Methoxy Oligo Research Articles

Distinguishing anti-PEG antibodies by specificity for the PEG terminus using nanoarchitectonics-based antibiofouling cello-oligosaccharide platforms.

The conjugation of poly(ethylene glycol) (PEG) to therapeutic proteins or nanoparticles is a widely used pharmaceutical strategy to improve their therapeutic efficacy. However, conjugation can make PEG immunogenic and induce the production of anti-PEG antibodies, which decreases both the therapeutic efficacy after repeated dosing and clinical safety. To address these concerns, it is essential to analyze the binding characteristics of anti-PEG antibodies to PEG. However, distinguishing anti-PEG antibodies is still a difficult task. Herein, we demonstrate the use of antibiofouling cello-oligosaccharide assemblies tethering one-terminal methoxy oligo(ethylene glycol) (OEG) ligands for distinguishing anti-PEG antibodies in a simple manner. The OEG ligand-tethering two-dimensional crystalline cello-oligosaccharide assemblies were stably dispersed in a buffer solution and had antibiofouling properties against nonspecific protein adsorption. These characteristics allowed enzyme-linked immunosorbent assays (ELISAs) to be simply performed by cycles of centrifugation/redispersion of aqueous dispersions of the assemblies. The simple assays revealed that the specific OEG ligand-tethering assemblies could distinguish anti-PEG antibodies to detect a specific antibody that preferentially binds to the methoxy terminus of the PEG chain with 3 repeating ethylene glycol units. Furthermore, quantitative detection of the antibodies was successfully performed with high sensitivity even in the presence of serum. The detectable and quantifiable range of antibody concentrations covered those required clinically. Our findings open a new avenue for analyzing the binding characteristics of anti-PEG antibodies in biological samples.

Amide-Containing Bottlebrushes via Continuous-Flow Photoiniferter Reversible Addition-Fragmentation Chain Transfer Polymerization: Micellization Behavior.

Herein, a series of ternary amphiphilic amide-containing bottlebrushes were synthesized by photoiniferter (PI-RAFT) polymerization of macromonomers in continuous-flow mode using trithiocarbonate as a chain transfer agent. Visible light-mediated polymerization of macromonomers under mild conditions enabled the preparation of thermoresponsive copolymers with low dispersity and high yields in a very short time, which is not typical for the classical reversible addition-fragmentation chain transfer process. Methoxy oligo(ethylene glycol) methacrylate and alkoxy(C12-C14) oligo(ethylene glycol) methacrylate were used as the basic monomers providing amphiphilic and thermoresponsive properties. The study investigated how modifying comonomers, acrylamide (AAm), methacrylamide (MAAm), and N-methylacrylamide (-MeAAm) affect the features of bottlebrush micelle formation, their critical micelle concentration, and loading capacity for pyrene, a hydrophobic drug model. The results showed that the process is scalable and can produce tens of grams of pure copolymer per day. The unmodified copolymer formed unimolecular micelles at temperatures below the LCST in aqueous solutions, as revealed by DLS and SLS data. The incorporation of AAm, MAAm, and N-MeAAm units resulted in an increase in micelle aggregation numbers. The resulting bottlebrushes formed uni- or bimolecular micelles at extremely low concentrations. These micelles possess a high capacity for loading pyrene, making them a promising choice for targeted drug delivery.

Thermogels based on biocompatible OEGMA-MEGMA diblock copolymers

A series of biocompatible thermoresponsive copolymers were successfully synthesised via group transfer polymerisation (GTP) from methoxy ethylene glycol methacrylate (MEGMA) and methoxy oligo (ethylene glycol) methacrylate (OEGMA, Mn = 300 g mol -1). Statistical and diblock copolymers with molar mass around 8100 g mol−1 and various compositions were investigated. Specifically, the content in OEGMA and MEGMA was varied from 80 to 20, 70–30, 60–40, to 50–50 w/w%. The thermoresponsive and self-assembly behaviour of the copolymers was investigated throughvisual tests, rheology, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Interestingly, the diblock copolymers with higher MEGMA content were able to form gels at relatively low concentrations (as low as 5% w/w) when increasing the temperature, something that is reported for the first time for linear ethylene glycol based copolymers. A transition of spherical micelle to worm-like micelle was observed in these diblock copolymers that promotes gelation. Furthermore, these in-house synthesised polymers were mixed with Pluronic® F127. It was found that the gelation area of Pluronic® F127 was broadened by the addition of the synthesised copolymers with one formulation, specifically a combination of 12.5% w/w Pluronic® F127 and 12.5% w/w of a statistical OEGMA-co-MEGMA, forming a stable gel from 34 °C to 48 °C that is a desirable temperature range for biological applications. Finally, cell viability experiments were performed for the three most promising diblock copolymers and they were confirmed to be non-toxic.

