Poly(vinyl alcohol)-graft-poly(ethylene glycol) resins and their use in solid-phase synthesis and supported TEMPO catalysis

New poly(vinyl alcohol)-graft-poly(ethylene glycol) (PVA-g-PEG) resins with various PEG chain lengths, which have high loadings and good swelling both in water and organic solvents, have been prepared via an anionic polymerization of ethylene oxide onto PVA beads and applied in solid-phase synthesis, supported TEMPO catalysis and in HR-MAS 1H NMR spectral analysis.     

Functionalized cross-linked poly(vinyl alcohol) resins as reaction scavengers and as supports for solid-phase organic synthesis

New hydrophilic poly(vinyl alcohol) (PVA-OH) resins were prepared by an inverse suspension polymerization using epichlorohydrin as a cross-linker. These novel resins swell in a variety of solvents commonly used in solid-phase organic synthesis, such as dicholomethane, dioxane, methanol, tetrahydrofuran, and dimethylformamide. In addition, PVA-OH shows excellent swelling in water. The cross-linked PVA-OH beads were functionalized with an aldehyde group and were tested as scavengers for primary amines in three different reactions: amide bond formation, reductive amination reaction, and urea formation. With 1-2 equiv of the PVA aldehyde resin, all the excess primary amines were successfully scavenged. The utility of PVA-OH resins as solid supports in mono- and dipeptide synthesis was also investigated using symmetrical anhydride and MSNT/MeIm (2,4,6-mesitylenesulfonyl-3-nitro-1,2,4-triazolide in the presence of 1-methylimidazol) methods.     

Synthesis and characterization of novel photoactive polymer poly(vinyl alcohol)‐graft‐poly(vinyl naphthalene)

A copolymer of poly(vinyl naphthalene) grafted onto poly(vinyl alcohol) has been synthesized with nitroxide‐mediated controlled radical polymerization. By separating the processes of the generation of grafting sites and polymerization, we can avoid the formation of the homopolymer. Because of its architecture, the polymer is soluble in water, despite the high content of hydrophobic groups. The naphthalene chromophores tend to aggregate, forming hydrophobic microdomains in an aqueous solution. Those aggregates exist in a very constrained environment that leads to extraordinarily large redshifts of both the absorption and emission of the polymer. The polymer acts as an efficient photosensitizer in photoinduced electron transfer. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2675–2683, 2006     

Preparation, characterization and application of pyrene-loaded methoxy poly(ethylene glycol)–poly(lactic acid) copolymer nanoparticles

Pyrene-loaded biodegradable polymer nanoparticles were prepared by incorporating pyrene into the polymer nanoparticles formulated from amphiphilic diblock copolymer, methoxy poly(ethylene glycol)–poly(lactic acid) (MePEG–PLA). Their morphological structure and physical properties were characterized by nuclear magnetic resonance (NMR), dynamic light scattering, fluorescence spectroscopy, transmission electronic microscopy and zeta potential measurements. Further, MePEG–PLA nanoparticles containing pyrene as fluorescent marker were administered intranasally to rats, and the distribution of nanoparticles in the nasal mucosa and the olfactory bulb were visualized by fluorescence microscopy. NMR results confirmed that MePEG–PLA copolymer can form nanoparticles in water, and hydrophilic PEG chains were located on the surface of the nanoparticles. The particle size, zeta potential and pyrene loading efficiency of MePEG–PLA nanoparticles were dependent on the PLA block content in the copolymer. Following nasal administration, the absorption of nanoparticles across the epithelium was rapid, with fluorescence observed in the olfactory bulb at 5 min, and a higher level of fluorescence persisted in the olfactory mucosa than that in the respiratory mucosa. These results show that pyrene could serve as a useful fluorescence probe for incorporation into polymer nanoparticles to study tissue distribution and MePEG–PLA nanoparticles might have a great potential as carriers of hydrophobic drugs.     

Preparation and characterization of iodinated poly(vinyl alcohol) microfibril

Iodination of poly(vinyl alcohol) (PVA) microfibril, which was obtained from saponification of poly(vinyl pivalate), was conducted before and after zone drawing at various conditions. The resulting PVA microfibrils were characterized by differential scanning calorimeter and scanning electron microscopy. Surface morphologies of these PVA microfibrils showed some differences between PVA microfibril iodinated after and before drawing. Crude shapes of PVA microfibrils iodinated after drawing indicated that iodine decreased the structural regularity severely. On the other hand, PVA microfibrils iodinated before drawing showed relatively ordered surfaces. This was ascribed to the enhanced molecular ordering of PVA microfibrils due on zone drawing. Iodinated PVA microfibrils showed a decrease in crystal melting temperature of about 100°C compared to the untreated sample. PVA microfibrils drawn after iodination showed relatively higher crystal melting temperature than those of microfibrils iodinated after drawing. These results were considered as the proofs of the changes in crystalline lattice of the PVA microfibrils. Effects, of drawing temperature on sublimation of iodine were also evaluated.     

