Bis‐hydrophilic and functional triblock terpolymers based on polyethers: Synthesis and self‐assembly in solution

A well‐defined triblock terpolymer, poly(ethylene glycol)‐block‐poly(allyl glycidyl ether)‐block‐poly(tert‐butyl glycidyl ether) (PEG‐b‐PAGE‐b‐Pt‐BGE), with a narrow molar mass distribution has been synthesized by sequential living anionic ring‐opening polymerization. Afterward, the PAGE block was modified via thiol‐ene chemistry and different sugar moieties or cysteine as a model compound for peptides could be covalently attached to the polymer backbone. The solution self‐assembly of the obtained bis‐hydrophilic triblock terpolymers in aqueous media has been studied in detail by turbidimetry, dynamic light scattering, and transmission electron microscopy (TEM and cryo‐TEM). © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Multiblock copolymers of ε–caprolactone and ethylene glycol containing periodic side‐chain carboxyl groups: Synthesis,characterization, and nanoparticle preparation

Multiblock copolymers containing periodically spaced side‐chain carboxyl groups were obtained by a two‐step synthesis involving the preparation of ABA triblock prepolymers of ε‐caprolactone (A blocks) and ethylene glycol (B block) followed by chain extension to ABA_n multiblock copolymers by reaction with pyromellitic dianhydride (PMDA). NMR analysis demonstrated the incorporation of PMDA in polymer chain and revealed the possibility of PMDA units to exist in two isomers, cisoid and transoid forms. Chain extension resulted in the incorporation of free carboxylic groups in polymer backbone and in an almost twofold increase of molecular weight. Thermal analysis indicated that the presence of PMDA residues interferes with the formation of crystalline phases by the chain‐extended polymers. The polymers were found to slowly degrade in buffer solution at 37 °C. Further, the carboxylated polymers can be processed into nanoparticulates by nanoprecipitation. Depending on the selected organic solvent, the particulate was constituted by either a monodispersed nanoparticles with average size of 150 nm or a bimodal distribution centered at about 100 nm and 7 μm. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3800–3809     

Facile synthesis of dopa‐functional polycarbonates via thiol‐Ene‐coupling chemistry towards self‐healing gels

Since extraction of the naturally occurring mussel‐foot proteins is expensive and time‐consuming, routes towards synthetic analogues are continuously being explored. Often, these methods involve several protection and deprotection steps, making the synthesis of synthetic analogues time‐consuming and expensive as well. Herein, we show that UV‐initiated thiol‐ene coupling between a thiol‐functional dopamine derivative and an allyl‐functional aliphatic polycarbonate can be used as a fast and facile route to dopa‐functional materials. Different thiol‐to‐allyl ratios and irradiation protocols were used and it was found that nearly 50% of the allyl groups could be functionalized with dopa within short reaction times, without the need of protecting the catechol. It is also demonstrated herein that the dopa‐functional polymers can be used to form self‐healing gels through complexation with Fe³⁺ ions at increased pH. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2370–2378     

PEG‐Amine‐Initiated Polymerization of Sarcosine N‐Thiocarboxyanhydrides Toward Novel Double‐Hydrophilic PEG‐b‐Polysarcosine Diblock Copolymers

Amino acid N‐thiocarboxyanhydride (NTA), the thioanalog of N‐carboxyanhydride (NCA), is much more stable than NCA against moisture and heat. The convenient monomer synthesis without rigorous anhydrous requirements makes the ring‐opening polymerization of NTA a competitive alternative to prepare polypeptoid‐containing materials with potential of large‐scale production. Polysarcosines (PSars) with high yields (>90%) and low polydispersities (<1.2) are synthesized from sarcosine N‐thiocarboxyanhydride (Sar‐NTA) at 60 °C initiated by primary amines including poly(ethylene glycol) amine (PEG–NH₂). The lengths of PSar segments are controlled by various feed ratios of Sar‐NTA to initiator. PEG‐b‐PSar products, a class of novel double‐hydrophilic diblock copolymers, are effective in stabilizing oil‐in‐water emulsions at nano‐ and microscale, which demonstrates promising encapsulation applications in food, cosmetics, and drug delivery. Due to the different solubility of PEG and PSar blocks, PEG‐b‐PSar copolymers form micelles in organic solvents with the capability to incorporate metal cations including Cu²⁺ and Ni²⁺.

