Synthesis of molecular brushes by "grafting onto" method: combination of ATRP and click reactions

Molecular brushes (densely grafted polymers or bottle-brush macromolecules) were synthesized by the "grafting onto" method via combination of atom transfer radical polymerization (ATRP) and "click" reactions. Linear poly(2-hydroxyethyl methacrylate) (PHEMA) polymers were synthesized first by ATRP. After esterification reactions between pentynoic acid and the hydroxyl side groups, polymeric backbones with alkynyl side groups on essentially every monomer unit (PHEMA-alkyne) were obtained. Five kinds of azido-terminated polymeric side chains (SCs) with different chemical compositions and molecular weights were used, including poly(ethylene glycol)-N3 (PEO-N3), polystyrene-N3, poly(n-butyl acrylate)-N3, and poly(n-butyl acrylate)-b-polystyrene-N3. All click coupling reactions between alkyne-containing polymeric backbones (PHEMA-alkyne) and azido-terminated polymeric SCs were completed within 3 h. The grafting density of the obtained molecular brushes was affected by several factors, including the molecular weights and the chemical structures of the linear SCs, as well as the initial molar ratio of linear chains to alkynyl groups. When linear polymers with "thinner" structure and lower molecular weight, e.g., PEO-N3 with Mn = 775 g/mol, were reacted with PHEMA-alkyne (degree of polymerization = 210) at a high molar ratio of linear chains to alkynyl groups in the backbone, the brush copolymers with the highest grafting density were obtained (Y(grafting) = 88%). This result indicates that the average number of SCs was ca. 186 per brush molecule and the average molecular weight of the brush molecules was ca. 190 kg/mol.     

ATRP法合成两亲的含氟柱状刷PBIEM-g-(PAA-b-PFA)

以聚甲基丙烯酸[2-(2-溴异丁酰氧)]乙酯(PBIEM)为大分子引发剂,采用接出(grafting from)原子转移自由基聚合(ATRP)技术合成了以聚丙烯酸叔丁酯-b-聚含氟丙烯酸酯为侧链的柱状分子刷PBIEM-g-(PtBA-b-PFA).通过GPC,1H-NMR和FTIR对PBIEM-g-(PtBA-b-PFA)组成和结构进行了表征,证实ATRP过程中没有发生分子间或分子内偶合反应,制备得到可控性好的含氟嵌段共聚物刷.利用大分子链中叔丁酯基团的水解反应生成两亲的含氟柱状刷PBIEM-g-(PAA-b-PFA),原子力显微镜可直接观察到PBIEM-g-(PAA-b-PFA)特征的核壳型柱状结构,得到聚合物刷的整体长度为ln=54~72 nm.     

Functionalization of polymers prepared by ATRP using radical addition reactions

Low molecular weight linear poly(methyl acrylate), star and hyperbranched polymers were synthesized using atom transfer radical polymerization (ATRP) and end‐functionalized using radical addition reactions. By adding allyltri‐n‐butylstannane at the end of the polymerization of poly(methyl acrylate), the polymer was terminated by allyl groups. When at high conversions of the acrylate monomer, allyl alcohol or 1,2‐epoxy‐5‐hexene, monomers which are not polymerizable by ATRP, were added, alcohol and epoxy functionalities respectively were incorporated at the polymer chain end. Functionalization by radical addition reactions was demonstrated to be applicable to multi‐functional polymers such as hyperbranched and star polymers.     

An efficient way to tune grafting density of well‐defined copolymers via an unusual Br‐containing acrylate monomer

A series of well‐defined amphiphilic graft copolymers, containing hydrophilic poly(acrylic acid) backbone and hydrophobic poly(butyl acrylate) side chains, were synthesized by sequential reversible addition fragmentation chain transfer (RAFT) polymerization and atom transfer radical polymerization (ATRP) without any postpolymerization functionality modification followed by selective acidic hydrolysis of poly(tert‐butyl acrylate) backbone. tert‐Butyl 2‐((2‐bromopropanoyloxy)methyl)‐acrylate was first homopolymerized or copolymerized with tert‐butyl acrylate by RAFT in a controlled way to give ATRP‐initiation‐group‐containing homopolymers and copolymers with narrow molecular weight distributions (M_w/M_n < 1.20) and their reactivity ratios were determined by Fineman‐Ross and Kelen‐Tudos methods, respectively. The density of ATRP initiation group can be regulated by the feed ratio of the comonomers. Next, ATRP of butyl acrylate was directly initiated by these macroinitiators to synthesize well‐defined poly(tert‐butyl acrylate)‐g‐poly(butyl acrylate) graft copolymers with controlled grafting densities via the grafting‐from strategy. PtBA‐based backbone was selectively hydrolyzed in acidic environment without affecting PBA side chains to provide poly(acrylic acid)‐g‐poly(butyl acrylate) amphiphilic graft copolymers. Fluorescence probe technique was used to determine the critical micelle concentrations in aqueous media and micellar morphologies are found to be spheres visualized by TEM. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2622–2630, 2010     