ChemMatrix, a poly(ethylene glycol)-based support for the solid-phase synthesis of complex peptides

CM (ChemMatrix) resin is a new, totally poly(ethylene glycol) (PEG)-based resin, made exclusively from primary ether bonds and, therefore, highly chemically stable. It exhibits good loading and is user-friendly because of its free-flowing form upon drying. It performs excellently for the preparation of hydrophobic, highly structured, and poly-Arg peptides, as compared to polystyrene (PS) resins. In the most striking example, stepwise solid-phase assembly of the highly complex beta-amyloid (1-42) peptide resulted in a crude material of 91% purity. In contrast, literature procedures using PS or PEG-PS-based resins for this peptide required convergent approaches, additional time-consuming steps, or both. In addition to the difficulties of its synthesis, characterization of the beta-amyloid (1-42) peptide as a monomer is also a challenge, and methods for characterization by HPLC and MALDI-TOF have also been developed.     

Preparation and preliminary characterization of poly(ethylene glycol)-pepstatin conjugate

The carboxyl function of pepstatin has been coupled, through an amide bond, to methoxypoly(ethylene glycol) (5 kDa), to which an amino function had been previously grafted. The mPEG-pepstatin conjugate inhibits hog pepsin (aspartic proteinase) in vitro as pepstatin itself, however, with a 400 times higher apparent K_i. The conjugate apparently does not inhibit proteinases belonging to other proteinase families such as serine (trypsin, carboxypeptidase Y), cysteine (Papaya proteinase III), or metallo (collagenase) proteinases.     

Green polymer chemistry: Precision synthesis of novel multifunctional poly(ethylene glycol)s using enzymatic catalysis

This paper gives an overview about enzyme catalysis, and reports the precision synthesis of multifunctional poly(ethylene glycol)s using this green chemistry approach. Specifically, vinyl acrylate was transesterified with tetraethylene glycol (TEG) and a PEG with DP_n = 23, and then (HO)₂–TEG–(OH)₂ and (HO)₂–PEG–(OH)₂ were synthesized by the Michael addition of diethanolamine to the acrylate double bonds. These structures will serve as the core of novel dendrimers designed for drug delivery applications.     

Polystyrene resins cross-linked with di- or tri(ethylene glycol) dimethacrylates as supports for solid-phase peptide synthesis

Polystyrene resins cross-linked with di(ethylene glycol) dimethacrylate (DEGDMA) and tri(ethylene glycol) dimethacrylate (TEGDMA), DEGDMA-PS and TEGDMA-PS, were synthesized by suspension copolymerization. Four functionalized resins, chloromethyl resin, 4-hydroxymethylphenoxymethyl resin (Wang resin), 4-methylbenzhydrylamine resin (MBHA resin) and 2-chlorotrityl chloride resin, were prepared from DEGDMA-PS and TEGDMA-PS. DEGDMA-PS and TEGDMA-PS showed high reactivity in the functionalization reactions in comparison with Merrifield resin (polystyrene cross-linked with divinylbenzene, DVB-PS). DEGDMA-PS-Wang resin and TEGDMA-PS-Wang resin were used as the solid-phase support for the synthesis of a difficult sequence, the fragment of acyl carrier protein 65-74. The yields of the crude peptide synthesized using DEGDMA-PS-Wang resin, TEGDMA-PS-Wang resin and DVB-PS-Wang resin were 92.3%, 91.6% and 78.8%, respectively. The purities of the crude peptides were 85.7%, 88.1% and 73.3%, respectively.     

紫外光交联可降解聚对二氧环己酮/聚乙二醇薄膜制备与表征

以2,2-二甲氧基-2-苯基苯乙酮(DMPA)为引发剂,将四臂端丙烯酸酯聚对二氧环己酮(PPDO-4AC)和聚乙二醇双丙烯酸酯(PEG-DA)经紫外光照射制得PPDO/PEG交联薄膜.研究了光照时间和DMPA用量对PPDO/PEG交联薄膜凝胶含量的影响.DSC研究表明共聚物中两组分的相容性较好,Tg随着共聚物中PEG链...     

