A New Family of Thermo-, pH-, and CO2-Responsive Homopolymers

Article pubs.acs.org/Macromolecules

A New Family of Thermo‑, pH‑, and CO2‑Responsive Homopolymers of Poly[Oligo(ethylene glycol) (N‑dialkylamino) methacrylate]s Ke Wang,† Shengli Chen,† and Wangqing Zhang*,†,‡ †

Key Laboratory of Functional Polymer Materials of the Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China ‡ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China S Supporting Information *

ABSTRACT: A new family of thermo-, pH-, and CO2-responsive homopolymers of poly[oligo(ethylene glycol)(N-dialkylamino)methacrylate]s combining the pendants of oligo ethylene glycol (OEG) moiety and dialkylamine are synthesized by RAFT polymerization. In these poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s, the OEG moiety as well as the dialkylamine group affords thermoresponse, and the dialkylamine group affords pH-, and CO2-response. The phase transition temperature (CP) of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s is firmly correlative to the number of the OEG moiety and the dialkylamine group, and it is found that higher number of the OEG moiety and higher CP, and the longer dialkylamine group and the lower CP, respectively. By tuning the OEG moiety and the dialkylamine group, eight thermo-, pH-, and CO2-responsive homopolymers with CPs ranging from 7 to 79 °C are synthesized. The thermoresponsive phase transition of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s is investigated by temperature-variable 1H NMR analysis, and the parameters affecting thermoresponsive phase transition of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s including polymerization degree, polymer concentration, terminals attached to the polymer backbone, salt, and urea are investigated. Multithermoresponsive diblock copolymer and triblock copolymer exhibiting two and three CPs are synthesized, and their versatile micellization upon temperature changing is demonstrated.

1. INTRODUCTION Stimuli-responsive polymers also called smart polymers can give response to a small variation of temperature, pH, light, and/or ions by making a great change in their physical characters such as solubility, conformation, and morphology1,2 and therefore are very promising for smart materials such as biosensors, matrices for tissue engineering, and drug delivery carriers.1,2 Of all the stimuli-responsive polymers, these possessing reversible and controllable thermoresponsive properties are highly interesting.3−5 Up to now, various thermoresponsive polymers such as poly(meth)acrylamides,5−18 poly[oligo(ethylene glycol) (meth)acrylate]s,4,11,19−25 poly(aminoethyl methacrylate)s,26−32 poly(2-alkyl-2oxazoline)s,33,34 and poly(vinyl methyl ether)s,35,36 have been reported. Poly(meth)acrylamides, which exhibit a lower critical solution temperature (LCST), may be the largest group of thermoresponsive polymers.5−18 Poly(N-isopropylacrylamide) (PNIPAM) as summarized in Scheme 1 showing a LCST (around 32 °C) close to body temperature is the most popular one,5−13 and the LCST of PNIPAM at case of molecular weight above 15.0 × 103 g/mol is almost independent of polymer concentration, pH and ionic strength. However, the pronounced hysteresis in phase transition−due to formation of inter- and intramolecular hydrogen bonding in its collapsed © 2017 American Chemical Society

state delaying hydration of PNIPAM during cooling−may impair its application.11,12 An emerging class of thermoresponsive polymers that may compete with PNIPAM are those bearing short oligo(ethylene glycol) (OEG) side chains,4,11,19−25,37,38 e.g., poly[oligo(ethylene glycol) (meth)acrylate]s. It is deemed that their thermoresponse arises from the reversible dehydration and rehydration of the OEG moieties upon temperature change.4,11,19−25 Their LCST can be tuned through variation of the repeated number of the OEG moiety or copolymerization of different monomers, and poly[2(2-methoxyethoxy)ethyl methacrylate] (PMEO2MA, Scheme 1) has a LCST of 28 °C close to that of PNIPAM.4,11,19−25 Poly(aminoethyl methacrylate)s bearing a pendent tertiary amine group are another kind of thermoresponsive polymers,26−32 and they can give response to pH and CO2, which makes them much different from thermoresponsive poly(meth)acrylamides and poly[oligo(ethylene glycol) (meth)acrylate]s as discussed above. For example, poly(N,Ndimethylaminoethyl methacrylate) (PDMAEMA, Scheme 1) is a typical thermo-, pH-, and CO2- responsive homopolReceived: April 12, 2017 Revised: May 28, 2017 Published: June 9, 2017 4686

DOI: 10.1021/acs.macromol.7b00763 Macromolecules 2017, 50, 4686−4698

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Macromolecules Scheme 1. Typical Thermoresponsive and Multistimuli-Responsive Homopolymers

Scheme 2. Synthesis of the Oligo(ethylene glycol) (N-Dialkylamino) Methacrylate Monomers

ymer.26−30 The LCST of PDMAEMA, 32−46 °C, is firmly dependent on the solvent character. Because of existence of tertiary amine, PDMAEMA is pH-responsive since tertiary amine can accept proton under acidic condition, and hence the polymer chains tend to expand due to coulomb repulsion. Besides, PDMAEMA can react with CO2 to form a charged ammonium bicarbonate, which can be reversibly switched back upon exposure to argon or nitrogen.39,40 Multistimuli-responsive polymers bear two or more pendent responsive moieties, and therefore can response to two or more external stimuli.1 Most of multistimuli-responsive polymers are block and random copolymers consisting of more than two monomer units,41−47 e.g., the double-thermoresponsive poly(N-n-propylacrylamide)-b-poly(N-ethylacrylamide)46 and the triple-thermoresponsive poly(N-n-propylacrylamide)-b-poly(Nisopropylacrylamide)-b-poly(N,N-ethylmethylacrylamide),47 each of which is responsive to different stimuli. Recently, growing attention has been paid to multistimuli-responsive homopolymers.48−55 However, in comparison with the large amount of multistimuli-responsive block and random copoly-

mers, multistimuli-responsive homopolymers are very rare. The thermo-, pH-, and CO2-responsive homopolymer of PDMAEMA as discussed above may be the most representative multistimuli-responsive homopolymer.26−30 By comparing the thermoresponsive homopolymers of PNIPAM and PMEO2MA and the multistimuli-responsive PDMAEMA, it is found that introduction of dialkylamine into a suitable polymeric backbone leads to the thermo-, pH-, and CO2-response. Inspired by these successes, a new multistimuli-responsive homopolymer, poly[N-(4-vinylbenzyl)-N,N-diethylamine] (PVEA, Scheme 1), which has a LCST in alcohol and is pH-responsive in water, is designed.53 Shortly later, a thermo-, pH-, and CO2-responsive homopolymer of poly[N-[2-(diethylamino)ethyl]acrylamide] (PDEAEAM, Scheme 1) is designed by introduction of diethylamine in the water-soluble polyacrylamide backbone.54 It is further revealed that diethylamine plays an important role in the thermoresponsive phase transition of PDEAEAM at temperature above LCST.55 However, for these multistimuliresponsive homopolymers, e.g., PDMAEMA, PVEA and PDEAEAM, their LCSTs are limited within a specified range. 4687


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Table 1. Summary of Poly[Oligo(ethylene glycol) (N-dialkylamino) methacrylate]s Synthesized by RAFT polymerization Mn (kg/mol) run

monomer

RAFT

time (h)

convn (%)a

DP

Mn,thb

Mn,GPCc

Mn,NMRd

Đe

1 2 3 4 5 6 7 8 9 10 11

M2 M2 M2 M2 M1 M3 M4 M5 M6 M7 M8

CDTPA CETPA BDMAT BDTB CDTPA CDTPA CDTPA CDTPA CDTPA CDTPA CDTPA

6 6 8 20 6 6 6 6 6 6 6

54.2 59.2 45.5 (35.5f) 61.1 (29.8f) 61.3 53.4 54.2 53.3 52.6 51.3 50.6

108 118 91 122 123 107 108 107 105 103 101

23.9 26.2 20.2 27.0 25.3 24.9 26.6 28.5 29.1 36.1 36.8

9.3 9.8 8.2 12.3 10.1 13.3 10.7 14.6 14.7 17.6 17.8

20.2 22.6 − 23.5 21.2 21.3 22.3 25.4 26.2 32.4 31.8

1.32 1.35 1.34 1.34 1.29 1.34 1.36 1.35 1.34 1.36 1.38

a f

Monomer conversion determined by 1H NMR. bCalculated according to eq 1. cMeasured by GPC. dObtained by 1H NMR. eDetermined by GPC. Monomer conversion in 6 h.

