Synthesis of amphiphilic block copolymers via ring opening polymerization and reversible addition-fragmentation chain transfer polymerization

Amphiphilic block copolymers were synthesized via a dual initiator chain transfer agent (inifer) that successfully initiated the ring opening polymerization (ROP) of l -lactide (LLA) and subsequently mediated the reversible addition-fragmentation chain transfer (RAFT) polymerization of poly(ethylene glycol) ethyl ether methacrylate (PEGEEMA). The formation of each polymer block was confirmed using ¹H nuclear magnetic resonance spectroscopy, as well as gel permeation chromatography, and comprehensive kinetics studies provide valuable insights into the factors influencing the synthesis of well-defined block copolymers. The effect of monomer concentration, reaction time, and molar ratios of inifer to catalyst on the ROP of LLA are discussed, as well as the ability to produce poly(lactide) blocks of different molecular weights. The synthesis of hydrophilic PPEGEEMA blocks was also monitored via kinetics to provide a better understanding of the role the chain transfer agent plays in facilitating the complex and sterically demanding RAFT polymerization of PEGEEMA.     

Synthesis and characterization of hyperbranched amphiphilic block copolymers prepared via self‐condensing RAFT polymerization

Four families of hyperbranched amphiphilic block copolymers of styrene (Sty, less polar monomer) and 2‐vinylpyridine (2VPy, one of the two more polar monomers) or 4‐vinylpyridine (4VPy, the other polar monomer) were prepared via self‐condensing vinyl reversible addition‐fragmentation chain transfer polymerization (SCVP‐RAFT). Two families contained 4VPy as the more polar monomer, one of which possessing a Sty‐b‐4VPy architecture, and the other possessing the reverse block architecture. The other two families bore 2VPy as the more polar monomer and had either a 2VPy‐b‐Sty or a Sty‐b‐2VPy architecture. Characterization of the hyperbranched block copolymers in terms of their molecular weights and compositions indicated better control when the VPy monomers were polymerized first. Control over the molecular weights of the hyperbranched copolymers was also confirmed with the aminolysis of the dithioester moiety at the branching points to produce linear polymers with number‐average molecular weights slightly greater than the theoretically expected ones, due to recombination of the resulting thiol‐terminated linear polymers. The amphiphilicity of the hyperbranched copolymers led to their self‐assembly in selective solvents, which was probed using atomic force microscopy and dynamic light scattering, which indicated the formation of large spherical micelles of uniform diameter. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1310–1319     

Controlled synthesis of amphiphilic block copolymers based on poly(isobutylene) macromonomers

The synthesis of a monoacrylate functionalized poly(isobutylene) (PIB) macromonomer (PIBA) has been achieved by a two‐step reaction starting from a commercially available PIB. Firstly, terminal olefins (vinylidene and trisubstituted olefin) of PIB were transformed to a phenolic residue by Friedel‐Crafts alkylation followed by subsequent esterification of the phenol with acryloyl chloride, catalyzed by triethylamine. PIBA structure was confirmed by ¹H‐NMR, ¹³C‐NMR and GPC before utilizing in the RAFT copolymerization with N,N‐dimethylacrylamide (DMA) to obtain statistical copolymers (P[(DMA‐co‐(PIBA)]). Monomer conversions were consistently higher than 85% for both DMA and PIBA as monomer feed composition was varied. Chain extension of poly(N,N‐dimethylacrylamide) with PIBA to synthesize block copolymers (P[(DMA‐b‐(PIBA)]) was also achieved with near quantitative monomer conversions (>97%). Block formation efficiency was not quantitative but purification of block copolymers was possible by selective precipitation. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 634–643     

Synthesis of transparent block copolymers consisting of poly(diisopropyl fumarate) and poly(2-ethylhexyl acrylate) segments by reversible addition-fragmentation chain transfer polymerization using trithiocarbonates as the chain transfer agents

