**1. Chemistry of polyethylene glycol, its derivatives, and copolymers**

Poly(ethylene glycol) or PEG is a synthetic water-soluble polymer with the formula C2nH4n+2On+1 which is available in a wide range of molecular weights where n value can go up to thousands. The molecular weight of PEG has a significant effect on its properties. Low-molecular-weight compounds (molecular weight < 1000) exist in liquid form, whereas higher molecular weight compounds are in waxlike solid form. The highest melting point of the solid-state material is reached at around 67°C, depending on the molecular weight [1]. In certain instances, PEG is also denoted as poly(oxyethylene) (POE) and polyoxirane. Additionally, PEG

is called poly(ethylene oxide) (PEO), when the molecular weight exceeds 20000. Other than water PEG is also soluble in certain organic solvents like acetonitrile, ethylene dichloride, carbon tetrachloride, trichloroethylene, methylene dichloride, and dimethylformamide [2]. The favorable properties of PEG such as solubility in both aqueous and organic solvents, nontoxicity, and reduced immunogenicity have made it a good candidate to be used for conjugation with other molecules [3].

PEG is available as linear or branched chain polymers with terminal hydroxyl groups. The structure of PEG allows the attachment of varying functional groups at the end groups of the polymer. The attachment of different molecules to PEG is known as PEGylation, and it provides means of improving the solubility, stability, and biocompatibility of the attached molecules/compounds. PEG is commonly synthesized starting with ethylene oxide via an anionic ring-opening reaction, through a nucleophilic attack on the epoxide ring by the hydroxide ion. Conjugation of PEG to other molecules can be categorized into two groups as (1) first-generation PEGylation and (2) second-generation PEGylation. The first-generation PEGylation involves random attachment of PEG polymers to other molecules and is widely used with modifying polypeptides. This method can usually generate various undesired products as the attachment is nonselective. Also, it is mostly limited to low-molecular-weight derivatives and unstable bonds. On the other hand, the second-generation PEGylation is site-specific and leads toward the production of more stable and pure derivatives [4].

#### **1.1 Hetero- and homobifunctional PEG derivatives**

Various hetero- and homobifunctional products of PEG can be synthesized by different methods. Bentley et al. have shown a method to synthesize heterobifunctional PEG derivatives in high purity and high yield, by going through an intermediate with an easily removable group [5]. Here, they have first attached a benzyloxy group as the removable group to one end of PEG. Then, after modifying the other terminal OH group with a required molecule, the first group was removed by hydrogenolysis or hydrolysis. Afterward, another functional group can be attached to the newly available OH group, or the new OH can be converted to a different functional group. Also, another group has synthesized a heterobifunctional PEG with acetal and thiol groups starting with polymerization of ethylene oxide with potassium 3,3-diethoxypropanolate. Then, an excess of methansulfonyl chloride was used to convert a terminal alkoxide group to a methansulfonyl groups [6]. Within the two procedures above, the polymerization-based process is the most frequently used method in the synthesis of heterobifunctional derivatives. Although the second method is more cost-effective and efficient than the intermediate based method, it requires the availability of proper anionic polymerization initiators and precautions to avoid the formation of PEG diols [4].

A homobifunctional PEG derivative of α-lipoic acid (LA) ester was synthesized by Lu et al. to improve its properties for potential medical applications [7]. In this synthesis an esterification reaction driven by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide was carried out with PEG in the presence of 4-(dimethylamino) pyridine as a catalyst. Additionally, homobifunctional PEG has been used in metal nanoparticle synthesis as a stabilizing agent. For instance, Ge et al. have synthesized supramagnetic nanoparticles to be used as draw solutes in forward osmosis (FO) membrane using polyethylene glycol activated with two carboxylic acid groups at the terminal ends [8].

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**Figure 1.**

*Association of Polyethylene Glycol Solubility with Emerging Membrane Technologies, Wastewater…*

Monomethoxy PEG (mPEG), where one terminal of the PEG is capped with a relatively inert methoxy group, is commonly utilized in producing monofunctional PEG derivatives. The synthesis of mPEG is carried out via anionic ring-opening polymerization reaction initiated by methoxide ions. The presence of trace amounts of water during the synthesis process of mPEG can result in the formation of PEG diols, which can reach above 15% in the composition. Hence, during the synthesis of monofunctional PEG, necessary steps must be taken to remove PEG diols from the starting materials. Otherwise, the final product will contain bifunctional PEG as impurities. Therefore, conversion of diols to inert compounds such as PEG-dimethyl ether or PEG carboxylic acids followed by purification was used as a strategy to overcome this issue [4, 9]. A group of monofunctional PEG derivatives called NHS esters, where N-hydroxysuccinimide based group is attached to mPEG, are widely used in

*Structures of PEG, PEG derivatives, and copolymers used in membranes (PEG-(COOH)-MNPs adapted from [8]).*

*DOI: http://dx.doi.org/10.5772/intechopen.89060*

**1.2 Monofunctional PEG derivatives**

*Association of Polyethylene Glycol Solubility with Emerging Membrane Technologies, Wastewater… DOI: http://dx.doi.org/10.5772/intechopen.89060*

## **1.2 Monofunctional PEG derivatives**

*Water Quality - Science, Assessments and Policy*

more stable and pure derivatives [4].

