Synthesis and Characterization of Novel “Schizophrenic” Water-Soluble Triblock Copolymers and Shell Cross-Linked Micelles Vural Bu 1 tu 1 n,* Rukiye B. Top, and Senem Ufuklar Eskis ¸ ehir Osmangazi UniVersity, Faculty of Arts and Science, Department of Chemistry, Campus of Mes ¸ elik, 26040, Eskis ¸ ehir, Turkey ReceiVed September 21, 2005; ReVised Manuscript ReceiVed NoVember 19, 2005 ABSTRACT: A series of novel “schizophrenic” ABC triblock copolymers, 2-(diethylamino)ethyl methacrylate- b-2-(dimethylamino)ethyl methacrylate-b-2-(N-morpholino)ethyl methacrylate [PDEA-PDMA-PMEMA], has been synthesized by using group transfer polymerization. These triblock copolymers dissolved molecularly in aqueous solution at low pH (<6.6) due to protonation of all tertiary amine residues of the three blocks and formed three-layer “onionlike” micelles at pH 7.6 by PDEA block forming the micelle cores, PDMA block forming the inner shells, and PMEMA forming the coronas. On the other hand, by the addition of Na 2 SO 4 to the molecularly soluble polymer solution at pH 6.5 the neutral PMEMA-block became hydrophobic due to the salting-out effect and another three-layer “onionlike” micellization occurred, comprising PMEMA cores, PDMA inner shells, and PDEA coronas. DLS studies indicated nearly-monodisperse micelles in both cases. The intensity-average radii of the PMEMA-core and the PDEA-core micelles were 10.1 nm (polydispersity index, μ 2 /Γ 2 ) 0.10) and 12.9 nm (μ 2 /Γ 2 ) 0.08), respectively. It was also observed that these triblock copolymers formed PMEMA-core micellization in n-hexane. Finally, two types of novel shell cross-linked micelles (PDEA-core in aqueous media and PMEMA-core in n-hexane) were also prepared from these remarkable PDEA-PDMA-PMEMA triblock copolymers by cross-linking the inner PDMA shell of the micelles. In shell cross-linking of both micelles, the outer PDEA or PMEMA shell acted as steric stabilizer and prevented intermicelle aggregation even when the cross-linking chemistry was carried out at high polymer concentrations. Introduction Since 1998 numerous examples of novel water-soluble diblock copolymers that exhibit so-called “schizophrenic” character have been reported. 1-14 That is, the copolymer chains can self-assemble in dilute aqueous solution in the absence of any organic cosolvent to form two distinct micelle structures. In each case, the individual blocks can be independently tuned to become either hydrophilic or hydrophobic by subtle adjust- ment of the solution temperature, solution pH or ionic strength. The original report in this new sub-field involved a tertiary amine methacrylate-based AB diblock copolymer, 2-(diethyl- amino)ethyl methacrylate-b-2-(N-morpholino)ethyl methacryl- ate [PDEA-PMEMA], 1,2 synthesized by using group transfer polymerization that was both pH- and salt-responsive, allowing the formation of either PMEMA-core micelles or PDEA-core micelles in aqueous solution with the diameter of 26 and 33 nm, respectively. The synthesis of a second “schizophrenic” diblock copolymer, poly(propylene oxide)-b-2-(diethylamino)ethyl methacrylate [PPO-PDEA] was reported using atom transfer radical poly- merization (ATRP) chemistry. 3 While the PDEA block has pH- sensitive water-solubility the PPO block exhibits inverse tem- perature solubility behavior. The PPO-PDEA diblock dissolved molecularly at 5 °C at pH 6, with the PDEA block in its protonated, cationic form. When the solution pH was adjusted to pH 8.5, PDEA-core micelles were formed at 5 °C. Alternatively, warming the original solution at pH 6 up to 40 °C led to PPO-core micelles. Later on, various novel zwitterionic diblock copolymers, (4- vinylbenzoic acid)-b-DEA [PVBA-PDEA], 4 PVBA-PME- MA, 5 2-(dimethylamino)ethyl methacrylate-b-methacrylic acid [PDMA-PMAA], 6 PMAA-PDEA, 7 succinyl ethyl methacryl- ate-b-DEA [PSEMA-PDEA] 8, and MAA-b-methoxy-capped oligo(ethylene glycol) methacrylate [PMAA-OEGMA], 9 were also reported having “schizophrenic” character merely by adjusting the solution pH and temperature. In the cases of PMAA-core micelles, it was not possible to obtain conclusive spectroscopic evidence. 9,7 There are a few reports on the purely thermoresponsive “schizophrenic” diblock copolymers, (N-isopropylacrylamide)- b-(sulfobetaine methacrylamide) [PNIPAM-PSBMAM], 10,11 selectively betainized PDMA-PMEMA diblock copolymer [PSBMA-PMEMA] 12 and selectively betainized DMA-b-N,N′- diethyl acrylamide 13 which forms A-core micelles below the lower consolute solution temperature (LCST) and B-core micelles above the consolute solution temperature (UCST). Only one ABC type block copolymer was reported as “schizophrenic” triblock copolymer in the literature. 14 A PEO- based macroinitiator was used to first polymerize 2-(diethyl- amino)ethyl methacrylate (DEA) and then 2-hydroxyethyl methacrylate (HEMA) in a one-pot synthesis via ATRP. The resulting PEO-PDEA-PHEMA triblock copolymer precursors were converted into the corresponding PEO-PDEA-PSEMA zwitterionic triblock copolymers by esterification of the hydroxy groups on the HEMA block using succinic anhydride. A “trinity” of micellar aggregates was formed by these PEO-PDEA- PSEMA triblock copolymers in aqueous solution simply by adjusting the solution pH at ambient temperature. 14 Three types of micelles were formed in aqueous solution: (i) the hydrogen- bonded PSEMA/PEO-core micelles at low pH, (ii) the PDEA- core micelles in alkaline, and (iii) the PSEMA/PDEA inter- polyelectrolyte-core micelles formed at around the IEP. In all micellizations of PEO-PDEA-PSEMA triblock copolymer, there were two layers (core and corona). * To whom correspondence should be addressed. E-mail: vbutun@ogu.edu.tr. 1216 Macromolecules 2006, 39, 1216-1225 10.1021/ma052052k CCC: $33.50 © 2006 American Chemical Society Published on Web 01/13/2006