Table 2. Summary of the synthesis of di- and triblock copolymers Mn (kg/mol)

a

polymer

time (h)

convn (%)

P1137 P1137-b-P278 P1137-b-P278-b-P350

7 4 4

68.5 39.0 25.1

a

Mn,thb

Mn,GPCc

Mn,NMRd

Đe

27.9 44.9 56.6

13.1 19.4 21.2

23.6 38.2 47.3

1.32 1.42 1.47

Determined by 1H NMR. bCalculated according to eq 1. cMeasured by GPC. dObtained from 1H NMR. eMeasured by GPC. from anhydrous ethanol. Other chemical reagents were commercially available. Deionized water was used. 2.2. Monomer Synthesis. Scheme 2 summarizes the synthesis of oligo(ethylene glycol) (N-dialkylamino) methacrylates.60 Herein, synthesis of 2-(2-(ethyl(methyl)amino)ethoxy)ethyl methacrylate (EMAEEOMA, M2) is typically introduced. 2-(2-Chloroethoxy)ethanol (80 mmol, 10.0 g), K2CO3 (120 mmol, 16.7 g), KI (120 mmol, 19.9 g), and CH3CN (180 mL) were weighed into a 500 mL flask with a magnetic stir. The mixture was degassed and heated to 80 °C for 15 min. Subsequently, N-methylethanamine (320 mmol, 18.8 g) dissolved in CH3CN (50 mL) was added. After being heated at 80 °C for 24 h, the mixture was cooled to room temperature and quenched with water, finally extracted with CH2Cl2 (3 × 100 mL), and concentrated in vacuo to provide 2-(2-(ethyl(methyl)amino)ethoxy)ethanol (8.8 g, 74.5% yield). Into a 250 mL flask were added the synthesized 2-(2-(ethyl(methyl)amino)ethoxy)ethanol (60 mmol, 8.8 g), Et3N (90 mmol, 9.1 g) and CH2Cl2 (100 mL), and addition of methacryloyl chloride (90 mmol, 8.7 mL) at 0 °C was followed. After 1 h reaction under nitrogen atmosphere, the reaction mixture was quenched with saturated NaHCO3 solution. The product was obtained by evaporation of the organic phase and purified by column chromatography using ethyl acetate (containing 1% Et3N) as eluent to afford M2 (10.6 g, 82.2% yield). 1H NMR (CDCl3) δ 6.08 (dd, 1H, CH2C(CH3)−), 5.52 (p, 1H, CH2C(CH3)−), 4.26 (q, 2H, −COOCH2−), 3.70−3.62 (m, 2H, −CH2OCH2−), 3.56 (dd, 2H, −CH2OCH2−), 2.54 (t, 2H, −OCH2CH2N−), 2.42 (qd, 2H, −N(CH3)CH2CH3), 2.22 (s, 3H, −N(CH3)CH2CH3), 1.90 (dd, 3H, CH2C(CH3)−), 1.01 (t, 3H, −N(CH3)CH2CH3). 13C NMR (CDCl3) δ 166.9, 135.8, 125.1, 69.1, 68.5, 64.1, 55.9, 51.4, 41.7, 17.8, 11.7. The 1H NMR and 13C NMR spectra shown in Figure S1 confirm the successful synthesis of M2. See the synthesis of the M1, M3, M4, M5, M6, M7 and M8 monomers as summarized in Scheme 2 in Supporting Information. 2.3. Synthesis of Poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s. Poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s were prepared by solution RAFT polymerization under [monomer]0:[RAFT]0:[AIBN]0 = 1200:6:1. Herein, a typical synthesis of poly(M2) (P2) is introduced. Into a Schlenk flask, M2 (1.00 g, 4.65 mmol), CDTPA (9.37 mg, 0.0232 mmol), and AIBN (0.064 mg, 0.00040 mmol) dissolved in 1,4-dioxane (1.00 g) were weighed. The

Therefore, seeking for multistimuli-responsive homopolymers with tunable LCST is important for their application. Herein, a new family of thermo-, pH-, and CO2-responsive homopolymers of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s (Scheme 1) are synthesized by RAFT polymerization. As shown in Scheme 1, these poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s combine OEG moiety and dialkylamine within the polymer chain. The combination of OEG and dialkylamine affords four characters for the designed polymers. First, LCST can be continently tuned by the repeated number of OEG (m) and the alkyls of R1 and/or R2 in dialkylamine (Scheme 1). Second, the introduced dialkylamine makes poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s to be thermo-, pH-, and CO2- responsive. Third, an ignorable or very slight hysteresis in the reversible soluble-to-insoluble phase transition is detected due to the absence of strong hydrogen bond donor in the polymer chains but just weak van der Waals interaction. Fourth, since poly(ethylene glycol) (PEG) side chains are nontoxic, poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s are probably suitable for biotechnology application.

2. EXPERIMENTAL SECTION 2.1. Materials. 2-(2-Chloroethoxy)ethanol (>98%), 2-(2-(2chloroethoxy)ethoxy)ethanol (>98%), 2-(2-(diethylamino)ethoxy)ethanol (>98%), pentaethylene glycol (>98%), methacryloyl chloride (>99%) and N-methylethanamine (>98%) were purchased from Heowns (China). 2-(2-(Dimethylamino)ethoxy)ethanol (>98%, TCI, China), dimethylamine (2.0 mol/L in THF, Annaiji, China), and diethylamine (>98%, Tianjin Chemical Company, China) were used as received. The RAFT agents (Scheme S1), e.g., 4-cyano-4(dodecylsulfanylthiocarbonyl)sulfanyl pentanoic acid (CDTPA), 4cyano-4-(ethylsulfanylthiocarbonyl)sulfanyl pentanoic acid (CETPA), s,s′-bis(a,a′-dimethyl-a″-acetic acid) trithiocarbonate (BDMAT), and benzyl dithiobenzoate (BDTB), were synthesized according to previous literatures. 56−59 2,2′-Dimethyl-2,2′-azodipropionitrile (AIBN, > 99%, Tianjin Chemical Company, China) was recrystallized 4688


