Backfilling‐Free Strategy for Biopatterning on Intrinsically Dual‐Functionalized Poly[2‐Aminoethyl Methacrylate‐co‐Oligo(Ethylene Glycol) Methacrylate] Films

We demonstrated protein and cellular patterning with a soft lithography technique using poly[2‐aminoethyl methacrylate‐co‐oligo(ethylene glycol) methacrylate] films on gold surfaces without employing a backfilling process. The backfilling process plays an important role in successfully generating biopatterns; however, it has potential disadvantages in several interesting research and technical applications. To overcome the issue, a copolymer system having highly reactive functional groups and bioinert properties was introduced through a surface‐initiated controlled radical polymerization with 2‐aminoethyl methacrylate hydrochloride (AMA) and oligo(ethylene glycol) methacrylate (OEGMA). The prepared poly(AMA‐co‐OEGMA) film was fully characterized, and among the films having different thicknesses, the 35 nm‐thick biotinylated, poly(AMA‐co‐OEGMA) film exhibited an optimum performance, such as the lowest nonspecific adsorption and the highest specific binding capability toward proteins.     

Well‐defined succinylated chitosan‐O‐poly(oligo(ethylene glycol)methacrylate) for pH‐reversible shielding of cationic nanocarriers

A novel type of well‐defined graft copolymer, succinylated chitosan‐O‐poly(oligo(ethylene glycol)methacrylate) (SC‐POEGMA), was developed for pH‐reversible poly(ethylene glyocol) (PEG) shielding of cationic nanocarriers. Chitosan‐O‐POEGMA (CS‐POEGMA) was first synthesized via single electron transfer‐living radical polymerization of oligo(ethylene glyol) methacrylate (OEGMA) using O‐brominated chitosan (CS‐Br) as a macromolecular initiator and Cu(I)Br/1,1,4,7,10,10‐hexamethyltriethylenetetramine as a catalyst. The subsequent succinylation of the chitosan backbone gave the titled copolymers. The content of POEGMA in CS‐POEGMA could be widely modulated by varying the degree of bromination and feed ratio of OEGMA to CS‐Br, without compromising the amino density of chitosan backbone. The hierarchical assembly between SC‐POEGMA and trimethylated chitosan‐O‐poly(ε‐caprolactone) (TMC‐PCL) micelles was further studied. At pH 7.4, the stoichiometric interactions between SC and TMC segments to form polyampholyte–polyelectrolyte complexes led to the formation of PEG‐shielded micelles. The hierarchially assembled micelles could be disassembled into the pristine TMC‐PCL micelles, when the medium pH was below a certain pH (pH_φ). By varying the degree of succinylation of SC‐POEGMA, the pH_φ value could be facilely modulated from 6.5 to 3.5 to meet the needs for specific biomedical applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Surface‐Initiated Atom Transfer Radical Polymerization of Oligo(ethylene glycol) Methacrylate: Effect of Solvent on Graft Density

Summary: Oligo(ethylene glycol) methacrylate (OEGMA) was grafted from silicon wafer surfaces by surface‐initiated atom transfer radical polymerization (ATRP) with Cu^I Br/2,2′‐bipyridine (bpy) as a catalyst and various water/alcohol mixtures as solvents. The ellipsometric thickness of the poly(OEGMA) layer on the surface increased linearly with monomer conversion in solution. High graft densities were achieved in alcohols. The graft density of poly(OEGMA) in methanol was found to be 0.26 chains · nm⁻², which is 50% higher than that in water/methanol (30:70, v/v). The differences in graft density were correlated to the conformation of tethered poly(OEGMA) chains. Large poly(OEGMA) coils on the surface in the presence of water limited the access of initiation sites to the catalyst complex and monomer molecules.

Development of poly(OEGMA) layer thickness on the silicon surface vs monomer conversion.     

