Thermosensitive and pH-Sensitive Polymers Based on Maleic Anhydride Copolymers Xiangchun Yin and Harald D. H. Sto 1 ver* Department of Chemistry, McMaster University, Hamilton, Ontario, Canada L8S 4M1 Received July 15, 2002; Revised Manuscript Received October 3, 2002 ABSTRACT: Amphiphilic copolymers with thermosensitive and pH-sensitive properties were prepared by grafting methoxy poly(ethylene glycol) (MPEG) of different molecular weights onto alternating copolymers of maleic anhydride with styrene and 4-tert-butylstyrene. Aqueous solutions of these graft copolymers exhibit lower critical solution temperatures (LCST). These LCST’s are highly sensitive to changes in pH and salinity and to the presence of hydrophobic and hydrogen-bonding additives. The phase transitions are attributed to the cooperative effects of both hydrophobic interactions and intra/ intermolecular hydrogen-bonding interactions. Introduction Recently, polymer systems that undergo phase transi- tion in response to external stimuli such as changes in temperature and pH have attracted much atten- tion. 1 Aqueous solutions of poly(N-isopropylacrylamide), pNIPAM, the most well-known temperature-responsive polymer, exhibit a lower critical solution temperature (LCST) around 32 °C. The reason for this phase transi- tion lies in the balance of hydrophilic and hydrophobic interactions in the system. At low temperature, where water is a good solvent for the polymer, the polymer- solvent interactions are stronger than the polymer- polymer interactions, and the polymer chains are in the expanded “coil” conformation. The solvent quality de- creases with increasing temperature, and the polymer- polymer interactions increase due to the hydrophobic interactions. At the Θ-temperature for the system, the polymer-polymer interactions are equal to the polymer- solvent interactions. Above this critical temperature, water becomes a poor solvent for the polymer, and the polymer chains collapse into compact “globules” and phase separation takes place. 2-5 Hence, any factor affecting the polymer-solvent, polymer-polymer, or solvent-solvent interactions will influence the phase transition temperature. For example, the LCST of NIPAM copolymers usually increases with copolymer- ization of hydrophilic monomers and decreases with incorporation of hydrophobic monomers. 6 However, Cho et al. found that the LCST of poly(N,N-(dimethylamino)- ethyl methacrylate) copolymers decreased with increas- ing hydrophilic comonomer content, which was attrib- uted to the enhanced intra/intermolecular hydrogen bonding. 7,8 Amphiphilic graft copolymers have been extensively studied due to their wide applications in cosmetics, foods, coatings, and pharmaceuticals. They can be used to modify viscosity and interfacial structures and to encapsulate active compounds in controlled delivery systems. Polymers with hydrophobic backbones and with poly(ethylene oxide) grafts are among the most studied amphiphilic graft copolymers. 9,10 One of the questions in the area of amphiphilic graft copolymers has been the nature of the association of the polymer chains in aqueous solutions, which has been described as monomolecular as well as polymolecular micelles and also higher order aggregates. 11,12 Particular attention has been given to the solution properties of amphiphilic copolymers based on maleic anhydride copolymers, as these polymers are widely used as surfactants and materials for biomedical applications. 11-18 In this study, we describe the temperature- and pH- responsive properties of poly(ethylene glycol) (PEG) grafted amphiphilic copolymers based on alternating copolymers of maleic anhydride with styrene and 4-tert- butylstyrene, respectively. The phase transitions of the resulting amphiphilic graft copolymers are attributed to the combination of hydrophobic interactions and intra/intermolecular hydrogen bonding. These copoly- mers have potential applications in developing new types of hydrogel and surfactants with pH/temperature- responsive properties. Experimental Section Materials. Styrene, 4-tert-butylstyrene, maleic anhydride, methoxy poly(ethylene glycol) of different molecular weights, and butyllithium (1.60 mol L -1 in hexane) were purchased from Aldrich. Maleic anhydride was recrystallized in chloro- form before use; others were used as received. 2,2′-Azobis- (isobutyronitrile) (AIBN) was obtained from American Polymer Standards Laboratories and recrystallized in methanol. The solvents, methyl ethyl ketone (MEK), tetrahydrofuran (THF), and anhydrous diethyl ether, were obtained from Caledon. The THF solvent was dried by refluxing with metallic sodium followed by distillation. Preparation of Maleic Anhydride Copolymer. The styrene-alt-maleic anhydride copolymer (SMA) and the 4-tert- butylstyrene-alt-maleic anhydride copolymer (tBSMA) were prepared by solution copolymerization of styrene/maleic an- hydride or 4-tert-butylstyrene/maleic anhydride. 4.91 g of maleic anhydride (0.05 mol) was dissolved in 100 mL of MEK in a 120 mL glass flask. 5.25 g of styrene (99%, 0.05 mol) was added. The solution was deoxygenated with nitrogen, and 0.055 g of AIBN (3.35 × 10 -4 mol) was added. The polymerization was carried out at 70 °C for 7 h. The polymer product was precipitated in 500 mL of diethyl ether and dried in a vacuum. 6.25 g of product was obtained, in a yield of 62%. t-BSMA was prepared by the same procedure. Preparation of Grafted Amphiphilic Copolymers. For a typical procedure, a solution of lithium alcoholate obtained by reacting 1.80 g (5.14 × 10 -3 mol) of methoxy poly(ethylene glycol) (Mn: 350) with 3.2 mL of 1.6 mol L -1 butyllithium (5.12 × 10 -3 mol) in 10 mL of THF was added dropwise to a solution of 1.0 g of SMA (4.95 × 10 -3 mol) in 100 mL of THF. The reaction was carried out at room temperature under a nitrogen atmosphere for 24 h. The grafted copolymer was precipitated 10178 Macromolecules 2002, 35, 10178-10181 10.1021/ma021110o CCC: $22.00 © 2002 American Chemical Society Published on Web 12/07/2002