One-Step Synthesis of Amphiphilic, Double Thermoresponsive

Article pubs.acs.org/Macromolecules

One-Step Synthesis of Amphiphilic, Double Thermoresponsive Diblock Copolymers Jan Weiss†,§ and André Laschewsky*,†,‡ †

Department of Chemistry, University of Potsdam, Karl-Liebknecht-Strasse 24-25, 14476 Potsdam-Golm, Germany Fraunhofer Institute for Applied Polymer Research, Geiselbergstrasse 69, 14476 Potsdam-Golm, Germany

‡

S Supporting Information *

ABSTRACT: The copolymerization of an excess of a functionalized styrene monomer, 4-vinylbenzyl methoxytetrakis(oxyethylene) ether, with various Nsubstituted maleimides yields tapered diblock copolymers in a one-step procedure, when applying reversible deactivation radical polymerization (RDRP) methods, such as ATRP and RAFT. The particular chemical structure of the diblock copolymers prepared results in reversible temperature-responsive two-step aggregation behavior in dilute aqueous solution. In this way, a double hydrophilic block copolymer is transformed step by step into an amphiphilic macrosurfactant, and finally into a double hydrophobic copolymer, as followed by turbidimetry and dynamic light scattering. Copolymers in which the maleimide repeat units bear short hydrophobic side chains are freely watersoluble at low temperature and form micellar aggregates above their cloud point. Further heating above the phase transition temperature of the second block results in secondary aggregation. Copolymers with maleimides that bear strongly hydrophobic substituents undergo two thermally induced aggregation steps upon heating, too, but show in addition intramolecular hydrophobic association in water already at low temperatures, similar to the behavior of polysoaps.

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INTRODUCTION So-called controlled polymerization techniques enable to synthesize block copolymers of defined compositions, molar mass, and high chain end functionality. Among those, the reversible deactivation radical polymerization (RDRP)1 methods (often referred to as controlled radical polymerization techniques) have become very prominent to date, including methods such as nitroxide-mediated polymerization (NMP),2,3 atom transfer radical polymerization (ATRP),4−6 and reversible addition−fragmentation chain transfer polymerization (RAFT).7,8 Though in general much more convenient than using living ionic polymerization, the synthesis of block copolymers by RDRP methods typically requires a two-step process, comprising the synthesis and isolation of a homopolymer block, bearing a high content of active end groups as reactive intermediate. Only the subsequent use of this intermediate as macroinitiator or macro-chain-transfer agent in a second polymerization step, which adds another polymer block via chain extension with a second monomer, yields the desired block copolymer. Some elegant studies have shown that it is possible to reduce the experimental setup to one-pot (but still multistep) procedures in particular cases, if e.g. the polymerization mechanism is switched by transforming the nature of the growing chain ends in situ.9−11 Yet, every additional polymerization or transformation step goes along with an inherent loss of a small, but notable, amount of reactive polymer chains, i.e., produces some unwanted polymeric impurities.10 In order to avoid such side reactions, and also to reduce the overall needed practical effort by simplifying the typical two-step reaction sequence by a one-step procedure, we explored the possibility of an one-pot−one-step synthesis of © XXXX American Chemical Society

functional diblock copolymers via RDRP under homogeneous reaction conditions, exemplified by the preparation of double thermoresponsive water-soluble polymers. Our approach is based on the well-known alternating copolymerization of styrene and a number of electron-poor comonomers. The most intensely studied system of this type is undoubtedly the copolymerization of styrene and maleic anhydride,12,13 which is the textbook case for alternating free radical copolymerization. Moreover, by using an excess of styrene in the presence of maleic anhydride, block copolymers have been successfully prepared via RDRP.14−16 In order to extend this strategy to functional polymers, we aimed at the alternating copolymerization of substituted styrene derivatives with N-substituted maleimides.17−21 The use of an excess of styrene monomer the copolymerization with a given maleimide using RDRP should provide functionalized diblock copolymers in a single polymerization step (Scheme 1). During Scheme 1. One-Step Synthesis of Double Thermoresponsive Block Copolymers via RDRP Methods

Received: February 10, 2012 Revised: April 27, 2012

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dx.doi.org/10.1021/ma300285y | Macromolecules XXXX, XXX, XXX−XXX

