Sophie Monge

Phosphorus-Containing Polymers: A Great Opportunity for the Biomedical Field

This Review is focused on the growing interest brought to phosphorus-containing organic materials for applications in the biomedical field, mainly because of their properties such as biocompatibility, hemocompatibility, and protein adsorption resistance. It mainly describes relevant works achieved on these materials for various applications: dentistry, regenerative medicine, and drug delivery. Special attention was given to 2-methacryloyloxyethyl phosphorylcholine (MPC) monomer as the latter appeared of great importance because of its biomimetic structure due to the presence of the phospholipid group on its structure. As a result, much research effort is currently concentrated on the development of phosphorylcholine-containing (co)polymers that represent a promising class of materials.

Self-Assembly of Poly(ethylene glycol)-Poly(alkyl phosphonate) Terpolymers on Titanium Oxide Surfaces: Synthesis, Interface Characterization, Investigation of Nonfouling Properties, and Long-Term Stability

This contribution deals with the self-assembling of a terpolymer on titanium oxide (TiO(2)) surface. The polymer structure was obtained by polymerization of different methacrylates, i.e., alkyl-phosphonated, butyl and PEG methacrylate, in the presence of a chain transfer agent. The resulting PEG-poly(alkyl phosphonate) material, characterized mainly by SEC and NMR, self-organized at the interface of TiO(2). AR-XPS demonstrated the binding of phosphonate groups to TiO(2) substrate and the formation of a PEG-brush layer at the outermost part of the system. The stability of this terpolymer adlayer, after exposure to solutions of pH 2, 7.4, and 9 up to 3 weeks, was evaluated quantitatively by XPS and ellipsometry. We demonstrated an overall stability improvements of this coating against desorption in contact with aqueous solutions in comparison with reference self-assembly systems. Finally, the PEG-terpolymer adlayer proved to impart to TiO(2) substrate antifouling properties when exposed to full blood serum.

Polymer nanocomposite ionogels, high-performance electrolyte membranes

A sol–gel synthesis using modified poly(methyl methacrylate) (PMMA) bearing trimethoxysilane groups and tetraethoxysilane (TEOS) allowed immobilization of very high loadings of ionic liquid [BMIm][NTf2] within nanocomposite PMMA-silica membranes. The ionic liquid (IL) provided both flexibility and ionic conductivity, while the silica nanofiller covalently bonded to the polymer chains maintained mechanical strength, as shown by a DMA and tensile test. Complex impedance spectroscopy evidenced a critical threshold in ionic conductivity around 76%, which was ascribed to an unusual transition from “polymer-in-salt” to “quasi-liquid” electrolyte behaviour. Outstanding IL loadings as high as 90 wt% were reached, resulting in the same ionic conductivity as the pure IL.

Removal of nickel ions from aqueous solution by low energy-consuming sorption process involving thermosensitive copolymers with phosphonic acid groups

In order to remove metal ions from wastewaters, thermosensitive copolymers bearing sorption properties toward metal cations were prepared by free radical copolymerization between the N-n-propylacrylamide (NnPAAm) and the (dimethoxyphosphoryl)methyl 2-methylacrylate (MAPC1), followed by a hydrolysis of the phosphonated esters into phosphonic diacid groups ((h)MAPC1). The thermosensitivity and the sorption abilities of the resulting poly(NnPAAm-stat-(h)MAPC1) copolymers were studied. Lower Critical Solution Temperatures (LCST) of these copolymers ranged from 22 °C to 26 °C, depending on the molar ratio of phosphonated monomers and were lower than those obtained with usual poly(N-isopropylacrylamide)-based polymers. The influence of both the temperature and the pH on the sorption properties of the copolymers was evaluated for Ni(2+) cations. The most interesting results were obtained for temperatures around the LCST, i.e. when the proximity of the complexing groups favored the sorption of metallic cations. Concerning the pH effect, the maximum sorption capacity was obtained at pH 7, i.e. in the absence of competition between the sorption of H(+) and Ni(2+) ions on the phosphonic acid groups. The influence of the molar ratio of metal ions and phosphonate moieties was also studied and different sorption mechanisms were proposed.

Organophosphonates as anchoring agents onto metal oxide-based materials: synthesis and applications

Besides usual coupling agents such as, for instance, silane, thiol, or carboxylic acids, phosphonated-based low molecular weight molecules and polymers appear of great interest for the modification of metal oxides. In such contexts, this Review is focused on the use of phosphonated derivatives for the surface treatment of metal oxides as such compounds are known to establish strong and stable links with inorganic phases. Functionalization of metal oxides leads to the obtaining of hybrid materials that can find applications in numerous fields. As a result, an interesting prospect will be to enhance the development of new hybrid materials in the future, especially bio-based ones.

Synthesis by RAFT of innovative well-defined (co)polymers from a novel phosphorus-based acrylamide monomer

The present contribution reports on the synthesis and controlled polymerization of a novel acrylamide monomer containing phosphonated moieties, namely diethyl-2-(acrylamido)ethylphosphonate. This monomer appears to be of great interest due to the phosphonated moieties, which can lead to a wide range of applications, associated with the chemical stability of the acrylamide compared to more common (meth)acrylate monomers. Reversible Addition–Fragmentation Transfer (RAFT) polymerization of this monomer was investigated using two different trithiocarbonate chain transfer agents, and it allowed the synthesis of poly(diethyl-2-(acrylamido)ethylphosphonate) with controlled molecular weight and low dispersity. Additionally, a diblock copolymer was successfully prepared by a similar RAFT procedure using thermosensitive poly(N-n-propylacrylamide) as a macro-chain transfer agent. A combination of both stimuli-responsive and phosphonated ester or phosphonic diacid (after hydrolysis) containing blocks appears valuable for drug delivery or water treatment, for instance.