Design and use of organic nanoparticles prepared from star-shaped polymers with reactive end groups

Star-shaped poly(isobornyl acrylate) (PiBA) was prepared by atom transfer radical polymerization (ATRP) using multifunctional initiators. The optimal ATRP conditions were determined to minimize star-star coupling and to preserve high end group functionality (>90%). Star-shaped PiBA with a narrow polydispersity index was synthesized with 4, 6, and 12 arms and of varying molecular weight (10,000 to 100,000 g x mol(-1)) using 4 equiv of a Cu(I)Br/PMDETA catalyst system in acetone. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis, NMR spectroscopy, and size exclusion chromatography (SEC) confirmed their controlled synthesis. The bromine end group of each arm was then transformed to a reactive end group by a nucleophilic substitution with methacrylic acid or cinnamic acid (conversion >90%). These reactive star polymers were used to prepare PiBA nanoparticles by intramolecular polymerization of the end groups. The successful preparation of this new type of organic nanoparticles on a multigram scale was proven by NMR spectroscopy and SEC. Subsequently, they have been used as additives for linear, rubbery poly(n-butyl acrylate). Rheology measurements indicated that the viscoelastic properties of the resulting materials can be fine-tuned by changing the amount of incorporated nanoparticles (1-20 wt %), as a result of the entanglements between the nanoparticles and the linear polymers.     

“活性”/可控自由基聚合反应制备聚合物-蛋白质/多肽生物结合物

将蛋白质或多肽连接到高分子链上,能够改善蛋白质/多肽的稳定性、生物相溶性和溶解性而赋予其优异的应用性能,所得聚合物-蛋白质/多肽生物结合物已经被广泛应用于药物载体、生物材料、纳米材料等领域。本文介绍借助"活性"/可控自由基聚合反应制备新型功能高分子材料的原理与方法,以及其合成聚合物-蛋白质/多肽生物结合物的国内外研究进展。     

Graft modification of chitosan,cellulose and alginate using reversible deactivation radical polymerization (RDRP)

This perspective covers the most recent literature on the graft-modification of the natural polymers celluloses, chitosan and alginate through reversible deactivation radical polymerization (NMP, ATRP and RAFT). The different routes to obtain well-defined polysaccharide-based hybrids including “grafting from” and “grafting to” approaches, and their applications as composite, stimuli-responsive, and biomaterials are discussed.     

Nitroxide-mediated miniemulsion polymerization of n-butyl acrylate: synthesis of controlled homopolymers and gradient copolymers with styrene

Controlled free-radical homopolymerization of n-butyl acrylate and its copolymerization with styrene have been studied in aqueous miniemulsion, using an acyclic β-phosphonylated nitroxide as a mediator, the N-tert-butyl-N-(1-diethylphosphono-2,2-dimethylpropyl) nitroxide, also called SG1. Polymerization kinetics have been studied and characterization of the (co)polymers has been performed, demonstrating the successful synthesis of well-defined poly(n-butyl acrylate) homopolymers and poly(n-butyl acrylate-co-styrene) gradient copolymers.     

Synthesis of densely grafted comblike copolymers

Densely grafted copolymers were synthesized using the “grafting from” approach via the combination of reversible addition‐fragment chain transfer polymerization (RAFT) and atom transfer radical polymerization (ATRP). First, a novel functional monomer, 2,3‐di(2‐bromoisobutyryloxy)ethyl acrylate (DBPPA), with two initiating groups for ATRP was synthesized. It was then polymerized via RAFT polymerization to give macroinitiators for ATRP with controlled molecular weights and narrow molecular weight distributions. Last, ATRP of styrene was carried out using poly(DBPPA)s as macroinitiators to prepare comblike poly(DBPPA)‐graft‐polystyrenes carrying double branches in each repeating unit of backbone via “grafting from” approach. Furthermore, poly(DBPPA)‐graft‐[polystyrene‐block‐poly(t‐BA)]s and their hydrolyzed products poly(DBPPA)‐graft‐[polystyrene‐block‐poly(acrylic acid)]s were also successfully prepared. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 362–372, 2008     

