Recent advances in the preparation of glycopolymer bioconjugates

The significant progress made in understanding the role of carbohydrates and carbohydrates based therapeutics at molecular level has highlighted the importance of carbohydrate bioconjugates in the field of biology, chemistry and therapeutics. The glycosylation of biomolecules is a nature-inspired approach, to impart structural and functional properties to the biomolecules. The availability of facile techniques to synthesize well-defined glycopolymers of varying molecular weights, compositions and shape and their facile conjugation with biomolecules of interest have helped researchers in understanding many aspects of their biological functions at the molecular level. This review focuses on the development of glycopolymer-bioconjugates and provides a comprehensive overview of the present bioconjugation tools for their synthesis. The glycosylation of biomolecules is achieved by either pre or post-polymerization modification approaches. The review highlights the potential of living radical polymerization for the facile synthesis of glycopolymer bioconjugates using both pre and post-polymerization bioconjugation approaches, and without disrupting the native structure and functions of the biological molecules. Non-covalent carbohydrate–carbohydrate and carbohydrate–protein interactions play a significant role in many biological and pathological events. The non-covalent interactions of synthetic glycopolymers with biomolecules are also discussed in this review.     

丙烯腈可控/"活性"自由基聚合研究进展

可控/"活性"自由基聚合能有效控制聚合物的分子量及其分布,并且能调控其微观拓扑结构。聚丙烯腈及其共聚物具有良好的成纤成膜性能,是一类应用十分广泛的聚合物。本文综述了可控/"活性"自由基聚合法合成聚丙烯腈及其共聚物的研究现状与进展,从氮氧自由基法(NMP)、引发转移终止剂法(iniferter)、原子转移自由基聚合(ATRP)和可逆加成-断裂链转移(RAFT)聚合等方面对丙烯腈均聚物和共聚物的合成研究作了全面的总结,提出了存在的问题,并且对今后的研究方向作了展望。     

具有温敏特性的光学活性嵌段聚合物Click合成与表征

以末端含有炔基的2-十二烷基三硫代碳酸酯-2-甲基-丙酸丙炔醇酯(DMPE)为链转移剂(CTA),2,2′偶氮二异丁腈(AIBN)为引发剂,在N,N-二甲基甲酰胺(DMF)中,利用可逆加成-断裂链转移(RAFT)聚合反应制备了分子链末端带炔基的均聚物聚(N-丙烯酰基-L-缬氨酰甲胺)(PAVMA—C帒CH),然后与叠氮基封端的聚乙二醇单甲醚(MPEG-N3)进行"click"偶合反应,制备具有温敏特性的光学活性嵌段聚合物MPEG-b-PAVMA.利用1H-NMR和体积排阻色谱(SEC)等表征了所合成的均聚物和共聚物的结构和分子量分布.1H-NMR结果表明所合成的嵌段共聚物中MPEG和PAVMA链段的重复单元数分别为115和55.利用紫外分光光度计测试了均聚物及嵌段聚合物的温敏特性,结果表明均聚物和共聚物在水中的低临界溶解温度(LCST)分别为6.5℃和19.5℃.比旋光度测试结果表明,均聚物和共聚物具有旋光性,同时相比于单体,其旋光能力有所降低.圆二色谱法(CD)的测试结果显示,均聚物和嵌段共聚物在220nm和197nm附近分别有一个较弱的正Cotton效应峰和一个较强的负Cotton效应峰,并且在水溶液中主要以无规的二级构象结构存在。     

Effect of water addition on the coupling of homopolymers by click chemistry

Homopolymers bearing terminal azide and alkyne groups can be coupled via click chemistry to yield diblock copolymers. When performed in solvents that dissolved both homopolymers, the click reaction was found in this study to be inefficient, probably due to the embedding of the reactive end groups inside the random coils of the polymers. The efficiency was only slightly affected by the addition of a small amount of water into the reaction mixture. However, the reaction efficiency increased dramatically near the water volume fraction where one or both of the reacting polymers began to precipitate. Further increases in water content caused the polymer(s) to undergo macroscopic phase separation and the click reaction efficiency decreased once again. A possible explanation for the observed effect of water on the polymer coupling reaction is proposed. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

ATRP与点击化学结合制备树状星型聚合物

本文通过将ATRP技术和点击化学相结合的方法来制备树状星型聚合物[(PMMA)2PSt]4. 首先通过1,3-偶极环加成反应对ATRP的核预聚物进行端基修饰, 得到后继ATRP反应的大分子引发剂, 进而引发第二单体的ATRP聚合生成树状星型聚合物.     

