UCST or LCST? Composition-Dependent Thermoresponsive Behavior

Mar 2, 2017 - The LCST- and UCST-type transitions are tunable with respect to composition, degree of polymerization, polymer concentration, isotope ef...
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UCST or LCST? Composition-Dependent Thermoresponsive Behavior of Poly(N‑acryloylglycinamide-co-diacetone acrylamide) Wenhui Sun,† Zesheng An,*,‡ and Peiyi Wu*,† †

The State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China ‡ Institute of Nanochemistry and Nanobiology, College of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China S Supporting Information *

ABSTRACT: Copolymerization has been widely used to tune the thermoresponsive behavior of water-soluble polymers. However, the observation of both upper and lower critical solution temperature (UCST and LCST) from the same type of copolymer comprising only one monomer whose homopolymer is thermosensitive and the other monomer whose homopolymer is nonthermosensitive has not been reported. In this work, well-defined thermoresponsive copolymers with tunable compositions have been synthesized by copolymerization of N-acryloylglycinamide (NAGA) and diacetone acrylamide (DAAM) via reversible addition−fragmentation chain transfer (RAFT) polymerization. The thermal transitions of these copolymers are investigated using a combination of turbidimetry, dynamic light scattering (DLS), proton nuclear magnetic resonance (1H NMR), and Fourier transform infrared (FTIR) spectroscopy. The solubility of these copolymers shows a distinct dependence on the composition. While copolymers with up to 30 mol % NAGA are essentially insoluble, copolymers with 35−55 mol % NAGA or 90−100 mol % NAGA have either LCST- or UCST-type transitions respectively, and soluble copolymers are obtained with 60−85 mol % NAGA. The LCST- and UCST-type transitions are tunable with respect to composition, degree of polymerization, polymer concentration, isotope effect and the presence of electrolyte. Insights from variable-temperature 1H NMR and FTIR spectroscopies reveal the key role of hydrogen-bonding between the NAGA and DAAM units in determining the thermal transitions.

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reversible H-bonding.29−32 The glycinamide moiety of PNAGA can act as both a hydrogen donor (mainly primary amide) and acceptor (carbonyl group). Previous reports regarding the UCST-type transition of PNAGA suggest that the polymer is able to form intra- and intermolecular complexes via H-bonding between its own units.33 Copolymerization is a powerful strategy used to adjust the transition temperatures of thermoresponsive polymers, in addition to the manipulation of external conditions such as counterions, redox potential, light, or pH.23,34−36 For example, we have reported that thermoresponsive copolymers of poly(2methoxyethyl acrylate-co-poly(ethylene glycol) methyl ether acrylate) (P(MEA-co-PEGA480)) have a linear relationship between the LCST and the molar ratio of MEA/PEGA,37 while Cai and co-workers have reported that gradient copolymers of poly(diacetone acrylamide-grad-N,N-dimethyl acrylamide) (P(DAAM-grad-DMA)) show adjustable LCST by changing the comonomer sequence from 16 °C to permanently watersoluble.38 In addition, poly(acrylamide-co-acrylonitrile) (poly-

INTRODUCTION Thermoresponsive polymers play an important role in the development of advanced technologies including switchable surfaces,1,2 drug release,3−5 catalysis,6−8 gene therapy,9,10 optical switching,11 and bioimaging.12−14 Polymers with lower or upper critical solution temperature (LCST or UCST) in solution show a miscibility gap at high or low temperatures, respectively, and phase separation into a polymer-poor and polymer-rich phase could be observed.15 Many thermoresponsive polymers are known to be LCST-type, such as poly(Nisopropylacrylamide) (PNIPAM),16−18 poly(N-vinylcaprolactam) (PVCL)19,20 and poly(oligo(ethylene glycol) (meth)acrylate) (PPEG(M)A).21,22 However, there exist far less UCST-type polymers. Although some zwitterionic polymers and polyelectrolytes display UCST-type response in water due to Coulombic interactions, their thermoresponsive behavior is highly dependent on the molar mass, type of salts, ionic strength and valency of ions.23−27 In recent years, increasingly more attention has been given to nonionic UCST-type polymers with their phase transitions being dominated by hydrogen- (H-) bonding.28,29 Poly(N-acryloylglycinamide) (PNAGA) is the most studied nonionic polymer exhibiting UCST-type phase transition due to thermally controlled © XXXX American Chemical Society

