Block and Gradient Copolymers of 2-Hydroxyethyl Acrylate and 2

Article pubs.acs.org/Macromolecules

Block and Gradient Copolymers of 2‑Hydroxyethyl Acrylate and 2‑Methoxyethyl Acrylate via RAFT: Polymerization Kinetics, Thermoresponsive Properties, and Micellization Wiktor Steinhauer,† Richard Hoogenboom,†,‡,* Helmut Keul,† and Martin Moeller† †

DWI an der RWTH Aachen e.V. and Institute of Technical and Macromolecular Chemistry, RWTH Aachen, Forckenbeckstrasse 50, 52056 Aachen, Germany ‡ Supramolecular Chemistry Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Ghent, Belgium S Supporting Information *

ABSTRACT: Well-defined homopolymers of 2-hydroxyethyl acrylate (HEA) with different degrees of polymerization are synthesized via reversible addition−fragmentation chain transfer polymerization (RAFT), using dibenzyltrithiocarbonate (DBTTC) as chain transfer agent. Subsequently, well-defined triblock copolymers of HEA and 2-methoxyethyl acrylate (MEA) with the general microstructure P(HEA)-block-P(MEA)-blockP(HEA) and P(HEA)-block-P(HEA-grad-MEA)-block-P(HEA) are synthesized via RAFT, using previously prepared HEAbased homopolymers with degrees of polymerization of Pn ∼ 20− 70 as macro-chain transfer agents (MCTAs). Kinetic investigations on all of the performed (co)polymerizations are summarized, revealing that all polymerizations proceed in a controlled manner. The thermoresponsive properties of aqueous solutions of the synthesized copolymers with block or gradient microstructures are determined and discussed, revealing adjustable cloud point (CP) temperatures between 0 and 80 °C for copolymers with the pure block microstructure and between 0 and 60 °C for copolymers with gradient microstructures, showing differently pronounced hysteresis on heating and cooling. All of the obtained copolymers feature a temperature dependent amphiphilic character resulting in the formation of spherical aggregates above the CP temperature as proven by fluorescence spectroscopy, cryo-SEM, and DLS. Thus, new thermoresponsive materials were successfully prepared revealing insights into the differences between block and gradient microstructures.

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INTRODUCTION Self-assembling molecules are of ever increasing theoretical and experimental interest. Among the most important selfassembling systems are polymeric micelles. These micelles differ from the more familiar detergent micelles, based on low molar mass amphiphiles, by their larger size and higher stability.1 Polymeric micelles are often used as molecular tools in medicine and farmacy, such as drug delivery, imaging agents and diagnostics, 2−17 in separation techniques such as chromatography,18,19 in the synthesis of nanomaterials,20−32 and in many other applications.33 It is well-known that block copolymers, when dissolved in selective solvents (e.g., solvents that are good for one block but poor for the other), assemble into micelles (with a dense core formed by the insoluble blocks and a corona consisting of the soluble blocks), whose properties can be tailored by the chemical nature, the molecular weight of each block,34−38 solvent/block interactions,39,40 the concentration,41,42 the microstructure and/or architecture43−47 of the block copolymer. However, block copolymers can be prepared by two general routes: (i) generation of reactive sites on the chain end of the polymer A, followed by polymerization of monomer B (C, D and so on) using the activated polymer as (macro)initiator and (ii) coupling of preformed polymers A © 2013 American Chemical Society

and B (C, D and so on) having at one chain end functional groups able to undergo covalent bond formation. Free radical polymerization is the method of choice for the preparation of block copolymers of a wide variety of vinyl monomers. But, conventional free radical polymerization does not allow preparing polymers of narrow molecular weight distribution, severely hampering the synthesis of block polymers of controlled architectures, narrow dispersity and controlled molecular weight. The development of controlled radical polymerization techniques (CRP), such as nitroxide-mediated polymerization (NMP),48−50 atom transfer radical polymerization (ATRP),51−54 and reversible addition−fragmentation chain transfer (RAFT) polymerization,55−57 has widened the scope for block polymer synthesis, making it possible to polymerize vinyl monomers, in contrast to, e.g., living anionic polymerization, under less demanding reaction conditions. However, current research focuses on the design of more complex associative polymers in order to develop stimuliresponsive systems (so-called “smart” polymers), able to Received: December 19, 2012 Revised: January 22, 2013 Published: February 11, 2013 1447

dx.doi.org/10.1021/ma302606x | Macromolecules 2013, 46, 1447−1460

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of six parallel temperature controlled sample holders are connected to a Cary temperature controller allowing 12 simultaneous measurements. Turbidity of the solutions was measured by the transmission of light at wavelengths of 400, 500, 600, and 700 nm through the sample vial as a function of the temperature. Solutions of the polymers (c = 5 mg/mL) were prepared in deionized water and were stirred at room temperature until all polymer was dissolved or dispersed. Two heating/cooling cycles were applied from 1 to 97 °C at 1.0 °C/min while stirring with hold steps of 5 min at the extreme temperatures. The cloud points are given as the 50% transmittance point during the second heating ramp. Steady-state fluorescence spectra were recorded on a Perkin-Elmer LS50 spectrometer. The temperature control of the samples was achieved using a MGW Lauda K20 temperature controller. The measurements were carried out at 5, 15, 25, 35, and 45 °C unless otherwise stated. 8-Anilino-1-naphthalenesulfonic acid (sodium salt) (ANS) was used as a fluorescence probe (c = 2.5 × 10−5 mol·L−1). The slit settings were 8.0 nm for excitation and 3.0 nm for emission. Emission spectra were recorded with an excitation wavelength of 350 nm. Solutions were kept at room temperature for 24 h prior to measurements and were not degassed. The hydrodynamic diameters Dh of the aggregates/micelles formed in water solutions at c = 1 g/L were measured using an ALV/CGS-3 Goniometer with an ALV/LSE 7004 Tau Digital Correlator and a JDS Uniphase laser operating at 633 nm. The measurements were performed at 5, 15, 25, 35, and 45 °C at an angle of 90 °C after equilibrating the samples for at least 24 h. The value of the hydrodynamic diameter and dispersity index of the aggregates/micelles were obtained by cumulant analysis using the appendant ALVcorrelator software V. 3.0. SEM images were measured of cryo-fractured specimens using a Hitachi S-4800. Polymerizations. Synthesis of PHEA MCTA. HEA (11.61 g, 99.98 mmol) and DBTTC (0.86 g, 2.97 mmol) were dissolved in DMF (50 mL). After degassing the solution three times by freezevacuum-thaw cycles, the mixture was immersed in an oil bath thermostated at 70 °C while stirring. The polymerization was started by adding AIBN (0.10 g, 0.59 mmol) and proceeded for 2.3 h at 70 °C. PHEA (P5) was isolated and purified by triple precipitation in diethyl ether, collected and dried under reduced pressure at room temperature. PHEA-MCTA: Mn,SEC(DMF) = 4100 g/mol; Mw/Mn = 1.2 monomodal. 1H NMR (DMSO-d6): δ 1.2−2.0 (b, −CH2−CH− (−C(O)OR)−), 2.1−2.4 (b, −CH2−CH-(−C(O)OR)−), 3.4−3.7 (b, −C(O)O−CH2−CH2−OH), 3.8−4.2 (b, −C(O)O−CH2−CH2− OH), 4.7−4.9 (b, −OH), 7.1−7.4 (m, Ar−H) ppm. PHEA MCTAs with different degrees of polymerization were synthesized according to the above-described procedure using different molar ratios of the HEA and DBTTC in the feed and/or varying the reaction time using a ratio of [DBTTC]:[I] = 1.0:0.2 (Table S1; Supporting Information). Conversion, Pn, Mn, and PDI values of the PHEA polymers obtained are summarized in Table 1. Synthesis of PHEA-block-PMEA-block-PHEA Triblock Copolymers. PHEA MCTA (PHEA-5, 1.17 g, 0.22 mmol) and MEA (2.87 g, 19.80 mmol) were dissolved in DMF (11.0 mL). After degassing the solution three times by freeze-vacuum-thaw cycles, the mixture was immersed in an oil bath thermostated at 70 °C while stirring. The polymerization was started by adding AIBN (0.01 g, 0.04 mmol) and proceeded for 0.5 h at 70 °C. The triblock-copolymer (HEA-MEA-HEA-block-3) was isolated and purified by triple precipitation in diethyl ether, collected and dried under reduced pressure at room temperature. PHEA-block-PMEA-block-PHEA: Mn,SEC(DMF) = 11700 g/mol; Mw/Mn = 1.2 monomodal. 1H NMR (DMSO-d6): δ 1.2−2.0 (b, −CH2−CH−(−C(O)OR)−), 2.1−2.4 (b, −CH2−CH−(−C(O)OR)−), 3.2−3.3 (b, −O−CH3), 3.4−3.7 (b, −C(O)O−CH2−CH2− OH and −C(O)O−CH2−CH2-O−CH3), 3.8−4.2 (b, −C(O)O− CH2−CH2−OH and −C(O)O−CH2−CH2−OCH3), 4.7−4.9 (b, −OH), 7.1−7.4 (m, Ar−H) ppm.