Stereoelectronic control of oxazolidine ring-opening: structural and chemical evidences

Abstract Ring opening of oxazolidines derived from tris(hydroxymethyl)aminomethane, l -serine and l -threonine was investigated. It was shown that n(N)→σ∗(C–O) electron delocalization (endo-anomeric effect) occurring in the five-membered ring plays a major role in the cleavage of the intracyclic C–O bond. The present work establishes that when the nitrogen lone pair is conjugated with a carbonyl group (n(N)→π(CO) delocalization) as happens in N-acyloxazolidines, both hydrolysis and reductive ring-opening become much more difficult as a consequence of a concomitant decrease of oxygen basicity and of an increase of the intracyclic C–O bond strength.

Thermo-responsive drug release from self-assembled micelles of brush-like PLA/PEG analogues block copolymers.

Thermo-responsive brush-like amphiphilic poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo(ethylene glycol) methacrylate]-b-poly(l-lactide)-b-poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo(ethylene glycol) methacrylate] [P(MEO2MA-co-OEGMA)-b-PLLA-b-P(MEO2MA-co-OEGMA)] triblock copolymers were synthesized by atom transfer radical polymerization of MEO2MA and OEGMA co-monomers using a α,ω-Bromopropionyl poly(l-lactide) (Br-PLLA-Br) macroinitiator. The resulting copolymers with MEO2MA/OEGMA molar ratio ranging from 79/21 to 42/58 were characterized by (1)H nuclear magnetic resonance and size exclusion chromatography. Thermo-responsive micelles were obtained by self-assembly of copolymers in aqueous medium. The micelles are spherical in shape with sizes varying from 20.7 to 102.5 nm. A hydrophobic anticancer drug, curcumin, was encapsulated in micelles by using membrane hydration method. The properties of drug loaded micelles were determined by dynamic light scattering, transmission electron microscopy and lower critical solution temperature (LCST) measurements. The micelles size decreases from 102.5 nm for blank micelles to 37.6 nm with 10.8% drug loading, suggesting that the drug plays an important role in the micellization procedure. The LCST decreases from 45.1°C for blank micelles to 40.6 and 38.3°C with 5.9 and 10.8% drug loading, respectively. In vitro drug release was performed in pH 7.4 PBS at different temperatures. Data show that the release rate was significantly enhanced above the LCST comparing with that below the LCST. The amount of released drug at 41°C was ca. 20% higher than that at 37°C. Burst-like release was depressed due to enhanced interaction between drug with hydrophobic PLA and PMA chains.

Tunable thermo-responsive P(NIPAAm-co-DMAAm)-b-PLLA-b-P(NIPAAm-co-DMAAm) triblock copolymer micelles as drug carriers

Thermo-responsive triblock copolymers were synthesized by atom transfer radical polymerization of N-isopropyl acrylamide (NIPAAm) and N,N-dimethyl acrylamide (DMAAm) using α,ω-bromopropionyl poly(l-lactide) as the macro-initiator and a CuCl/tris(2-dimethylaminoethyl) amine (Me6TREN) complex as the catalyst. The polymerization was realized at 25 °C in a DMF-water mixture. DMAAm was incorporated in the copolymer as a hydrophilic comonomer in order to tune the lower critical solution temperature (LCST). The LCST linearly increases from 32.2 to 39.1 °C upon increasing the DMAAm content from 0 to 24%. The phase transition of polymeric micelles at the LCST occurs in a narrow temperature interval below 0.5 °C. Reversible size changes are observed when the temperature increases from 25 to 45 °C and then decreases down to 25 °C. Nano-size micelles (37 to 54 nm) with narrow distribution were obtained by self-assembly of amphiphilic copolymers in aqueous medium. The critical micelle concentration (CMC) ranges from 0.010 to 0.015 mg mL-1. In vitro drug release studies show a much faster release at temperatures above the LCST. The MTT assay was conducted to evaluate the cytotoxicity of copolymers. Therefore, the nano-scale size, low CMC, rapid phase transition, LCST slightly above body temperature and thermo-responsive drug release indicate that these copolymers could be potential candidates for applications in targeted delivery of drugs.

Poly(tris(hydroxymethyl)acrylamidomethane)-based copolymers: a new class of acid-labile thermosensitive polymers

The present contribution reports on an original new class of acid-labile thermosensitive polyacrylamides, namely poly(tris(hydroxymethyl)acrylamidomethane-co-(5-acrylamido-5-hydroxymethyl-2,2-dimethyl-1,3-dioxane)) (P(THAM-co-pTHAM)), in which pTHAM only differed from THAM by an acetal group. The lower critical solution temperature (LCST) was controlled by varying the comonomer composition. Additionally, the properties of these new statistical copolymers were investigated and proved that such chemical structures were interesting for smart applications, notably for drug delivery due to the biocompatibility of low molecular weight PTHAM already demonstrated.