Received: January 4, 2017 Revised: February 2, 2017

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Macromolecules Scheme 1. Synthesis of Statistical Copolymers of NAGA with DAAM

Table 1. Synthetic Conditions and Results of P(NAGA-co-DAAM) Copolymersa

U C S T L C S T

polymer code

composition

convn (%)b

Mn,thc (g/mol)

Mn(GPC)d (g/mol)

Đ (GPC)d

UCST/LCST (°C)f (heating/cooling)

NAGA61 NAGA30 PNAGA NAGA99 NAGA95 NAGA90 NAGA34 NAGA41 NAGA45 NAGA50 NAGA56

P(NAGA113-co-DAAM72) P(NAGA58-co-DAAM138) PNAGA191 P(NAGA190-co-DAAM2) P(NAGA177-co-DAAM9) P(NAGA172-co-DAAM19) P(NAGA67-co-DAAM131) P(NAGA80-co-DAAM116) P(NAGA90-co-DAAM109) P(NAGA96-co-DAAM95) P(NAGA110-co-DAAM87)

92 96 91 91 90 92 96 95 95 93 92

26700 30800 24500 24700 24200 25300 30800 29900 30000 28400 28800

30700 33100 28100e 28900e 28000e 30200e 33400 32200 33500 28800 30800

1.24 1.21 1.23e 1.25e 1.22e 1.23e 1.22 1.24 1.20 1.22 1.21

soluble insoluble 20/8.5 18/7.5 13.5/4.5 −/∼0 18.5/18 20/19 22/21 26/25 41/40

Target DP = ∼ 200. bMonomer conversion determined by 1H NMR. cTheoretical molecular weight of copolymers = (target DPNAGA × monomer conversion) × MNAGA + (target DPDAAM × monomer conversion) × MDAAM + MCTA. dMolecular weight determined by GPC (DMF, PMMA). e Molecular weight determined by GPC (DMSO, pullulan). fThe temperature at 50% transmittance of the thermal transition was taken as the UCST or LCST. a

Figure 1. RAFT copolymerization of NAGA and DAAM in water with different molar ratios of NAGA/DAAM, [monomer]/[CTA]/[V-50] = 200:1:0.08, concentration = 10%: (a) conversion vs polymerization time, (b) pseudo-first order kinetic plots, (c) NAGA50 molecular weight and dispersity vs conversion, and (d) evolution of GPC traces of NAGA50.

(AAm-co-AN)) is another type of nonionic UCST-type polymer and exhibits tunable UCST on varying the composition of the monomers.28,39 However, the AN monomer is highly toxic, limiting its use in biomedical applications. Tuning the UCST of PNAGA by copolymerization with Nacetylacrylamide (NAcAAm) has also been reported by Agarwal et al.33 (Co)polymers of NAGA29 or other monomers27 whose homopolymers show UCST-type transitions with monomers whose homopolymers exhibit LCST-type behaviors have been

shown to exhibit LCST-, UCST-type, or both behaviors at precisely tuned molar compositions. Herein, we report the development of a new class of thermoresponsive copolymers based on copolymers of NAGA and DAAM whose homopolymer is nonthermosensitive. A series of statistical copolymers of poly(N-acryloylglycinamideco-diacetone acrylamide) (P(NAGA-co-DAAM)) has been synthesized via reversible addition−fragmentation chain transfer (RAFT) polymerization. Significantly, the thermoresponsive behavior of these copolymers is highly dependent on the B

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Figure 2. Thermal transitions of UCST-type (co)polymers measured by turbidimetry upon cooling in water (a), dependence of UCST on DAAM molar fraction in H2O and D2O, respectively (b), dependence of UCST of NAGA95 on the polymer concentration in water (c), and effect of salts on the UCST of NAGA99 (d). The polymer concentration is 1 wt % except for part c.