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Figure 1. 1H NMR spectra of P1, P2, P3, P4, P5, P6, P7, and P8 dissolved in CDCl3.. Poly(M1) (P1), poly(M3) (P3), poly(M4) (P4), poly(M5) (P5), poly(M6) (P6), poly(M7) (P7) and poly(M8) (P8) were also synthesized by solution RAFT polymerization, and the synthetic detail is summarized in Table 1. 2.4. Synthesis of Di- and Triblock Copolymers. The di- and triblock copolymers as summarized in Table 2 were obtained through sequential RAFT polymerization. Herein, synthesis of the P1137-b-P278

reaction mixture was initially degassed by repeatedly cycles of freezingpumping-thawing and then polymerization was run at 70 °C. After a given time, polymerization was stopped by cooling the flask into iced water. The monomer conversion was determined by 1H NMR. The crude polymer was dissolved in 1,4-dioxane, precipitated in n-hexane at 0 °C, and dried in vacuo at 25 °C overnight. 4689


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Figure 2. Time-dependent monomer conversion (A) and kinetic plot (B) of RAFT polymerization, GPC traces (C) and molecular weight and molecular weight distribution (D) of P2 synthesized at different monomer conversion. diblock copolymer was typically introduced. M2 (0.1913 g, 0.89 mmol), the macro-RAFT agent of P1137 synthesized employing CDTPA (0.124 g, 0.00445 mmol, Mn = 27.92 kg/mol, Đ = 1.32), AIBN (0.122 mg, 0.00074 mmol), and the internal standard of 1,3,5trioxane (8.02 mg, 0.089 mmol) and 1,4-dioxane (0.90 g) were added into a Schlenk flask. The reaction mixture was degassed, and then polymerization was initiated at 70 °C. After 4 h, polymerization was quenched, and 39% monomer conversion was determined by 1H NMR. The synthesized P1137-b-P278 was precipitated in n-hexane and dried in vacuo overnight. The P1137-b-P278-b-P350 triblock copolymer was also synthesized similarly by sequential RAFT polymerization. 2.5. Characterization. A Bruker Avance III 400 MHz NMR spectrometer was applied for 1H NMR and 13C NMR analysis. A Waters 600E GPC system was applied for gel permeation chromatography (GPC) analysis, in which a series of polystyrene samples with narrow molar mass distribution were used calibration standard and THF was used as eluent. Cloud points were measured on a Varian 100 UV−vis spectrophotometer equipped with a thermoregulator (±0.1 °C) at 500 nm, in which the heating/cooling rate was at 1 °C/min. TEM observation was carried on a JEOL 100CX-II electron microscope at 100 kV or a Tecnai G2 F20 electron microscope at 200 kV. Dynamic light scattering (DLS) analysis was carried on a NanoBrook Omni (Brookhaven) laser light scattering spectrometer at the wavelength of 659 nm at 90° angle.

RAFT polymerization, BDMAT leads to the moderate, and BDTB leads to the lowest, respectively. The Đ value of all P2 samples locates at 1.3−1.4, suggesting that these four RAFT agents exert similar control on polymer molecular weight distribution. The P2 molecular weight Mn,NMR determined by NMR is very close to the theoretical molecular weight Mn,th, suggesting that RAFT affords good control on polymer molecular weight. Note: Mn,NMR of P2 was calculated by comparing the characteristic signals at δ = 3.22 and 3.95−4.18 ppm (see the 1H NMR spectra in Figure S2), and Mn,th was determined by monomer conversion according to eq 1,61 respectively. However, the molecular weight Mn,GPC determined by GPC analysis is less than Mn,th. The underestimation of Mn,GPC is possibly ascribed to the interaction between Ncontaining polymers and GPC columns, and no or slight improvement is achieved, despite some eluents including THF, THF containing 3 wt % triethylamine, DMF, and DMF containing 0.012 M LiBr are tried as discussed elsewhere.62,63 M n,th =

[monomer]0 × M monomer × conversion [RAFT]0 + M n,RAFT

3. RESULTS AND DISCUSSION 3.1. Synthesis of Poly[oligo(ethylene glycol) (Ndialkylamino) methacrylate]s. Poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s were synthesized by solution RAFT polymerization. To optimize polymerization condition, RAFT polymerization of M2 employing four RAFT agents, e.g., three of them, CDTPA, CETPA, and BDMAT, being trithiocarbonates and one of them, BDTB, being a dithiobenzoate, was checked. The results summarized in Table 1 indicate that CDTPA and CETPA lead to the fastest

(1)

Balancing the Đ value of P2 and the polymerization rate (runs 1−4, Table 1), CDTPA was chosen to mediate the RAFT polymerization of oligo(ethylene glycol) (N-dialkylamino) methacrylates. It is found that, either dialkylamine or the number of the OEG moiety (m, 1 and 2) seems to have no or slight influence on the RAFT polymerization rate (runs 5−11, Table 1). All synthesized polymers were characterized by GPC (Figure S3) and 1H NMR (Figure 1). As summarized in Table 1, the Đ values of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s locate at 1.29−1.38, and Mn,NMR is close to Mn,th. 4690


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Macromolecules These confirm the controlled RAFT synthesis of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s. With sketchy information on the solution RAFT polymerization in hand, the typical RAFT synthesis of P2 under [M2]0: [CDTPA]0:[AIBN]0 = 1200:6:1 was further investigated. As shown in Figures 2A and 2B, the RAFT polymerization follows pseudo-first-order kinetics as indicated by the linear ln([M]0/ [M])-time plot in the initial 10 h, and then the ln([M]0/[M]) value levels off at 70% monomer conversion. Figure 2C shows the GPC traces of the P2 samples synthesized at different monomer conversion, from which Mn,GPC and Đ are obtained. As summarized in Figure 2D, Mn,NMR is very close to Mn,th. Whereas, Mn,GPC is lower than Mn,th and the reason is discussed above. The Đ value of the P2 samples locates at 1.2−1.4, and it slightly increases with monomer conversion. All these indicate controlled RAFT synthesis of P2. 3.2. Thermoresponse of Poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s. In this section, thermoresponse of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s is investigated. To check effect of the appending dialkylamine and the OEG moiety on thermoresponse of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s, eight samples, e.g., P1123, P2108, P3107, P4108, P5107, P6105, P7103, and P8101, were synthesized by RAFT polymerization using the same RAFT agent of CDTPA. The eight polymers have similar polymerization degree (DP) around 110 and have the same terminals, and therefore they are used to check how polymer structure affects thermoresponse. Parts A−C of Figure 3 show the temperature-dependent transmittance of 1.0% aqueous solution of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s, in which the N-alkyl in dialkylamine changes from dimethyl to methyl/ethyl and finally to diethyl, and the number of the OEG moiety m = 1, 2 and 4, respectively. The CPs of poly[oligo(ethylene glycol) (Ndialkylamino) methacrylate]s are summarized in Figure 3D. On the basis of the results shown in Figure 3, four conclusions are made. First, CP of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s is firmly correlative to the N-alkyl in dialkylamine. For examples, CP of P1123 containing two symmetric N-methyl substitutes is 52 °C, and CP of P3107 containing two symmetric N-ethyl substitutes is 7 °C. Interestingly, CP of P2108 containing two asymmetric Nsubstitutes of methyl and ethyl, 27 °C, is just close to the middle of the two CPs of P1123 and P3107. This suggests that CP of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s can be tuned by the N-alkyl substitutes in dialkylamine. As is known, with the C-number of N-alkyl increases, dialkylamine becomes more hydrophobic.13 Thus, it is deemed that the increased hydrophobic character of dialkylamine leads to the decreased CP of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s. Second, CP of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s increases with the increasing number of the OEG moiety (m). For examples, P2108 (m = 1) has a CP at 27 °C, P5107 (m = 2) has a CP at 39 °C, and P7103 (m = 4) has a CP at 79 °C. Third, the thermoresponsive phase transition of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s takes place within a very narrow temperature window of ∼2 °C. Fourth, no or very slight hysteresis in the reversible phase transition is detected, and the reason is due to the absence of proton-donor and/or proton-acceptor and therefore weak inter- and intramolecular hydrogen bonds in the collapsed state of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s.22 Because of the

