pH- and temperature-responsive amphiphilic diblock copolymers of 4-vinylpyridine and oligoethyleneglycol methacrylate synthesized by RAFT polymerization

Diblock copolymers of 4-vinylpyridine (4VP) and oligoethyleneglycol methyl ether methacrylate (OEGMA) were synthesized for the first time using RAFT polymerization technique as potential drug delivery systems. Effects of the number of ethylene glycol units in OEGMA, chain length of hydrophobic P4VP block, pH, concentration and temperature on the solution behavior of the copolymers were investigated comprehensively. Copolymer chains formed micelles at pH values higher than 5 whereas unimeric polymers were observed to exist below pH 5, owing to the repulsion between positively charged P4VP blocks. The size of the micelles was dependent on the relative length of blocks, P4VP and POEGMA. Thermo-responsive properties of copolymers were investigated depending on the pH and length of P4VP block. The increase in the length of P4VP block decreased the LCST substantially at pH 7. At pH 3, LCST of copolymers shifted to higher temperatures due to the increased interaction of copolymers with water through positively charged P4VP block.     

Synthesis and pH-dependent micellization of 2-(diisopropylamino)ethyl methacrylate based amphiphilic diblock copolymers via RAFT polymerization

The polymerization of 2-(diisopropylamino)ethyl methacrylate (DPA) by RAFT mechanism in the presence of 4-cyanopentanoic acid dithiobenzoate in 1,4-dioxane was studied. The DPA homopolymer was employed as a macro chain transfer agent to synthesize pH-sensitive amphiphilic block copolymers using poly(ethylene glycol) methyl ether methacrylate (PEGMA) as the hydrophilic block. ¹H NMR and GPC measurements confirmed the successful synthesis of these copolymers. Potentiometric titrations and fluorescence experiments proved that the copolymers underwent a sharp transition from unimers to micelles at a pH of ∼6.7 in phosphate buffered saline solutions. It was found that the hydrophilic/hydrophobic balance of these block copolymers had no apparent effect on their pH-induced micellization behaviors. The DLS investigation revealed that the micelles have a mean hydrodynamic diameter below 60 nm with a narrow size distribution.     

Honeycomb structured porous films from amphiphilic block copolymers prepared via RAFT polymerization

The synthesis of polystyrene-block-poly(N,N-dimethylacrylamide) (PS-b-PDMA) via RAFT polymerization was investigated in detail. Two different RAFT agents - benzyl dithiobenzoate and 3-(benzylsulfanylthiocarbonylsufanyl) propionic acid, were employed to prepare polystyrene macroRAFT agents with molecular weights varying between 3000 g mol⁻¹ and 62,000 g mol⁻¹ and polydispersities between 1.1 and 1.4. Chain extensions with N,N-dimethylacrylamide (DMA) were carried out using a constant monomer to RAFT agent concentration ([DMA]/[RAFT] = 500), to compare the rate of polymerization in dependency of the polystyrene chain length. A decreasing rate of polymerization with increasing block length was observed. Depending on the sizes of the first block and type of RAFT agents used, chain extension polymerization with DMA was found to be incomplete, leading to significant low molecular weight tailing in the GPC analyses. Block copolymers prepared using 3-(benzylsulfanylthiocarbonylsufanyl) propionic acid, followed the expected molecular weight evolutions with polydispersity indices of 1.2-1.4. In contrast, block copolymers using benzyl dithiobenzoate clearly showed bimodal molecular weight distributions, especially when the longest PS macroRAFT agent with a molecular weight of 38,000 g mol⁻¹ was employed. These amphiphilic block copolymers were used to fabricate honeycomb structured porous films using the breath figure technique. The regularity of the film was considerably influenced by the humidity of the environment, which could be controlled by the rate of the airflow or the humidity in the casting chamber. The interaction between the hydrophilic block copolymer and the humidity was found responsible for the delicate equilibrium during the casting process, which prevented high pores regularity at very low (below 50%) and at elevated (above 80%) humidity. The interactions of the hydrophilic block with the humidity were observed to superimpose an additional nano-scaled order onto the hexagonal micron-sized porous array. Pores, which are created by encapsulation of water droplets, were found to be more hydrophilic than the surface. Confocal microscopy studies were employed to locate hydrophilic blocks within the film using a fluorescence labeled PDMA polymer.     