reactivity of DAAM units was slightly higher than that of NAGA units, as confirmed by 1H NMR analysis during copolymerization, suggesting that the two monomers form statistical copolymers (Figure S3). The molecular weight of the NAGA50 copolymers scaled linearly with conversion, and the dispersity (Đ) remained ∼1.2 up to near-quantitative conversions (Figure 1c). The GPC traces exhibited a gradual shift toward high molecular weights as the conversion increased, suggesting successful formation of well-defined copolymers (Figure 1d). All these features indicate that the aqueous copolymerization of NAGA with DAAM was well controlled by the RAFT process. Tunable Solution Behavior. With the series of welldefined copolymers in hand (Table 1 and Table S1), their thermoresponsive behavior was investigated using a combination of turbidity, dynamic light scattering (DLS), 1H NMR, and Fourier transform infrared (FTIR) spectroscopy. Copolymers with the NAGA molar fraction varying from 5 to 30 mol % were only slightly soluble or completely insoluble in water with no cloud point being observed upon heating or cooling at a copolymer concentration of 1 wt %, which resembles the aqueous solution behavior of the PDAAM homopolymer.40 However, when the NAGA molar fraction was varied from 60 to 85 mol %, the copolymers were permanently water-soluble. Interestingly, copolymers with other compositions exhibited either UCST- or LCST-type behavior. UCST Properties. Copolymers with NAGA as the major composition (≥95 mol %) show tunable UCST-type transitions (Figure 2). The UCST decreases from 8.5 to 4.5 °C upon cooling and from 20 to 13.5 °C upon heating (Figure 2a,b), when the DAAM molar fraction is increased from 0 to 5 mol %. PNAGA has been shown to build interpolymer complexes with poly(acrylic acid)(PAAc)41 or PNAcAAm33 via H-bonding. Similar to PNAGA, the DAAM units also possess both a hydrogen donor (secondary amide) and an acceptor (carbonyl group) that can form inter/intramolecular H-bonds. The decrease of the UCST with increasing molar fraction of DAAM suggests that the segments formed via H-bond

composition with both UCST and LCST being observed for the same type of copolymer. For the first time, changes in the copolymer compositions lead to the appearance of both UCST and LCST for the same type of copolymer. We present a detailed study of the copolymerization kinetics and the effects of copolymer composition, concentration, deuterium isotope and electrolytes on the thermal transitions of these well-defined copolymers.

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RESULTS AND DISCUSSION Polymer Synthesis and Characterization. The P(NAGA-co-DAAM) copolymers were synthesized by RAFT using 2-ethylsulfanylthiocarbonylsulfanyl-propionic acid methyl ester as the chain transfer agent (CTA) and 2,2′-azobis(2methylpropionamidine) dihydrochloride (V-50) as the radical initiator at 70 °C in water (Scheme 1). The molar fraction of DAAM was varied from 1 to 95 mol % to adjust the composition and thus the aqueous solubility of the copolymers. For all the homopolymers and copolymers, the target degree of polymerization (DP) was 200 and the conversion of monomers was above 90% (Table 1). The resulting copolymers were named as NAGA-X, where X corresponds to the molar percentage of NAGA in the copolymer. The composition of the copolymers was characterized by 1H NMR (Figure S2) and the macromolecular parameters were characterized by gel permeation chromatography (GPC). The thermal transition temperature of the UCST-type and LCST-type copolymers (1 wt %) was determined by turbidimetry upon cooling and heating, respectively. Figure 1 shows the polymerization kinetics for the copolymerization of NAGA with DAAM at molar ratios of 95:5, 90:10, and 50:50. In all cases, near-quantitative conversion was achieved within 3 h (Figure 1a), and the polymerization followed pseudo-first-order kinetics up to medium to high conversions (Figure 1b). Only a slight increase in the polymerization rate on increasing DAAM from 5 to 50 mol % was observed. In addition, the two monomers in the NAGA50 copolymers had relatively close reactivities, and the C

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Figure 3. Thermal transitions of LCST-type copolymers measured by turbidimetry upon heating in water (a), dependence of LCST of the copolymers on DAAM molar fraction in H2O and D2O, respectively (b), dependence of LCST of NAGA50 on the polymer concentration in water (c), and effect of salts on the LCST of NAGA50 (d). The polymer concentration is 1 wt % except for part c.

