Thermosensitive Diblock Copolymer of Poly(N-isopropylacrylamide) and Poly(ethylene glycol) in Water: Polymer Preparation and Solution Behavior Ryuhei Motokawa, †,§ Kanae Morishita, ‡ Satoshi Koizumi, § Takayuki Nakahira, ⊥ and Masahiko Annaka* ,‡ Graduate School of Science and Technology, Chiba University, Chiba 263-8522, Japan; Department of Chemistry, Kyushu University, Fukuoka 812-8581, Japan; Advanced Science Research Center, JAERI, Ibaraki 319-1195, Japan; and Department of Chemistry and Biotechnology, Chiba University, Chiba 263-8522, Japan Received December 20, 2004; Revised Manuscript Received March 26, 2005 ABSTRACT: This investigation focused on the self-assembly of poly(N-isopropylacrylamide)-block-poly- (ethylene glycol) (PNIPA-block-PEG) in water. A quasi-living radical polymerization technique including a Ce(IV) ion redox system enabled us to prepare block copolymers with relatively narrow molecular weight distributions. We distinguish five regions in the phase diagram: a transparent sol, opaque sol, transparent gel, opaque gel, and syneresis. By examining the extent of changes in the spectroscopic properties of a fluorescence probe, pyrene, as a function of block polymer concentration and/or temperature, we determined the critical association concentration as well as the partition coefficient K v for pyrene. The spectroscopic properties indicate that the hydrophobicity around the probe starts to increase far below the demixing line of the PNIPA-block-PEG, a remarkable finding which suggests that even in the temperature region below the LCST temperature of a PNIPA block (∼32 °C), this block copolymer provides more space for a preferential transfer of pyrene molecules than a bulk water medium at a higher temperature. This result may be attributed to the action of water, which starts to behave as a selective solvent for PEG blocks; the PEG chains are more swollen with water than are the PNIPA chains. Dynamic light scattering measurements also indicate that contraction of the PNIPA block starts to occur around 18 °C, which is consistent with results obtained by fluorescence measurements. By employing small-angle neutron scattering, it is also confirmed that microphase separation occurs above 17 °C to form disordered micelles, which includes a range of states from (i) asymmetric swelling to (ii) micelle formation with only short- range liquidlike order. Above 30 °C, network domains are formed as a result of macrophase separation due to dehydration of PNIPA blocks. As the temperature increased up to 40 °C, the network domain is collapsed along a direction parallel to PNIPA-block-PEG interface, leading to increase in interfacial thickness and to macroscopic syneresis. 1. Introduction The behavior of amphiphilic block copolymers in aqueous solutions has attracted considerable attention in recent decades. This interest is sustained by new uses for these block copolymers in gene and drug delivery systems, microreactors for chemical synthesis and ca- talysis, polymeric surfactants for stabilization of colloid dispersions, etc. 1-16 Block copolymers not only have colloidal behavior similar to that of low-molecular- weight surfactants but also exhibit unique molecular architecture. Their self-aggregation depends on solvent quality, concentration, and composition. Any change in temperature, ionic strength, or pH can result in selective solvent conditions under which a medium is a solvent for at least one component of a block polymer but a nonsolvent for the other block(s). Nonionic poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (Pluronic) is a typical example. 2,17-21 Spherical aggregates (or micelles) of block copolymers are composed of a hydrophobic core and a hydrophilic corona. These spherical aggregates may interact with each other to form networks or domain structures. Polymeric micelles are composed of a hydrophobic, water-insoluble block that associates in aqueous solu- tion plus a hydrophilic block that inhibits the precipita- tion of the aggregates. This inhibition is due to a repulsive elastic energy interaction between the corona chains emanating from the cores. Because of the simi- larity of such aggregates to micelles made from low molar mass surfactants, amphiphilic block copolymers are often referred to as “polymeric surfactants”. An interesting combination in a block copolymer is exemplified by double-hydrophilic block copolymers in which one of the hydrophilic blocks is thermoresponsive, i.e., undergoes a transition from soluble to insoluble in water. 22 When passing through the critical temperature, one of the hydrophilic blocks collapses, thus creating hydrophobic microdomains in a manner analogous to that of a polymeric surfactant. Or, should the thermal stimulus be applied in the other direction, the aggregate formed by such block copolymers dissociates. Poly(N- isopropylacrylamide) (PNIPA) is well-known for its thermosensitive properties, exhibiting a lower critical solution temperature (LCST) type phase behavior in water: at room temperature, PNIPA is hydrophilic and exists as individual random coil chains, while above ∼32 °C, PNIPA becomes hydrophobic and collapses into a molecular globule. † Graduate School of Science and Technology, Chiba University. ‡ Kyushu University. § JAERI. ⊥ Department of Chemistry and Biotechnology, Chiba Univer- sity. * To whom correspondence should be addressed: Fax +81-92- 642-2607; e-mail annaka-scc@mbox.nc.kyushu-u.ac.jp. 5748 Macromolecules 2005, 38, 5748-5760 10.1021/ma047393x CCC: $30.25 © 2005 American Chemical Society Published on Web 05/24/2005