One-pot synthesis of octablock copolymers of high-molecular weight via RAFT emulsion polymerization

Multiblock copolymers (mBCPs) could offer new opportunities to design new nanomaterials with multifunctions or enhanced properties in a cost-effective way. However, it is still very challenging to obtain high degree of polymerization in each block of mBCPs with large block number using one-pot synthesis via controlled radical polymerizations. This is due to the accumulation of the dead chains throughout the many step polymerization. In this work, we developed a new highly efficient strategy for preparing mBCPs with large block number using one-pot reversible addition–fragmentation chain transfer (RAFT) emulsion polymerization, where every polymer block was formed by sequential addition of monomers. We achieved high block degree of polymerizations (~100 per block) for a model system of “octablock” polystyrene (PS) in just 2 hr per block. Experimentally measured molecular weights are in excellent agreement with theoretical predictions. The dead chains generated through the polymerization are negligible due to the low initiator concentration. Yet the polymerization rates are still very fast due to the heterogeneous advantages of emulsion polymerization. We have also applied this strategy to a series of mBCPs from diblock (PS₁₇₆-PnBA₂₈₆)₁ to octablock (PS₁₇₆-PnBA₂₈₆)₄ (PnBA for poly(n-butyl acrylate)). The high degree of polymerization in our mBCPs ensures microphase separation even though PS/PnBA system is known for small χ values. We have also found that the tensile properties of our mBCPs increase significantly with increased number of blocks. Our work reveals that the number of blocks is an important molecular variable for tuning the mechanical properties of block copolymers.     

One-step synthesis of poly(2-oxazoline)-based amphiphilic block copolymers using a dual initiator for RAFT polymerization and CROP

A range of poly(2-oxazoline) (POx)-based amphiphilic block copolymers were synthesized using 4-cyano-4-(dodecylthiocarbonothioylthio)pentyl-4-methylbenzenesulfonate (CDPS) as a dual initiator for reversible addition-fragmentation chain transfer (RAFT) polymerization and cationic ring-opening polymerization (CROP) in a one-step procedure. Methyl (meth)acrylate, butyl (meth)acrylate, tert-butyl (meth)acrylate, and N-isopropylacrylamide were polymerized for the hydrophobic block, and 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline were used as the hydrophilic block. RAFT polymerization and CROP proceeded independently in a controlled manner and resulted in amphiphilic block copolymers with a narrow molecular weight distribution. CDPS was found to be a useful dual initiator for the one-step synthesis of POx-based amphiphilic block copolymers via a combination of RAFT polymerization and CROP.     

Controlled synthesis of vinyl-functionalized homopolymers and block copolymers by RAFT polymerization of vinyl methacrylate

Reversible addition-fragmentation chain transfer (RAFT) polymerization of an asymmetrical divinyl monomer, vinyl methacrylate (VMA), was investigated under various conditions. RAFT polymerization of VMA using a dithioester-type chain transfer agent (CTA) under suitable conditions afforded soluble polymers with a high content of pendant vinyl ester side chains in sufficient yields (>70%). The monomer concentration, the nature of the CTA, and the CTA/initiator ratio were found to affect the polymerization reaction and the structure of the resulting polymers; this behavior is attributed to the relative propensities for intermolecular propagating/cross-linking reactions and intramolecular cyclization. A kinetic study of the RAFT polymerization of VMA with the dithioester-type CTA 1 suggested that the propagation reaction of the methacryloyl group proceeded predominantly with a certain level of intramolecular cyclization during the early stage of the polymerization and intermolecular cross-linking during the final stage of the polymerization. Block copolymers with one segment featuring pendant vinyl functionality were synthesized by RAFT polymerization of VMA using poly(methyl methacrylate) as a macro-chain transfer agent (macro-CTA).     

