Polyethylene Glycol as a Nonionic Liquid Solvent for the Synthesis of N-Alkyl and N-Arylimides

Polyethylene glycol (PEG) an inexpensive, nontoxic, environmentally friendly reaction medium for the synthesis of N-alkyl and N-arylphthalimides to afford the corresponding adducts in excellent yields under mild reaction conditions. The use of PEG avoids the use of acidic or basic catalysts, and moreover PEG could be recovered and reused.     

Stealth star polymers: a new high-loading scaffold for liquid-phase organic synthesis

[formula: see text] Polyethylene glycol (PEG) has proven to be a versatile soluble-polymer support for organic synthesis, though the use of PEG has been limited by its relatively low loading (0.5 mmol/g or less). We have developed a new high-loading (1 mmol/g) soluble-star polymer based on a cyclotriphosphazene core with PEG arms that exhibit superior precipitation properties compared with those of linear PEG. Additionally, the heterocyclic core does not add interfering signals to the 1H or 13C NMR.     

Identification and reduction of ion suppression effects on pharmacokinetic parameters by polyethylene glycol 400

Ion suppression in mass spectrometry has been described recently in detail and should always be considered during analysis by liquid chromatography/tandem mass spectrometry (LC/MS/MS) in a drug metabolism and pharmacokinetics (DMPK) environment. At best, ion suppression leads to decreased sensitivity but at worst could lead to incorrectly determined pharmacokinetic (PK) parameters. Our investigations centred on polyethylene glycol (PEG 400), an excipient often used in pre-clinical dosing vehicles. PEG was also found to be present in large quantities in the blood collection tubes used for pre-clinical PK studies. Ion suppression was observed for many analytes, either due to the use of PEG in the dosing vehicle or in blood collection tubes. The elimination of large ion suppression effects was attained by simple chromatographic gradient changes and the use of alternative blood collection tubes. The effect of the above was to increase the detected plasma concentration levels, which resulted in a change in key PK parameters.     

Spontaneous formation of Ag nanoparticles in dimethylacetamide solution of poly(ethylene glycol)

The spontaneous formation of Ag nanoparticles in a dimethylacetamide (DMAC) solution of poly(ethylene glycol) (PEG) was studied. FTIR analysis showed the formation of carbonyl groups, revealing that PEG acted as not only a protective agent but also a reducing agent in the formation of Ag nanoparticles. Since no significant reactions were observed when poly(tetramethylene glycol) (PTMG) was used to replace PEG or acetonitrile was used to replace DMAC, it was suggested that PEG molecules might be coiled to form pseudo-crown ether cavities, in which Ag complexes were bound to the oxyethylene groups and reduced, and that the use of a solvent which might appropriately solvate the Ag salt was important for the formation of Ag nanoparticles. In addition, the mean diameters of the resultant Ag nanoparticles were 3.8-9.0 nm, increasing with increasing AgNO(3) concentration. A sufficiently high PEG concentration relative to AgNO(3) was necessary for the formation of smaller Ag nanoparticles. This work provided a simple route for the in situ synthesis of Ag nanoparticles.     

Insight into the interactions that control the phase behaviour of new aqueous biphasic systems composed of polyethylene glycol polymers and ionic liquids

New polyethylene glycol (PEG)/ionic liquid aqueous biphasic systems (ABS) are presented. Distinct pairs of PEG polymers and ionic liquids can induce phase separation in aqueous media when dissolved at appropriate concentrations. Phase diagrams have been determined for a large array of systems at 298, 308 and 323 K. A comparison of the binodal curves allowed the analysis of the tunable structural features of the ionic liquid (i.e., anionic nature, cationic core, cationic alkyl side chain length and functionalisation, and number of alkyl substituents in the cation) and the influence of the molecular weight of the PEG polymer on the ability of these solutes to induce an ABS. It was observed that contrary to typical ABS based on ionic liquids and inorganic salts, in which the phase behaviour is dominated by the formation of the hydration complexes of the ions, the interactions between the PEG polymers and ionic liquids control the phase demixing in the polymer-type ABS studied herein. It is shown that both the ionic liquids and PEG polymers can act as the salting-out species; that is, it is an occurrence that is dependent on the structural features of the ionic liquid. For the first time, PEG/ionic liquid ABS are reported and insight into the major interactions that govern the polymer/ionic liquid phase behaviour in aqueous media are provided. The use of two different nonvolatile and tunable species (i.e., ionic liquids and PEG polymers) to form ABS allows the polarities of the phases to be tailored. Hence, the development of environmentally friendly separation processes that make use of these novel systems is envisaged.     

