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Remarkable structure effects on thermoresponsive properties of dendritic macromolecules
Polymer 55 (2014) 3672e3679
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Remarkable structure effects on thermoresponsive properties of dendritic macromolecules Xiong Tao, Kun Liu, Wen Li*, Afang Zhang* Lab of Polymer Chemistry, Department of Polymer Materials, College of Materials Science and Engineering, Department of Chemistry, Shanghai University, Nanchen Street No. 333, Shanghai 200444, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 19 March 2014 Received in revised form 10 May 2014 Accepted 4 June 2014 Available online 11 June 2014
Amphiphilic dendritic macromonomers and their corresponding dendronized polymers were synthesized, and their thermoresponsive properties investigated. These dendritic macromolecules are constructed with a second generation lysine-based dendron as the interior (hydrophobic part) and oligoethylene glycol (OEG) linear chains or dendrons (hydrophilic part) covered in their periphery. By changing from OEG linear chains to OEG dendrons, these dendritic macromolecules carry on their periphery different density of OEG moieties, to investigate the structural effects on their thermoresponsiveness. Topology of dendritic macromolecules changes through polymerization, and the fan-shaped dendritic macromonomers transfer into the corresponding cylindrically shaped dendronized polymers. Furthermore, the amphiphilic characteristic of these dendritic entities can be switched due to the thermally-induced dehydration of OEG moieties. It was found that topology, OEG density in the periphery and switchable amphiphilicity of these dendritic macromolecules show significantly effects on their thermoresponsiveness. © 2014 Elsevier Ltd. All rights reserved.
Keywords: Dendritic macromolecules Dendronized polymers Thermoresponsive polymers
1. Introduction Thermoresponsive polymers undergo a thermally-induced entropy-driven dehydration, followed by chain collapse and aggregation around their phase transition temperatures, consequently, their aqueous solutions turn from homogeneous (transparent) into heterogeneous (turbid) [1,2]. This process involves the transformation of polymer chains (partially) from hydrophilic to hydrophobic. A variety of thermoresponsive polymers with various chemical structures and architectures have been developed to date through covalent [3e6] or non-covalent linkages [7e9] to show tunable thermoresponsive properties, and been utilized for applications ranging from surface modifications to biomaterials [10e15]. These representatives with phase transition temperature in the vicinity of physiological temperature and capable of fast and sharp response to temperature variation are especially attractive due to their promising applications in bio-related materials [16]. Generally speaking, the phase transition temperatures are dominated by the over-all hydrophilicity and hydrophobicity balance in the polymers. The more hydrophilic ones show higher
* Corresponding authors. Tel.: þ86 21 66138053; fax: þ86 21 66131720. E-mail addresses: [email protected] (W. Li), [email protected] (A. Zhang). http://dx.doi.org/10.1016/j.polymer.2014.06.010 0032-3861/© 2014 Elsevier Ltd. All rights reserved.
phase transition temperatures than the more hydrophobic counterparts. Besides the structural hydrophilicity, topology (architecture) was recently proved to show significant influence on the phase transition temperatures [17,18]. On changing polymer architecture from linear shape into cyclic [19] or dendritic ones [20e22], the thermoresponsive properties change obviously. The phase transition temperature can also be regulated through supramolecular interactions. With introduction of hydrophilic or hydrophobic guest molecules, the thermoresponsiveness of host polymers can be tuned [23e25]. Furthermore, secondary structures of polymers, such as helical conformations, have recently been proven to show influence on the phase transition temperatures. Polymers with the higher ordered structures possess a lower transition temperature due to the better arrangement of pendants [26]. By combination of two different types of thermoresponsive polymer segments together, it is possible to have doubly thermoresponsive behavior, which displays more than one phase transitions [27e30]. Recently we have developed a novel series of thermoresponsive dendritic macromolecules, including dendrimers and dendronized polymers [31e34], which show intriguing thermoresponsive properties with unprecedented fast and sharp phase transitions in the temperature range of 30e65 C [35e39]. These dendritic macromolecules were constructed with OEG dendrons in the
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entire, periphery, or pendent groups. OEG units were selected because they can not form strong hydrogen bondings with water. Notably, the phase transition temperatures are dominated by the hydrophilicity of periphery units, and the interiors show minor influence on the aggregation but collapse heterogeneously [40,41]. This property makes these dendritic macromolecules act as a smart molecular box, and provides chances to change the interiors to have functionalities but still retain the responsive properties by choosing proper peripheral units [38,42]. In order to examine deeply the structural effects on their thermoresponsive properties, we here report on synthesis and thermoresponsiveness of closely related dendritic macromolecules. These dendritic analogs are constructed with hydrophobic lysine-based G2 dendron as the interior and hydrophilic OEG chains or dendrons on the periphery (Fig. 1). After polymerization, the fan-shaped dendritic macromonomers transfer into cylindrical dendronized polymers. The thermoresponsive properties of both dendritic macromonomers and dendronized polymers were examined with regard to structural amphiphilicity, molecular topology, as well as shielding efficiency of the periphery.
2. Experimental section 2.1. Materials Compounds 3 and 5 were synthesized according to our previous report [35,43]. Tetrahydrofuran (THF) was refluxed over lithium aluminum hydride and dichloromethane (DCM) over CaH2 for drying. Diisopropyl ethyl amine (DiEA) and triethyl amine (TEA) were dried over NaOH pallets. Methacryloyl chloride (MAC) was freshly distilled before used. Azobis(isobutyronitrile) (AIBN) was recrystallized twice from methanol. Other reagents and solvents were purchased at reagent grade and used without further purification. MachereyeNagel precoated TLC plates (silica gel 60 G/ UV254, 0.25 mm) were used for thin-layer chromatography (TLC) analysis. Silica gel 60 M (MachereyeNagel, 0.04e0.063 mm, 200e300 mesh) was used as the stationary phase for column chromatography.
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2.2. Instrumentation and measurements 1 H NMR spectra were recorded on a Bruker AV 500 (1H: 500 MHz) spectrometer, and chemical shifts are reported as d value (ppm) relative to internal Me4Si. Gel permeation chromatography (GPC) measurements were carried out on a Waters GPC e2695 instrument with 3 column set (Styragel HR3þHR4þHR5) equipped with refractive index detector (Waters 2414), and DMF (containing 1 g L1 LiBr) as eluant at 45 C. Multiangle light scattering detector (Wyatt Technology Corporation, Down EOS 243-E) was used for some of the measurements. The calibration was performed with poly(methyl methacrylate) standards with molar masses in the range of Mp ¼ 2580e981,000 (Polymer Standards Service USA). The refractive index increment (dn/dc) of the polymers were measured with SEC-3010 RI detector (WGE Dr. Bures Corporation) operated with a monochromatic light source (l ¼ 620 nm). The measured dn/ dc values of PTEG and PG3 at 30 C and in DMF were 0.162 and 0.098 mL g1, respectively. AFM measurements were conducted on Bruker Nanoscope VIII Multi-Mode operated with a “J” scanner (scan range 125 mm 125 mm) and operated in Peak Force Mode at room temperature in air. Bruker silicon Tip on Nitride Lever cantilevers (T: 0.65 mm, L: 115 mm, W: 25 mm, fo: 70 mm, k: 0.4 N/m) were used. UV/vis turbidity measurements were carried out on a PE UV/vis spectrophotometer (Lambda 35) equipped with a thermocontrolled bath. Aqueous polymer solutions were placed in the spectrophotometer (path length 1 cm) and heated or cooled at a rate of 0.2 C min1. The absorptions of the solution at l ¼ 500 nm were recorded every 5 s. The cloud point temperature (Tcp) is determined to be that at which the transmittance at l ¼ 500 nm had reached 50% of its initial value. General Procedure for Etherification (A). NaH (6.00 mmol) and KI (0.20 mmol) were added to triethylene glycol monoethyl ether (Et-TEG, 1.20 mmol) in THF (15 mL). The solution was stirred at 0e5 C for 0.5 h, and then bromoacetic acid (1.00 mmol) in THF (5 mL) was slowly added over 0.5 h. The resulting reaction mixture was stirred at 0 C under nitrogen atmosphere for another 12 h, and then quenched with MeOH. After evaporation of the solvent the residue was dissolved in H2O and then extracted with DCM. After
Fig. 1. Chemical structures of the dendritic macromonomers MTEG and MG3, as well as their corresponding polymers PTEG and PG3. EtG1 represents the first generation OEG dendron.
