Polyethylene glycol

Polyethylene glycol

Polyethylene glycol
Names
IUPAC names
poly(oxyethylene) {structure-based},
poly(ethylene oxide) {source-based}[1]
Other names
Carbowax, GoLYTELY, GlycoLax, Fortrans, TriLyte, Colyte, Halflytely, Macrogol, MiraLAX, MoviPrep
Identifiers
 YesY
ATC code A06
ChEMBL  N
ChemSpider  YesY
UNII  N
Properties
C2nH4n+2On+1
Molar mass 18.02 + 44.05n g/mol
Hazards
Flash point 182 to 287 °C; 360 to 549 °F; 455 to 560 K
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 N  (: YesY/N?)

Polyethylene glycol (PEG) is a polyether compound with many applications from industrial manufacturing to medicine. The structure of PEG is (note the repeated element in parentheses):

H-(O-CH2-CH2)n-OH

PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular weight.

Contents

  • Available forms and nomenclature 1
  • Production 2
  • Medical uses 3
    • Research for new clinical uses 3.1
  • Other uses 4
    • Chemical uses 4.1
    • Biological uses 4.2
    • Commercial uses 4.3
    • Industrial uses 4.4
  • See also 5
  • References 6
  • External links 7

Available forms and nomenclature

PEG, PEO, or POE refers to an oligomer or polymer of ethylene oxide. The three names are chemically synonymous, but historically PEG is preferred in the biomedical field, whereas PEO is more prevalent in the field of polymer chemistry. Because different applications require different polymer chain lengths, PEG has tended to refer to oligomers and polymers with a molecular mass below 20,000 g/mol, PEO to polymers with a molecular mass above 20,000 g/mol, and POE to a polymer of any molecular mass.[2] PEG and PEO are liquids or low-melting solids, depending on their molecular weights. PEGs are prepared by polymerization of ethylene oxide and are commercially available over a wide range of molecular weights from 300 g/mol to 10,000,000 g/mol. While PEG and PEO with different molecular weights find use in different applications, and have different physical properties (e.g. viscosity) due to chain length effects, their chemical properties are nearly identical. Different forms of PEG are also available, depending on the initiator used for the polymerization process – the most common initiator is a monofunctional methyl ether PEG, or methoxypoly(ethylene glycol), abbreviated mPEG. Lower-molecular-weight PEGs are also available as purer oligomers, referred to as monodisperse, uniform, or discrete. Very high purity PEG has recently been shown to be crystalline, allowing determination of a crystal structure by x-ray diffraction.[3] Since purification and separation of pure oligomers is difficult, the price for this type of quality is often 10-1000 fold that of polydisperse PEG.

PEGs are also available with different geometries.

  • Branched PEGs have three to ten PEG chains emanating from a central core group.
  • Star PEGs have 10 to 100 PEG chains emanating from a central core group.
  • Comb PEGs have multiple PEG chains normally grafted onto a polymer backbone.

The numbers that are often included in the names of PEGs indicate their average molecular weights (e.g. a PEG with n = 9 would have an average molecular weight of approximately 400 daltons, and would be labeled PEG 400. Most PEGs include molecules with a distribution of molecular weights (i.e. they are polydisperse). The size distribution can be characterized statistically by its weight average molecular weight (Mw) and its number average molecular weight (Mn), the ratio of which is called the polydispersity index (Mw/Mn). MW and Mn can be measured by mass spectrometry.

PEGylation is the act of covalently coupling a PEG structure to another larger molecule, for example, a therapeutic protein, which is then referred to as a PEGylated protein. PEGylated interferon alfa-2a or −2b are commonly used injectable treatments for Hepatitis C infection.