Betulin‐containing bioactive amphiphilic copolymers: Synthesis, characterization and self‐assembly

AbstractBetulin, a natural triterpene possessing a wide range of biological activities, has been modified via Steglich esterification to produce a methacrylate derivative capable of participating in radical polymerization. The modification is intended to increase the solubility of betulin, which is almost insoluble in water, by incorporating into the composition of an amphiphilic copolymer. The resulting solubility of betulin in water increased from 8·10−5 mg/mL to more than 10 mg/mL per betulin. For this, well‐defined biocompatible thermoresponsive copolymers with high betulin content have been synthesized through the conventional and RAFT copolymerizations of betulin methacrylate (BeMA) with methoxy oligo(ethylene glycol) methacrylate (MOEGMA). BeMA was more reactive in the BeMA‐MOEGMA pair; the resulting copolymers were slightly enriched with BeMA units (r1 = 1.70, r2 = 0.93). The copolymers exhibited LCST‐type behavior. LCST was tuned by balancing the hydrophobic betulin and hydrophilic OEG fragments. The molecular weight characteristics of polymers and their behavior in aqueous and organic solutions have been studied. Copolymers obtained by conventional polymerization had lower cloud points than RAFT copolymers of the same composition. The copolymers are characterized by low critical micelle concentrations that decrease as the BeMA fraction in the copolymers increases. RAFT copolymers were shown to form unimolecular micelles resistant to dissociation, which is promising for their use in targeted drug delivery.

The Solution Properties of Polymethacrylate Molecular Brushes with Oligo(ethylene glycol) and Oligo(propylene glycol) Side Chains.

The properties of polymer brushes based on three macromonomers were investigated in aqueous and organic solutions. Methacrylic monomers with different compositions of the oligo(oxyalkylene) substituents and arrangements of the oligo(ethylene glycol) and oligo(propylene glycol) blocks were used for the synthesis of polymers. There were methoxy [oligo(ethylene glycol)10.3-block-oligo(propylene glycol)4.7] methacrylate, methoxy [oligo(propylene glycol)8.3-block-oligo(ethylene glycol)6.6] methacrylate, and methoxy oligo(propylene glycol)4.2 methacrylate. Molecular brushes were investigated by the methods of molecular hydrodynamics and optics in dilute solutions in acetonitrile, chloroform, and water. The peculiarities of behavior of poly[oligo(oxyalkylene) methacrylates] in aqueous solutions and water-toluene systems have been found; in particular, the solubility of the polymers in water and organic solvents, the polymers equilibrium distribution between the phases, and the surface activity in the water-toluene system have been established. The thermo-responsibility in aqueous solutions and values of a critical concentration of micelle formation were shown. Depending on the arrangement of blocks in the side chains of molecular brushes, they are characterized by different intramolecular density.

Hierarchical Self-Assembly of Triphilic Main-Chain-Type Semifluorinated Alternating Graft Copolymers in Aqueous Solution.

Fluorinated copolymers can self-assemble in solution and form micelles with rare properties due to the peculiar behavior of fluorinated groups. However, the process description of the self-assembly is still largely phenomenological and difficult to explain due to the tendency of the fluorinated segments to segregate from both the hydrophilic and lipophilic segments, which can result in various morphologies. Herein, the controlled formation of ellipsoidal micelles, disklike micelles, and sheets by hierarchical self-assembly of triphilic main-chain-type semifluorinated alternating graft copolymers (AB)n A-g-mOEG is presented (where A represents unit of α,ω-diiodoperfluoroalkane, B represents the unit of α,ω-unconjugated diene, and mOEG represents methoxy oligo(ethylene glycol)), which are synthesized by step transfer-addition and radical-termination (START) polymerization and azide-alkyne click chemistry. Furthermore, the possible self-assembly mechanism of these micron-level aggregates is proposed, which is ascribed to the hierarchical self-assembly, crowding effect of hydrophilic chains and the interfacial tension between the fluoroalkane and alkane segments. This study can provide a facile and highly efficient approach to the synthesis of main-chain-type fluorinated graft copolymers and expand the research field for the solution self-assembly of fluorinated copolymers.