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washed with KHSO4, the organic phase was washed three times with water, and then dried over MgSO4 to provide the target product. General Procedure for Esterification (B). p-Nitrophenol or pentafluorophenol (1.20 mmol) in dry DCM (15 mL) was added dropwise to a solution of compound 2a or 3 (1.00 mmol) and 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDC,HCl, 1.20 mmol) in dry DCM (20 mL) at 15 C. The mixture was stirred for 12 h at 15 C and then extracted with DCM. The combined organic phase was dried over MgSO4. Purification by column chromatography afforded the target compound as colorless oil. General Procedure for Amide Coupling (C). Compound 2b or 4 (6.00 mmol) in DMF (30 mL) was added dropwise into a solution of compound 5 (1.00 mmol) and DiEA (6.00 mmol) in water (10 mL) at 0 C. The mixture was kept at that temperature for 2 h, and then allowed to reaction overnight at room temperature. Evaporation of the solvents in vacuo at room temperature gave a residue. It was treated with DCM, and washed successively with NaHCO3 and brine. All aqueous phases were extracted with DCM three times. The combined organic phases were dried over MgSO4, and purified with column chromatography to afford the product as colorless oil. General Procedure for Macromonomer synthesis (D). MAC (2.00 mmol) was added dropwise to a mixture of the dendron alcohol (1.00 mmol), TEA (10.00 mmol) and DMAP (0.10 g) in dry THF (25 mL) at 0 C over 2 h. The mixture was stirred for 6 h at r.t., and then the reaction was quenched with MeOH. After washing successively with aqueous NaHCO3 solution and brine, the organic phase was dried over MgSO4. Purification by column chromatography afforded the monomer as colorless oil. General Procedure for Free Radical Polymerization (E). A solution of macromonomer (0.30e0.50 g) and AIBN (0.5 wt% based on the macromonomer) in DMF (0.2 mL) inside a Schlenk tube was degassed by several freezeepumpethaw cycles, and then kept at 70 C with stirring for a predetermined time. The polymerization was stopped by cooling, and the polymer was dissolved in DCM and purified by column chromatography (silica gel, DCM eluant). Compound 2a. According to the general procedure A from 1 (0.77 g, 4.32 mmol), bromoacetic acid (0.50 g, 3.60 mmol), NaH (95%, 0.55 g, 21.60 mmol) and KI (0.12 g, 0.72 mmol), compound 2a was yielded as a colorless oil (0.59 g, 70%). 1H NMR (CDCl3): d ¼ 1.23e1.26 (t, 3H, CH3), 3.55e3.59 (q, 2H, CH2), 3.62e3.68 (m, 6H, CH2), 3.69e3.72 (m, 4H, CH2), 3.75e3.77 (m, 2H, CH2), 4.16 (s, 2H, CH2). Compound 2b. According to the general procedure B from 2a (0.50 g, 2.12 mmol), p-nitrophenol (0.35 g, 2.54 mmol) and EDC,HCl (0.49 g, 2.54 mmol), purification by column chromatography (hexane/ethyl acetate ¼ 2:1, v/v) afforded 2b as a colorless oil (0.60 g, 80%). 1H NMR (CDCl3): d ¼ 1.22e1.25 (t, 3H, CH3), 3.52e3.57 (q, 2H, CH2), 3.60e3.62 (m, 2H, CH2), 3.66e3.70 (m, 6H, CH2), 3.76e3.78 (m, 2H, CH2), 3.85e3.87 (m, 2H, CH2), 4.49 (s, 2H, CH2), 7.35e7.37 (d, 2H, CH), 8.30e8.32 (d, 2H, CH). Compound 4. According to the general procedure B from 3 (0.90 g, 1.38 mmol), pentafluorophenol (0.31 g, 1.66 mmol) and EDC.HCl (0.32 g, 1.66 mmol), purification by column chromatography with ethyl acetate eluant afforded 4 as a colorless oil (0.83 g, 73%). 1H NMR (CDCl3): d ¼ 1.20e1.24 (m, 9H, CH3), 3.51e3.56 (m, 6H, CH2), 3.59e3.61 (m, 6H, CH2), 3.65e3.70 (m, 12H, CH2), 3.73e3.76 (m, 6H, CH2), 3.83e3.85 (t, 2H, CH2), 3.90e3.92 (t, 4H, CH2), 4.24e4.26 (t, 4H, CH2), 4.30e4.32 (t, 2H, CH2), 7.46 (s, 2H, CH). Compound 6a. According to the general procedure C from 5 (0.68 g, 1.27 mmol), 2b (2.73 g, 7.63 mmol) and DiEA (0.99 g, 7.63 mmol), purification by column chromatography (DCM/ MeOH ¼ 10:1, v/v) afforded 6a as a colorless oil (1.58 g, 92%). 1H NMR (CDCl3): d ¼ 1.21e1.24 (t, 12H, CH3), 1.33e1.44 (m, 8H, CH2),
1.49e1.58 (m, 8H, CH2), 1.66e1.75 (m, 2H, CH2), 1.87e1.92 (m, 2H, CH2), 3.16e3.35 (m, 6H, CH2 þ CH3), 3.52e3.56 (q, 8H, CH2), 3.59e3.61 (m, 9H, CH2), 3.65e3.66 (m, 9H, CH2), 3.68e3.7 (m, 32H, CH2), 3.84e3.9 (m, 3H, CH2 þ CH3), 3.99 (s, 4H, CH2), 4.01e4.07 (m, 4H, CH2), 4.38e4.43 (q, 4H, CH2 þ CH3), 6.84e6.85 (d, 1H, NH), 6.98e6.99 (t, 1H, NH), 7.16e7.18 (t, 1H, NH), 7.3e7.31 (d, 1H, NH), 7.41e7.43 (dd, 2H, NH). Compound 6b. According to the general procedure C from 5 (0.37 g, 0.69 mmol), 4 (3.4 g, 4.16 mmol) and DiEA (0.54 g, 4.16 mmol), purification by column chromatography (DCM/ MeOH ¼ 40:1) afforded 6b as a colorless oil (1.50 g, 74%). 1H NMR (CDCl3): d ¼ 1.17e1.22 (m, 34H, CH3), 1.26e2.00 (br, 18H, CH2), 2.49 (br, 5H, CH2), 3.08 (br, 1H, CH2), 3.29e3.43 (br, 5H, CH2 þ CH), 3.48e3.54 (m, 24H, CH2), 3.56e3.59 (m, 24H, CH2), 3.62e3.65 (m, 46H, CH2), 3.67e3.70 (m, 24H, CH2), 3.77e3.79 (m, 24H, CH2), 4.08e4.15 (m, 23H, CH2), 4.63e4.68 (m, 2H, CH), 7.08e7.12 (br, 10H, CH þ NH), 7.41 (s, 2H, NH), 7.59 (s, 1H, NH), 7.72e7.74 (d, 1H, NH). Monomer MTEG. According to the general procedure D from 6a (0.46 g, 0.37 mmol), TEA (0.37 g, 3.68 mmol), MAC (77 mg, 0.74 mmol), and DMAP (0.10 g), purification by column chromatography (DCM/MeOH ¼ 20:1) afforded MTEG as a colorless oil (0.47 g, 96%). 1H NMR (CDCl3): d ¼ 1.20e1.23 (t, 12H, CH3), 1.26e1.40 (m, 8H, CH2), 1.54e1.58 (m, 8H, CH2), 1.66e1.70 (m, 2H, CH2), 1.83e1.92 (m, 2H, CH2), 1.94 (s, 3H, CH3), 3.10e3.14 (m, 1H, CH2), 3.20e3.33 (m, 5H, CH2 þ CH), 3.51e3.56 (q, 8H, CH2), 3.59e3.61 (m, 8H, CH2), 3.64e3.66 (m, 8H, CH2), 3.68e3.70 (m, 32H, CH2), 3.97e3.98 (m, 4H, CH2), 4.00e4.06 (m, 4H, CH2 þ CH), 4.10e4.18 (m, 3H, CH2 þ CH), 4.38e4.41 (m, 2H, CH), 5.59e5.60 (t, 1H, CH), 6.13 (s, 1H, CH), 7.12e7.14 (m, 2H, NH), 7.22e7.24 (t, 2H, NH), 7.44e7.48 (t, 2H, NH). HRMS (ESI): m/z calcd for C62H116N6O24 [M þ Na]þ 1351.7939. Found: 1351.7893. Monomer MG3. According to the general procedure D from 6b (1.30 g, 0.45 mmol), TEA (0.10 g, 4.45 mmol), MAC (93 mg, 0.89 mmol), and DMAP (0.10 g), purification by column chromatography (DCM/MeOH ¼ 30:1) afforded MG3 as a colorless oil (1.30 g, 98%). 1H NMR (CDCl3): d ¼ 1.17e1.23 (m, 36H, CH3), 1.27e1.85 (m, 18H, CH2), 1.91 (s, 3H, CH3), 2.01e2.16 (m, 10H, CH2), 3.06e3.07 (br, 1H, CH2), 3.37e3.43 (br, 7H, CH2 þ CH), 3.49e3.54 (m, 24H, CH2), 3.57e3.60 (m, 24H, CH2), 3.63e3.73 (m, 72H, CH2), 3.78e3.81 (m, 24H, CH2), 4.06e4.17 (m, 27H, CH2), 4.65e4.69 (m, 2H, CH), 5.58 (s, 1H, CH2), 6.13 (s, 1H, CH2), 7.05e7.13 (m, 10H, CH þ NH), 7.39e7.42 (d, 2H, NH), 7.71 (s, 2H, NH). HRMS (ESI): m/z calcd for C146H252N6O56 [M þ Na]þ 3008.6923. Found: 3008.6948. Polymer PTEG. According to the general procedure E from MTEG (0.34 g) and AIBN (1.70 mg) in DMF (0.15 mL) (5 h at 70 C), PTEG was yielded as a colorless foam (0.28 g, 82%). 1H NMR (d6-DMSO, 80 C): d ¼ 0.81 þ 1.00 (br, 3H, CH3), 1.05e1.11 (m, 12H, CH3), 1.23e2.06 (br, 3H, CH3), 3.39e3.52 (m, 42H, CH2), 3.69 (br, 9H, CH2 þ CH), 4.02 (br, 9H, CH2 þ CH), 4.80 (br, 3H, NH), 5.40 (br, 1H, CH), 6.57 (br, 3H, NH). Some proton signals from the backbone were not resolved in the 1H NMR spectrum. Polymer PG3(L). According to the general procedure E from MG3 (0.50 g) and AIBN (2.00 mg) in DMF (0.15 mL) (24 h at 70 C), PG3(L) was yielded as a colorless foam (0.10 g, 20%). 1H NMR (d6-DMSO, 80 C): d ¼ 1.07e1.08 (br, 36H, CH3), 1.28e1.80 (br, 24H, CH2), 3.21 (br, 6H, CH2), 3.44e3.70 (br, 150H, CH2), 4.08 (br, 26H, CH2), 2.09 (br, 2H, CH), 7.12e7.18 (br, 8H, CH), 7.53e7.94 (br, 6H, NH). Some proton signals from the backbone were not resolved in the 1H NMR spectrum. Polymer PG3(H). AIBN (0.37 mg) was added into liquid monomer MG3 (0.27 g) inside a Schlenk tube, and dissolved. The mixture was then thoroughly deoxygenated by three freezeepumpethaw cycles and stirred at 70 C for 24 h. After cooling to r.t., the polymer was dissolved in DCM and purified by silica gel column chromatography with DCM as an eluant. PG3(H) was yielded (0.13 g, 50%)
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as a colorless solid. 1H NMR (d6-DMSO, 80 C): d ¼ 1.04e1.09 (br, 36H, CH3), 1.24e1.58 (br, 15H, CH2), 3.39e3.66 (br, 172H, CH2), 4.50e4.59 (br, 3H, CH2), 7.07 (br, 8H, CH þ NH), 7.82e8.05 (br, 4H, NH). Some proton signals from the backbone were not resolved in the 1H NMR spectrum. 3. Results and discussion 3.1. Synthesis of dendritic macromonomers and polymers The synthesis procedure for two dendritic macromonomers cored with a second generation lysine-based dendron but carrying different oligoethylene glycol (OEG) units were illustrated in Scheme 1. Triethylene glycol monoethyl ether (1) was reacted with bromoacetic acid through etherification reaction to afford compound 2a. Followed by the esterification reaction with p-nitrophenol, the active ester 2b was formed, which was reacted with lysine-based G2 dendron (5) to afford the dendron alcohol (6a). Esterification with MAC afforded the target macromonomer MTEG. With similar procedures, the dendritic macromonomer MG3 carrying four branched OEG dendrons were prepared. The polymerization of MTEG and MG3 was carried out in DMF solutions at 70 C in the presence of AIBN as initiator to yield the corresponding polymers PTEG and PG3(L), respectively. For comparison, MG3 was also polymerized in bulk at 70 C to afford PG3(H). All macromonomers and polymers were characterized by 1H NMR spectroscopy (for the spectra, see supporting Information). The molar masses of these polymers were determined by GPC measurements with DMF as eluant and PMMA as standards, and results are summarized in Table 1. As expected, PG3(H) obtained from bulk polymerization shows a much larger molar mass than that from polymerization in DMF. It is necessary to point out that, GPC measurements underestimate greatly the molar masses of these