Synthesis,characterization, and temperature‐responsive behaviors of novel hybrid amphiphilic block copolymers containing polyhedral oligomeric silsesquioxane

Organic/inorganic hybrid amphiphilic block copolymer poly(methacrylate isobutyl POSS)‐b‐poly(N‐isopropylacrylamide‐co‐oligo(ethylene glycol) methyl ether methacrylate) (PMAPOSS‐b‐P(NIPAM‐co‐OEGMA)) was synthesized via reversible addition–fragmentation chain transfer polymerization. The self‐assembly behavior of this block copolymer in aqueous solution was investigated by dynamic light scattering (DLS) and transmission electron microscopy. The results indicate that the novel block copolymer can self‐assemble into spherical micelles with PMAPOSS segment as the hydrophobic part and P(NIPAM‐co‐OEGMA) segment as the hydrophilic part. The temperature‐responsive characteristics of the assemblies were tested by UV–Vis spectra and DLS. Some factors such as the concentration, molecular weight, and copolymer generation that may affect the cloud point were studied systematically. The results reveal that this copolymer exhibits a sharp and intensive lower critical solution temperature (LCST). The essentially predetermined LCST can be conveniently achieved by adjusting the content of NIPAM or OEGMA domain. In addition, these novel hybrid micelles can undergo an association/disassociation cycle with the heating and cooling of solution and the degree of reversibility displaying a tremendous concentration dependence, as a novel organic/inorganic hybrid material with distinctive virtues can be potentially used in biological and medical fields, especially in drug nanocarriers for targeted therapy. Copyright © 2014 John Wiley & Sons, Ltd.     

Poly(ε‐caprolactone)‐Based Organogels and Hydrogels with Poly(ethylene glycol) Cross‐Linkings

Summary: The reaction of triphosgene with poly(ethylene glycol) yielded poly(ethylene glycol) dichloroformate. This difunctional cross‐linker was allowed to react with poly(ε‐caprolactone) bearing carbanionic sites obtained by activation with lithium diisopropylamide. The reaction resulted in the cross‐linking of poly(ε‐caprolactone) chains by poly(ethylene glycol) segments, giving copolymer networks that gel in both organic and aqueous media.

Schematic of the PCL‐g‐PEG copolymers synthesized here.     

Photo‐Degradable,Protein–Polyelectrolyte Complex‐Coated,Mesoporous Silica Nanoparticles for Controlled Co‐Release of Protein and Model Drugs

The fabrication of photo‐degradable, protein–polyelectrolyte complex (PPC)‐coated, mesoporous silica nanoparticles (MSNs) and their controlled co‐release of protein and model drugs is reported. Random copolymers composed of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), and a photolabile o‐nitrobenzyl‐containing monomer, 5‐(2′‐(dimethylamino)ethoxy)‐2‐nitrobenzyl methacrylate (DENBMA), are first anchored onto the MSNs and then quaternary aminated, to obtain positively charged P(OEGMA‐co‐TENBMA) which exhibits photo‐induced charge conversion characteristics. PPCs consisting of P(OEGMA‐co‐TENBMA) and the protein bovine serum albumin (BSA) are utilized as capping agents for the nanopores of the MSNs. Upon UV irradiation, charge conversion of P(OEGMA‐co‐TENBMA) can lead to the disruption of PPCs on MSNs and co‐release of BSA and rhodamine B by electrostatic repulsion.     

Synthesis and micellization of thermoresponsive galactose‐based diblock copolymers

Thermoresponsive double hydrophilic diblock copolymers poly(2‐(2′‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol) methacrylate)‐b‐poly(6‐O‐methacryloyl‐D ‐galactopyranose) (P(MEO₂MA‐co‐OEGMA)‐b‐PMAGP) with various compositions and molecular weights were obtained by deprotection of amphiphilic diblock copolymers P(MEO₂MA‐co‐OEGMA)‐b‐poly(6‐O‐methacryloyl‐1,2:3,4‐di‐O‐isopropylidene‐D ‐galactopyranose) (P(MEO₂MA‐co‐OEGMA)‐b‐PMAlpGP), which were prepared via reversible addition‐fragmentation chain transfer (RAFT) polymerization using P(MEO₂MA‐co‐OEGMA) as macro‐RAFT agent. Dynamic light scattering and UV–vis studies showed that the micelles self‐assembled from P(MEO₂MA‐co‐OEGMA)‐b‐PMAlpGP were thermoresponsive. A hydrophobic dye Nile Red could be encapsulated by block copolymers P(MEO₂MA‐co‐OEGMA)‐b‐PMAGP upon micellization and released upon dissociation of the formed micelles under different temperatures. The galactose functional groups in the PMAGP block have specific interaction with HepG2 cells, and P(MEO₂MA‐co‐OEGMA)‐b‐PMAGP has potential applications in hepatoma‐targeting drug delivery and biodetection. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Novel synthesis of biodegradable amphiphilic linear and star block copolymers based on poly(ε‐caprolactone) and poly(ethylene glycol)

