Temperature Response of Self-Assembled Micelles of Telechelic Hydrophobically Modified Poly(2-alkyl-2-oxazoline)s in Water Rodolphe Obeid, † Elena Maltseva, ‡ Andreas F. Thu ¨ nemann, ‡ Fumihiko Tanaka, § and Franc ¸oise M. Winnik* ,† Department of Chemistry and Faculty of Pharmacy, UniVersity of Montreal, CP 6128 Succursale Centre Ville, Montreal, QC H3C 3J7, Canada; BAM Federal Institute for Materials Research and Testing, Richard Willsta ¨tter Strasse 11, 12489 Berlin, Germany; and Department of Polymer Science, Kyoto UniVersity, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan ReceiVed NoVember 18, 2008; ReVised Manuscript ReceiVed January 15, 2009 ABSTRACT: Hydrophobically end-modified (HM) poly(2-ethyl-2-oxazolines) (PEtOx) and poly(2-isopropyl- 2-oxazolines) (PiPrOx) bearing an n-octadecyl chain on both termini or on one chain end only were prepared by cationic ring-opening polymerization of 2-ethyl-2-oxazoline and 2-isopropyl-2-oxazoline, respectively, and subsequent end-group modification. The polymers had a molar mass (M n ) ranging from 7000 to 13 000 g mol -1 , a size distribution M w /M n < 1.20, and end-group functionality > 0.97. All polymers, except the semitelechelic sample C 18 -PiPrOx-OH 13K (M n ) 13 000 g mol -1 ), formed core-shell micelles in cold water with a hydrodynamic radius (R H ), measured by dynamic light scattering, between 7 and 12 nm and a core of radius (R c ), determined by analysis of small-angle X-ray scattering (SAXS) data, of ∼1.3 nm. Aqueous solutions of all polymers underwent a heat-induced phase transition detected by an increase in solution turbidity at a temperature (T cp , cloud point) ranging from 32 to 62 °C, depending on polymer structure and size. Temperature-dependent light scattering (LS) measurements and fluorescence depolarization studies with the probe diphenylhexatriene (DPH) revealed that extensive intermicellar bridging takes place in solutions heated in the vicinity of T cp leading to large assemblies (R H g 1 μm). Further heating caused these assemblies to shrink into objects with R H ∼ 300-700 nm, depending on the size and structure of the polymer. The formation of H-bonds between water molecules and the main-chain amide nitrogen atoms imparts distinct features to the flower/star micelles formed by telechelic/semitelechelic PiPrOx and PEtOx, compared to the micelles formed by other hydrophobically end-modified water-soluble polymers, such as poly(ethylene oxide) or poly(N-isopropylacrylamide). Introduction The creation of organized nanostructured materials and fluids remains one of the major challenges in polymer science, even though it has been the focus of intensive research over several decades. The current thrust in this field is geared toward the design of waterborne organized systems, partly for environ- mental considerations and partly in view of specific needs in biotechnology and medicine. Amphiphilic polymers consisting of a water-soluble block linked to two hydrophobic chains, also known as associative polymers, have proven to be particularly useful in this context. The structure of associative polymers can be tailored at will so that their aqueous solutions exhibit rheological properties enabling applications in coatings, oil production and transportation fluids, water treatment systems, or as thickeners for food and health care products. 1 In most cases, the hydrophilic moiety is poly(ethylene oxide) (PEO) or a block copolymer with a PEO block and a block of a second hydrophilic monomer. The hydrophobic end groups may be alkyl- or aralkyl chains, as in the case of the industrial polymers known as “hydrophobic ethylene oxide-urethane copolymers” (HEUR), 2 or short water-insoluble blocks made up of poly(eth- ylene-co-propylene) or polystyrene. 3,4 Current research focuses on the design of more complex associative polymers in order to develop stimuli-responsive systems able to respond repeatedly and reversibly to an external trigger, such as a change of solution pH or temperature, or upon irradiation with a beam of light. 5,6 Stimuli-responsive “smart” polymers often contain blocks able to change rapidly from being hydrophobic to hydrophilic, or vice versa, on the basis of acid-base reactions, changes in pH, or irradiation with light of a specific wavelength. They may also take advantage of the changes in the hydration and conformation of a polymer chain in water as the solution is heated or cooled through its lower critical solution temperature (LCST). Poly(N-isopropylacrylamide) (PNIPAM) is the most studied thermosensitive water-soluble polymers. 7 Other ther- mosensitive aqueous polymers of industrial or academic interest include cellulose ethers, 8 certain poly(2-alkyl-2-oxazolines), 9 and poly(methyl vinyl ether) 10 as well as various poly(acrylates) and poly(methacrylates). 11 We reported recently the synthesis and properties of a family of thermoresponsive associative polymers consisting of a PNIPAM chain carrying an n-octadecyl group at each chain end (C 18 -PNIPAM-C 18 ). 12,13 In aqueous media below their LCST, the C 18 -PNIPAM-C 18 samples self-assemble following the well-established patterns typical of HEUR copolymers: formation of flower micelles in solutions of low concentration and, above a critical concentration, intermicellar bridging leading to clusters of micelles and, eventually, to a cross-linked micellar network. Aqueous C 18 -PNIPAM-C 18 solutions also respond to changes in temperature in a controlled manner: in the dilute regime, they form stable mesoglobules in solutions heated above the LCST, 14 while in the concentrated regime, syneresis takes place. We describe here a new class of thermoresponsive associative polymers in which the water-soluble main chain is either poly(2-ethyl-2-oxazoline) (PEtOx) or poly(2-isopropyl- 2-oxazoline) (PiPrOx). Poly(2-alkyl-2-oxazolines), where the alkyl group is methyl, ethyl, or isopropyl, are biocompatible, biodegradable, and possess stealth characteristics in vitro and in vivo comparable to those of poly(ethylene glycols). 15 They are used increasingly as biomaterials, hydrogels, proteins * Corresponding author: Ph (514) 340 5179; Fax (514) 340 5292; e-mail francoise.winnik@umontreal.ca. † University of Montreal. ‡ BAM Federal Institute for Materials Research and Testing. § Kyoto University. 2204 Macromolecules 2009, 42, 2204-2214 10.1021/ma802592f CCC: $40.75  2009 American Chemical Society Published on Web 02/18/2009