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bulk polymers [44]. Examining the structural difference of PTEG and PG3, it should not be difficult to find that the latter is much thicker than the former due to the peripheral OEG dendrons, therefore, these polymers should be able to be directly identified with AFM. Actually, AFM measurements verified this conjecture, and PG3 shows a height of about 2 nm (Fig. S1a), which is much larger than that for PTEG (height ~ 1 nm, Fig. S1b). Therefore, AFM image shown in Fig. 2a obtained from a mixture of PTEG and PG3(H) in chloroform solution contains molecular objects of two distinct heights. The more bright objects with apparent height of ~2 nm represent the polymer chains from PG3(H), while the less bright objects with apparent height of ~1 nm correspond to the polymer chains from PTEG (Fig. 2b). 3.2. Thermoresponsive behavior of dendritic macromonomers The thermoresponsive properties of the amphiphilic macromonomers were first checked. Due to the abundant hydrophilic amide linkages between OEG chains and the lysine dendron, MTEG is too hydrophilic to show any thermally-induced aggregation behavior even up to 100 C. In contrast, these hydrophilic amide linkages were shielded efficiently by the densely covered OEG dendrons, therefore, MG3 shows a typical thermoresponsive behavior upon heated to elevated temperature (30e45 C). Its thermally-induced aggregation was thus followed with UV/vis spectroscopy, and the transmittance curves at different concentrations were recorded (Fig. 3). At low concentration (c < 0.50 wt %) the transmittance curves seems normal but the aggregation spans a broad temperature range (D ~ 10 K). As expected, the macromonomer starts to aggregate at a lower temperature with increase of solution concentration. These are typical for the thermoresponsive motifs of low molar masses [45]. Notably, the transmittance curves exhibit a platform during the thermally-induced
Scheme 1. Synthesis procedure for the monomers (MTEG and MG3). Reagents and conditions: a) bromoacetic acid, NaH, KI, THF, 0 C, 12 h, (70%). b) p-nitrophenol, EDC.HCl, DCM, 15 C, overnight (80%). c) Pfp-OH, EDC.HCl, DCM, 15 C, N2, overnight (73%). d) 2b or 4, DiEA, DMF/H2O, 0 C, overnight (93% and 74% for 6a and 6b, respectively). e) 6a or 6b, MAC, TEA, DMAP, THF, 0 C, 8 h (96% and 98% for MTEG and MG3, respectively). Abbreviations: DCM ¼ dichloride methane, DiEA ¼ diisopropyl ethyl amine, DMF ¼ N,Ndimethylformamide, DMAP ¼ N,N-dimethyl amino pyridine, MAC ¼ methacryloyl chloride, NpeOH ¼ 4-nitrophenol, Pfp-OH ¼ pentafluorophenol, TEA ¼ triethyl amine, THF ¼ tetrahydrofuran.
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Table 1 Conditions for and results of the polymerization of MTEG and MG3. Entry
PTEG PG3(L) PG3(H)
Polymerization conditionsa
Yield (%)
Monomers
[M] (mol L1)
Time (h)
MTEG MG3 MG3
0.51 0.26 0.37
5 24 24
82 20 50
GPCb Mn 104
PDI
25.13 2.93 9.91
1.94 1.83 2.39
Mwc 104
Tcpd ( C)
54.37 13.57 94.94
55.6 40.4 33.1
Polymerizations were carried out at 70 C in the present of AIBN (0.5 wt % based on monomer). Determined by GPC with DMF as eluant containing 0.1 wt % LiBr (calibrated with poly(methyl methacrylate) standards); Mn represents the numbereaverage molecular weight. c Mw represents the weighteaverage molecular weight, and was determined by multiangle light scattering measurements. d The cloud point temperatures (Tcps) of the polymers were determined as the temperature at 50% of the initial transmittance at l ¼ 500 nm. Concentration of polymers ¼ 0.25 wt%. a
b
Fig. 2. (a) AFM height image from a mixture of PTEG and PG3(H). (b) Cross-sectional profile of AFM images at the position indicated at the dotted line in (a). The sample was prepared through spin-coating (3000 rpm) from a chloroform solution onto mica.
aggregation processes in case concentration is higher than 1.00 wt % (Fig. 3). Appearance of the platform suggests that aggregation of the macromonomer induced by dehydration of OEG units is hindered by rehydration of the molecule (or part of the molecule) with increase of solution temperature. Through examining chemical structure of the macromonomer, it's not difficult to find the hydrophobic lysine moieties can not be easily hydrated. The hydration enhancement with temperature should mainly come from the amide linkages between lysine dendron and OEG dendrons, which balances the driving force from the collapse of OEG units, and results in hindering the aggregation process. However, when solution temperature increases further to a higher stage, the enhanced hydrophobicity from the collapsed OEG units compensates the
Fig. 3. Plots of transmittance versus temperature for MG3 at different concentrations. Heating rate ¼ 0.2 K min1.
temperature enhanced hydrophilicity from the amide units, leading to a further aggregation. The transmittance below the phase transition temperature reduces from 97% to 53% when solution concentration increases from 0.12% to 3.00%, indicating that obvious aggregations formed in higher concentration solutions. This concentration-induced preaggregation should be originated from the amphiphilicity of MG3, which may the prerequisite for the formation of the platform during the phase transition processes. The monomer concentration showed minor influence on the first transition temperature, suggesting that aggregation at this stage is dominated by collapse of densely packed OEG moieties from the same preaggregates. However, the second transition temperature reduced significantly with the increase of monomer concentration, indicating that aggregation at this stage is mainly processed from collapse of OEG moieties within different preaggregates, where concentration plays an important role in aggregation kinetics. In order to verify above hypothesis, 1H NMR spectra of MG3 were recorded in mixed solutions of D2O and H2O at different temperatures (Fig. 4. For full spectra, see Fig. S2 in Supporting Information) [46]. The proton signals corresponding to aromatic ring (Ph-CH) and ethoxyl terminals (EteCH2) from the OEG-based dendron become broad and start to decrease their intensities at 28e30 C, which is a direct prove for the dehydration of the dendron at this temperature stage. This result shows good agreement with UV measurements that the first phase transition for MG3 starts at 28e30 C for the concentration used (2.00 wt %). The dehydration tendencies for OEG moieties enhance with the increase of solution temperature, indicating their continuous dehydration and collapse. In contrast, the heights and intensities of proton signals from lysine moieties including methylene (LysCH2) and the amide (CONH) increase initially at a lower temperature, and start to reduce at a much higher temperature (Fig. S3).
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Fig. 4. Partial temperature-dependent 1H NMR spectra of MG3 in H2O: D2O (v:v ¼ 3:1). Polymer concentration ¼ 2.00 wt %.
Around 29 C, where the proton signals from OEG dendron decays, the intensities for the proton signal from amide and lysine moieties increase with temperature. Further increase of temperature to 35 C, proton signals from amide and lysine moieties start to broaden and reduce their intensities, indicating enhanced collapse and aggregation of the molecule [47]. The different tendency of proton signal intensities from amide and lysine moieties by comparing to those from OEG dendrons upon increase of temperature provides a solid support that, hydration enhancement of amide and lysine moieties with the increase of temperature contributes significantly to the over-all hydrophilicity of the molecule, which hinders the aggregation progress thermally-induced by collapse of OEG units. This effect diminishes at a higher temperature when enriched hydrophobicity from the extensively collapsed OEG moieties overcomes the contribution from hydrophilicity enhancement of the amide and lysine units.
influence on their Tcps. Polymer with high molar mass [PG3(H)] shows a much smaller Tcp than its counterpart of lower molar mass [PG3(L)]. The effects of polymer concentration on their thermoresponsive properties are also remained. With decrease of solution concentration from 2.0% to 0.12%, DTcp < 4 K for PTEG, and DTcp < 2 K for PG3(L) and PG3(H), indicating that polymer concentration shows minor effects (see Fig. S4 for the transmittance curves). This is a typical feature for thermoresponsive dendronized polymers [35e37]. It's interesting to point out that the phase transition temperatures for MG3 and PG3(L) are happen to be similar. MG3 carries at its both ends hydrophobic groups, and the hydrophobic contribution from methacrylate moiety compensates the hydrophilicity from the amide linkages, resulting in a much low phase transition temperature. In contrast, the cylindrical geometry from PG3(L) provides sufficient shielding effect from the periphery, which diminishes contribution of the hydrophobic interior on the phase transition, leading to the phase transition temperature dependent on the periphery.
3.3. Thermoresponsive behavior of the dendronized polymers Both types of polymers PTEG and PG3 are water-soluble below 25 C. In contrast to its monomer counterpart MTEG which is not thermoresponsive, PTEG with the same hydrophilicity show typical thermoresponsive properties, suggesting that cylindrical molecular topology contribute significantly to mediate the thermoresponsive properties [42]. The aqueous solutions of PG3s are clear but turn into turbid at elevated temperature. Their thermoresponsive behaviors are then investigated on macro level by using UV/vis spectroscopy, and the results are plotted in Fig. 5. Overall, all polymers show reversible transitions with a small hysteresis (D ~ 2 K). Tcps for PTEG, PG3(L), and PG3(H) are 55.6, 40.4 and 33.1 C, respectively. PTEG carrying linear OEG chains on its periphery shows a much higher Tcp than these carrying branched OEG dendrons, indicating that grafting density of OEG chains shows significant contribution to the kinetics of OEG collapse, and higher grafting density facilitates considerably the thermally-induced aggregation. Molar mass of polymers also show accessory
Fig. 5. Plots of transmittance versus temperature for 0.25 wt % aqueous solutions of PTEG, PG3(L) and PG3(H). Heating and cooling rate ¼ 0.2 K min1.