Synthesis and characterization of poly(ethylene glycol) derivatives

Five general routes for the preparation of polyoxyethylene [generally referred to as poly(ethylene glycol) or PEG] derivatives are described. These routes are (1) nucleophilic displacements with the alkoxide of PEG, (2) nucleophilic displacement on PEG–tosylate, –mesylate, or –bromide, (3) reductive amination of PEG–aldehyde, (4) reductive amination of PEG–amine, and (5) nucleophilic displacements on the s-triazine derivatives prepared from s-triazine trichloride (cyanuric chloride) and PEG. Eighteen derivatives are prepared and potential applications to catalysis, cell purifications, and other areas are discussed briefly.     

Synthesis and characterization of poly(ethylene glycol) grafted poly(L-lactide)

Poly(ethylene glycol) grafted poly(L -lactide) was prepared by ring opening polymerization of L -lactide and epoxy-terminated poly(ethylene glycol) methyl ether (PEGME). Stannous octoate and Al(Et)₃·0.5 H₂O were tested as polymerization catalysts, and Al(Et)₃·0.5 H₂O was found to be more effective for the ring-opening of the epoxy group of the modified PEGME monomer. The synthesized polymers were characterized by NMR and the efficiency of the incorporation of epoxy-terminated PEGME in the copolymer was determined.     

Synthesis and characterization of poly(ethylene glycol) methyl ether endcapped poly(ethylene terephthalate)

Linear and branched poly(ethylene terephthalate) (PET) copolymers with polyethylene glycol) (PEG) methyl ether (700 or 2000 g/mol) end groups were synthesized using conventional melt polymerization. DSC analysis demonstrated that low levels of PEG end groups accelerated PET crystallization. The incorporated PEG end groups also decreased the crystallization temperature of PET dramatically, and copolymers with a high content of PEG (>17.6 wt%) were able to crystallize at room temperature. Rheological analysis demonstrated that the presence of PEG end groups effectively decreased the melt viscosities and facilitated melt processing. XPS and ATR-FTIR revealed that the PEG end groups tended to aggregate on the surface, and the surface of compression molded films containing 34.0 wt% PEG were PEG rich (85 wt% PEG). PEG end-capped PET (34.0 wt% PEG) and PET films were immersed into a fibrinogen solution (0.7 mg/mL BSA) for 72 h to investigate the propensity for protein adhesion. XPS demonstrated that the concentration of nitrogen (1.05%) on the surface of PEG endcapped PET film was statistically lower than PET (7.67%). SEM analysis was consistent with XPS results, and revealed the presence of adsorbed protein on the surface of PET films.     

Study of the self‐diffusion of poly(ethylene glycol)s in poly(vinyl alcohol) aqueous systems

We have measured the self‐diffusion coefficients of a series of oligo‐ and poly(ethylene glycol)s with molecular weights ranging from 150 to 10,000, in aqueous solutions and gels of poly(vinyl alcohol) (PVA), using the pulsed‐gradient spin‐echo NMR techniques. The PVA concentrations varied from 0 to 0.38 g/mL which ranged from dilute solutions to polymer gels. Effects of the diffusant size and polymer concentration on the self‐diffusion coefficients have been investigated. The temperature dependence of the self‐diffusion coefficients has also been studied for poly(ethylene glycol)s with molecular weights of 600 and 2,000. Several theoretical models based on different physical concepts are used to fit the experimental data. The suitability of these models in the interpretation of the self‐diffusion data is discussed. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 2396–2403, 1999     

Preparation and characterization of novel physically cross-linked hydrogels composed of poly(vinyl alcohol) and amine-terminated polyamidoamine dendrimer

Poly(vinyl alcohol) (PVA) and polyamidoamine (PAMAM) dendrimers are water-soluble, biocompatible and biodegradable polymers, which have been widely applied in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of PVA and amine-terminated PAMAM dendrimer G6-NH(2) were prepared by cyclic freezing/thawing treatment of aqueous solutions containing PVA and G6-NH(2). The FT-IR analysis and elemental analysis indicated that PAMAM dendrimer G6-NH(2) was successfully introduced into the formed hydrogels, possibly via hydrogen bonds among hydroxyl groups, amide groups and amino groups in PVA and PAMAM dendrimer in the process of freezing-thawing cycle. Compared with physically cross-linked PVA hydrogel, PVA/G6-NH(2) hydrogels show higher swelling ratios and faster re-swelling rate due to the higher hydrophilicity of PAMAM dendrimer G6-NH(2). Higher contents of G6-NH(2) in PVA/G6-NH(2) hydrogels resulted in higher swelling ratios and faster re-swelling rates. With increasing freezing/thawing cyclic times, the swelling ratios and re-swelling rates of PVA/G6-NH(2) hydrogels decreased, which is similar to that of physically cross-linked PVA hydrogel. Combining the special host property of polyamidoamine dendrimer, these novel physically cross-linked hydrogels are expected to have potential use in drug delivery, including improving drug-loading amounts in hydrogels and prolonging drug release time. Swelling ratios of physically cross-linked PVA/G6-NH(2)-50 hydrogels prepared by three, six, nine freezing/thawing cycles. The swelling equilibrium experiments were carried out in distilled water at 25 degrees C.     