respond repeatedly and reversibly to an external trigger, such as a change of solution pH or temperature or upon light irradiation.58−71 As in many other applications, stimuliresponsive polymers often contain blocks able to change rapidly from being hydrophobic to hydrophilic (or vice versa), on the basis of pH-changes or irradiation with light of a specific wavelength. They may also take advantage of the changes in the hydration and conformation of a polymer chain in water as the solution is heated or cooled through its lower critical solution temperature (LCST). The most widely studied thermoresponsive water-soluble polymer with LCST behavior is poly(Nisopropylacrylamide) (P(NIPAM)), which has been known since 1956 and still attracts much attention, because its LCST of 32 °C is close to physiological conditions and is quite insensitive to variations in molecular weight and concentration.65 Other thermoresponsive aqueous polymers include cellulose ethers,72 poly(2-alkyl-2-oxazolines,73−75 poly(methyl vinyl ether)s76 as well as various poly(acrylate)s and poly(methacrylate)s.77−79 In the present work, the synthesis of well-defined homopolymers of 2-hydroxyethyl acrylate (HEA) with different degrees of polymerization via reversible addition−fragmentation chain transfer (RAFT), using dibenzyltrithiocarbonate (DBTTC) as chain transfer agent (CTA), is presented. Furthermore, well-defined triblock copolymers of HEA and 2methoxyethyl acrylate (MEA) with the general microstructures P(HEA)-block-P(MEA)-block-P(HEA) and P(HEA)-block-P(HEA-grad-MEA)-block-P(HEA) were synthesized via RAFT polymerization, using previously prepared HEA-based homopolymers as macro-chain transfer agents (MCTA). Adjusting the addition rate of MEA to the preset HEA/MCTA ratio during the polymerization reaction a good control over the microstructure of the middle block of the P(HEA)-blockP(HEA-grad-MEA)-block-P(HEA)-copolymer was provided. The influence of the polymer microstructure on the cloud point (CP) temperatures as well as on the self-organization behavior of the copolymers in aqueous solutions were determined and the effect of both the ratio of hydrophilic and hydrophobic monomers and the microstructure on the cloud points and the self-organization are discussed.

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EXPERIMENTAL SECTION

Materials and Instrumentation. N,N-Dimethylformamide (DMF), HEA and MEA were obtained from Sigma-Aldrich and passed through a neutral aluminum oxide column before use to remove the inhibitor. DBTTC was kindly provided by Arkema and used as received. 2,2′-Azobis(isobutyronitrile) (AIBN) was obtained from Aldrich and purified by double recrystallization from methanol. The sodium salt of the 8-anilino-1-naphthalenesulfonic acid (ANS) was obtained from Aldrich and used without further purification. 1 H NMR spectra were recorded on a Bruker DPX-400 FT-NMR spectrometer at 400 MHz, using deuterated dimethyl sulfoxide (DMSO-d6) as solvent, and tetramethylsilane (TMS) as an internal standard. Size exclusion chromatography (SEC) was measured on a combined SEC system with a high pressure liquid chromatography pump (Bischoff HPLC), a Jasco 2035-plus RI detector and four MZ-DVB gel columns (30 Å, 100 Å and 2 × 3000 Å) in series at 30 °C. A solution of DMF containing 1.0 g LiBr/L was used as eluent at a flow rate of 1.0 mL/min. The molecular weights were calculated using a poly(methyl methacrylate) (PMMA) calibration (9 standards with molar masses ranging from 2.2 kDa to 675 kDa) and the PSS WinGPC Unity software. Cloud points of aqueous polymer solutions were determined by turbidity measurements in a Cary 100 BIO by VARIAN. Two blocks 1448


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grad-MEA) blocks were synthesized according to the above-described procedure using MCTA with different degrees of polymerization in the feed, varying the addition rates of MEA (purged with argon for 1 h) and the reaction time using a ratio of [MCTA]:[I] = 1.0:0.2 (Table S3; Supporting Information). Conversion, Pn, Mn and PDI values of the polymers HEA-MEA-HEA-grad-1 to HEA-MEA-HEA-grad-6 obtained are summarized in Table 3. For the kinetic investigations, samples (250 μL) were taken from the polymerization mixture after 15, 30, 60, 120, 240, 300, and 360 min. These samples were characterized using SEC and 1H NMR spectroscopy. General Procedure for the Synthesis of Poly(2-hydroxyethyl acrylate-co-2-methoxyethyl acrylate) Diblock Copolymers by Cleavage of Triblock Copolymers with AIBN. HEA-MEA-HEAblock-3 (0.70 g, 0.07 mmol) was dissolved in DMF (13.4 mL). After the mixture was immersed in an oil bath and thermostated at 100 °C while stirring, the reaction was started by adding AIBN (1.11 g, 6.75 mmol) and proceeded for 3 h at 100 °C. The resulting diblock copolymer HEA-MEA-block-3 was isolated and purified by precipitation in diethyl ether, collected and dried in vacuum at room temperature. Mn,SEC(DMF) = 7100 g/mol; Mw/Mn = 1.2 monomodal. 1H NMR (DMSO-d6): δ 1.2−2.0 (b, −CH2−CH−(−C(O)OR)−), 1.5 (s, NC− C((−CH3)2)−R−), 2.1−2.4 (b, −CH2−CH−(−C(O)OR)−), 3.2− 3.3 (b, −O−CH3), 3.4−3.7 (b, −C(O)O−CH2−CH2−OH and −C(O)O−CH2-CH2−O−CH3), 3.8−4.2 (b, −C(O)O−CH2−CH2− OH and −C(O)O−CH2−CH2−OCH3), 4.7−4.9 (b, −OH), 7.1−7.4 (m, Ar−H) ppm. HEA-MEA diblock copolymers with different length of each block and/or micro structure were synthesized according to the abovedescribed procedure with different triblock (gradient) copolymers in the feed (Table S4; Supporting Information). All of the cleavage reactions with AIBN were performed according to the literature in degassed DMF (purged with argon for 1 h).80 Conversion, Pn, Mn and PDI values of the HEA-MEA copolymers obtained are summarized in Table 4.

Table 1. Characterization of Poly(hydroxyethyl acrylate) Macro-Chain Transfer Agents (PHEA) Synthesized by Homopolymerization of 2-Hydroxyethyl Acrylate via RAFT in DMF at 70 °C Using DBTTC as RAFT-Agent and AIBN as Initiator ([DBTTC]:[I] = 1.0:0.2) polymer

conversiona [%]

Pn,thb

Pna

Mna [g/mol]

Mnc [g/mol]

PDIc

PHEA-1 PHEA-2 PHEA-3 PHEA-4 PHEA-5 PHEA-6 PHEA-7 PHEA-8 PHEA-9 PHEA-10 PHEA-11

45 45 76 77 83 76 62 47 69 72 63

8 8 14 26 28 36 47 47 53 54 63

23 25 28 41 43 51 63 63 69 70 81

2940 3190 3540 5020 5310 6240 7550 7560 8270 8440 9700

2900 2600 3100 3800 4100 4800 6100 6100 6800 6800 6900

1.1 1.2 1.1 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2

a Determined using 1H NMR spectroscopy. bCalculated applying the equation Pn,th = ([Mt0]/[I]) × xp with xp = conversion (in %)/100%. c Determined by SEC (DMF) using PMMA standards.

