Multifunctional Poly(ethylene glycol)s

In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf‐PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and defined with state‐of‐the‐art characterization techniques—for example real‐time ¹H NMR spectroscopy monitoring of the EO polymerization kinetics—this emerging class of polymers embodies a powerful platform for bio‐ and drug conjugation.     

Molecular Dynamics and Organization of Micellar Complexes of Poly(acrylic acid) with Poly(ethylene glycol)-Based Surfactants

The structure and molecular dynamics of complexes of poly(acrylic acid) with dodecyl-substituted poly(ethylene glycol)s in aqueous solutions are studied by viscometry and spin probe ESR spectroscopy. It is shown that, at low surfactant concentrations, the complexes have a compact globular conformation. The local mobility of the surfactant molecules in the complexes under consideration is much lower than their mobility in free micelles. As a result of increasing surfactant concentration in solution, the hydrophilic associates of the surfactant micelles with the polyacid having an unfolded coil conformation are formed. In an associate, a significant fraction of poly(ethylene glycol) fragments incorporated into micelles is in the free state, i.e., these fragments are not bound with a polymer chain. The local mobility of the surfactant molecules in the associate is considerably higher than in the complex with a compact conformation, and this mobility grows with the increasing number of micelles involved in the associate.     

聚乙烯/聚乙二醇共混物中极性组分的表面富集

采用衰减全反射傅立叶变换红外光谱(FTIR-ATR)和扫描电子显微镜研究了极性组分聚乙二醇在聚乙烯／聚乙二醇共混物中的表面富集特性。研究结果认为不同组分表面自由能的差异以及聚乙烯基体的结晶异相排斥作用是导致聚乙二醇组分向共混物表面富集的主要驱动力，而极性组分相区的大小和分布则是影响其选择性迁移过程的重要因素。因此，可以通过添加合适相容剂的办法对聚乙二醇组分的表面富集程度进行有效的调控。     

Micellization and Thermogelation of Poly(ether urethane)s Comprising Poly(ethylene glycol) and Poly(propylene glycol)

A series of multiblock poly(ether urethane)s comprising poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments were synthesized. Their aqueous solutions exhibited thermogelling behavior at critical gelation concentrations (CGC) ranging from 8 to 12 wt%. The composition and structural information of the copolymers were studied by GPC and ¹H NMR. The critical micellization concentration (CMC) and thermodynamic parameters for micelle formation were determined at different temperatures. The temperature response of the copolymer solutions were studied and found to be associated with the composition of the copolymers.     

Poly(ethylene glycol)-based shape-memory polymers

Poly(ethylene glycol) (PEG) blends photo-curable and thermal activated shape-memory polymers (SMPs), with different activation temperature (T_switch), have been synthesized and characterized. PEG blends with different molecular weights were chain-end functionalized with isocyanate ethyl methacrylate and photo-cured with UV lamp. Degree of cross-linking of the blend network, determined by gel content measurement, resulted as higher than 95%. The thermal and thermomechanical properties of these SMPs PEG blends were characterized by differential scanning calorimetry and dynamic mechanical analysis. The shape-memory properties of the networks were quantified using thermomechanical three-point bending experiments and showed strain fixity rates higher than 99% and a minimum strain recovery ratio of 82%.     

聚L-丙氨酸-聚乙二醇嵌段共聚物纳米胶束的研究

分别以氨基聚乙二醇和氨基聚乙二醇单甲醚为大分子引发剂,采用开环聚合的方法合成了两亲性聚L-丙氨酸-聚乙二醇(PAE)和聚L-丙氨酸-聚乙二醇单甲醚(PAME)两种嵌段共聚物,其结构经1H NMR,IR,DSC,GPC等表征;利用园二色技术研究了其在水溶液中的二级结构,用芘荧光探针技术研究了其胶束的形成及其临界胶束浓度(CMC),利用透射电镜研究了胶束的形态。结果表明,在水溶液中共聚物链以α-螺旋构象形式存在,在一定条件下嵌段共聚物PAE-1,PAE-2,PAME-1和PAME-2能够形成球形的稳定胶束,PAE-1形成胶束的CMC为3.36×10-5mol.L-1,CMC值受嵌段类型和共聚物中聚L-丙氨酸链段含量的影响。     

Electrostatic Assembly of Poly(ethylene glycol) Nanotubes

Poly(ethylene glycol) (PEG)‐based films, nanotubes, and nanotube arrays were successfully made using layer‐by‐layer (LbL) assembly ion‐containing PEO derivatives on porous templates and planar substrates. PEG nanotubes are challenging to produce because PEG dissolves into solutions and solvents used during nanotube processing, but our techniques circumvent the issue. Nanotube dimensions were verified using microscopy and the average observed diameter was 155 nm. The PEG‐based structures showed remarkable stability in water, salt water, and sodium hydroxide solution.