Biodegradable, amphiphilic, diblock poly(ε‐caprolactone)‐block‐poly(ethylene glycol) (PCL‐b‐PEG), triblock poly(ε‐caprolactone)‐block‐poly(ethylene glycol)‐block‐poly(ε‐caprolactone) (PCL‐b‐PEG‐b‐PCL), and star shaped copolymers were synthesized by ring opening polymerization of ε‐caprolactone in the presence of poly(ethylene glycol) methyl ether or poly(ethylene glycol) or star poly(ethylene glycol) and potassium hexamethyldisilazide as a catalyst. Polymerizations were carried out in toluene at room temperature to yield monomodal polymers of controlled molecular weight. The chemical structure of the copolymers was investigated by ¹H and ¹³C NMR. The formation of block copolymers was confirmed by ¹³C NMR and DSC investigations. The effects of copolymer composition and molecular structure on the physical properties were investigated by GPC and DSC. For the same PCL chain length, the materials obtained in the case of linear copolymers are viscous whereas in the case of star copolymer solid materials are obtained with low T_g and T_m temperatures. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3975–3985, 2007     

Synthesis of Thermo‐Responsive Polymers With Both Tunable UCST and LCST

New water‐soluble block copolymers of 2‐(2‐methoxyethoxy)ethyl methacrylate (MEO₂MA), oligo(ethylene glycol) methacrylate (OEGMA), and N‐(3‐(dimethylamino) propyl) methacrylamide (DMAPMA) (poly(OEGMA‐co‐MEO₂MA)‐b‐poly(DMAPMA)) were prepared via sequential reversible addition‐fragmentation chain transfer (RAFT) polymerization. Selective quaternization of poly(DMAPMA) block gives poly(OEGMA‐co‐MEO₂MA)‐b‐poly((3‐[N‐(3‐methacrylamidopropyl)‐N,N‐dimethyl]ammoniopropane sulfonate)‐co‐N‐(3‐(dimethylamino) propyl) methacrylamide), such block copolymer exhibits double thermo‐responsive behavior in water, poly(MEO₂MA‐co‐OEGMA) block shows a lower critical solution temperature (LCST), and poly((3‐[N‐(3‐methacrylamidopropyl)‐N,N‐dimethyl]ammoniopropane sulfonate)‐co‐N‐(3‐(dimethylamino) propyl) methacrylamide) block shows a upper critical solution temperature (UCST). Both of LCST and UCST can be controlled: LCST could be tuned by the fraction of OEGMA units in poly(OEGMA‐co‐MEO₂MA), and UCST was found to be dependent on the degree of quaternization (DQ).

     

Liquid–liquid phase separation in aqueous solutions of poly(ethylene glycol) methacrylate homopolymers

Here, the liquid–liquid phase separation (LLPS) in aqueous solutions containing poly(ethylene glycol) (PEG) methacrylate homopolymers is reported for the first time. In this study, the thermoresponse of concentrated solutions of DEGMA₆₀ (two ethylene glycol, EG, groups) TEGMA₇₁ (three EG groups), OEGMA300_x (4.5 in average EG groups) of varying molar masses (MM), and OEGMA500₂₈ (nine in average EG groups) is discussed. Interestingly, the temperature of LLPS (T_LLPS) is controlled by the length of the PEG side chain, the MM of the OEGMA300_x and the polymer concentration. More specifically, the transition temperature decreases with: (i) Decrease in the length of the PEG side chain, (ii) increase in MM of the OEGMA300_x, and increase in concentration. In addition, LLPS is also observed in mixtures of OEGMA300_x with Pluronic® F127. In conclusion, these systems present a thermally induced LLPS, with the transition temperature being finely tuned to room temperature when DEGMA is used. These systems find potential use in numerous applications, varying from purification to “water-in-water” emulsions.     