Synthesis of amphiphilic (meth)acrylates with oligo(ethylene glycol) and (or) oligo(propylene glycol) blocks by the esterification of (meth)acrylic acid

AbstractThermoresponsive PEG‐based (PEG stands polyethylene glycol) polymers are unique for use in medicine because of their low toxicity, good biocompatibility and biodegradability, but usually more hydrophobic and more toxic comonomers are used to adjust lower critical solution temperature (LCST). A convenient way to overcome this problem and to finely tune LCST is to use alkoxy oligo(ethylene glycol)‐ or alkoxy oligo(propylene glycol) (meth)acrylates as starting comonomers. Here we report on the conditions for the simple and affordable synthesis of methoxy oligo(propylene glycol) (meth)acrylate‐ and methoxy oligo(propylene glycol)‐block‐oligo(ethylene glycol) (meth)acrylate‐based macromonomers with high yields (80%–98.7%) by the acid‐catalyzed esterification of (meth)acrylic acid with alkoxy oligo(alkylene glycols) containing oligo(ethylene glycol) (OEG) and/or oligo(propylene glycol) (OPG) blocks. p‐Toluene sulphonic acid (pTSA), alkyl(C12–C14)benzene sulfonic acid (ABSA) and H2SO4 were used as catalysts. It has been shown that pTSA and ABSA are practically the same in catalytic activity and are superior to sulfuric acid. The reaction orders with respect to catalyst was found to be close to 1 in all cases. It has been shown that the reaction is actually insensitive to the lengths of OEG and OPG blocks, as well as to the structure of the terminal alkyl group, while the esterification of acrylic acid (AA) proceeds much faster compared to methacrylic acid (MAA) one under the same conditions. The influence of temperature on the equilibrium conversions of alcohols was determined, which were found to be 89%–93% for the esterification of AA and 61%–86% for MAA in the temperature range of 60–120°C. A further increase in conversion was achieved by introducing an azeotropic agent (toluene), its optimal concentration was found to be 10%–15%.

Amphiphilic thermoresponsive copolymer bottlebrushes: synthesis, characterization, and study of their self-assembly into flower-like micelles

Amphiphilic thermoresponsive copolymer bottlebrushes based on methoxy oligo(ethylene glycol)7 methacrylate and alkoxy(C12–C14) oligo(ethylene glycol)6 methacrylate have been successfully synthesized via RAFT and conventional free-radical polymerization in toluene. The thermoresponsive behavior of the copolymers in dilute aqueous solutions was studied by turbidimetry and laser light scattering. In water, the copolymer brushes form flower-like micelles with a hydrophobic core consisting of a polymer backbone and alkyl(C12–C14) groups and poly(ethylene glycol) linear chains and loops forming a hydrophilic shell. The size and aggregation number of the micelles and the cloud point of solutions were found to depend on the copolymer composition and chain length, as well as on the synthesis method. The conditions needed for the formation of uni- and multimolecular micelles were determined. Fluorescence techniques were used to determine the CMC of the copolymers and the drug loading capacity of the micelles using pyrene as a model hydrophobic drug. Amphiphilic thermoresponsive copolymer bottlebrushes based on methoxy oligo(ethylene glycol) methacrylate (MOEGM) and alkoxy(C12-C14) oligo(ethylene glycol) methacrylate (DOEGM) have been synthesized via RAFT and conventional free-radical polymerization in toluene. In water, these copolymer brushes form flower-like micelles with a hydrophobic core consisting of a polymer backbone and alkyl(C12–C14) groups and poly(ethylene glycol) linear chains and loops forming a hydrophilic shell. The size and aggregation number of the micelles depend on the copolymer composition and chain length, as well as on the synthesis method.