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It is important to point out both amphiphilic polymers PTEG and PG3 exhibit normal transmittance curves during the thermallyinduced aggregation process, and the abnormal platform discovered for the amphiphilic macromonomer MG3 does not appear. This indicates the amphiphilicity of the polymers does not contribute apparently to the polymer aggregation process, suggesting periphery of cylindrical dendronized polymers dominates the dehydration and collapse, as well as the aggregation process thereafter. This result is in good agreement with that phase transition temperature of dendronized polymers carrying solely OEG dendrons is dominated by the peripheries, and the interior part of the cylindrical polymers dehydrates at a much higher temperature [40]. The amphiphilic dendronized polymers reported in present work should also follow this rule, and the peripheral OEG units
dominate the thermally-induced collapse and aggregation, which shields the possible effects from the thermally-enhanced hydrophilicity of interior lysine dendrons. 1 H NMR spectroscopy was used to follow the dehydration process of these polymers on the micro level, and the spectra for PTEG from 40 C to 65 C and for PG3(L) from 25 C to 45 C are shown in Fig. 6. All proton signals from PTEG are resolved at lower temperatures but increasingly broaden with increase of solution temperature, and their intensities decrease simultaneously, indicating the dehydration or collapse of polymers. Notably, the intensities of the proton signals from OEG units of PTEG at d ¼ 1.2e1.5, 3.5e4.0, and 4.1e4.4 start to decrease (dehydration point) about 45 C, which is 9 K lower than its corresponding Tcp (53.7 C, aggregation point). This huge difference between the temperature for dehydration and
Fig. 6. Temperature-dependent 1H NMR spectra of PTEG (Tcp ¼ 54 C) (a, 1.00 wt %) and PG3(L) (Tcp ¼ 40 C) (b, 0.50 wt %) in D2O.
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that for aggregation indicates that PTEG dehydrates at a much earlier stage, and a much higher temperature is necessary to provide sufficient driving force to initiate the chain collapse and to form aggregation. This remarkable hysteresis between dehydration and aggregation should be related to the specific structure of this polymer: low OEG density on the periphery for the polymer PTEG can not shield efficiently the enhanced hydrophilicity of interior amide and lysine moieties with increase of temperature, leading to competition of solvation of the interior against collapse of the peripheries. This situation changes when polymer periphery covers densely with OEG units for the case of PG3. From the temperaturevaried 1H NMR spectra of PG3(L), proton signals show significant changes of shape and intensities at 40 C, indicating that the polymer starts to dehydrate around this point, which is very close to its corresponding Tcp (40.1 C) for used concentration. This result suggests densely grafted OEG units on the periphery of cylindrical dendronized polymers provide sufficient shielding effects to the interior structures.
Appendix A. Supplementary data
4. Conclusions
[12]
Structurally novel dendritic macromolecules were efficiently synthesized. These macromolecules are constructed with lysinebased G2 dendron in the interior and OEG linear chains or dendron in the periphery. They show different thermoresponsive properties, depending on topology of the molecules, amphiphilicity, OEG density on the periphery, as well as their molar masses. The thermoresponsive properties of fan-shaped dendritic macromonomers depend mainly on OEG density on their periphery: dendritic monomer carrying linear OEG chains (MTEG) is too hydrophilic, while dendritic monomer carrying OEG dendrons (MG3) is thermoresponsive with a broad phase transition. Notably, revealed by NMR and UV/vis spectroscopies, the amphiphilicity of MG3 contributes significantly to its thermoresponsive properties, and the thermally-induced aggregation is governed by the balance between dehydration of OEG dendrons and rehydration of amide and lysine moieties. In contrast to fan-shaped dendritic macromonomers, the cylindrical topology from dendronized polymers provides significant architecture effects on their thermoresponsiveness. Dendronized polymer PTEG from the thermally unresponsive monomer MTEG shows typical thermoresponsive properties, and similarly, dendronized polymers PG3 from the thermally responsive monomer MG3 adopt sharp phase transitions with Tcps dependent partially on their molar masses. The amphiphilicity of dendronized polymers play different rules. Their cylindrical architecture helps the periphery to shield the interior, and dominates the thermoresponsive behavior of the polymers, but the shielding efficiency is dependent on OEG density on the periphery. Therefore, amphiphilicity of dendronized polymers makes competition against the cylindrical architecture in the thermallyinduced dehydration and aggregation, and can lead to enhanced solvation of the polymer against peripheral collapse-induced aggregation. These findings enrich understanding of structure effects on thermoresponsive properties of macromolecules, which may find broad interest in developing various smart polymer materials. Acknowledgment Dr. Hongmei Deng from the Instrumental Analysis of Research Center (Shanghai University) is thanked for her assists in NMR measurements. This work is financially supported by National Natural Science Foundation of China (Nos. 21034004, 21104043, & 21374058) and the Ph.D. Programs Foundation of Ministry of Education of China (Nos. 201131081200177 & 201331081100166).
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Supplementary data related to this article can be found free of charge at http://dx.doi.org/10.1016/j.polymer.2014.06.010. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
[13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46]
[47]
Aseyev V, Tenhu H, Winnik FM. Adv Polym Sci 2011;242:29e89. Roy D, Brooks WLA, Sumerlin BS. Chem Soc Rev 2013;42:7214e43. Mua X-R, Tong J-G, Liu Y, Liu X-Y, Liu H-J, Chen Y. Polymer 2013;54:2341e6. pez-Cabarcos E, Serrano-Ruiz D, Alonso-Cristobal P, Laurenti M, Frick B, Lo Rubio-Retama J. Polymer 2013;54:4963e71. Men Y, Drechsler M, Yuan J. Macromol Rapid Commun 2013;34:1721e7. Gil ES, Hudson SM. Prog Polym Sci 2004;29:1173e222. Yan J, Li W, Liu K, Wu D, Chen F, Wu P, et al. Chem Asian J 2011;6:3260e9. Ji X, Chen J, Chi X, Huang F. ACS Macro Lett 2014;3:110e3. Schmidt BVKJ, Hetzer M, Ritter H, Barner-Kowollik C. Macromol Rapid Commun 2013;34:1306e11. Yamato M, Akiyama Y, Kobayashi J, Yang J, Kikuchi A, Okano T. Prog Polym Sci 2007;32:1123e33. Brites CDS, Lima PP, Silva NJO, Mill an A, Amaral VS, Palacio F, et al. Nanoscale 2012;4:4799e829. Rotzetter ACC, Schumacher CM, Bubenhofer SB, Grass RN, Gerber LC, Zeltner M, et al. Adv Mater 2012;24:5352e6. Lai BFL, Zou Y, Yang X, Yu X, Kizhakkedathu JN. Biomaterials 2014;35: 2518e28. Summers MJ, Phillips DJ, Gibson MI. Chem Commun 2013;49:4223e5. Zayas HA, Lu A, Valade D, Amir F, Jia Z, O’Reilly RK, et al. ACS Macro Lett 2013;2:327e31. Alarcon CH, Pennadam S, Alexander C. Chem Soc Rev 2005;34:276e85. Plummer R, Hill DJT, Whittaker AK. Macromolecules 2006;39:8379e88. Durme KV, Assche GV, Aseyev V, Raula J, Tenhu H, Mele BV. Macromolecules 2007;40:3765e72. Ye J, Xu J, Hu J, Wang X, Zhang G, Liu S, et al. Macromolecules 2008;41: 4416e22. Roeser J, Moingeon F, Heinrich B, Masson P, Arnaud-Neu F, Rawiso M, et al. Macromolecules 2011;44:8925e35. Gao M, Jia X, Kuang G, Li Y, Liang D, Wei Y. Macromolecules 2009;42: 4273e81. Jia Z, Chen H, Zhu X, Yan D. J Am Chem Soc 2006;128:8144e5. Kretschmann O, Steffens C, Ritter H. Angew Chem Int Ed 2007;46:2708e11. Ohashi H, Hiraoka Y, Yamaguchi T. Macromolecules 2006;39:2614e20. Yan J, Zhang X, Li W, Zhang X, Liu K, Wu P, et al. Soft Matter 2012;8:6371e7. Hu G, Li W, Hu Y, Xu A, Yan J, Liu L, et al. Macromolecules 2013;46:1124e32. Hua F, Jiang X, Zhao B. Macromolecules 2006;39:3476e9. Zhang Z-X, Liu KL, Li J. Macromolecules 2011;44:1182e93. Weiss J, Bȍttcherb C, Laschewsky A. Soft Matter 2011;7:483e92. Peng B, Grishkewich N, Yao Z, Han X, Liu H, Tam KC. ACS Macro Lett 2012;1: 632e5. Schlüter AD, Rabe JP. Angew Chem Int Ed 2000;39:864e83. Zhang A, Shu L, Bo Z, Schlüter AD. Macromol Chem Phys 2003;204:328e39. Rosen BM, Wilson CJ, Wilson DA, Peterca M, Imam MR, Percec V. Chem Rev 2009;109:6275e540. Chen Y, Xiong X. Chem Commun 2010;46:5049e60. Li W, Zhang A, Feldman K, Walde P, Schlüter AD. Macromolecules 2008;41: 3659e67. Li W, Zhang A, Schlüter AD. Chem Commun 2008:5523e5. Li W, Wu D, Schlüter AD, Zhang A. J Polym Sci A Polym Chem 2009;47: 6630e40. Li W, Zhang X, Zhao X, Zhang A. J Polym Sci A Polym Chem 2013;51:5143e52. Li W, Yan J, Zhang A. Encycl Polym Sci Technol 2012. http://dx.doi.org/ 10.1002/0471440264.pst548. Junk MJN, Li W, Schlüter AD, Wegner G, Spiess HW, Zhang A, et al. Angew Chem Int Ed 2010;49:5683e7. Junk MJN, Li W, Schlüter AD, Wegner G, Spiess HW, Zhang A, et al. J Am Chem Soc 2011;133:10832e8. Liu L, Li W, Liu K, Yan J, Hu G, Zhang A. Macromolecules 2011;44:8614e21. Liu K, Zhang X, Tao X, Yan J, Kuang G, Li W, et al. Polym Chem 2012;3: 2708e11. €chtersbach E, Schmidt M, Schlüter AD. Chem Eur J Zhang A, Zhang B, Wa 2003;9:6083e92. Chen F, Zhang X, Li W, Liu K, Guo Y, Yan J, et al. Soft Matter 2012;8:4869e72. This mixed solvent is selected for the purpose to visualize the active protons in 1H NMR spectra. See, for example Bartoloni M, Kadam RU, Schwartz J, Furrer J, Darbre T, Reymond J-L. Chem Commun 2011;47:12634e6. There are two possibilities for these protons to show broadened and reduced signals with temperature: (1) dehydration themselves, or (2) physically imbedded within the collapsed phase. For the protons from amide and lysine moieties in present polymers, their peaks broadening and intensity reduction at elevated temperature should be originated from the second case.