活性正离子聚合与原子转移自由基聚合转换合成聚β-蒎烯接枝共聚物

通过活性正离子聚合与原子转移自由基聚合(ATRP)转换合成了β-蒎烯与甲基丙烯酸甲酯(MMA)、丙烯酸丁酯(BA)、苯乙烯(St)的新型接枝共聚物.首先以α-氯代乙苯/TiCl4/Ti(OiPr)4/nBu4NCl体系引发β-蒎烯活性正离子聚合,合成预定分子量大小和窄分子量分布的聚β-蒎烯,然后经N-溴代琥珀酰亚胺(NBS)定量溴化,得到溴化聚β-蒎烯大分子引发剂(Br/β-蒎烯链节摩尔比为0.5).然后将该大分子引发剂与溴化亚铜(CuBr)/2,2′-联吡啶(bpy)复合,引发MMA、BA、St进行ATRP接枝聚合.接枝反应显示一级动力学特征,且产物的分子量及分子量分布可控,表明上述ATRP接枝聚合反应具有可控聚合特征.接枝产物的结构经1H-NMR分析得到进一步证实.     

Modification of cellulose by graft polymerization for use in drug delivery systems

Cellulose-based biodegradable polymers—as microspheres or hydrogels—are suitable for drug delivery systems. In this work, cellulose microfibers were converted to cellulose esters for subsequent graft copolymerization either by free radical or atom transfer radical polymerization (ATRP). For the former, carboxymethyl cellulose (CMC) was prepared and then modified through grafting of poly(hydroxyethyl acrylate) or polyacrylamide. ATRP was achieved by chloroacetylation of cellulose followed by graft copolymerization of hydroxyethyl acrylate or acrylamide monomers. The degree of substitution for CMC and chloroacetylated cellulose (CAC) was determined by the method described in US Pharmacopeia NF24 and by titration method, respectively. CMC, CAC, and the grafted copolymers were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, thermal gravimetric analysis, X-ray diffraction, and atomic force microscopy; the latter technique clearly shows the chain growth of the synthetic polymers on the backbone surface. Furthermore, cephalexin antibiotic was loaded on the copolymers, and the resultant in vitro drug release studied in three different media (buffer solutions with pH equal to 3, 6.1, and 8).     

结构规整的高密度两亲性接枝聚合物刷的合成及其自组装研究

大分子单体通过两种可控聚合方法, 即开环易位聚合(ROMP)和原子转移自由基聚合(ATRP)的联用, 合成一种新型两亲性接枝聚合物刷. 具有高环张力的降冰片烯单侧链大分子单体norbornene-graft-poly(ε-caprolactone)/Br (PCL- NBE-Br)首先进行ROMP反应, 生成聚合物主链, 每个单体单元上含有一条PCL链和一个溴官能团; 然后用含溴的ROMP聚合物poly(norbornene)-graft-poly(ε-caprolactone)/Br (PCL-PNBE-Br)作为大分子引发剂引发单体2-(dimethyl- amino)ethyl methacrylate)的ATRP反应, 生成结构明确的高密度两亲性接枝聚合物刷poly(norbornene)-graft-poly(ε- caprolactone)/poly(2-(dimethylamino)ethyl methacrylate) (PCL-PNBE-PDMAEMA), 其主链每个单体单元上均含有一条疏水性PCL接枝链和一条亲水性PDMAEMA接枝链. 最后, 研究此类高密度两亲性接枝聚合物刷的自组装行为, 用动态激光光散射(DLS)研究其在混合溶剂(THF/H2O)中的胶束行为, 考察胶束溶液的浓度以及不同长度的亲水性接枝链对胶束尺寸的影响; 利用透射电镜(TEM)观察胶束为球形, 具有类似线团或草莓状的形态.     