Synthesis of poly(ethylene glycol)/polypeptide/poly(D,L‐lactide) copolymers and their nanoparticles

Core‐shell structured nanoparticles of poly(ethylene glycol) (PEG)/polypeptide/poly(D ,L ‐lactide) (PLA) copolymers were prepared and their properties were investigated. The copolymers had a poly(L ‐serine) or poly(L ‐phenylalanine) block as a linker between a hydrophilic PEG and a hydrophobic PLA unit. They formed core‐shell structured nanoparticles, where the polypeptide block resided at the interface between a hydrophilic PEG shell and a hydrophobic PLA core. In the synthesis, poly(ethylene glycol)‐b‐poly(L ‐serine) (PEG‐PSER) was prepared by ring opening polymerization of N‐carboxyanhydride of O‐(tert‐butyl)‐L ‐serine and subsequent removal of tert‐butyl groups. Poly(ethylene glycol)‐b‐poly(L ‐phenylalanine) (PEG‐PPA) was obtained by ring opening polymerization of N‐carboxyanhydride of L ‐phenylalanine. Methoxy‐poly(ethylene glycol)‐amine with a MW of 5000 was used as an initiator for both polymerizations. The polymerization of D ,L ‐lactide by initiation with PEG‐PSER and PEG‐PPA produced a comb‐like copolymer, poly(ethylene glycol)‐b‐[poly(L ‐serine)‐g‐poly(D ,L ‐lactide)] (PEG‐PSER‐PLA) and a linear copolymer, poly(ethylene glycol)‐b‐poly(L ‐phenylalanine)‐b‐poly(D ,L ‐lactide) (PEG‐PPA‐PLA), respectively. The nanoparticles obtained from PEG‐PPA‐PLA showed a negative zeta potential value of ?16.6 mV, while those of PEG‐PSER‐PLA exhibited a positive value of about 19.3 mV. In pH 7.0 phosphate buffer solution at 36 °C, the nanoparticles of PEG/polypeptide/PLA copolymers showed much better stability than those of a linear PEG‐PLA copolymer having a comparable molecular weight. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Atom transfer radical polymerization directly from poly(vinylidene fluoride): Surface and antifouling properties

The direct preparation of grafting polymer brushes from commercial poly (vinylidene fluoride) (PVDF) films with surface‐initiated atom transfer radical polymerization (ATRP) is demonstrated. The direct initiation of the secondary fluorinated site of PVDF facilitated grafting of the hydrophilic monomers from the PVDF surface. Homopolymer brushes of 2‐(N,N‐dimethylamino)ethyl methacrylate (DMAEMA) and poly (ethylene glycol) monomethacrylate (PEGMA) were prepared by ATRP from the PVDF surface. The chemical composition and surface topography of the graft‐functionalized PVDF surfaces were characterized by X‐ray photoelectron spectroscopy, attenuated total reflectance/Fourier transform infrared spectroscopy, and atomic force microscopy. A kinetic study revealed a linear increase in the graft concentration of poly[2‐(N,N‐dimethylamino)ethyl methacrylate] (PDMAEMA) and poly[poly(ethylene glycol) monomethacrylate] (PPEGMA) with the reaction time, indicating that the chain growth from the surface was consistent with a controlled or living process. The living chain ends were used as macroinitiators for the synthesis of diblock copolymer brushes. The water contact angles on PVDF films were reduced by the surface grafting of DMAEMA and PEGMA. Protein adsorption experiments revealed a substantial antifouling property of PPEGMA‐grafted PVDF films and PDMAEMA‐grafted PVDF films in comparison with the pristine PVDF surface. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3434–3443, 2006     

Synthesis of double hydrophilic graft copolymer containing poly(ethylene glycol) and poly(methacrylic acid) side chains via successive ATRP

A well‐defined double hydrophilic graft copolymer, with polyacrylate as backbone, hydrophilic poly(ethylene glycol) and poly(methacrylic acid) as side chains, was synthesized via successive atom transfer radical polymerization followed by the selective hydrolysis of poly(methoxymethyl methacrylate) side chains. The grafting‐through strategy was first used to prepare poly[poly(ethylene glycol) methyl ether acrylate] comb copolymer. The obtained comb copolymer was transformed into macroinitiator by reacting with lithium diisopropylamine and 2‐bromopropionyl chloride. Afterwards, grafting‐from route was employed for the synthesis of poly[poly(ethylene glycol) methyl ether acrylate]‐g‐poly(methoxymethyl methacrylate) amphiphilic graft copolymer. The molecular weight distribution of this amphiphilic graft copolymer was narrow. Poly(methoxymethyl methacrylate) side chains were connected to polyacrylate backbone through stable C? C bonds instead of ester connections. The final product, poly[poly(ethylene glycol) methyl ether acrylate]‐g‐poly(methacrylate acid), was obtained by selective hydrolysis of poly(methoxymethyl methacrylate) side chains under mild conditions without affecting the polyacrylate backbone. This double hydrophilic graft copolymer was found be stimuli‐responsive to pH and ionic strength. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4056–4069, 2008     