PHEA-block-PMEA-block-PHEA triblock copolymers with different length of PHEA and PMEA blocks were synthesized according to the above-described procedure using MCTAs with different degrees of polymerization, a ratio of [M]:[MCTA]:[I] = 100:1.0:0.2 in the feed and different reaction times (Table S2; Supporting Information). Conversion, Pn, Mn, and PDI values of the polymers HEA-MEA-HEAblock-1 to HEA-MEA-HEA-block-6 obtained are summarized in Table 2. Synthesis of PHEA-block-(PHEA-grad-MEA)-block-PHEA Triblock Copolymers. PHEA MCTA (PHEA-4, 1.02 g, 0.20 mmol) and HEA (1.40 g, 12.08 mmol) were dissolved in DMF (10.2 mL). After degassing the solution three times by freeze−vacuum−thaw cycles, the mixture was immersed in an oil bath thermostated at 70 °C while stirring. The polymerization was started by adding AIBN (0.01 g, 0.04 mmol) and proceeded for 25 min at 70 °C while MEA (6.03 g/h; 46.36 mmol/h) was added dropwise via syringe pump (addition rate: 6.11 mL/h). The triblock-gradient-copolymer (HEA-MEA-HEA-grad2) was isolated and purified by triple precipitation in diethyl ether, collected and dried under reduced pressure at room temperature. P(HEA)-block-P(HEA-grad-MEA)-block-P(HEA): Mn,SEC(DMF) = 7700 g/mol; Mw/Mn = 1.3 monomodal. 1H NMR (DMSO-d6): δ 1.2− 2.0 (b, −CH2−CH−(−C(O)OR)−), 2.1−2.4 (b, −CH2−CH− (−C(O)OR)−), 3.2−3.3 (b, −O−CH3), 3.4−3.7 (b, −C(O)O− CH2−CH2−OH and −C(O)O−CH2−CH2−O−CH3), 3.8−4.2 (b, −C(O)O−CH2−CH2−OH and −C(O)O−CH2−CH2−OCH3), 4.7− 4.9 (b, −OH), 7.1−7.4 (m, Ar-H) ppm. P(HEA)-block-P(HEA-grad-MEA)-block-P(HEA) triblock gradient copolymers with different microstructure and length of the P(HEA-

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RESULTS AND DISCUSSION The present work describes the RAFT polymerization of MEA using previously synthesized PHEA MCTAs II (PHEA MCTA; Table 1) and AIBN as initiator with [M]:[MCTA]:[AIBN] ratios of 100:1:0.2. Performing the polymerizations at 70 °C and at ∼1.4−1.6 M monomer solutions in DMF resulted in triblock copolymers with a general microstructure III and degree of polymerization of Pn ∼ 80 (Scheme 1). Additionally, the RAFT copolymerization of HEA and MEA using PHEA MCTA (II) with degrees of polymerization of 25 and 41 and AIBN as initiator with initial [HEA]:[MCTA]:[AIBN] ratios of 80:1:0.2 and 60:1:0.2, are described. As we reported previously,81 the RAFT copolymerization of HEA and MEA in DMF at 70 °C proceeds as ideal random copolymerization

Table 2. Characterization of Poly(2-hydroxyethyl acrylate)-block-poly(2-methoxyethyl acrylate)-block-poly(2-hydroxyethyl acrylate)] triblock copolymers (HEA-MEA-HEA-block) Synthesized by Application of Different Poly(2-hydroxyethyl acrylate) Macro-Chain Transfer Agents in Polymerization of 2-Methoxyethyl Acrylate via RAFT in DMF at 70 °C Using AIBN as Initiator and a Ratio of [MCTA]:[I] = 1.0:0.2 polymer

Pn,HEA

conversiona [%]

Pn,th,MEAb

Pn,MEAa

HEA/MEAa [mol %]

Mna [g/mol]

Mnc [g/mol]

PDIc

HEA-MEA-HEA-block-1 HEA-MEA-HEA-block-2 HEA-MEA-HEA-block-3 HEA-MEA-HEA-block-4 HEA-MEA-HEA-block-5 HEA-MEA-HEA-block-6

23 28 43 51 63 70

66 50 40 28 21 17

71 51 44 28 19 13

56 51 40 26 15 10

29/71 35/65 52/48 67/33 81/19 88/12

10 200 10 190 10 450 9900 9590 9910

12 100 11 300 11 700 7800 8700 8200

1.2 1.2 1.2 1.3 1.2 1.2

Determined using 1H NMR spectroscopy. bCalculated applying the equation Pn,th = ([Mt0]/[I]) × xp with xp = conversion (in %)/100%. Determined by SEC (DMF) using PMMA standards.

a c

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Table 3. Characterization of Poly{(2-hydroxyethyl acrylate)-block-[(2-hydroxyethyl acrylate)-grad-(2-methoxyethyl acrylate)]block-(2-hydroxyethyl acrylate)} Triblock Copolymers (HEA-MEA-HEA-grad) Synthesized by Application of Different Poly(2hydroxyethyl acrylate) Macro-Chain Transfer Agents in Polymerization of 2-Methoxyethyl Acrylate via RAFT in DMF at 70 °C Using AIBN as Initiator and [MCTA]:[I] Ratio of 1.0:0.2 grad-blocka

a

polymer

macro-CTA Pn,HEA

Pn,HEA

Pn,MEA

HEA/MEA [mol %]

HEA/MEAa total [mol %]

Mna [g/mol]

Mnb [g/mol]

PDIb

HEA-MEA-HEA-grad-1 HEA-MEA-HEA-grad-2 HEA-MEA-HEA-grad-3 HEA-MEA-HEA-grad-4 HEA-MEA-HEA-grad-5 HEA-MEA-HEA-grad-6

41 41 41 25 25 25

8 19 28 27 17 12

39 22 16 26 46 43

17/83 46/54 64/26 51/49 27/73 21/79

56/44 73/27 82/18 66/33 48/52 47/53

11 000 10 180 10 320 9730 11 170 9470

10 800 7700 8600 10 500 12 600 9800

1.3 1.3 1.2 1.2 1.3 1.3

Determined using 1H NMR spectroscopy. bDetermined by SEC (DMF) using PMMA standards.

Table 4. Characterization of Diblock Copolymers with Different Micro Structures Synthesized by Cleavage of the Corresponding Poly(2-hydroxyethyl acrylate)-block-poly(2-methoxyethyl acrylate)-block-poly(2-hydroxyethyl acrylate)] or Poly(2-hydroxyethyl acrylate)-block-poly(2-hydroxyethyl acrylate-grad-2-methoxyethyl acrylate)-block-poly(2-hydroxyethyl acrylate) Triblock Copolymers with AIBN in 3 h in DMF at 100 °C Using a [AIBN]:[triblock copolymer] Ratio of 100:1 starting polymer (triblock)

a

cleaved polymer (diblock)

polymer

no.