Molecular brushes based on copolymers of alkoxy oligo(ethylene glycol) methacrylates and dodecyl(meth)acrylate: features of synthesis by conventional free radical polymerization

Amphiphilic copolymer molecular brushes of three different types with side chains consisting of alkyl and oligo(ethylene glycol) blocks based on higher alkoxy oligo(ethylene glycol) methacrylates (HAOEGM), methoxy oligo(ethylene glycol) methacrylates (MOEGM) and dodecyl(meth)acrylate have been successfully synthesized via conventional radical polymerization in toluene. In case of the copolymerization of HAOEGM with MOEGM, the monomer reactivity ratios were independent of the structure of higher alkyl groups (C12–C18) and the degree of ethoxylation (n = 6–11) and were equal to 0.76–0.81 and 1.19–1.27, respectively. In case of the copolymerization of HAOEGM or MOEGM with dodecyl methacrylate, the reactivity ratios were even closer to each other (1.00–1.17). Applicability of the reactivity ratios calculated at low conversions for estimating copolymer compositions at high conversions was shown. In all systems, compositionally homogeneous copolymers with a narrow molecular weight distribution were formed. For the HAOEGM (C12, n = 9)—dodecyl acrylate monomer system, the reactivity ratios were 0.88 and 0.25 and the resulting copolymers had high compositional heterogeneity.

Assembly of oligo(ethylene glycol)- and amine-containing methacrylic esters in water and water–hexane mixtures

Abstract The monomer assembly in aqueous solutions of N,N-dimethylaminoethyl methacrylate (DMAEMA), ethylene glycol methacrylate (EGMA), oligo(ethylene glycol) methacrylate (OEGMA) and a series of methoxy oligo(ethylene glycol) methacrylates (MOEGMAs) with a variable number of ethylene glycol moieties was investigated by viscosity, surface and interfacial tension measurements, IR and NMR spectroscopy. All monomers were shown to exhibit interfacial activity. The isotherms of the specific viscosity for OEGMA and MOEGMAs exhibit the exponential growth which indicates the presence of sufficiently strong intermolecular noncovalent interactions; for DMAEMA and EGMA the isotherms pass through maxima. It is associated with the formation of monomer complexes due to hydrogen bonding. A combination of computer simulations, IR data analysis and viscosity isotherms allowed one to distinguish three concentration ranges in aqueous solutions of MEG and MOEGMA. These ranges are characterized by predominant types of assemblies with the participation of oxygen-containing functional groups of the monomers.

Solid polymer electrolytes based on alternating copolymers of vinyl ethers with methoxy oligo(ethyleneoxy)ethyl groups and vinylene carbonate

Alternating copolymers (poly(1a-g-alt-VC)) of vinyl ethers with various methoxy oligo(ethyleneoxy)ethyl groups and vinylene carbonate (VC) were prepared, and the thermal and electrochemical properties of their polymer electrolytes with LiTFSI and interfacial stability between the polymer electrolyte and Li metal electrode were investigated. Tg's increased linearly with salt contents, and decreased with an increase in the chain length of methoxy oligo(ethyleneoxy)ethyl groups in the vinyl ethers at constant salt concentration. The slopes of Tg vs. [Li]/[O] were identical, independent of the polymer structure. The ionic conductivities of the polymer electrolytes increased with increasing the side-chain ethyleneoxy (EO) unit length of the vinyl ether unit in the alternating copolymers, and also their temperature dependences became relatively smaller in the polymer electrolytes having longer EO units in the vinyl ethers. The highest ionic conductivity, 1.2×10−4S/cm at 30°C, was obtained in the alternating copolymer with a side-chain EO unit length of 23.5 in the vinyl ether unit. Ion transport coupled with the segmental motion of the polymer is dominant in these polymer electrolytes. Interfacial resistance increased gradually with contact time, indicative of the formation of passivation films on the Li metal electrode. These polymer electrolytes are thermally stable and have large electrochemical windows of use.