     

Effect of PLGA block molecular weight on gelling temperature of PLGA‐PEG‐PLGA thermoresponsive copolymers

Thermoresponsive, biodegradable polymeric hydrogel networks are used widely in medicinal applications. Poly(d ,l ‐lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(d ,l ‐lactic acid‐co‐glycolic acid) (PLGA‐PEG‐PLGA) triblock copolymers exhibit a sol–gel transition upon heating. The effect of PLGA block and PEG chain molecular weights (MWs) on the gelling temperature of polymer aqueous solution (20% w/w) is described. All polymer solutions convert into a hard gel within 2 °C of the gelling temperature. The release properties of the gels were displayed using paracetamol as a representative drug. A linear relation is described between the gelling temperature and PLGA block MW. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 35–39     

Synthesis and characterization of block copolymers by metal‐ and solvent‐free ring‐opening polymerization of cyclic carbonates initiated from PEG‐based surfactants

Ring‐opening polymerizations of trimethylene carbonate (TC) and 2,2‐dimethyltrimethylene carbonate (DTC) are initiated from hydroxyl‐terminated polyethylene glycol (PEG) and PEG‐based surfactants (Triton X‐100 or Triton X‐405) in the absence of any catalysts. The metal‐ and solvent‐free polymerizations proceed under melt at 150 °C, affording Triton X‐100‐block‐poly(TC) with M_n of 1400–5200 and Triton X‐100‐block‐poly(DTC) with M_n of 1800–7100 in excellent yields. The molecular weights and the comonomer composition of the resulting copolymers are controlled by the feed ratios of the monomers to the initiators, confirmed by gel permeation chromatography and ¹H NMR spectroscopy. The solubilities of the block copolymers composed of hydrophilic PEG segment and hydrophobic poly(TC) or poly(DTC) segment depend on both the compositions and the components. For example, Triton X‐100‐block‐poly (TC) (TC/EG = 9.5/9.5) and Triton X‐405‐block‐poly(TC) (TC/EG = 28/40, 46/40) milky suspend in water, while Triton X‐405‐block‐poly(TC) (TC/EG = 9.7/40) dissolves in water. A dynamic light scattering study reveals that the particle distribution of a copolymer, Triton X‐405‐block‐poly(TC) (TC/EG = 9.7/40) in water, has a monodisperse unimodal pattern ranging from 92 to 368 nm. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1985–1996, 2006     

ABC type miktoarm star copolymers through combination of controlled polymerization techniques with thiol‐ene and azide‐alkyne click reactions

ABC type miktoarm star copolymer with polystyrene (PS), poly(ε‐caprolactone) (PCL) and poly(ethylene glycol) (PEG) arms was synthesized using controlled polymerization techniques in combination with thiol‐ene and copper catalyzed azide‐alyne “click” reactions (CuAAC) and characterized. For this purpose, 1‐(allyloxy)‐3‐azidopropan‐2‐ol was synthesized as the core component in a one‐step reaction with high yields (96%). Independently, ω‐thiol functionalized polystyrene (PS‐SH) was synthesized in a two‐step protocol with a very narrow molecular weight distribution. The bromo end function of PS obtained by atom transfer radical polymerization was first converted to xanthate function and then reacted with 1, 2‐ethandithiol to yield desired thiol functional polymer (PS‐SH). The obtained polymer was grafted onto the core by thiol‐ene click chemistry. In the following stage, ε‐caprolactone monomer was polymerized from the core by ring opening polymerization (ROP) using tin octoate as catalyst through hydroxyl groups to form the second arm. Finally, PEG‐acetylene, which was simply synthesized by the esterification of Me‐PEG and 5‐pentynoic acid, was clicked onto the core through azide groups present in the structure. The intermediates at various stages and the final miktoarm star copolymer were characterized by ¹H NMR, FTIR, and GPC measurements. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Influence of the polymer structure over self‐assembly and thermo‐responsive properties: The case of PEG‐b‐PCL grafted copolymers via a combination of RAFT and ROP