Pna

Mnb/[g/mol]

PDIb

Pna

Mnb/[g/mol]

PDIb

HEA-MEA-block-1 HEA-MEA-block-2 HEA-MEA-block-3 HEA-MEA-block-4 HEA-MEA-block-5 HEA-MEA-block-6 HEA-MEA-grad-1 HEA-MEA-grad-2 HEA-MEA-grad-3 HEA-MEA-grad-4 HEA-MEA-grad-5 HEA-MEA-grad-6

HEA-MEA-HEA-block-1 HEA-MEA-HEA-block-2 HEA-MEA-HEA-block-3 HEA-MEA-HEA-block-4 HEA-MEA-HEA-block-5 HEA-MEA-HEA-block-6 HEA-MEA-HEA-grad-1 HEA-MEA-HEA-grad-2 HEA-MEA-HEA-grad-3 HEA-MEA-HEA-grad-4 HEA-MEA-HEA-grad-5 HEA-MEA-HEA-grad-6

79 79 83 80 81 82 88 82 85 78 88 80

12 100 11 300 11 700 7800 8700 8200 10 800 7700 8600 10 500 11 000 9800

1.2 1.2 1.2 1.3 1.2 1.2 1.3 1.3 1.2 1.2 1.3 1.3

45 45 46 42 45 45 51 45 49 41 42 39

7500 7400 7100 6500 6600 6400 7100 6200 6400 7400 7500 6900

1.1 1.2 1.2 1.2 1.2 1.2 1.3 1.2 1.2 1.2 1.2 1.4

Determined using 1H NMR spectroscopy. bDetermined by SEC (DMF) using PMMA standards.

lower initial monomer to RAFT agent ratio resulting from the higher concentration of AIBN. However, there is no linear correlation between the amount of AIBN and the polymerization rate, i.e. increasing the amount of AIBN ∼ 6 fold when lowering the [M]/[CTA] ratio from 99.5 to 17.3 lead to ∼2 fold increase in polymerization rate. On the basis of these HEA homopolymerization kinetics, a series of well-defined PHEA MCTA II with DP of ∼20, 30, 40, 50, 60, 70, and 80 was prepared (Table 1). Subsequent to the synthesis of MCTAs, the kinetics of the MEA polymerization using PHEA based MCTAs with degrees of polymerization of ∼20, 40, 60, and 80 were investigated. The first order kinetic plots for the MEA polymerization revealed a linear dependence indicating a constant free radical concentration indicating the absence of significant termination reactions (Figure 1, top). A linear increase of Mn,SEC with conversion as well as reasonably low dispersities (PDI ≤ 1.4) (Figure 1, bottom) were observed for all polymerizations demonstrating that these proceeded in a controlled manner. Furthermore, the polymerization rates of MEA using MCTAs with different DPs were found to be very similar, indicating a dependency of the reaction rates on the monomer concentration, but not on the degree of polymerization of the used MCTAs. After determination of the copolymerization kinetics two series of block copolymers of HEA and MEA with different degrees of polymerization (HEA-MEA-HEA-block with DP∼80

with reactivity ratios equal to 1. Thus, changing the HEA/MEA ratio in the solution during the copolymerization affects the ratio of the comonomers incorporated into the growing copolymer yielding copolymers with gradient microstructures. Therefore, varying the addition rates of MEA during the copolymerization will linearly change the amount of incorporated HEA and MEA leading to gradient triblock microstructure IV and degree of polymerization of Pn ∼ 80. Treatment of the triblock copolymers III and IV with AIBN results in diblock copolymers V and VI with degree of polymerization of Pn/2− 40 while retaining the same absolute composition as the precursor copolymers. Furthermore, a comparison of the synthesized copolymers on the cloud point (CP) temperatures as well as on the self-organization behavior in aqueous solutions as a function of both, the ratio of hydrophilic and hydrophobic monomers and the microstructure are presented. The kinetics of the homopolymerization of HEA with different monomer to RAFT transfer agent ratios in the feed revealed a linear first order kinetic plot indicating a constant free radical concentration indicative for the absence of significant termination reactions (Supporting Information, Figure S1, top). A linear increase of molecular weight with conversion as well as the relatively narrow molecular weight distributions (dispersity index (PDI) ≤ 1.2) further demonstrated good control over the polymerization of HEA (Supporting Information, Figure S1, bottom). As might be expected, the homopolymerization of HEA was faster with a 1450


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Scheme 1. Synthesis of PHEA-block-PMEA-block-PHEA (III; HEA-MEA-HEA-block) and PHEA-block-P(HEA-grad-MEA)block-PHEA (IV; HEA-MEA-HEA-grad) Triblock Copolymers with Degrees of Polymerization of Pn via RAFT, Followed by Treatment of the Copolymers (III and IV) with AIBN Leading to PHEA-block-PMEA (V; HEA-MEA-block) and PHEA-blockP(HEA-grad-MEA) (VI; HEA-MEA-grad) Diblock Copolymers with Pn/2

and HEA-MEA-block with DP∼40) but the same monomer composition were prepared in order to investigate the effect of the monomer composition and the copolymer structure on the cloud point and their temperature-responsive self-assembly (micellization) behavior. The first copolymer series with DP of

80 (HEA-MEA-HEA-block) was prepared by changing both the length of the MCTA (DP 20−80) and the PMEA-block (Table S2, Supporting Information). The second copolymer series was prepared by controlled cleavage of these triblock copolymers with DP 80 using AIBN (Table S4, Supporting Information) 1451


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polymerizations. Furthermore, the copolymerization rate of HEA and MEA with an addition rate of MEA of 1500 equiv/h was reproducibly found to be slower than the corresponding copolymerizations with MEA-addition rates of ∼227 and 836 equiv/h, whereas the reaction rate of the copolymerization with the addition rate of 836 equiv/h was found to be the highest. In general, the polymerization rate depends on the concentration of free radicals only and should not be affected by changing the monomer concentration. However, due to addition of the MEA in time, the polymerization volume increases and, thus, the radical concentration decreases theoretically leading to a decrease in polymerization rate. This decrease in polymerization rate should be more pronounced at higher monomer addition rates. Using the PHEA-MCTA with DP 41 five different copolymerizations with the addition rates of MEA of ∼56, ∼113, 227, ∼836, and 1500 equiv/h were investigated. The linear dependence of the first order kinetic plots for the overall monomer conversions (Figure 2b) and a linear increase of the molecular weights (SECDMF) with the theoretical molecular weights calculated from the monomer conversions, as well as the relatively narrow molecular weight destributions (PDI ≤ 1.3; Figure 2d), again demonstrate good control over the copolymerizations. Additionally, the reaction rates of the copolymerization reactions with different addition rates of MEA were found to be rather similar using MCTA with DP of 43, demonstrating an unexpected independency of the polymerization reaction on the addition rate of the second monomer. Using PHEA-based MCTA with different degrees of polymerization (DP 25 and DP 41) and changing the addition rates of MEA (56−1500 equiv/h with respect to the PHEA MCTA) different copolymers with well-defined gradient copolymers (Scheme 1; IV; PHEA-MEA-HEA-grad) were obtained. The transition regime where the monomers are mixed begins immediately at the start of the polymerization of the middle block, i.e., upon addition of the second monomer, and continues in all cases until the final degree of polymerization of the formed copolymers (DP ∼ 80) was reached. Furthermore, the local amount of the incorporated MEA remains always below 100%, making sure that no additional MEA-homopolymer block was formed. The difference of the obtained copolymers was evaluated by calculating the monomer distribution (MEA amounts) along the copolymer chains from the copolymerization kinetics (Figure 2) and fitting them with an exponential decrease function to estimate the monomer gradients (Figure 3). Generally, when comparing PHEA MCTA with Pn 25 and 41, the maximum number of MEA repeating units incorporated into the copolymer chain was found, as expected, to increase with increasing addition rate of the second momoner: the higher the addition rate the more MEA was incorporated. The only exception to this rule was the copolymerization reaction using a macro-CTA with DP 41 and a MEA-addition rate of 113 equiv/h, when the incorporated MEA amount at DP 80 was found to be higher than for the copolymerization with the MEA-addition rate of 227 equiv/h (Figure 3, bottom; 36 mol % (113 equiv/h) vs 32 mol % (227 equiv/h)). This can be explained, since the copolymerization reaction using a MEA-addition rate of 113 equiv/h needed more time to achieve a degree of polymerization of 80 due to its lowest reactivity ratio as observed during the corresponding kinetic studies (Figure 2b). During this additional time (until DP 80 was reached) more HEA could be added to the copolymerization mixture with a MEA-addition rate of 113 equiv/h in comparison to the corresponding polymerization

Figure 1. Top: Kinetic plot of ln([M]0/[M]t) versus time for the RAFT polymerizations of 2-methoxyethyl acrylate (MEA) using P(HEA) based macro-chain transfer agents with different degrees of polymerization. Bottom: Plot of the experimental number-average molecular weight (Mn) and dispersity index (PDI) versus conversion for the RAFT polymerizations of MEA using PHEA-based macrochain transfer agents with different degrees of polymerization.

