Scheme 1

Article pubs.acs.org/Macromolecules

A New Thermo‑, pH‑, and CO2‑Responsive Homopolymer of Poly[N‑[2-(diethylamino)ethyl]acrylamide]: Is the Diethylamino Group Underestimated? Zefeng Song,‡ Ke Wang,‡ Chengqiang Gao, Shuang Wang, and Wangqing Zhang* Key Laboratory of Functional Polymer Materials of the Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China S Supporting Information *

ABSTRACT: A new multi-stimuli-responsive homopolymer of poly[N-[2(diethylamino)ethyl]acrylamide] (PDEAEAM), which combines the thermoresponsive and pH/CO2-responsive moieties of the diethylamino and acrylamide groups, was proposed and synthesized by RAFT polymerization. Well-defined PDEAEAM was synthesized by solution RAFT polymerization as indicated by the linear increase in the polymer molecular weight with the monomer conversion and the narrow molecular weight distribution. The appending diethylamino group in the polymer backbone was found to be crucial to determine the thermoresponse of PDEAEAM in water. The parameters including the polymerization degree, the polymer concentration, the deuterated solvent, the terminal attached on the polymer backbone, the additives of salt and urea, and pH and bubbling CO2 affecting the thermoresponse of PDEAEAM in aqueous solution at the lower critical solution temperature (LCST) were investigated. The temperature-variable 1H NMR analysis suggests that the dehydration of PDEAEAM at temperature above LCST is ascribed to the weakened hydrogen bonding between the CONHCH2 and/or (CH2N(CH2CH3)2) moieties with the solvent of water. The proposed multi-stimuli-responsive homopolymer of PDEAEAM has two advantages of (1) the convenient and controllable RAFT synthesis and (2) the pH/CO2 tunable LCST at ∼36 °C being very close to body temperature. dimethylacrylamide) is soluble in water,9,11 poly(N-isopropylacrylamide) (PNIPAM)5−17 and poly(N,N-diethylacrylamide) (PDEAAM)11,12 have the similar LCST of 32−33 °C in water, and poly(N-n-butylacrylamide) is insoluble in water.11 For the N-alkyl-substituted polyacrylamides, e.g. PNIPAM, the LCST is hardly dependent on the molar mass of the polymer and the polymer concentration,14 although some controversy is reported.15−17 It is revealed that the LCST of N-alkylsubstituted polyacrylamides is due to a balance of hydrogen bonding and the interactions among polymer−solvent and/or polymer−polymer.3 Other LCST-type thermoresponsive polymers are based on N-alkyl-substituted poly(aminoethyl methacrylate)s,18−24 e.g., poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA),18−24 poly(2-(N-morpholine)ethyl methacrylate) (PMEMA),23 poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA),23,24 and poly(N,N-diisopropylaminoethyl methacrylate) (PDiPAEMA)23,24 as shown in Scheme 1. For these N-alkyl-substituted poly(aminoethyl methacrylate)s, e.g., PDMAEMA with LCST at 32−46 °C, PMEMA with LCST at 34−53 °C, and PDEAEMA being insoluble in neutral water, the LCST is pH-dependent,18−24 and the polymer molecular weight and the polymer concentration have been found to exert somewhat influence on the LCST.22−24 Besides

1. INTRODUCTION In the past two decades, stimuli-responsive polymers have attracted great interest in polymer science.1−4 Of all the stimuliresponsive polymers, the thermoresponsive polymers showing the soluble-to-insoluble phase transition at the lower critical solution temperature (LCST) are probably the most interest.2−4 The polymers of N-alkyl-substituted polyacrylamides as shown in Scheme 1 form the largest group of the LCST-type thermoresponsive polymers.5−17 It is found that the structure of the N-substitution group in the N-alkyl-substituted polyacrylamides are important to determine the thermoresponsive behavior in solvent.9−17 For examples, poly(N,NScheme 1. Typical Thermoresponsive Polymers of PNIPAM, PDMAEMA, and PVEA and the Present Multi-StimuliResponsive Homopolymer of PDEAEAM

Received: November 12, 2015 Revised: December 14, 2015

© XXXX American Chemical Society

A

DOI: 10.1021/acs.macromol.5b02458 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules

and pH-responsive homopolymers in aqueous solution. Herein, the hydrophilic monomer of N-[2-(diethylamino)ethyl]acrylamide (DEAEAM) containing both the diethylamino group and the acrylamide group was synthesized, and the new thermo- and pH/CO2-responsive homopolymer of poly[N-[2-(diethylamino)ethyl]acrylamide] (PDEAEAM, Scheme 1) was prepared by RAFT polymerization. Compared with the multi-stimuli-responsive homopolymers reported previously,39−46 the present thermo- and pH/CO2-responsive homopolymer of PDEAEAM has two advantages of (1) the convenient synthesis of the DEAEAM monomer with concise structure and the multi-stimuli response and (2) the LCST of PDEAEAM being very close to body temperature, which can be tuned by polymer concentration, pH, and the terminals attached on the polymer backbone, and therefore it is expected to have promising applications.

