Synthesis of Fluorinated Amphiphilic Block Copolymers Based on PEGMA , HEMA , and MMA via ATRP and CuAAC Click Chemistry

1 Department of Chemistry, Faculty of Arts and Science, Yildiz Technical University, Davutpasa Campus, Esenler, 34220 Istanbul, Turkey 2Department of Chemistry, Faculty of Arts and Science, Fatih University, Buyukcekmece, 34500 Istanbul, Turkey 3 Department of Chemistry, Medical Laboratory Techniques, Vocational School of Medical Sciences, Fatih University, Maltepe, 34840 Istanbul, Turkey 4Department of Chemical Engineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, Davutpasa Campus, Esenler, 34220 Istanbul, Turkey

Quite recently, click reactions have attracted considerable attention in synthetic polymer chemistry owing to their high specificity, high tolerance of functional groups, and quantitative reaction yields.Cu(I) catalyzed Huisgen 1,3dipolar cycloaddition (CuAAC), which occurs between an azide and an alkyne to give 1,2,3-triazole ring [30,31], has emerged as a powerful tool in the preparation of versatile macromolecular structures when used in conjunction with controlled/living radical polymerization techniques [9,32].
Herein, we report the synthesis of a fluorinated amphiphilic block copolymer on the basis of combined ATRP and Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAC) methods.To the best of our knowledge, this is the first study to report the preparation of perfluoroalkylated amphiphilic block copolymer brushes by this approach.Furthermore, the method allows for facile adaptation of a variety of other click moieties and fine-tunes their concentration without altering the size of hydrophobic segment.

Block Copolymerization of PEGMA Using Poly(HEMAco-MMA) Macroinitiator via ATRP (2b, 2d).
In a typical procedure, P(HEMA(20)-co-MMA(80)) (1b) macroinitiator (0.41 g, 0.045 mmol), PEGMA (8.72 g, 18 mmol) monomer, CuBr (0.007 g, 0.045 mmol), and PMDETA (0.016 g, 0.09 mmol) were dissolved in methanol/water mixture (MeOH/water = 2 : 1 v/v) in a Schlenk tube equipped with a magnetic stirring bar.The reaction mixture was degassed by three freeze-pump-thaw cycles, backfilled with nitrogen, and kept in a magnetic stirrer at room temperature.After the given period, the Schlenk tube was immersed into liquid nitrogen to terminate the reaction.Upon reaching room temperature, the mixture was diluted with THF and passed through a silica gel column to remove the copper salt.The solution was completely dried in a rotary evaporator and then subjected to dialysis against regularly replaced distilled water to remove PEGMA monomer (spectra/Por membranes, cutoff 1,000 Da).The solution was again evaporated to dryness in a rotary evaporator.The residue was dissolved in THF and precipitated into 10-fold excess hexane.The precipitate was collected by filtration and dried in vacuo overnight.Yield: 75%.