One‐pot synthesis of well‐defined multiblock polymer: Combination of ATRP and RAFT polymerization involving cyclic trithiocarbonate

Multiblock polymers were prepared by combination of ATRP (CuBr/tris[(2‐pyridyl)methyl]amine) and RAFT polymerization involving cyclic trithiocarbonate (CTTC). In the combined polymerization system, the ATRP was introduced as constant radical source, CTTC underwent ring‐opening polymerization, and the incorporated trithiocarbonate moieties derived from CTTCs performed as RAFT agent. Through the integrated process, multiblock polymers containing predictable average block number together with controlled molecular weight of the blocks were prepared by one‐pot polymerization. The average block number of polymer was controlled by concentration ratio of CTTC to alkyl halide in ARTP, and the molecular weight of block were well regulated by concentration of CTTC and monomer conversion. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2425–2429, 2010     

Synthesis of mikto‐topology star polymer containing one cyclic arm

Well‐defined mikto‐topology star polystyrene composed of one cyclic arm and four linear arms was synthesized by a combination of atom transfer radical polymerization (ATRP) and Cu‐catalyzed azide‐alkyne cycloaddition (CuAAC) click reaction. First, the bromine‐alkyne α,ω‐linear polystyrenes containing four hydroxyl groups protected with acetone‐based ketal groups were synthesized by ATRP of styrene using a designed initiator. Then, the bromine end‐group was converted to the azide and the linear polystyrene was cyclized intra‐molecularly by the CuAAC reaction. The four hydroxyl groups were released by deprotection and then esterified with 2‐bromoisobutyryl bromide to produce a cyclic polymer bearing four ATRP initiating units. By subsequent ATRP of styrene to grow linear polymers with the cyclic polystyrene as a macroinitiator, the mikto‐topology star polymers were prepared. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Grafting polymer nanoshell onto the exterior surface of mesoporous silica nanoparticles via surface reversible addition-fragmentation chain transfer polymerization

Reversible addition-fragmentation chain transfer (RAFT) functionalities were anchored to the exterior surface of mesoporous silica nanoparticles (MSNs) without changing the mesoporous structure, RAFT polymerization of styrene was subsequently conducted to graft polystyrene (PSt) onto the exterior surface of MSNs, forming a novel core-shell nanostructure with a mesoporous core and a polymer nanoshell. Fourier transform infrared spectroscopy (FT-IR), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA) were used to characterize the produced mesoporous core-shell nanostructure, the results showed that the thickness of the nanoshell increased with the increasing time of polymerization.     

可逆加成-断裂链转移自由基聚合与点击化学相结合在制备特殊结构聚合物中的应用

可逆加成一断裂链转移(RAFT)聚合作为一种新型活性自由基聚合方法,由于其具有单体适用面广、聚合条件温和、不受聚合方法的限制等优点,已经成为聚合物分子设计的有效手段之一.点击化学(Click chaemistry)是近几年发展起来的一种快速合成的新方法,是指选用易得原料,通过可靠、高效而又具有选择性的化学反应来实现碳杂...     

Synthesis of PNIPAM polymer brushes on reduced graphene oxide based on click chemistry and RAFT polymerization