these two kinds of LCST-type thermoresponsive polymers, poly[oligo(ethylene glycol) (meth)acrylate],25−27 poly(2-alkyl2-oxazolines),28,29 poly(vinyl methyl ether),30 and the elastinlike polypeptides (ELPs)31−33 exhibiting the soluble-toinsoluble phase transition in water at LCST have also been reported. Polymer simply having thermoresponsive property does not necessarily meet the requirement at some cases, and therefore synthesis of multi-stimuli-responsive polymer undergoing sequential and predictable changes in morphology and properties under different stimuli, e.g., temperature and pH, temperature and photo, temperature and temperature, and temperature and redox, is needed.34−46 The addition of more than one stimulus is particularly advantageous because it can improve the switching condition and therefore affords better control on the polymer conformation due to the higher level of complexity of the polymer. In general, these multi-stimuliresponsive polymers, e.g., temperature- and pH-responsive polymers, are usually prepared through the copolymerization of a monomer with a pH-responsive moiety and another monomer with a thermoresponsive moiety in block or random fashion.35−38 However, the time-consuming multiple steps are usually involved in the synthesis of well-defined multi-stimuliresponsive block copolymers,35,36 and for the multi-stimuliresponsive random copolymers the phase transition usually occurs within a broad temperature or pH window.37,38 Therefore, synthesis of multi-stimuli-responsive homopolymers may be a promising alternative. Of all the multi-stimuliresponsive homopolymers,39−46 PDMAEMA,39 which are thermo- and pH/CO2-responsive, may be the most popular one. In recent years, some multi-stimuli-responsive homopolymers such as the elastin-based macromolecules and poly(Nmethacryloyl-L-amino acid)s have been prepared.40,41 Huang and co-workers prepared thermo- and pH/CO2-responsive homopolymer of poly(N-(2-(diethylamino)ethyl)-N-(3(isopropylamino)-3-oxopropyl)acrylamide) by combining the thermoresponsive and pH/CO2-responsive moieties of amide and amine in one polymer backbone,44,45 and the tunable thermoresponse by pH and CO2 was demonstrated. However, synthesis of the precursory monomer of these multi-stimuliresponsive homopolymers was not an easy thing, and usually complex procedures were involved. Therefore, convenient synthesis of multi-stimuli-responsive homopolymers with concise chemical composition is urgently needed. In the previous study,47 poly[N-(4-vinylbenzyl)-N,N-diethylamine] (PVEA, Scheme 1) bearing the appending diethylamino group was synthesized by RAFT polymerization, and it was found that poly[N-(4-vinylbenzyl)-N,N-diethylamine] (PVEA) bearing the appending diethylamino group shows both the LCST-type thermoresponsive phase transition in alcoholic solvent and the pH response in aqueous solution. Clearly, PVEA and PDMAEMA have the similar appending groups of diethylamine or dimethylamine, which endow them with the ability of the LCST-type response and pH response. However, the diethylamine or dimethylamine motif in the design of thermoresponsive polymers is somehow underestimated, and just two multi-stimuli-responsive homopolymers of PDMAEMA and PVEA have been reported. Inspired by the success design of the multi-stimuli-responsive PVEA showing the LCST-type thermoresponsive phase transition in alcoholic solvent,47 it is expected that the introduction of the dialkylamino group into the hydrophilic backbone of poly(acrylamide)s may be a strategy to prepare new temperature-

2. EXPERIMENTAL SECTION 2.1. Materials. N,N-Diethylethylenediamine (>98%, Aladdin, China), N,N-dimethylethylenediamine (>98%, Aladdin, China), N,Ndibutylethylenediamine (>98%, TCI, China), and acryloyl chloride (>99%, Heowns, China) were used as received. 2,2′-Azobis(2methylpropionitrile) (AIBN, >99%, Tianjin Chemical Company, China) was recrystallized from ethanol before being used. The RAFT agents of 4-cyano-4-(dodecylsulfanylthiocarbonyl)sulfanylpentanoic acid (CDTPA), 4-cyano-4-(ethylsulfanylthiocarbonyl)sulfanylpentanoic acid (CETPA), and S,S′-bis(α,α′-dimethyl-α″-acetic acid) trithiocarbonate (BDMAT) as shown in Scheme S1 were synthesized as discussed elsewhere.48−50 Other chemical reagents were of analytical grade and were used as received. Deionized water was used in the present experiment. 2.2. Synthesis of the Monomers of N-[2-(Diethylamino)ethyl]acrylamide and Its Analogues. The monomer of N-[2(diethylamino)ethyl]acrylamide (DEAEAM) was synthesized as shown in Scheme 2.51 Typically, into a flask with a magnetic stir,