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Remarkable structure effects on thermoresponsive properties of dendritic macromolecules Xiong Tao, Kun Liu, Wen Li*, Afang Zhang* Lab of Polymer Chemistry, Department of Polymer Materials, College of Materials Science and Engineering, Department of Chemistry, Shanghai University, Nanchen Street No. 333, Shanghai 200444, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 19 March 2014 Received in revised form 10 May 2014 Accepted 4 June 2014 Available online 11 June 2014
Amphiphilic dendritic macromonomers and their corresponding dendronized polymers were synthesized, and their thermoresponsive properties investigated. These dendritic macromolecules are constructed with a second generation lysine-based dendron as the interior (hydrophobic part) and oligoethylene glycol (OEG) linear chains or dendrons (hydrophilic part) covered in their periphery. By changing from OEG linear chains to OEG dendrons, these dendritic macromolecules carry on their periphery different density of OEG moieties, to investigate the structural effects on their thermoresponsiveness. Topology of dendritic macromolecules changes through polymerization, and the fan-shaped dendritic macromonomers transfer into the corresponding cylindrically shaped dendronized polymers. Furthermore, the amphiphilic characteristic of these dendritic entities can be switched due to the thermally-induced dehydration of OEG moieties. It was found that topology, OEG density in the periphery and switchable amphiphilicity of these dendritic macromolecules show significantly effects on their thermoresponsiveness. © 2014 Elsevier Ltd. All rights reserved.
Keywords: Dendritic macromolecules Dendronized polymers Thermoresponsive polymers
1. Introduction Thermoresponsive polymers undergo a thermally-induced entropy-driven dehydration, followed by chain collapse and aggregation around their phase transition temperatures, consequently, their aqueous solutions turn from homogeneous (transparent) into heterogeneous (turbid) [1,2]. This process involves the transformation of polymer chains (partially) from hydrophilic to hydrophobic. A variety of thermoresponsive polymers with various chemical structures and architectures have been developed to date through covalent [3e6] or non-covalent linkages [7e9] to show tunable thermoresponsive properties, and been utilized for applications ranging from surface modifications to biomaterials [10e15]. These representatives with phase transition temperature in the vicinity of physiological temperature and capable of fast and sharp response to temperature variation are especially attractive due to their promising applications in bio-related materials [16]. Generally speaking, the phase transition temperatures are dominated by the over-all hydrophilicity and hydrophobicity balance in the polymers. The more hydrophilic ones show higher
* Corresponding authors. Tel.: þ86 21 66138053; fax: þ86 21 66131720. E-mail addresses: [email protected] (W. Li), [email protected] (A. Zhang). http://dx.doi.org/10.1016/j.polymer.2014.06.010 0032-3861/© 2014 Elsevier Ltd. All rights reserved.
phase transition temperatures than the more hydrophobic counterparts. Besides the structural hydrophilicity, topology (architecture) was recently proved to show significant influence on the phase transition temperatures [17,18]. On changing polymer architecture from linear shape into cyclic [19] or dendritic ones [20e22], the thermoresponsive properties change obviously. The phase transition temperature can also be regulated through supramolecular interactions. With introduction of hydrophilic or hydrophobic guest molecules, the thermoresponsiveness of host polymers can be tuned [23e25]. Furthermore, secondary structures of polymers, such as helical conformations, have recently been proven to show influence on the phase transition temperatures. Polymers with the higher ordered structures possess a lower transition temperature due to the better arrangement of pendants [26]. By combination of two different types of thermoresponsive polymer segments together, it is possible to have doubly thermoresponsive behavior, which displays more than one phase transitions [27e30]. Recently we have developed a novel series of thermoresponsive dendritic macromolecules, including dendrimers and dendronized polymers [31e34], which show intriguing thermoresponsive properties with unprecedented fast and sharp phase transitions in the temperature range of 30e65 C [35e39]. These dendritic macromolecules were constructed with OEG dendrons in the
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entire, periphery, or pendent groups. OEG units were selected because they can not form strong hydrogen bondings with water. Notably, the phase transition temperatures are dominated by the hydrophilicity of periphery units, and the interiors show minor influence on the aggregation but collapse heterogeneously [40,41]. This property makes these dendritic macromolecules act as a smart molecular box, and provides chances to change the interiors to have functionalities but still retain the responsive properties by choosing proper peripheral units [38,42]. In order to examine deeply the structural effects on their thermoresponsive properties, we here report on synthesis and thermoresponsiveness of closely related dendritic macromolecules. These dendritic analogs are constructed with hydrophobic lysine-based G2 dendron as the interior and hydrophilic OEG chains or dendrons on the periphery (Fig. 1). After polymerization, the fan-shaped dendritic macromonomers transfer into cylindrical dendronized polymers. The thermoresponsive properties of both dendritic macromonomers and dendronized polymers were examined with regard to structural amphiphilicity, molecular topology, as well as shielding efficiency of the periphery.
2. Experimental section 2.1. Materials Compounds 3 and 5 were synthesized according to our previous report [35,43]. Tetrahydrofuran (THF) was refluxed over lithium aluminum hydride and dichloromethane (DCM) over CaH2 for drying. Diisopropyl ethyl amine (DiEA) and triethyl amine (TEA) were dried over NaOH pallets. Methacryloyl chloride (MAC) was freshly distilled before used. Azobis(isobutyronitrile) (AIBN) was recrystallized twice from methanol. Other reagents and solvents were purchased at reagent grade and used without further purification. MachereyeNagel precoated TLC plates (silica gel 60 G/ UV254, 0.25 mm) were used for thin-layer chromatography (TLC) analysis. Silica gel 60 M (MachereyeNagel, 0.04e0.063 mm, 200e300 mesh) was used as the stationary phase for column chromatography.
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2.2. Instrumentation and measurements 1 H NMR spectra were recorded on a Bruker AV 500 (1H: 500 MHz) spectrometer, and chemical shifts are reported as d value (ppm) relative to internal Me4Si. Gel permeation chromatography (GPC) measurements were carried out on a Waters GPC e2695 instrument with 3 column set (Styragel HR3þHR4þHR5) equipped with refractive index detector (Waters 2414), and DMF (containing 1 g L1 LiBr) as eluant at 45 C. Multiangle light scattering detector (Wyatt Technology Corporation, Down EOS 243-E) was used for some of the measurements. The calibration was performed with poly(methyl methacrylate) standards with molar masses in the range of Mp ¼ 2580e981,000 (Polymer Standards Service USA). The refractive index increment (dn/dc) of the polymers were measured with SEC-3010 RI detector (WGE Dr. Bures Corporation) operated with a monochromatic light source (l ¼ 620 nm). The measured dn/ dc values of PTEG and PG3 at 30 C and in DMF were 0.162 and 0.098 mL g1, respectively. AFM measurements were conducted on Bruker Nanoscope VIII Multi-Mode operated with a “J” scanner (scan range 125 mm 125 mm) and operated in Peak Force Mode at room temperature in air. Bruker silicon Tip on Nitride Lever cantilevers (T: 0.65 mm, L: 115 mm, W: 25 mm, fo: 70 mm, k: 0.4 N/m) were used. UV/vis turbidity measurements were carried out on a PE UV/vis spectrophotometer (Lambda 35) equipped with a thermocontrolled bath. Aqueous polymer solutions were placed in the spectrophotometer (path length 1 cm) and heated or cooled at a rate of 0.2 C min1. The absorptions of the solution at l ¼ 500 nm were recorded every 5 s. The cloud point temperature (Tcp) is determined to be that at which the transmittance at l ¼ 500 nm had reached 50% of its initial value. General Procedure for Etherification (A). NaH (6.00 mmol) and KI (0.20 mmol) were added to triethylene glycol monoethyl ether (Et-TEG, 1.20 mmol) in THF (15 mL). The solution was stirred at 0e5 C for 0.5 h, and then bromoacetic acid (1.00 mmol) in THF (5 mL) was slowly added over 0.5 h. The resulting reaction mixture was stirred at 0 C under nitrogen atmosphere for another 12 h, and then quenched with MeOH. After evaporation of the solvent the residue was dissolved in H2O and then extracted with DCM. After
Fig. 1. Chemical structures of the dendritic macromonomers MTEG and MG3, as well as their corresponding polymers PTEG and PG3. EtG1 represents the first generation OEG dendron.