2.7.
Characterizations.FT-IR spectra were recorded using a Bruker Alpha-P in ATR in the range of 4000-400 cm −1 . 1 H-NMR spectra were recorded using a 400 MHz Bruker Avance spectrometer in CDCl 3 .Chemical shifts are reported in ppm relative to TMS as internal standard.
Thermal stabilities of the membranes were analyzed by a PerkinElmer STA 6000 Thermal Analyzer.The samples (∼ 10 mg) were heated between 30-750 ∘ C under N 2 atmosphere at a scanning rate of 10 ∘ C/min.PerkinElmer JADE Differential Scanning Calorimetry (DSC) was used to investigate the thermal transitions of the samples.The samples (∼10 mg) were put into aluminum pans and then heated to the desired temperature at a rate of 10 ∘ C/min under nitrogen atmosphere.
Gel-permeation chromatography (GPC) measurements were performed on THF solutions of the polymers using an Agilent GPC 1100 instrument.The measurements were standardized against THF solutions of polystyrene standards.CuBr/PMDETA r.t
Chemical structures of the copolymers were identified using several techniques.The FT-IR spectra of four different compositions of copolymers P(HEMA-co-MMA) are given in Figure 3.The broad band at 3540 cm −1 due to the -OH stretching, increasing with the HEMA content in the copolymers, was an apparent characteristic peak of the series.The -CH stretching appeared around 2957 cm −1 .The characteristic -C=O stretching band in both HEMA and MMA units in the copolymer occurred at 1726 cm −1 [37,38].The strong -C-O-C-type ester stretching band appeared at 1151 cm −1 [38].
The 1 H-NMR spectra of P(HEMA-co-MMA) copolymers are given in Figure 4.The signal for methyl protons of -OCH 3 (a) in MMA units appeared at 3.55 ppm [38,39].The signals of -CH 3 protons were seen at 0.88-1.36ppm in both MMA and HEMA units, while for methylene protons they were in the range of 1.5-2.1 ppm.The signals at 3.78 ppm (b) and 4.05 ppm (c) correspond to -CH 2 OH and -CH 2 O protons, respectively [38].
Copolymer compositions from 1 H-NMR were calculated by integral area of the -OCH 3 and -OCH 2 protons using the following [38]: The copolymer compositions obtained from 1 H-NMR agreed well with the charged monomer ratio in feed as shown in Table 2. Polymerization of poly(ethylene glycol) methyl ether acrylate was carried out via ATRP using P(HEMA(20)-co-MMA(80)) (1b) and P(HEMA(50)-co-MMA(50)) (1d) as macroinitiator and CuBr/PMDETA as catalyst system at room temperature in methanol/water.Conditions and results are summarized in Table 3.
Figure 6 shows the DSC curves of P(HEMA-co-MMA) copolymers (1b and 1d), recorded between 0-180 ∘ C. A substantial decrease in the glass transition temperature with increasing HEMA content was observed, which agreed with the literature [38].The   of P(HEMA( 20   around 100 ∘ C and 57 ∘ C [38], respectively.PHEMA and PMMA homopolymers as well as their copolymers are amorphous and do not show any melting temperature, as expected.Figure 7 shows DSC analysis of P(HEMA-co-MMA)-block-PPEGMA (2b and 2d), evaluated during the heating process from -48 to 180 ∘ C. P(HEMA-co-MMA)block-PPEGMA shows a   due to the presence of crystalline domains originating from PPEGMA blocks.The presence of   at around 0 ∘ C supports the block copolymer formation.
It is also noteworthy that   values for (2b) and (2d) are almost the same although different feed ratios of precursor P(HEMA-co-MMA) were employed in the block copolymer formation, which might have resulted in an evident shifting of   since variation of HEMA and MMA content can possibly affect the crystallinity in the microstructure.However, a careful inspection reveals that the final copolymer content (in mol) of 2b (HEMA/MMA/PEGMA ∼ 1/4/22) and 2d (HEMA/MMA/PEGMA ∼ 4/4/22) is very close and the fact that   values are nearly the same is just as expected.
The thermal stabilities of P(HEMA-co-MMA) copolymers (1b and 1d) and P(HEMA-co-MMA)-block-PPEGMA (2b and 2d) block copolymers were analyzed as well, as  shown in Figure 8.The TGA curves of P(HEMA-co-MMA) copolymers with varying composition of HEMA indicated a thermal stability up to 340-350 ∘ C [38].On the other hand, in the analysis of P(HEMA-co-MMA)-block-PPEGMA block copolymers, the decomposition temperatures are shifted to relatively lower values with the incorporation of PEGMA units.
The temperature of 5% weight loss, the temperature of 10% weight loss, the temperature of the rapid weight loss ( max ) before 750 ∘ C, and the char yield at 750 ∘ C in nitrogen are summarized in Table 4.   DMAP at room temperature [35].The GPC analysis provided evidence for the success of reaction.As expected, there was a slight increase in the   values.
Further proof was supplied by FT IR analysis as depicted in Figure 9.As compared to the spectrum of P(HEMA-co-MMA)-block-PPEGMA, two new bands (2b, 2d) appeared at around 2350 and 3320 cm −1 in the spectrum of alkyne-P(HEMA-co-MMA)-block-PPEGMA (3b, 3d), which were assigned to the stretching vibration of the alkyne group [35].
In the second step, Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAC) was carried out between propargyl side functionalities on the backbone and 2,3,4,5,6pentafluorobenzyl azide.The 1 H-NMR spectra of the click products are illustrated in Figure 11.The appearance of the new signals at 7.64 (f) and 5.59 (e) ppm, regarding the methine proton and the methylene protons adjacent to the triazole ring, respectively, were observed [32, 34-36, 42, 43].

Conclusions
The strategy of combining ATRP with Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAC) in the preparation of a novel clickable amphiphilic block copolymer was demonstrated.First, P(HEMA-co-MMA) copolymers were prepared via ATRP.Molar ratio of MMA and HEMA was varied to get random copolymers with different HEMA contents.The copolymer compositions were obtained from 1 H-NMR and agreed well with the charged monomer ratio in feed.
Polymerization of poly(ethylene glycol) methyl ether acrylate was carried out via ATRP using P(HEMA(20)-co-MMA( 80)) (1b) and P(HEMA(50)-co-MMA( 50)) (1d) as macroinitiator to get block copolymers.GPC analysis of the obtained block copolymers was measured as   = 112620 (PDI = 1.58) and   = 58040 (PDI = 1.39), respectively.Both 1 H-NMR and FT-IR spectra showed peaks associated with MMA, HEMA, and PEGMA repeating units.Thermal properties of the copolymers and the block copolymers were also studied by TGA and DSC.For the copolymers, a thermal stability of up to 340-350 ∘ C was detected.In the next step, alkyne-P(HEMA-co-MMA)-block-PPEGMA (3b, 3d) was prepared by the Steglich esterification between hydroxyl groups of HEMA and propiolic acid in the presence of DCC and DMAP at room temperature.Finally, Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAC) was employed as a tool for postfunctionalization.The click coupling between propargyl side functionalities on the backbone and 2,3,4,5,6pentafluorobenzyl azide were evidenced by 1 H-NMR and 19 F-NMR.This synthetic route might be useful in tuning the lengths of the hydrophilic and hydrophobic segments in amphiphilic polymers as well as the average number of functionalities situated in the side chain.

Figure 1 :
Figure 1: Schematic illustration of click coupling between PEGMA based amphiphilic block copolymers bearing pendant clickable sites and azide-functional group.
F-NMR analysis as presented in Figure 12.The signals which appeared in the spectrum of 2,3,4,5,6-pentafluorobenzyl azide also existed in that of click product.The signals detected at -142 ppm, -151 ppm, and -161 ppm originated from the aromatic fluorines: 2F at o-position, 1F at p-position, and 2F at m-position, respectively [44].

Table 1 :
Conditions a and results for the synthesis of P(HEMA-co-MMA).

Table 2 :
Compositions of P(HEMA-co-MMA) obtained from 1 H-NMR data.a by volume, b by moles, and c calculated from 1 H-NMR.