The reversible addition-fragmentation chain transfer polymerization of diisopropyl fumarate (DiPF) was carried out using ethyl 2-[[(dodecylthio)thioxymethyl]thio]-2-methylpropionate (T1) and 1,1′-(1,2-ethanediyl) bis[2-[[(dodecylthio)thioxymethyl]thio]-2-methylpropionate] (T2) as the monofunctional and difunctional chain transfer agents (CTAs) to synthesize poly(diisopropyl fumarate) (PDiPF) with a rigid chain conformation. The obtained PDiPF had a well-controlled molecular weight, molecular weight distribution, and structure of the chain ends. Size exclusion chromatography and NMR measurements revealed an excellent introduction efficiency (84–98%) of the terminal trithiocarbonate group into the polymer chain end. They were available as the monofunctional and difunctional macro-CTAs to synthesize the AB and ABA block copolymers, respectively. While the well-controlled block copolymers were solely obtained by the polymerization of 2-ethylhexyl acrylate as the second monomer in the presence of PDiPF as the macro-CTA, the block copolymerization of DiPF using poly(2-ethylhexyl acrylate) as the macro-CTA failed. The trithiocarbonate group at the chain end was completely removed by the reaction with n-butylamine and it was valid for the improvement of the coloration and other optical properties of the transparent polymers. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2584–2594     

Amphiphilic well-defined degradable star block copolymers by combination of ring-opening polymerization and atom transfer radical polymerization: Synthesis and application as drug delivery carriers

Atom transfer radical polymerization (ATRP) is one of the most popular advanced polymerization techniques in macromolecular science, allowing the synthesis of tailor-made polymers with controlled molecular weight, architecture, composition, and functionality. The combination of ATRP and ring-opening polymerization (ROP) provides a straightforward route for the preparation of polymers exhibiting both targeted and well-defined features and biodegradability, which is very interesting for the development of new materials for biomedical applications. Among the different types of polymer architectures, amphiphilic star block copolymers (BCPs) represent a very attractive one, due to their high degree of functionality at the molecular surface, low hydrodynamic volume and higher encapsulation ability, compared to molecular systems based on linear polymers. This review article highlights the research focused on the synthesis of amphiphilic well-defined degradable star BCPs by combination of ROP and ATRP, with particular focus on the development of polymers for biomedical applications, such as anticancer drug delivery, diagnosis therapy, or photodynamic therapy, which is the most investigated field regarding these polymers.     

Synthesis and characterization of graft copolymers based on polyepichlorohydrin via reversible addition-fragmentation chain transfer polymerization

In this study, synthesis of poly(epichlorohydrin-g-methyl methacrylate) graft copolymers by reversible addition-fragmentation chain transfer (RAFT) polymerization was reported. For this purpose, epichlorohydrin was polymerized by using HNO₃ via cationic ring-opening mechanism. A RAFT macroinitiator (macro-RAFT agent) was obtained by the reaction of potassium ethyl xanthogenate and polyepichlorohydrin. The graft copolymers were synthesized using macro-RAFT agent as initiator and methyl methacrylate as monomer. The synthesis of graft copolymers was conducted by changing the time of polymerization and the amount of monomer-initiator concentration that affect the RAFT polymerization. The effects of these parameters on polymerization were evaluated via various analyses. The characterization of the products was determined using ¹H-nuclear magnetic resonance (¹H-NMR), Fourier-transform infrared spectroscopy, gel-permeation chromatography, thermogravimetric analysis, elemental analysis, and fractional precipitation techniques. The block lengths of the graft copolymers were calculated by using ¹H-NMR spectrum. It was observed that the block length could be altered by varying the monomer and initiator concentrations.     

两亲性嵌段共聚物PGMA-b-PMAPEG的制备及其胶束的布洛芬药物控制释放性能

利用自由基可逆加成-断链链转移(RAFT)活性/可控聚合法成功合成了两亲性嵌段共聚物聚(甲基丙烯酸缩水甘油酯)-b聚(甲基丙烯酸聚乙二醇酯)(PGMA-b-PMAPEG).利用傅立叶变换红外光谱、核磁共振谱仪、凝胶渗透色谱仪及透射电镜等分析了所合成聚合物的结构、胶束粒径及形貌.以布洛芬作为模型药物负载于聚合物胶束内,考...     

新型线状-树枝状两亲嵌段共聚物的合成

本文设计合成了一系列由不同链长的聚丙烯酸(PAA)为亲水嵌段和不同代数聚苄醚树枝体(Dendr.PBE)为疏水嵌段的杂化共聚物(PAA-Dendr.PBE)。     

Synthesis of a ‐shaped amphiphilic block copolymer by the combination of atom transfer radical polymerization and living anionic polymerization