Preparation and characterization of poly(N‐isopropylacrylamide) (PNIPAM) polymer brushes on the surfaces of reduced graphene oxide (RGO) sheets based on click chemistry and reversible addition‐fragmentation chain transfer (RAFT) polymerization was reported. RGO sheets prepared by thermal reduction were modified by diazonium salt of propargyl p‐aminobenzoate, and alkyne‐functionalized RGO sheets were obtained. RAFT chain transfer agent (CTA) was grafted to the surfaces of RGO sheets by click reaction. PNIPAM on RGO sheets was prepared by RAFT polymerization. Fourier transform‐infrared spectroscopy, thermogravimetric analysis, X‐ray photoelectron spectroscopy, and transmission electron microscopy (TEM) results all demonstrated that RAFT CTA and PNIPAM were successfully produced on the surfaces of RGO sheets. Nanosized PNIPAM domains on RGO sheets were observed on TEM. Micro‐DSC result indicated that in aqueous solution PNIPAM on RGO sheets presented a lower critical solution temperature at 33.2 °C. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of oligo(ethylene glycol) methacrylate polymer brushes

Here we report a study into controlling the polymerization of mono-hydroxy and mono-methoxy terminated oligo(ethylene glycol) methacrylates (HOEGMA and MeOEGMA, respectively) from functionalised, planar surfaces via atom transfer radical polymerization (ATRP). The effects of initiator structure, initiator density, temperature, and monomer ratios have been investigated for these polymerizations. The polymer brushes grown in this way were found to convey protein resistance to the underlying inorganic substrates, prone to facile protein adsorption in their native state.     

A novel amphotropic polymer based on cellulose nanocrystals grafted with azo polymers

A novel amphotropic polymer which could exhibit liquid-crystalline behavior both in the solvent and in the heating process was synthesized through azo polymers grafting from cellulose nanocrystals (CNCs). The CNCs, prepared by acid hydrolysis of filter paper, were characterized by Atomic Force Microscopy (AFM). Poly{6-[4-(4-methoxyphenylazo)phenoxy] hexyl methacrylate}(PMMAZO), which was a liquid-crystalline polymers (LCP), was successfully to graft from CNC via Atom transfer radical polymerization (ATRP). The structure and thermal properties of the PMMAZO-grafted CNC were investigated using Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analyses (TGA). Its phase structures and transitions were studied by differential scanning calorimetry (DSC) and polarized optical microscopy (POM). The experimental results showed that the PMMAZO-grafted CNC exhibited both types of liquid crystal formation, thermotropic and lyotropic.     

Heterograft brush copolymers via romp and triple click reaction strategies involving CuAAC,diels–alder,and nitroxide radical coupling reactions

In this study, an equimolar mixture of oxanorbornenyl‐anthracene (ONB‐anthracene), oxanorbornenyl‐bromide (ONB‐Br), and oxanorbornenyl tosylate (ONB‐OTs) was polymerized via ring opening metathesis polymerization using the first generation Grubbs' catalyst in CH₂Cl₂ at room temperature to form poly(ONB‐anthracene‐co‐ONB‐Br‐co‐ONB‐OTs)₁₀ copolymer as a main backbone. Next, this main backbone was sequentially clicked with a furan protected maleimide‐terminated poly(methyl methacrylate), 2,2,6,6‐tetramethyl‐1‐piperidinyloxy‐terminated poly(ethylene glycol), and alkyne‐terminated poly(ε‐caprolactone) (PCL₂₀‐alkyne) via Diels–Alder, nitroxide radical coupling, and copper‐catalyzed azide‐alkyne cycloaddition, respectively, to yield a poly(ONB‐g‐PMMA‐co‐ONB‐g‐PEG‐co‐ONB‐g‐PCL)₁₀ heterograft brush copolymer © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Synthesis and characterizations of 1,2,3-triazole containing polymers via reversible addition-fragmentation chain transfer (RAFT) polymerization

A novel monomer containing triazole and naphthalene ring, 2-(1-naphthalen-1-ylmethyl-1H-[1,2,3]triazol-4-yl)-ethyl methacrylate (NTEMA), was designed and synthesized via “click” chemistry method. The RAFT polymerization of NTEMA was successfully carried out using 2-cyanoprop-2-yl dithiobenzoate (CPDB) as a RAFT agent, 2,2′-azobisisobutyronitrile (AIBN) as an initiator in tetrahydrofuran (THF) solution. The results showed that the polymerizations exhibited “living”/controlled characteristics. The obtained poly(2-(1-naphthalen-1-ylmethyl-1H-[1,2,3]triazol-4-yl)-ethyl methacrylate) homopolymers, PNTEMAs, were further coordinated with samarium ion to prepare rare earth containing polymers (PNTEMA-Sm(III) complexes) which were characterized by FT-IR, DSC and ICP-AES. The characterization data confirmed that triazole in side chain of the polymer could coordinate with Sm(III). The fluorescence property of the polymers and polymer Sm(III) complexes were investigated in solution and in film.     