Degradable Thermoresponsive Polyesters by Atom Transfer Radical Polyaddition and Click Chemistry

Three types of linear polyesters containing monodisperse methoxy oligo(ethylene glycol)s (mOEG, x = 6, 7, or 8) side chains (P1-mOEG, P2-mOEG, and P3-mOEG) have been synthesized by atom transfer radical polyaddition and click chemistry. Degradable disulfide and ketal groups were incorporated into the polymer backbone of P2-mOEG and P3-mOEG respectively. All of these three series of mOEG-grafted polyesters are water-soluble and display reversible thermoresponsive properties with tunable cloud point (CP). Aqueous solution properties and thermo-induced phase transitions were studied by 1H NMR, turbidimetry, DLS, and fluorescence probe method. The results indicate that these polyesters mainly adopt single chain conformations in aqueous solution below CP. OEG length has a significant effect on the CP, the CP increases by ca. 10 °C when the repeating units of OEG side chains increase from 6 to 7, and by ca. 6 °C when they increase from 7 to 8. The main chain structures also affect the CP values, which decrease ...

Hydration of phosphorylcholine groups attached to highly swollen polymer hydrogels studied by thermal analysis

Hydration of polymer chains plays a key role for determining the extent of protein adsorption on polymeric materials. Here we investigated the hydration of poly(2-methacryloyloxyethyl phosphorylcholine (MPC)) chains, which resist protein adsorption and following cell adhesion effectively. The hydration was compared with that of poly(methoxy oligo(ethylene glycol)-monomethacrylate (Me(EG)nMA)) chains, which also have hydrophilic units. The poly(MPC) and poly(Me(EG)nMA) hydrogels with equilibrium water contents (EWCs) in the range from 86 to 97wt% were prepared. By differential scanning calorimetric measurements, water in both the hydrogels was classified into two states: freezable and nonfreezable water. The poly(MPC) hydrogels had larger nonfreezable water than the poly(Me(EG)nMA) hydrogels even when their EWCs were similar, which indicated the higher hydrating ability of poly(MPC) chains. We suggested that the difference in the amount of nonfreezable water around polymer chains may influence the degree of protein adsorption resistance after contact with body fluid for a long period.

Surface Characterization of Block Copolymers with Water-soluble Block by using Sum-Frequency Generation Spectroscopy

A series of amphiphilic block copolymers containing poly[oligo(ethylene glycol) methacrylate] segments and the corresponding poly[methyl ethers of oligo(ethylene glycol) methacrylate] block copolymer surfaces are investigated by using sum-frequency generation (SFG) vibrational spectroscopy. The terminal moiety on the oligo(ethylene glycol) side chain played an important role in determining the surface structure of the block copolymer films. Due to the amphiphilic character of the methoxy oligo(ethylene glycol) side chain, the PME3MA block exposes the terminal methyl group to the surface and reduces the surface tension in air or vacuum, and it is possible that configurational entropy may also favor the presence of side chains at the surface. The molecular orientation of the block copolymer at the surface is modified due to the multilayered structures of the block copolymers. [DOI: 10.1380/ejssnt.2006.515]

Ionic conductivity and lithium ion transport characteristics of gel-type polymer electrolytes using lithium p-[methoxy oligo(ethyleneoxy)] benzenesulfonates

Lithium p-[methoxy oligo(ethyleneoxy)] benzenesulfonates (LiEOnBS) with different repeating units of ethylene oxide were synthesized, and gel-polymer electrolytes were fabricated using them. The ionic conductivity and lithium ion transport number were measured as a function of salt concentration and repeating unit of ethylene oxide of the LiEOnBS. Temperature dependence of ionic conductivity was well fitted to the Vogel–Tamman–Fulcher (VTF) equation. Lithium ion transport number ( t L i + ) was measured to be in the range of 0.6–0.91 for the gel-polymer electrolytes containing LiEOnBS. The maximum t L i + was obtained to be 0.91 for the 0.1 M LiEO3BS in polymer electrolyte. The synthesized LiEOnBS showed single ion transport like characteristics when n was larger than 3.

Controlled structure copolymers for the dispersion of high-performance ceramics in aqueous media