The functionalization of monomer units in the form of macroinitiators in an orthogonal fashion yields more predictable macromolecular architectures and complex polymers. Therefore, a new ‐shaped amphiphilic block copolymer, (PMMA)₂–PEO–(PS)₂–PEO–(PMMA)₂ [where PMMA is poly(methyl methacrylate), PEO is poly (ethylene oxide), and PS is polystyrene], has been designed and successfully synthesized by the combination of atom transfer radical polymerization (ATRP) and living anionic polymerization. The synthesis of meso‐2,3‐dibromosuccinic acid acetate/diethylene glycol was used to initiate the polymerization of styrene via ATRP to yield linear (HO)₂–PS₂ with two active hydroxyl groups by living anionic polymerization via diphenylmethylpotassium to initiate the polymerization of ethylene oxide. Afterwards, the synthesized miktoarm‐4 amphiphilic block copolymer, (HO–PEO)₂–PS₂, was esterified with 2,2‐dichloroacetyl chloride to form a macroinitiator that initiated the polymerization of methyl methacrylate via ATRP to prepare the ‐shaped amphiphilic block copolymer. The polymers were characterized with gel permeation chromatography and ¹H NMR spectroscopy. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 147–156, 2007     

Controlled synthesis of amphiphilic block copolymers with pendant glucose residues by living cationic polymerization

Amphiphilic block copolymers of vinyl ethers (VEs) of the type —[CH₂CH(OCH₂CH₂OR)]_m—[CH₂CH(OiBu)]_n—were synthesized by living cationic polymerization, where R is a D-glucose residue, and m and n are the degrees of polymerization (m = 20–50; n = 11–89). To obtain them, sequential living block copolymerization of isobutyl vinyl ether (IBVE) and the vinyl ether carrying 1,2:5,6-diisopropylidene-D -glucose residue was conducted by using the HCl adduct of IBVE, CH₃CH(OiBu)Cl, as initiator in conjunction with zinc iodide. These precursor block copolymers had a narrow molecular weight distribution (M̄_w/M̄_n ∼ 1.1) and a controlled composition. Treatment of them with a trifluoroacetic acid/water mixture led to the target amphiphiles. The solubility of the amphiphilic block copolymers in various solvents depended strongly on composition or the m/n ratio. Their solvent-cast thin films were observed, under a transmission electron microscope, to exhibit various microphase-separated surface morphologies such as spheres, cylinders, and lamellae, depending on composition. © 1997 John Wiley & Sons, Inc.     

两亲性嵌段共聚物mPEG-b-PCL/FA的合成及其药物释放性能

以苯甲醇为引发剂,在辛酸亚锡催化下引发ε-环己内酯(ε-CL )开环聚合,合成了聚己内酯(PCL).分别利用端甲氧基聚乙二醇(mPEG)、PCL及叶酸(FA)与三氯三嚎中不同的氯反应,得到两亲性嵌段共聚物mPEG-b-PCL/FA;采用傅立叶变换红外光谱仪和核磁共振谱仪等表征了mPEG-b-PCL/FA的组成和结构;采...     

Dendrimer‐star polymer and block copolymer prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization with dendritic chain transfer agent

A new reversible addition‐fragmentation chain transfer (RAFT) agent, dendritic polyester with 16 dithiobenzoate terminal groups, was prepared and used in the RAFT polymerization of styrene (St) to produce star polystyrene (PSt) with a dendrimer core. It was found that this polymerization was of living characters, the molecular weight of the dendrimer‐star polymers could be controlled and the polydispersities were narrow. The dendrimer‐star block copolymers of St and methyl acrylate (MA) were also prepared by the successive RAFT polymerization using the dendrimer‐star PSt as macro chain transfer agent. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6379–6393, 2005     

Synthesis of a well-defined glycopolymer by atom transfer radical polymerization

Controlled free radical polymerization of sugar-carrying methacrylate, 3-O-methacryloyl-1,2 : 5,6-di-O-isopropylidene-d-glucofuranose (MAIpGlc) was achieved by the atom transfer radical polymerization (ATRP) technique with an alkyl halide/copper-complex system in veratrole at 80°C. The time–conversion first-order plot was linear and the number-average molecular weight increased in direct proportion to the ratio of the monomer conversion to the initial initiator concentration, providing PMAIpGlc with a low polydispersity. The sequential addition of the two monomers styrene (S) and MAIpGlc afforded a block copolymer of the type PS-b-PMAIpGlc. The acidolysis of the homo- and block copolymers gave well-defined glucose-carrying water-soluble polymers PMAGlc and PS-b-PMAGlc, respectively. The amphiphilic PS-b-PMAGlc block copolymer exhibited a microdomain surface morphology with spherical PS domains in a PMAGlc matrix. © 1998 John Wiley & Sons, Inc. J. Polym. Sci. A Polym. Chem. 36: 2473–2481, 1998     