Scheme 2. Synthesis of the Monomer of DEAEAM

N,N-diethylethylenediamine (150 mmol, 17.43 g) and CHCl3 (150 mL) were added under a nitrogen atmosphere, and then the flask was put in an ice−water bath. Subsequently, acryloyl chloride (180 mmol, 14.55 mL) dissolved in CHCl3 (100 mL) was added dropwise in 1 h. After the complete addition of acryloyl chloride, the reaction was performed for another 1 h at room temperature. The chloroform solution was washed with aqueous NaOH solution (200 mL, 1 mol/L) and water (200 mL) and finally dried over anhydrous MgSO4. The solvent of CHCl3 was removed via rotary evaporation under reduced pressure, and the crude product was purified by column chromatography using ethyl acetate as eluent to afford DEAEAM (23.3 g, 91% yield). The 1H NMR and 13C NMR spectra shown in Figure 1 confirm the successful synthesis of DEAEAM. The other two monomers of N-[2-(dimethylamino)ethyl]acrylamide (DMAEAM) and N-[2-(dibutylamino)ethyl]acrylamide (DBAEAM) were synthesized with the similar procedures of DEAEAM introduced above, and their 1H NMR and 13C NMR spectra are shown in Figures S1 and S2. 2.3. Synthesis of Poly[N-[2-(dialkylamino)ethyl]acrylamide]s and by RAFT Polymerization. Poly[N-[2-(diethylamino)ethyl]acrylamide] (PDEAEAM) was prepared by solution RAFT polymerization using CDTPA, CETPA, or BDMAT as RAFT agent and AIBN as initiator under [DEAEAM]0:[RAFT]0:[AIBN]0 = 600:3:1. Herein, a typical RAFT polymerization employing CDTPA as RAFT agent was introduced. Into a Schlenk flask with a magnetic bar, DEAEAM (1.00 g, 5.88 mmol), CDTPA (11.84 mg, 0.0294 mmol), the internal B


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Figure 1. 1H NMR and 13C NMR spectra of DEAEAM.

Table 1. Summaries of the Solution RAFT Polymerization and the Synthesized Poly[N-[2-(dialkylamino)ethyl]acrylamide]s Mn (kg/mol) a

b

entry

monomer

RAFT

[M]0:[CTA]0:[I]0

time (h)

conv (%)

DP

Mn,th

1 2 3 4 5

DEAEAM DEAEAM DEAEAM DMAEAM DBAEAM

CDTPA CETPA BDMAT CDTPA CDTPA

600:3:1 600:3:1 600:3:1 600:3:1 600:3:1

6 7 7 6 6

65.0 63.2 61.9 71.8 31.3

130 126 124 144 62

22.5 21.7 21.3 20.8 14.6

Mn,GPCc

Mn,NMRd

Đe

9.9 9.4 9.1 5.0 6.5

19.8

1.11 1.14 1.09 1.11 1.42

17.6

a The monomer conversion determined by 1H NMR analysis. bTheoretical molecular weight according to eq 1. cMolecular weight determined by GPC analysis. dMolecular weight determined by 1H NMR analysis. eThe Đ (Mw/Mn) values determined by GPC analysis.

Figure 2. Time-dependent monomer conversion and the ln([M]0/[M])−time plots of the solution RAFT polymerization (A), the GPC traces (B), and the typical NMR spectra (C) of PDEAEAM and the evolution of the molecular weight and the Đ (Mw/Mn) value of PDEAEAM with the monomer conversion in the solution RAFT polymerization (D). polymerization was performed at 70 °C under magnetically stirring. After a given time, the polymerization was quenched by rapid cooling upon immersion of the flask in iced water. To detect the monomer

standard of 1,3,5-trioxane (52.90 mg, 0.588 mmol) and AIBN (1.61 mg, 0.0098 mmol) dissolved in 1,4-dioxane (1.00 g) were added. The flask content was degassed with nitrogen at 0 °C, and then the C