PEG is soluble in water, methanol, ethanol, acetonitrile, benzene, and dichloromethane, and is insoluble in diethyl ether and hexane. It is coupled to hydrophobic molecules to produce non-ionic surfactants.[4]

PEGs contain potential toxic impurities, such as ethylene oxide and 1,4-dioxane. Ethylene Glycol and its ethers are nephrotoxic if applied to damaged skin.[5]

Polyethylene oxide (PEO, Mw 4 kDa) nanometric crystallites (4 nm)

Polyethylene glycol (PEG) and related polymers (PEG phospholipid constructs) are often sonicated when used in biomedical applications. However, as reported by Murali et al., PEG is very sensitive to sonolytic degradation and PEG degradation products can be toxic to mammalian cells. It is, thus, imperative to assess potential PEG degradation to ensure that the final material does not contain undocumented contaminants that can introduce artifacts into experimental results. Murali et al., Exp Biol Med (Maywood), September 2015, volume 240, pages 1147-1151, doi: 10.1177/1535370214567615

PEGs and methoxypolyethylene glycols are manufactured by Dow Chemical under the tradename Carbowax for industrial use, and Carbowax Sentry for food and pharmaceutical use. They vary in consistency from liquid to solid, depending on the molecular weight, as indicated by a number following the name. They are used commercially in numerous applications, including as surfactants, in foods, in cosmetics, in pharmaceutics, in biomedicine, as dispersing agents, as solvents, in ointments, in suppository bases, as tablet excipients, and as laxatives. Some specific groups are lauromacrogols, nonoxynols, octoxynols, and poloxamers.

Macrogol, used as a laxative, is a form of polyethylene glycol. The name may be followed by a number which represents the average molecular weight (e.g. macrogol 4000, macrogol 3350 or macrogol 6000).

Production

Polyethylene glycol is produced by the interaction of ethylene oxide with water, ethylene glycol, or ethylene glycol oligomers.[6] The reaction is catalyzed by acidic or basic catalysts. Ethylene glycol and its oligomers are preferable as a starting material instead of water, because they allow the creation of polymers with a low polydispersity (narrow molecular weight distribution). Polymer chain length depends on the ratio of reactants.

HOCH2CH2OH + n(CH2CH2O) → HO(CH2CH2O)n+1H

Depending on the catalyst type, the mechanism of polymerization can be cationic or anionic. The anionic mechanism is preferable because it allows one to obtain PEG with a low polydispersity. Polymerization of ethylene oxide is an exothermic process. Overheating or contaminating ethylene oxide with catalysts such as alkalis or metal oxides can lead to runaway polymerization, which can end in an explosion after a few hours.

Polyethylene oxide, or high-molecular weight polyethylene glycol, is synthesized by coagulation of polymer chains from solution, chelating additives such as dimethylglyoxime are used.

Alkali catalysts such as sodium hydroxide (NaOH), potassium hydroxide (KOH), or sodium carbonate (Na2CO3) are used to prepare low-molecular-weight polyethylene glycol.

Medical uses

PEG is the basis of a number of laxatives (e.g., macrogol-containing products, such as Movicol and polyethylene glycol 3350, or SoftLax, MiraLAX,ClearLAX, Osmolax or GlycoLax). Whole bowel irrigation with polyethylene glycol and added electrolytes is used for bowel preparation before surgery or colonoscopy. The preparation is sold under the brand names GoLYTELY, GaviLyte C, NuLytely, GlycoLax, Fortrans, TriLyte, Colyte, Halflytely, Softlax, Lax-a-Day, ClearLax and MoviPrep. In the United States, MiraLAX and Dulcolax Balance are sold without prescription for short-term relief of chronic constipation. Therapeutic classification is as an Osmotic Laxative that works by drawing water into the lumen of the intestinal tract. Shown to decrease consistency and increase weight of stool in constipated patients at low doses.[7]

Miralax is currently FDA approved for adults for a period of seven days, and is not approved for children.[8] A 2007 comparison showed that patients suffering from constipation had a better response to PEG medications than to tegaserod.[9] These medications soften the fecal mass by osmotically drawing water into the GI tract. It is generally well tolerated; however, possible side effects are bloating, nausea, gas, and diarrhea (with excessive use).

When attached to various protein medications, polyethylene glycol allows a slowed clearance of the carried protein from the blood. This makes for a longer-acting medicinal effect and reduces toxicity, and it allows longer dosing intervals. Examples include PEG-interferon alpha, which is used to treat hepatitis C, and PEGfilgrastim (Neulasta), which is used to treat neutropenia. It has been shown that polyethylene glycol can improve healing of spinal injuries in dogs.[10] One of the earlier findings, that polyethylene glycol can aid in nerve repair, came from the University of Texas (Krause and Bittner).[11] Polyethylene glycol is also commonly used to fuse B-cells with myeloma cells in monoclonal antibody production.