Figure 3. Thermoresponse of 1.0 wt % aqueous solutions of P1123, P2108, and P3107 (A), P4108, P5107, and P6105 (B), and P7103 and P8101 (C) and a summary of CPs (D).

tunable CP with a wide range from 7 to 79 °C and the smart response, these poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s will have potential application. 4691


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P1123. To diagnose dehydration of the P1123 chains in water, four typical characteristic signals, i.e, CH2OCH2 (j and k, δ = 3.77−4.05 ppm), CH2NCH3 (l, δ = 2.82 ppm) and CH2NCH3 (m, δ = 2.50 ppm) are summarized in Figure 5B. These four signals are chosen, since they can take part in formation of hydrogen bonding. As indicated, with temperature increasing from 40 to 60 °C, all the four signals decrease. In comparison, the signals of j and k assigned to the OEG moiety decrease more than the signals of l and m assigned to the pendent alkylamine. In the thermoresponsive phase transition of PDEAEAM,54 it is concluded that both amide and alkylamine take part in the hydrogen bonding formation and therefore contribute to the thermoresponsive phase transition. Since the signals of l and m decrease synchronously with the signals of j and k as shown in Figure 5B, herein it is deemed that the OEG moiety and alkylamine afford the thermo-response of P1, although the hydrogen bonding between the OEG moiety and water contributes more than that between alkylamine and water to the thermoresponsive phase transition of P1123. Besides, the CP at 49 °C is determined at the 50% change of the signal of CH2OCH2 (j and k), which is 3 °C lower than in H2O determined by the turbidity analysis as discussed above. Generally, most of the thermoresponsive polymers exhibit very similar LCST in the deuterated and nondeuterated solvents under the other same condition. Whereas, Winnik and co-workers revealed that PNIPAM had a higher LCST in D2O than in H2O,64 and on the contrary we found that PDEAEAM had a higher LCST in H2O than in D2O.54 Herein, the result indicates that the deuterated solvent effect on P1 is similar to that on PDEAEAM. Figure 6A shows the temperature-dependent transmittance of the aqueous solution of P2 with DP ranging from 26 to 156, and the CPs are summarized in Figure 6B. As shown, the increasing DP of P2 results in a steady CP decrease from 30.0 to 25.2 °C. Parts A and B of Figure 7 also indicate that CP of P2 108 decreases from 31.0 to 24.8 °C with polymer concentration increasing from 0.20 to 2.0 wt %. This suggests that CP of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s is correlative to polymer concentration and polymer DP. This is somewhat similar to the typical thermoresponsive poly(aminoethyl methacrylate) of PDMAEMA26,27 but different from PNIPAM,8,9 the LCST or CP of which is independent with polymer concentration and polymer DP when DP is higher than a critical point.8,9

The present poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s are somewhat similar to the poly[oligo(ethylene glycol) (meth)acrylate]s of P(MEOMA)19 and P(MEO2MA)4 except the appending dialkylamine group. As summarized in Figure 4, introduction of diethylamine in the outer-side of the

Figure 4. Comparison between poly[oligo(ethylene glycol) (Ndialkylamino) methacrylate]s and P(MEOMA)/P(MEO2MA).

OEG moiety generally leads to a lower CP of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s than P(MEOMA) and P(MEO2MA), and introduction of dimethylamine leads to a higher CP, respectively. This is not surprised, since dimethylamine containing a short N-methyl is more hydrophilic than diethylamine, which therefore increases CP of the thermoresponsive polymers. The introduction of dialkylamine affords two advantages of (1) the tunable CP and (2) the pH-, and CO2-response, which will be discussed subsequently. Temperature-variable 1H NMR analysis is a valid method to diagnose phase transition of thermoresponsive polymers.23−25 To deeply sight the thermoresponsive phase transition of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s, temperature-variable 1H NMR analysis of the P1123 solution at temperature across below CP to above CP is made. Figure 5A shows, with temperature increasing from 40 to 60 °C the signals decrease, indicating thermoresponsive dehydration of

Figure 5. 1H NMR spectra of 1.0 wt % P1123-CDTPA in D2O (A) and summary of the signals of four typical protons at different temperature (B). Note: the signals are normalized by the solvent peak at δ = 4.79 ppm as pointed out by star. 4692


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Figure 6. DP effect on thermoresponse of P2 (A) and summary of CPs (B). Note: P2 was synthesized by employing CDTPA as RAFT agent.

Figure 7. Effect of polymer concentration on thermoresponse of P2 (A) and summary of CPs (B). Note: P2 was synthesized by employing CDTPA as RAFT agent.

Figure 8. Effect of NaCl (A) and urea (B) on CP of 1.0 wt % P2108 solution. Note: P2108 was synthesized by employing CDTPA as RAFT agent.

solubility. As shown in Figure 8A, CP of P2108 decreases from 27.0 to 16.5 °C with NaCl concentration increasing from 0 to 0.9 mol/L. Herein, it is thought that the water molecules adjacent to the P2108 chains are polarized by the salt of NaCl, which weakens the hydrogen bonding between P2108 and water, and therefore CP is decreased. Figure 8B indicates that the CP of P2108 increases from 27.0 to 34.5 °C when the concentration of the fed urea increases from 0 to 3.0 mol/L. Urea leading to an increase CP of P2108 is discussed. It is thought there exists intramolecular hydrogen bonding between dialkylamine and the OEG moiety in P2108, and the intramolecular hydrogen bonding tends to decrease the solubility of P2108 in water. When urea, which is a Lewis base, is added, the intramolecular hydrogen bonding between dialkylamine and OEG is broken or

Generally, thermoresponsive phase transition is ascribed to the hydrogen bonding between solute and solvent or the interor intramolecular hydrogen bonding being weakened or broken.3−5 To diagnose hydrogen bonding, salt and urea are usually used as indicator.11,37,50,54 For example, for the thermoresponsive polymer having a LCST, e.g. PNIPAM, addition of urea leads to a decreasing CP since urea breaks the hydrogen bonding between polymer and solvent;65 whereas for the thermoresponsive polymer having a upper critical solution temperature (UCST), e.g., the PDMAAm-PAAc complexes,66 addition of urea leads to an insoluble-to-soluble transition or a decreased UCST, since urea weakens the inter- or intramolecular hydrogen bonding, improves the interaction between polymer and water and therefore increases the polymer 4693


