Véronique Montembault

Functional Iron Oxide Magnetic Nanoparticles with Hyperthermia‐Induced Drug Release Ability by Using a Combination of Orthogonal Click Reactions

Click and drug: A combination of orthogonal click reactions is employed for the preparation of functional iron oxide nanoparticles (IONPs) that show unprecedented hyperthermia-induced drug release through a magnetically stimulated retro-Diels-Alder (rDA) process. Magnetic stimulation induces sufficient local energy in close proximity to the cycloadduct to initiate the rDA process

Synthesis and Nonlinear Optical Properties of a Peripherally Functionalized Hyperbranched Polymer by DR1 Chromophores

The first peripheral postfunctionalization of a hyperbranched polyimide by nonlinear optic chromophores (DR1 derivative) was achieved using two different routes. The first one consists in the esterification of the terminal carboxylic acid groups, whereas the second is based on copper-catalyzed Huisgen reaction of the terminal propargylic ester groups. The resulting polymers display good solubility in classical organic solvents and good filmability because thick films can be prepared (up to 2.7 mum). The second-order nonlinear optical properties were measured by SHG at 1064 nm and we show that these hyperbranched polymers exhibit good poling efficiency and good thermal stability since the electro-optic activity remains stable up to 130 degrees C. These results illustrate the potential of hyperbranched polymers to host second-order nonlinear optical chromophores to replace dendrimers or classical linear polymers generally used in this area.

Introducing the Azlactone Functionality into Polymers through Controlled Radical Polymerization: Strategies and Recent Developments

Polymers containing the highly reactive azlactone group have emerged as a powerful platform useful in various application areas. This Highlight summarizes recent developments in the field of azlactone-derived polymers made in our group using controlled radical polymerizations (ATRP and RAFT) and ‘click’ chemistry methodology (thiol-Michael addition), leading to well defined reactive polymers.

Thermoresponsive block copolymers containing reactive azlactone groups and their bioconjugation with lysozyme

Thermoresponsive block copolymers based on poly(ethylene oxide) (PEO) and poly(N-isopropyl acrylamide) (PNIPAM) containing azlactone groups along the backbone and at the chain-end of the macromolecular chain were synthesized by statistically reversible addition–fragmentation chain transfer (RAFT) copolymerization and by using a combination of RAFT polymerization and thiol–ene Michael addition. Well-defined poly(ethylene oxide)-b-poly(2-vinyl-4,4-dimethylazlactone-co-N-isopropyl acrylamide) (PEO-b-P(VDM-co-NIPAM)) block copolymers and azlactone-terminated poly(ethylene oxide)-b-poly(N-isopropyl acrylamide) (PEO-b-PNIPAM-VDM) diblock copolymers with low polydispersity indices (PDIs ≤ 1.10) were prepared and fully characterized by 1H NMR spectroscopy, FT-IR spectroscopy, and SEC. Such PEO-b-P(VDM-co-NIPAM) block copolymers and azlactone-terminated PEO-b-PNIPAM block copolymers present tunable lower critical solution temperature (LCST) depending on PEO, PNIPAM, and PVDM molar ratios. The reactivity of the PEO44-b-P(VDM20-co-NIPAM80) copolymer (Mn,NMR = 14 200 g mol−1, PDI = 1.08) and of the PEO44-b-PNIPAM101-VDM copolymer (Mn,NMR = 13 700 g mol−1, PDI = 1.08) was studied with lysozyme as a model protein. A bioconjugate with a higher apparent molecular weight was obtained with the PEO44-b-P(VDM20-co-NIPAM80) copolymer in comparison with the one obtained using the PEO44-b-PNIPAM101-VDM copolymer as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The results suggest promising applications of azlactone-functionalized polymers within the field of bioconjugation.

Ring-opening metathesis polymerization (ROMP) of isomerically pure functional monomers and acyclic diene metathesis depolymerization (retro-ADMET) of functionalized polyalkenamers

ROMP and retro-acyclic diene metathesis (ADMET) were used for the synthesis of new functional polymers and functional oligomers, respectively. Purely exo and enantiomerically pure norbornene and 7-oxanorbornene derivatives were prepared using stereospecific synthesis, effective fractionation and high yield condensation reactions. Successful ROMPs of those monomers were performed using either the new carbenic Schrock’s or Grubb’s catalysts or in some cases a classical bicomponent catalyst. New functional polymers such as optically active poly(norbornene-2-carboxylic acid), reactive poly(norbornene-2-azlactone), and side-chain liquid crystal polyoxanorbornenes were fully characterized. On the other hand, successful depolymerizations of 1,4-polyisoprene and of epoxidized 1,4-polybutadiene via cross-metathesis with 4-octene were performed using a stabilized bicomponent catalyst and the Grubb’s catalyst, respectively. Conditions for the controlled synthesis of epoxidized oligobutadienes and of epoxydienic monomers via retro-ADMET were clearly defined.

Synthesis and ITC characterization of novel nanoparticles constituted by poly(gamma-benzyl L-glutamate)-beta-cyclodextrin.

