Magnetic poly(N‐isopropylacrylamide) microspheres by dispersion and inverse emulsion polymerization

The aim of this study was to develop novel thermally responsive polymer microspheres with magnetic properties. Dispersion and inverse emulsion copolymerization of N‐isopropylacrylamide (NIPAAm) and N,N′‐methylenebisacrylamide (MBAAm) was investigated in the presence of γ‐Fe₂O₃ nanoparticles. The resulting microspheres were characterized in terms of morphology, size, polydispersity, iron content, and temperature‐dependent swelling using optical microscopy, transmission electron microscopy, scanning electron microscopy, QELS, and AAS. The effects of several variables, such as the concentration of γ‐Fe₂O₃, MBAAm crosslinking agent, Span 80 surfactant, 2,2′‐azobis(2‐methyloctanenitrile) (AMON) initiator, and polymerization temperature on the properties of the microspheres were studied. Swelling and thermoresponsive behavior of the microspheres containing γ‐Fe₂O₃ nanoparticles were also investigated. The microspheres contained about 8 wt % of iron. The presence of magnetic nanoparticles and their concentration changes did not have any significant effect on the temperature sensitivity of the composites. The particles gradually shrink into an increasingly collapsed state when the temperature is raised to 40 °C since the increase in temperature weakens the hydration and PNIPAAm chains gradually become more hydrophobic, which leads to the collapse of the particles. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5884–5898, 2007     

Synthesis of thermo‐responsive poly(N‐vinylcaprolactam)‐containing block copolymers by cobalt‐mediated radical polymerization

Thermo‐responsive block copolymers based on poly(N‐vinylcaprolactam) (PNVCL) have been prepared by cobalt‐mediated radical polymerization (CMRP) for the first time. The homopolymerization of NVCL was controlled by bis(acetylacetonato)cobalt(II) and a molecular weight as high as 46,000 g/mol could be reached with a low polydispersity. The polymerization of NVCL was also initiated from a poly(vinyl acetate)‐Co(acac)₂ (PVAc‐Co(acac)₂) macroinitiator to yield well‐defined PVAc‐b‐PNVCL block copolymers with a low polydispersity (M_w/M_n = 1.1) up to high molecular weights (M_n = 87,000 g/mol), which constitutes a significant improvement over other techniques. The amphiphilic PVAc‐b‐PNVCL copolymers were hydrolyzed into unprecedented double hydrophilic poly(vinyl alcohol)‐b‐PNVCL (PVOH‐b‐PNVCL) copolymers and their temperature‐dependent solution behavior was studied by turbidimetry and dynamic light scattering. Finally, the so‐called cobalt‐mediated radical coupling (CMRC) reaction was implemented to PVAc‐b‐PNVCL‐Co(acac)₂ precursors to yield novel PVAc‐b‐PNVCL‐b‐PVAc symmetrical triblock copolymers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and characterization of graphene‐containing thermoresponsive nanocomposite hydrogels of poly(N‐vinylcaprolactam) prepared by frontal polymerization

Thermoresponsive poly(N‐vinylcaprolactam) nanocomposite hydrogels containing graphene were successfully prepared by frontal polymerization. High concentration of graphene (5.0 mg/mL) was obtained by direct graphite sonication in the self‐same liquid monomer, thus avoiding any chemical manipulation and obtaining “real” graphene as nanofiller instead of one of its more or less oxidized derivative, which is what generally reported in published reports. Furthermore, the corresponding nanocomposites were obtained without using any solvent to be eventually removed. The materials were fully characterized by RAMAN, SEM, and TEM, and their swelling behavior and rheological properties were investigated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

N‐vinylcaprolactam‐based microgels: Synthesis and characterization

Poly(N‐vinylcaprolactam) (PVCL) is well known for its thermoresponsive behavior in aqueous solutions. PVCL combines useful and important properties; it is biocompatible polymer with the phase transition in the region of physiological temperature (32–38 °C). This combination of properties allows consideration of PVCL as a material for design biomedical devices and use in drug delivery systems. In this work, PVCL based temperature‐sensitive crosslinked particles (microgels) were synthesized in a batch reactor to analyze the effect of the crosslinker, initiator, surfactant, temperature, and VCL concentration on polymerization process and final microgels characteristics. The mean particle diameters at different temperatures and the volume phase‐transition temperature of the final product were analyzed. To obtain information about the inner structure of microgel particles, semicontinuous polymerizations were carried out and the evolution of the hydrodynamic average particle diameters at different temperatures of the microgel synthesized was investigated. In the case of microgel particles obtained in a batch reactor the size and the swelling‐de‐swelling behavior as a function of the temperature of the medium can be tuned by modulating the reaction variables. When the microgel particles were synthesized in a semibatch reactor different swelling‐de‐swelling behaviors were observed depending on particles inner structure. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2510–2524, 2008     