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Figure 3. Summary of the solution behavior of PDMAEAM, PDEAEAM, and PDBAEAM. conversion, a drop of the polymerization solution was diluted with CDCl3 and subjected to 1H NMR analysis. The synthesized polymer of PDEAEAM was precipitated in n-hexane at 0 °C, washed with cold n-hexane, and finally dried under vacuum at room temperature overnight to afford a powder sample. Poly(N-[2-(dimethylamino)ethyl]acrylamide) (PDMAEAM) and poly(N-[2-(dibutylamino)ethyl]acrylamide) (PDBAEAM) were also synthesized by solution RAFT polymerization, and the synthesis details are summarized in Table 1. 2.4. Characterization. The molecular weight and the polydispersity index (Đ, Đ = Mw/Mn) of the synthesized polymers were determined by gel permeation chromatography (GPC) equipped with a Waters 600E GPC system, where THF was used as the eluent and the narrow-polydispersity polystyrene was used as the calibration standard. The 1H NMR and 13C NMR analysis was performed on a Bruker Avance III 400 MHz NMR spectrometer, and for polymers dissolved in CDCl3 and D2O, the proton signals at δ = 7.26 ppm and δ = 4.79 ppm of the internal solvents were used as standard. The LCST of the thermoresponsive polymers was determined by turbidity analysis at 500 nm on a Varian 100 UV−vis spectrophotometer equipped with a thermoregulator (±0.1 °C) with the heating/cooling rate at 1 °C/min, in which the LCST or cloud temperature was determined at 50% transmittance or at the half of the maximal and minimal transmittance. The differential scanning calorimetry (DSC) analysis was performed on a NETZSCH DSC 204 differential scanning calorimeter under a nitrogen atmosphere, in which the sample was heated to 120 °C at the heating rate of 10 °C/min, cooled to 0 °C in 5 min, and then heated to 120 °C at the heating rate of 10 °C/min. The IR measurements were performed on a Bio-Rad FTS-6000 IR spectrometer. For the FTIR spectra, the mixture of the synthesized polymer and KBr was first pressed to form a pellet, and subsequently the spectra were recorded.

GPC traces, and the reason is ascribed to the interaction between the nitrogen-containing polymer and the GPC columns as discussed elsewhere.52 As summarized in Figure 2D, the molecular weight Mn,NMR by 1H NMR analysis, which is calculated by comparing the characteristic chemical shift at δ = 0.81 ppm (a) corresponding to the RAFT terminal to the signal at δ = 3.22 ppm (m) corresponding to the polymer backbone, is very close to the theoretical molecular weight Mn,th determined by the monomer conversion according to eq 1. Whereas, the molecular weight Mn,GPC by GPC analysis is lower than Mn,th, and the reason is possibly due to the interaction between the tertiary amine groups in PDEAEAM and the GPC columns as discussed above, which leads to the underestimated molecular weight of the synthesized polymer. Although the difference between Mn,NMR and Mn,GPC is found, the two cases of polymer molecular weight increase linearly with the monomer conversion. Besides, the Đ value of PDEAEAM is generally below 1.2. These suggest that the RAFT polymerization affords the good control on both the molecular weight and the molecular weight distribution of PDEAEAM. The synthesized PDEAEAM was further characterized by DSC analysis (Figure S3) and by FT-IR analysis (Figure S4). As shown by the DSC thermograms shown in Figure S3, PDEAEAM has a glass transition temperature (Tg) at 47 °C, which is lower than that of PNIPAM,53 and is slightly higher than that of PVEA and PDMAEMA,47,54 respectively.

3. RESULTS AND DISCUSSION 3.1. Synthesis of Poly[N-[2-(dialkylamino)ethyl]acrylamide]s by Solution RAFT Polymerization. To prepare PDEAEAM with well-defined polymer molecular weight and with suitable terminal, solution RAFT polymerization of DEAEAM employing three different RAFT agents, CDTPA, CETPA, and BDMAT, under the constant ratio of [DEAEAM]0:[RAFT]0:[AIBN]0 = 600:3:1 was performed. Figure 2A shows the polymerization kinetics of the typical solution RAFT polymerization employing CDTPA as RAFT agent. It indicates that the monomer conversion increases quickly to 73.0% in the initial 10 h, and the further increase in polymerization time just leads to very slight monomer conversion. From the ln([M]0/[M])−time plots, the pseudofirst-order polymerization, which verifies the living nature of controlled radical polymerization, for the solution RAFT polymerization in the initial 10 h is confirmed. From the GPC traces shown in Figure 2B and the typical 1H NMR spectra shown in Figure 2C, the molecular weight of PDEAEAM and the Đ values are obtained. Note: the slight shoulder is observed at the low molecular weight side in the

The solution RAFT polymerization of DEAEAM mediated with other two RAFT agents of CETPA and BDMAT under the similar conditions was also performed, and the results are summarized in Table 1. Note: the RAFT terminal of PDEAEAM synthesized through CETPA and BDMAT cannot be identified from the 1H NMR spectra shown in Figure S5, and therefore Mn,NMR is not shown. The results indicate that all the three RAFT polymerizations afford the synthesis of PDEAEAM with controllable molecular weight and the narrow molecular weight distribution, although the latter two RAFT polymerizations run slightly slower than those mediated by the RAFT agent of CDTPA. The solution RAFT polymerization of DMAEAM mediated with the CDTPA RAFT agent ran a little faster, and 71.8% monomer conversion in 6 h was achieved. The solution RAFT polymerization afforded good control on the molecular weight and the molecular weight distribution (Đ) of the synthesized PDMAEAM (entry 4 in Table 1). The solution RAFT polymerization of DBAEAM mediated with the CDTPA RAFT agent ran much slow and just 31.3% monomer conversion was achieved in 6 h (entry 5 in Table 1). The Đ

