Anionic Polymerization Of Ethylene Oxide Research Articles

Synthesis and Characterization of Furan-Based Non-Ionic Surfactants (fbnios).

Two series of furan-based non-ionic surfactants (fbnios) were prepared by a combination of Williamson ether synthesis and anionic polymerization of ethylene oxide (EO). The reaction of 1-bromooctane and 1-bromododecane with 2,5-bis(hydroxymethyl)furan after deprotonation with potassium tert-butoxide yielded the corresponding alkane furfuryl alcohols (Cx-F-OH with x = 8 or 12). Deprotonation of Cx-F-OH with potassium tert-pentoxide enabled the anionic polymerization of EO, which yielded four C8-F-EOy samples with y = 3, 6, 9, and 14 and four C12-F-EOy samples with y = 9, 12, 18, and 23. The chemical composition of the fbnios was determined by NMR and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-ToF MS) analysis, while their dispersity (Đ) was characterized by gel permeation chromatography (GPC) and MALDI-ToF MS. The purity of the Cx-F-EOy samples exceeded 92%, and they were produced with narrow molecular weight distributions (Đ ≤ 1.02, as determined by GPC analysis). The critical micelle concentration (CMC) of the Cx-F-EOy samples was determined by surface tension and pyrene fluorescence measurements. These showed that the CMC of the fbnios could be tuned by adjusting the molecular parameters x and y, with the CMC increasing for decreasing x and increasing y. In particular, the CMC of the C8-F-EOy and C12-F-EOy samples was significantly higher and lower, respectively, than for typical non-ionic surfactants (nios) like the Triton X and Brij surfactant families. The efficiency, effectiveness, and cross section of the EOy headgroup of the fbnios were also determined. Together, the CMC, efficiency, and effectiveness of the fbnios demonstrate that this new surfactant family displays tensioactive properties that match and even exceed those of traditional nios, suggesting that they could extend further the already broad range of applications for nios.

Synthesis and Self-Assembly of Amphiphilic Triblock Terpolymers with Complex Macromolecular Architecture.

Two star triblock terpolymers (PS-b-P2VP-b-PEO)3 and one dendritic-like terpolymer [PS-b-P2VP-b-(PEO)2]3 of PS (polystyrene), P2VP (poly(2-vinylpyridine)), and PEO (poly(ethylene oxide)), never reported before, were synthesized by combining atom transfer radical and anionic polymerizations. The synthesis involves the transformation of the -Br groups of the previously reported Br-terminated 3-arm star diblock copolymers to one or two -OH groups, followed by anionic polymerization of ethylene oxide to afford the star or dendritic structure, respectively. The well-defined structure of the terpolymers was confirmed by static light scattering, size exclusion chromatography, and NMR spectroscopy. The self-assembly in solution and the morphology in bulk of the terpolymers, studied by dynamic light scattering and transmission electron microscopy, respectively, reveal new insights in the phase separation of these materials with complex macromolecular architecture.

Universal Concept for the Implementation of a Single Cleavable Unit at Tunable Position in Functional Poly(ethylene glycol)s

Poly(ethylene glycol) (PEG) with acid-sensitive moieties gained attention particularly for various biomedical applications, such as the covalent attachment of PEG (PEGylation) to protein therapeutics, the synthesis of stealth liposomes, and polymeric carriers for low-molecular-weight drugs. Cleavable PEGs are favored over their inert analogues because of superior pharmacodynamic and/or pharmacokinetic properties of their formulations. However, synthetic routes to acetal-containing PEGs published up to date either require enormous efforts or result in ill-defined materials with a lack of control over the molecular weight. Herein, we describe a novel methodology to implement a single acetaldehyde acetal in well-defined (hetero)functional poly(ethylene glycol)s with total control over its position. To underline its general applicability, a diverse set of initiators for the anionic polymerization of ethylene oxide (cholesterol, dibenzylamino ethanol, and poly(ethylene glycol) monomethyl ether (mPEG)) was modified and used to synthesize the analogous labile PEGs. The polyether bearing the cleavable lipid had a degree of polymerization of 46, was amphiphilic and exhibited a critical micelle concentration of 4.20 mg·L(-1). From dibenzylamino ethanol, three heterofunctional PEGs with different molecular weights and labile amino termini were generated. The transformation of the amino functionality into the corresponding squaric acid ester amide demonstrated the accessibility of the cleavable functional group and activated the PEG for protein PEGylation, which was exemplarily shown by the attachment to bovine serum albumin (BSA). Furthermore, turning mPEG into a macroinitiator with a cleavable hydroxyl group granted access to a well-defined poly(ethylene glycol) derivative bearing a single cleavable moiety within its backbone. All the acetal-containing PEGs and PEG/protein conjugates were proven to degrade upon acidic treatment.