Preparation and characterization of nonfouling polymer brushes on poly(ethylene terephthalate) film surfaces

In this study, a surface grafting of nonfouling poly(ethylene glycol) methyl ether acrylate (PEGMA) on poly(ethylene terephthalate) (PET) was carried out via surface-initiated atom-transfer radical polymerization (SI-ATRP) to improve hemocompatibility of polymer based biomaterials. To do this, the coupling agent with hydroxyl groups for the ATRP initiator was first anchored on the surface of PET films using photochemical method, and then these hydroxyl groups were esterified by bromoisobutyryl bromide, from which PET with various main chain lengths of PEGMA was prepared. The structures and properties of modified PET surfaces were investigated using water contact angle (WAC), ATR-FTIR, X-ray photoelectron spectroscopy (XPS) and Atomic force microscopy (AFM). The molecular weights of the free polymer from solution were determined by gel permeation chromatography (GPC). These results indicated that grafting of PEGMA on PET film is a simple way to change its surface properties. The protein adsorption resistance on the surfaces of PET was primarily evaluated by an enzyme-linked immunosorbent assay (ELISA). The result demonstrated that the protein adsorption could be well suppressed by poly(PEGMA) brush structure on the surface of PET. This work provides a new approach for polymers to enhance their biocompatibility.     

Patterning on nonplanar substrates: flexible honeycomb films from a range of self-assembling star copolymers

The effect of glass transition temperature, Tg, on the self-assembly of "honeycomb" microstructures on nonplanar substrates was probed by the synthesis of a library of core cross-linked star polymers with different arm compositions. Star polymers based on poly(dimethyl siloxane), poly(ethyl acrylate), poly(methyl acrylate), poly(tert-butyl acrylate), and poly(methyl methacrylate) were synthesized by the "arm first" strategy using atom-transfer radical polymerization. Reaction conditions were optimized, and a series of high molecular weight star polymers were prepared in high yield. The glass transition temperature of the star polymers ranged from -123 to 100 degrees C which allowed the suitability for the formation of porous honeycomb-like films via the "breath figure" technique on nonplanar surfaces to be investigated. All star compositions successfully formed ordered films on flat surfaces. However, only star polymer compositions with a Tg below 48 degrees C could form homogeneous honeycomb coatings on the surface of nonplanar substrates.     

Grafting acrylic polymers from flat nickel and copper surfaces by surface-initiated atom transfer radical polymerization

Acrylic polymers, including poly(methyl methacrylate), poly(2,2,2-trifluoroethyl methacrylate), poly( N,N'-dimethyaminoethyl methacrylate), and poly(2-hydroxyethyl methacrylate) were grafted from flat nickel and copper surfaces through surface-initiated atom transfer radical polymerization (ATRP). For the nickel system, there was a linear relationship between polymer layer thickness and monomer conversion or molecular weight of "free" polymers. The thickness of the polymer brush films was greater than 80 nm after 6 h of reaction time. The grafting density was estimated to be 0.40 chains/nm2. The "living" chain ends of grafted polymers were still active and initiated the growth of a second block of polymer. Block copolymer brushes with different block sequences were successfully prepared. The experimental surface chemical compositions as measured by X-ray photoelectron spectroscopy agreed very well with their theoretical values. Water contact angle measurements further confirmed the successful grafting of polymers from nickel and copper surfaces. The surface morphologies of all samples were studied by atomic force microscopy. This study provided a novel approach to prepare stable functional polymer coatings on reactive metal surfaces.     

Quantitation of functionality of poly(methyl methacrylate) by liquid chromatography under critical conditions followed by evaporative light-scattering detection. Comparison with NMR and titration

Atom transfer radical polymerisation (ATRP) is a versatile 'living' controlled polymerisation technique for the synthesis of well-defined architectures such as block copolymers, gradient copolymers, hyperbranched polymers and telechelic polymers. ATRP provides control over molecular mass and molecular mass distribution and is suitable for the polymerisation of a wide variety of monomers, including methyl methacrylate. A chromatographic method was developed for an endgroup-based separation of low-molecular-mass poly(methyl methacrylate) (PMMA), based on liquid chromatography under critical conditions. With this method the PMMA, irrespective of its low-molecular-mass, is separated according to endgroups (functionality) due to interactions of the polar endgroups with the non-modified silica based stationary phase. The different series were identified using on-line atmospheric pressure ionisation electrospray mass spectrometry and quantified by evaporative light scattering detection. These results were compared with those obtained by NMR and titration.     