Synthesis of poly(trioctylammonium p-styrenesulfonate) homopolymers and block copolymers by RAFT polymerization

A method to prepare sulfonated polystyrene-containing block copolymers has been investigated by neutralizing styrene sulfonic acid with trioctylamine to produce the hydrophobic monomer trioctylammonium p-styrenesulfonate (SS-TOA). This monomer was polymerized by reversible addition fragmentation chain transfer (RAFT) polymerization to produce PSS-TOA homopolymers. A PSS-TOA homopolymer was then used as a macro-RAFT agent for the polymerization of styrene to prepare poly(trioctylammonium p-styrenesulfonate)-block-poly(styrene) (PSS-TOA-b-PS). These block copolymers could be ion-exchanged to produce either the hydrophilic sodium salt form of PSS or a hydrophobic quaternary ammonium salt. This approach will be useful for preparing PSS-containing block copolymers with a range of hydrophobic blocks for applications such as ion-exchange membranes.     

Synthesis and characterization of dual stimuli-responsive block copolymers based on poly(N-isopropylacrylamide)-b-poly(pseudoamino acid)

The current study synthesized amphiphilic thermal/pH-sensitive block copolymers PNiPAAm-b-PHpr by condensation polymerization of trans-4-hydroxy-l-proline (Hpr) initiated from hydroxy-terminated poly(N-isopropylacrylamide) (PNiPAAm) as the macroinitiator in the presence of the catalyst, SnOct₂. ¹H NMR, FTIR, and gel permeation chromatography (GPC) characterized these copolymers. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. The LCST values depended on the polymer composition and the media. With critical micelle concentrations (CMCs) in the range of 1.23-3.73 mg L⁻¹, the block copolymers formed micelles in the aqueous phase owing to their amphiphilic characteristics. Increased hydrophobic segment length or decreased hydrophilic segment length in an amphiphilic diblock copolymer produced lower CMC values. The current work proved the core-shell structure of micelles by ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopy analyzed micelle morphology, showing a spherical core-shell structure. The micelles had an average size in the range of 170˜210 nm (blank), and 195˜280 nm (with drug). Observations showed high drug entrapment efficiency and drug-loading content for the drug micelles.     

Well-defined diblock copolymers of poly(tert-butyldimethylsilyl methacrylate) and poly(dimethylsiloxane) synthesized by RAFT polymerization

We report the application of reversible addition-fragmentation chain transfer (RAFT) polymerization using poly(dimethylsiloxane) (PDMS) chain transfer agents toward the synthesis of a variety of diblock copolymers containing tert-butyldimethylsilyl methacrylic (MASi) monomer units. The methodology relies on the synthesis of PDMS monofunctional chain transfer agents easily available in one synthetic step from commercially available hydroxylated PDMSs. The RAFT process enables access to polymer chains with narrow molar mass distributions and high conversions. Data from differential scanning calorimetric measurements revealed that the diblock copolymers exhibited two glass transition temperatures, corresponding to the PDMS- and PMASi-enriched phases, respectively. Copolymerizations of MASi and butyl methacrylate (BMA) within the second block led to immiscible phases with lower glass transition temperatures than PDMS-block-PMASi copolymers.     

RAFT synthesis of poly(N‐isopropylacrylamide) and poly(methacrylic acid) homopolymers and block copolymers: Kinetics and characterization