Synthesis of ω-phosphonated poly(ethylene oxide)s through the combination of kabachnik-fields reaction and “click” chemistry

The synthesis of new ω-phosphonic acid-terminated poly(ethylene oxide) (PEOs) monomethyl ethers was investigated by the combination of Atherton–Todd or Kabachnik–Fields reactions and the “click” copper-catalyzed 1,3-dipolar cycloaddition of azides and terminal alkynes. The Atherton–Todd route fails to give the corresponding phosphonic acid-terminated PEOs due to competitive cleavage of the PN bond during the dealkylation step. In contrast, the Kabachnik–Fields route leads with very good yields to ω-phosphonic acid-PEO through “click” reaction of azido-PEO onto dimethyl aminopropargyl phosphonate prepared by Kabachnik–Fields reaction between propargylbenzylimine and dimethyl phosphonate, followed by acidic hydrolysis. The reported methodology, precluding the use of anionic polymerization of ethylene oxide, leads to novel well-defined phosphonic acid-terminated PEOs from commercially available products in good yields. Moreover, such a strategy can be adapted to anchor phosphonic acid functionality onto a wide range of polymers. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

Aggregation behavior and in vitro biocompatibility study of octopus-shaped macromolecules based on tert-butylcalix[4]arenes

A series of products based on tert-butylcalix[4]arene have been synthesized by anionic polymerization of ethylene oxide. The resulting products are amphiphilic octopus-shaped macromolecules, consisting of a hydrophobic calix[4]arene core and four arms of hydrophilic poly(ethylene oxide) chains. In aqueous solutions the polyoxyethylated tert-butylcalix[4]arenes were found to self-associate above certain CMC determined by dye solubilization technique. The light scattering study reveals that the polyoxyethylated tert-butylcalix[4]arenes form aggregates of narrow size distribution and hydrodynamic diameters ranging from about 155 to 245 nm and aggregation numbers from tens to hundreds macromolecules per particle depending on the degree of polymerization of the PEO chains. An in vitro biocompatibility study showed that the tested compounds are practically devoid of intrinsic cytotoxic and hemolytic effects and moreover they failed to modulate the mitogen-induced interleukin-2 release from the human T-lymphocyte cell line Jurkat E6-1. Taken together the excellent in vitro biocompatibility profile and the favorable physicochemical characteristics of the tested polyoxyethylated calix[4]arenes give us reason to consider them as promising for further evaluation as drug delivery platforms.

Polymerization of ethylene oxide initiated by lithium derivatives via the monomer-activated approach: Application to the direct synthesis of PS-b-PEO and PI-b-PEO diblock copolymers

The anionic polymerization of ethylene oxide (EO) initiated by lithium derivatives is extremely sluggish and only yields very low molar mass EO oligomers because of the low reactivity of lithium alkoxide species. We show here that using the monomer-activated anionic polymerization approach, one can activate the C–O–Li bonds towards EO polymerization at low temperature and in non polar media. Starting from living polystyryllithium and polyisoprenyllithium, addition of triisobutylaluminum (i-Bu3Al) in excess to lithium species triggers the propagation reaction of EO, allowing the direct synthesis, in a few hours, of poly(styrene-b-ethylene oxide) and poly(isoprene-b-ethylene oxide) diblock copolymers, with a molar mass of the PEO block up to 10 000 g/mol.