and the copolymer became completely soluble at a NaSCN concentration of 0.3 mol L−1. These results indicate that Hbonding is the main driving force for the phase separation at temperatures below the UCST. LCST Properties. Interestingly, further adjusting of the copolymer composition led to the unexpected observation of LCST properties for the copolymers with closer molar fractions. The LCST-type copolymers with DPs ∼ 200 exhibited a sharp response to temperature change and a relatively small hysteresis (Figures 3a and S7). The hysteresis for the LCST-type copolymers is smaller than that for the UCST-type copolymers, implying a much weaker H-bonding involved in the LCST-type copolymers.44 Since the molar fraction of NAGA and DAAM in the copolymers is close, there is a greater possibility for H-bonds to form between NAGA and DAAM. For these copolymers (from NAGA56 to NAGA34) the LCST of the copolymers decreased from 41 to 18.5 °C upon heating with increasing molar fractions of the more hydrophobic DAAM (Figure 3a). As shown in Figures 3b and S8, the lower LCSTs of the copolymers in D2O than that in H2O are due to stronger polymer chain interactions in D2O than in H2O and hence stronger inclination of aggregation during heating. The LCST of NAGA50 was found to decrease with concentration over the 5 wt % concentration range (Figures 3c and S9), due to the HB-driven LCST-type behavior caused by strong H-bonding of DAAM units.45,46 Figure 3d displays the LCST of the NAGA50 as a function of ionic strength. Addition of NaCl decreased the LCST from 26 °C in water to 21.5 °C in the presence of 0.5 mol L−1 of NaCl. In contrast, the LCST increased from 26 to 39 °C upon increasing the concentration of NaSCN from 0 to 0.5 mol L−1, due to the effect of hydrogen bond-construct agent on the H-bonding of DAAM units. Furthermore, the LCST-type transition of NAGA50 in aqueous solution was almost unaffected by pH or phosphate-buffered saline (PBS, pH = 7.4, 0.1M) (Figure S10). To investigate the influence of the molecular weight on the LCST-type behavior, copolymers with an equal molar ratio of

interactions between NAGA and DAAM may act as hydrophilic moieties and higher molar fractions of DAAM lead to morehydrophilic segments. The turbidity curves of these UCST-type copolymers showed a large hysteresis (Figure S4). From a thermodynamic point of view the cloud point upon cooling and heating should be identical when the solution is given sufficient time to equilibrate. Indeed, the observed hysteresis has been suggested to be a kinetic phenomenon.31 The molecular weights of the UCST-type copolymers with thermal transitions above 0 °C were in the same range from 28000 to 28900 g mol−1, thus ruling out the effect of molecular weight on the UCST or on the sharpness of the transition.33 In addition, the highly stable H-bonds of PNAGA are relatively difficult to break or to form.42 Therefore, the decreased hysteresis with increasing molar fractions of DAAM is possibly due to intermolecular H-bonds of NAGA and DAAM, which are weaker than the inter/intra-molecular H-bonds of PNAGA. As shown in Figures 2b and S5, the UCST of PNAGA (1 wt %) in D2O is almost 10 °C higher than that in H2O during the cooling cycle. This could be explained by the fact that CO··· D−N is more stabilized than CO···H−N and therefore the interactions among the polymer chains in D2O are relatively stronger than that in H2O.43 Moreover, it is observed that with decreasing DAAM contents in the copolymer, the difference between the UCSTs of the copolymers in H2O and D2O is enhanced, suggesting that such a strong isotope effect is mainly dominated by the NAGA units. The cloud point of the UCSTtype copolymers is highly dependent on the polymer concentration, taking PNAGA95 as the example, that is, a higher concentration leads to a higher cloud point (Figures 2c and S6). However, in dilute solution the UCST is less concentration dependent. This observation is similar to the phase transition behavior of PNAGA.31 In addition, electrolytes significantly affect the UCST of NAGA99 (Figure 2d). The cloud point decreased from 7.5 °C in pure water to 3.5 °C in the presence of 0.5 mol L−1 of NaCl. Moreover, the cloud point decreased drastically in sodium thiocyanate (NaSCN) solution, which is known to be a strong hydrogen bond-construct agent, D

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Figure 4. RAFT copolymerization of NAGA and DAAM in water at a molar ratio of [Monomer]/[V-50] = 2500 for the synthesis of copolymers of different DPs: monomer conversion vs time (a); pseudo-first-order kinetic plots (b), thermal transitions of the copolymers measured by turbidimetry (1 wt %) in water upon heating (c) and dependence of LCST of the copolymers on DP (d).

Figure 5. Temperature-dependent DLS results of (a) NAGA99 (1 wt %) on cooling and (b) NAGA50 with various concentrations on heating in H2O and D2O.

Figure 6. (a) FTIR spectra of PDAAM, PNAGA and NAGA50, and temperature dependence of phase separation fraction p for different protons of (b) NAGA90 from 40 to 0 °C and (c) NAGA50 from 10 to 45 °C, respectively.

tration under a fixed monomer concentration and [monomer]/ [V-50] ratio (Figure 4b). The LCST was lowered from 40 °C down to 20.5 °C upon increasing the actual DP from 45 to 485, indicating that this LCST-type behavior was also affected by hydrophobicity, in addition to being induced by H-bonding of DAAM units.38,47 In order to investigate the change in the aggregate structure dynamic light scattering (DLS) measurements were conducted (Figure 5). When the temperature was below the UCST of NAGA99 or above the LCST of NAGA50, the hydrodynamic

NAGA/DAAM on varying the target DP from 50 to 500 were synthesized (Table S2). The obtained copolymers were named as NAGA50-x, where x corresponds to the actual DP. Kinetic studies were conducted with target DPs being 100, 200, and 500. Representative sampling experiments showed that the polymerization was very fast and >90% conversion was achieved within 3 h of polymerization (Figure 4a). The polymerization followed pseudo-first-order kinetics up to medium to high conversions. Lower target DP resulted in a lower polymerization rate owing to a higher CTA concenE

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Macromolecules Scheme 2. Schematic Representation of Solution Behavior of P(NAGA-co-DAAM) (Co)polymers

diameter (Dh) of the copolymers first sharply increased, and then gradually leveled off, indicating that the chains formed stable aggregates. The PDAAM homopolymer was insoluble in water, while the LCST-type copolymers could form stable aggregates above the LCSTs probably due to the hydrophilic nature of PNAGA at higher temperatures which could act as stabilizing segments around the hydrophobic PDAAM segments. With regard to the effect of deuterium isotopic substitution, we could clearly find that the size of the aggregates in D2O (1 wt %) is larger than that in H2O after the thermal transition, indicating that the interactions among P(NAGA-coDAAM) chains in D2O are stronger than that in H2O,48 which is in agreement with the turbidimetry analysis. FTIR and 1H NMR Analysis. In order to elucidate the significance of H-bonding between NAGA and DAAM in the copolymers, PDAAM, PNAGA, and NAGA50 were probed by FTIR spectroscopy (Figure 6a). The Amide-I48/Amide-II49 vibrations were 1653/1551 cm−1 for PNAGA, 1666/1538 cm−1 for PDAAM, and 1659/1541 cm−1 for NAGA50, indicating that H-bonding exists between NAGA and DAAM. It is widely known that lower frequency means stronger interaction in the Amide I region of the IR spectra.50 Thus, the appearance of the band at 1659 cm−1 for NAGA50, which falls between that for PNAGA and PDAAM, suggests the H-bond between NAGA and DAAM units is weaker than that in PNAGA, which explains the smaller hysteresis of the copolymers than that of PNAGA. Variable-temperature 1H NMR analysis was used to follow the interactions and the solution behavior using UCST-type copolymer NAGA90 and LCST-type copolymer NAGA50 as the example. The peaks attributed to NAGA90 and NAGA50 both displayed an intensity reduction upon cooling or heating respectively, suggesting the occurrence of collapse and aggregation of the copolymers during their corresponding phase transitions (Figure S11). To quantitatively characterize the phase transitions of the copolymers, the phase transition fraction p was defined as p = 1 − (I/I0), where I is the integrated intensity of the given polymer signal in the spectrum of the partly separated system, and I0 is the integrated intensity of this signal when no phase separation occurs.51,52 We take the integrated intensities obtained for the respective D2O solution at 40 °C for NAGA90 and 10 °C for NAGA50 as I0. The