Imparting desired technological characteristics to polymeric nanoparticles requires the development of original polymers. In the present work, the synthesis and characterization of a novel PBLG‐derivative, the poly(γ‐benzyl L‐glutamate)‐β‐cyclodextrin (PBLG‐β‐CD‐50), have been carried out. Nanoparticles from either PBLG‐β‐CD‐50 polymer or from mixtures with PBLG have been prepared using a modified nanoprecipitation method. Spherically shaped nanoparticles with diameter in the range of 50–70 nm were obtained, as determined by dynamic laser light scattering and transmission electron microscopy. The presence of a surfactant in the suspension medium had almost no influence on these parameters and was not necessary to the shelf‐stability of the suspension. Further, isothermal titration microcalorimetry (ITC) experiments have been used to show unambiguously that about 20% of the cyclodextrins remain functional within the particles. Consequently, this system may be of interest when association of large amounts of hydrophobic drugs to nanoparticles is required. Copyright

Synthesis and characterization of functionalized poly(γ-benzyl-l-glutamate) derivates and corresponding nanoparticles preparation and characterization

For being fully efficient a targeted delivery system should associate simultaneously multiple functionalities. In this context, the association of several polymeric materials to form composite multifunctional particles can be foreseen. The present work describes the synthesis of different derivates of poly(gamma-benzyl-L-glutamate) and their use for the preparation of nanoparticles exhibiting different properties, including surface hydrophilization by PEG, fluorescence imaging by FITC and target recognition through easy attachment of desired ligands by using the avidin-biotin interaction, after the nanoparticles preparation. Four PBLG derivates were successfully obtained by ring-opening polymerization (ROP) of NCA, using various initiators corresponding to the molecules to be introduced into the copolymers. Further, nanoparticles smaller than 100 nm could be prepared using a nanoprecipitation technique and the presence of the active moieties introduced within the particles as well as their functionality has been checked. Very interestingly, it has been shown that biotin molecules could be efficiently introduced at the surface of the nanoparticles, which (for 75% of the theoretical amount) could be engaged in a complexation with avidin. It is suggested that this strategy offers the possibility to easily decorate these nanoparticles with various recognition ligands for specific targeting applications by using the well known biotin-avidin sandwich technique.

Synthesis of thermoresponsive oxazolone end-functional polymers for reactions with amines using thiol-Michael addition “click” chemistry

Well-defined poly(N-isopropylacrylamide) (PNIPAM) polymers with an oxazolone ring at the chain end have been synthesized by combining controlled radical polymerization and thiol-Michael addition “click” chemistry. First, PNIPAM was synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization to afford polymers of controlled molecular weight and molecular weight distribution (Mn (1H NMR) = 3200 g mol−1; PDISEC = 1.05). The chain end was quantitatively converted to a thiol by aminolysis. Then, the functional monomer vinyl azlactone (VDM) was quantitatively “clicked” onto the chain end using a thiol-Michael addition reaction. The polymers were reacted with a model amine in order to demonstrate the potential of these polymers for bioconjugation.

Synthesis of chelating molecules as agents for magnetic resonance imaging, 31. Polycondensation of diethylenetriaminepentaacetic acid bisanhydride with diols and diamines

Abstract The polycondensation of diethylenetriaminepentaacetic acid (DTPA) bisanhydride with diols and diamines was investigated in order to obtain new complexing agents bearing aminoacetic groups along the polymer chain whose complexing properties should be better than their monomolecular homologues: EDTA (ethylenediaminetetraacetic acid), DTPA … Synthesis conditions have been studied to get linear water-soluble polymers destined to gadolinium complexation. Use of several types of comonomers has allowed us to obtain polycondensates having a varied density of COOH functions which will permit us to study its influence on their complexing properties towards different metallic cations.

Scope and limitation of the copper free thermal Huisgen cross-linking reaction to stabilize the chromophores orientation in electro-optic polymers

New methacrylate copolymers incorporating two complementary thermally cross-linkable groups (azide or ethynyl) for implementation in electro-optic devices were synthesized and their nonlinear optical properties were investigated. These copolymers were prepared from a monomer containing Disperse Red 1 (DR1) as active NLO chromophore which is end substituted either by an azide or ethynyl group connected via a rigid (phenyl) or flexible spacer (alkyl chain). The second monomer is either a trimethylsilyl-propargyl methacrylate, or an azidopropyl methacrylate or a trimethylsilyl-phenyl methacrylate. The determination of the reactivity ratios showed that the monomer containing the DR1 chromophore is more reactive than trimethylsilyl-propargyl methacrylate. The cross-linking temperatures of these polymers range from 150 °C to 187 °C depending on the rigidity of the spacers connecting the cross-linkable units. These polymers displayed relatively high macroscopic electro-optic stability, enhanced upon cross-linking by more than 40 °C relative to non-cross-linked polymers. The results underscore the importance of the flexibility of the spacers to achieve the stable bulk electro-optic response. While rigidity is favorable to maintain the orientation of the chromophores, the optimal polymer is the one containing a flexible and a rigid spacer, since the mobility of the reactive groups is a key parameter which guarantees a high cross-linking conversion within the polymer. This study demonstrates the versatility of this new cross-linking process because we showed that the reactive groups (azide or trimethylsilylacetylated groups) can be interconverted (on the chromophore or as polymer side chain) with no change on the overall electro-optic activity and its thermal stability. Furthermore, preliminary kinetic study indicates that the Huisgen reaction rate can be controlled by the substituent on the ethynyl group opening the possibility to tune the cross-linking temperature by the careful choice of this substituent.