Reversible addition‐fragmentation chain transfer (RAFT) polymerization was used successfully to synthesize temperature‐responsive poly(N‐isopropylacrylamide) (PNIPAAm), poly(methacrylic acid) (PMAA), and their temperature‐responsive block copolymers. Detailed RAFT polymerization kinetics of the homopolymers was studied. PNIPAAm and PMAA homopolymerization showed living characteristics that include a linear relationship between M _n and conversion, controlled molecular weights, and relatively narrow molecular weight distribution (PDI < 1.3). Furthermore, the homopolymers can be reactivated to produce block copolymers. The RAFT agent, carboxymethyl dithiobenzoate (CMDB), proved to control molecular weight and PDI. As the RAFT agent concentration increases, molecular weight and PDI decreased. However, CMDB showed evidence of having a relatively low chain transfer constant as well as degradation during polymerization. Solution of the block copolymers in phosphate buffered saline displayed temperature reversible characteristics at a lower critical solution temperature (LCST) transition of 31°C. A 5 wt % solution of the block copolymers form thermoreversible gels by a self‐assembly mechanism above the LCST. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1191–1201, 2006     

The amphiphilic block copolymers of 2-(dimethylamino)ethyl methacrylate and methyl methacrylate: Synthesis by atom transfer radical polymerization and solution properties

Amphiphilic di- and tri-block copolymers of poly(methyl methacrylate) (PMMA) and poly(2-dimethylamino)ethyl methacrylate (PDMAEMA) have been synthesized by atom transfer radical polymerization (ATRP) at ambient temperature (35 °C) in the environment-friendly solvent, aqueous ethanol (water 16 vol%) using CuCl/o-phenanthroline as the catalyst. The PDMAEMA blocks are contaminated with ethyl methacrylate (EMA) residues to the extent of 1-2 mol% of DMAEMA depending on the length of the PDMAEMA block. The EMA forms through the autocatalyzed ethanolysis of the DMAEMA monomer and undergoes random copolymerization with the latter. The rate of ethanolysis is unexpectedly greater in the aqueous ethanol than in neat ethanol, which has been attributed to the higher polarity of the former than of the latter. In contrast to the ethanolysis no hydrolysis of DMAEMA in the aqueous ethanol medium could be detected for 133 h. The block copolymers form micelles in water. Their solubility and CMC in neutral water have been studied. Dynamic light scattering (DLS) studies reveal that for a fixed degree of polymerization (DP) of the PMMA block the hydrodynamic diameter of the micelles in methanolic water (water 95 vol%) increases at a faster rate with the DP of the PDMAEMA block when it is much greater than that of the PMMA block compared to when it is less than or close to that of the latter.     

Synthesis of amphiphilic poly(methyl methacrylate)‐block‐poly(methacrylic acid) diblock copolymers by atom transfer radical polymerization

Atom transfer radical polymerization (ATRP) of 1‐(butoxy)ethyl methacrylate (BEMA) was carried out using CuBr/2,2′‐bipyridyl complex as catalyst and 2‐bromo‐2‐methyl‐propionic acid ester as initiator. The number average molecular weight of the obtained polymers increased with monomer conversion, and molecular weight distributions were unimodal throughout the reaction and shifted toward higher molecular weights. Using poly(methyl methacrylate) (PMMA) with a bromine atom at the chain end, which was prepared by ATRP, as the macro‐initiator, a diblock copolymer PMMA‐block‐poly [1‐(butoxy)ethyl methacrylate] (PMMA‐b‐PBEMA) has been synthesized by means of ATRP of BEMA. The amphiphilic diblock copolymer PMMA‐block‐poly(methacrylic acid) can be further obtained very easily by hydrolysis of PMMA‐b‐PBEMA under mild acidic conditions. The molecular weight and the structure of the above‐mentioned polymers were characterized with gel permeation chromatography, infrared spectroscopy and nuclear magnetic resonance. Copyright © 2005 Society of Chemical Industry     

Controlled/living RAFT polymerization of N‐phenyl maleimide and synthesis of its block copolymers

The controlled/living radical polymerization of N‐phenyl maleimide (NPMI) was achieved using 2,2′‐azobisisobutyronitrile as the initiator and 2‐cyanopropyl‐2‐yl dithiobenzoate as the reversible addition‐fragmentation chain transfer agent at 75°C in dichloroethane/ethylene carbonate (60/40, w/w) mixed solvent. The block copolymers of polystyrene‐b‐polyNPMI and poly(n‐butyl methacrylate)‐b‐polyNPMI were successfully prepared by chain extension from dithiobenzoate‐terminated polystyrene and poly (n‐butyl methacrylate) to NPMI, respectively. The obtained NPMI‐based (co)polymers were characterized by gel permeation chromatography and ¹H‐NMR spectroscopy. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