N‐vinylcaprolactam‐based microgels: Effect of the concentration and type of cross‐linker

New microgel particles produced by using N‐vinylcaprolactam (VCL) and poly(ethylene glycol) diacrylate (PEGDA) or N,N′‐methylenbisacrylamide (BA) were synthesized in a batch reactor. The influence of the concentration and type of crosslinker on polymerization kinetics and colloidal characteristics of such temperature‐sensitive particles was studied. The partial and total conversion evolutions of VCL, PEGDA, and BA were determined by quantitative ¹H NMR and the average diameters of microgel particles together with the swelling–deswelling behavior were analyzed by means of photon correlation spectroscopy (PCS). Partial and total conversions, final average diameters at collapsed state, and the swelling–deswelling behavior varied as a function of the type of crosslinker. These results were attributed to the higher solubility and stabilizing ability of PEGDA compared with that of BA. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2766–2775, 2008     

Synthesis and self‐assembly of thermosensitive double‐hydrophilic poly(N‐vinylcaprolactam)‐b‐poly(N‐vinyl‐2‐pyrrolidone) diblock copolymers

We report on novel diblock copolymers of poly(N‐vinylcaprolactam) (PVCL) and poly(N‐vinyl‐2‐pyrrolidone) (PVPON) (PVCL‐b‐PVPON) with well‐defined block lengths synthesized by the MADIX/reversible addition‐fragmentation chain transfer (RAFT) process. We show that the lower critical solution temperatures (LCST) of the block copolymers are controllable over the length of PVCL and PVPON segments. All of the diblock copolymers dissolve molecularly in aqueous solutions when the temperature is below the LCST and form spherical micellar or vesicular morphologies when temperature is raised above the LCST. The size of the self‐assembled structures is controlled by the molar ratio of PVCL and PVPON segments. The synthesized homopolymers and diblock copolymers are demonstrated to be nontoxic at 0.1–1 mg mL^?1 concentrations when incubated with HeLa and HEK293 cancer cells for various incubation times and have potential as nanovehicles for drug delivery. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2725–2737     

Synthesis of backbone thermo and pH dual‐responsive hyperbranched poly(amine‐ether)s through proton‐transfer polymerization

Stimuli‐responsive hyperbranched polymers have attracted great attention in recent years because of their wide applications in biomedicine. Through proton‐transfer polymerization of triethanolamine and 1,2,7,8‐diepoxyoctane with the help of potassium hydride, a series of novel backbone thermo and pH dual‐responsive hyperbranched poly(amine‐ether)s were prepared successfully in one‐pot. The degrees of branching of the resulting polymers were at 0.40–0.49. Turbidity measurements revealed that hyperbranched poly(amine‐ether)s exhibited thermo and pH dual‐responsive properties in water. Importantly, these responsivities could be readily adjusted by changing the polymer composition as well as the polymer concentration in aqueous solution. Moreover, in vitro evaluation demonstrated that hyperbranched poly(amine‐ether)s showed low cytotoxicity and efficient cell internalization against NIH 3T3 cell lines. These results suggest that these backbone thermo and pH dual‐responsive hyperbranched poly(amine‐ether)s are promising materials for biomedicine. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Heterotactic‐specific radical polymerization of N‐isopropylacrylamide and phase transition behavior of aqueous solution of heterotactic poly(N‐isopropylacrylamide)

Radical polymerization of N‐isopropylacrylamide (NIPAAm) in toluene at low temperatures, in the presence of fluorinated‐alcohols, produced heterotactic polymer comprising an alternating sequence of meso and racemo dyads. The heterotacticity reached 70% in triads when polymerization was carried out at ?40 °C using nonafluoro‐tert‐butanol as the added alcohol. NMR analysis revealed that formation of a 1:1 complex of NIPAAm and fluorinated‐alcohol through C?O···H? O hydrogen bonding induces the heterotactic specificity. A mechanism for the heterotactic‐specific polymerization is proposed. Examination of the phase transition behavior of aqueous solutions of heterotactic poly(NIPAAm) revealed that the hysteresis of the phase transition between the heating and cooling cycles depended on the average length of meso dyads in poly(NIPAAm). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2539–2550, 2009     

Synthesis strategies to incorporate acrylic acid into N‐vinylcaprolactam‐based microgels