resulting in copolymers with DP of 40 (HEA-MEA-block) with the same monomer composition as the precursor copolymers, carrying a benzyl group on one chain end and an isobutyronitrile group on the other. The molecular weight and PDI values of the purified block-copolymers are summarized in Table 2 and 4 (experimental part). In a next step, the kinetics of the HEA-MEA copolymerizations using PHEA-MCTAs with DP of 25 and 41 and different addition rates of MEA (∼56, 113, 227, 836, and 1500 equiv/h with respect to the PHEA MCTA) were investigated. All the copolymerization reactions were initiated by the addition of AIBN to the MCTA/HEA mixtures in DMF at 70 °C, while at the same time the continuous addition of MEA to the reaction mixture was started (syringe pump). The MCTA and HEA concentrations in the initial copolymerization mixtures were in all cases 0.02 M for the MCTA and 1.2−1.5 M for the HEA using the MCTA with DP of 25 and 0.9 M using the MCTA with DP of 41. Using the PHEA-MCTA with DP 25 three different copolymerizations with the addition rates of MEA of ∼227, ∼836, and 1500 equiv/h were investigated, showing linear first order kinetic plots for the overall monomer conversions (Figure 2a) and a linear increase of the molecular weights (SECDMF) with the theoretical molecular weights calculated from the monomer conversions, as well as relatively narrow molecular weight destributions (PDI ≤ 1.4; Figure 2c), clearly demonstrating good control over these continuously fed 1452


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Figure 2. (a and b) First order plots of the RAFT polymerizations of 2-hydroxyethyl acrylate (HEA)/2-methoxyethyl acrylate (MEA) with different addition rates of MEA using PHEA based macro-chain transfer agents with degrees of polymerization of ∼25 (a) and ∼41 (b). (c and d) Corresponding plots of the experimental number-average molecular weight (Mn) and dispersity index (PDI) versus theoretical number-average molecular weight (Mn,th; calculated from the monomer to macro-CTA ratio and monomer conversion) of the RAFT polymerizations of HEA/MEA with different addition rates of MEA using PHEA macro-chain transfer agents with degrees of polymerization of ∼25 (c) and ∼41 (d). The dashed line represents the ideal situation where Mn,th = Mn,SEC.

MEA-HEA-block-4 to HEA-MEA-HEA-block-6) were prepared by changing the length of the PHEA MCTA (DP 25 and 43) and thus the polymerization time as well as the addition rate of MEA (Tab. S3, Supporting Information). The third and fourth copolymer series (VI; HEA-MEA-block-1 to HEA-MEA-block-3 and HEA-MEA-block-4 to HEA-MEA-block-6) were prepared by controlled cleavage of the copolymers with DP∼80 using AIBN (Tab. S4, Supporting Information) resulting in copolymers with DP 40 (diblock) with the same monomer composition as the precursor copolymers, carrying a benzyl group on the one end and an isobutyronitrile group on the other. The molecular weights and PDI values of the purified gradient copolymers are summarized in Tables 3 and 4 (experimental part). Thermoresponsive Properties of the Copolymers. The thermoresponsive properties of the synthesized copolymers were investigated by turbidimetry. For this purpose aqueous polymer solutions (c = 5 mg/mL) were heated and cooled between 1 and 97 °C at 1 °C/min while stirring and cloud points were determined at 50% transmittance of light at wavelengths of 700 nm during polymer precipitation in the second heating run as well as dissolution in the second cooling run. All observed phase transitions were found to be fully reversible, showing differently pronounced hysteresis between heating and cooling as indicated by different proximity of open

with the MEA-addition rate of 227 equiv/h resulting in the observed difference of the final MEA amounts in the investigated copolymers. However, starting with a MCTAs with DP 41 and adjusting MEA-addition rates between 56− 1500 equiv/h well-defined HEA-MEA-HEA triblock copolymers containing about 26−57 mol % of MEA repeating units were obtained until DPs of ∼80 were achieved (Figure 3, bottom). Adjusting MEA-addition rates of 227−1500 equiv/h to polymerization mixtures using MCTAs with DP 25, the maximum amounts of the incorporated MEA repeating units were further incresed (Figure 3, top; e.g., 57 mol % (MCTA ∼ 43, 1500 equiv/h) vs 71 mol % (MCTA ∼ 25, 1500 equiv/h)). Using shorter MCTAs the total polymerization time (DP 43 → ∼80 vs DP 25 → ∼80) increases, leading to longer MEAaddition periods and, thus, a higher MEA-amount in the resulting copolymers. After determination of the copolymerization kinetics, four series of HEA-MEA copolymers with well-defined gradients and different degrees of polymerization (HEA-MEA-HEAblock with DP ∼80 and HEA-MEA-block with DP ∼40) but same composition were prepared in order to investigate the effect of the monomer composition and the structure on the cloud point and their self-organization (micellization) behavior (Table 5). The first two copolymer series with DP of 80 (IV; HEA-MEA-HEA-block-1 to HEA-MEA-HEA-block-3 and HEA1453


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polymerization was found to be less pronounced,77 the measured differences for the corresponding block- and gradient-copolymers can be ascribed to different microstructures. Nevertheless, with increasing HEA-content of the copolymers the cloud points were found to increase, too. This was expected, at least within the same polymer series, due to the higher hydrophilicity of HEA. Additionally, the cloud points of the block copolymers (Table 5) were found to be less dependent on the composition (HEA-content) than the corresponding gradient copolymers (Table 5). This might be expected since the cloud point temperatures of the block copolymers depend on the collapse of the pure PMEA-blocks and CP will only vary due to changes in PMEA length and the effect of the hydrophilic PHEA block. In contrast, the CP temperatures of the gradient copolymers depend on the collapse of the PHEA-grad-MEA-blocks (composition dependent). Furthermore, exchanging one of the benzyl end-groups (hydrophobic) by an isobutyronitrile end-group (hydrophilic) while decreasing the DP of the copolymers upon cleavage (DP ∼ 80 → DP ∼ 80/2) also resulted in increased CPtemperatures (Table 5), as expected. However, the copolymers with the microstructures III (pure triblock; HEA-MEA-HEAblock) and V (pure diblock; HEA-MEA-block) were found to be more hydrophobic than the corresponding copolymers with the microstructure IV (triblock gradient; HEA-MEA-HEAgrad) and VI (diblock gradient; HEA-MEA-grad) resulting in lower cloud point temperatures for the block copolymers, as highlighted in Figure 5 for copolymers with comparable HEAcontents of 66−73 mol % (HEA-MEA-HEA-block-4 and HEAMEA-block-4: 67 mol %; HEA-MEA-HEA-grad-4 and HEAMEA-grad-4: 67 mol %; HEA-MEA-HEA-grad-2 and HEAMEA-grad-2: 73 mol %). Determination of the Critical Micelle Concentration (cmc). Since the synthesized copolymers are amphiphilic their micellization behavior in aqueous solutions was investigated. The critical micelle concentrations of the synthesized copolymers were investigated by fluorescence spectroscopy at

Figure 3. Calculated monomer distributions of the investigated poly(2-hydroxyethyl acrylate)-block-poly(2-hydroxyethyl acrylate-grad2-methoxyethyl acrylate)]-block-poly(2-hydroxyethyl acrylate)} triblock copolymers (HEA-MEA-HEA-block using PHEA macro-chain transfer agents with DP = 25 (top) and DP = 43 (bottom) and different addition rates of 2-methoxyethyl acrylate.

and closed symbols in Figure 4. Since the hysteresis observed for the HEA-ran-MEA copolymers with comparable degrees of

Table 5. Characterization Data of the Synthesized Triblock (HEA-MEA-HEA-block and HEA-MEA-HEA-grad) and Diblock (HEA-MEA-block and HEA-MEA-grad) Copolymers in Water Solutions triblock copolymers a

xMEA [wt %] 71 65 48 33 19 12 44 27 18 33 52 53

b

diblock copolymers c

polymer no.

CP [°C]

cmc [g/L]

HEA-MEA-HEA-block-1 HEA-MEA-HEA-block-2 HEA-MEA-HEA-block-3 HEA-MEA-HEA-block-4 HEA-MEA-HEA-block-5 HEA-MEA-HEA-block-6 HEA-MEA-HEA-grad-1 HEA-MEA-HEA-grad-2 HEA-MEA-HEA-grad-3 HEA-MEA-HEA-grad-4 HEA-MEA-HEA-grad-5 HEA-MEA-HEA-grad-6

− − 5.5 13.6 26.8 54.2 12.2 29.5 (>97.0) 26.7 14.8 6.6

− − 0.018e 0.075 0.098 0.123 0.087 0.087 0.093 0.056 0.040 0.027

Dhd

[nm]

57 74 77 68 127 130 40 200 188 140 29 31

polymer no. HEA-MEA-block-1 HEA-MEA-block-2 HEA-MEA-block-3 HEA-MEA-block-4 HEA-MEA-block-5 HEA-MEA-block-6 HEA-MEA-grad-1 HEA-MEA-grad-2 HEA-MEA-grad-3 HEA-MEA-grad-4 HEA-MEA-grad-5 HEA-MEA-grad-6

CPb [°C] 14.4 7.9 21.1 23.0 72.4 (>97.0) 20.7 58.4 (>97.0) 50.0 30.8 10.8

cmcc [g/L] f

0.038 0.045f 0.059f 0.083f 0.094f 0.101f 0.100f 0.115f 0.120f 0.066 0.045 0.033

Dhd [nm] 61 68 74 81 115 233 30 75 154 102 42 102

a

Mass fraction of MEA determined using 1H NMR spectroscopy. bCP (cloud point) determined by turbidimetry [700 nm] with cpolymer = 5 mg/mL in water (second heating cycle). cCmc (critical micelle concentration) determined by fluorescence spectroscopy at 25 °C in water using 8-Anilino-1naphthalenesulfonic acid as fluorescence probe (c = 2.5 × 10−5 mol·L−1). dDh (hydrodynamic diameter) determined by dynamic light scattering (DLS) with cpolymer = 1 mg/mL in water. eCmc (critical micelle concentration) determined by fluorescence spectroscopy at 15 °C in water using 8anilino-1-naphthalenesulfonic acid as fluorescence probe (c = 2.5 × 10−5 mol·L−1). fCmc (critical micelle concentration) determined by fluorescence spectroscopy at 25 °C in water using 8-anilino-1-naphthalenesulfonic acid as fluorescence probe (c = 2.5 × 10−5 mol·L−1). 1454


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different polymer concentration using ANS as fluorescence dye and full details are given in the Supporting Information.82 The plots of the cmc and the corresponding CP temperatures as a function of the mass fraction of MEA of the synthesized copolymers with different microstructures and degrees of polymerization of Pn ∼ 80 and Pn ∼ 80/2, determined at 25 °C (or at room temperature) are presented in Figure 6. Increasing the mass fraction of MEA in the

Figure 4. Top: Cloud points (CP; full symbols, heating; open symbols, cooling) of the HEA-MEA-HEA block copolymers with different degrees of polymerizations and end-groups as a function of HEA fraction (FHEA). Bottom: Cloud points (CP; full symbols, heating; open symbols, cooling) of the HEA-MEA-HEA-grad copolymers with different degrees of polymerizations and end-groups as a function of FHEA. CPs were determined by turbidimetry at 700 nm in demineralized water with a polymer concentration of c = 5 mg/mL. Full and dashed lines were added to guide the eyes. Figure 6. Top: Critical micelle concentration (cmc; upper part) and cloud point temperatures (lower part) as a function of the mass fraction of MEA (xMEA) of the synthesized copolymers with different microstructure and Pn ∼ 80 determined at T* = 25 °C using fluorescence spectroscopy and ANS as fluorescence dye. Dashed lines represent linear fits of the values below or above the CP-temperatures. Dotted lines were drawn to guide the eyes. Bottom: Critical micelle concentration (cmc, upper part) and cloud point temperatures (lower part) as a function of xMEA of the synthesized copolymers with different microstructure and Pn∼80/2 determined at room temperature (RT) or T* = 25 °C using fluorescence spectroscopy and ANS (Na+-salt) as fluorescence dye. Dashed lines represent linear fits of the values while dotted lines were drawn to guide the eyes.

synthesized copolymers led to lower cmc. This was expected, since increasing the length (the hydrophobicity) of the hydrophobic part of a block or a gradient copolymer enhances the hydrophobic interactions, and thus, decreases the cmc.1 Furthermore, a clear dependency of the cmc on the microstructure was observed. The cmcs of the copolymers HEA-MEA-HEA-grad-4 to HEA-MEA-HEA-grad-6 (Table 3; gradient microstructure VI; MCTA Pn ∼ 25) were found to decrease faster (Figure 6, top) than the cmcs of the copolymers HEA-MEA-HEA-block-4 to HEA-MEA-HEA-block-6 (Table 2;

Figure 5. Transmittance of light with wavelength of 700 nm (full symbols, heating; empty symbols, cooling) of the synthesized copolymers with HEA content of 66−73 mol %, DP ∼ 80 and different microstructures as a function of temperature determined in demineralized water with a polymer concentration of c = 5 mg/mL.

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block microstructure III) and HEA-MEA-HEA-grad-1 to HEAMEA-HEA-grad-3 (Table 3; gradient microstructure IV; MCTA Pn ∼ 41). The latter was observed to be nearly independent of the mass fraction of the MEA (Table 5; cmcHEA‑MEA‑HEA‑grad‑3 (18 wt % MEA) = 0.093 g/L vs cmcHEA‑MEA‑HEA‑grad‑2 (27 wt % MEA) = 0.087 g/L vs cmcHEA‑MEA‑HEA‑grad‑1 (44 wt % MEA) = 0.087 g/L), which might be ascribed to the rather steep monomer gradient resulting from fast MEA addition. In contrast, the cmc of the copolymers with nearly the same microstructure (TP 21−23) but slightly different length of the PHEA-blocks (Pn,PHEA = 41 vs Pn,PHEA = 25) revealed a strong dependency on the MEA content. Furthermore, in aqueous solutions the micelle formation behavior of the copolymers with DP ∼ 80 was found to remain unaffected by their cloud point temperatures (slope of the fits does not change exceeding the CP temperatures) possibly due to the triblock copolymer structure in which the two outer hydrophilic blocks shield the inner block. However, in case of diblock copolymers with Pn/2− 40 a slightly different situation was observed (Figure 6, bottom). While the cmc of the diblock copolymers with the gradient microstructure (HEA-MEA-grad) were found to show nearly the same tendencies as the corresponding triblock copolymers with DP ∼ 80 (HEA-MEA-HEA-grad), the micelle formation behavior of the block copolymers with DP ∼ 40 (HEA-MEA-block) was found to be different from their DP ∼ 80 pendants (HEA-MEA-HEA-block). Exceeding the cloud point temperatures of the block copolymers a clear break in the devolution of the cmc was observed (xMEA ∼ 36 wt %), revealing a clear dependency of the MEA-content (respectively the length of the hydrophobic block) of the block copolymers on their micelle formation behavior (the decrease of the cmc with increasing MEA-content becomes faster). The plots of the cmc as a function of the temperature for the synthesized copolymers (Pn ∼ 80) with different microstructure but comparable mass fraction of MEA (Table 5; HEA-MEAHEA-block-3, xMEA = 48 mol vs HEA-MEA-HEA-grad-1, xMEA = 44 mol; HEA-MEA-HEA-block-4, xMEA = 33 mol vs HEA-MEAHEA-grad-2, xMEA = 27 mol and HEA-MEA-HEA-block-5, xMEA = 19 mol vs HEA-MEA-HEA-grad-3, xMEA = 18 mol) are presented in Figure 7. The missing cmc-values of the copolymers with block microstructure (Table 5; HEA-MEAHEA-block-1 and HEA-MEA-HEA-block-2) could not be determined due to agglomeration taking place when the temperature of the copolymer solutions was increased beyond the CP temperature making the interpretation of the obtained curves unreliable. But, since the cmc determined for the copolymers with the block microstructure were found to show nearly the same temperature dependency (parallel drift), the missing cmc might be assumed to develop in the same manner as observed for the cmc of HEA-MEA-HEA-block-5. When changing the microstructure of the copolymers, the observed cmc of the copolymers with block microstructure (HEA-MEAHEA-block; e.g. HEA-MEA-HEA-block-5: Δcmc5°C→45°C = +0.017 g/L) were found to be less temperature dependent than the cmc of the corresponding copolymers with gradient microstructure (HEA-MEA-HEA-grad; e.g., HEA-MEA-HEAgrad-3: Δcmc5°C→45°C = +0.054 g/L), as expected.83 Furthermore, no abrupt changes of the cmc exceeding the CP temperatures of the copolymers (at least for triblock copolymer series) could be observed, revealing no significant dependencies of the micelle formation behavior of the different copolymers on their CP temperatures.