During the last years, the field of drug delivery has experienced a growing interest toward the so‐called thermo‐responsive polymers: synthetic materials that, due to the specific hydrophilic–lipophilic balance of their repeating units, exhibit a lower critical solution temperature (LCST) in water associated to a characteristic coil–globule transition. In this work, thermo‐responsive amphiphilic block copolymers are synthesized via reversible addition‐fragmentation transfer (RAFT) polymerization starting from thermo‐responsive monomers and a hydrophobic biodegradable macromonomer, oligo(caprolactone)methacrylate (CL₃MA), produced via ring opening polymerization (ROP). The obtained copolymers exhibit an interesting self‐assembly behavior leading to nanoparticles (NPs) as long as temperature is kept below the LCST. Otherwise, once this value is overcome, the destabilization of the NPs causes the formation of hydrophobic superstructures that enhance the release of an entrapped lipophilic drug. This characteristic behavior has been systematically studied and related to the copolymer structure. In particular, the self‐assembly behavior as well as temperature‐triggered NP destabilization have been related to the relative length of the two blocks constituting the copolymers and to their hydrophilic–lipophilic balance (HLB). Finally, the efficacy of the thermo‐responsive triggered drug release has been tested in the case of Paclitaxel (PTX). © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2919–2931     

Antibacterial poly(ethylene glycol) hydrogels from combined epoxy‐amine and thiol‐ene click reaction

Antibacterial hydrogels containing quaternary ammonium (QA) groups were prepared via a facile thiol‐ene “click” reaction using multifunctional poly(ethylene glycol) (PEG). The multifunctional PEG polymers were prepared by an epoxy‐amine ring opening reaction. The chemical and physical properties of the hydrogels could be tuned with different crosslinking structures and crosslinking densities. The antibacterial hydrogel structures prepared from PEG Pendant QA were less well‐defined than those from PEG Chain‐End QA. Furthermore, functionalization of the PEG‐type hydrogels with QA groups produced strong antibacterial abilities against Staphylococcus aureus, and therefore has the potential to be used as an anti‐infective material for biomedical devices. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 656–667     

Non‐Catalyst Synthesis of Functionalized Biodegradable Polycarbonate

The thermal ring‐opening polymerization of 5‐benzyloxy‐trimethylene carbonate (BTMC) in bulk in the absence of any catalyst resulted in high molecular weight poly(BTMC) ( = 80 300) and subsequent catalytic hydrogenolysis resulted in functional poly(5‐hydroxyl‐trimethylene carbonate) (PHTMC). Similar spontaneous polymerization of BTMC in the presence of PEG ( = 2 000) as a macroinitiator can provide amphiphilic block polymers. The results revealed that the thermal non‐catalyst (co)polymerization of BTMC is a highly attractive preparative method because of the lack of usage of toxic initiators or catalysts. Furthermore, an evaluation of the degradation and cytotoxicity of PHTMC demonstrated enhanced degradability compared to poly(trimethylene carbonate) and similar toxicity compared to PLGA, showing PHTMC to be a promising biomaterial.

     

Facile Synthesis of Thiol‐Functionalized Long‐Chain Highly Branched ROMP Polymers and Surface‐Decorated with Gold Nanoparticles

The synthesis of thiol‐functionalized long‐chain highly branched polymers (LCHBPs) has been accomplished in combination of ring‐opening metathesis polymerization (ROMP) and thiol‐Michael addition click reaction. A monotelechelic polymer with a terminal acrylate and many pendent thiol groups is first prepared through adding an internal cis‐olefin terminating agent to the reaction mixture immediately after the completion of the living ROMP, and then utilized as an AB_n‐type macromonomer in subsequent thiol‐ene reaction between acrylate and thiol, yielding LCHBPs as the reaction time prolonged. Au nanoparticles are then covalently conjugated onto the surface of thiol‐functionalized LCHBP to fabricate novel hybrid nanostructures, which is shown as one interesting application of such functionalized metathesis polymers. This facile approach can be extended toward the fabrication of novel nanomaterials with sophisticated structures and tunable multifunctionalities.