Two different synthesis strategies were used to synthesize N‐vinylcaprolactam (VCL)‐acrylic acid (AA)‐based temperature‐ and pH‐sensitive microgels under the adequate conditions to avoid possible hydrolysis of VCL due to the presence of carboxylic groups provided by AA. Polymeric and colloidal features of the microgels were analyzed: the partial conversion evolutions of each comonomer were determined by ¹H NMR and the swelling/deswelling behavior by means of Photon Correlation Spectroscopy. Considering that microgels are porous soft nanoparticles, conductimetric titrations at the swollen state were carried out to calculate the volumetric charge density. The results indicate that the addition of AA after 30 minutes of reaction time helped to incorporate higher amounts of AA into microgels and as a result, to obtain both temperature‐ and pH‐sensitive nanoparticles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Hydrophilic CO2‐based biodegradable polycarbonates: Synthesis and rapid thermo‐responsive behavior

Common CO₂‐based biodegradable polycarbonates like poly(propylene carbonate) or poly(cyclohexene carbonate) are generally hydrophobic, leading to slow biodegradation rate and poor cell adhesion, which limit their applications in the biomedical field. Here hydrophilic polycarbonates were prepared by one‐pot terpolymerization of CO₂, propylene oxide (PO), and 2‐((2‐(2‐(2‐methoxyethoxy)ethoxy)ethoxy)methyl)oxirane (ME₃MO) using binary Salen Co(III)‐Cl/PPNCl catalyst system. The resultant terpolymers showed one glass transition temperature (T_g), which decreased with the increase of ME₃MO units in the terpolymers (F_ME3MO). Water contact angles of the resultant terpolymers with F_ME3MO of 4.2?23.6% were 68?25°, while that of poly(propylene carbonate) was 90°, indicating that the terpolymers became hydrophlilic. Furthermore, the terpolymers with F_ME3MO more than 25.8% exhibited reversible and rapid thermo‐responsive property in water, and the lower critical solution temperature (LCST) was highly sensitive to F_ME3MO. In particular, aqueous solution of the terpolymer with F_ME3MO of 72.6% showed a LCST around 35.2 °C, close to body temperature, which was promising for biomedical applications, especially for in vivo applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2834–2840.     

Synthesis of low‐polydispersity poly(N‐ethylmethylacrylamide) by controlled radical polymerizations and their thermal phase transition behavior

Controlled radical polymerizations of N‐ethylmethylacrylamide (EMA) by atom transfer radical polymerization and reversible addition‐fragmentation chain transfer processes were investigated in detail for the first time, employing complementary characterization techniques including gel permeation chromatography, ¹H NMR spectroscopy, and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry. In both cases, relatively good control of the polymerization of EMA was achieved, as revealed by the linear evolution of molecular weights with monomer conversions and the low polydispersity of poly(N‐ethylmethylacrylamide) (PEMA). The thermal phase transitions of well‐defined PEMA homopolymers with polydispersities less than 1.2 and degrees of polymerization up to 320 in aqueous solution were determined by temperature‐dependent turbidity measurements. The obtained cloud points (CPs) vary in the range of 58–68 °C, exhibiting inverse molecular weight and polymer concentration dependences. Moreover, the presence of a carboxyl group instead of an alkyl one at the PEMA chain end can elevate its CP by ～3–4 °C. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 60–69, 2008     

o‐nitrobenzyl acrylate is polymerizable by single electron transfer‐living radical polymerization

Polymers containing o‐nitrobenzyl esters are promising for preparation of light sensitive materials. o‐Nitrobenzyl methacrylate has already been polymerized by controlled ATRP or RAFT. Unfortunately, the radical polymerization of o‐nitrobenzyl acrylate (NBA) was not controlled until now due to inhibition and retardation effects coming from the nitro‐aromatic groups. Recent developments in the Single Electron Transfer–Living Radical Polymerization (SET–LRP) provide us an access to control this NBA polymerization and living character of this NBA SET–LRP is demonstrated. Effects of CuBr₂ and ligand concentrations, as well as Cu(0) wire length on SET–LRP kinetics are shown presently. A first‐order kinetics with respect to the NBA concentration is observed after one induction period. SET–LRP proceeds with a linear evolution of molecular weight and a narrow distribution. High initiation efficiency close to 1 and high chain‐end functionality (～93%) are reached. Chain extension of poly(o‐nitrobenzyl acrylate) is realized with methyl acrylate (MA) to obtain well defined poly(o‐nitrobenzyl acrylate)‐b‐poly(methyl acrylate) (PNBA‐b‐PMA). Finally, light‐sensitive properties of PNBA are checked upon UV irradiation. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2192–2201     