Multifunctional PEG-grafted chitosan copolymer possessing amino and carboxyl (or formyl) groups

Abstract New multifunctional PEG-grafted chitosan copolymers possessing both amino and carboxyl (4) or formyl (5) groups were synthesized by the grafting reaction method between chitosan and heterobifunctional PEG from anionic polymerization of ethylene oxide. Completion of the reactions and characterization of the resulting polymers were demonstrated by 1H NMR, FT-IR and GPC studies. The multifunctional polymers may have potential utility in gene/drug co-delivery or heterogeneous catalysis.

Pearl Necklace Architecture: New Threaded Star-Shaped Copolymers

The synthesis of star-shaped polymers, which are threaded regularly along a common backbone, is described. Thus, two different approaches for preparation of so-called pearl necklace polymers (synonyms: multigraft copolymers, barbwire or centipedes polymers, multiple dumbbells or star-oligomers) are presented. Poly(ethylene oxide) (PEO) was used as a thread and poly(dimethylaminoethyl methacrylate) (PDMAEMA) stars were used as pearls. In the first approach, a polycondensation reaction of PEO macromonomers with partly protected dipentaerythritol leads first to a multiblock PEO. Afterward, the protected hydroxy groups of dipentaerythritol, which is situated at the junction points of the blocks, can be released for the anchoring of PDMAEMA chains. In the second approach, anionic polymerization of ethylene oxide leads directly to a diblock PEO with an interior dipentaerythritol unit. The chain ends can be modified with further dipentaerythritols, giving access after selective deprotection to either star dimers...

Hyperbranched Polyglycerol-Based Lipids via Oxyanionic Polymerization: Toward Multifunctional Stealth Liposomes

We describe the synthesis of linear-hyperbranched lipids for liposome preparation based on linear poly(ethylene glycol) (PEG) and hyperbranched polyglycerol (PG). Molecular weights were adjusted to values around 3000 g/mol with varying degrees of polymerization of the linear and the branched segments in analogy to PEG-based stealth lipids; polydispersities were generally low and below 1.3. The hydrophobic anchors were introduced into the lipid structures as initiators for the anionic polymerization of ethylene oxide and are either based on cholesterol or on different aliphatic glyceryl ethers. Complete incorporation of the apolar initiators was evidenced by MALDI-ToF analysis at all stages of the reaction. The linear-hyperbranched polyether lipid is incorporated as the polyfunctional shell in liposome formulations together with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The resulting liposomes were subsequently characterized via dynamic light scattering (DLS) and small angle neutron scattering (SANS) as well as transmission electron microscopy (TEM), demonstrating the formation of unilamellar liposomes in the size range of 40 to 50 nm.

Synthesis of three‐arm poly(ethylene glycol) by combination of controlled anionic polymerization and ‘click’ chemistry

AbstractPoly(ethylene glycol) (PEG) is an important water‐soluble polymer, which is widely used in the biomedical field because of its good biodegradability, biocompatibility and permeability. It is usually synthesized by anionic polymerization of ethylene oxide but side reactions lead to the formation of some oligomers. High molecular weight PEG can be obtained, however, through coordinated anionic polymerization. Recently a novel controlled anionic polymerization based on the initiating system ammonium bromide/trialkylaluminium was reported. Related studies have shown that the controlled anionic polymerization allows the synthesis of linear polyethers with low dispersity in a wide range of molecular weights at ambient temperature. Unfortunately, so far this controlled anionic polymerization has not been used to synthesize polymers with complex architectures. In the work reported here, controlled anionic polymerization was combined with ‘click’ chemistry for the first time to synthesize polyethers with multiple arms. Firstly, controlled anionic polymerization was employed to synthesize a linear bromine‐terminated PEG (PEG‐Br) using ethylene oxide as the monomer and tetraoctylammonium bromide/triisobutylaluminium as the initiating system at room temperature. The terminal bromine in the PEG thus synthesized was then converted into an azide group by the reaction of PEG‐Br and sodium azide. A trifunctional linking agent was also prepared by the reaction of trimethylolpropane and propiolic acid. By using ‘click’ chemistry, a three‐arm PEG was finally obtained through the reaction of the azide‐terminated PEG and the trifunctional linking agent. The chemical structure of the polymer thus synthesized was characterized using infrared spectroscopy, NMR spectroscopy, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and size‐exclusion chromatography with multi‐angle laser light scattering. It was found that the synthesized polyether possesses the designed structure. Considering the wide applicability of controlled anionic polymerization and ‘click’ chemistry, their combination is a valuable way to synthesize various polyethers with multiple arms. Copyright © 2009 Society of Chemical Industry