基于RAFT聚合策略合成功能化聚烯烃嵌段聚合物的研究进展

首先介绍了可逆加成-断裂链转移聚合（RAFT）的聚合机理及其常用的RAFT试剂,并与其它两种活性可控自由基聚合[氮氧化合物媒介的自由基聚合（NMP）和原子转移自由基聚合（ATRP）]进行了简单的优缺点对比。其次,介绍了近些年在基于RAFT聚合制备功能化聚烯烃嵌段聚合物研究中取得的进展,重点综述了制备功能化聚烯烃嵌段聚合物时所采用的6种方法,包括①烯烃配位聚合与RAFT聚合相结合;②阴离子聚合与RAFT聚合相结合;③阳离子聚合与RAFT聚合相结合;④Click反应与RAFT聚合相结合;⑤开环聚合与RAFT聚合相结合;⑥叶立德活性聚合与RAFT聚合相结合。最后,对基于RAFT聚合策略设计合成功能化聚烯烃嵌段聚合物的研究前景与实际应用进行了展望。     

The influence of hydrophobic substitution on self-association of poly(ethylene oxide)-b-poly(n-alkyl glycidyl carbamate)s-b-poly(ethylene oxide) triblock copolymers in aqueous media

A series of amphiphilic poly(ethylene oxide)-b-poly(n-alkyl glycidyl carbamate)s-b-poly(ethylene oxide) triblock copolymers were synthesized by reaction between poly(ethylene oxide)-b-polyglycidol-b-poly(ethylene oxide) precursor copolymer and four n-alkyl isocyanates: ethyl, propyl, butyl and pentyl. After dissolution in water at room temperature the copolymers spontaneously form micelles. The critical micellization concentrations were determined by UV-VIS spectroscopy. The dimensions of the micelles, the aggregation numbers, and in some cases the micellar shape were determined by dynamic and static light scattering in a relatively broad temperature range. Special attention has been paid to the influence of the number of the carbon atoms in the alkyl chains, and respectively, the relative hydrophobicity of the middle block upon the self-association process. Clouding transition was observed for all of the copolymers, the clouding point being dependent upon the length of the alkyl chain.     

Syntheses of well-defined poly(siloxane)-b-poly(styrene) and poly(norbornene)-b-poly(styrene) block copolymers using functional alkoxyamines

Functional alkoxyamines, 1-[4-(4-lithiobutoxy)phenyl]-1-(2,2,6,6-tetramethylpiperidinyl-N-oxyl)ethane (2) and 1-[4-(2-vinyloxyethoxy)phenyl]-1-(2,2,6,6-tetramethylpiperidinyl-N-oxyl)ethane (3) were prepared, and well-defined poly(hexamethylcyclotrisiloxane)-b-poly(styrene)[poly(D₃)-b-poly(St)] and poly(norbornene)-b-poly(St) [poly(NBE)-b-poly(St)] were prepared using the alkoxyamines. The first step was preparation of poly(D₃) and poly(NBE) macroinitiators, which were obtained by the ring-opening anionic polymerization of D₃ using 2 as an initiator and the ring-opening metathesis polymerization of NBE using 3 as a chain transfer. The radical polymerization of St by the poly(D₃) and poly(NBE) macroinitiators proceeded in the ‘living’ fashion to give well-defined poly(D₃)-b-poly(St) and poly(NBE)-b-poly(St) block copolymers.     