M n,th =

D

[monomer]0 × M monomer × conversion + M n,macro‐RAFT [RAFT]0 (1)


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Figure 4. Temperature-dependent transmittance of the PDEAEAM aqueous solution and the summary of LCST of PDEAEAM: (A, B) the effect of DP on LCST of PDEAEAM and (C, D) the effect of the polymer concentration on LCST of PDEAEAM.

becomes transparent when cooling to room temperature, confirming the reversible soluble-to-insoluble phase transition of PDEAEAM at LCST. Subsequently, the parameters, e.g. the DP of PDEAEAM, the polymer concentration, the deuterated solvent, the terminal attached on the polymer backbone, and the additives of salt and urea, affecting the LCST/cloud temperature or the thermoresponse of PDEAEAM are investigated. Figure 4A shows the temperature-dependent transmittance of the 1.0 wt % aqueous solution of PDEAEAM with different DP synthesized by the RAFT agent of CDTPA. It indicates that the LCST-type soluble-to-insoluble phase transition of PDEAEAM occurs within a narrow temperature window of ∼1 °C, and a very slight delay during the cooling process is observed. As summarized in Figure 4B, the polymer with the lowest DP, PDEAEAM22, has a slightly higher LCST at 35.0 °C. When DP exceeds the minimum of 48, the LCST of PDEAEAM almost keeps constant at 34.5 °C, suggesting that the DP of PDEAEAM just has no or very slight influence on LCST, which is somewhat similar to the typical thermoresponsive PNIPAM.14 As shown in Figure 4C, the LCST of PDEAEAM is correlative to the polymer concentration, and the LCST decreases from 37.5 to 33.5 °C when the polymer concentration increases from 0.20 to 2.0 wt % as summarized in Figure 4D. Besides, with the polymer concentration decreasing to 0.20 wt %, the LCST-type phase transition of PDEAEAM occurs within a broader temperature window of 36.5−39.5 °C, which is somewhat similar to the typical thermoresponsive PDMAEMA as discussed elsewhere.22,23 Generally, isotopic solvent just exhibits slight or no influence on LCST of thermoresponsive polymers.55 However, some exceptions have been found. For examples, LCST of PNIPAM in D2O is ∼1 °C higher than in H2O,56 and whereas the LCST

value of the syntheized PDBAEAM is a little higher than those of PDMAEAM and PDEAEAM, and the optimization of the RAFT synthesis of PDBAEAM is undergoing. 3.2. Solution Behavior of Poly[N-[2-(dialkylamino)ethyl]acrylamide]s and the Thermoresponse of PDEAEAM. The solution behavior of poly[N-[2-(dialkylamino)ethyl]acrylamide]s is firmly dependent on the appending dialkylamino group as summarized in Figure 3. It is found that PDMAEAM containing an appending dimethylamino group is soluble in water and in pH 14 alkaline solution even at the boiling temperature of water (Figure S6), suggesting PDMAEAM being an aqueous soluble polymer. PDBAEMA containing an appending dibutylamino group is insoluble in neutral water, and it becomes soluble when pH decreasing to 6.5. When the acidified solution of PDBAEMA is initially neutralized by NaOH to form cloudy dispersion and then bubbling with CO2, the solution becomes transparent (Figure S7). This pH- and CO2-response of PDBAEMA is ascribed to the appending dibutylamino group in the polymer backbone. Besides, when the acidified aqueous solution PDBAEMA, e.g. at pH 5, is heated to the boiling temperature of water, no solubleto-insoluble phase transition is found. All these results suggest that PDBAEMA is pH/CO2-responsive but not thermoresponsive as the general thermoresponsive polyacrylamides.3 The thermoresponse of PDEAEAM can be easily confirmed just by initially heating the aqueous solution of PDEAEAM at temperature above LCST and then cooling at temperature below LCST. For example, it is found that the typical 1.0 wt % aqueous solution of PDEAEAM130, which is synthesized by the RAFT agent of CDTPA and the subscript represents the polymerization degree (DP) herein and in the next discussion, is transparent at room temperature, it becomes cloudy when heating to the cloud temperature of 37 °C, and it further E


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Macromolecules of elastin-like polypeptides in D2O is lower than in H2O.32 Figure 5 indicates that the cloud temperature of PDEAEAM in