PEG is used as an excipient in many pharmaceutical products. Lower-molecular-weight variants are used as solvents in oral liquids and soft capsules, whereas solid variants are used as ointment bases, tablet binders, film coatings, and lubricants.[12]

PEG is also used in lubricating eye drops.

Research for new clinical uses

  • PEG, when labeled with a near-infrared fluorophore, has been used in preclinical work as a vascular agent, lymphatic agent, and general tumor-imaging agent by exploiting the Enhanced permeability and retention effect (EPR) of tumors.[13]
  • High-molecular-weight PEG (e.g., PEG 8000) has been shown to be a dietary preventive agent against colorectal cancer in animal models.[14]
  • The Chemoprevention Database shows PEG is the most effective known agent for the suppression of chemical carcinogenesis in rats. Cancer prevention applications in humans, however, have not yet been tested in clinical trials.[15]
  • The injection of PEG 2000 into the bloodstream of guinea pigs after spinal cord injury leads to rapid recovery through molecular repair of nerve membranes.[16] The effectiveness of this treatment to prevent paraplegia in humans after an accident is not known yet.
  • PEG is being used in the repair of motor neurons damaged in crush or laceration incidents in vivo and in vitro. When coupled with melatonin, 75% of damaged sciatic nerves were rendered viable.[17]
  • PEG is proposed as the 'glue' to reconnect the spinal cord in the world's first head transplant operation.[18]

Other uses

The remains of the 16th century carrack Mary Rose undergoing conservation treatment with PEG in the 1980s

Chemical uses

  • Polyethylene glycol has a low toxicity and is used in a variety of products.[19] The polymer is used as a lubricating coating for various surfaces in aqueous and non-aqueous environments.[20]
  • Since PEG is a flexible, water-soluble polymer, it can be used to create very high osmotic pressures (on the order of tens of atmospheres). It also is unlikely to have specific interactions with biological chemicals. These properties make PEG one of the most useful molecules for applying osmotic pressure in biochemistry and biomembranes experiments, in particular when using the osmotic stress technique.
  • Polyethylene glycol is also commonly used as a polar stationary phase for gas chromatography, as well as a heat transfer fluid in electronic testers.
  • PEG has also been used to preserve objects that have been salvaged from underwater, as was the case with the warship Vasa in Stockholm,[21] the Mary Rose in England, the Ma'agan Michael Ship in Israel,[22] and artifacts from the Steamboat Arabia in Kansas City, Missouri.[23] It replaces water in wooden objects, making the wood dimensionally stable and preventing warping or shrinking of the wood when it dries. In addition, PEG is used when working with green wood as a stabilizer, and to prevent shrinkage.[24]
  • PEG is often used (as an internal calibration compound) in mass spectrometry experiments, with its characteristic fragmentation pattern allowing accurate and reproducible tuning.
  • PEG derivatives, such as narrow range ethoxylates, are used as surfactants.
  • PEG has been used as the hydrophilic block of amphiphilic block copolymers used to create some polymersomes.[25]

Biological uses

  • PEG is commonly used as a precipitant for plasmid DNA isolation and protein crystallization. X-ray diffraction of protein crystals can reveal the atomic structure of the proteins.
  • Polymer segments derived from PEG polyols impart flexibility to polyurethanes for applications such as elastomeric fibers (spandex) and foam cushions.
  • In microbiology, PEG precipitation is used to concentrate viruses. PEG is also used to induce complete fusion (mixing of both inner and outer leaflets) in liposomes reconstituted in vitro.
  • The size of the PEG polymer has been shown to be important, with larger polymers achieving the best immune protection. [26]
  • PEG is a component of stable nucleic acid lipid particles (SNALPs) used to package siRNA for use in vivo.[27][28]
  • In blood banking, PEG is used as a potentiator to enhance detection of antigens and antibodies.[29]
  • When working with phenol in a laboratory situation, PEG 300 can be used on phenol skin burns to deactivate any residual phenol.