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therefore the pH responsive character is reasonable. The triple relationship of CP/pH and dialkylamine is summarized in Figure S4. Typically, as indicated in Figure 10A, pH of the 1.0 wt % P2108 solution is 8.8, and CP of P2108 is 27.0 °C. The slight decrease in pH to 8.5 leads to a great CP increase from 27.0 to 41.4 °C, and finally P2108 become soluble at pH = 8.0. On the contrary, the increase to pH 10.0 and further to pH 12.0 results in a slight CP decrease from 27.0 to 25.2 °C and further to 22.1 °C. All these are similar to those of the pH- and thermoresponsive polymers discussed before.26,27,50,51,54,55 As similarly as amidine, the appending dialkylamine in poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s can react with CO2 to yield a charged ammonium bicarbonate or quaternary ammonium, which reversibly switches back during exposure to argon or nitrogen.39 As shown in Figure 10B, before treating with CO2, the P2108 solution is turbid at 45.0 °C (above the CP of 27.0 °C), and it becomes transparent after bubbling with CO 2 at the atmosphere pressure accompanied by the decrease of pH from 8.8 to 7.5, which indicates the protonation of dimethylamine to quaternary ammonium, and the transparent solution further becomes turbid by bubbling N2 to remove CO2 to deprotonate the quaternary ammonium. More than 10 repeatable transparent/ turbid cycles under an alternating CO2/N2 stimulation can be fulfilled, indicating the CO2-response of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s. 3.4. Synthesis and Characterization of MultistimuliResponsive Block Copolymers. As discussed above, poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s have different CPs, and therefore the di- and triblock copolymers containing different blocks of poly[oligo(ethylene glycol) (Ndialkylamino) methacrylate]s should have two or three CPs. Herein, the typical di- and triblock copolymers of P1137-b-P278 and P1137-b-P278-b-P350 are synthesized by sequential RAFT polymerization. Figure 11 shows the 1H NMR spectra (A) and the GPC traces (B) of the di- and triblock copolymers and their precursor of P1137. On the basis of the 1H NMR and GPC analysis, the molecular weight and its distribution of the di- and triblock copolymers are obtained and are summarized in Table 2. Figure 12A shows the temperature-dependent transmittance of aqueous solution of the P1137-b-P278 diblock copolymer as well as the P1137 and P275 homopolymers. From Figure 12A, two CPs of P1137-b-P278 at 32.5 °C (CP1) and 48.3 °C (CP2) are observed. The lower CP1 at 32.5 °C is assigned to the P278

weakened, and the intermolecular hydrogen bonding between P2108 and water (also urea) is enhanced, and therefore the solubility and CP of P2108 is increased. Terminal effect on thermoresponse of P2 is also investigated. To fulfill this investigation, four polymers with the similar DP around 110 but different RAFT terminals, P291-BDMAT, P2118CETPA, P2108-CDTPA, and P2122-BDTB, are prepared by employing different RAFT agents. As shown in Scheme S1 and Figure S2, P291-BDMAT has two hydrophilic terminals of C(CH3)2COOH, P2118-CETPA has two terminals of the hydrophobic ethyl and the hydrophilic C(CH 3 )CNCH2CH2COOH, P2108-CDTPA has a hydrophobic dodecyl terminal and a hydrophilic terminal of C(CH 3 )CNCH2CH2COOH, and P2122-BDTB has two hydrophobic terminals of phenyl terminal, respectively. As Figure 9 shows,

Figure 9. Thermoresponse of the 1.0 wt % aqueous solution of P2 including different RAFT terminals.

P291-BDMAT exhibits the highest CP at 29.0 °C, P2118-CETPA and P2108-CDTPA have a similar and moderate CP at 27.0 °C, and P2122-BDTB displays the lowest CP at 23.8 °C, respectively. These results indicate that a hydrophilic terminal leads to a CP increase and whereas a hydrophobic terminal leads to a CP decrease, respectively. 3.3. pH- and CO2-Response of Poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s. Poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s containing an appending dialkylamine are expected to be pH- and CO2responsive. The dialkylamine group is a Lewis base, and

Figure 10. PH effect on thermoresponse of 1.0 wt % P2108 aqueous solution (A) and 1.0 wt % P2108 aqueous solution at 45.0 °C upon the N2/CO2 bubbling (B). Note: P2108 was synthesized by employing CDTPA as RAFT agent. 4694


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block and the higher CP2 at 48.3 °C is assigned to the P1137 block, which is also confirmed by temperature-variable 1H NMR analysis (Figure S5). By comparing the diblock copolymer with the reference homopolymers, two conclusions are made. First, the CP1 of the P278 block is higher than that of the P275 homopolymer (32.5 vs 27.5 °C) and the CP2 of the P1137 block is lower than that of the P1137 homopolymer (48.3 vs 51.7 °C). For thermoresponsive copolymers,46,47,67 insertion of a hydrophilic block usually leads to a CP increase, and insertion of a hydrophobic block usually leads to a CP decrease, and the reason is ascribed to the hydrophilic (hydrophobic) block increasing (decreasing) solubility of the thermoresponsive block. For the present P1137-b-P278 diblock copolymer, at temperature below CP1 of the P278 block, the P1137 block is hydrophilic, and therefore the solubility of the P278 block is enhanced and CP1 of the P278 block is increased; at temperature above CP1 of the P278 block, the P278 block becomes solvophobic, and therefore the solubility of the P1137 block is weakened and CP2 of the P1137 block is decreased. Second, at temperature above CP1 but below CP2, the transmittance initially decreases fast and then increases until to a plateau. Similarity was also observed in the phase transition of the thermoresponsive block copolymers of PEtOx80-b-P(EtOxxstat-PropOx40−x) (x = 0, 4 or 8) and PTEGMA 66-bPTEGSt72.68,69 This reason was due to fast micellization of thermoresponsive block copolymers at temperatures above CP1 to form metastable micelles, which were further rearranged to form stable micelles with temperature increasing. It is deemed that the thermoresponsive micellization of P1137-bP278 follows the similar procedures. This hypothesis is confirmed by DLS analysis of P1137-b-P278 at three typical temperatures, e.g., 32.5 °C (CP1), 34.0 °C (above CP1 at the bottom point of inflection) and 45.0 °C (at plateau). As shown in Figure S6, the hydrodynamic diameter (Dh) of the P1137-bP278 micelles/aggregates at the three typical temperatures is 127 nm, 242 and 121 nm, indicating the reconstitution of the P1137-b-P278 micelles/aggregates with temperature increasing. The nanoassemblies of P1137-b-P278 at temperature above CP1 and CP2 are checked by TEM, and 20 and 23 nm micelles are formed (Figure S7). At temperature above CP1, the P278 block becomes dehydrated and the P1137 block is hydrophilic, and therefore, the dehydrated P278 block forms the body of the micelles and the P1137 block keeps the micelles suspending in solvent. At temperature above CP2, the P1137 block deposits and therefore leads to a larger size of the micelles by TEM. Note: TEM just shows the dehydrated block in the micelles as discussed elsewhere.53,70 The P1137-b-P278-b-P350 triblock copolymer has a character that the CPs of the three blocks are in the order of P1137 > P278 > P350. This design can make it convenient to check the gradual dehydration of the three blocks in the triblock copolymers.47 As shown in Figure 12B, three CPs, 13.2 °C assigned to the P350 block (CP1), 35.6 °C assigned to the P278 block (CP2) and 49.8 °C assigned to the P1137 block (CP3), are detected just as expected. At temperature above CP1, the P350 block is dehydrated and the P1137/P278 blocks keep solvated; with temperature increasing above CP2, the P278 block further becomes dehydrated and the P1137 block keeps soluble in the solvent; with temperature further increasing above CP3, all the three blocks are dehydrated. This sequential dehydration of the P1137-b-P278-b-P350 triblock copolymer leads to the size and/or morphology change of the triblock copolymer micelles with temperature. As shown in Figure 13, with temperature

Figure 11. 1H NMR spectra in CDCl3 (A) and GPC traces (B) of P1137, P1137-b-P278, and P1137-b-P278-b-P350..

Figure 12. Thermoresponse of the 1.0 wt % aqueous solution of P275, P1137, and P1137-b-P278 (A) and P1137-b-P278-b-P350 (B).