Synthesis and characterization of a film‐forming,crosslinked, amphiphilic block copolymer of butadiene and acrylamide

An amphiphilic block copolymer of acrylamide and butadiene was synthesized by the polymerization of acrylamide in the presence of the crosslinker N,N′‐methylene bisacrylamide initiated by a hydroxyl‐terminated polybutadiene/V(V) macroredox initiator. The product had good film‐forming ability. It was characterized by IR and NMR spectroscopy, viscosity, swelling, and microhardness measurements, scanning electron micrography, and differential scanning calorimetry. A good film was obtained from the block copolymer with a greater proportion of butadiene; it had greater permeability for nonpolar solvents, and it was poorly permeable to water and other polar solvents. The film swelled in polar and nonpolar solvents and had almost the same capacity for the loading and release of hydrophilic and hydrophobic dyes. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3290–3303, 2006     

Synthesis and characterization of isoprene polymers with polar groups via reversible addition-fragmentation chain-transfer polymerization

Homo and copolymerization of isoprene (IP) with small amounts (1% wt) of glycidyl methacrylate) were conducted using the reversible addition-fragmentation chain-transfer process (RAFT) at 125 °C in a solution polymerization process using toluene as solvent. Suitable reaction conditions to avoid Diels–Alder dimerization of IP and crosslinking were determined; and 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid was found to be the best transfer agent among those tested. Theoretical calculations were used to understand why some RAFT agents work better than others in these polymerizations. Molecular weights M_n higher than 100,000 Da were reached by successive chain extension experiments, confirming the livingness of the intermediate polymers. All the successful polymerizations yielded average molar masses (M_n) of about 75% compared to the theoretical M_n (M_n,theo) depending on the agent used for control. The dispersity (Ð) ranged from 1.20 to 1.70 being a function of the control agent. The polymers were characterized by FTIR spectroscopy, ¹H NMR, and gel permeation chromatography. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2463–2474     

Evaluation of the clenbuterol imprinted monolithic column prepared by reversible addition-fragmentation chain transfer polymerization

To make more homogenous organic monolithic structure,reversible addition-fragmentation chain transfer(RAFT) process was employed in the synthesis of the clenbuterol imprinted polymer.In the synthesis,the influence of synthetic conditions on the polymer structure and separation efficiency was studied.The result demonstrated that the imprinted columns prepared with RAFT process have higher column efficiency and selectivity than the columns prepared with conventional polymerization in the present study,whic...     

Comparison of micelles formed by amphiphilic star block copolymers prepared in the presence of a nonmetallic monomer activator

In this article, we describe the synthesis of PEG‐b‐polyester star block copolymers via ring‐opening polymerization (ROP) of ester monomers initiated at the hydroxyl end group of the core poly(ethylene glycol) (PEG) using HCl Et₂O as a monomer activator. The ROP of ε‐caprolactone (CL), trimethylene carbonate (TMC), or 1,4‐dioxan‐2‐one (DO) was performed to synthesize PEG‐b‐polyester star block copolymers with one, two, four, and eight arms. The PEG‐b‐polyester star block copolymers were obtained in quantitative yield, had molecular weights close to the theoretical values calculated from the molar ratio of ester monomers to PEG, and exhibited monomodal GPC curves. The crystallinity of the PEG‐b‐polyester star block copolymers was determined by differential scanning calorimetry and X‐ray diffraction. Copolymers with a higher arm number had a higher tendency toward crystallization. The crystallinity of the PEG‐b‐polyester star block copolymers also depended on the nature of the polyester block. The CMCs of the PEG‐b‐PCL star block copolymers, determined from fluorescence measurements, increased with increasing arm number. The CMCs of the four‐arm star block copolymers with different polyester segments increased in the order 4a‐PEG‐b‐PCL < 4a‐PEG‐b‐PDO < 4a‐PEG‐b‐PLGA < 4a‐PEG‐b‐PTMC, suggesting a relationship between CMC and star block copolymer crystallinity. The partition equilibrium constant, K_v, which is an indicator of the hydrophobicity of the micelles of the PEG‐polyester star block copolymers in aqueous media, increased with decreasing arm number and increasing crystallinity. A key aspect of the present work is that we successfully prepared PEG‐b‐polyester star block copolymers by a metal‐free method. Thus, unlike copolymers synthesized by ROP using a metal as the monomer activator, our copolymers do not contain traces of metals and hence are more suitable for biomedical applications. Moreover, we confirmed that the PEG‐b‐polyester star block copolymers form micelles and hence may be potential hydrophobic drug delivery vehicles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2084–2096, 2008     