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Figure 1. Structure of the monomers used (top line) and idealized structure of the tapered diblock copolymers prepared (bottom line). columns with pore sizes of 103, 105, and 106 Å (flow rate 1 mL min−1, refractive index detector Shodex RI-71). Linear polystyrene standards (PSS, Germany) were used for calibration. Turbidity measurements were performed on a Tepper TP1 photometer (Mainz, Germany). Transmittance of polymer solutions in pure deionized water with a concentration of 0.5 or 1.0 g L−1 was monitored at 670 nm as a function of temperature (cell path length: 12 mm; one heating/cooling cycle at rate of 1 °C min−1). The temperature of the onset of turbidity upon heating was defined as transition temperature. Dynamic light scattering was performed on a thermostated Malvern HPPS-ET equipped with a He−Ne laser (λ = 633 nm) at concentrations of 1.0 g L−1, using the backscattering mode at a fixed angle of 173°. Materials. Initiators 2,2-azobis(isobutyronitrile) (AIBN) and 1[(1-cyano-1-methylethyl)azo]formamide (V30) were kind gifts from WAKO. 1,1,4,7,10,10-Hexamethyltriethylenetetramine (HMTETA, 97%, Aldrich), CuBr (>98%, Aldrich), and triethylene glycol (99%, Aldrich) were used as received. The synthesis of 3-trimethylsilyl benzyl bromide and of 3-(trimethylsilyl)benzyl 3′-(trimethylsilyl)propyl trithiocarbonate are described elsewhere.46 Monomer methoxytetraethylene glycol-4-vinylbenzyl ether (M1) was prepared as described before.23 Comonomers N-methylmaleimide (M2) and N-propylmaleimide (M3) were purchased from Aldrich, and N-decylmaleimide (M4) was a gift from Peter Hendlinger. N-(3-Trimethylsilyl)propylmaleimide (M5) and N-(3-triethylsilyl)propargylmaleimide (M6) were made following extablished procedures.21,47 Experimental and analytical details of the synthesized monomers were reported previously21 or are provided in the Supporting Information. Dialysis membranes (ZelluTrans, Roth, Germany) had a nominal cutoff of 4−6 kDa. RAFT Polymerization of M1 and M3. In a typical procedure, monomer M1 (280 mg, 0.86 mmol), 3-(trimethylsilyl)benzyl 3′(trimethylsilyl)propyltrithiocarbonate (2.1 mg, 0.0054 mmol), Npropylmaleimide M3 (6.0 mg, 0.043 mmol), and 1-[(1-cyano-1methylethyl)azo]formamide (V30, 0.5 mg, 0.004 mmol) in triethylene glycol (250 mg) were purged with nitrogen for 20 min. The mixture was polymerized at 100 °C for 5 days, cooled to ambient temperature, dialyzed against water, and lyophilized to yield copolymer P(1-alt3)12-b-P152 as slightly yellow, viscous oil (60 mg, 21%). ATRP Polymerization of M1 and M5. In a typical procedure, monomer M1 (500 mg, 1.54 mmol), 3-trimethylsilylbenzyl bromide (3.6 mg, 0.015 mmol), and HMTETA (8.0 mg, 0.034 mmol) in triethylene glycol (500 mg) were purged with N2 for 20 min. The

the initial stage of the polymerization, alternating copolymers are formed due to the much faster cross-propagation reactions of the styrene monomer and the maleimide as compared to homopropagation.22 Once the maleimide is consumed, homopolymerization of the excess styrene monomer takes over, thus yielding tapered block copolymers. Recently, we demonstrated that alternating copolymerization of a water-soluble styrene derivative, namely of 4-vinylbenzyl methoxytetrakis(oxyethylene) ether, M1,23 with various Nsubstituted maleimides allows for preparing thermoresponsive polymers, the lower critical solution temperature (LCST) of which can be fine-tuned.21 This is an attractive alternative to partial postpolymerization modification24−27 or to statistical or random copolymerization of suited monomer pairs28−33 as applied so far. Now, we extend this approach to the synthesis of double thermoresponsive diblock copolymers made in one single polymerization step by using an excess of M1 in the copolymerization with various N-substituted maleimides (Figure 1). The resulting polymers of the architecture P(1alt-maleimide)-b-P1 contain two blocks exhibiting two separate volume phase transition temperatures of the LCSTtype in aqueous solution. Such block copolymers with dual LCST behavior have been occasionally described, being typically made via living ionic polymerization with sequential monomer addition,34,35 via macroinitiator approaches,11,36 via postpolymerization modification,37 or via a two-step RDRP process so far.38−43 They are increasingly under consideration as “smart” surfactants, e.g., for induced (de)emulsification, associative thickening, or controlled release of active agents.44,45 Thus, the temperature-controlled self-organization of the new double thermoresponsive amphiphilic polymers in aqueous solution was studied.