NAGA and DAAM units in both copolymers seemed to cooperatively participate in the phase transition process (Figure 6b,c), indicating that there exist H-bond interactions between the NAGA and DAAM units, which is in line with the FTIR analysis. Note that the copolymer segments connected via Hbonding between the NAGA and DAAM units are hydrophilic as confirmed by the good solubility of NAGA50 in water at lower temperatures. In addition, the pmax which appears after the phase transition of NAGA90 (∼1) is relatively large compared to that of NAGA50 (∼0.6) during the phase transitions, suggesting that the UCST-type transition has a rather higher degree of phase separation. In contrast, the LCST-type transition of NAGA50 was less complete presumably because the NAGA units were hydrophilic at higher temperatures. On the basis of the analysis probed by various techniques, the distinct solubility properties of the P(NAGA-co-DAAM) copolymers during heating/cooling are summarized in Scheme 2. The copolymers with NAGA as the major component show UCST-type behavior; in contrast, LCST-type behavior for the copolymers with close molar fractions is observed. Note that the UCST-type copolymers are more completely dehydrated after the phase transition than that for the LCST-type copolymers. In addition, the copolymers with less molar fractions of NAGA were only slightly soluble or completely insoluble in water.

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CONCLUSION We have developed a novel family of thermoresponsive copolymers of P(NAGA-co-DAAM) that have both UCSTand LCST-type thermal transitions. Well-defined copolymers of tunable compositions are effectively synthesized by RAFT aqueous copolymerization using different feeding recipe. The copolymer segments formed through H-bonding between the NAGA and DAAM units act as hydrophilic moieties, which is revealed by turbidimetry, DLS, FTIR and variable-temperature 1 H NMR analysis. Decreased cloud point and smaller hysteresis between the heating and cooling cycles of the UCST-type copolymers are observed with increasing molar fractions of DAAM. The LCST-type behavior is believed to be associated with the H-bonding and hydrophobic effects of the polymer chains, and the cloud point of the LCST-type copolymers decreases with increasing molar fractions of the more F

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(8) Lu, Y.; Yuan, J.; Polzer, F.; Drechsler, M.; Preussner, J. In Situ Growth of Catalytic Active Au - Pt Bimetallic Nanorods in Thermoresponsive Core - Shell Microgels. ACS Nano 2010, 4 (12), 7078−7086. (9) Dincer, S.; Tuncel, A.; Piskin, E. A potential gene delivery vector: N-isopropylacrylamide-ethyleneimine block copolymers. Macromol. Chem. Phys. 2002, 203 (10−11), 1460−1465. (10) Twaites, B. R.; de las Heras Alarcon, C.; Lavigne, M.; Saulnier, A.; Pennadam, S. S.; Cunliffe, D.; Gorecki, D. C.; Alexander, C. Thermoresponsive polymers as gene delivery vectors: Cell viability, DNA transport and transfection studies. J. Controlled Release 2005, 108 (2−3), 472−483. (11) Reese, C. E.; Mikhonin, A. V.; Kamenjicki, M.; Tikhonov, A.; Asher, S. A. Nanogel nanosecond photonic crystal optical switching. J. Am. Chem. Soc. 2004, 126 (5), 1493−1496. (12) Zhu, H.; Li, Y.; Qiu, R.; Shi, L.; Wu, W.; Zhou, S. Responsive fluorescent Bi2O3@PVA hybrid nanogels for temperature-sensing, dual-modal imaging, and drug delivery. Biomaterials 2012, 33 (10), 3058−3069. (13) Wu, W.; Zhou, T.; Berliner, A.; Banerjee, P.; Zhou, S. Smart Core-Shell Hybrid Nanogels with Ag Nanoparticle Core for Cancer Cell Imaging and Gel Shell for pH-Regulated Drug Delivery. Chem. Mater. 2010, 22 (6), 1966−1976. (14) Liu, S.; Qiao, W.; Cao, G.; Chen, Y.; Ma, Y.; Huang, Y.; Liu, X.; Xu, W.; Zhao, Q.; Huang, W. Smart Poly(N-isopropylacrylamide) Containing Iridium(III) Complexes as Water-Soluble Phosphorescent Probe for Sensing and Bioimaging of Homocysteine and Cysteine. Macromol. Rapid Commun. 2013, 34 (1), 81−86. (15) Seuring, J.; Agarwal, S. Polymers with Upper Critical Solution Temperature in Aqueous Solution: Unexpected Properties from Known Building Blocks. ACS Macro Lett. 2013, 2 (7), 597−600. (16) Zhang, P.; Li, W. C.; Zhai, X. Y.; Liu, C. J.; Dai, L. M.; Liu, W. G. A facile and versatile approach to biocompatible ″fluorescent polymers’’ from polymerizable carbon nanodots. Chem. Commun. 2012, 48 (84), 10431−10433. (17) 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 (6), 2325−2329. (18) Zhang, Z. H.; Sun, W. H.; Wu, P. Y. Highly Photoluminescent Carbon Dots Derived from Egg White: Facile and Green Synthesis, Photoluminescence Properties, and Multiple Applications. ACS Sustainable Chem. Eng. 2015, 3 (7), 1412−1418. (19) Lau, A. C. W.; Wu, C. Thermally sensitive and biocompatible poly(N-vinylcaprolactam): Synthesis and characterization of high molar mass linear chains. Macromolecules 1999, 32 (3), 581−584. (20) Kjoniksen, A. L.; Laukkanen, A.; Galant, C.; Knudsen, K. D.; Tenhu, H.; Nystrom, B. Association in aqueous solutions of a thermoresponsive PVCL-g-C11EO42 copolymer. Macromolecules 2005, 38 (3), 948−960. (21) Boyer, C.; Whittaker, M. R.; Luzon, M.; Davis, T. P. Design and Synthesis of Dual Thermoresponsive and Antifouling Hybrid Polymer/Gold Nanoparticles. Macromolecules 2009, 42 (18), 6917− 6926. (22) Wischerhoff, E.; Uhlig, K.; Lankenau, A.; Borner, H. G.; Laschewsky, A.; Duschl, C.; Lutz, J. F. Controlled cell adhesion on PEG-based switchable surfaces. Angew. Chem., Int. Ed. 2008, 47 (30), 5666−5668. (23) Maji, T.; Banerjee, S.; Biswas, Y.; Mandal, T. K. Dual-StimuliResponsive L-Serine-Based Zwitterionic UCST-Type Polymer with Tunable Thermosensitivity. Macromolecules 2015, 48 (14), 4957− 4966. (24) Zhao, J.; Burke, N. A. D.; Stover, H. D. H. Preparation and study of multi-responsive polyampholyte copolymers of N-(3aminopropyl) methacrylamide hydrochloride and acrylic acid. RSC Adv. 2016, 6 (47), 41522−41531. (25) Cao, X. T.; An, Z. S. RAFT Synthesis in Water of Cationic Polyelectrolytes with Tunable UCST. Macromol. Rapid Commun. 2015, 36 (23), 2107−2110.

hydrophobic DAAM units. Thermoresponsive profiles of the copolymers are present over a wide range of concentration, different composition, deuterium isotopic substitution, varying targeting DPs and the presence of electrolytes. The appearance of both UCST- and LCST-type thermal transitions for the same type of copolymer at different composition regimes is unprecedented and is expected to facilitate their applications due to the simplicity of the copolymerization. The copolymerization of monomers with the ability to form different types of H-bonds also provides a potential for discovering new types of thermosensitive polymers.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b00020. Experimental details, data of polymer characterization, 1 H NMR spectra, and turbidity curves of NAGA and copolymers (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (P.W.). *E-mail: [email protected] (Z.A.). ORCID

Zesheng An: 0000-0002-2064-4132 Peiyi Wu: 0000-0001-7235-210X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We express thanks for the financial support from the National Natural Science Foundation of China (51473038 and 21674025).

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DOI: 10.1021/acs.macromol.7b00020 Macromolecules XXXX, XXX, XXX−XXX

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DOI: 10.1021/acs.macromol.7b00020 Macromolecules XXXX, XXX, XXX−XXX