Figure 7. Critical micelle concentration (cmc; upper part) as a function of the temperature and cloud point (CP) temperatures for the synthesized copolymers (Pn ∼ 80; lower part) with different microstructure but comparable mass fractions of 2-methoxyethyl acrylate (HEA-MEA-HEA-block-3, xMEA = 50.8 mol vs HEA-MEAHEA-grad-1, xMEA = 46.8 mol; HEA-MEA-HEA-block-4, xMEA = 35.6 mol vs HEA-MEA-HEA-grad-2, xMEA = 29.3 mol; and HEA-MEAHEA-block-5, xMEA = 20.8 mol vs HEA-MEA-HEA-grad-3, xMEA = 20.6 mol) determined using fluorescence spectroscopy and ANS (Na+-salt) as fluorescence dye. Full and dotted lines were drawn to guide the eyes.

Size and Shape of the Micelles. Determining the cmc of the aqueous solutions of the synthesized copolymers demonstrated their ability to form self-assembled structures. In order to obtain information on the size and the shape of the formed micelles dynamic light-scattering (DLS) and cryo-SEM measurements were performed. For this purpose, the synthesized copolymers were dissolved in water at concentrations of 1 g/L and thermostated at different temperatures (5, 15, 25, 35, and 45 °C) for 24 h before use. All solutions were filtered through 0.2 μm filters for the DLS-measurements and no filters were used before cryo-SEM measurements. For all DLS measurements bimodal distributions of hydrodynamic diameters were observed. The first peak at Dh ∼ 1−4 nm (with relative amounts of above 99%) was ascribed to the presence of individual copolymer chains in solution, while the second peak (with the relative amounts of less than 1%) represented the hydrodynamic diameter of the formed aggregates. The obtained results are summarized in Table 5. Plots of the hydrodynamic diameters (Dh; at 25 °C) and CP temperatures (at c = 5 g/L) as a function of the mass fraction of MEA (xMEA) of the synthesized copolymers with different microstructure and degrees of polymerization are presented in Figure 8, clearly demonstrating a strong dependency of the microstructure as well as the MEA-content of the synthesized copolymers on their aggregation behavior in aqueous solutions. Furthermore, the hydrodynamic diameters of the aggregates formed by fully hydrated copolymers (CP > 25 °C), were always found, as expected, to be bigger than the diameters of the aggregates formed by copolymers which are only partially hydrated leading to more compact structures (CP < 25 °C). However, no clear differences of the sizes of the formed aggregates between the corresponding copolymers (concerning their MEA content) of different series could be observed. The results for the hydrodynamic diameters of the aggregates of the copolymers of the HEA-MEA-HEA series are plotted in Figure 8, top. The diameters of the aggregates formed by the 1456


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MEA-HEA-block). The synthesized copolymers (HEA-MEAHEA-grad-1 to HEA-MEA-HEA-grad-3 series; MCTA∼41) with the MEA-content of up to xMEA ∼ 27 mol % (Table 5; CP > 25 °C; HEA-MEA-HEA-grad-2 and HEA-MEA-HEA-grad-3) were found to form aggregates with comparable hydrodynamic diameters (Dh,HEA‑MEA‑HEA‑grad‑2 = 200 nm and Dh,HEA‑MEA‑HEA‑grad‑3 = 188 nm). When increasing the MEA content up to xMEA ∼ 44 mol % (HEA-MEA-HEA-grad-1; CP < 25 °C), the hydrodynamic diameter of the formed aggregates decreased significantly (Dh,HEA‑MEA‑HEA‑grad‑2 = 200 nm vs Dh,HEA‑MEA‑HEA‑grad‑1 = 40 nm). Furthermore, increasing the MEA-content of the copolymers of the HEA-MEA-HEA-grad series based on PHEA MCTA with Pn = 25 from xMEA ∼ 33 mol % (HEA-MEA-HEA-grad-4; CP > 25 °C) to xMEA ∼ 52 mol % (HEA-MEA-HEA-grad-5; CP < 25 °C) also resulted in a significant decrease of the size of the formed aggregates (Dh,HEA‑MEA‑HEA‑grad‑4 = 140 nm vs Dh,HEA‑MEA‑HEA‑grad‑5 = 29 nm), while further increasing of the MEA-amount up to 53 mol % resulted in no change of the hydrodynamic diameter of the aggregates formed in aqueous solution (Dh,HEA‑MEA‑HEA‑grad‑5→ Dh,HEA‑MEA‑HEA‑grad‑6 = 29−31 nm). However, due to the partial overlapping of the Dh vs MEA-content curves of the HEAMEA-HEA-grad series based on PHEA with Pn of 41 and 25, respectively, the aggregation behavior of the copolymers with gradient microstructure was found to be dependent on the monomer composition of the gradient block exclusively, but not on the length of each block within the copolymer chain. The results for the hydrodynamic diameters of the aggregates of the copolymers of the diblock copolymer series are plotted in Figure 8, bottom. The HEA-MEA-block copolymers (Table 5) were found, as expected, to form the smaller aggregates the higher the content of MEA was (D h ,H E A‑MEA‑b lo c k‑1→ Dh,HEA‑MEA‑block‑6 = 61−233 nm). However, both series of the copolymers with the gradient microstructure (Table: 5; HEAMEA-grad) were found to behave similar: decreasing the amount of HEA in the copolymers, the diameters of the formed aggregates in aqueous solutions were found to decrease, too. The only exception represents the copolymer with the MEAcontent of xMEA ∼ 53 mol % (Table 5; HEA-MEA-grad-6). Against the expectations, increasing the amount of MEA from xMEA ∼ 52 mol % (HEA-MEA-grad-5; CP > 25 °C) to xMEA ∼ 56 mol % (HEA-MEA-grad-6; CP < 25 °C) the diameter of the formed aggregates was also found to increase (Dh,HEA‑MEA‑grad‑5 = 42 nm vs Dh,HEA‑MEA‑grad‑6 = 102 nm), although it should be mentioned that the differences in composition between these two polymers are rather minor. In Figure 9 the hydrodynamic diameters of the synthesized copolymers with different microstructures but comparable monomer compositions (Table 5; HEA-MEA-HEA-block-3, xMEA = 48 wt %; HEA-MEA-HEA-grad-1, xMEA = 44 wt %; and HEA-MEA-HEA-grad-5, xMEA = 52 wt %) as well as the relative amounts of the species (number weight %) existing in solution were plotted over temperature. As mentioned before, for all polymers two different species were found to exist in their aqueous solutions: single polymer chains (open symbols; 1 ≤ Dh ≤ 4 nm) and the corresponding aggregates (full symbols; 15 ≤ Dh ≤ 240 nm). Furthermore, even after crossing the CP temperatures of each of the copolymers (dashed lines) the expected full aggregation of the single chains was not observed. However, increasing the temperature of the solutions revealed a clear dependency of the microstructure of the different copolymers on their aggregation behavior. Upon increasing the temperature of the aqueous solution of the copolymer with

Figure 8. Hydrodynamic diameters (Dh; upper part) and cloud point temperatures (at c = 5 g/L; lower part) as a function of the mass fraction of 2-methoxyethyl acrylate (xMEA) of the synthesized copolymers with different microstructure and Pn ∼ 80 (top) and Pn ∼ 80/2 (bottom), respectively, determined in water via dynamic light scattering at T* = 25 °C and θ = 90°. Full and dotted lines were drawn to guide the eyes.