     

聚L-丙氨酸-聚乙二醇嵌段共聚物的胶束化行为研究

以氨基聚乙二醇单甲醚(MPEG-NH₂)为大分子引发剂, 采用开环聚合方法合成了聚L-丙氨酸-聚乙二醇嵌段共聚物(PAME), 并对其结构进行了表征; 用圆二色谱(CD)研究了嵌段共聚物在水溶液中的二级结构, 用芘荧光探针技术研究了共聚物胶束的形成及其临界胶束浓度(CMC), 利用动态光散射(DLS)和透射电镜(TEM)研究了胶束的粒径分布和形态. 结果表明, 在水溶液中共聚物链以α-螺旋构象形式存在, 在一定条件下嵌段共聚物能够形成球形的稳定胶束, PAME-1形成胶束的CMC为1.99×10^-5 mol/L, CMC值受共聚物中聚L-丙氨酸(PLA)链段含量的影响.     

Poly(ethylene glycol) Surface Coated Magnetic Particles

Summary: A methacrylate‐functionalized poly(ethylene glycol) macromonomer was copolymerized at the surface of methacrylate‐derivatized maghemite nanoparticles. After silylation of the magnetic core with methacryloxypropyltrimethoxysilane, two grafting procedures based on either a direct copolymerization reaction in water or an inverse emulsion polymerization were compared. A direct copolymerization led to low polymer surface amounts, whereas an inverse emulsion process allowed nanocomposite particles containing up to 90 wt.‐% polymer to be obtained.

TEM picture of maghemite‐PEG hybrid particles.     

Poly(ethylene glycol) gradient for biochip development

A novel method of producing a poly(ethylene glycol) (PEG)-based gradient matrix that varies gradually in thickness from 0 to 500 A over a distance of 5-20 mm is presented. The gradient matrix is graft copolymerized from a mixture of PEG methacrylates onto organic thin films providing free radical polymerization sites initiated by UV irradiation at 254 nm. The films used as grafting platforms consist of either a spin-coated cycloolefin polymer or a self-assembled monolayer on planar gold. The thickness/irradiation gradient is realized by means of a moving shutter that slowly uncovers the modified gold substrate. The structural and functional characteristics of the gradient matrix are investigated with respect to thickness profile, degree of carboxylation, and subsequent immobilization of two model proteins of different sizes and shapes. These characteristics are studied with ellipsometry and infrared reflection-absorption microscopy using a grazing angle objective. It is revealed that the relatively small carboxylation agent used offers homogeneous activation throughout the gradient, even in the thick areas, whereas the diffusion/interpenetration and subsequent immobilization of large proteins is partially hindered. This is crucial information in biosensor design that can be easily obtained from a gradient experiment on a single sample. Moreover, the partially hindered protein interpenetration, the marginal swelling upon hydration, and the unspecific nature of the graft polymerization suggest a matrix growth mechanism that favors the formation of a bushlike polymer structure with a certain degree of cross linking.     

Lecithin Organogels Containing Poly(ethylene glycol) Monolaurate

The effect of added poly(ethylene glycol) monolaurate (PEGML) on the formation and properties of lecithin organogels composed of polymer-like micelles was studied by the methods of dynamic rheology and the Fourier transform IR spectroscopy. It was established that the addition of even small amounts of PEGML causes a significant decrease in viscosity, whereas the elastic properties of organogels remained almost unchanged. The analysis of the scaling dependences indicated that the formation mechanism of polymer-like lecithin micelles remained also unchanged. Spectral studies revealed that the PEGML molecules affect intermolecular hydrogen bonding during their incorporation into micelles, thus stabilizing micellar structure. This effect is caused by the partial dehydration of the lecithin polar region. This leads to a decrease in the number of hydrogen bonds or their weakening and, as a result, to the disintegration of polymer-like lecithin micelles into shorter micellar aggregates.     

