP), as an early stage in the usual process of nanocarrier design. To do so, NMP of oligo(ethylene glycol) methyl ether methacrylate (MeOEGMA) has been for the first time combined to the radical ring-opening polymerization (rROP) of various cyclic ketene acetals (CKAs), known as ester precursors.Among three CKAs tested, 2-methylene-4-phenyl-1,3-dioxolane (MPDL) has shown a unique ability to copolymerize with methacrylate derivatives, likely due to a styrene-like open structure allowing for its use in NMP. Through a careful study of the control and livingness properties of these copolymers, MPDL was also demonstrated to be the first degradable controlling comonomer for polymethacrylate synthesis. The degradability of the resulting PEG-based copolymers was proven to be proportional to the adjustable amount of MPDL inserted, up to complete degradation. These copolymers showed no cytotoxic effect on various cell types (fibroblasts, endothelial cells and macrophages), and an additional study of the innocuousness of their degradation products led to similar results, underlining their potential biocompatibility which, if confirmed, would allow these materials to be used for biomedical applications.A second project about a new azlactone-functionalized SG1-based alkoxyamine (AzSG1) was also set up, as initiator for the synthesis of functionalizable polymers by NMP. Using the AzSG1 alkoxyamine, the NMP of styrene, n-butyl acrylate and methyl methacrylate were successfully performed, as well as a quantitative coupling of benzylamine as proof of concept. In the near future, making use of this functionalizable initiator for copolymerizing MeOEGMA with MPDL may allow the easy synthesis of functionalized degradable copolymers by NMP, for bioconjugation and drug delivery applications.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-09-23T12:23:32Z No. of bitstreams: 1 pedropossadecastro.pdf: 5686031 bytes, checksum: 9e1207fe7ed0dbf820e7976d236128f3 (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-09-26T20:30:37Z (GMT) No. of bitstreams: 1 pedropossadecastro.pdf: 5686031 bytes, checksum: 9e1207fe7ed0dbf820e7976d236128f3 (MD5) / Made available in DSpace on 2016-09-26T20:30:37Z (GMT). No. of bitstreams: 1 pedropossadecastro.pdf: 5686031 bytes, checksum: 9e1207fe7ed0dbf820e7976d236128f3 (MD5) Previous issue date: 2016-07-22 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A síntese de aminoácidos biologicamente funcionais e pequenos peptídeos tem se mostrado uma área promissora da química orgânica. As azalactonas podem atuar como aminoácidos protegidos e serem utilizadas na síntese de derivados de aminoácidos e heterociclos complexos. Neste trabalho são descritas reações de abertura de azalactonas por aminoácidos catalisadas por um ácido de Brønsted, o (+/)-ácido canforsulfônico (ACS), resultando na formação de dipeptídeos. Os heterociclos azalactônicos foram preparados em duas etapas: uma acilação dos aminoácidos com cloreto de benzoíla em meio alcalino, levando aos N-benzoil aminoácidos com até 75% de rendimento, e uma reação de ciclização intramolecular mediada pelo EDC, um ativador de ácido carboxílico, culminando nas azalactonas desejadas em rendimentos que variaram de 8298%. As condições otimizadas para a reação para a formação dos dipeptídeos consistiram na utilização de 5 mol % de ácido canforsulfônico como catalisador, diclorometano como solvente, agitação e temperatura ambiente. Avaliou-se o escopo de reação variando as azalactonas utilizadas e também os aminoácidos empregados como nucleófilos. Os rendimentos foram de bons a excelentes (entre 66 e 99%) e mesmo o uso de aminoácidos e azalactonas mais impedidos do ponto de vista estéreo, como nos derivados de valina e leucina, forneceu os respectivos dipeptídeos em bons rendimentos. Os produtos foram caracterizados por RMN de 1H, 13C, DEPT135, IV e de EMAR. Foi demonstrada a possibilidade de ciclização intramolecular dos dipeptídeos obtidos utilizando-se EDC, resultando em uma nova azalactona de estrutura mais complexa. Finalmente, a substituição do grupo N-benzoil por terc-butil carbamato tornou possível a síntese de uma azalactona sem que houvesse epimerização do centro estereogênico alfa à carbonila, sendo realizada ainda a posterior abertura deste heterociclo pela octilamina. / The synthesis of biologically functional amino acids and small peptides has been a promising area of organic chemistry. The azlactones can act as protected amino acids and are used in the synthesis of amino acid derivatives and complex heterocycles. This work describes azlactones ring opening by amino acids catalyzed by a Brønsted acid, the (+/-)-camphorsulfonic acid (CSA), resulting in the formation of dipeptides. The azlactone heterocycles were prepared in two steps: an acylation of the amino acid with benzoyl chloride under alkaline conditions leading to N-benzoyl amino acids with up to 75% yield, and an intramolecular cyclization reaction mediated by EDC, a carboxylic acid activator, affording the desired azlactones in yields ranging from 82-98%. The optimized conditions for the dipeptide formation reaction consisted of 5 mol % of camphorsulfonic acid as a catalyst, dichloromethane as solvent, stirring and at room temperature. The scope was evaluated varying the azlactones and the amino acids. Yields were satisfactory (ranging from 66 to 99%). Even the use of more sterically hindered amino acids and azlactones, such as valine and leucine derivatives, the dipeptides were obtained in good yields. The products were characterized by 1H NMR, 13C, DEPT135, IR and HRMS. The possibility of an intramolecular cyclization of the dipeptides using EDC has been demonstrated, resulting in a more complex azlactone. Finally, the substitution of the N-benzoyl group by tert-butyl carbamate allowed the synthesis of an azalactone without epimerization of the stereogenic center alpha to the carbonyl, a subsequent opening of the heterocycle by octylamine was also performed.

