Laetitia Mespouille

Synthesis of well-defined hydrogel networks using Click chemistry

New PEG-based hydrogel materials have been synthesized by Click chemistry and shown to result in well-defined networks having significantly improved mechanical properties; the selectivity of the azide/acetylene coupling reaction also allows for the incorporation of various additives and functional groups leading to chemical tailoring of the hydrogels.

Expanding the role of chemistry to produce new amphiphilic polymer (co)networks

Preparation of model amphiphilic polymer networks (APNs) using various polymerization mechanisms and/or organic coupling reactions are reviewed. A particular emphasis is made on controlled/“living” polymerization techniques in their diversities and how they impact on the structure-reactivity relationships. Advantages and limitations of each technique, as well as improvement of final physical/dynamical properties, are thoroughly discussed and compared for some of the mechanisms. Confrontation of experimental data with Flory’s theory is also displayed in the particular case of controlled radical polymerization (CRPs) techniques. Synthesis of model APNs by the end-linking process using efficient organic coupling reactions such as Michael-type addition, Huisgen 1,3-dipolar cycloaddition and thiol-ene click reactions are deeply illustrated and discussed.

Amphiphilic poly(D- or L-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) block copolymers: controlled synthesis, characterization, and stereocomplex formation.

Novel well-defined amphiphilic poly(D-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PDLA-b-PDMAEMA) and poly(L-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PLLA-b-PDMAEMA) copolymers were obtained. The synthesis strategy consisted of a three-step procedure: (i) controlled ring-opening polymerization (ROP) of (D- or L-)lactide initiated by Al(O(i)Pr)(3), followed by (ii) quantitative conversion of the polylactide (PLA) hydroxyl end-groups with bromoisobutyryl bromide and (iii) atom transfer radical polymerization (ATRP) of DMAEMA. The PLA block molecular weight was kept below 5000 g/mol. The macromolecular parameters of the (co)polymers were determined by (1)H NMR spectroscopy and size exclusion chromatography (SEC). The stereocomplexes of PDLA-b-PDMAEMA/PLLA-b-PDMAEMA diblock copolymers were prepared via solvent casting. The stereocomplex formation was evidenced by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses. The obtained stereocomplexes had melting temperature of about 65 degrees C above that of the individual copolymers and exhibited diffraction patterns assigned to the stereocomplex crystallites. In addition, for the first time it was shown that the replacement of one of the PLA partners with high molecular weight PLLA or PDLA did not hamper the stereocomplex formation. The presence of PDMAEMA blocks proved to impart hydrophilicity of the synthesized copolymers and related stereocomplexes, as determined by static water contact angle measurements.

Organocatalysis Paradigm Revisited: Are Metal-Free Catalysts Really Harmless?

Catalysts are commonly used in polymer synthesis. Traditionally, catalysts used to be metallic compounds but some studies have pointed out their toxicity for human health and environment, and the removal of metal impurities from synthetic polymer is quite expensive. Organocatalysts have been intensively synthesized and are now widely used in ring-opening polymerization (ROP) reactions to address these issues. However, for most of them, there is not any evidence of their safety. The present study attempts to assess whether well-established organo-based ROP catalysts used for the preparation of FDA-approved polyesters may present a certain level of cytotoxicity. In vitro toxicity is evaluated using a methyl-thiazol-tetrazolium cytotoxicity assay on two cell models (FHs74Int and HepaRG). Among the investigated organocatalysts, only functionalized thiourea shows an important cytotoxicity on both cell models. 4-Dimethylaminopyridine (DMAP), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and meta-(trimethylammonio)phenolate betaine (m-BE) show cytotoxicity against HepaRG cell line only at a high concentration.

Organocatalytic synthesis and post-polymerization functionalization of propargyl-functional poly(carbonate)s

The synthesis of well-defined propargyl-functional poly(carbonate)s was achieved via the organocatalytic ring-opening polymerization of 5-methyl-5-propargyloxycarbonyl-1,3-dioxan-2-one (MPC) using the dual catalyst system of 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea (TU) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The resulting homopolymers showed low dispersities and high end-group fidelity, with the versatility of the system being demonstrated by the synthesis of telechelic copolymers and block copolymers. The synthesized homopolymers with varying degree of polymerization were functionalized with a range of azides via copper-catalyzed Huisgen-1,3-dipolar addition or thiols via radical thiylation, to produce functional aliphatic poly(carbonate)s from a single polymeric scaffold.

Novel biodegradable adaptive hydrogels: controlled synthesis and full characterization of the amphiphilic co-networks.