Commercial uses

  • PEG is the basis of many skin creams (as cetomacrogol) and personal lubricants (frequently combined with glycerin).
  • PEG is used in a number of toothpastes as a dispersant. In this application, it binds water and helps keep xanthan gum uniformly distributed throughout the toothpaste.
  • PEG is also under investigation for use in body armor, and in tattoos to monitor diabetes.[30][31]
  • In low-molecular-weight formulations (i.e. PEG 400), it is used in Hewlett-Packard designjet printers as an ink solvent and lubricant for the print heads.
  • PEG is also one of the main ingredients in paintball fills, because of its thickness and flexibility. However, as early as 2006, some Paintball manufacturers began substituting cheaper oil-based alternatives for PEG.
  • PEG is also used as an anti-foaming agent in food[32] – its INS number is 1521[33] or E1521 in the EU.[34]

Industrial uses

  • Nitrate ester-plasticized polyethylene glycol is used in Trident II ballistic missile solid rocket fuel.[35]
  • Dimethyl ethers of PEG are the key ingredient of Selexol, a solvent used by coal-burning, integrated gasification combined cycle (IGCC) power plants to remove carbon dioxide and hydrogen sulfide from the gas waste stream.
  • PEG has been used as the gate insulator in an electric double-layer transistor to induce superconductivity in an insulator.[36]
  • PEG is also used as a polymer host for solid polymer electrolytes. Although not yet in commercial production, many groups around the globe are engaged in research on solid polymer electrolytes involving PEG, with the aim of improving their properties, and in permitting their use in batteries, electro-chromic display systems, and other products in the future.
  • PEG is injected into industrial processes to reduce foaming in separation equipment.
  • PEG is used as a binder in the preparation of technical ceramics.[37]

See also

References

  1. ^
  2. ^ For example, in the online catalog of Scientific Polymer Products, Inc., poly(ethylene glycol) molecular weights run up to about 20,000, while those of poly(ethylene oxide) have six or seven digits.
  3. ^
  4. ^ Moritz Winger, Alex H. de Vries & Wilfred F. van Gunsteren. Force-field dependence of the conformational properties of α,ω-dimethoxypolyethylene glycol. Molecular Physics, 107 (13) pp 1313-1321. 10 July 2009.
  5. ^
  6. ^ Polyethylene glycol, Chemindustry.ru
  7. ^ nih.gov, more text.
  8. ^
  9. ^
  10. ^
  11. ^
  12. ^
  13. ^ Kovar, J., Wang, Y., Simpson, M.A., and Olive, D.M., "Imaging Lymphatics With A Variety of Near-Infrared-Labeled Optical Agents", World Molecular Imaging, (2009)
  14. ^
  15. ^ Chemoprevention Database. Inra.fr. Retrieved on 30 November 2012.
  16. ^
  17. ^
  18. ^ Head Transplant Patient: 'We're Making Science', Sky News, 12 June 2015
  19. ^
  20. ^
  21. ^ Lars-Åke Kvarning, Bengt Ohrelius (1998), The Vasa – The Royal Ship, ISBN 91-7486-581-1, pp. 133–141
  22. ^
  23. ^ Hawley, Greg (2005). Treasure in a Cornfield, p. 175-186. Paddle Wheel Publishing, Kansas City. ISBN 0965761258.
  24. ^ Anti-Freeze is Not a Green Wood Stabilizer – Buzz Saw, The Rockler Blog. Rockler.com (2 May 2006). Retrieved on 30 November 2012.
  25. ^
  26. ^
  27. ^
  28. ^ (free with registration)
  29. ^
  30. ^
  31. ^
  32. ^ US Government – Food and Drug Agency
  33. ^
  34. ^ UK Government – Food Standards Agency
  35. ^
  36. ^
  37. ^ Volume 4, Engineered Materials Handbook: Ceramics and Glasses, ASM International, 1991, ISBN 0-87170-282-7, p 49.

External links

  • Oregon State University informational paper on using PEG as a wood stabilizer