Ce travail de thèse porte sur la synthèse de (co)polymères thermosensibles présentant une fonctionnalité azlactone par polymérisation radicalaire contrôlée RAFT pour l'ancrage de biomolécules. Trois stratégies différentes ont été étudiées. La première stratégie a consisté en la synthèse d'un nouvel agent de transfert permettant d'obtenir des polymères thermosensibles à fonctionnalité azlactone en position . La seconde approche a permis d'introduire la fonctionnalité azlactone en position ω de copolymères thermosensibles via la combinaison de la polymérisation RAFT et de l'addition de Michaël " thiol-ène ". La dernière stratégie a conduit à des copolymères thermosensibles à fonctionnalité azlactone en position latérale par copolymérisation RAFT de la 2-vinyl-4,4-diméthylazlactone avec d'autres monomères. Enfin, la réactivité de ces copolymères thermosensibles pour l'ancrage d'une protéine modèle (lysozyme) a été mise en évidence.

This thesis reports diverse synthetic and mechanistic studies in six chapters, as summarized below. Chapter 1. Revised mechanism and improved methodology for the perkin condensation.1 The generally accepted mechanism for the well-known Perkin condensation is unviable for at least two reasons: (1) the normally employed base, acetate ion, is too weak to deprotonate acetic anhydride (Ac2O, the substrate); and (2) even were Ac2O to be derprotonated , its anion would rapidly fragment to ketene and acetate ion at the high temperatures employed for the reaction. It has proved in this study that the Perkin condensation occurs most likely via the initial formation of a fem-diacetate (3, Scheme 1) from benzaldehyde (2) and acetic anhydride (1).1 The key nucleophile appears to be the enolate of 3 (and not of 1), which adds t the C=O group of the aldehyde 2 (present in equilibrium with 3). Thus cinnamic acid (4a) was formed in -75% yield with 3 as the substrate under the normal conditions of the Perkin reaction. The deprotonation of the diacetate appears to be electrophilically assisted by the neighbouring acetate group, the resulting enolate being also thermodynamically stabilized in form of an orthoester (I). The possibility that the diacetate 3 is the actual substrate in the Perkin reaction indicates that the reaction can be effected under far milder conditions, with a base much stronger than acetate ion. This was indeed realized with potassium t-butoxide in dioxane, which converted the gem-diacetates derived from a variety of aromatic aldehydes to the corresponding cinnamic acids (4), rapidly and in good yields at room temperature (Scheme 2). This represents a vast improvement in the synthetic protocol for the classical Perkin reaction, which remains an important carbon-carbon bond forming reaction to this day. Chapter 2. Aromaticity in azlactone anions and its sifnificance for the Erlenmeyer synthesis.2 The classical Erlenmeyer azlactone synthesis of amino acids occur via the formation of an intermediate azlactone, and its subsequent deprotonation by a relatively weak base(acetate ion),. The resulting azlactone anion (cf. II, Scheme 3) functions as a glycine enolate equilvalent, and is considered in situ with an aromatic aldehyde, subsequent dehydration leading to the 4-alkylidene oxazolone(analogously to the Perkin reaction). Interestingly, azlactone anions are possibly aromatic, as they possess 6π electrons in cyclic conjugation; this would explain their facile formation as also the overall success of the Erlenmeyer synthesis. The following studies evidence this possibility. The strategy involved studying the rates of base-catalyzed deprotonation in 2-phenyl-5(4H)-oxazolone (azlactone, 5) and its amide and ketone analogs, 3-methyl-2-phenyl-4(5H)-imidazolone (6), and 3,3-dimethyl-2-phenyl-493H)-pyrrolone (7) respectively.2 Two processes were studied, deuterium exchange and condensation with hexadeuteroacetone (Scheme3): both are presumably mediated by the anions II-IV, so their stabilities would govern the overall rates. These were followed by 1H NMR spectroscopy by monitoroing the disappearance of the resonance of the proton α to the carbonyl group. The order of deprotonation was found to be 6 > 5 > 7. However, the expected order based on pKa values would be ketone > ester > amide, i.e. 7 > 5 > 6. The inverted order observed strongly indicates the incursion