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EXPERIMENTAL PART

Methods. 1H NMR spectra were recorded on a Bruker DPX-400 spectrometer operating at 400 MHz at room temperature. Molar masses and molar mass distributions were determined by SEC with eluents THF or DMF + 0.1% LiBr at 25 °C, using three 5 μ-MZ-SDV B


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Table 1. Analytical Data of the Synthesized Tapered Copolymers by ATRP or RAFT Polymerization polymer

RDRP method

yielda (%)

Mntheor b

Mnapp c

PDIc,d

cloud point [°C]

second transition temp [°C]

P(1-alt-2)8-b-P131 P(1-alt-3)6-b-P116 P(1-alt-3)12-b-P152 P(1-alt-4)26-b-P163 P(1-alt-5)6-b-P120 P(1-alt-6)7-b-P123

ATRP ATRP RAFT ATRP ATRP ATRP

41 27 21 38 44 33

13 600 8 200 9 000 10 300 15 100 11 700

13 600 7 600 7 700 14 300 12 300 13 300

1.6 1.8 1.4 2.0 2.4 1.7

38 27 20 22 22 24

41 51 46 31 34 46

a Determined by gravimetry. bCalculated according to engaged ratio of monomer/initiator or of monomer/CTA, respectively, and yield.71 cBy SEC in DMF + 0.1% LiBr or THF using polystyrene standards. dMw/Mn.

Figure 2. 1H NMR spectra in DMSO-d6 of (a) P(1-alt-6)7-b-P123 bearing TES-protected propargyl side chains and (b) P(1-alt-7)7-b-P1E23 after removal of the TES moiety applying TBAF. mixture was transferred under N2 to a flask with CuBr (6.0 mg, 0.02 mmol), and N-(3-trimethylsilyl)propargylmaleimide M5 (29.8 mg, 0.14 mmol) was added. After polymerizing for 64 h at 110 °C, the mixture was cooled to ambient temperature, dialyzed against water, and lyophilized to yield copolymer P(1-alt-5)6-b-P120 as viscous oil (230 mg, 44%). ATRP Polymerization of M1 and M6. In a typical procedure, monomer M1 (760 mg, 2.34 mmol), 1-bromoethylbenzene (4.4 mg, 0.023 mmol), and HMTETA (5.4 mg, 0.023 mmol) in triethylene glycol (760 mg) were purged with N2 for 20 min. The mixture was transferred under N2 to a flask with CuBr (4.0 mg, 0.03 mmol), and N(3-triethylsilyl)propargylmaleimide M6 (91.8 mg, 0.37 mmol) was added. After polymerizing for 60 h at 110 °C, the mixture was cooled to ambient temperature, dialyzed against water, and lyophilized to yield copolymer P(1-alt-6)7-b-P123 as viscous oil (280 mg, 33%). Removal of the Triethylsilyl Moiety in P(1-alt-6)7-b-P123. TBAF (0.1 mL) was added to P(1-alt-6)7-b-P123 (38.5 mg) in dry THF (1 mL), and the solution was stirred at room temperature overnight. Purification by dialysis against water and lyophilization yielded copolymer P(1-alt-7)6-b-P120 as viscous oil in quantitative yield.

substituents, which render the alternating copolymer blocks with M1 water-insoluble at any temperature.21 In addition to these recently described copolymer systems, we reasoned that replacing the N-propyl group of maleimide M3 by the propargyl moiety should give rise to copolymer P(1-alt-7). Such a copolymer should bear reactive alkyne groups suited for additional postpolymerization functionalization, while virtually preserving the hydrophilic−hydrophobic balance, and thus the LCST-type transition of copolymer P(1-alt-3). Alkyne functionalities are useful for, e.g., 1,3 dipolar cycloaddition reactions (the currently most popular example of “click chemistry”),48,49 thiol−yne additions (another popular example of “click chemistry”),50,51 or C−C coupling reactions such as Glaser52,53 or Sonogashira coupling.54 Furthermore, selfassembled block copolymer micelles bearing alkyne functions allow for facile formation of core or shell cross-linked micelles.55,56 However, the copolymerization of styrene with N-propargylmaleimide was reported to suffer from side reactions during the ATRP polymerization, including premature cross-linking.22 Therefore, we employed a protected alkyne group and copolymerized styrene M1 with N-(3-triethylsilyl)propargylmaleimide M6 instead of with maleimide M7, removing the TES protecting group after polymerization by treatment with fluoride.57 Different from our previous studies, the copolymerization mixtures of styrene monomer M1 with the various maleimides were modified such that they contained M1 in large excess. As illustrated in Scheme 1, this setup produces tapered block copolymers by superposing the strong preference for heteropropagation of the comonomer pair with the quasi-living character of RDRP. Indeed, the one-step copolymerizations proceeded smoothly under standard ATRP or RAFT conditions to yield homogeneous products in 20−50% yields (Table 1). The compositions of the tapered block copolymers