Adaptive and amphiphilic poly(N,N-dimethylamino-2-ethyl methacrylate-graft-poly[epsilon-caprolactone]) co-networks (netP(DMAEMA-g-PCL)) were synthesized from a combination of controlled polymerization techniques. Firstly, PCL cross-linkers were produced by ring-opening polymerization (ROP) of epsilon-CL initiated by 1,4-butane-diol and catalyzed by tin(II) 2-ethylhexanoate ([Sn(Oct)2]), followed by the quantitative esterification reaction of terminal hydroxyl end-groups with methacrylic anhydride. Then, PCL cross-linkers were copolymerized to DMAEMA monomers by atom-transfer radical polymerization (ATRP) in THF at 60 degrees C using CuBr complexed by 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA) and 2-ethyl isobutyrylbromide (EiBBr) as catalytic complex and initiator, respectively. A comprehensive study of gel formation was carried out by employing dynamic light scattering (DLS) to determine the gel point as a function of several parameters and to characterize the viscous solutions obtained before the gel point was reached. The evolution of the mean diameters was compared to a model previously developed by Fukuda and these attest to the living formation of the polymer co-network. Furthermore, we also demonstrated the reliability of ATRP for producing well-defined and homogeneous polymer co-networks by the smaller deviation from Florys theory in terms of cross-linking density. For sake of clarity, the impact of polymerization techniques over the final structure and, therefore, properties was highlighted by comparing two samples of similar composition, but that were produced by either ATRP or thermal-initiated free-radical polymerization (FRP).

Preparation of Well‐Defined Poly[(ethylene oxide)‐block‐(sodium 2‐acrylamido‐2‐methyl‐1‐propane sulfonate)] Diblock Copolymers by Water‐Based Atom Transfer Radical Polymerization

Sodium2-acrylamido-2-methyl-1-propane sulfonate (AMPS) based (co)polymers are used in awide range of applications such as detergents, thickeners, paper-coatings, and dental adhesives but they have also gained interest due to their anticoagulant properties and their ability to improve the compatibility of polymers with blood. Similarly, poly(ethylene oxide) (PEO) segments are well-known to highly reduce non-specific interactions with blood proteins by a steric repulsion mechanism and might increase further blood compatibility of AMPS-based copolymers. In 2001, the preparation of well-defined PAMPS homopolymer and block copolymers with sodium 3-acrylamido-3methylbutanoate has been achieved by reversible additionfragmentation chain transfer (RAFT) polymerization using 4,40-azobis(4-cyanopentanoic acid) and 4-cyanopentanoic acid dithiobenzoate as initiator and chain transfer agent, respectively, at 70 8C in water. The solution pH was adjusted at 9.6. As far as water-based atom transfer radical Summary:Well-defined poly[(ethylene oxide)-block-(sodium 2-acrylamido-2-methyl-1-propane sulfonate)] diblock copolymers [P(EOm-b-AMPSn)], have been obtained by water-based ATRP using a-methoxy-o-(2-methylbromoisobutyrate) poly(ethylene oxide)s (MeO-P[EO]m-Br Bwithm ranging from 12 to 113) and CuBr 2Bpy (Bpy for 2,20-bipyridyl) as macroinitiator and catalytic complex, respectively.Compared to direct polymerization inwater, it has beendemonstrated that thewater/ methanol (3:1, v/v) mixture is better suited for predicting the final number-average molar mass from the initial monomer-tomacroinitiator molar ratio and achieving a quite narrow polydispersity, even at high monomer conversion (Mw=Mn 1.4 at 80% conversion). The effect of temperature, solvent mixture composition and addition of NaCl salt on the polymerization rate and extent of control over the copolymer molecular parameters have been highlighted as well.

Exploring the versatility of hydrogels derived from living organocatalytic ring-opening polymerization

In this work we have bridged the use of mild and living organocatalytic ring-opening polymerization to facilitate the synthesis of cross-linked networks with an emphasis on hydrogels. Amidine-catalyzed ring-opening polymerization of bis-carbonate macromonomers in the presence of an alcohol provides the onset for the reaction and various building blocks issued from the initiator, macromonomer and comonomer can be used in different proportions to tailor the swelling behavior and mechanical integrity of final networks. Easy modifications of the building blocks additionally allow for finely tuning the hydrogel functionality and/or promoting responsiveness in the final structure.

One-step synthesis of polylactide macrocycles from sparteine-initiated ROP

The ring-opening polymerization (ROP) of L-lactide in dichloromethane with (+)-sparteine is described. Under aprotic conditions, (+)-sparteine leads to controlled cyclic polyesters mainly obtained by a backbiting process from the in situ generated tertiary amine-containing symmetrical binary zwitterion.

Molecularly Imprinted Polymers: Compromise between Flexibility and Rigidity for Improving Capture of Template Analogues

New synthetic strategies for molecularly imprinted polymers (MIPs) were developed to mimic the flexibility and mobility exhibited by receptor/enzyme binding pockets. The MIPs were prepared by bulk polymerization with quercetin as template molecule, acrylamide as functional monomer, ethylene glycol dimethacrylate as cross-linker, and THF as porogen. The innovative grafting of specific oligoethylene glycol units onto the imprinted cavities allowed MIPs to be obtained that exhibit extended selectivity towards template analogues. This synthetic strategy gives promising perspectives for the design of molecular recognition of molecules based on a congruent pharmacophore, which should be of interest for drug development.