     

The synthesis of poly[6,8‐dioxabicyclo[3.2.1]octane‐b‐(ethylene glycol)‐b‐6,8‐dioxabicyclo[3.2.1]octane] by controlled cationic ring‐opening polymerization

The triblock copolymer poly[6,8‐dioxabicyclo[3.2.1]octane‐b‐(ethylene glycol)‐b‐6,8‐dioxabicyclo[3.2.1]octane] was prepared by the controlled cationic ring‐opening polymerization of 6,8‐dioxabicyclo[3.2.1]octane (6,8‐DBO) from a macroinitiator. The macroinitiator, poly(ethylene glycol) (PEG) di(1‐chloroethyl ether), was prepared via the addition of HCl to PEG divinyl ether and was characterized with ¹³C NMR, ¹H NMR, and gel permeation chromatography (GPC). Upon preparation, a small fraction of the chain ends underwent a cyclization reaction to form inactive chain ends. When the macroinitiator was used in polymerizations of 6,8‐DBO with ZnI₂ as an activator, linear kinetic plots were observed, a linear increase in the copolymer molecular weight with conversion was seen, and the molecular weight distributions of the copolymer samples remained constant at about 1.40. Confirmation of the triblock structure of the final product was obtained with ¹H NMR spectra, ¹³C DEPT spectra, and GPC chromatograms. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4081–4087, 2000     

Synthesis of polybenzoxazine precursors using thiols: Simultaneous thiol–ene and ring‐opening reactions

A new class of polybenzoxazine precursors of combined molecular structure of benzoxazine in the open and ring form has been developed. Thermally curable benzoxazine networks were obtained by simultaneous photoinduced thiol‐ene and Catalytic Opening of the Lateral Benzoxazine Rings by Thiols (COLBERT). The thiol‐ene reactions were initiated by photolysis of a free radical photoinitiator, 2, 2‐dimethoxy‐2‐phenyl acetophenone (DMPA), and the competing COLBERT reaction was triggered by thiol compound, 1,2‐ethanedithiol, present in the reaction mixture. The extent of reactions was evaluated by conducting experiments both under UV irradiation and in dark using model benzoxazines. The precursor soft films (pre‐P(B‐ala‐DTE)) were prepared by irradiating solutions of diallyl functional benzoxazine (B‐ala), 1,2‐ethanedithiol and DMPA. The obtained pre‐P(B‐ala‐DTE) films were then cured through thermally activated ring opening reaction of remaining benzoxazine groups yielding a more rigid and tough film. Thermal and mechanical properties of the films were investigated by DSC, DMA and TGA and compared with a typical polybenzoxazine, P(B‐ala). © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

One‐pot synthesis of polymeric nanoparticle by ring‐opening metathesis polymerization

Shell‐functionalized polymeric nanoparticle was prepared through the method of polymerization‐induced self‐assembly of block copolymers [poly(2,3‐bis(2‐bromoisobutyryloxymethyl)‐5‐norbornene)‐block‐poly(7‐oxanorborn‐5‐ene‐exo‐exo‐2,3‐dicarboxylic acid dimethyl ester), PBNBE‐b‐PONBDM] via one‐pot ring‐opening metathesis polymerization of 2,3‐bis(2‐bromoisobutyryloxymethyl)‐5‐norbornene (BNBE) and 7‐oxanorborn‐5‐ene‐exo‐exo‐2,3‐dicarboxylic acid dimethyl ester (ONBDM) in a selective solvent. The compositions and the molecular weights of the copolymers were estimated by ¹H‐NMR and gel permeation chromatography. The micelles were characterized by dynamic light scattering, transmission electron micrograph, and atomic force microscopy. The results indicated that the spherical micelles constructed with bromine‐bearing PBNBE shell and PONBDM core were stable and reproducible in toluene. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

RGD peptide grafted biodegradable amphiphilic triblock copolymer poly(glutamic acid)‐b‐poly(L‐lactide)‐b‐poly(glutamic acid): Synthesis and self‐assembly