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RESULTS AND DISCUSSION The hydrophilic styrene monomer M1 was copolymerized with various functional maleimides, namely M2−M6 via either the ATRP or the RAFT technique (Figure 1 and Table 1). Maleimides M2 and M3 bear short alkyl chains as hydrophobic N-substituents. In agreement with the more hydrophobic character of comonomers M2 and M3 compared to M1, the LCST-type transition temperatures of the corresponding alternating copolymers are lower than the transition temperature of the homopolymer P1. While the latter is about 44 °C for elevated molar masses, alternating copolymers P(1-alt-2) and P(1-alt-3) were found to be water-soluble only at temperatures below 28 and 18 °C, respectively.21 In contrast, maleimides M4 and M5 bear strongly hydrophobic NC


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were determined by 1H NMR spectroscopy comparing the integral of the benzylic −CH2− signal of the M1 units at about 4.5 ppm with the integral of characteristic signals of the maleimide engaged. Taking the close to alternating copolymerization behavior of the monomer pairs into account,21 the analytical data show that tapered block copolymers were obtained, with the alternating copolymer block produced first, followed by the P1 homopolymer block. The successful attempts of P(1-alt-3)6-b-P116 and P(1-alt-3)12-b-P152 exemplify, that the one-pot−one-step strategy can be implemented for the maleimide/styrene copolymerization system by either ATRP or RAFT methods (Table 1). Further, the triethylsilyl (TES) protecting group of the alkyne functionality could be removed under mild conditions by treating water-insoluble diblock copolymer P(1-alt-6)7-b-P123 with tetra-n-butylammonium fluoride (TBAF). The reaction at room temperature overnight in dry THF gave the reactive copolymer P(1-alt-7)7b-P123, which is soluble in cold water. The complete disappearance of the TES signal at about 0 ppm in the 1H NMR spectra (Figure 2) indicated quantitative deprotection of the alkyne moieties of the precursor polymer. As mentioned, homopolymer P1 exhibits a LCST-type transition in aqueous solution at about 44 °C, while alternating copolymerization with various maleimide comonomers enables to modulate the phase transition temperature.21 Thus, we reasoned that polymerization of appropriate mixtures of styrene M1 and substituted maleimides should yield double thermoresponsive block copolymers in a one-step reaction, when the styrene is engaged in sufficient excess (see Scheme 1). Indeed, this approach turned out to be a most convenient pathway to such multiresponsive copolymers. For instance, copolymerization of M1 with M2 resulted in double thermoresponsive tapered diblock copolymers made of an alternating copolymer block P(1-alt-2), which has a cloud point around 28 °C, and of a P1 homopolymer block, presenting a cloud point around 39 °C. Moreover, DLS measurements showed that P(1-alt-2)8-bP131, in which the homopolymer block is about twice as long as the copolymer block, undergoes aggregation in dilute aqueous solution above 36 °C, due to the collapse of the P(1-alt-2) block (Figure 3). After reaching an initial maximum of the hydrodynamic diameter Dh of about 75 nm, the P(1-alt-2) core−P1 shell micelles underwent secondary aggregation when the solution was heated to 41 °C and passed the second phase transition temperature. The still hydrated clusters with a Dh of 500−600 nm shrank with further heating due to ongoing