Synthesis,self‐assembly,fluorescence, and thermosensitive properties of star‐shaped amphiphilic copolymers with porphyrin core

Star‐shaped amphiphilic poly(ε‐caprolactone)‐block‐poly(oligo(ethylene glycol) methyl ether methacrylate) with porphyrin core (SPPCL‐b‐POEGMA) was synthesized by combination of ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Star‐shaped PCL with porphyrin core (SPPCL) was prepared by bulk polymerization of ε‐caprolactone (CL) with tetrahydroxyethyl‐terminated porphyrin initiator and tin 2‐ethylexanote (Sn(Oct)₂) catalyst. SPPCL was converted into SPPCLBr macroinitiator with 2‐bromoisobutyryl bromide. Star‐shaped SPPCL‐b‐POEGMA was obtained via ATRP of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). SPPCL‐b‐POEGMA can easily self‐assemble into micelles in aqueous solution via dialysis method. The formation of micellar aggregates were confirmed by critical micelle formation concentration, dynamic light scattering, and transmission electron microscopy. The micelles also exhibit property of temperature‐induced drug release and the lower critical solution temperature (LCST) was 60.6 °C. Furthermore, SPPCL‐b‐POEGMA micelles can reversibly swell and shrink in response to external temperature. In addition, SPPCL‐b‐POEGMA can present obvious fluorescence. Finally, the controlled drug release of copolymer micelles can be achieved by the change of temperatures. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Methoxy poly(ethylene glycol)‐b‐poly(octadecanoic anhydride)‐b‐methoxy poly(ethylene glycol) amphiphilic triblock copolymer nanoparticles as delivery vehicles for paclitaxel

A series of amphiphilic triblock copolymers, methoxy poly(ethylene glycol)‐b‐poly(octadecanoic anhydride)‐b‐methoxy poly(ethylene glycol) (mPEG‐b‐POA‐b‐mPEG), were prepared via melt polycondensation of methoxy poly(ethylene glycol) (mPEG) and poly(octadecanoic anhydride) (POA). mPEG‐b‐POA‐b‐mPEG were characterized by FTIR, ¹H‐NMR, GPC, DSC, and XRD. Drug‐loaded mPEG‐b‐POA‐b‐mPEG nanoparticles (NPs) with spherical morphology and narrow size polydispersity index were prepared by nanoprecipitation technique with paclitaxel as the model drug. In vitro release behaviors of drug‐loaded NPs present that the biphasic process and the release mechanism of each phase are zero order drug releases. According to this study, mPEG‐b‐POA‐b‐mPEG NPs could serve as suitable delivery agents for paclitaxel and other hydrophobic drugs. Copyright © 2009 John Wiley & Sons, Ltd.     

Effect of poly(ethylene glycol) on the dielectric properties of poly(vinylidene fluoride)/BiFeO<Subscript>3</Subscript>/poly(ethylene glycol) composite films for electronic applications

In the present work a series of poly(vinylidene fluoride)/BiFeO₃/poly(ethylene glycol) composite films were prepared by solvent casting method with poly(vinylidene fluoride) as polymer matrix, bismuth ferrite as ceramic filler and poly(ethylene glycol) as binding agent as well as enhancer. The structural analysis of the composite films by X-ray diffraction confirms that the composites have a distorted rhombohedral structure. The micro-structural analysis shows that the use of poly(ethylene glycol)in the composite films enhances the homogeneity as well as compatibility of BiFeO₃ particles within the poly(vinylidene fluoride) matrix. The dielectric and electrical study done by impedance analyzer reveals that with an increase in poly(ethylene glycol) concentration, there is a subsequent increase in dielectric constant as well as AC electrical conductivity. Finally, the ferroelectric behavior of the composite confirms that the ferroelectric properties of the composites are enhanced by the addition of BiFeO₃ with an increase in poly(ethylene glycol) concentrations. These preliminary results give an idea for possible applications of this type of composites in the field of electronic applications.     