copolymers with the block microstructure (Table 5; HEAMEA-HEA-block) were found to be nearly constant up to the MEA-content of x MEA ∼ 21 mol % (CP > 25 °C; Dh,HEA‑MEA‑HEA‑block‑6 = 130 nm and Dh,HEA‑MEA‑HEA‑block‑5 = 128 nm). Increasing the MEA-content up to xMEA ∼ 36 mol % (HEA-MEA-HEA-block-4; CP < 25 °C) the hydrodynamic diameter of the formed aggregates decreased (Dh,HEA‑MEA‑HEA‑block‑5 = 128 nm vs Dh,HEA‑MEA‑HEA‑block‑4 = 68 nm). But, further increase of the MEA amount in the aggregates-forming copolymers up to xMEA = 73 mol % resulted in no significant changes of the size of the formed aggregates (Dh,HEA‑MEA‑HEA‑block‑1→ Dh,HEA‑MEA‑HEA‑block‑4 = 57−68 nm). This was unexpected, since the higher the MEA-contents in the aggregate-forming copolymers, the more hydrophobic and less hydrated are they, and thus, the smaller the hydrodynamic diameters of the aggregates formed in aqueous solutions. It should be noted that also the form factor might play a role, i.e. further increasing the hydrophobic PMEA part will change the hydrophilic−hydrophobic balance possibly leading to the formation of cylindrical micelles or vesicles. The copolymers with the gradient microstructure (HEAMEA-HEA-grad) were found to behave very similar in comparison to their block microstructure pendants (HEA1457


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38−43 nm). Furthermore, the hydrodynamic diameters of the second copolymer with the gradient microstructure (Figure 9; HEA-MEA-HEA-grad-1 (■); MCTA ∼ 25) were found to be constant up to the temperature of 25 °C (Dh,5−25°C = 36−40 nm), while further increasing the temperature up to 45 °C resulted in an enormous increase of the size of the aggregates formed in the aqueous solution (Dh,25°C = 40 nm → Dh,35°C = 124 nm → Dh,45°C = 216 nm) associated with further aggregation of the initially formed aggregates driven by further dehydration of the gradient microstructure. Cryofractured samples of the aggregates formed in aqueous solutions were visualized by SEM. Examples of SEM images obtained using aqueous solutions of the copolymers with block(Table 5; HEA-MEA-HEA-block) as well as gradient- (Table 5; HEA-MEA-HEA-grad) microstructures are presented in Figure 10, confirming the formation of spherical aggregates in all cases. Additionally, for nearly all copolymer solutions the size distribution of the formed aggregates was found to vary a lot, despite the relatively narrow molecular weight distributions (Table 4; PDI = 1.1−1.4) of the synthesized/investigated copolymers. This might be explained by the fast reaction of the formed aggregates on the freezing process of the solutions during the sample preparation. Therefore, no direct comparison of the aggregate sizes estimated from the cryo-SEM with the corresponding results obtained from the DLS measurements could be performed.

Figure 9. Temperature dependence of the hydrodynamic diameters (upper part) and relative amount of the species (number weight %; lower part) existing in solutions on example of synthesized copolymers with Pn ∼ 80 with comparable mass fraction of 2-methoxyethyl acrylate (Table 5; HEA-MEA-HEA-block-3, xMEA = 48 wt %; HEAMEA-HEA-grad-1, xMEA = 44 wt %; and HEA-MEA-HEA-grad-5, xMEA = 52 wt %) but different microstructures determined in water via dynamic light scattering at θ = 90°. Full and dotted lines were drawn to guide the eyes. Dashed lines represent the cloud point temperatures (at c = 5 g/L) of each copolymer.

■

the block microstructure (Figure 9; HEA-MEA-HEA-block-3 (blue ◆)) from 5 to 25 °C the hydrodynamic diameter of the formed aggregates was found to decrease first (Dh,5 °C = 35 nm vs Dh,15°C = 15 nm) and then to increase significantly (Dh,15°C = 15 nm → Dh,25°C = 77 nm) while further increase of the temperature up to 45 °C resulted in no changes of the size of the formed aggregates (Dh,25°C = 77 nm → Dh,35°C = 92 nm → Dh,45°C = 90 nm). In contrast, the hydrodynamic diameters of the aggregates formed by the copolymer with the gradient microstructure (Figure 9; HEA-MEA-HEA-grad-5 (red ▲); MCTA∼41) were found to have its maximum at 5 °C (Dh,5°C = 55 nm). By increasing the temperature to 15 °C the observed hydrodynamic diameters were first found to decrease slightly (Dh,5°C = 55 nm vs Dh,15°C = 38 nm) and to stay constant with further increase of the temperature up to 45 °C (Dh,15−45°C =

SUMMARY

In the present work, well-defined homopolymers of HEA with different degrees of polymerization were synthesized via RAFT polymerization, using DBTTC as CTA. Kinetic investigations revealed that the polymerizations proceeded in a controlled manner showing increased reaction rates when monomer to RAFT-agent ratios were decreased. Subsequently, well-defined triblock copolymers of HEA and MEA with the general microstructure PHEA-block-PMEA-block-PHEA were synthesized via RAFT, using previously prepared PHEA-MCTA with degrees of polymerization of Pn ∼ 20−70. Kinetic studies demonstrated good control over the polymerization reactions, indicating no dependency of the reaction rates of MEA on the degree of polymerization of the used MCTA. Furthermore,

Figure 10. SEM images of cryo-fractured samples of aggregates formed by synthesized copolymers with comparable monomer compositions, degrees of polymerization (Pn ∼ 80), block- (HEA-MEA-HEA-block) and gradient- (HEA-MEA-HEA-grad) microstructures, respectively, microstructures in water solutions with cCopolymer = 1 g/L. 1458


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well-defined triblock copolymers of HEA and MEA with the general microstructure PHEA-block-P(HEA-grad-MEA)-blockPHEA were prepared via RAFT, using previously prepared PHEA MCTA with degrees of polymerization of Pn ∼ 25 and 41. The gradient of the middle block was adjusted by the addition rate of MEA to the preset HEA/MCTA ratio during the polymerization reaction. The thermoresponsive properties of aqueous solutions of the synthesized copolymers at 5 g/L were found to depend on the polymer composition, the microstructure and the chain length. The CP-temperature of the synthesized copolymers increases with the content of HEA. Exchanging one of the hydrophobic benzylic end-groups of the copolymers by isobutyronitrile using AIBN resulted in copolymers with Pn/2 (HEA-MEA-series; Pn ∼ 40), which are more hydrophilic (higher cloud point temperatures) than the corresponding precursor copolymers (HEA-MEA-HEAseries; Pn ∼ 80; lower CP temperatures), while decreasing the degree of polymerization leads to more enhanced hydrophilicity with increasing HEA amount. Furthermore, the copolymers with gradient microstructure are more hydrophilic resulting in higher CP temperatures than the corresponding copolymers with block microstructure. Nevertheless, the CP temperatures of the block copolymers are adjustable between 0−80 °C and between 0−60 °C using gradient copolymers, while both, block and gradient copolymers, show differently pronounced hysteresis on heating and cooling. All of the obtained copolymers feature a temperature dependent amphiphilic character resulting in the formation of self-assembled aggregates as proven by the fluorescence spectroscopy, SEM and DLS. The cmc of the synthesized copolymers decreases with increasing content of MEA. SEM and DLS characterization revealed the formation of spherical aggregates with temperature dependent sizes and broad size distributions. The size of the aggregates formed in aqueous solutions of the copolymers at 1 g/L and 25 °C can be tuned by controlling the polymer composition, microstructure and chain length (endgroups). Furthermore, aggregates formed by fully hydrated copolymers (measurement at temperatures below each CP) showed generally bigger hydrodynamic diameters than the aggregates formed by the corresponding copolymers with only partial hydration (measurement at temperatures above each CP). Thus, new copolymers with adjustable cloud points and variable size of the in aqueous solutions formed aggregates were successfully prepared.

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Netherlands Scientific Organisation (NWO; Veni-grant) and Ghent University for financial support.

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ASSOCIATED CONTENT

S Supporting Information *

Recipes for the synthetic procedures, HEA homopolymerization kinetics, and details on the determination of the cmc. This material is available free of charge via the Internet at http:// pubs.acs.org.

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REFERENCES

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Arkema is thanked for the generous supply of DBTTC. R.H. is grateful to the Alexander von Humboldt foundation, The 1459


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Block and Gradient Copolymers of 2-Hydroxyethyl Acrylate and 2

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