dehydration, resulting in stable particles of about 180 nm above 46 °C. When copolymerizing M1 with M3, i.e., upon increasing the length of the hydrophobic side chain of the maleimide moderately, double thermoresponsive tapered diblock copolymers P(1-alt-3)6-b-P116 and P(1-alt-3)12-b-P152 were obtained. As the cloud point of the alternating block P(1-alt-3) of about 18 °C is considerably lower temperature than the cloud point of P1,21 thermally induced two-step aggregation is observed (Figure 4a,b). The small block copolymer P(1-alt3)6-b-P116 started to form large aggregates above 25 °C. These grew in size with increasing temperature until about 36 °C, beyond which they shrank to Dh values of about 60 nm (Figure 4a). When passing 48 °C, the aggregates start to grow again, reaching finally Dh values of 300−400 nm. Aggregate formation is accompanied by a continuous drop in transmittance. For this copolymer, the onset of aggregation is about 8 °C higher than the reported phase transition temperature for the isolated alternating copolymer block.21 This may be explained by the combined effects of the small block size together with covalent binding to an adjacent hydrophilic block (namely of P1). Both features are known to make rise LCST-type phase transition temperatures.39,42,49,58,59 According to their large size (compared to the contour length of the copolymer in the order of 10 nm), the aggregates presumably consist of clustered micelles. When the second cloud point is crossed, the collapse of the solubilizing shell first makes the aggregates shrink, before secondary aggregation starts and size increases again. The temperature-induced aggregation behavior of this tapered block copolymer obtained by the one-step procedure is, hence, comparable to the one of double thermoresponsive block copolymers obtained by a classical stepwise synthesis.39,59 In comparison, the analogous block copolymer P(1-alt-3)12-bP152, in which the high LCST block P1 has about 4 times the size of the low LCST block, formed aggregates of about 45 nm Dh above 18 °C, in good agreement with the cloud point of the isolated P(1-alt-3) block (Figure 4b). Further heating did not change the aggregate size significantly until reaching 38 °C, i.e., the phase transition temperature of the isolated P1 block. Then again, Dh shrank initially but rapidly increased above 44 °C to values of about 400 nm, suggesting secondary aggregation once the micellar shell has collapsed. In the tapered diblock copolymers made with maleimides M4 and M5, the maleimide side chains are considerably more hydrophobic than in copolymers containing M2 or M3. Though the corresponding isolated alternating copolymer blocks are insoluble in water at any temperature,21 both block copolymers P(1-alt-4)26-b-P163 and P(1-alt-5)6-b-P120 with a relatively long P1 block gave clear aqueous solutions below 20 °C without any indication for aggregation detected by DLS (Figure 4c,d). Accordingly, the hydrophilicity of the P1 block must suffice to allow the dispersion of the alternating block. Still, a comparison of the 1H NMR spectra of these copolymers in an organic solvent with the ones obtained in D2O (Figure 5) exhibited strong attenuation of the signals of the hydrophobic side chains in D2O. This suggests that the alternating blocks are not fully solvated in D2O even below 20 °C. Probably, the alternating copolymer blocks characterized by the alternation of hydrophilic and strongly hydrophobic side chains undergo intramolecular hydrophobic association at low temperatures, behaving analogously to polysoaps.60−63 While the hydrophobic maleimide residues microphase separate along the polymer backbone forming hydrophobic domains, they are

Figure 3. Dynamic light scattering measurements of P(1-alt-2)8-bP131 in dilute aqueous solution (0.5 g L−1). The line is meant as guide to the eye. D


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Figure 4. Dynamic light scattering and turbidity measurements in dilute aqueous solutions of block copolymers: (a) P(1-alt-3)6-b-P116 (0.5 g L−1), (b) P(1-alt-3)12-b-P152 (0.5 g L−1), (c) P(1-alt-4)26-b-P163 (1 g L−1), (d) P(1-alt-5)6-b-P120 (1 g L−1), (e) P(1-alt-6)7-b-P123 (1 g L−1), (f) P(1alt-7)7-b-P123 (1 g L−1). The dotted lines are guides to the eye.

Above the first thermal transition, P(1-alt-4)26-b-P163 and P(1-alt-5)6-b-P120 form relatively small aggregates with Dh values of 100−120 and 35−45 nm, respectively (Figure 4c,d). These aggregates presumably consist of collapsed hydrophobic alternating blocks forming the core surrounded by a solubilizing shell of P1. After a slight gradual increase of the Dh with increasing temperature, P(1-alt-4)26-b-P163 and P(1-alt-5)6-bP120 exhibited a sudden, strong increase of the hydrodynamic diameters above 31 and 34 °C, respectively. This is attributed to a second phase transition, namely the collapse of the P1 shell, and led to secondary aggregation into large aggregates with a Dh of 600−700 nm for both polymers. This is accompanied by a drastic drop in transmittance. The collapse of the P1 block is lowered by about 10 °C in these copolymers in comparison to block copolymers made from M1 and M2 or M3. This may be explained by the more hydrophobic alternating blocks when copolymerizing M4 or M5, which

at least partially shielded from water by the hydrophilic oligoethylene glycol side chains of the M1 repeat units, as depicted in Scheme 2. Apparently, the hydrophilic repeat units are only capable of keeping the polymers dispersed when supported by an additional hydrophilic block of P1. However, with increasing temperature, the hydrophilicity of the oligoethylene glycol side chains is gradually reduced. Above 20 °C, intermolecular aggregation of both polymers occurs, as seen by DLS as well as by the naked eye according to the increasing turbidity of the solutions. For the assumed polysoap-like structures, the onset temperature for aggregation seems to be mainly determined by the presence of hydrophobic microdomains rather than by the detailed nature of the maleimide substituent. The interface of the oligoethylene glycol protected hydrophobic microdomains should not differ much for the two maleimides employed and therefore should result in similar cloud points. E