Thermoresponsive PPEGMEA‐g‐PPEGEEMA well‐defined double hydrophilic graft copolymer synthesized by successive SET‐LRP and ATRP

A series of well‐defined double hydrophilic graft copolymers containing poly[poly(ethylene glycol) methyl ether acrylate] (PPEGMEA) backbone and poly[poly(ethylene glycol) ethyl ether methacrylate] (PPEGEEMA) side chains were synthesized by the combination of single electron transfer‐living radical polymerization (SET‐LRP) and atom transfer radical polymerization (ATRP). The backbone was first prepared by SET‐LRP of poly(ethylene glycol) methyl ether acrylate macromonomer using CuBr/tris(2‐(dimethylamino)ethyl)amine as catalytic system. The obtained comb copolymer was treated with lithium diisopropylamide and 2‐bromoisobutyryl bromide to give PPEGMEA‐Br macroinitiator. Finally, PPEGMEA‐g‐PPEGEEMA graft copolymers were synthesized by ATRP of poly(ethylene glycol) ethyl ether methacrylate macromonomer using PPEGMEA‐Br macroinitiator via the grafting‐from route. The molecular weights of both the backbone and the side chains were controllable and the molecular weight distributions kept narrow (M_w/M_n ≤ 1.20). This kind of double hydrophilic copolymer was found to be stimuli‐responsive to both temperature and ion (0.3 M Cl^? and SO). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 647–655, 2010     

Synthesis and characterization of particles consisting of a biodegradable poly(l-lactide) core and a functional hydrophilic shell

Block copolymers consisting of poly(solketal acrylate) and poly(l-lactide) were synthesized by combination of atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP) technique. Block copolymerization has been done by two different pathways, simultaneously and sequentially by using a dual functional initiator. Well defined block copolymers were obtained by sequential block copolymerization first implementing ROP of l-lactide followed by ATRP of solketal acrylate. After hydrolysis of the solketal acrylate segments hydrophilic poly(2,3-dihydroxypropyl acrylate) blocks were obtained. The amphiphilic block copolymers were able to self-organize in aqueous solution. Aggregation behavior was studied by means of dynamic and static light scattering. Time dependent enzymatic and hydrolytic degradation of the poly(l-lactide) cores was detected by dynamic light scattering. If enzymatic solutions were used the degradation process proceeded faster and was completed within 4000 min.     

Synthesis and characterizations of the four‐armed amphiphilic block copolymer S[poly(2,3‐dihydroxypropyl acrylate)‐block‐poly(methyl acrylate)]4

The polymers poly[(2,2‐dimethyl‐1,3‐dioxolane‐4yl) methyl acrylate] (PDMDMA) and four‐armed PDMDMA with well‐defined structures were prepared by the polymerization of (2,2‐dimethyl‐1,3‐dioxolane‐4yl) methyl acrylate (DMDMA) in the presence of an atom transfer radical polymerization (ATRP) initiator system. The successive hydrolyses of the polymers obtained produced the corresponding water‐soluble polymers poly(2,3‐dihydroxypropyl acrylate) (PDHPA) and four‐armed PDHPA. The controllable features for the ATRP of DMDMA were studied with kinetic measurements, gel permeation chromatography (GPC), and NMR data. With the macroinitiators PDMDMA–Br and four‐armed PDMDMA–Br in combination with CuBr and 2,2′‐bipyridine, the block polymerizations of methyl acrylate (MA) with PDMDMA were carried out to afford the AB diblock copolymer PDMDMA‐b‐MA and the four‐armed block copolymer S{poly[(2,2‐dimethyl‐1,3‐dioxolane‐4yl) methyl acrylate]‐block‐poly(methyl acrylate)}₄, respectively. The block copolymers were hydrolyzed in an acidic aqueous solution, and the amphiphilic diblock and four‐armed block copolymers poly(2,3‐dihydroxypropyl acrylate)‐block‐poly(methyl acrylate) were prepared successfully. The structures of these block copolymers were verified with NMR and GPC measurements. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3062–3072, 2001     

结构明确的梳形支化聚合物的合成与表征

通过活性聚苯乙烯(PS)和聚异戊二烯(PI)负离子与含1,1-二苯基乙烯(DPE)侧基的聚苯乙烯(PSe)的偶联反应合成了结构明确的每个重复单元含一条侧链的梳形支化聚合物,其中,PSe是通过Sc单体的原子转移自由基聚合(ATRP)和Wittig反应制得的.用IR1、H-NMR、GPC和SLS等测试方法对所得梳形支化聚合物进行了详细表征,讨论了活性负离子链与PSe的DPE基团的配比对接枝率的影响.结果表明,活性负离子链与DPE基团的偶联反应是高效的,可以通过调节活性负离子链与DPE基团的加料比来控制接枝率.另外,还讨论了PSe和活性负离子链的分子量对接枝率的影响.结果表明,在实验范围内当活性负离子链过量时可获得几乎定量的接枝率.