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washed with KHSO4, the organic phase was washed three times with water, and then dried over MgSO4 to provide the target product. General Procedure for Esterification (B). p-Nitrophenol or pentafluorophenol (1.20 mmol) in dry DCM (15 mL) was added dropwise to a solution of compound 2a or 3 (1.00 mmol) and 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDC,HCl, 1.20 mmol) in dry DCM (20 mL) at 15 C. The mixture was stirred for 12 h at 15 C and then extracted with DCM. The combined organic phase was dried over MgSO4. Purification by column chromatography afforded the target compound as colorless oil. General Procedure for Amide Coupling (C). Compound 2b or 4 (6.00 mmol) in DMF (30 mL) was added dropwise into a solution of compound 5 (1.00 mmol) and DiEA (6.00 mmol) in water (10 mL) at 0 C. The mixture was kept at that temperature for 2 h, and then allowed to reaction overnight at room temperature. Evaporation of the solvents in vacuo at room temperature gave a residue. It was treated with DCM, and washed successively with NaHCO3 and brine. All aqueous phases were extracted with DCM three times. The combined organic phases were dried over MgSO4, and purified with column chromatography to afford the product as colorless oil. General Procedure for Macromonomer synthesis (D). MAC (2.00 mmol) was added dropwise to a mixture of the dendron alcohol (1.00 mmol), TEA (10.00 mmol) and DMAP (0.10 g) in dry THF (25 mL) at 0 C over 2 h. The mixture was stirred for 6 h at r.t., and then the reaction was quenched with MeOH. After washing successively with aqueous NaHCO3 solution and brine, the organic phase was dried over MgSO4. Purification by column chromatography afforded the monomer as colorless oil. General Procedure for Free Radical Polymerization (E). A solution of macromonomer (0.30e0.50 g) and AIBN (0.5 wt% based on the macromonomer) in DMF (0.2 mL) inside a Schlenk tube was degassed by several freezeepumpethaw cycles, and then kept at 70 C with stirring for a predetermined time. The polymerization was stopped by cooling, and the polymer was dissolved in DCM and purified by column chromatography (silica gel, DCM eluant). Compound 2a. According to the general procedure A from 1 (0.77 g, 4.32 mmol), bromoacetic acid (0.50 g, 3.60 mmol), NaH (95%, 0.55 g, 21.60 mmol) and KI (0.12 g, 0.72 mmol), compound 2a was yielded as a colorless oil (0.59 g, 70%). 1H NMR (CDCl3): d ¼ 1.23e1.26 (t, 3H, CH3), 3.55e3.59 (q, 2H, CH2), 3.62e3.68 (m, 6H, CH2), 3.69e3.72 (m, 4H, CH2), 3.75e3.77 (m, 2H, CH2), 4.16 (s, 2H, CH2). Compound 2b. According to the general procedure B from 2a (0.50 g, 2.12 mmol), p-nitrophenol (0.35 g, 2.54 mmol) and EDC,HCl (0.49 g, 2.54 mmol), purification by column chromatography (hexane/ethyl acetate ¼ 2:1, v/v) afforded 2b as a colorless oil (0.60 g, 80%). 1H NMR (CDCl3): d ¼ 1.22e1.25 (t, 3H, CH3), 3.52e3.57 (q, 2H, CH2), 3.60e3.62 (m, 2H, CH2), 3.66e3.70 (m, 6H, CH2), 3.76e3.78 (m, 2H, CH2), 3.85e3.87 (m, 2H, CH2), 4.49 (s, 2H, CH2), 7.35e7.37 (d, 2H, CH), 8.30e8.32 (d, 2H, CH). Compound 4. According to the general procedure B from 3 (0.90 g, 1.38 mmol), pentafluorophenol (0.31 g, 1.66 mmol) and EDC.HCl (0.32 g, 1.66 mmol), purification by column chromatography with ethyl acetate eluant afforded 4 as a colorless oil (0.83 g, 73%). 1H NMR (CDCl3): d ¼ 1.20e1.24 (m, 9H, CH3), 3.51e3.56 (m, 6H, CH2), 3.59e3.61 (m, 6H, CH2), 3.65e3.70 (m, 12H, CH2), 3.73e3.76 (m, 6H, CH2), 3.83e3.85 (t, 2H, CH2), 3.90e3.92 (t, 4H, CH2), 4.24e4.26 (t, 4H, CH2), 4.30e4.32 (t, 2H, CH2), 7.46 (s, 2H, CH). Compound 6a. According to the general procedure C from 5 (0.68 g, 1.27 mmol), 2b (2.73 g, 7.63 mmol) and DiEA (0.99 g, 7.63 mmol), purification by column chromatography (DCM/ MeOH ¼ 10:1, v/v) afforded 6a as a colorless oil (1.58 g, 92%). 1H NMR (CDCl3): d ¼ 1.21e1.24 (t, 12H, CH3), 1.33e1.44 (m, 8H, CH2),
1.49e1.58 (m, 8H, CH2), 1.66e1.75 (m, 2H, CH2), 1.87e1.92 (m, 2H, CH2), 3.16e3.35 (m, 6H, CH2 þ CH3), 3.52e3.56 (q, 8H, CH2), 3.59e3.61 (m, 9H, CH2), 3.65e3.66 (m, 9H, CH2), 3.68e3.7 (m, 32H, CH2), 3.84e3.9 (m, 3H, CH2 þ CH3), 3.99 (s, 4H, CH2), 4.01e4.07 (m, 4H, CH2), 4.38e4.43 (q, 4H, CH2 þ CH3), 6.84e6.85 (d, 1H, NH), 6.98e6.99 (t, 1H, NH), 7.16e7.18 (t, 1H, NH), 7.3e7.31 (d, 1H, NH), 7.41e7.43 (dd, 2H, NH). Compound 6b. According to the general procedure C from 5 (0.37 g, 0.69 mmol), 4 (3.4 g, 4.16 mmol) and DiEA (0.54 g, 4.16 mmol), purification by column chromatography (DCM/ MeOH ¼ 40:1) afforded 6b as a colorless oil (1.50 g, 74%). 1H NMR (CDCl3): d ¼ 1.17e1.22 (m, 34H, CH3), 1.26e2.00 (br, 18H, CH2), 2.49 (br, 5H, CH2), 3.08 (br, 1H, CH2), 3.29e3.43 (br, 5H, CH2 þ CH), 3.48e3.54 (m, 24H, CH2), 3.56e3.59 (m, 24H, CH2), 3.62e3.65 (m, 46H, CH2), 3.67e3.70 (m, 24H, CH2), 3.77e3.79 (m, 24H, CH2), 4.08e4.15 (m, 23H, CH2), 4.63e4.68 (m, 2H, CH), 7.08e7.12 (br, 10H, CH þ NH), 7.41 (s, 2H, NH), 7.59 (s, 1H, NH), 7.72e7.74 (d, 1H, NH). Monomer MTEG. According to the general procedure D from 6a (0.46 g, 0.37 mmol), TEA (0.37 g, 3.68 mmol), MAC (77 mg, 0.74 mmol), and DMAP (0.10 g), purification by column chromatography (DCM/MeOH ¼ 20:1) afforded MTEG as a colorless oil (0.47 g, 96%). 1H NMR (CDCl3): d ¼ 1.20e1.23 (t, 12H, CH3), 1.26e1.40 (m, 8H, CH2), 1.54e1.58 (m, 8H, CH2), 1.66e1.70 (m, 2H, CH2), 1.83e1.92 (m, 2H, CH2), 1.94 (s, 3H, CH3), 3.10e3.14 (m, 1H, CH2), 3.20e3.33 (m, 5H, CH2 þ CH), 3.51e3.56 (q, 8H, CH2), 3.59e3.61 (m, 8H, CH2), 3.64e3.66 (m, 8H, CH2), 3.68e3.70 (m, 32H, CH2), 3.97e3.98 (m, 4H, CH2), 4.00e4.06 (m, 4H, CH2 þ CH), 4.10e4.18 (m, 3H, CH2 þ CH), 4.38e4.41 (m, 2H, CH), 5.59e5.60 (t, 1H, CH), 6.13 (s, 1H, CH), 7.12e7.14 (m, 2H, NH), 7.22e7.24 (t, 2H, NH), 7.44e7.48 (t, 2H, NH). HRMS (ESI): m/z calcd for C62H116N6O24 [M þ Na]þ 1351.7939. Found: 1351.7893. Monomer MG3. According to the general procedure D from 6b (1.30 g, 0.45 mmol), TEA (0.10 g, 4.45 mmol), MAC (93 mg, 0.89 mmol), and DMAP (0.10 g), purification by column chromatography (DCM/MeOH ¼ 30:1) afforded MG3 as a colorless oil (1.30 g, 98%). 1H NMR (CDCl3): d ¼ 1.17e1.23 (m, 36H, CH3), 1.27e1.85 (m, 18H, CH2), 1.91 (s, 3H, CH3), 2.01e2.16 (m, 10H, CH2), 3.06e3.07 (br, 1H, CH2), 3.37e3.43 (br, 7H, CH2 þ CH), 3.49e3.54 (m, 24H, CH2), 3.57e3.60 (m, 24H, CH2), 3.63e3.73 (m, 72H, CH2), 3.78e3.81 (m, 24H, CH2), 4.06e4.17 (m, 27H, CH2), 4.65e4.69 (m, 2H, CH), 5.58 (s, 1H, CH2), 6.13 (s, 1H, CH2), 7.05e7.13 (m, 10H, CH þ NH), 7.39e7.42 (d, 2H, NH), 7.71 (s, 2H, NH). HRMS (ESI): m/z calcd for C146H252N6O56 [M þ Na]þ 3008.6923. Found: 3008.6948. Polymer PTEG. According to the general procedure E from MTEG (0.34 g) and AIBN (1.70 mg) in DMF (0.15 mL) (5 h at 70 C), PTEG was yielded as a colorless foam (0.28 g, 82%). 1H NMR (d6-DMSO, 80 C): d ¼ 0.81 þ 1.00 (br, 3H, CH3), 1.05e1.11 (m, 12H, CH3), 1.23e2.06 (br, 3H, CH3), 3.39e3.52 (m, 42H, CH2), 3.69 (br, 9H, CH2 þ CH), 4.02 (br, 9H, CH2 þ CH), 4.80 (br, 3H, NH), 5.40 (br, 1H, CH), 6.57 (br, 3H, NH). Some proton signals from the backbone were not resolved in the 1H NMR spectrum. Polymer PG3(L). According to the general procedure E from MG3 (0.50 g) and AIBN (2.00 mg) in DMF (0.15 mL) (24 h at 70 C), PG3(L) was yielded as a colorless foam (0.10 g, 20%). 1H NMR (d6-DMSO, 80 C): d ¼ 1.07e1.08 (br, 36H, CH3), 1.28e1.80 (br, 24H, CH2), 3.21 (br, 6H, CH2), 3.44e3.70 (br, 150H, CH2), 4.08 (br, 26H, CH2), 2.09 (br, 2H, CH), 7.12e7.18 (br, 8H, CH), 7.53e7.94 (br, 6H, NH). Some proton signals from the backbone were not resolved in the 1H NMR spectrum. Polymer PG3(H). AIBN (0.37 mg) was added into liquid monomer MG3 (0.27 g) inside a Schlenk tube, and dissolved. The mixture was then thoroughly deoxygenated by three freezeepumpethaw cycles and stirred at 70 C for 24 h. After cooling to r.t., the polymer was dissolved in DCM and purified by silica gel column chromatography with DCM as an eluant. PG3(H) was yielded (0.13 g, 50%)
X. Tao et al. / Polymer 55 (2014) 3672e3679
as a colorless solid. 1H NMR (d6-DMSO, 80 C): d ¼ 1.04e1.09 (br, 36H, CH3), 1.24e1.58 (br, 15H, CH2), 3.39e3.66 (br, 172H, CH2), 4.50e4.59 (br, 3H, CH2), 7.07 (br, 8H, CH þ NH), 7.82e8.05 (br, 4H, NH). Some proton signals from the backbone were not resolved in the 1H NMR spectrum. 3. Results and discussion 3.1. Synthesis of dendritic macromonomers and polymers The synthesis procedure for two dendritic macromonomers cored with a second generation lysine-based dendron but carrying different oligoethylene glycol (OEG) units were illustrated in Scheme 1. Triethylene glycol monoethyl ether (1) was reacted with bromoacetic acid through etherification reaction to afford compound 2a. Followed by the esterification reaction with p-nitrophenol, the active ester 2b was formed, which was reacted with lysine-based G2 dendron (5) to afford the dendron alcohol (6a). Esterification with MAC afforded the target macromonomer MTEG. With similar procedures, the dendritic macromonomer MG3 carrying four branched OEG dendrons were prepared. The polymerization of MTEG and MG3 was carried out in DMF solutions at 70 C in the presence of AIBN as initiator to yield the corresponding polymers PTEG and PG3(L), respectively. For comparison, MG3 was also polymerized in bulk at 70 C to afford PG3(H). All macromonomers and polymers were characterized by 1H NMR spectroscopy (for the spectra, see supporting Information). The molar masses of these polymers were determined by GPC measurements with DMF as eluant and PMMA as standards, and results are summarized in Table 1. As expected, PG3(H) obtained from bulk polymerization shows a much larger molar mass than that from polymerization in DMF. It is necessary to point out that, GPC measurements underestimate greatly the molar masses of these