Polymerization of oligo(ethylene glycol) (meth)acrylates: Toward new generations of smart biocompatible materials

Monomers composed of a (meth)acrylate moiety connected to a short poly(ethylene)glycol (PEG) chain are versatile building‐blocks for the preparation of “smart” biorelevant materials. Many of these monomers are commercial and can be easily polymerized by either anionic, free‐radical, or controlled radical polymerization. The latter approach allows synthesis of well‐defined PEG‐based macromolecular architectures such as amphiphilic block copolymers, dense polymer brushes, or biohybrids. Furthermore, the resulting polymers exhibit fascinating solution properties in aqueous medium. Depending on the molecular structure of their monomer units, non linear PEG analogues can be either insoluble in water, readily soluble up to 100 °C, or thermoresponsive. Thus, these polymers can be used for building a wide variety of modern materials such as biosensors, artificial tissues, smart gels for chromatography, and drug carriers. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3459–3470, 2008     

Synthesis and characterization of thermoresponsive polymers containing reduction‐sensitive disulfide linkage

A novel class of thermoresponsive and reduction‐sensitive polymer, p(PEG‐MEMA‐co‐Boc‐Cyst‐MMAm), containing disulfide linkages and removable hydrophobic tert‐butyloxycarbonyl side chains was synthesized. The cloud points (CP) of p(PEG‐MEMA‐co‐Boc‐Cyst‐MMAm) in water determined by UV/VIS spectrometer were between 20 °C and 57 °C, which shows that the CP can be tuned by adjusting the copolymer composition. Moreover, the thermosensitive polymers p(PEG‐MEMA‐co‐Boc‐Cyst‐MMAm) formed stable nanoparticles in neutral aqueous medium, but rapidly destabilized in an reductive environment mimicking the intracellular space making them suitable for cytoplasmic drug delivery. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5989–5997, 2009     

Synthesis of well‐defined 7‐arm and 21‐arm poly(N‐isopropylacrylamide) star polymers with β‐cyclodextrin cores via click chemistry and their thermal phase transition behavior in aqueous solution

The syntheses of well‐defined 7‐arm and 21‐arm poly(N‐isopropylacrylamide) (PNIPAM) star polymers possessing β‐cyclodextrin (β‐CD) cores were achieved via the combination of atom transfer radical polymerization (ATRP) and click reactions. Heptakis(6‐deoxy‐6‐azido)‐β‐cyclodextrin and heptakis[2,3,6‐tri‐O‐(2‐azidopropionyl)]‐β‐cyclodextrin, β‐CD‐(N₃)₇ and β‐CD‐(N₃)₂₁, precursors were prepared and thoroughly characterized by nuclear magnetic resonance and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. A series of alkynyl terminally functionalized PNIPAM (alkyne‐PNIPAM) linear precursors with varying degrees of polymerization (DP) were synthesized via atom transfer radical polymerization (ATRP) of N‐isopropylacrylamide using propargyl 2‐chloropropionate as the initiator. The subsequent click reactions of alkyne‐PNIPAM with β‐CD‐(N₃)₇ and β‐CD‐(N₃)₂₁ led to the facile preparation of well‐defined 7‐arm and 21‐arm star polymers, namely β‐CD‐(PNIPAM)₇ and β‐CD‐(PNIPAM)₂₁. The thermal phase transition behavior of 7‐arm and 21‐arm star polymers with varying molecular weights were examined by temperature‐dependent turbidity and micro‐differential scanning calorimetry, and the results were compared to those of linear PNIPAM precursors. The anchoring of PNIPAM chain terminal to β‐CD cores and high local chain density for star polymers contributed to their considerably lower critical phase separation temperatures (T_c) and enthalpy changes during phase transition as compared with that of linear precursors. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 404–419, 2009     

AB2‐type amphiphilic block copolymers composed of poly(ethylene glycol) and poly(N‐isopropylacrylamide) via single‐electron transfer living radical polymerization: Synthesis and characterization