Synthesis and characterization of a novel methoxy poly(ethylene glycol)-Tat peptide-chitosan copolymers

In this paper, a novel chitosan-g-(-O-methyl poly (ethylene glycol))-g-(-N-Tat peptide) (CS-mPEG-Tat) copolymer was synthesized. The synthesized intermediates and final products were characterized and confirmed by Fourier transform infrared spectrum, ¹H nuclear magnetic resonance spectrum, and X-ray diffraction, respectively. The particle sizes, size distributions, and zeta potentials can also be determined by dynamic light scattering. Agarose gel electrophoresis study showed effective DNA-binding ability of CS-mPEG-Tat. In vitro cytotoxicity assay indicated that CS-mPEG-Tat copolymers were low toxic and cell compatible as the polymer concentration was smaller than 5 mg/ml. This work provides a facile approach to prepare biocompatible PEG-peptide-chitosan copolymer nanoparticles with controllable performances. In conclusion, the obtained CS-mPEG-Tat copolymer might be attractive cationic polymers for nonviral gene therapy.     

Preparation and Characterization of Chitosan Composite Membranes Crosslinked by Carboxyl-capped Poly（ethylene glycol）

In this study a series of chemically crosslinked chitosan/poly（ethylene glycol） （CS/PEG） composite membranes were prepared with PEG as a crosslinking reagent other than an additional blend. First, carboxyl-eapped poly（ethylene glycol） （HOOC-PEG-COOH） was synthesized. Dense CS/PEG composite membranes were then prepared by casting/evaporation of CS and HOOC-PEG-COOH mixture in acetic acid solution. Chitosan was chemically crosslinked due to the amidation between the carboxyl in HOOC-PEG-COOH and the amino in chitosan under heating, as confirmed by FTIR analysis. The hydrophilicity, water-resistance and mechanical properties of pure and crosslinked chitosan membranes were characterized, respectively. The results of water contact angle and water absorption showed that the hydrophilicity of chitosan membranes could be significantly improved, while no significant difference of weight loss between pure chitosan membranes and crosslinked ones was detected, indicating that composite membranes with amidation crosslinking possess excellent water resistanance ability. Moreover, the tensile strength of chitosan membranes could be significantly enhanced with the addition of certain amount of HOOC-PEG-COOH crosslinker, while the elongation at break didn＇t degrade at the same time. Additionally, the results of swelling behaviors in water at different pH suggested that the composite membranes were pH sensitive.     

Ethylene glycol aluminum as a novel catalyst for the synthesis of poly(ethylene terephthalate)

Ethylene glycol aluminum was prepared efficiently and characterized by FT-IR and NMR.It exhibited higher catalytic activity and had profitable effect than titanium glycolate and ethylene glycol antimony for the synthesis of poly(ethylene terephthalate) (PET).It was only used as polycondensation catalyst because it was sensitive to water.For this catalyst,the degree of esterification of the theoretical amount of water was produced up to 95%at 260℃,while the intrinsic viscosity and content of terminal carboxyl groups of the corresponding PET polyester,polymerized at 280℃,70 Pa for 39 min,was 0.87 dL/g and 23.0μmol/g,respectively. Ethylene glycol aluminum was a promising catalyst for the synthesis of PET polyester.     

Preparation and characteristics of photocross-linkable poly(vinyl alcohol)

The reaction of poly(vinyl alcohol) with styrylpyridinium and quinolinium salts which contain formyl group produced water-soluble photosensitive polymers. The sensitivity was high, although the content of the styryl groups was extraordinarily low. Spectroscopical studies revealed that the high sensitivity is due to the aggregation of photofunctional group in the polymer matrix which leads to cyclodimerization on exposure to ultraviolet (UV) light.