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hydrophobic microdomains, which is formed already at low temperature due to the polysoap character of the alternating copolymer blocks and which is decorated for the three copolymers by the same oligoethylene glycol chains, mainly determines the onset of aggregation. After passing a maximum, Dh dropped to about 70 nm between 40 and 46 °C, probably for the same reasons as discussed for the diblock copolymers of M1 with M3 or M4. Also, DLS reveals a second thermal transition at 45 °C, leading to large aggregates with Dh of about 150 nm, due to the collapse of the P1 shell. After removal of the strongly hydrophobic TES moieties, the thermally induced aggregation of the resulting copolymer P(1alt-7)7-b-P123 changed markedly and ressembled much more to the behavior observed for P(1-alt-3)12-b-P152 (cf. Figures 4b and 4f). While being completely soluble below 20 °C, micelles with a Dh of about 60 nm are formed when passing the cloud point (Figure 4f). Furthermore, at about 37 °C, where Dh reached a plateau value, a marked drop in transmittance is seen, suggesting the occurrence of a second thermal transition around this temperature. This is attributed to the collapse of the P1 shell, paving the way to secondary aggregation and clustering above 55 °C, with Dh increasing to more than 200 nm. Comparing the different behaviors of the various tapered block copolymers made, it becomes clear that, on one hand, all block copolymers showed the expected double thermosensitive behavior in dilute aqueous solution. On the other hand, it is also evident that the N-substituent of the maleimide comonomer employed has a predominant influence on the detailed associative behavior. While relatively small hydrophobic substituents moieties give rise to a behavior as known from other diblock copolymers disposing of two separate LCST transitions, strongly hydrophobic substituents induce a temperature-modulated superposition of intramolecular and intermolecular hydrophobic association, as typical for polysoaps and macrosurfactants, respectively.64 This type of stimulusresponsive association may provide an interesting alternative for the triggered release of active agents solubilized in the hydrophobic domains in comparison to the standard systems, in which the hydrophobic domain is completely “switched off” when passing the transition temperature.49,65−67

Figure 5. 1H NMR spectra at 20 °C of (a) P(1-alt-4)26-b-P163 in DMSO-d6 (bottom) and D2O (top) and (b) P(1-alt-5)6-b-P120 in CDCl3 (bottom) and D2O (top) at concentrations of 10 g L−1.

should reduce the LCST of the attached second thermoresponsive block. Finally, copolymers P(1-alt-6)7-b-P123 and P(1-alt-7)7-bP123 were studied in dilute aqueous solution by turbidimetry and DLS. Although the alternating copolymer of M1 with M6 was not soluble in water, P(1-alt-6)7-b-P123 gave clear solutions below 22 °C without any indication for aggregate formation by DLS (Figure 4e). This behavior corresponds to the one of alternating blocks of M1 with M4 or M5 described above, and we assume that the same reasoning concerning their dispersion in water applies. Moreover above 22 °C, P(1-alt-6)7b-P123 started to aggregate according to DLS (Figure 4e), the aggregates reaching gradually a size of Dh 190 nm with increasing temperature. This process is accompanied by a marked drop of the solution’s transmittance (Figure 4e). The cloud point occurs at a temperature very close to the cloud points found for P(1-alt-4)26-b-P163 and P(1-alt-5)6-b-P120. This finding supports our hypothesis that the interface of the

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CONCLUSION Using an excess of a thermoresponsive styrene derivative in the alternating copolymerization system with N-substituted maleimides, double thermoresponsive tapered block copolymers can be conveniently produced in a one-step procedure. These block copolymers show temperature induced two-step aggregation behavior in dilute aqueous solution similar to

Scheme 2. Model for the Aggregation of Copolymers P(1-alt-4)26-b-P163 and P(1-alt-5)6-b-P120 in Aqueous Solution below and above the First Cloud Point (20 °C)