Synthesis of poly(vinyl alcohol) combs via MADIX/RAFT polymerization

Poly(vinyl acetate) combs have been prepared via macromolecular design via interchange of xanthate (MADIX)/reversible addition-fragmentation chain-transfer (RAFT) polymerization using xanthate functionalized polymer cores. The comb backbones were prepared using well-defined poly(vinyl alcohol) PVA polymers with a degree of polymerization of 20, 100 and 170, respectively. Functionalization with xanthates via R-group or a Z-group approach resulted in the formation of macromolecular MADIX agents. While Z group designed macromolecular xanthate agents appeared to inhibit the polymerization of vinyl acetate (VAc), R group designed macromolecular xanthate agents achieved to mediate efficiently the bulk polymerization of VAc affording PVAc combs. However, the growth of the combs was accompanied at low conversions by the formation of linear polymer chains as a result of the constant initiation (AIBN) and shoulders, which can be attributed to intermolecular coupling reactions. The proportions of single chains and termination products were observed to increase with the degree of polymerization of the macromolecular MADIX agents broadening the molecular weight distribution. As a result of a stable ester link between the branches and the PVA backbone, the branched PVAc architectures were finally hydrolyzed to afford poly(vinyl alcohol) combs.     

Physical properties of poly(cyclohexyl methacrylate)-b-poly(iso-butyl acrylate)-b-poly(cyclohexyl methacrylate) triblock copolymers synthesized by controlled radical polymerization

The microphase segregation of different poly(cyclohexyl methacrylate)-b-poly(iso-butyl acrylate)-b-poly(cyclohexyl methacrylate), PCH-b-PiBA-b-PCH, triblock copolymers obtained by atom transfer radical polymerization has been evaluated by dynamic mechanical thermal analysis through location of the two relaxations ascribed to cooperative motions of each block. Additionally, other secondary relaxations have been found, whose characteristics are also dependent on molecular weight of outer and rigid segments. The length of these hard blocks influences significantly the stiffness and microhardness found in these triblock copolymers. These two mechanical parameters increase as molecular weight of poly(cyclohexyl methacrylate) does. The morphological aspects have been examined by small angle X-ray scattering and atomic force microscopy.     

Synthesis and self-assembly of poly(benzyl ether)-b-poly(methyl methacrylate) dendritic-linear polymers

Here, the dendritic chloric poly(benzyl ether) (G₁-Cl, G₂-Cl and G₃-Cl) as the macroinitiator for the controlled atom transfer radical polymerization (ATRP) of methyl methylacrylate was investigated. Polymers obtained were characterizated by GPC, ¹H NMR, FT-IR, TGA and DSC. These dendritic-linear block polymers that consist of linear and dendritic segments have very good solubility in common organic solvents at room temperature. In a selective solvent (THF/H₂O), polymers can self-assembled into the micelles that have a spherical morphology in shape due to the lowest of the surface energies.     

Synthesis and characterization of pH/temperature-sensitive block copolymers via atom transfer radical polymerization

In order to prepare well-defined pH-sensitive block copolymers with a narrow molecular weight distribution (MWD), we synthesized a pH-sensitive block copolymer via atom transfer radical polymerization (ATRP) of sulfamethazine methacrylate monomer (SM) and amphiphilic diblock copolymers by the ring-opening polymerization of d,l-lactide/?-caprolactone (LA/CL), and their sol-gel phase transition was investigated. SM, which is a derivative of sulfonamide, was used as a pH responsive moiety, while PCLA-PEG-PCLA was used as a biodegradable, as well as a temperature sensitive one, amphiphilic triblock copolymer. The pentablock copolymer, OSM-PCLA-PEG-PCLA-OSM, was synthesized using Br-PCLA-PEG-PCLA-Br as an ATRP macroinitiator. The number average molecular weights of SM were controlled by adjusting the monomer/initiator feed ratio. The macroinitiator was synthesized by the coupling of 2-bromoisobutyryl bromide with PCLA-PEG-PCLA in the presence of triethyl amine catalyst in dichloromethane. The resultant block copolymer shows a narrow polydispersity. The block copolymer solution shows a sol-gel transition in response to a slight pH change in the range of 7.2-8.0. Gel permeation chromatography (GPC) and NMR were used for the characterization of the polymers that were synthesized.