PDEAEAM. The reason that a hydrophobic terminal of dodecyl attached onto the PDEAEAM backbone decreasing the cloud temperature or LCST is due to the hydrophobic terminal decreasing the hydrophilicity of the polymer chains as discussed elsewhere.25 The salt, e.g. NaCl, affecting the LCST of PDEAEAM is investigated. For the thermoresponsive polymers such as polyacrylamides and the analogues,5,12 poly[oligo(ethylene glycol) (meth)acrylate],27 poly(2-alkyl-2-oxazolines),29 and the elastin-like polypeptides,33 adding inorganic salts into the aqueous solution of thermoresponsive polymers usually decreases the LCST, and the reason is ascribed to the saltingout effect, which disrupts the hydrogen bonding between the polymer chains with water to promote the hydrophobic polymer−polymer interactions. As shown in Figure 7A, similarly with the LCST-type thermoresponsive polymer mentioned above,5,12,27,29,33 the cloud temperature of the 1.0 wt % aqueous solution of PDEAEAM130−CDTPA decreases from 34.3 to 23.9 °C when the NaCl concentration increases from 0 to 1.0 mol/L. Urea was widely used as protein denaturant57,58 and therefore was usually used to diagnose the hydrogen bonding between the polymer chains and the solvent to check the solution-to-insoluble phase transition of thermoresponsive polymers at LCST.57,58 For the thermoresponsive polymers capable of undergoing hydrogen bonding with urea, e.g. PNIPAM, the LCST usually decreases with the addition of urea.57,58 Whereas, for the thermoresponsive polymers incapable of forming hydrogen bonding with urea, e.g. PDMAEMA, poly(vinyl ether)s, poly(2-oxazoline)s, and the elastin-like polypeptides,56 the LCST usually increases with the addition of urea. As discussed above, the diethylamino group and the acrylamide group are combined within PDEAEAM, and therefore PDEAEAM is somehow a joint of PNIPAM and PDMAEMA. Figure 7B indicates that the cloud temperature of the 1.0 wt % aqueous solution of PDEAEAM130−CDTPA increases from 34.4 to 40.0 °C when the concentration of the fed urea increases from 0 to 3.3 mol/L. This suggests that the present thermoresponsive polymer of PDEAEAM in the presence of urea undergoes the phase transition similarly with PDMAEMA but differently with PNIPAM. As discussed above, the thermoresponse of the soluble-toinsoluble phase transition of PDEAEAM at LCST is neither similar to PNIPAM nor PDMAEMA. In order to gain deep insight into the phase transition of PDEAEAM at LCST, the temperature-variable 1H NMR analysis of the phase transition of the 1.0 wt % PDEAEAM130−CDTPA solution in the absence or in the presence of 2.0 mol/L urea was performed. Figure 8A shows the 1H NMR spectra of PDEAEAM130−CDTPA in the absence of urea recorded from 30.0 to 44.0 °C. It indicates the characteristic chemical shift (m, k, j, i) weakening upon heating at temperature above the LCST of 32.0 °C and the disappearance of the characteristic chemical shift at 1.25−2.25 ppm corresponding to the polymer backbone, and therefore the dehydration of the polymer chains at temperature above LCST is confirmed. Since the dehydration of the polymer chains is generally ascribed to the weakened hydrogen bonding between the polymer chains and water with temperature increasing above LCST, three typical characteristic signals, (CONHCH2) with δ = 3.30 ppm, (CH2N(CH2CH3)2) with δ = 2.58 ppm, and (N(CH2CH3)2) with δ = 1.03 ppm, which are normalized by the internal standard of H2O at δ = 4.70 ppm, at different temperature are recorded and summarized in Figure 8B. These

Figure 5. Temperature-dependent transmittance of the aqueous solution of PDEAEAM130 in H2O and D2O, in which the polymer concentration is 1.0 wt %.

deuterated water (D2O) is slightly lower than those in water (H2O) (32.0 vs 34.3 °C), which is as similarly as those of PVEA in deuterated alcohol and the elastin-like polypeptides in deuterated water.32,47 The terminal attached on the polymer backbone affecting the LCST of PDEAEAM is also investigated. To fulfill this investigation, three polymers with the similar DP at 124−130 but different RAFT terminals, PDEAEAM 130 −CDTPA, PDEAEAM126−CETPA, and PDEAEAM124−BDMAT, were prepared, in which the subscript represents the DP of the polymer and the capital letters after the dash represent the RAFT agent employed in the RAFT polymerization. As shown in Figure S8, PDEAEAM130−CDTPA has a hydrophobic dodecyl terminal originated from the Z-group of the RAFT agent of CDTPA, PDEAEAM126−CETPA has an ethyl terminal, and PDEAEAM124−BDMAT has a dimethylacetic acid terminal. Figure 6 indicates that PDEAEAM130−CDTPA including a hydrophobic dodecyl terminal has a low cloud temperature of 34.3 °C, and PDEAEAM126−CETPA and PDEAEAM124−BDMAT have a high and alike cloud temperature of 36.8 °C, suggesting that the slight difference between the ethyl and dimethylacetic acid terminals exerts no or very slight influence on the LCST of thermoresponse of

Figure 6. Temperature-dependent transmittance of the 1.0 wt % aqueous solution of PDEAEAM with different RAFT terminals. F


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Figure 7. Effect of NaCl (A) and urea (B) on the cloud temperature of the 1.0 wt % PDEAEAM130−CDTPA aqueous solution.