F


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(15) Zhu, M.-Q.; Wei, L.-H.; Li, M.; Jiang, L.; Du, F.-S.; Li, Z.-C.; Li, F.-M. Chem. Commun. 2001, 37, 365−366. (16) Lessard, B.; Maric, M. Macromolecules 2010, 43, 879−885. (17) Chen, G.-Q.; Wu, Z.-Q.; Wu, J.-R.; Li, Z.-C.; Li, F.-M. Macromolecules 2000, 33, 232−234. (18) Mohamed, A. A.; Jebrael, F. H.; Elsabeé, M. Z. Macromolecules 1986, 19, 32−37. (19) El-Guweri, M.; Hendlinger, P.; Laschewsky, A. Macromol. Chem. Phys. 1997, 198, 401−418. (20) Pfeifer, S.; Lutz, J.-F. J. Am. Chem. Soc. 2007, 129, 9542−9543. (21) Weiss, J.; Li, A.; Wischerhoff, E.; Laschewsky, A. Polym. Chem. 2012, 3, 352−361. (22) Pfeifer, S.; Lutz, J.-F. Chem.Eur. J. 2008, 14, 10949−10957. (23) Zhao, B.; Li, D.; Hua, F.; Green, D. R. Macromolecules 2005, 38, 9509−9517. (24) Ritter, H.; Stock, A. Macromol. Rapid Commun. 1994, 15, 271− 277. (25) Laschewsky, A.; Rekai, E. D.; Wischerhoff, E. Macromol. Chem. Phys. 2001, 202, 276−286. (26) Christova, D.; Ivanova, S.; Ivanova, G. Polym. Bull. 2003, 50, 367−372. (27) Dworak, A.; Trzebicka, B.; Utrata-Wesotek, A.; Walach, W. Polym. Bull. 2003, 50, 47−54. (28) Taylor, L. D.; Cerankowski, L. D. J. Polym. Sci., Part A: Polym. Chem. 1975, 13, 2551−2570. (29) Lutz, J.-F.; Hoth, A. Macromolecules 2006, 39, 893−896. (30) Huber, S.; Jordan, R. Colloid Polym. Sci. 2008, 286, 395−402. (31) Chung, J. E.; Yokoyama, M.; Aoyagi, T.; Sakurai, Y.; Okano, T. J. Controlled Release 1998, 53, 119−130. (32) Priest, J. H.; Murray, S. L.; Nelson, R. J.; Hoffman, A. S. ACS Symp. Ser. 1987, 350, 255−264. (33) Akdemir, Ö .; Badi, N.; Pfeifer, S.; Zarafshani, Z.; Laschewsky, A.; Wischerhoff, E.; Lutz, J.-F. ACS Symp. Ser. 2009, 1023, 189−202. (34) Sugihara, S.; Kanaoka, S.; Aoshima, S. J. Polym. Sci., Part A: Polym. Chem. 2004, 42, 2601−2611. (35) Sugihara, S.; Kanaoka, S.; Aoshima, S. Macromolecules 2005, 38, 1919−1927. (36) Liu, S.; Billingham, N. C.; Armes, S. P. Angew. Chem. 2001, 113, 2390−2393. (37) Jochum, F. D.; Roth, P. J.; Kessler, D.; Theato, P. Biomacromolecules 2010, 11, 2432−2439. (38) Mertoglu, M.; Garnier, S.; Laschewsky, A.; Skrabania, K.; Storsberg, J. Polymer 2005, 46, 7726−7740. (39) Skrabania, K.; Kristen, J.; Laschewsky, A.; Akdemir, Ö .; Hoth, A.; Lutz, J.-F. Langmuir 2007, 23, 84−93. (40) Hua, F.; Jiang, X.; Zhao, B. Macromolecules 2006, 39, 3476− 3479. (41) Xie, D.; Ye, X.; Ding, Y.; Zhang, G.; Zhao, N.; Wu, K.; Cao, Y.; Zhu, X. X. Macromolecules 2009, 42, 2715−2720. (42) Weiss, J.; Laschewsky, A. Langmuir 2011, 27, 4465−4473. (43) Lessard, B. H.; Ling, E. J. Y.; Maric, M. Macromolecules 2012, 45, 1879−1891. (44) Dimitrov, I.; Trzebicka, B.; Müller, A. H. E.; Dworak, A.; Tsvetanov, C. B. Prog. Polym. Sci. 2007, 32, 1275−1343. (45) Laschewsky, A. SOFW J. 2011, 137 (1/2), 34−40. (46) Päch, M.; Zehm, D.; Lange, M.; Dambowsky, I.; Weiss, J.; Laschewsky, A. J. Am. Chem. Soc. 2010, 132, 8757−8765. (47) Bodtke, A.; Otto, H.-H. Pharmazie 2005, 60, 803−813. (48) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004−2021. (49) McCormick, C. L.; Sumerlin, B. S.; Lokitz, B. S.; Stempka, J. E. Soft Matter 2008, 4, 1760−1773. (50) Yu, B.; Chan, J. W.; Hoyle, C. E.; Lowe, A. B. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 3544−3557. (51) ten Brummelhuis, N.; Schlaad, H. Polym. Chem. 2011, 2, 1180− 1184. (52) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed. 2000, 39, 2632−2657. (53) Yamamoto, T.; Tezuka, Y. Polym. Chem. 2011, 2, 1930−1941.

block copolymers obtained by the classical sequential approach. When incorporating strongly hydrophobic maleimide residues, the alternating blocks can additionally form polysoap-like intramolecular aggregates with hydrophobic nanodomains in water already at low temperatures below the cloud point. Still as for the other block copolymers, they display also two thermal transitions with the accompanying changes of self-organization. Taking potential applications of “smart” block copolymers into account,68−70 the one-step synthesis is particularly convenient and enables for a straightforward access to complex functional polymers. This approach is not limited to styrene derivatives and maleimides but can be extended to all monomer pairs which undergo alternating copolymerization and which contain at least one comonomer that is capable of homopolymerization.