在交联聚合物微球GMA/MMA表面接枝固载聚乙二醇的研究

以乙二醇二甲基丙烯酸酯为交联剂,采用悬浮聚合方法,制备了甲基丙烯酸缩水甘油酯(GMA)和甲基丙烯酸甲酯(MMA)的交联微球GMA/MMA.使用Lewis酸催化剂,通过环氧键的开环反应,将聚乙二醇(PEG)偶合接枝在交联微球GMA/MMA表面,实现了PEG的固载化,制得了三相相转移催化剂PEG-GMA/MMA.重点考察了各种因素对PEG接枝固载过程的影响,并研究了反应机理.实验结果表明,以交联微球GMA/MMA为载体,可以顺利地实现PEG的固载化,这是制备PEG三相相转移催化剂的简捷途径.实验发现,Lewis酸也能催化环氧键的开环反应,而且比质子酸的催化更加有效.溶剂的极性对偶合接枝反应的影响较大,采用极性大的溶剂有利于PEG的接枝固载.偶合接枝体系中,过高的催化剂用量会导致PEG双端羟基参与接枝反应,使载体表面大分子之间发生附加交联,不利于PEG的接枝固载.在适宜的反应条件下,接枝微球PEG-GMA/MMA表面的PEG接枝度可达0.20 g/g.     

Effects of polydepsipeptide side‐chain groups on the temperature sensitivity of triblock copolymers composed of polydepsipeptides and poly(ethylene glycol)

To develop new types of biodegradable polymers possessing predictable responses to changes in temperature, ABA‐type and BAB‐type triblock copolymers composed of various polydepsipeptides (PDP) and poly(ethylene glycol) (PEG) (PDP‐PEG‐PDP and PEG‐PDP‐PEG) were synthesized. The specific focus of this study was on the effect of the different side‐chain groups of various amino acids on the temperature‐responsive behavior of the triblock copolymers. An ABA‐type triblock copolymer containing the less hydrophobic glycine (PGG‐PEG‐PGG) did not exhibit any temperature‐responsive behavior; however, ABA‐type triblock copolymers containing the hydrophobic α‐amino acids, L ‐leucine and L ‐phenylalanine (PGL‐PEG‐PGL or PGF‐PEG‐PGF), did exhibit temperature‐responsive behavior. The cloud point of PGF‐PEG‐PGF was 10 °C lower than that of PGL‐PEG‐PGL. It can be possible to control temperature‐sensitivity by changing not only PDP segment length but also kind of α‐amino acid in PDP segment. Moreover, BAB‐type triblock copolymer containing L ‐leucine (PEG‐PGL‐PEG) showed temperature‐responsive sol‐gel transition. Because polydepsipeptides are biodegradable polymers, the information obtained in this study is useful to design biodegradable injectable polymers having controllable temperature‐sensitivity for biomedical use.© 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3892–3903, 2009     

丙烯酰胺在聚乙二醇水溶液中的聚合动力学

用改进溴法对丙烯酰胺 (AM)在聚乙二醇 (PEG)水溶液中聚合动力学进行研究 .在单一和氧化还原引发体系中分别考察了引发剂、单体和PEG用量、不同HLB值乳化剂以及聚合温度等因素对动力学的影响 .得到AM聚合速率与过硫酸铵 (APS)浓度的 0 91次方成正比 ;单一APS和APS 三乙醇胺 (TEA)氧化还原引发体系中的AM聚合表观活化能分别为 96 1和 4 2 3kJ mol.     

