Water plays a key role in nature. It functions as the primary solvent and is involved in determining surface interactions, molecular recognition events and lock and key mechanisms in cells and biomolecules. Polymers which can interact with, and structure, water are of particular interest to a variety of industrial applications since the ability to control and manipulate water can have a profound effect on both surface bulk material properties and surface events. As a result, water-loving poly (ethylene glycol) (abbreviated to PEG), polymers have found considerable use in commercial applications. The so-called PEGs are synthesised from ethylene oxide from which is derived the alternative more general name for this group, poly (ethylene oxide). This latter name is independent of the nature of the end group.
This article briefly explores and selectively reviews the structure and properties of PEGs with water, and explores some uses of this valuable class of PEG, and PEG-derived synthetic polymers.
PEGs are a family of water-soluble polymers which share a common chemical structure, a linear polyether chain, consisting of multiple oxyethylene (-CH2-CH2O-) sub units with primary hydroxyl groups at each end of the chain. The general formula is shown below
In this formula ‘n” may represent any integer from two to infinity.
By virtue of the two different processes for their manufacture, these materials fall into two distinct groups: a) those with a number average molecular weight less than 20,000 and b) those with a number average molecular weights of over 100,000. The commercially-available materials of a) above are of most interest from the point of view of providing starting materials for the synthesis of a wide range of useful PEG-containing hydrophilic polymers.
At room temperature, those PEGs in the 10,000 to 20,000 molecular weight range vary from transparent liquids (used as oral laxatives or as excipients in pharmaceutical injections) to waxy crystalline solids, which are soluble in water and in a variety of organic solvents. Those of >100,000 molecular weight number average are used as viscosity modifiers and interestingly can be useful in reducing friction of aqueous liquid flow thereby reducing the energy required for pumping. They can also be used to increase the speed of a variety of boats by reducing their drag. These high molecular weight polymers of ethylene oxide phase-separate in water near to 100oc and the derivatives with modified end groups may show phase separation at much lower temperatures. The formation of linear block copolymers can provide water-insoluble, but water swellable hydrogels at room temperatures, which are soluble in some organic solvents. Totally water-insoluble crosslinked PEG’s can be synthesised by appropriate reaction with the terminal hydroxyl groups. In the absence of degradation, these are of course totally insoluble in either water or solvents.
From the biomedical perspective, the structure and interaction of PEGs with water can render them of very low toxicity in contact with living organisms, which has led to many applications in internal and external medicaments. Many people will be familiar with their use as laxatives and wound dressings. Much research is currently being undertaken for their use, inter alia, in the manufacture of contact lenses.
Crystallographic studies of solid PEG has shown that it exhibits a coiled helical structure, which has been well defined. On dissolution in water this helical structure is modified in a strongly exothermic association with water. The precise nature of the structure of any hydrates so-formed is not yet fully understood. Various hydrates first proposed from studies on PEG non ionic surface active surfactants (mono, di, tri, tetra and hexa) have been postulated and it may be that different hydrates prevail for different ranges of molecular weights of PEG, with different solutes in water swelling and at different temperatures. Only two hydrates can be in equilibrium existence in any one time within a given system.
It also appears possible that the stability of hydrates may vary with end-capping or co-reaction of PEG’s with other moieties. As would be expected from an exothermic hydration, the degree of hydration reduces with increasing temperature. Cross-linked PEGs thus have been found to synerise (exude) their water with increasing temperature. The molecular state of water would relate to the biological interactions of PEG’s and may be important in seeking effective function for various applications.
The dominant chemical reactivity of PEGs results from the primary hydroxyl groups at the end of each molecule. The polyether chain is relatively inert. This allows the terminal hydroxyl groups to be reacted to form new modified polymers and networks, which are in turn accessible to large classes of materials having the characteristics of water-soluble and water-insoluble materials and surface active agents.
PEGs are capable of forming strong hydrogen bonding interactions with water. This results from the interaction between the lone pair of electrons on the ether oxygen atoms of PEG and the hydrogen atoms in water molecules, which carry a positive charge and can form directly orientated hydrogen bonds. It has been proposed that in water PEG molecules often form a strongly hydrogen bonded complex in which three water molecules are engaged with each oxyethylene unit and these hydrates require significant input of energy to disrupt. It is also believed that this strong internal water binding helps to minimise the adhesion of proteins and cells to PEG surfaces and to the well established low toxicity of PEGs, making them suitable for incorporation into foodstuffs which can be ingested, and for food packaging. PEG’s are well-recognised ingredients of oral and injectable medications.
Other key characteristics of PEGs are that they are hydroscopic to a degree which depends of the molecular weight of the PEG involved and on the ambient relative humidity. The unmodified PEGs show a decrease in water uptake. as their molecular weight increases. The inverse relationship between the hydroscopicity and molecular weight occurs because the thermodynamics of an exothermic binding reaction between the ether groups and water hydrogens as well as the chain length increases as the proportion of terminal hydroxyl groups, which are very hydrophilic, decreases. The predominance of one effect over the other is clearly molecular weight dependant. A wide range of hydroscopicities is available and makes PEGs particularly desirable as plasticizers and humectants. When PEGs are part of covalent molecular networks the hydroxyl groups are usually no longer present. The remaining polyether chains are capable of providing significant swelling with water. These structures can have similar water contents to living tissue, which is perhaps one of the key reasons why PEGs are compatible with living tissue. PEGs are unique among polyethers in forming such complexes with water.
PEGs and their derivatives are frequently used in medicine. They have been used as pliable, non-adherent films for surgical dressings and open wounds. They have been used in the pharmaceutical industry because of their solvency, water solubility and low reactivity. Thus water-insoluble drugs can sometimes be dissolved in PEG’s to generate drug release dosage forms, used as dispersions to provide drugs to be released and delivered in vivo. The ability of the PEGs to “hide” from the recticulo-endothelial system of the body defence has lead to the term “pegylation”. The discovery that pegylated enzymes have been found to have a much-prolonged in vivo lifetime has led to a spectacular advance in the treatment of enzyme-deficiency illnesses. The biomedical applications of PEGs are discussed more fully in later articles from Ocutec.
PEG’s are commonly used in the cosmetics industry in cosmetics and toiletries due to their blandness, water solubility and solvency action. They can add stability to cosmetic products without making them greasy. They can also be found in toothpastes, denture adhesives, antiperspirants, perfumes and cosmetic regimes.
PEGs are widely utilised in the manufacture of paints, inks and surface coatings. They are also used in inkjet printing inks where they remove unwanted water. If turned into thermosetting materials they can be used to produce hard, impact resistant formulations for use in the automotive industry. In the form of water swelling granules they have found significant application in horticultural and agricultural applications.
PEG’s are also found in many household products. Their use as a major constituent of non-ionic surface-active agents is ubiquitous.
PEG’s are a family of hydrophilic, hydroscopic, chemically rather inert, non-toxic and sometimes crystalline polymers.
Their solubility in, and their strong interactions with water render them of major interest and importance in a diverse range of industries.
In particular it is the properties stemming from the strong and unique interactions with water, which make this class of materials so attractive for biomedical applications such as contact lenses and other medical devices.