**1.1 Hetero- and homobifunctional PEG derivatives**

molecules [3].

is called poly(ethylene oxide) (PEO), when the molecular weight exceeds 20000. Other than water PEG is also soluble in certain organic solvents like acetonitrile, ethylene dichloride, carbon tetrachloride, trichloroethylene, methylene dichloride, and dimethylformamide [2]. The favorable properties of PEG such as solubility in both aqueous and organic solvents, nontoxicity, and reduced immunogenicity have made it a good candidate to be used for conjugation with other

PEG is available as linear or branched chain polymers with terminal hydroxyl groups. The structure of PEG allows the attachment of varying functional groups at the end groups of the polymer. The attachment of different molecules to PEG is known as PEGylation, and it provides means of improving the solubility, stability, and biocompatibility of the attached molecules/compounds. PEG is commonly synthesized starting with ethylene oxide via an anionic ring-opening reaction, through a nucleophilic attack on the epoxide ring by the hydroxide ion. Conjugation of PEG to other molecules can be categorized into two groups as (1) first-generation PEGylation and (2) second-generation PEGylation. The first-generation PEGylation involves random attachment of PEG polymers to other molecules and is widely used with modifying polypeptides. This method can usually generate various undesired products as the attachment is nonselective. Also, it is mostly limited to low-molecular-weight derivatives and unstable bonds. On the other hand, the second-generation PEGylation is site-specific and leads toward the production of

Various hetero- and homobifunctional products of PEG can be synthesized by different methods. Bentley et al. have shown a method to synthesize heterobifunctional PEG derivatives in high purity and high yield, by going through an intermediate with an easily removable group [5]. Here, they have first attached a benzyloxy group as the removable group to one end of PEG. Then, after modifying the other terminal OH group with a required molecule, the first group was removed by hydrogenolysis or hydrolysis. Afterward, another functional group can be attached to the newly available OH group, or the new OH can be converted to a different functional group. Also, another group has synthesized a heterobifunctional PEG with acetal and thiol groups starting with polymerization of ethylene oxide with potassium 3,3-diethoxypropanolate. Then, an excess of methansulfonyl chloride was used to convert a terminal alkoxide group to a methansulfonyl groups [6]. Within the two procedures above, the polymerization-based process is the most frequently used method in the synthesis of heterobifunctional derivatives. Although the second method is more cost-effective and efficient than the intermediate based method, it requires the availability of proper anionic polymerization initiators and precautions to avoid the formation

A homobifunctional PEG derivative of α-lipoic acid (LA) ester was synthesized by Lu et al. to improve its properties for potential medical applications [7]. In this synthesis an esterification reaction driven by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide was carried out with PEG in the presence of 4-(dimethylamino) pyridine as a catalyst. Additionally, homobifunctional PEG has been used in metal nanoparticle synthesis as a stabilizing agent. For instance, Ge et al. have synthesized supramagnetic nanoparticles to be used as draw solutes in forward osmosis (FO) membrane using polyethylene glycol activated with two carboxylic acid groups at

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of PEG diols [4].

the terminal ends [8].

Monomethoxy PEG (mPEG), where one terminal of the PEG is capped with a relatively inert methoxy group, is commonly utilized in producing monofunctional PEG derivatives. The synthesis of mPEG is carried out via anionic ring-opening polymerization reaction initiated by methoxide ions. The presence of trace amounts of water during the synthesis process of mPEG can result in the formation of PEG diols, which can reach above 15% in the composition. Hence, during the synthesis of monofunctional PEG, necessary steps must be taken to remove PEG diols from the starting materials. Otherwise, the final product will contain bifunctional PEG as impurities. Therefore, conversion of diols to inert compounds such as PEG-dimethyl ether or PEG carboxylic acids followed by purification was used as a strategy to overcome this issue [4, 9].

A group of monofunctional PEG derivatives called NHS esters, where N-hydroxysuccinimide based group is attached to mPEG, are widely used in

**Figure 1.**

*Structures of PEG, PEG derivatives, and copolymers used in membranes (PEG-(COOH)-MNPs adapted from [8]).*

protein and peptide modifications. This type of PEG derivatives is commonly used as acylating agents to modify amino groups of lysine residues and also has some reactivity with histidine imidazole and tyrosine hydroxyl groups. For example, PEG succinimidyl succinate (PEG-SS) produced by reacting mPEG with succinic anhydride followed by carboxylic acid activation to form succinimidyl ester is an NHS ester that has been successfully coupled to the enzyme asparaginase [4, 9]. Also, PEG derivatives such as trichlorophenyl carbonate and carbonylimidazole were synthesized by reacting mPEG hydroxyl group with chloroformates or carbonylimidazole. Alkylating reagents derived from mPEG include PEG tresylate and PEG dichlorotriazine. Other examples of monofunctional PEG derivatives that are specific to sulfhydryl groups include PEG-maleimide, PEG-vinylsulfone, and PEGiodoacetamide [10]. In addition to protein modifications, monofunctional PEG derivatives were also used in osmosis membrane-related applications. For instance, PEG conjugated to fatty acid and PEG monolaurate was used as draw solutes to test forward osmosis membranes [10].

According to the abovementioned chemistry and properties of PEG, it has been widely used in many different areas such as biomedical, biotechnology, and membrane technology-based applications. The main focus of this chapter is to discuss the usage of PEG, its derivatives, and copolymers (**Figure 1**) in emerging membrane technologies, such as forward osmosis and membrane distillation, as their applications relate to wastewater treatment and desalination.