Synthesis of Half‐Channels by the Anionic Polymerization of Ethylene Oxide Initiated by Modified Cyclodextrin

Synthesis of Half‐Channels by the Anionic Polymerization of Ethylene Oxide Initiated by Modified Cyclodextrin

Study on anionic polymerization of ethylene oxide initiated by ammonium/triisobutylaluminum

In this paper, ammonium/triisobutylaluminum was used as an initiating system for anionic polymerization of ethylene oxide (EO). When the amount of triisobutylaluminum versus ammonium was in excess, a fast polymerization rate was achieved at room temperature and allowed polyethylene glycol synthesized with a high molecular weight and narrow molecular weight distribution. It was found that triisobutylaluminum may play two roles during the polymerization, one is that it can react with ammonium to form “ate” complex as an efficient initiator for EO polymerization, and the other is that it exerts a significant activating effect on the monomer. The catalytic effect of triisobutylaluminum in EO polymerization was elucidated by using quantum chemical calculations at density functional theory level, involving thermo-chemistry parameters. The studies show that EO homopolymerization cannot be conducted without the aid of catalyst due to the big energy difference of bonding orbitals. The interaction between EO and trialkylaluminum makes the electron cloud distribution and energy gap of EO molecule change, which indicates trialkylaluminum can activate the monomer. In addition, because of the lower enthalpy of formation, the formation of “ate” complex is prior to the interaction of trialkylaluminum and EO.

Imidazolium ionic liquids with short polyoxyethylene chains

It has been observed by us earlier that imidazolium ionic liquids ([bmim][BF4] react with paraformaldehyde giving in nearly quantitative yield imidazolium ionic liquids substituted at 2-position with hydroxymethyl group ([bhmim][BF4]). In this article, we describe the application of those ionic liquids (after converting hydroxyl group into alkoxide anion by reaction with sodium hydride) as initiators for anionic polymerization of ethylene oxide (EO). Up to DPn ∼ 30 polymerization proceeds without side reactions, and the product is exclusively low-molecular-weight polyoxyethylene containing imidazolium head group (POE-IL) with DPn equal to [EO]/[bhmim] ratio. By increasing [EO]/[bhmim] ratio further, side reaction start to interfere, and macromolecules that does not contain imidazolium head groups are also formed, as evidenced by analysis of MALDI TOF spectra. Blending of POE-IL with high-molecular-weight POE leads to significant reduction of crystallinity of POE. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6961–6968, 2008

Asymmetric End-Capped Poly(ethylene oxide). Synthesis and Rheological Behavior in Aqueous Solution

A method was developed to prepare asymmetric end-capped poly(ethylene oxide)s (PEOs), containing an alkyl group on one chain end and a perfluoroalkyl group on the other one (C18H37−PEO−C2H4−C8F17 and C18H37−PEO−C10H20−C8F17). These new telechelic associative polymers (APs) were synthesized by anionic polymerization of ethylene oxide initiated by an alkoxide (C18H37−O−K+) followed by esterification. The rheological behavior of asymmetric and analogous symmetric APs in aqueous solutions has been investigated as a function of polymer concentration (C), hydrophobic end-cap and surfactant used to homogenize the system: sodium dodecyl sulfate (SDS) or lithium perfluorooctyl sulfonate (LiFOS). A steep increase of the static viscosity η, attributed to the formation of a multiconnected network, is observed for C ≈ 1 wt %. Semidilute solutions present a Maxwellian rheological behavior with only one relaxation time τ associated with the least hydrophobic end group. The viscoelastic response is modified by the interactions between hydrophobic end groups and surfactant inside mixed aggregates.