Size-selective protein adsorption to polystyrene surfaces by self-assembled grafted poly(ethylene glycols) with varied chain lengths

We report about the surface modification of polystyrene (PSt) with photoreactive alpha-4-azidobenzoyl-omega-methoxy poly(ethylene glycol)s (ABMPEG) of three different molecular weights (MWs of approximately 2, approximately 5, and approximately 10 kg/mol) and with two poly(ethylene glycol)/poly(propylene glycol) triblock copolymers (PEG-PPG-PEG) of about identical PEG/PPG ratio (80/20, w/w) and MW(PEG) of approximately 3 and approximately 6 kg/mol, all via adsorption from aqueous solutions. For ABMPEGs, an additional UV irradiation was used for photografting to the PSt. Contact angle (CA) and atomic force microscopy data revealed pronounced differences of the hydrophilicity/hydrophobicity and topography of the surfaces as a function of PEG type and concentration used for the modification. In all cases, an incomplete coverage of the PSt was observed even after modification at the highest solution concentrations (10 g/L). However, clear differences were seen between PEG-PPG-PEGs and ABMPEGs; only for the latter was a nanoscale-ordered interphase structure with an influence of MW(PEG) on the PEG density observed; after modification at the same solution concentrations, the density was significantly higher for lower MW(PEG). The adsorption of three proteins, myoglobin (Mgb), bovine serum albumin (BSA), and fibrinogen to the various surfaces was analyzed by surface plasmon resonance. Pronounced differences between the two PEG types with respect to the reduction of protein adsorption were found. At high, but still incomplete, surface coverage and similar CA, the shielding of ABMPEG layers toward the adsorption of Mgb and BSA was much more efficient; e.g., the adsorbed Mgb mass relative to that of unmodified PSt was reduced to 10% for ABMPEG 2 kg/mol while for both PEG-PPG-PEGs the Mgb mass was still around 100%. In addition, for the ABMPEG layers an effect of MW(PEG) on adsorbed protein mass-decrease with decreasing MW-could be confirmed; and the highest Mgb/BSA selectivities were also observed. A "two-dimensional molecular sieving", based on PEG molecules having a nanoscale order at the hydrophobic substrate polymer surface has been proposed, and the main prerequisites were the use of PEG conjugates which are suitable for an "end-on" grafting (e.g., ABMPEGs), the use of suitable (not too high) concentrations for the surface modification via adsorption/self-assembly, optionally the photografting on the substrate (possible only for ABMPEG), and presumably, a washing step to remove the excess of unbound PEGs. The results of this study also strongly support the hypothesis that the biocompatibility of hydrophobic materials can be very much improved by PEG modifications at surface coverages that are incomplete but have an ordered layer structure controlled by the size and steric interactions of surface-bound PEGs.     

Ammonium persulphate promoted synthesis of polyethylene glycol entrapped potassium tribromide and its application in acylation and bromination of some selective organic compounds

In this study, a new method of synthesis of polyethylene glycol supported potassium tribromide (PEG KBr3) and its application in acylation and bromination reactions are reported. Ammonium persulphate oxidizes KBr to the corresponding tribromide which is entrapped by polyethylene glycol leading to stable PEG KBr3. The reagent is proved to be highly efficient for the acylation of variety of alcohols and bromination of activated aromatic substrates. Themethod is a mild, one pot reaction and involves no use of toxic reagents.     

Adsorption Equilibrium of Polyethylene Glycol in the Copper Electroplating Solution on Activated Carbon