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dehydration of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s is investigated. The parameters affecting the thermoresponse of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s are investigated. It is found that CP of poly(2-(2-(ethyl(methyl)amino)ethoxy)ethyl methacrylate) slightly decreases with the increase of DP and the polymer concentration, and the CP decreases with addition of NaCl and whereas it increases with addition of urea. The pH- and CO2response of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s similar to the typical multistimuli-responsive homopolymers, e.g., PDMAEMA, is also demonstrated. Taking the advantage of poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s having different CPs, multithermoresponsive P1137-b-P278 diblock copolymer and P1137-b-P278-b-P350 triblock copolymer exhibiting two and three CPs are synthesized and their versatile micellization upon temperature changing is demonstrated. We deem that these poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s are new thermo-, pH-, and CO2-responsive homopolymers, and they may have potential application in biotechnology.

Figure 13. Hydrodynamic diameter (Dh) of P1137-b-P278-b-P350 triblock copolymer at 18 (A), 40 (B) and 52 °C (C) in water (1.0 wt %).

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increasing from above CP1 to above CP2 and finally to above CP3, Dh of the P1137-b-P278-b-P350 micelles initially decreases from 91 to 82 nm and then increases to 141 nm. The initial decrease of Dh is ascribed to the dehydration of the P278 block, and the subsequent increase of Dh is due to the aggregation of single micelles since all the three blocks become dehydrated, which are schematically shown by the insets in Figure 12B. This thermoresponsive micellization of P1137-b-P278-b-P350 micelles is also confirmed by TEM (Figure 14), by which 18 nm micelles, 21 nm micelles, and aggregated micelles or micelle clusters just as observed schematically in Figure 14 are observed at temperatures above CP1, CP2, and CP3, respectively.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b00763. Experimental details and supplementary figures (PDF)

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AUTHOR INFORMATION

Corresponding Author

*(W.Z.) E-mail: [email protected]. Telephone: +86-2223509794. Fax: +86-22-23503510.

4. CONCLUSIONS In conclusion, we propose a strategy to prepare thermo-, pH-, and CO2-responsive homopolymers by combining OEG moieties and dialkylamine within the polymethacrylate backbone. In these poly[oligo(ethylene glycol) (N-dialkylamino) methacrylate]s, the OEG moiety as well as dialkylamine affords the thermoresponse and dialkylamine affords the pH-, and CO2-response. The CP of poly[oligo(ethylene glycol) (Ndialkylamino) methacrylate]s is firmly dependent on the number (m) of the repeated units of the OEG moiety and the dialkylamine group. Generally, this is a higher m value and higher CP and more hydrophilic character of the alkyl group in dialkylamine and higher CP of poly[oligo(ethylene glycol) (Ndialkylamino) methacrylate]s, respectively. By tuning of the OEG moiety and dialkylamine, poly[oligo(ethylene glycol) (Ndialkylamino) methacrylate]s with a wide range of CPs from 7 to 79 °C are synthesized by RAFT polymerization. The

ORCID

Shengli Chen: 0000-0002-7546-5465 Wangqing Zhang: 0000-0003-2005-6856 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The financial support by the National Science Foundation for Distinguished Young Scholars (No. 21525419), the National Science Foundation of China (No. 21474054), and the National Key Research and Development Program of China (2016YFA0202503) is gratefully acknowledged.

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REFERENCES

(1) Schattling, P.; Jochum, F. D.; Theato, P. Multi-stimuli responsive polymers − the all-in-one talents. Polym. Chem. 2014, 5, 25−36.

Figure 14. TEM images of P1137-b-P278-b-P350 triblock copolymer micelles formed at 18 °C (A), 40 °C (B) and 52 °C (C) in water (1.0 wt %). 4696


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(22) Lutz, J.-F.; Weichenhan, K.; Akdemir, Ö .; Hoth, A. About the Phase Transitions in Aqueous Solutions of Thermoresponsive Copolymers and Hydrogels Based on 2-(2-methoxyethoxy)ethyl Methacrylate and Oligo(ethylene glycol) Methacrylate. Macromolecules 2007, 40, 2503−2508. (23) Qiao, Z.-Y.; Du, F.-S.; Zhang, R.; Liang, D.-H.; Li, Z.-C. Biocompatible Thermoresponsive Polymers with Pendent Oligo(ethylene glycol) Chains and Cyclic Ortho Ester Groups. Macromolecules 2010, 43, 6485−6494. (24) Han, S.; Hagiwara, M.; Ishizone, T. Synthesis of Thermally Sensitive Water-Soluble Polymethacrylates by Living Anionic Polymerizations of Oligo(ethylene glycol) Methyl Ether Methacrylates. Macromolecules 2003, 36, 8312−8319. (25) Maeda, Y.; Kubota, T.; Yamauchi, H.; et al. Hydration Changes of Poly(2-(2-methoxyethoxy)ethyl Methacrylate) during Thermosensitive Phase Separation in Water. Langmuir 2007, 23, 11259−11265. (26) Plamper, F. A.; Ruppel, M.; Schmalz, A.; Borisov, O.; Ballauff, M.; Müller, A. H. E. Tuning the Thermoresponsive Properties of Weak Polyelectrolytes: Aqueous Solutions of Star-Shaped and Linear Poly(N,N-dimethylaminoethyl Methacrylate). Macromolecules 2007, 40, 8361−8366. (27) Plamper, F. A.; Schmalz, A.; Ballauff, M.; Müller, A. H. E. Tuning the Thermoresponsiveness of Weak Polyelectrolytes by pH and Light: Lower and Upper Critical-Solution Temperature of Poly(N,N-dimethylaminoethyl methacrylate). J. Am. Chem. Soc. 2007, 129, 14538−14539. (28) Karjalainen, E.; Aseyev, V.; Tenhu, H. Influence of Hydrophobic Anion on Solution Properties of PDMAEMA. Macromolecules 2014, 47, 2103−2111. (29) Niskanen, J.; Wu, C.; Ostrowski, M.; Fuller, G. G.; Hietala, S.; Tenhu, H. Thermoresponsiveness of PDMAEMA. Electrostatic and Stereochemical Effects. Macromolecules 2013, 46, 2331−2340. (30) Bütün, V.; Armes, S. P.; Billingham, N. C. Synthesis and aqueous solution properties of near-monodisperse tertiary amine methacrylate homopolymers and diblock copolymers. Polymer 2001, 42, 5993−6008. (31) González, N.; Elvira, C.; Román, J. S. Novel Dual-StimuliResponsive Polymers Derived from Ethylpyrrolidine. Macromolecules 2005, 38, 9298−9303. (32) Deng, J.; Shi, Y.; Jiang, W.; Peng, Y.; Lu, L.; Cai, Y. Facile Synthesis and Thermoresponsive Behaviors of a Well-Defined Pyrrolidone Based Hydrophilic Polymer. Macromolecules 2008, 41, 3007−3014. (33) Diab, C.; Akiyama, Y.; Kataoka, K.; Winnik, F. M. Microcalorimetric Study of the Temperature-Induced Phase Separation in Aqueous Solutions of Poly(2-isopropyl-2-oxazolines). Macromolecules 2004, 37, 2556−2562. (34) Kempe, K.; Neuwirth, T.; Czaplewska, J.; Gottschaldt, M.; Hoogenboom, R.; Schubert, U. S. Poly(2-oxazoline) glycopolymers with tunable LCST behavior. Polym. Chem. 2011, 2, 1737−1743. (35) Spěvácě k, J.; Hanyková, L.; Labuta, J. Behavior of Water during Temperature-Induced Phase Separation in Poly(vinyl methyl ether) Aqueous Solutions. NMR and Optical Microscopy Study. Macromolecules 2011, 44, 2149−2153. (36) Maeda, Y. IR Spectroscopic Study on the Hydration and the Phase Transition of Poly(vinyl methyl ether) in Water. Langmuir 2001, 17, 1737−1742. (37) Chua, G. B. H.; Roth, P. J.; Duong, H. T. T.; Davis, T. P.; Lowe, A. B. Synthesis and Thermoresponsive Solution Properties of Poly[oligo(ethylene glycol) (meth)acrylamide]s: Biocompatible PEG Analogues. Macromolecules 2012, 45, 1362−1374. (38) Fu, X.; Shen, Y.; Fu, W.; Li, Z. Thermoresponsive Oligo(ethylene glycol) Functionalized Poly-L-cysteine. Macromolecules 2013, 46, 3753−3760. (39) Lin, S.; Theato, P. CO2-Responsive Polymers. Macromol. Rapid Commun. 2013, 34, 1118−1133. (40) Han, D.; Tong, X.; Boissière, O.; Zhao, Y. General Strategy for Making CO2-Switchable Polymers. ACS Macro Lett. 2012, 1, 57−61.