Amino end-functionalized poly(ethylene oxide)- block-poly(methylidene malonate 2.1.2) block copolymers: synthesis, characterization, and chemical modification for targeting purposes

Poly(ethylene oxide)- block-poly(methylidene malonate 2.1.2) block copolymers (PEO- b-PMM 2.1.2) bearing a primary amino group at the PEO chain end were synthesized by sequential anionic polymerization of ethylene oxide (EO) and methylidene malonate 2.1.2 (MM 2.1.2). It was demonstrated that the direct initiation with 2-aminoethanolate was the most efficient method in terms of simplicity and of α-end functionalization yield. In this one-step reaction, amino end-functionalization yields of 92 ± 4% could be obtained, in contrast to maximum yields of 60–80% for the two-step reactions, including the one performed with a protected 2-aminoethanolate initiator. The reactive amino end-group was subsequently modified by reaction with functional ligands such as mannose and fluorescein. The chemical modifications were performed as well in organic medium as in aqueous micellar solutions, with reaction yields varying between 21% and 88%.

Double-Hydrophilic Linear-Hyperbranched Block Copolymers Based on Poly(ethylene oxide) and Poly(glycerol)

A convenient 4-step (2-pot) approach for the synthesis of biocompatible, double hydrophilic linear-hyperbranched block copolymers based on poly(ethylene oxide) (PEO) and poly(glycerol) (PG) is described. The polymers consisting exclusively of an aliphatic polyether structure were prepared from linear PEO-b-(l-PG) precursor block copolymers, obtained via anionic polymerization of ethylene oxide and subsequently ethoxyethyl glycidyl ether (EEGE). In order to generate initiating functionalities for glycidol, the protected hydroxyl groups of the P(EEGE) block were recovered by hydrolysis with hydrochloric acid. Partial deprotonation of the linear poly(glycerol) block with cesium hydroxide permitted hypergrafting of glycidol onto the alkoxide initiating sites, using the slow monomer addition technique. Detailed studies showed that narrow polydispersity was only obtained with Cs counterions, while use of potassium resulted in larger polydispersities. The resulting linear-hyperbranched PEO-b-(hb-PG) block copolymers exhibited low polydispersities Mw/Mn in the range of 1.09−1.25, depending on the molecular weight of the hyperbranched block. Molecular weights of the block copolymers ranged from 3 700 to 15 700 g/mol, varying both the length of the linear PEO segments as well as the hyperbranched block.

Synthesis of novel asymmetric dendritic‐linear‐dendritic block copolymers via “living” anionic polymerization of ethylene oxide initiated by dendritic macroinitiators

AbstractThe first synthesis of asymmetric dendritic‐linear‐dendritic ABC block copolymers, that contain a linear B block and dissimilar A and C dendritic fragments is reported. Third generation poly(benzyl ether) monodendrons having benzyl alcohol moiety at their “focal” point were activated by quantitative titration with organometallic anions and the resulting alkoxides were used as initiators in the “living” ring‐opening polymerization of ethylene oxide. The reaction proceeded in controlled fashion at 40–50 °C affording linear‐dendritic AB block copolymers with predictable molecular weights (Mw = 6000–13,000) and narrow molecular weight distributions (Mw/Mn = 1.02–1.04). The propagation process was monitored by size‐exclusion chromatography with multiple detection. The resulting “living” copolymers were terminated by reaction either with HCl/tetrahydrofuran or with a reactive monodendron that differed from the initiating dendron not only in size, but also in chemical composition. The asymmetric triblock copolymers follow a peculiar structure‐induced self‐assembly pattern in block‐selective solvents as evidenced by size‐exclusion chromatography in combination with multi‐angle light scattering. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5136–5148, 2007

Mannosylated Poly(ethylene oxide)-b-Poly(ε-caprolactone) Diblock Copolymers: Synthesis, Characterization, and Interaction with a Bacterial Lectin