Glasses-shaped triblock copolymer prepared by combination of atom transfer radical polymerization and ring opening polymerization

A glasses-shaped triblock copolymer of poly(ε-caprolactone)-b-polystyrene-b-poly(ε-caprolactone) (PCL-b-PS-b-PCL) is prepared by combining atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP). Polystyrene (PS) star polymers are prepared via ATRP using a tetra-functional initiator, followed by azidation to yield azide end-functionalized star polymers. An alkyne-functionalized coupling agent, 2,2-bis[(2-propyn-1-yloxy)methyl]-1-propanol is employed to produce hydroxy 8-shaped PS via copper(I)-catalyzed alkyne-azide cycloaddition. Herein, hydroxy 8-shaped PS with high purity is obtained through preparative size exclusion chromatography (Prep SEC) and high-performance liquid chromatography, followed by the characterizations using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), size exclusion chromatography (SEC), infrared, and proton nuclear magnetic resonance (¹H NMR) spectroscopy. The hydroxy groups of the 8-shaped PS are utilized as initiators for the ROP of ε-caprolactone to obtain linear chains attached to the 8-shaped architecture. After SEC fractionation, the glasses-shaped triblock copolymer is characterized using ¹H NMR and SEC. This unprecedented topology possesses two free chain-ends and two cycles; thus, both the properties of linear and cyclic polymers may be expected to be observed.     

Non-surface activity and micellization behavior of cationic amphiphilic block copolymer synthesized by reversible addition-fragmentation chain transfer process

Cationic amphiphilic diblock copolymers of poly(n-butylacrylate)-b-poly(3-(methacryloylamino)propyl)trimethylammonium chloride) (PBA-b-PMAPTAC) with various hydrophobic and hydrophilic chain lengths were synthesized by a reversible addition-fragmentation chain transfer (RAFT) process. Their molecular characteristics such as surface activity/nonactivity were investigated by surface tension measurements and foam formation observation. Their micelle formation behavior and micelle structure were investigated by fluorescence probe technique, static and dynamic light scattering (SLS and DLS), etc., as a function of hydrophilic and hydrophobic chain lengths. The block copolymers were found to be non-surface active because the surface tension of the aqueous solutions did not change with increasing polymer concentration. Critical micelle concentration (cmc) of the polymers could be determined by fluorescence and SLS measurements, which means that these polymers form micelles in bulk solution, although they were non-surface active. Above the cmc, the large blue shift of the emission maximum of N-phenyl-1-naphthylamine (NPN) probe and the low micropolarity value of the pyrene probe in polymer solution indicate the core of the micelle is nonpolar in nature. Also, the high value of the relative intensity of the NPN probe and the fluorescence anisotropy of the 1,6-diphenyl-1,3,5-hexatriene (DPH) probe indicated that the core of the micelle is highly viscous in nature. DLS was used to measure the average hydrodynamic radii and size distribution of the copolymer micelles. The copolymer with the longest PBA block had the poorest water solubility and consequently formed micelles with larger size while having a lower cmc. The "non-surface activity" was confirmed for cationic amphiphilic diblock copolymers in addition to anionic ones studied previously, indicating the universality of non-surface activity nature.     

Synthesis of block copolymers by the transformation of cationic polymerization into reversible atom transfer radical polymerization

Azo-containing polytetrahydrofuran (PTHF) obtained by cationic polymerization was used as a macroinitiator in the reverse atom transfer radical polymerization (RATRP) of styrene and methyl acrylate in conjunction with CuCl₂/2,2′-bipyridine as a catalyst. Diblock PTHF–polystyrene and PTHF–poly(methyl acrylate) were obtained after a two-step process. In the first step of the reaction, stable chlorine-end-capped PTHF was formed with the thermolysis of azo-linked PTHF at 65–70 °C in the presence of the catalyst. Heating the system at temperatures of 100–110 °C started the polymerization of the second monomer, which resulted in the formation of block copolymers. The decomposition behavior of the azo-linked PTHF and the structure of the block copolymers were determined by ¹H NMR and gel permeation chromatography (GPC). Kinetic studies and GPC analyses further confirmed the controlled/living nature of the RATRP initiated by the polymeric radicals. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2199–2208, 2002