Novel AB₂‐type amphiphilic block copolymers of poly(ethylene glycol) and poly(N‐isopropylacrylamide), PEG‐b‐(PNIPAM)₂, were successfully synthesized through single‐electron transfer living radical polymerization (SET‐LRP). A difunctional macroinitiator was prepared by esterification of 2,2‐dichloroacetyl chloride with poly(ethylene glycol) monomethyl ether (PEG). The copolymers were obtained via the SET‐LRP of N‐isopropylacrylamide (NIPAM) with CuCl/tris(2‐(dimethylamino)ethyl)amine (Me₆TREN) as catalytic system and DMF/H₂O (v/v = 3:1) mixture as solvent. The resulting copolymers were characterized by gel permeation chromatography and ¹H NMR. These block copolymers show controllable molecular weights and narrow molecular weight distributions (PDI < 1.15). Their phase transition temperatures and the corresponding enthalpy changes in aqueous solution were measured by differential scanning calorimetry. As a result, the phase transition temperature of PEG₄₄‐b‐(PNIPAM₅₅)₂ is similar to that in the case of PEG₄₄‐b‐PNIPAM₁₁₀; however, the corresponding enthalpy change is much lower, indicating the significant influence of the macromolecular architecture on the phase transition. This is the first study into the effect of macromolecular architecture on the phase transition using AB₂‐type amphiphilic block copolymer composed of PEG and PNIPAM. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4420–4427, 2009     

Hydrogen‐bond‐assisted syndiotactic‐specific radical polymerizations of N‐alkylacrylamides: The effect of the N‐substituents on the stereospecificities and unusual large hysteresis in the phase‐transition behavior of aqueous solution of syndiotactic poly(N‐n‐propylacrylamide)

The radical polymerizations of N‐alkylacrylamides, such as N‐methyl‐(NMAAm), N‐n‐propyl‐(NNPAAm), N‐benzyl‐(NBnAAm), and N‐(1‐phenylethyl)acrylamides (NPhEAAm), at low temperatures were investigated in the absence or presence of hexamethylphosphoramide (HMPA) and 3‐methyl‐3‐pentanol (3Me3PenOH), which induced the syndiotactic specificities in the radical polymerization of N‐isopropylacrylamide (NIPAAm). In the absence of the syndiotactic‐specificity inducers, the syndiotacticities of the obtained polymers gradually increased as the bulkiness of the N‐substituents increased. Both HMPA and 3Me3PenOH induced the syndiotactic specificities in the NNPAAm polymerizations as well as in the NIPAAm polymerizations. The addition of 3Me3PenOH into the polymerizations of NMAAm significantly induced the syndiotactic specificities, whereas the tacticities of the obtained polymers were hardly affected by adding HMPA. In the polymerizations of bulkier monomers, such as NBnAAm and NPhEAAm, HMPA worked as the syndiotactic specificity inducer at higher temperatures, whereas 3Me3PenOH hardly influenced the stereospecificity, regardless of the temperatures. The phase‐transition behaviors of the aqueous solutions of poly(NNPAAm)s were also investigated. It appeared that the poly (NNPAAm) with racemo dyad content of 70% exhibited unusual large hysteresis between the heating and cooling processes. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4575–4583, 2008     

Sulfobetaine‐containing diblock and triblock copolymers via reversible addition‐fragmentation chain transfer polymerization in aqueous media

A novel bifunctional acrylamido‐based reversible addition–fragmentation chain transfer (RAFT) chain‐transfer agent (CTA), N,N′‐ethylenebis[2‐(thiobenzoylthio)propionamide] (CTA2), has been synthesized and used for the controlled free‐radical polymerization of N,N‐dimethylacrylamide (DMA). A comparative study of CTA2 and the monofunctional CTA N,N‐dimethyl‐s‐thiobenzoylthiopropionamide (CTA1) has been conducted. Polymerizations mediated by CTA1 result in poly(N,N‐dimethylacrylamide) (PDMA) homopolymers with unimodal molecular weight distributions, whereas CTA2 yields unimodal, bimodal, and trimodal distributions according to the extent of conversion. The multimodal nature of the PDMAs has been attributed to termination events and/or chains initiated by primary radicals. The RAFT polymerization of DMA with CTA2 also results in a prolonged induction period that may be attributed to the higher local concentration of dithioester functionalities early in the polymerization. A series of ω‐ and α,ω‐dithioester‐capped PDMAs have been prepared in organic media and subsequently employed as macro‐CTAs for the synthesis of diblock and triblock copolymers in aqueous media with the zwitterionic monomer 3‐[2‐(N‐methylacrylamido)‐ethyldimethylammonio] propane sulfonate (MAEDAPS). Additionally, an ω‐dithioester‐capped MAEDAPS homopolymer has been used as a macro‐CTA for the block polymerization of DMA. To our knowledge, this is the first example of a near‐monodisperse, sulfobetaine‐containing block copolymer prepared entirely in aqueous media. The diblock and triblock copolymers form aggregates in pure water that can be dissociated by the addition of salt, as determined by ¹H NMR spectroscopy and dynamic light scattering. In pure water, highly uniform, micellelike aggregates with hydrodynamic diameters of 71–93 nm are formed. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1262–1281, 2003