Orthogonal multiple click reactions in synthetic polymer chemistry

This review highlights the concept of multiple click reaction strategy which is utilized for design and synthesis of well‐defined complex macromolecular structures as well as multifunctionalization of well‐defined polymers. This review examines the click combinations mainly from double to quadruple and additionally from the most frequently used to the least. The present review may also be regarded as an update for recent reviews dealing with specifically double and triple click reaction combinations in synthetic polymer chemistry. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3147–3165     

Polymer end group modifications and polymer conjugations via “click” chemistry employing microreactor technology

This study presents the development of microreactor protocols for the successful continuous flow end group modification of atom transfer radical polymerization precursor polymers into azide end‐capped materials and the subsequent copper‐catalyzed azide alkyne click reactions with alkyne polymers, in flow. By using a microreactor, the reaction speed of the azidation of poly(butyl acrylate), poly(methyl acrylate), and polystyrene can be accelerated from hours to seconds and full end group conversion is obtained. Subsequently, copper‐catalyzed click reactions are executed in a flow reactor at 80 °C. Good coupling efficiencies are observed and various block copolymer combinations are prepared. Furthermore, the flow reaction can be carried out in only 40 min, while a batch procedure takes several hours to reach completion. The results indicate that the use of a continuous flow reactor for end group modifications as well as click reactions has clear benefits towards the development and improvement of well‐defined polymer materials. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1263–1274     

Synthesis of a novel restricted access chiral stationary phase based on atom transfer radical polymerization and click chemistry for the analysis of chiral drugs in biological matrices

A novel chiral restricted access material was synthesized via a combination of atom transfer radical polymerization (ATRP) and click chemistry. Poly(2-methyl-3-butyn-2-ol methacrylate) (pMBMA) was grafted onto porous silica gel by a surface-initiated ATRP in order to synthesize an inner layer for β-cyclodextrin (β-CD) immobilization. The azide-modified β-CD was bound to pMBMA by click chemistry. The results demonstrate that click chemistry provides an effective route for the immobilization of β-CD for chiral discrimination. A second ATRP reaction was then used to graft external poly(glycidyl methacrylate) (pGMA) layer onto the silica gel. The external hydrophilic layer was subsequently created by hydrolysis of the epoxy groups of the pGMA. This bi-layer grafted material exhibited both enantioseparation and protein exclusion. It can be used for the efficient separation of chiral compounds in biological samples with direct injection into an HPLC system.     

Comparison of surface confined ATRP and SET‐LRP syntheses for a series of amino (meth)acrylate polymer brushes on silicon substrates

A series of poly(amino (meth)acrylate) brushes, poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA), poly(2‐(diethylamino)ethyl methacrylate) (PDEAEMA), poly(2‐(dimethylamino)ethyl acrylate) (PDMAEA), poly(2‐(tert‐butylamino)ethyl methacrylate) (PTBAEMA), has been synthesized via surface‐confined controlled/living radical polymerizations using surface‐confined initiator from silane self‐assembled monolayers (SAMs) on silicon (Si) wafer substrates. Chemical methods and efficacies for two types of living radical polymerization, atom transfer radical (ATRP) and single electron transfer (SET‐LRP), are described and contrasted for the surface confined polymerization of poly(amino (meth)acrylate)s. Effects of solvent, catalyst/ligand system, and temperature on polymerization success were examined. Chemical compositions after each reaction step were characterized with FTIR spectroscopy, contact angle goniometry, and X‐ray photoelectron spectroscopy while the SAM and polymer brush thicknesses were measured with spectroscopic ellipsometry. For the first time, this study demonstrates successful surface‐confined polymerization of a series of poly(amine (meth)acrylate) brushes from Si‐SAM substrates using a copper metal electron donor catalyst. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 6552–6560, 2009