Synthesis,Self‐Assembly,and Multi‐Stimuli Responses of a Supramolecular Block Copolymer

A supramolecular block copolymer is prepared by the molecular recognition of nucleobases between poly(2‐(2‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol) methacrylate)‐SS‐poly(ε‐caprolactone)‐adenine (P(MEO₂MA‐co‐OEGMA)‐SS‐PCL‐A) and uracil‐terminated poly(ethylene glycol) (PEG‐U). Because the block copolymer is linked by the combination of covalent (disulfide bond) and noncovalent (A U) bonds, it not only has similar properties to conventional covalently linked block copolymers but also possesses a dynamic and tunable nature. The copolymer can self‐assemble into micelles with a PCL core and P(MEO₂MA‐co‐OEGMA)/PEG shell. The size and morphologies of the micelles/aggregates can be adjusted by altering the temperature, pH, salt concentration, or adding dithiothreitol (DTT) to the solution. The controlled release of Nile red is achieved at different environmental conditions.

     

Temperature‐sensitive poly(N‐isopropylacrylamide)‐grafted surfaces modulate blood platelet interactions

Interactions between a temperature‐responsive poly(N‐isopropylacrylamide)‐grafted surface and blood platelets have been analyzed with computerized image analysis. Platelet behavior on this surface is dramatically dependent upon temperature in contrast to that on poly(ethylene glycol) (PEG)‐grafted surfaces or polystyrene. The poly(N‐isopropylacrylamide)‐grafted surface interacts with platelets similarly as the poly(ethylene glycol)‐rafted surface at 18°C. At 37°C, platelets readily adhere onto the poly(N‐isopropylacrylamide)‐grafted surface similarly as to that of polystyrene.     

Ion conductivity studies of blends of poly(methyl methacrylate)-g-poly(ethylene glycol) and poly(ethylene glycol) complexed with LiCF3 SO3

Polymer electrolytes which are adhesive, transparent, and stable to atmospheric moisture have been prepared by blending poly(methyl methacrylate)-g-poly(ethylene glycol) with poly(ethylene glycol)/LiCF₃ SO₃ complexes. The maximum ionic conductivities at room temperature were measured to be in the range of 10⁻⁴ to 10⁻⁵ s cm⁻¹. The clarity of the sample was improved as the graft degree increased for all the samples studied. The graft degree of poly(methyl methacrylate)-g-poly(ethylene glycol) was found to be important for the compatibility between the poly(methyl methacrylate) segments in poly(methyl methacrylate)-g-poly(ethylene glycol) and the added poly(ethylene glycol), and consequently, for the ion conductivity of the polymer electrolyte. These properties make them promising candidates for polymer electrolytes in electrochromic devices. © 1996 John Wiley & Sons, Inc.     

Rapid metal‐free macromolecular coupling via In Situ nitrile oxide‐activated alkene cycloaddition

Nitrile oxide 1,3 dipolar cycloaddition is a simple and powerful coupling methodology. However, the self‐dimerization of nitrile oxides has prevented the widespread use of this strategy for macromolecular coupling. By combining an in situ nitrile oxide generation with a highly reactive activated dipolarophile, we have overcome these obstacles and present a metal‐free macromolecular coupling strategy for the modular synthesis of several ABA triblock copolymers. Nitrile oxides were generated in situ from chloroxime terminated poly(dimethylsiloxane) B‐blocks and coupled with several distinct hydrophilic (poly(2‐methyloxazoline) and poly(ethylene glycol)), and poly(N‐isopropylacrylamide) or hydrophobic (poly(l ‐lactide) A‐blocks terminated in activated dipolarophiles in a rapid fashion with high yield. This methodology overcomes many drawbacks of previously reported metal‐free methods due to its rapid kinetics, versatility, scalability, and ease of introduction of necessary functionality. Nitrile oxide cycloaddition should find use as an attractive macromolecular coupling strategy for the synthesis of biocompatible polymeric nanostructures. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3134–3141