(CH2CH3)2) moieties with the solvent of D2O contributes mainly to the dehydration of PDEAEAM at temperature above LCST. The temperature-dependent 1H NMR spectra of PDEAEAM in the presence of urea were also recorded, and the similar dehydration of the polymer chains with the increasing temperature is detected (Figure 8B). 3.3. pH and CO2 Response of PDEAEAM. Because of the appending diethylamino group, it is expected that PDEAEAM is pH- and CO2-responsive as similar as PDMAEMA. Figure 9A indicates that PDEAEAM130−CDTPA is soluble in the aqueous solution with pH 8.0, and no LCST-type phase transition is observed at the temperature window of 25−65 °C. Note: directly dissolving PDEAEAM130−CDTPA in neutral water leads to the 0.50 wt % aqueous solution with pH 9.0, and the pH 8.0 aqueous solution of PDEAEAM is prepared by adding suitable amount of pH 1.0 HCl aqueous solution. At case of pH > 8.5, the LCST-type phase transition of PDEAEAM130− CDTPA is observed. It is found that the cloud temperature of PDEAEAM130−CDTPA decreases from 50.2 to 33.1 °C when pH increases from 8.5 to 11.0, and the cloud temperature just slightly decreases to 31.5 °C when pH further increases to 13.0 as summarized in Figure 9B. When the pH of the PDEAEAM130−CDTPA aqueous solution further increases to pH = 14.0, possibly due to the salting-out effect caused by the pH regulator of NaOH, the cloud temperature decreases to 27.5 °C. CO2 attracts considerable attention due to its availability, nontoxicity, biocompatibility, low cost and abundance, and the use of CO2 as a trigger for responsive polymers may also hold promise for applications. Amidine-based polymers form the largest family of the CO2-responsive polymers.59,60 The appending amidine can react with CO2 and water to form a charged amidinium bicarbonate and be recovered upon CO2 removal by bubbling argon (or any nonacidic gas).58,59 Besides the amidine-based polymers, PDMAEMA is found to react directly with CO2 in water, and the LCST of PDMAEMA initially increases after bubbling with CO2 and then reversibly recovers upon removal of CO2 by bubbling argon.39,61 Figure 10A indicates that PDEAEAM is CO2-responsive. That is after bubbling CO2, no LCST of the 0.50 wt % PDEAEAM aqueous solution is detected, suggesting that PDEAEAM becomes soluble in the CO2-saturated solvent at the temperature window of 25−65 °C, and PDEAEAM becomes reversibly thermoresponsive with the cloud temperature at 45.3 °C after bubbling N2, and PDEAEAM further becomes soluble in water after bubbling CO2. Interestingly, the cloud temperature of the

Figure 8. 1H NMR spectra of PDEAEAM130−CDTPA in D2O at different temperature (A) and the temperature-dependent signals of the typical protons adjacent to the nitrogen (N) atom in the absence of urea (solid line) or in the presence of urea (dotted line) (B), in which the polymer concentration is 1.0 wt %.

three protons signals are chosen, since the corresponding protons signals can be affected by hydrogen bonding and therefore can provide the information about the hydrogen bonding between the polymer chains and the D2O solvent. As shown in Figure 8B, these three signals keep constant at temperature below LCST at 32 °C, and when temperature increases above LCST, these three signals become weakened gradually. In comparison, the signals of CONHCH2 and (CH 2 N(CH 2 CH 3 ) 2 ) decreased much faster than (N(CH2CH3)2), and therefore the weakened or disrupted hydrogen bonding between the CONHCH2 and/or (CH2NG


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Figure 9. pH-dependent transmittance of the 0.50 wt % PDEAEAM130−CDTPA aqueous solution (A) and the summary of the pH-dependent the cloud temperature of PDEAEAM130−CDTPA (B).

Figure 10. Temperature-dependent transmittance of the 0.50 wt % PDEAEAM130−CDTPA aqueous solution upon the N2/CO2 bubbling (A) and the 0.50 wt % PDEAEAM130−CDTPA aqueous solution at 48.0 °C upon the N2/CO2 bubbling (B).