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bulk polymers [44]. Examining the structural difference of PTEG and PG3, it should not be difficult to find that the latter is much thicker than the former due to the peripheral OEG dendrons, therefore, these polymers should be able to be directly identified with AFM. Actually, AFM measurements verified this conjecture, and PG3 shows a height of about 2 nm (Fig. S1a), which is much larger than that for PTEG (height ~ 1 nm, Fig. S1b). Therefore, AFM image shown in Fig. 2a obtained from a mixture of PTEG and PG3(H) in chloroform solution contains molecular objects of two distinct heights. The more bright objects with apparent height of ~2 nm represent the polymer chains from PG3(H), while the less bright objects with apparent height of ~1 nm correspond to the polymer chains from PTEG (Fig. 2b). 3.2. Thermoresponsive behavior of dendritic macromonomers The thermoresponsive properties of the amphiphilic macromonomers were first checked. Due to the abundant hydrophilic amide linkages between OEG chains and the lysine dendron, MTEG is too hydrophilic to show any thermally-induced aggregation behavior even up to 100 C. In contrast, these hydrophilic amide linkages were shielded efficiently by the densely covered OEG dendrons, therefore, MG3 shows a typical thermoresponsive behavior upon heated to elevated temperature (30e45 C). Its thermally-induced aggregation was thus followed with UV/vis spectroscopy, and the transmittance curves at different concentrations were recorded (Fig. 3). At low concentration (c < 0.50 wt %) the transmittance curves seems normal but the aggregation spans a broad temperature range (D ~ 10 K). As expected, the macromonomer starts to aggregate at a lower temperature with increase of solution concentration. These are typical for the thermoresponsive motifs of low molar masses [45]. Notably, the transmittance curves exhibit a platform during the thermally-induced
Scheme 1. Synthesis procedure for the monomers (MTEG and MG3). Reagents and conditions: a) bromoacetic acid, NaH, KI, THF, 0 C, 12 h, (70%). b) p-nitrophenol, EDC.HCl, DCM, 15 C, overnight (80%). c) Pfp-OH, EDC.HCl, DCM, 15 C, N2, overnight (73%). d) 2b or 4, DiEA, DMF/H2O, 0 C, overnight (93% and 74% for 6a and 6b, respectively). e) 6a or 6b, MAC, TEA, DMAP, THF, 0 C, 8 h (96% and 98% for MTEG and MG3, respectively). Abbreviations: DCM ¼ dichloride methane, DiEA ¼ diisopropyl ethyl amine, DMF ¼ N,Ndimethylformamide, DMAP ¼ N,N-dimethyl amino pyridine, MAC ¼ methacryloyl chloride, NpeOH ¼ 4-nitrophenol, Pfp-OH ¼ pentafluorophenol, TEA ¼ triethyl amine, THF ¼ tetrahydrofuran.
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Table 1 Conditions for and results of the polymerization of MTEG and MG3. Entry
PTEG PG3(L) PG3(H)
Polymerization conditionsa
Yield (%)
Monomers
[M] (mol L1)
Time (h)
MTEG MG3 MG3
0.51 0.26 0.37
5 24 24
82 20 50
GPCb Mn 104
PDI
25.13 2.93 9.91
1.94 1.83 2.39
Mwc 104
Tcpd ( C)
54.37 13.57 94.94
55.6 40.4 33.1
Polymerizations were carried out at 70 C in the present of AIBN (0.5 wt % based on monomer). Determined by GPC with DMF as eluant containing 0.1 wt % LiBr (calibrated with poly(methyl methacrylate) standards); Mn represents the numbereaverage molecular weight. c Mw represents the weighteaverage molecular weight, and was determined by multiangle light scattering measurements. d The cloud point temperatures (Tcps) of the polymers were determined as the temperature at 50% of the initial transmittance at l ¼ 500 nm. Concentration of polymers ¼ 0.25 wt%. a
b
Fig. 2. (a) AFM height image from a mixture of PTEG and PG3(H). (b) Cross-sectional profile of AFM images at the position indicated at the dotted line in (a). The sample was prepared through spin-coating (3000 rpm) from a chloroform solution onto mica.
aggregation processes in case concentration is higher than 1.00 wt % (Fig. 3). Appearance of the platform suggests that aggregation of the macromonomer induced by dehydration of OEG units is hindered by rehydration of the molecule (or part of the molecule) with increase of solution temperature. Through examining chemical structure of the macromonomer, it's not difficult to find the hydrophobic lysine moieties can not be easily hydrated. The hydration enhancement with temperature should mainly come from the amide linkages between lysine dendron and OEG dendrons, which balances the driving force from the collapse of OEG units, and results in hindering the aggregation process. However, when solution temperature increases further to a higher stage, the enhanced hydrophobicity from the collapsed OEG units compensates the
Fig. 3. Plots of transmittance versus temperature for MG3 at different concentrations. Heating rate ¼ 0.2 K min1.
temperature enhanced hydrophilicity from the amide units, leading to a further aggregation. The transmittance below the phase transition temperature reduces from 97% to 53% when solution concentration increases from 0.12% to 3.00%, indicating that obvious aggregations formed in higher concentration solutions. This concentration-induced preaggregation should be originated from the amphiphilicity of MG3, which may the prerequisite for the formation of the platform during the phase transition processes. The monomer concentration showed minor influence on the first transition temperature, suggesting that aggregation at this stage is dominated by collapse of densely packed OEG moieties from the same preaggregates. However, the second transition temperature reduced significantly with the increase of monomer concentration, indicating that aggregation at this stage is mainly processed from collapse of OEG moieties within different preaggregates, where concentration plays an important role in aggregation kinetics. In order to verify above hypothesis, 1H NMR spectra of MG3 were recorded in mixed solutions of D2O and H2O at different temperatures (Fig. 4. For full spectra, see Fig. S2 in Supporting Information) [46]. The proton signals corresponding to aromatic ring (Ph-CH) and ethoxyl terminals (EteCH2) from the OEG-based dendron become broad and start to decrease their intensities at 28e30 C, which is a direct prove for the dehydration of the dendron at this temperature stage. This result shows good agreement with UV measurements that the first phase transition for MG3 starts at 28e30 C for the concentration used (2.00 wt %). The dehydration tendencies for OEG moieties enhance with the increase of solution temperature, indicating their continuous dehydration and collapse. In contrast, the heights and intensities of proton signals from lysine moieties including methylene (LysCH2) and the amide (CONH) increase initially at a lower temperature, and start to reduce at a much higher temperature (Fig. S3).
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Fig. 4. Partial temperature-dependent 1H NMR spectra of MG3 in H2O: D2O (v:v ¼ 3:1). Polymer concentration ¼ 2.00 wt %.
Around 29 C, where the proton signals from OEG dendron decays, the intensities for the proton signal from amide and lysine moieties increase with temperature. Further increase of temperature to 35 C, proton signals from amide and lysine moieties start to broaden and reduce their intensities, indicating enhanced collapse and aggregation of the molecule [47]. The different tendency of proton signal intensities from amide and lysine moieties by comparing to those from OEG dendrons upon increase of temperature provides a solid support that, hydration enhancement of amide and lysine moieties with the increase of temperature contributes significantly to the over-all hydrophilicity of the molecule, which hinders the aggregation progress thermally-induced by collapse of OEG units. This effect diminishes at a higher temperature when enriched hydrophobicity from the extensively collapsed OEG moieties overcomes the contribution from hydrophilicity enhancement of the amide and lysine units.
influence on their Tcps. Polymer with high molar mass [PG3(H)] shows a much smaller Tcp than its counterpart of lower molar mass [PG3(L)]. The effects of polymer concentration on their thermoresponsive properties are also remained. With decrease of solution concentration from 2.0% to 0.12%, DTcp < 4 K for PTEG, and DTcp < 2 K for PG3(L) and PG3(H), indicating that polymer concentration shows minor effects (see Fig. S4 for the transmittance curves). This is a typical feature for thermoresponsive dendronized polymers [35e37]. It's interesting to point out that the phase transition temperatures for MG3 and PG3(L) are happen to be similar. MG3 carries at its both ends hydrophobic groups, and the hydrophobic contribution from methacrylate moiety compensates the hydrophilicity from the amide linkages, resulting in a much low phase transition temperature. In contrast, the cylindrical geometry from PG3(L) provides sufficient shielding effect from the periphery, which diminishes contribution of the hydrophobic interior on the phase transition, leading to the phase transition temperature dependent on the periphery.
3.3. Thermoresponsive behavior of the dendronized polymers Both types of polymers PTEG and PG3 are water-soluble below 25 C. In contrast to its monomer counterpart MTEG which is not thermoresponsive, PTEG with the same hydrophilicity show typical thermoresponsive properties, suggesting that cylindrical molecular topology contribute significantly to mediate the thermoresponsive properties [42]. The aqueous solutions of PG3s are clear but turn into turbid at elevated temperature. Their thermoresponsive behaviors are then investigated on macro level by using UV/vis spectroscopy, and the results are plotted in Fig. 5. Overall, all polymers show reversible transitions with a small hysteresis (D ~ 2 K). Tcps for PTEG, PG3(L), and PG3(H) are 55.6, 40.4 and 33.1 C, respectively. PTEG carrying linear OEG chains on its periphery shows a much higher Tcp than these carrying branched OEG dendrons, indicating that grafting density of OEG chains shows significant contribution to the kinetics of OEG collapse, and higher grafting density facilitates considerably the thermally-induced aggregation. Molar mass of polymers also show accessory
Fig. 5. Plots of transmittance versus temperature for 0.25 wt % aqueous solutions of PTEG, PG3(L) and PG3(H). Heating and cooling rate ¼ 0.2 K min1.