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ASSOCIATED CONTENT

S Supporting Information *

Detailed experimental procedures for the synthesis of 5; complete analytical data; 1H NMR and 13C NMR spectra; additional and enlarged figures as well as NMR and SEC data of the synthesized copolymers. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Present Address §

Institut Charles Sadron, UPR22-CNRS, 23 rue du Loess, 67034 Strasbourg, France. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The work was supported by the German Research Council (Deutsche Forschungsgemeinschaft DFG), grant LA611/4, and by Fonds der Chemischen Industrie.

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REFERENCES

(1) Jenkins, A. D.; Jones, R. G.; Moad, G. Pure Appl. Chem. 2010, 82, 483−491. (2) Hawker, C. J.; Bosman, A. W.; Harth, E. Chem. Rev. 2001, 101, 3661−3688. (3) Grubbs, R. B. Polym. Rev. 2011, 21, 104−137. (4) Kamigaito, M.; Ando, T.; Sawamoto, M. Chem. Rev. 2001, 101, 3689−3745. (5) Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101, 2921−2990. (6) Braunecker, W. A.; Matyjaszewski, K. Prog. Polym. Sci. 2007, 32, 93−146. (7) Moad, G.; Rizzardo, E.; Thang, S. H. Polymer 2008, 49, 1079− 1131. (8) Barner-Kowollik, C. Handbook of RAFT Polymerization; WileyVCH: Weinheim, 2008. (9) Hadjichristidis, N.; Pitsikalis, M.; Iatrou, H. Adv. Polym. Sci. 2005, 189, 1−124. (10) Schmid, C.; Weidner, S.; Falkenhagen, J.; Barner-Kowollik, C. Macromolecules 2012, 45, 87−99. (11) Sugihara, S.; Yamashita, K.; Matsuzuka, K.; Ikeda, I.; Maeda, Y. Macromolecules 2012, 45, 794−804. (12) Alfrey, T.; Lavin, E. J. Am. Chem. Soc. 1945, 67, 2044−2045. (13) Geukens, B.; Meersman, F.; Nies, E. J. Phys.Chem. B 2008, 112, 4474−4477. (14) Benoit, D.; Hawker, C. J.; Huang, E. E.; Lin, Z.; Russell, T. P. Macromolecules 2000, 33, 1505−1507. G


Macromolecules

Article

(54) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874−922. (55) O’Reilly, R. K.; Joralemon, M. J.; Wooley, K. L.; Hawker, C. J. Chem. Mater. 2005, 17, 5976−5988. (56) Zhang, S.; Zhao, Y. J. Am. Chem. Soc. 2010, 132, 10642−10644. (57) Wuts, P. G. M.; Greene, T. W. Greene’s Protective Groups in Organic Synthesis, 4th ed.; John Wiley & Sons: Hoboken, NJ, 2006. (58) Aseyev, V.; Tenhu, H.; Winnik, F. Adv. Polym. Sci. 2011, 242, 29−89. (59) Weiss, J.; Böttcher, C.; Laschewsky, A. Soft Matter 2011, 7, 483−492. (60) Strauss, U. P.; Jackson, E. G. J. Polym. Sci. 1951, 6, 649−659. (61) Laschewsky, A. Adv. Polym. Sci. 1995, 124, 1−86. (62) Köberle, P.; Laschewsky, A.; van den Boogaard, D. Polymer 1992, 33, 4029−4039. (63) Woermann, D.; Wall, F. T. J. Phys. Chem. 1960, 64, 581−584. (64) Laschewsky, A. Tenside, Surfactants, Deterg. 2003, 40, 246−249. (65) Arotçaréna, M.; Heise, B.; Ishaya, S.; Laschewsky, A. J. Am. Chem. Soc. 2002, 124, 3787−3793. (66) Bajpai, A. K.; Shukla, S. K.; Bhanu, S.; Kankane, S. Prog. Polym. Sci. 2008, 33, 1088−1118. (67) de las Heras Alarcon, C.; Pennadam, S.; Alexander, C. Chem. Soc. Rev. 2005, 34, 276−285. (68) Schmaljohann, D. Adv. Drug Delivery Rev. 2006, 58, 1655−1670. (69) Pasparakis, G.; Vamvakaki, M. Polym. Chem. 2011, 2, 1234− 1248. (70) Moughton, A. O.; Hillmyer, M. A.; Lodge, T. P. Macromolecules 2012, 45, 2−19. (71) Skrabania, K.; Miasnikova, A.; Bivigou-Koumba, A. M.; Zehm, D.; Laschewsky, A. Polym. Chem. 2011, 2, 2074−2083.

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One-Step Synthesis of Amphiphilic, Double Thermoresponsive

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