Poly(ethylene glycol) self-assembled monolayer island growth

Here, we report a study of the morphology and growth dynamics of a self-assembled monolayer (SAM) of the amide containing poly(ethylene glycol) (PEG) thiol (CH3O(CH2CH2O)17NHCO(CH2)2SH) on atomically flat Au(111) surfaces. SAM growth from a 20 muM ethanolic solution reveals island growth through three distinct steps: island nucleation, island growth, and coalescence. The coalescence-step, filling voids in the SAM, is by far slowest. The fine structure study reveals dendritic island formation, an observation which can be explained by attractive intermolecular interactions and surface diffusion-limited aggregation. We have also observed a change in the island height, which peaks during the island growth phase. This height change can be associated with a molecular conformational transition.     

Well-defined Poly(lactic acid)s Containing Poly(ethylene glycol) Side-chains

Poly(ethylene glycol) (PEG) side-chain functionalized lactide analogues have been synthesized in four steps from commercially available L-lactide. The key step in the synthesis is the 1,3-dipolar cycloaddition between PEG-azides and a highly strained spirolactide-heptene monomer, which proceeds in high conversions. The PEG-grafted lactides analogues were polymerized via ring-opening polymerization using triazacyclodecene as organocatalyst to give well-defined tri- and hepta-(ethylene glycol)-poly(lactide)s (PLA) with molecular weights above 10 kDa and polydispersity indices between 1.6 and 2.1. PEG-poly(lactide) (PLA) with PEG chain M(n) 2000 was also prepared but GPC analysis showed a bimodal profile indicating the presence of starting macromonomer. Cell adhesion assays were performed using MC3T3 E-1 osteoblast-like cells demonstrating that PEG-containing PLA reduces cell adhesion significantly when compared to unfunctionalized PLA.     

聚乙二醇支载的杂环化合物库的液相合成

随着组合化学的迅速发展, 兼容固相合成和溶液相合成优点的液相合成方法已成为实现组合化学的一条重要途径. 综述了近年来聚乙二醇为可溶性聚合物载体支载的杂环化合物库的研究, 并展望了其今后的发展方向.     

聚乙二醇-异黄酮复合物的合成

用聚乙二醇(PEG)修饰异黄酮类化合物(1)的侧链,并采用不同氨基酸做连接臂,合成了聚乙二醇-异黄酮复合物--聚乙二醇-异黄酮酯前药(6),其结构经1H NMR和IR表征.在磷酸缓冲溶液中,1能在10 h内释放完全;6的载药量有待进一步提高.     

Synthesis and Characterization of Poly(ethylene glycol) Dimethacrylate Hydrogels

Facile synthesis and detailed characterization of photo-polymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and their hydrogels are described. Combined analyses of ¹H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). A systematic investigation into the structure and mechanical properties of PEGDM hydrogels was performed to characterize the relationships between the network structure and gel properties. Small-angle neutron scattering was used to characterize the structural features of hydrogels with respect to their semidilute solution precursors. A well-defined structural length scale (correlation length) manifested as a maximum in the scattering intensity was observed for hydrogels derived from high molecular mass PEGDMs and/or high oligomer mass fractions. Hydrogels derived from lower molecular mass PEGDMs and/or low oligomer mass fractions exhibited multiple correlation lengths suggesting the formation of inhomogeneous gel structures. The shear moduli, determined from uniaxial compression measurement, showed that the gel structures correlate well with the gel mechanical properties.     

Poly(ethylene glycol) hydrogel microstructures encapsulating living cells

We present an easy and effective method for the encapsulation of cells inside PEG-based hydrogel microstructures fabricated using photolithography. High-density arrays of three-dimensional microstructures were created on substrates using this method. Mammalian cells were encapsulated in cylindrical hydrogel microstructures of 600 and 50 micrometers in diameter or in cubic hydrogel structures in microfluidic channels. Reducing lateral dimension of the individual hydrogel microstructure to 50 micrometers allowed us to isolate 1-3 cells per microstructure. Viability assays demonstrated that cells remained viable inside these hydrogels after encapsulation for up to 7 days.