A novel amphiphilic biodegradable triblock copolymer (PGL‐PLA‐PGL) with polylactide (PLA) as hydrophobic middle block and poly(glutamic acid) (PGL) as hydrophilic lateral blocks was successfully synthesized by ring‐opening polymerization (ROP) of L ‐lactide (LA) and N‐carboxy anhydride (NCA) consecutively and by subsequent catalytic hydrogenation. The results of cell experiment of PGL‐PLA‐PGL suggested that PGL could improve biocompatibility of polyester obviously. The copolymer could form micelles of spindly shape easily in aqueous solution. The pendant carboxyl groups of the triblock copolymer were further activated with N‐hydroxysuccinimide and combined with a cell‐adhesive peptide GRGDSY. Incorporation of the oligopeptide further enhanced the hydrophilicity and led to formation of spherical micelles. PGL‐PLA‐PGL showed better cell adhesion and spreading ability than pure PLA and the GRGDSY‐containing copolymer exhibited even further improvement in cell adhesion and spreading ability, indicating that the copolymer could find a promising application in drug delivery or tissue engineering. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3218–3230, 2007     

Magnetite‐polylactic acid core–shell nanoparticles by ring‐opening polymerization under microwave irradiation

The synthesis of magnetic core–shell nanoparticles consisting of magnetite cores surface‐functionalized by glycolic acid covered by polylactic acid was performed by applying the “grafting‐from” strategy, where the polymerization is initiated from the particle surface. The surface initiated ring‐opening polymerization of D,L ‐lactide was initiated by tin (II) 2‐ethylhexanoate using microwave irradiation. Core–shell nanoparticles of high colloidal stability in water were obtained in this way. The morphology of the magnetic core–shell nanostructure was determined by transmission electron microscopy, and the chemical structure was elucidated by Fourier transform infrared spectroscopy (FTIR) and X‐ray photoelectron spectroscopy. Magnetic measurements revealed superparamagnetic behavior and high magnetization values. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of amphiphilic A4B4 star‐shaped copolymers by mechanisms transformation combining with thiol‐ene reaction

Using core‐first strategy, the amphiphilic A₄B₄ star‐shaped copolymers [poly(ethylene oxide)]₄[poly(ε‐caprolactone)]₄ [(PEO)₄(PCL)₄], [poly(ethylene oxide)]₄[poly(styrene)]₄ [(PEO)₄(PS)₄], and [poly(ethylene oxide)]₄[poly(tert‐butyl acrylate)]₄ [(PEO)₄(PtBA)₄] were synthesized by mechanisms transformation combining with thiol‐ene reaction. First, using a designed multifunctional mikto‐initiator with four active hydroxyl groups and four allyl groups, the four‐armed star‐shaped polymers (PEO‐Ph)₄/(OH)₄ with four active hydroxyl groups at core position were obtained by sequential ring‐opening polymerization (ROP) of ethylene oxide monomers, capping reaction of living oxyanion with benzyl chloride, and transformation of allyl groups into hydroxyl groups by thiol‐ene reaction. Then, the A₄B₄ star‐shaped copolymers (PEO)₄(PS)₄ or (PEO)₄(PtBA)₄ were obtained by atom transfer radical polymerization (ATRP) of styrene or tert‐butyl acrylate (tBA) monomers from macroinitiator of (PEO‐Ph)₄/(Br)₄, which was obtained by esterification of (PEO‐Ph)₄/(OH)₄ with 2‐bromoisobutyryl bromide. The A₄B₄ star‐shaped copolymers (PEO)₄(PCL)₄ were also obtained by ROP of ε‐caprolactopne monomers from macroinitiator of (PEO‐Ph)₄/(OH)₄. The target copolymers and intermediates were characterized by size‐exclusion chromatography, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy, and nuclear magnetic resonance in detail. This synthetic route might be a versatile one to various A_nB_n (n ≥ 3) star‐shaped copolymers with defined structure and compositions. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4572–4583     

Chemo‐ and stereoselective polymerization of 3‐methylenehepta‐1,6‐Diene and Its thiol‐ene modification

Here we report on the coordination polymerization of a vinyl‐functionalized butadiene monomer, 3‐methylenehepta‐1,6‐diene (MHD) with exclusive conjugated diene chemoselectivity, high 1,2‐regioselectivity and moderate isotacticity (1,2‐selectivity > 99%, mm triad = 93%). Random copolymers of MHD and other conjugated diene (isoprene or myrcene) are also synthesized. The pendent vinyl groups of MHD homo or copolymers could be quantitatively converted into various functional groups via thiol‐ene click reaction. The resulting functionalized polybutadiene‐based material display versatile thermal and surface properties. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1031–1039