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It is important to point out both amphiphilic polymers PTEG and PG3 exhibit normal transmittance curves during the thermallyinduced aggregation process, and the abnormal platform discovered for the amphiphilic macromonomer MG3 does not appear. This indicates the amphiphilicity of the polymers does not contribute apparently to the polymer aggregation process, suggesting periphery of cylindrical dendronized polymers dominates the dehydration and collapse, as well as the aggregation process thereafter. This result is in good agreement with that phase transition temperature of dendronized polymers carrying solely OEG dendrons is dominated by the peripheries, and the interior part of the cylindrical polymers dehydrates at a much higher temperature [40]. The amphiphilic dendronized polymers reported in present work should also follow this rule, and the peripheral OEG units
dominate the thermally-induced collapse and aggregation, which shields the possible effects from the thermally-enhanced hydrophilicity of interior lysine dendrons. 1 H NMR spectroscopy was used to follow the dehydration process of these polymers on the micro level, and the spectra for PTEG from 40 C to 65 C and for PG3(L) from 25 C to 45 C are shown in Fig. 6. All proton signals from PTEG are resolved at lower temperatures but increasingly broaden with increase of solution temperature, and their intensities decrease simultaneously, indicating the dehydration or collapse of polymers. Notably, the intensities of the proton signals from OEG units of PTEG at d ¼ 1.2e1.5, 3.5e4.0, and 4.1e4.4 start to decrease (dehydration point) about 45 C, which is 9 K lower than its corresponding Tcp (53.7 C, aggregation point). This huge difference between the temperature for dehydration and
Fig. 6. Temperature-dependent 1H NMR spectra of PTEG (Tcp ¼ 54 C) (a, 1.00 wt %) and PG3(L) (Tcp ¼ 40 C) (b, 0.50 wt %) in D2O.
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that for aggregation indicates that PTEG dehydrates at a much earlier stage, and a much higher temperature is necessary to provide sufficient driving force to initiate the chain collapse and to form aggregation. This remarkable hysteresis between dehydration and aggregation should be related to the specific structure of this polymer: low OEG density on the periphery for the polymer PTEG can not shield efficiently the enhanced hydrophilicity of interior amide and lysine moieties with increase of temperature, leading to competition of solvation of the interior against collapse of the peripheries. This situation changes when polymer periphery covers densely with OEG units for the case of PG3. From the temperaturevaried 1H NMR spectra of PG3(L), proton signals show significant changes of shape and intensities at 40 C, indicating that the polymer starts to dehydrate around this point, which is very close to its corresponding Tcp (40.1 C) for used concentration. This result suggests densely grafted OEG units on the periphery of cylindrical dendronized polymers provide sufficient shielding effects to the interior structures.
Appendix A. Supplementary data
4. Conclusions
[12]
Structurally novel dendritic macromolecules were efficiently synthesized. These macromolecules are constructed with lysinebased G2 dendron in the interior and OEG linear chains or dendron in the periphery. They show different thermoresponsive properties, depending on topology of the molecules, amphiphilicity, OEG density on the periphery, as well as their molar masses. The thermoresponsive properties of fan-shaped dendritic macromonomers depend mainly on OEG density on their periphery: dendritic monomer carrying linear OEG chains (MTEG) is too hydrophilic, while dendritic monomer carrying OEG dendrons (MG3) is thermoresponsive with a broad phase transition. Notably, revealed by NMR and UV/vis spectroscopies, the amphiphilicity of MG3 contributes significantly to its thermoresponsive properties, and the thermally-induced aggregation is governed by the balance between dehydration of OEG dendrons and rehydration of amide and lysine moieties. In contrast to fan-shaped dendritic macromonomers, the cylindrical topology from dendronized polymers provides significant architecture effects on their thermoresponsiveness. Dendronized polymer PTEG from the thermally unresponsive monomer MTEG shows typical thermoresponsive properties, and similarly, dendronized polymers PG3 from the thermally responsive monomer MG3 adopt sharp phase transitions with Tcps dependent partially on their molar masses. The amphiphilicity of dendronized polymers play different rules. Their cylindrical architecture helps the periphery to shield the interior, and dominates the thermoresponsive behavior of the polymers, but the shielding efficiency is dependent on OEG density on the periphery. Therefore, amphiphilicity of dendronized polymers makes competition against the cylindrical architecture in the thermallyinduced dehydration and aggregation, and can lead to enhanced solvation of the polymer against peripheral collapse-induced aggregation. These findings enrich understanding of structure effects on thermoresponsive properties of macromolecules, which may find broad interest in developing various smart polymer materials. Acknowledgment Dr. Hongmei Deng from the Instrumental Analysis of Research Center (Shanghai University) is thanked for her assists in NMR measurements. This work is financially supported by National Natural Science Foundation of China (Nos. 21034004, 21104043, & 21374058) and the Ph.D. Programs Foundation of Ministry of Education of China (Nos. 201131081200177 & 201331081100166).
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Supplementary data related to this article can be found free of charge at http://dx.doi.org/10.1016/j.polymer.2014.06.010. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
[13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46]
[47]
Aseyev V, Tenhu H, Winnik FM. Adv Polym Sci 2011;242:29e89. Roy D, Brooks WLA, Sumerlin BS. Chem Soc Rev 2013;42:7214e43. Mua X-R, Tong J-G, Liu Y, Liu X-Y, Liu H-J, Chen Y. Polymer 2013;54:2341e6. pez-Cabarcos E, Serrano-Ruiz D, Alonso-Cristobal P, Laurenti M, Frick B, Lo Rubio-Retama J. Polymer 2013;54:4963e71. Men Y, Drechsler M, Yuan J. Macromol Rapid Commun 2013;34:1721e7. Gil ES, Hudson SM. Prog Polym Sci 2004;29:1173e222. Yan J, Li W, Liu K, Wu D, Chen F, Wu P, et al. Chem Asian J 2011;6:3260e9. Ji X, Chen J, Chi X, Huang F. ACS Macro Lett 2014;3:110e3. Schmidt BVKJ, Hetzer M, Ritter H, Barner-Kowollik C. Macromol Rapid Commun 2013;34:1306e11. Yamato M, Akiyama Y, Kobayashi J, Yang J, Kikuchi A, Okano T. Prog Polym Sci 2007;32:1123e33. Brites CDS, Lima PP, Silva NJO, Mill an A, Amaral VS, Palacio F, et al. Nanoscale 2012;4:4799e829. Rotzetter ACC, Schumacher CM, Bubenhofer SB, Grass RN, Gerber LC, Zeltner M, et al. Adv Mater 2012;24:5352e6. Lai BFL, Zou Y, Yang X, Yu X, Kizhakkedathu JN. Biomaterials 2014;35: 2518e28. Summers MJ, Phillips DJ, Gibson MI. Chem Commun 2013;49:4223e5. Zayas HA, Lu A, Valade D, Amir F, Jia Z, O’Reilly RK, et al. ACS Macro Lett 2013;2:327e31. Alarcon CH, Pennadam S, Alexander C. Chem Soc Rev 2005;34:276e85. Plummer R, Hill DJT, Whittaker AK. Macromolecules 2006;39:8379e88. Durme KV, Assche GV, Aseyev V, Raula J, Tenhu H, Mele BV. Macromolecules 2007;40:3765e72. Ye J, Xu J, Hu J, Wang X, Zhang G, Liu S, et al. Macromolecules 2008;41: 4416e22. Roeser J, Moingeon F, Heinrich B, Masson P, Arnaud-Neu F, Rawiso M, et al. Macromolecules 2011;44:8925e35. Gao M, Jia X, Kuang G, Li Y, Liang D, Wei Y. Macromolecules 2009;42: 4273e81. Jia Z, Chen H, Zhu X, Yan D. J Am Chem Soc 2006;128:8144e5. Kretschmann O, Steffens C, Ritter H. Angew Chem Int Ed 2007;46:2708e11. Ohashi H, Hiraoka Y, Yamaguchi T. Macromolecules 2006;39:2614e20. Yan J, Zhang X, Li W, Zhang X, Liu K, Wu P, et al. Soft Matter 2012;8:6371e7. Hu G, Li W, Hu Y, Xu A, Yan J, Liu L, et al. Macromolecules 2013;46:1124e32. Hua F, Jiang X, Zhao B. Macromolecules 2006;39:3476e9. Zhang Z-X, Liu KL, Li J. Macromolecules 2011;44:1182e93. Weiss J, Bȍttcherb C, Laschewsky A. Soft Matter 2011;7:483e92. Peng B, Grishkewich N, Yao Z, Han X, Liu H, Tam KC. ACS Macro Lett 2012;1: 632e5. Schlüter AD, Rabe JP. Angew Chem Int Ed 2000;39:864e83. Zhang A, Shu L, Bo Z, Schlüter AD. Macromol Chem Phys 2003;204:328e39. Rosen BM, Wilson CJ, Wilson DA, Peterca M, Imam MR, Percec V. Chem Rev 2009;109:6275e540. Chen Y, Xiong X. Chem Commun 2010;46:5049e60. Li W, Zhang A, Feldman K, Walde P, Schlüter AD. Macromolecules 2008;41: 3659e67. Li W, Zhang A, Schlüter AD. Chem Commun 2008:5523e5. Li W, Wu D, Schlüter AD, Zhang A. J Polym Sci A Polym Chem 2009;47: 6630e40. Li W, Zhang X, Zhao X, Zhang A. J Polym Sci A Polym Chem 2013;51:5143e52. Li W, Yan J, Zhang A. Encycl Polym Sci Technol 2012. http://dx.doi.org/ 10.1002/0471440264.pst548. Junk MJN, Li W, Schlüter AD, Wegner G, Spiess HW, Zhang A, et al. Angew Chem Int Ed 2010;49:5683e7. Junk MJN, Li W, Schlüter AD, Wegner G, Spiess HW, Zhang A, et al. J Am Chem Soc 2011;133:10832e8. Liu L, Li W, Liu K, Yan J, Hu G, Zhang A. Macromolecules 2011;44:8614e21. Liu K, Zhang X, Tao X, Yan J, Kuang G, Li W, et al. Polym Chem 2012;3: 2708e11. €chtersbach E, Schmidt M, Schlüter AD. Chem Eur J Zhang A, Zhang B, Wa 2003;9:6083e92. Chen F, Zhang X, Li W, Liu K, Guo Y, Yan J, et al. Soft Matter 2012;8:4869e72. This mixed solvent is selected for the purpose to visualize the active protons in 1H NMR spectra. See, for example Bartoloni M, Kadam RU, Schwartz J, Furrer J, Darbre T, Reymond J-L. Chem Commun 2011;47:12634e6. There are two possibilities for these protons to show broadened and reduced signals with temperature: (1) dehydration themselves, or (2) physically imbedded within the collapsed phase. For the protons from amide and lysine moieties in present polymers, their peaks broadening and intensity reduction at elevated temperature should be originated from the second case.