of aromaticity, which would be enhanced by the electron-donor capabilities of the heteroatoms is 5 and 6. This is further substantiated by the greater reactivity in the case of the nitrogen analog 6 relative to the oxygen 5, which parallel the electronegativity order. (The aromaticity order would thus be: III > II > IV. The imidazole nucleus is indeed to be considerably more aromatic than the oxazole.) The synthesis of the analogs 6 and 7 was accomplished via an interesting intramolecular aza-Wittig reaction (Schemes 4 & 5) Chapter 3. Umpolung approach to the Erlenmeyer process in the synthesis of dehydro amino acids. These studies are based on the general observation that most of the strategies for the synthesis of α-amino acids introduce the side chain (or part was inverted in an umpolung sense. The key reaction studied was that of 2-phenyl-4-ethoxymethylne-5(4H)-oxazolone (11) with Grignard reagents: this resulted in the opening to yield a protected dehydro amino acid (12), in good to excellent yields (65-87%)(Scheme ^). As the azlactone reactant 11 is the ekectrophilic partner, this may be viewed as a partial umpolung version of the classical Erlenmeyer process. The readily available reactants, simple procedure and mild reaction conditions make this a very attractive method for the synthesis of a variety of α-dehydro amino acids. Chapter 4. The Erlenmeyer azlactone synthesis with aliphatic aldehydes under solvent-free microwave conditions. 3 A serious limitation to the classical Erlenmeyer reaction is that it generally fails in the case of aliphatic aldehydes. This chapter describes a convenient approach to this problem that extends the scope of the Erlenmeyer synthesis, via a novel microwave-induced, solvent-free process. This, it was observed that azlactones (5) react with aliphatic aldehydes (13) upon adsorption on neutral alumina and irradiation with microwaves (< 2 min), forming the corresponding Erlenmeyer products (14) in good yields (62-78%, Scheme 7). (The possible mechanistic basis of the procedure, which is presumably mediated by V , is discussed).3 Chapter 5. 2,4, 10-Trioxaadamantane as a carboxyl protecting group: application to the asymmetric synthesis of α-amino acids (umpolung approach).It is known that the 2,4,10-trioxaadamantane moiety is not only remarkably stable to nucleophilic attack, but can also be easily hydrolyzed to the corresponding carboxylic acid.4 It was of interest to apply this carboxyl protection strategy for designing a synthesis of α-amino acids, essentially by starting with a protected glyoxylic acid. The corresponding aldimine was expected to (nucleophilically) add organometallic reagents at the C=N moiety (cf. Shceme 8), the side chain of the amino acid being thus introduced in umpolung fashion. Also, a chiral aldimine would define an asymmetric synthesis of amino acids. Indeed, the chiral aldimine 17, derived from 2,4,10-troxaadamantane-3-carbaldehyde 15 and [(S)-(-)-1-phenylethylamine] 16, reacted with a variety of Grignard reagents to furnish the corresponding protected α-amino acids (18) in good yields, with moderate diastereometric excess (Scheme 8). Better yields and ‘de’ values were obtained with organolithium reagents. Chapter 6: possible one-pot oligopeptide synthesis with azlactones or amino acid N-carboxyanhydrides (NCAs). This chapter describes a novel approach to oligopeptide synthesis employing azlactones or NCA’s as amino acid equivalents which are simultaneously protected and activated (Scheme 9). Thus, the addition of the 4-substituted 2-benzyloxyazlactone (19) to an N-protected amino acid under basic conditions, was initially explored. The reaction was expected to yield a dipeptide (21) via the rearrangement of the mixed anhydride intermediate (VI) (Scheme 9). The subsequent addition of a different azlactone to the dipeptide (21) would analogously lead to the formation of a tripeptide (22). This may be performed repetitively to define a strategy for C-terminal extension of an oligopeptide chain, noting that no intervening deprotecting and activating steps are necessary. (In toto deprotection may be effected finally via the hydrogenolyis of the bvenzyloxy groups, to obtain 23.) A closely analogous strategy may also be envisaged by employing N.carboxyanhydrides (NCA’S, 24) instead of azlactones, as shown in Scheme 10 (forming dipeptide 26 and tripeptide 27). The main difference n this case is that the carbamic acid moiety of the intermediate mixed anhydride (VII) is expected to undergo decarboxylation to VIII (thus obviating the need for a deprotection step). However, this putative advantage is offset by the instability of NCA’s and their tendency toward polymerization. However, only partial success could be achieved in these attempts, although a variety of conditions were explored. The strategy and the experimental results have been analyzed in detail, as this interesting approach appears to be promising, and worth further study. (For structural formula pl refer the pdf file)

Ce travail concerne la modification de surface de nanoparticules magnétiques (MNP) par des copolymères réactifs renfermant des cycles azlactone, aux fins de l’élaboration de nano-supports destinés à l’immobilisation de biomolécules. Trois stratégies basées sur des techniques de polymérisation radicalaire contrôlée ont été mises en œuvre.Dans la première, un copolymère poly(méthacrylate de poly(éthylène glycol)-stat-2-vinyl-4,4-diméthylazlactone) (poly(PEGMA-stat-VDM)) a été préparé par polymérisation radicalaire par transfert d’atome (ATRP) selon la technique « grafting from » à partir des MNP et utilisé pour la bioconjugaison de thymine peptide nucleic acid (PNA). La présence de l’écorce polymère et l’immobilisation du PNA ont été confirmées par différentes techniques complémentaires (FTIR, VSM).La deuxième stratégie est basée sur l’élaboration de MNP greffées pour la bioconjugaison de l’acide folique, via l’ARTP du PEGMA et de la VDM. L’analyse par microscopie électronique à transmission (TEM) a montré qu’après bioconjugaison les MNP possèdent une très bonne aptitude à la dispersion en milieu aqueux.La troisième stratégie met en œuvre la technique «grafting onto » de copolymères poly(oxyde d’éthylène)-bloc-poly(2-vinyl-4,4-dimethylazlactone) (PEO-b-PVDM) pour la préparation de nanosupports magnétiques recyclables. Des copolymères à blocs PEO-b-PVDM ont été préparés par la technique de polymérisation RAFT puis greffés sur des MNP fonctionnalisées amino-silane. Les analyses en TEM et par spectroscopie de corrélation de photons ont révélé l’aptitude à la dispersion aqueuse et à la formation de nanoclusters. Les clusters ainsi obtenus ont été utilisés en tant que nanosupports magnétiques recyclables pour l’adsorption d’anticorps. / We herein report the surface modification of magnetite nanoparticle (MNP) with copolymers containing active azlactone rings via a grafting ‘from’ and grafting ‘onto’ controlled radical polymerization (CRP) for use as a nano-solid support for immobilization with biomolecules. Three different approaches were presented as following. First, synthesis of poly(poly(ethylene glycol) methyl ether methacrylate-stat-2-vinyl-4,4-dimethylazlactone) (PEGMA-stat-VDM)-grafted MNP via a grafting ‘from’ atom transfer radical polymerization (ATRP) and its application as a platform for conjugating thymine peptide nucleic acid (PNA) monomer were presented. The presence of polymeric shell and the immobilization of thymine PNA on MNP core were confirmed by fourier transform infrared spectroscopy (FTIR) and vibrating sample magnetometry (VSM) techniques. The second strategy is based on the synthesis of MNP grafted with PEGMA and VDM via ATRP for conjugation with folic acid (FA). The existence of PEGMA and VDM in the structure was characterized by FTIR, TGA and VSM. After the FA conjugation, Transmission Electron Microscopy (TEM) results indicated that the FA-conjugated MNP having high VDM content exhibited good dispersibility in water.Third, the synthesis of MNP grafted with poly(ethylene oxide)-block-poly(2-vinyl-4,4-dimethylazlactone) (PEO-b-PVDM) block copolymer via a grafting ‘onto’ strategy and its application as recyclable magnetic nano-support for adsorption with antibody were studied. PEO-b-PVDM diblock copolymers were first synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization and then grafted onto amino-functionalized MNP. TEM images and photo correlation spectroscopy (PCS) indicated an improvement in the particle dispersibility in water after coating with the copolymers. The nanoclusters with PEO-b-PVDM copolymer coating were used as recyclable magnetic nano-supports for adsorption with antibody.