Statistical copolymers of a methoxy oligo(ethylene glycol) methacrylate (OEGMA) and either 2-(dimethylamino))ethyl methacrylate (DMA) or methacrylic acid (MAA) have been examined as dispersants for barium titanate powder in water and water isopropyl alcohol mixtures. The dispersing efficiency of the polymers was assessed using gravitational sedimentation and by measuring the particle size distributions of the dispersed powders by disk centrifuge photosedimentometry (DCP). OEGMA copolymers with MAA were very efficient, causing the mean particle size of the dispersed powder to decrease by an order of magnitude in the presence of dispersant. In contrast, OEGMA-DMA copolymers were completely ineffective. The best MAA copolymers gave higher dispersion efficiency over a wider pH range (pH 1 to 10) compared to a typical commercial dispersant Darvan-C, which was efficient only above pH 7. X-Ray photoelectron spectroscopy, zeta potential measurements, infra red spectroscopy and DCP studies all show that the acid-containing copolymers bind strongly to the barium titanate surface via the carboxylic acid groups resulting in good quality dispersions. There were no changes in the dispersion quality due to desorption of the dispersant even after extensive washing and drying of the copolymer-coated particles. The dried particles showed complete redispersion in water even after washing and drying, again indicating strong binding of the copolymer to the oxide surface.

Ion conduction of poly[methoxy oligo (oxyethylene) propylene] synthesized by the Et(Ind)2ZrCl2-MAO catalyst

Poly[methoxy oligo (oxyethylene) propylene] was synthesized by means of the Et(Ind)2ZrCl2-MAO catalyst. The ionic conductivity of poly[methoxy oligo (oxyethylene) propylene] with the lithium salt depends on the content of the lithium salt. The temperature dependence of conductivity was determined and the Vogel–Tammann/Hesser–Fulcher (VTF) plot agreed well with theoretical values, confirming the influence of the polymer segmental motion on conductivity. The ionic conductivity as high as 10−4.7 s/cm can be obtained at room temperature, and this can be increased one or two orders of magnitude by blending the polyelectrolyte with hydroxyl-containing additives such as tetraethylene glycol. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 1397–1400, 1999

Ion conduction of poly[methoxy oligo (oxyethylene) propylene] synthesized by the Et(Ind)2ZrCl2‐MAO catalyst

Ion conduction of poly[methoxy oligo (oxyethylene) propylene] synthesized by the Et(Ind)2ZrCl2‐MAO catalyst

THERMAL BEHAVIOR AND IONIC CONDUCTIVITY OF POLY[LITHIUM-N(4-SULFO-PHENYL) MALEIMIDE -CO-METHOXY OLIGO(OXYETHYLENE) METHACRYLATE

Poly[lithium-N(4-sulfophenyl) maleimide -co- methoxy oligo-(oxyethylene) methacrylates] [P(LiSMOEn)s] with three different oligoether side chains and different salt concentrations were synthesized. The copolyelectrolytes are essentially random in structure, with blocks of methoxy oligo(oxyethylene) meth-acrylate (MOEnM) recurring sporadically in between the salt units of N(4-sulfophenyl) maleimide. They all show two glass transitions in the temperature range of −100 to 100°C. The first one below −30°C is assigned to the oligo(oxyethylene) side chain (T g1), while the second one located between 20 and 50°C is attributed to the main chain of the polymer host (T g2). The maximum ionic conductivity of the copolymer electrolytes, 1.6 × 10−7 S cm−1 at 25°C, occurs at lithium salt concentration [Li+]/[EO] = 2.2 mol%. The ionic conductive behavior of the copolyelectrolytes follows the Vogel-Tammann-Fulcher (VTF) equation. Moreover, a special VTF behavior exists in the copolymers with shorter oligoether side chain and higher salt concentration. Sweep voltammetric results indicate that these copolyelectrolytes have a good electrochemical stability window.

Ionic conduction of lithium oligo(ethyleneoxy) phenylsulfonate and its complex with poly(ethylene oxide)

The organic lithium salt, lithium p-[methoxy oligo(ethyleneoxy)] phenylsulfonate (EO n PSLi), possesses the ability of self-dissociation which leads to the exhibition of ionic conduction. The length of the ethyleneoxy repeating units in EO n PSLi has effects on the morphology, the self-dissociation ability, the `salt' concentration, the ionic conductive behaviour and the activation energy of ion transport of the oligoether salt, which consequently influences the ionic conductivity. In the complex of poly(ethylene oxide) (PEO) and EO 2PSLi, with a decrease of EO 2PSLi content the phase structure of PEO changes gradually from a dispersed island-like structure to a well-distributed, continuous structure. The corresponding ionic conductive behaviour changes from Arrhenius type to non-Arrhenius type in which the transport of ion carriers depends on the segmental movement of PEO macromolecules.