A novel bioeliminable amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) diblock copolymer end-capped by a mannose residue was synthesized by sequential controlled polymerization of ethylene oxide and epsilon-caprolactone, followed by the coupling of a reactive mannose derivative to the PEO chain end. The anionic polymerization of ethylene oxide was first initiated by potassium 2-dimethylaminoethanolate. The ring-opening polymerization of epsilon-caprolactone was then initiated by the omega-hydroxy end-group of PEO previously converted into an Al alkoxide. Finally, the saccharidic end-group was attached by quaternization of the tertiary amine alpha-end-group of the PEO-b-PCL with a brominated mannose derivative. The copolymer was fully characterized in terms of chemical composition and purity by high-resolution NMR spectroscopy and size exclusion chromatography. Furthermore, measurements with a pendant drop tensiometer showed that both the mannosylated copolymer and the non-mannosylated counterpart significantly decreased the dichloromethane/water interfacial tension. Moreover, these amphiphilic copolymers formed monodisperse spherical micelles in water with an average diameter of approximately 11 nm as measured by dynamic light scattering and cryo-transmission electron microscopy. The availability of mannose as a specific recognition site at the surface of the micelles was proved by isothermal titration microcalorimetry (ITC), using the BclA lectin (from Burkholderia cenocepacia), which interacts selectively with alpha-D-mannopyranoside derivatives. The thermodynamic parameters of the lectin/mannose interaction were extracted from the ITC data. These colloidal systems have great potential for drug targeting and vaccine delivery systems.

Controlled Anionic Homo- and Copolymerization of Ethylene Oxide and Propylene Oxide by Monomer Activation

The anionic polymerization of ethylene oxide initiated by alkali metal-based initiators suffers from low polymerization rates even in polar media. We found that the addition of triisobutylaluminum to initiators like alkali metal alkoxides or tetraalkylammonium salts strongly enhances the ethylene oxide polymerization rate, while keeping its living character. At ratio [i-Bu3Al]/[initiator] = 1.5, the controlled synthesis of poly(ethylene oxide) of relatively high molar masses is achieved in short time at room temperature in dichloromethane or toluene. Beside the formation of an aluminate 1:1 complex involving i-Bu3Al and the initiator, a second complex between the trialkylaluminum and the oxirane is formed, which strongly increases the reactivity of the epoxide monomer. Gradient di- and triblock ethylene oxide/propylene oxide copolymers of high molar mass are readily prepared with this system.

Preparation, Characterization, and Application of Poly(vinyl alcohol)-graft-Poly(ethylene glycol) Resins: Novel Polymer Matrices for Solid-Phase Synthesis

Spherical crosslinked poly(vinyl alcohol) (PVA) beads with good mechanical stability were prepared by reverse-suspension polymerization, using dimethyl sulfoxide (DMSO) as a cosolvent in an aqueous phase. Poly(ethylene glycol)s with varying chain lengths were grafted onto the PVA beads by anionic polymerization of ethylene oxide. The thermal behavior, morphology, and swelling were evaluated for each of the new polymer matrices. High loading and good swelling in water and organic solvents were characteristic of the PEG-grafted PVA beads. The polymer beads also exhibited good mechanical and chemical stability and were unaffected by treatment with 6 N HCl and with 6 N NaOH. The hydroxyl groups of the PVA-PEG beads were converted into aldehyde, carboxylic acid, and isocyanate functions to provide scavenger resins and were extended by way of a benzyl alcohol in a Wang linker. The transglutaminase substrates dipeptides (Z-Gln-Gly) and heptapeptides (Pro-Asn-Pro-Gln-Leu-Pro-Phe) were synthesized on PVA-PEG_5, PVA-PEG_20, and the Wang linker-derivatized PVA-PEG resins. The cleavage of the peptides from the resins using MeOH/NH3 mixture at different temperatures (0 degrees C and room temp) and 50% TFA/DCM provided, respectively, peptide methyl esters, amides, and acids in good yields and purity as assessed by LC-MS analysis.