(2) Liu, F.; Urban, M. W. Recent advances and challenges in designing stimuli-responsive polymers. Prog. Polym. Sci. 2010, 35, 3− 23. (3) Roy, D.; Brooks, W. L. A.; Sumerlin, B. S. New directions in thermoresponsive polymers. Chem. Soc. Rev. 2013, 42, 7214−7243. (4) Weber, C.; Hoogenboom, R.; Schubert, U. S. Temperature responsive bio-compatible polymers based on poly(ethylene oxide) and poly(2-oxazoline)s. Prog. Polym. Sci. 2012, 37, 686−714. (5) Halperin, A.; Kröger, M.; Winnik, F. M. Poly(N-isopropylacrylamide) Phase Diagrams: Fifty Years of Research. Angew. Chem., Int. Ed. 2015, 54, 15342−15367. (6) Plummer, R.; Hill, D. J. T.; Whittaker, A. K. Solution Properties of Star and Linear Poly(N-isopropylacrylamide). Macromolecules 2006, 39, 8379−8388. (7) Yu, B.; Chan, J. W.; Hoyle, C. E.; Lowe, A. B. Sequential ThiolEne/Thiol-Ene and Thiol-Ene/Thiol-Yne Reactions as a Route to Well-Defined Mono and Bis End-Functionalized Poly(N-isopropylacrylamide). J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 3544−3557. (8) Xia, Y.; Yin, X.; Burke, N. A. D.; Stöver, H. D. H. Thermal Response of Narrow-Disperse Poly(N-isopropylacrylamide) Prepared by Atom Transfer Radical Polymerization. Macromolecules 2005, 38, 5937−5943. (9) Satokawa, Y.; Shikata, T.; Tanaka, F.; Qiu, X.-P.; Winnik, F. M. Hydration and Dynamic Behavior of a Cyclic Poly(N-isopropylacrylamide) in Aqueous Solution: Effects of the Polymer Chain Topology. Macromolecules 2009, 42, 1400−1403. (10) Van Durme, K. V.; Rahier, H.; Van Mele, B. V. Influence of Additives on the Thermoresponsive Behavior of Polymers in Aqueous Solution. Macromolecules 2005, 38, 10155−10163. (11) Lutz, J.-F.; Akdemir, Ö .; Hoth, A. Point by Point Comparison of Two Thermosensitive Polymers Exhibiting a Similar LCST: Is the Age of Poly(NIPAM) Over? J. Am. Chem. Soc. 2006, 128, 13046−13047. (12) Cheng, H.; Shen, L.; Wu, C. LLS and FTIR Studies on the Hysteresis in Association and Dissociation of Poly(N-isopropylacrylamide) Chains in Water. Macromolecules 2006, 39, 2325−2329. (13) Cao, Y.; Zhu, X. X.; Luo, J.; Liu, H. Effects of Substitution Groups on the RAFT Polymerization of N-Alkylacrylamides in the Preparation of Thermosensitive Block Copolymers. Macromolecules 2007, 40, 6481−6488. (14) Ito, D.; Kubota, K. Solution Properties and Thermal Behavior of Poly(N-n-propylacrylamide) in Water. Macromolecules 1997, 30, 7828−7834. (15) Idziak, I.; Avoce, D.; Lessard, D.; Gravel, D.; Zhu, X. X. Thermosensitivity of Aqueous Solutions of Poly(N,N-diethylacrylamide). Macromolecules 1999, 32, 1260−1263. (16) Akiyama, Y.; Shinohara, Y.; Hasegawa, Y.; Kikuchi, A.; Okano, T. Preparation of Novel Acrylamide-Based Thermoresponsive Polymer Analogues and Their Application as Thermoresponsive Chromatographic Matrices. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 5471−5482. (17) Yu, D.; Luo, C.; Fu, W.; Li, Z. New thermal-responsive polymers based on alanine and (meth)acryl amides. Polym. Chem. 2014, 5, 4561−4568. (18) Huang, X.; Du, F.; Ju, R.; Li, Z. Novel Acid-Labile, Thermoresponsive Poly(methacrylamide)s with Pendent Ortho Ester Moieties. Macromol. Rapid Commun. 2007, 28, 597−603. (19) Melle, A.; Balaceanu, A.; Kather, M.; Wu, Y.; Gau, E.; Sun, W.; Huang, X.; Shi, X.; Karperien, M.; Pich, A. Stimuli-responsive poly(Nvinylcaprolactam-co-2-methoxyethyl acrylate) core−shell microgels: facile synthesis, modulation of surface properties and controlled internalisation into cells. J. Mater. Chem. B 2016, 4, 5127−5137. (20) Miasnikova, A.; Laschewsky, A. Influencing the Phase Transition Temperature of Poly(methoxy diethylene glycol acrylate) by Molar Mass, End Groups, and Polymer Architecture. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 3313−3323. (21) Roth, P. J.; Jochum, F. D.; Forst, F. R.; Zentel, R.; Theato, P. Influence of End Groups on the Stimulus-Responsive Behavior of Poly[oligo(ethylene glycol) methacrylate] in Water. Macromolecules 2010, 43, 4638−4645. 4697