Polyethylene glycol (PEG) used as a brightening and stabilization agent at the concentration of 30 mg dm(-3) is a major organic additive in the copper electroplating solution. Activated carbon, Calgon Filtrasob 400, is used as the adsorbent to remove the PEG from the used electroplating solution in order to broaden the appeal of recycling it. The equilibrium of adsorption is attained within 14 days. The effect of the temperature on the amount of PEG adsorbed on the activated carbon is insignificant for the temperatures ranged from 288 to 313 K. The adsorption isotherm of PEG conforms to the Langmuir isotherm, q(e)=Q(L)K(L)C(e)/(1+K(L)C(e)), with a high correlation coefficient of 0.9979. The large values of the monolayer adsorption capacity, Q(L), of 303 mg g(-1) and the equilibrium constant, K(L), of 0.273 dm(3) mg(-1) show a great adsorption potential of PEG on the activated carbon. A high removal efficiency would be expected at such a low original concentration of PEG. From the results mentioned above, it is feasible to use activated carbon for removing PEG from the electroplating solution, thereby achieving the appeal of recycling. Copyright 2000 Academic Press.     

Controlled synthesis of cell-laden microgels by radical-free gelation in droplet microfluidics

Micrometer-sized hydrogel particles that contain living cells can be fabricated with exquisite control through the use of droplet-based microfluidics and bioinert polymers such as polyethyleneglycol (PEG) and hyperbranched polyglycerol (hPG). However, in existing techniques, the microgel gelation is often achieved through harmful reactions with free radicals. This is detrimental for the viability of the encapsulated cells. To overcome this limitation, we present a technique that combines droplet microfluidic templating with bio-orthogonal thiol-ene click reactions to fabricate monodisperse, cell-laden microgel particles. The gelation of these microgels is achieved via the nucleophilic Michael addition of dithiolated PEG macro-cross-linkers to acrylated hPG building blocks and does not require any initiator. We systematically vary the microgel properties through the use of PEG linkers with different molecular weights along with different concentrations of macromonomers to investigate the influence of these parameters on the viability and proliferation of encapsulated yeast cells. We also demonstrate the encapsulation of mammalian cells including fibroblasts and lymphoblasts.     

Polyethylene glycol as a green chemical solvent

Polyethylene glycol (PEG) is an industrial commodity produced for applications foremost in the medial and personal care business. This review focuses on the much less explored application of using PEG as a chemical solvent. This review highlights some of the successful chemical synthesis strategies to illustrate the advantages of using PEG as an environmentally friendly reaction medium. These advantages include its ability to (a) dissolve a wide range of chemicals including mineral salts, (b) serve as a catalyst because of its acid/base functionalities, (c) complex metal cations, and (d) engage in redox chemistry. New developments of combining PEG with other green solvents and/or functionalizing PEGs are covered as well. The present state of physicochemical studies of PEG as a solvent is also provided and clearly shows the need for future research in this area to further promote the effective use of PEG as a medium for chemistry.     

A Green and Highly Efficient Protocol for Catalyst‐free Knoevenagel Condensation and Michael Addition of Aromatic Aldehydes with 1,3‐Cyclic Diketones in PEG‐400

A convenient, highly efficient and green approach for synthesis of tetraketones from aromatic aldehydes with dimedone and 1,3‐indanedione at room temperature in PEG‐400 is described. The use of PEG‐400 as the reaction medium and avoiding the use of any catalyst makes the process environmentally benign. Seven new compounds are reported.     

Designing Visible Light‐Cured Thiol‐Acrylate Hydrogels for Studying the HIPPO Pathway Activation in Hepatocellular Carcinoma Cells

Various polymerization mechanisms have been developed to prepare peptide‐immobilized poly(ethylene glycol) (PEG) hydrogels, a class of biomaterials suitable for studying cell biology in vitro. Here, a visible light mediated thiol‐acrylate photopolymerization scheme is reported to synthesize dually degradable PEG‐peptide hydrogels with controllable crosslinking and degradability. The influence of immobilized monothiol pendant peptide is systematically evaluated on the crosslinking of these hydrogels. Further, methods are proposed to modulate hydrogel crosslinking, including adjusting concentration of comonomer or altering the design of multifunctional peptide crosslinker. Due to the formation of thioether ester bonds, these hydrogels are hydrolytically degradable. If the dithiol peptide linkers used are susceptible to protease cleavage, these thiol‐acrylate hydrogels can be designed to undergo partial proteolysis. The differences between linear and multiarm PEG‐acrylate (i.e., PEGDA vs PEG4A) are also evaluated. Finally, the use of the mixed‐mode thiol‐acrylate PEG4A‐peptide hydrogels is explored for in situ encapsulation of hepatocellular carcinoma cells (Huh7). The effects of matrix stiffness and integrin binding motif (e.g., RGDS) on Huh7 cell growth and HIPPO pathway activation are studied using PEG4A‐peptide hydrogels. This visible light poly­merized thiol‐acrylate hydrogel system represents an alternative to existing light‐cured hydrogel platforms and shall be useful in many biomedical applications.     