4. CONCLUSIONS In this study, a new multi-stimuli-responsive homopolymer of poly[N-[2-(diethylamino)ethyl]acrylamide] (PDEAEAM), which is thermo- and pH/CO2-responsive was proposed and synthesized by RAFT polymerization. The appending diethylamino and acrylamide groups in PDEAEAM endow the proposed homopolymer to give response to the stimulus of the temperature, pH, and CO2. Well-defined PDEAEAM was synthesized by solution RAFT polymerization mediated with the trithiocarbonate RAFT agent, e.g., CDTPA, CETPA, and BDMAT, as indicated by the linear increase in the polymer molecular weight with the monomer conversion and the narrow molecular weight distribution with Đ below 1.2. The parameters including the DP of PDEAEAM, the polymer concentration, the deuterated solvent, the terminal attached on the polymer backbone, and the additives of salt and urea affecting the LCST or the thermoresponse of PDEAEAM are investigated. It is found that the LCST of PDEAEAM is uncorrelative to the DP of PDEAEAM when DP is above the critical point, and the LCST slightly decreases with the increase in the polymer concentration, and the LCST of PDEAEAM in deuterated water (D2O) is slightly lower than those in water, and the LCST decreases with the addition of NaCl and whereas it increases with the addition of urea. The temperature-variable 1 H NMR analysis suggests that the dehydration of PDEAEAM at temperature above LCST is ascribed to the weakened or disrupted hydrogen bonding between the CONHCH2 and/or (CH2N(CH2CH3)2) moieties with the solvent of water. The

recycled PDEAEAM aqueous solution is much higher than that of the fresh PDEAEAM aqueous solution (44.4−45.3 °C vs 35.8 °C), even the CO2 bubbling extends to 6 h. This suggests that the PDEAEAM in the CO2-saturated solvent cannot recover to the starting point just by bubbling N2. Clearly, the CO2 response of PDEAEAM is slightly different from that of PDMAEMA,39,60 in which the cloud temperature of the recycled PDMAEMA is close to that of the fresh polymer. The 1H NMR analysis of the fresh PDEAEAM solution of D2O, the PDEAEAM solution after CO2 bubbling, and the recycled PDEAEAM solution by N2 bubbling shows the switch of the characteristic chemical shifts of CONHCH2 (3.35, 3.56, and finally 3.37 ppm), CH2N(CH2CH3)2 (2.66, 3.24, and finally 2.72 ppm) and N(CH2CH3)2 (1.11, 1.33, and finally 1.13 ppm) during these procedures (Figure S9), and the result indicates that the CO2 charged amidinium bicarbonate in PDEAEAM just can be partly recovered by N2 bubbling. The reason is ascribed to interaction between CO2 and PDEAEAM being stronger than that between CO2 and PDMAEMA,39,60 since the appending diethylamino group in PDEAEAM is a stronger Lewis base than the dimethylamino group in PDMAEMA. Note: the calculated pKa values of DEAEAM and DMAEMA are 10 and 7.3, respectively. Despite this, the cloud temperature of PDEAEAM in the N2-saturated solvent almost keeps constant at 44.4−45.3 °C after several cycles of the N2/CO2 bubbling as shown in Figures 10A and 10B. H


Article

Macromolecules

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pH also affects the thermoresponse of PDEAEAM, as indicated by the decreasing LCST of PDEAEAM with the pH increasing. Besides, the thermoresponse of PDEAEAM can be reversibly tuned by N2/CO2 bubbling. The proposed multi-stimuliresponsive homopolymer of PDEAEAM combining the thermoresponsive and pH/CO2-responsive moieties has two advantages of (1) the convenient and controllable RAFT synthesis and (2) the pH/CO2 tunable LCST very close to body temperature. The multi-stimuli-responsive PDEAEAM is compared with its analogues of PMEAEAM and PDEAEAM, and it is found that the appending diethylamino group in the polymer backbone exerts the dominated influence on the thermoresponse of the multi-stimuli-responsive homopolymer of PDEAEAM. Our finding helps to open a new way to design thermoresponsive polymers other than the widely discussed PNIPAM and PDMAEMA.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.5b02458. Scheme S1 and Figures S1−S9 showing the chemical structure of the RAFT agents, the 1H NMR spectra, DSC thermogram and FTIR spectra of PDEAEAM, the 1H NMR and 13C NMR spectra of DMAEAM and DBAEAM, respectively (PDF)

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AUTHOR INFORMATION

Corresponding Author

*(W.Z.) E-mail [email protected], Tel 86-22-23509794, Fax 86-22-23503510. Author Contributions ‡

Z.S. and K.W. contributed equally to this manuscript.

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. 21274066 and 21474054), and PCSIRT (IRT125) is gratefully acknowledged.

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