Article

Macromolecules (41) Klaikherd, A.; Nagamani, C.; Thayumanavan, S. Multi-Stimuli Sensitive Amphiphilic Block Copolymer Assemblies. J. Am. Chem. Soc. 2009, 131, 4830−4838. (42) Fournier, D.; Hoogenboom, R.; Thijs, H. M. L.; Paulus, R. M.; Schubert, U. S. Tunable pH- and Temperature-Sensitive Copolymer Libraries by Reversible Addition-Fragmentation Chain Transfer Copolymerizations of Methacrylates. Macromolecules 2007, 40, 915− 920. (43) Gao, L.; Kong, T.; Huo, Y. Dual Thermoresponsive and pHResponsive Poly(vinyl alcohol) Derivatives: Synthesis, Phase Transition Study, and Functional Applications. Macromolecules 2016, 49, 7478−7489. (44) Zhang, Y.; Chen, S.; Pang, M.; Zhang, W. Synthesis and micellization of a multi-stimuli responsive block copolymer based on spiropyran. Polym. Chem. 2016, 7, 6880−6884. (45) Roy, D.; Cambre, J. N.; Sumerlin, B. S. Triply-responsive boronic acid block copolymers: solution self-assembly induced by changes in temperature, pH, or sugar concentration. Chem. Commun. 2009, 2106−2108. (46) Weiss, J.; Böttcher, C.; Laschewsky, A. Self-assembly of double thermoresponsive block copolymers end-capped with complementary trimethylsilyl groups. Soft Matter 2011, 7, 483−492. (47) Xie, D.; Ye, X.; Ding, Y.; Zhang, G.; Zhao, N.; Wu, K.; Cao, Y.; Zhu, X. X. Multistep Thermosensitivity of Poly(N-n-propylacrylamide)-block-poly(N-isopropylacrylamide)-block-poly(N,N-ethylmethylacrylamide) Triblock Terpolymers in Aqueous Solutions As Studied by Static and Dynamic Light Scattering. Macromolecules 2009, 42, 2715−2720. (48) Shoji, K.; Nakayama, M.; Koseki, T.; Nakabayashi, K.; Mori, H. Threonine-based chiral homopolymers with multi-stimuli-responsive property by RAFT polymerization. Polymer 2016, 97, 20−30. (49) Jung, S.-H.; Song, H.-Y.; Lee, Y.; Jeong, H. M.; Lee, H. Novel Thermoresponsive Polymers Tunable by pH. Macromolecules 2011, 44, 1628−1634. (50) Jiang, X.; Feng, C.; Lu, G.; Huang, X. Synthesis of temperature and pH/CO2 responsive homopolymer bearing oligo(ethylene glycol) unit and N,N-diethylamino ethyl group and its solution property. Polymer 2015, 64, 268−276. (51) Jiang, X.; Feng, C.; Lu, G.; Huang, X. Thermoresponsive Homopolymer Tunable by pH and CO2. ACS Macro Lett. 2014, 3, 1121−1125. (52) Sato, E.; Masuda, Y.; Kadota, J.; Nishiyama, T.; Horibe, H. Dual stimuli-responsive homopolymers: Thermo- and photo-responsive properties of coumarin-containing polymers in organic solvents. Eur. Polym. J. 2015, 69, 605−615. (53) Dan, M.; Su, Y.; Xiao, X.; Li, S.; Zhang, W. A New Family of Thermo-Responsive Polymers Based on Poly[N-(4-vinylbenzyl)-N,Ndialkylamine]. Macromolecules 2013, 46, 3137−3146. (54) Song, Z.; Wang, K.; Gao, C.; Wang, S.; Zhang, W. A New Thermo-, pH-, and CO2- Responsive Homopolymer of Poly[N-[2(diethylamino)ethyl]acrylamide]: Is the Diethylamino Group Underestimated? Macromolecules 2016, 49, 162−171. (55) Wang, K.; Song, Z.; Liu, C.; Zhang, W. RAFT synthesis of triply responsive poly[N-[2-(dialkylamino)ethyl]acrylamide]s and their Nsubstitute determined response. Polym. Chem. 2016, 7, 3423−3433. (56) Moad, G.; Chong, Y. K.; Postma, A.; Rizzardo, E.; Thang, S. H. Advances in RAFT polymerization: the synthesis of polymers with defined end-groups. Polymer 2005, 46, 8458−8468. (57) Johnson, R. N.; Burke, R. S.; Convertine, A. J.; Hoffman, A. S.; Stayton, P. S.; Pun, S. H. Synthesis of Statistical Copolymers Containing Multiple Functional Peptides for Nucleic Acid Delivery. Biomacromolecules 2010, 11, 3007−3013. (58) Lai, J. T.; Filla, D.; Shea, R. Functional Polymers from Novel Carboxyl-Terminated Trithiocarbonates as Highly Efficient RAFT Agents. Macromolecules 2002, 35, 6754−6756. (59) Davies, M. C.; Dawkins, J. V.; Hourston, D. J. Radical copolymerization of maleic anhydride and substituted styrenes by reversible addition-fragmentation chain transfer (RAFT) polymerization. Polymer 2005, 46, 1739−1753.

(60) Cardoso, J.; Manrique, R.; Albores-Velasco, M.; Huanosta, A. Synthesis, Characterization, and Thermal and Dielectric Properties of Three Different Methacrylate Polymers with Zwitterionic Pendant Groups. J. Polym. Sci., Part B: Polym. Phys. 1997, 35, 479−488. (61) De Brouwer, H.; Schellekens, M. A. J.; Klumperman, B.; Monteiro, M. J.; German, A. L. Controlled Radical Copolymerization of Styrene and Maleic Anhydride and the Synthesis of Novel Polyolefin-Based Block Copolymers by Reversible Addition−Fragmentation Chain-Transfer (RAFT) Polymerization. J. Polym. Sci., Part A: Polym. Chem. 2000, 38, 3596−3603. (62) Li, Q.; Gao, C.; Li, S.; Huo, F.; Zhang, W. Doubly thermoresponsive ABC triblock copolymer nanoparticles prepared through dispersion RAFT polymerization. Polym. Chem. 2014, 5, 2961−2972. (63) Narrainen, A. P.; Pascual, S.; Haddleton, D. M. Amphiphilic Diblock, Triblock, and Star Block Copolymers by Living Radical Polymerization: Synthesis and Aggregation Behavior. J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 439−450. (64) Kujawa, P.; Winnik, F. M. Volumetric Studies of Aqueous Polymer Solutions Using Pressure Perturbation Calorimetry: A New Look at the Temperature-Induced Phase Transition of Poly(Nisopropylacrylamide) in Water and D2O. Macromolecules 2001, 34, 4130−4135. (65) Sagle, L. B.; Zhang, Y.; Litosh, V. A.; Chen, X.; Cho, Y.; Cremer, P. S. Investigating the Hydrogen-Bonding Model of Urea Denaturation. J. Am. Chem. Soc. 2009, 131, 9304−9310. (66) Aoki, T.; Kawashima, M.; Katono, H.; Sanui, K.; Ogata, N.; Okano, T.; Sakurai, Y. Temperature-Responsive Interpenetrating Polymer Networks Constructed with Poly(acry1icacid) and Poly(N,N-dimethylacrylamid). Macromolecules 1994, 27, 947−952. (67) Zhou, Y.; Jiang, K.; Song, Q.; Liu, S. Amphiphilic Diblock, Triblock, and Star Block Copolymers by Living Radical Polymerization: Synthesis and Aggregation Behavior. Langmuir 2007, 23, 13076−13084. (68) Trinh, L. T. T.; Lambermont-Thijs, H. M. L.; Schubert, U. S.; Hoogenboom, R.; Kjøniksen, A.-L. Thermoresponsive Poly(2-oxazoline) Block Copolymers Exhibiting Two Cloud Points: Complex Multistep Assembly Behavior. Macromolecules 2012, 45, 4337−4345. (69) Hua, F.; Jiang, X.; Zhao, B. Temperature-Induced SelfAssociation of Doubly Thermosensitive Diblock Copolymers with Pendant Methoxytris(oxyethylene) Groups in Dilute Aqueous Solutions. Macromolecules 2006, 39, 3476−3479. (70) Lin, S.-T.; Fuchise, K.; Chen, Y.; Sakai, R.; Satoh, T.; Kakuchi, T.; Chen, W.-C. Synthesis, thermomorphic characteristics, and fluorescent properties of poly[2,7-(9,9-dihexylfluorene)]-block-poly(N-isopropylacrylamide)-block-poly(N-hydroxyethylacrylamide) rodcoil-coil triblock copolymers. Soft Matter 2009, 5, 3761−3770.

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