Enantioreversal in the sharpless asymmetric epoxidation reaction controlled by the molecular weight of a covalently appended achiral polymer

Polymers such as poly(ethylene glycol) (PEG) have proven use in a variety of applications including organic synthesis. We now disclose our investigations into the recently disputed report that PEG tartrate esters can reverse the enantioselectivity of the Sharpless asymmetric epoxidation reaction. The results presented herein have clarified that the enantioselectivity of this reaction can be reproducibly reversed solely as a function of the molecular weight of the appended PEG. By preparing a range of tartrate ligands with varying PEG chains lengths, the reversal was found to occur within a molecular weight change of only 800. As the PEG chain did not affect the inherent chirality of the ligand, the enantioreversal was proposed to occur as a result of two Ti-ligand complexes which differ in their molecularity of ligand, one monomeric in ligand and the other dimeric. Support for this hypothesis was given through equilibrium measurements which revealed that the predominant species in Ti/PEG tartrate ester mixtures is a distinct 2:1 Ti-ligand complex, as opposed to the 2:2 Ti-ligand complex of traditional Sharpless asymmetric epoxidations. In total, these data represent an unrecognized property of PEG-supported catalysts that could open up new venues in the control of asymmetric reactions by means of achiral appended polymers.     

Decorated rods: a "bottom-up" self-assembly of monomolecular DNA complexes

Fluorescence correlation spectroscopy (FCS) and gel electrophoresis measurements are performed to investigate both the number and size of complexes of linear double-stranded DNA (dsDNA) fragments with 1:1 diblock copolymers consisting of a cationic moiety, branched polyethyleneimine (bPEI) of 2, 10, or 25 kDa, covalently bound to a neutral shielding moiety, poly(ethylene glycol) (PEG; 20 kDa). By systematically decreasing the bPEI length, the PEG grafting density along the DNA chain can be directly controlled. For 25 and 10 kDa bPEI-PEG copolymers, severe aggregation is observed despite the presence of the shielding PEG. Upon decreasing the bPEI length to 2 kDa, controlled self-assembly of monomolecular DNA nanoparticles is observed. The resulting complexes are in quantitative agreement with a theoretical model based on a single DNA encased in a dense PEG polymer brush layer. The resulting PEGylated complexes show high stability against both salt and protein and hence are of potential use for in vivo gene delivery studies.     

Introduction of click chemistry to carotenoids

We describe the synthesis of carotenoid derivatives via the azide–alkyne click reaction and optimize the conditions for these sensitive molecules. After finding the mildest conditions possible for the reaction we were able to use the click reaction for the synthesis of PEG–carotenoid conjugates starting from carotenoid pentynoates and PEG azides.     

An efficient method to synthesize HMX by nitrolysis of DPT with N_2O_5 and a novel ionic liquid

A novel polyethylene glycol(PEG)-200-based dicationic acidic ionic liquid(PEG200-DAIL)was used to synthesize HMX from DPT by nitrolysis with N2O5.It was found that either N2O5 or PEG200-DAIL could improve the yield.Furthermore,the combined use of PEG200-DAIL and N2O5 could increase the yield of HMX to 64%with the used quantity of HNO3 decreased.dramatically     

Enhancing the Activity of Surface Immobilized Antimicrobial Peptides Using Thiol-Mediated Tethering to Poly(ethylene glycol)

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol-mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol-mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two-step thiol–ene “photo-click” reaction or a “one-pot” thiol–maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG-AMP-modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol-mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections.