TUNING THE CLOUD POINT OF METHACRYLIC ACID AND OLIGOETHYLENEGLYCOL METHACRYLATE BASED RANDOM COPOLYMERS C. Remzi Becer, Richard Hoogenboom, Sabine Hahn, Ulrich S. Schubert* Laboratory of Macromolecular Chemistry and Nanoscience, Eindhoven University of Technology and Dutch Polymer Institute (DPI), P.O. Box 513, 5600 MB Eindhoven, The Netherlands Laboratory of Organic and Macromolecular Chemistry, Friedrich-Schiller-University Jena and Dutch Polymer Institute (DPI), Humboldtstr. 10, 07743 Jena, Germany E-mail:
[email protected], Internet: www.schubert-group.com. Introduction The developments in advanced polymerization techniques to obtain well defined polymers, the improved characterization tools to gain more information from the materials and the commercialization of high-tech automated parallel synthesis platforms have been the consequence of screening a wide range of materials in a relatively short period of time with high reproducibility. Advanced materials with well defined structures and specific responses, so-called “smart” materials, have become of special interest to researchers. Intelligence of these materials is mostly based on their response to environmental changes or external stimulation. It is well known that small organic molecules as well as polymeric structures can exhibit a phase transition upon heating or altering the acidity of the environment. This phenomenon is called lower critical solution temperature (LCST) behavior and is based on the existence of hydrogen bonds between water molecules and the polymeric chain. The polymers with LCST behavior show a reversible sudden change from hydrophilic to hydrophobic behavior and vice versa that makes them attractive for using as ‘smart’ switchable materials in applications, ranging from, e.g., actuators,1 hydrogels2 and drug delivery.3 The reproducibility and the accuracy of an intended LCST can be enhanced by utilizing living and controlled polymerization techniques, such as anionic,4 radical5,6,7 and cationic8,9 polymerizations. These techniques have enabled the synthesis of advanced structures with the targeted length of polymer; architecture as well as monomer composition and distribution along the backbone can be controlled in an excellent manner. Reversible addition fragmentation chain transfer (RAFT) polymerization mechanism is one of the most successful controlled radical polymerization techniques because of its tolerance to various functionalities and ease of application. Further challenge in obtaining a material for specific application can be overcome by mapping the structure-property relationships of the polymeric structures. It is an inevitable fact that polymer scientists should prepare libraries of well-defined polymers having systematical changes in, e.g., polymer molecular weight, length and/or architecture to be able to determine structure-property relationships.10 The synthesis and screening of such polymer libraries can be accelerated by the use of high-throughput synthesis and screening equipment.11,12 In addition, the use of automated parallel synthesis platforms increases the comparability of the different copolymers based on the elimination of handling errors.13 In this contribution, the synthesis and characterization as well as cloud point determination of oligo(ethyleneglycol) methacrylate (OEGMA) homopolymers with various lengths of polymer chains will be discussed. Furthermore, the investigation of random copolymers of OEGMAs with pH sensitive monomers, such as methacrylic acid (MAA), will be reported resulting in double-responsive copolymers. Experimental Materials and instrumentation. Methacrylic acid (MAA, Aldrich) and oligo(ethylene glycol) methyl ether methacrylate (OEGMA475, Mn ~ 475 g.mol-1, Aldrich) were purified by passing over a neutral aluminum oxide column. Oligo(ethylene glycol) methyl ether methacrylate (PEGMA1100, Mn ~ 1 100 g.mol-1, Aldrich) was dissolved in dichloromethane, passed over a neutral aluminium oxide column and dried under vacuum. Azobis(isobutyronitrile) (AIBN, Aldrich) was recrystallized from methanol. 2-Cyano-2-butyl dithiobenzoate (CBDB, chain transfer agent) was kindly provided by AGFA. Solvents were purchased from Biosolve Ltd. All polymerizations were performed on a Chemspeed AcceleratorTM SLT100 automated synthesizer. The robot was equipped with a four needle head and an array of 16 parallel 13 mL glass reactors. All reactors were
connected to a Huber Unistat Tango (heating range: –40 °C to 145 °C) and were equipped with a cold-finger reflux condenser in which the temperature can be fixed from –5 °C to 40 °C. A double inert atmosphere was maintained by applying a 1.1 bar flow over the reactors and a 1.5 bar argon flow through the hood of the AcceleratorTM. The inert atmosphere in the hood of the AcceleratorTM SLT100 was obtained by flushing with argon for at least 90 minutes prior to the experiments. In addition, the reaction vessels were heated to 120 °C, evacuated for 15 minutes, and then filled with argon. This procedure was repeated three times to perform the reactions under inert atmosphere. Different amounts of the RAFT agent (CBDB in toluene), AIBN (in toluene) and the desired monomers were transferred into the reaction vessels. The monomer concentration was kept at [2M] and the ratio of RAFT to AIBN was 0.25. The kind of monomers, the ratio of monomers and the monomer to RAFT were varied in the experiments. The polymerization mixtures were heated to 70 °C and vortexed at 600 rpm. After 10 hours stirring at 70 ºC, the reaction vessels were cooled down to room temperature and purified by precipitating to an appropriate non-solvent. After removal of solvents and residual monomers, the polymers were dried in a vacuum oven at 40 °C overnight prior to analysis. GPC measurements were performed on a Shimadzu system equipped with a SCK-10A system controller, a LC-10A pump, a RID-10A refractive index detector, and a PL gel 5 µm Mixed-D column at 50 °C, using a mixture of chloroform, triethylamine and isopropanol (94:4:2) as eluent at a flow rate of 1 mL.min-1. GC measurements were performed on an Interscience Trace GC used with a Trace Column RTX-5 connected to a PAL autosampler. 1HNMR spectra were recorded on a Varian Mercury 400 spectrometer using deuterated acetonitrile as solvent. UV-Vis transmission measurements were performed at a wavelength of 500 nm on a Perkin Elmer Lamda-45 UV-VIS spectrophotometer equipped with a PTP-1 Peltier system to heat the UV cell. The reported cloud points correspond to the 50% transmission point upon heating the aqueous polymer solutions. Results and Discussion Stimuli-responsive polymers based on oligoethyleneglycol methacrylate (OEGMA) monomers are known to exhibit a sharp reversible phase transition in water at its unique LCST.14,15 It has been reported that well-defined pOEGMA copolymers have been mainly prepared via living anionic polymerization14 and atom transfer radical polymerization.16 Recently, we demonstrated that the reversible addition-fragmentation chain transfer (RAFT) free radical polymerization method is also well-suited to create OEGMA based copolymers.17 Here, we further elaborate on the tuning of the cloud point of the polymeric materials by changing the chain lengths or monomer compositions. As seen in Scheme 1, random copolymers of methacrylic acid with OEGMA (k=8.5 or 23) were prepared by using AIBN as an initiator and CBDB as a chain transfer agent. The parallel polymerizations were conducted at 70 °C in ethanol as a solvent. S
AIBN
+ O
OH
O
O
S N
n
*
Ethanol 70 oC
O
O
O
*
O
O
k
Scheme 1. Synthesis of methacrylic acid methacrylate random copolymers. (k ~ 8.5 or 23).
OH
m
k
and
oligoethyleneglycol
Besides, the homopolymer libraries of two different OEGMA (Mn ~ 475 or 1 100 g.mole-1) were prepared with varying chain lengths. The parallel synthesis by systematic variation was performed by using the automated synthesis robot. This robot system performs all the tasks as it is programmed and with minimized human errors. A typical program consists of several steps starting with the inertization of the reactors and followed by the transfer of stock solutions in different portions to the reactors. Liquids transfers were performed in parallel by using a 4-needle head. The reactors were continuously vortexed and heated up to the polymerization temperature until the reaction time was completed. Sampling from the reactors at different time intervals (for a kinetic experiment) or only at the beginning and at the end of
the reaction (for a batch reaction) can be performed depending on the requirements. Homopolymers of OEGMA475 were synthesized by the automated standard procedure summarized above. Cloud points of the purified polymers were determined by measuring the UV-transmission of aqueous polymer solutions (5 mg/mL; pH = 2, 4, 7 and 10) as a function of temperature at 500 nm. The transmission through the polymer solution was monitored while the temperature was increased with 1 ºC per minute. At the start of the measurement, the solution is clear resulting in 100% transmission. Upon heating, a sharp decrease from 100% to 0% transmission is observed indicative of a turbid solution. The point at 50% transmission is taken as the cloud point. These measurements were performed at four different pH values and there is no significant difference observed in the cloud points of the homopolymers even at increased chain length of p(OEGMA475) since this monomer does not contain pH-active groups, as depicted in Figure 1.
50000
Mn, GPC [Dalton]
40000 30000 20000 10000 0
P(OEGMA)1100 (mole %) Figure 3. Number average molecular weight and polydispersity index versus the initial mole percent of OEGMA1100 to MAA in the polymerization mixture.
o
Cloud point [ C]
90 80 70
pH 2 pH 4 pH 7 pH 10
60 50
0
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[P(OEGMA)475]/[CBDB] Figure 1. Measurement at different pH values for the cloud point determination of p(OEGMA475) homo-polymers with various chain lengths.
Moreover, a library of random copolymers of OEGMA475 and MAA was prepared with different monomer contents. It was clearly observed that the cloud point of the copolymer was increased by increasing the OEGMA475 content in the polymer, as shown in Figure 2. Besides, the cloud points measured at pH 2 were found to be slightly lower than the ones at pH 4. pH 2 pH 4
90 80
In addition, preliminary results demonstrated that the LCST of pOEGMA homopolymers can be tuned by the length of the OEGMA side chains. This will be investigated in more detail in future work as well as the preparation of copolymers with other OEGMA monomers via the RAFT polymerization method. Conclusions In conclusion, we have demonstrated that well-defined copolymers based on OEGMA can be prepared via RAFT polymerization. Homo- and copolymer libraries of MAA with OEGMA475 or OEGMA1100 were synthesized using an automated parallel synthesis robot leading to very comparable polymers. Furthermore, UV-transmission measurements at 500 nm revealed that it is possible to tune the cloud point of MAA and OEGMA random copolymers by simply changing the content of two monomers in the polymer. Acknowledgement. The authors would like to thank the Dutch Polymer Institute (DPI), the Dutch Scientific Organization (NWO) and the Fonds der Chemischen Industrie for financial support.
References (1) (2) (3)
100
(4)
o
Cloud point [ C]
70
(5) (6) (7)
60 50 40
(8) (9)
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1.3 1.2 1.1 1.0 10 20 30 40 50 60 70 80 90 100
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P(OEGMA)475 (mole %)
Figure 2. Cloud points of poly[(OEGMA475)-r-(MAA)] random copolymers at different compositions. The molecular weight and polydispersity index of the homo- and copolymer libraries were measured by GPC and the results for the poly(OEGMA1100)-r-(MAA) are depicted in Figure 3. A linear trend in the molecular weight of the copolymers was observed by increased content of OEGMA1100 monomers. Structural analysis of the synthesized copolymers by 1 H-NMR spectroscopy and GPC demonstrated that the polymers had the desired composition and relatively low polydispersity indices of 1.30 or lower indicating that they were synthesized in a controlled manner.
(10) (11) (12) (13) (14) (15) (16) (17)
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