Polymerization of N-isopropylacrylamide in the presence of poly(acrylic acid) and poly(methacrylic acid) containing ω-unsaturated end-groups



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Poly(N-Isopropylacrylamide, NIPAM) propagating radicals add to acrylic acid (AA) macromonomer and methacrylic acid polymer containing unsaturated ω-end-group to respectively give novel graft copolymer (represented as • (AA) and ○ (NIPAM) units) and addition fragmentation chain transfer (AFCT). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley. com.]


Poly(N-Isopropylacrylamide, NIPAM) and poly(acrylic acid, AA) are temperature- and pH-responsive polymers, respectively. Poly(NIPAM) exhibits a phase separation in aqueous solutions at ∼ 32 °C, which is known as the lower critical solution temperature.1–3 This property, which may be modified by copolymerization,4, 5 has found many biological applications because of its proximity to physiological temperature.

Recently, reversible addition fragmentation chain transfer (RAFT) polymerizations have been used to prepare poly(NIPAM)4, 6 and poly(AA)6 homopolymers of controlled number average molecular weight (Mn), and narrow molecular weight distribution (MWD), with such living polymers suitably chain extended. Interest in preparing double stimuli responsive materials that can respond to both temperature and pH has led to the preparation of copolymers of NIPAM and AA.7–12 Schilli et al.7 reported the block copolymer poly(NIPAM)-block-poly(AA) synthesized using living/controlled RAFT polymerization. Chen and Hoffman8 copolymerized AA with poly(NIPAM) macromonomer to give a graft copolymer with poly(NIPAM) branches and poly(AA) main chain. The poly(NIPAM) macromonomer was prepared by reacting amino-terminated poly(NIPAM) oligomers with vinyl azlactone. Other researchers have grafted onto poly(AA) main chain by amide condensation with amino-terminated poly(NIPAM).9–11 Conversely, this article describes the first preparation of graft copolymer with poly(NIPAM) main chain and poly(AA) branches. This new graft copolymer is prepared via copolymerization of excess NIPAM monomer with the macromonomer of poly(AA) {poly(AA)[BOND]CH2C(CO2Et)=CH2} (which will subsequently be refered to as PAA[BOND]C=CH2), prepared by addition fragmentation chain transfer (AFCT).13, 14 AFCT uses chain transfer agents (e.g. α-(bromomethyl)acrylates) with sufficient reactivity towards propagating radicals to efficiently introduce ω-unsaturated chain-ends into polymers. The degree of polymerization decreases, and the number of macromonomer molecules produced increases with the amount of chain transfer agent relative to monomer in the initial reaction mixture.14 Furthermore, we have used the latter technique to perform the first preparation of poly(methacrylic acid, MAA) containing an unsaturated end-group {poly(MAA)[BOND]CH2C(CO2Et)=CH2}(which will subsequently be refered to as PMAA[BOND]C=CH2), and we compare its reactivity with PAA[BOND]C=CH2 in polymerizations with NIPAM.



Commercially available tert-butyl acrylate (t-BA, 98%) and methacrylic acid (MAA, 99%) (both Aldrich) were purified prior to use by distillation under reduced pressure. Commercially available N-isopropylacrylamide (NIPAM) (Aldrich, 97%) was purified by recrystallization from a 3:2 (v/v) solution of benzene:hexane. 2,2′-Azoisobutyronitrile (AIBN; DuPont Chemical Solution Enterprise, 98%) was doubly recrystallized from methanol. Ethyl α-(bromomethyl)acrylate (EBMA) was prepared by bromination of ethyl α-(hydroxylmethyl)acrylate using phosphorous tribromide (Aldrich).15 The latter alcohol was prepared by the base catalyzed reaction of ethyl acrylate with paraformaldehyde in dimethyl sulfoxide and water.16 Trifluoroacetic acid (TFA, Aldrich, >99%) and 2.0 M (trimethylsilyl)diazomethane in diethyl ether (Aldrich) were used without purification. All polymerization solvents (ethanol, water, and 1,4-dioxane) were distilled prior to use by conventional methods.

All reactions described were carried out in Pyrex ampoules, subjected to three freeze-thaw-evacuation cycles and sealed under vacuum prior to polymerization.

Synthesis of Poly(acrylic acid) Macromonomer (PAA[BOND]C[DOUBLE BOND]CH2)

PAA[BOND]C=CH2 (Mn = 2,000 g/mol, Mw/Mn = 1.48; the number fraction of chains possessing an unsaturated ω-end group,13f ˜ 0.9) was prepared by the hydrolysis of the poly(t-BA) macromonomer (poly(t-BA)[BOND]CH2C(CO2Et)=CH2).13 The latter was prepared by the polymerization of tBA (1.770 g, 1.38 × 10−2 mol), EBMA (0.068 g, 3.52 × 10−4 mol), and AIBN (16.4 mg, 1 × 10−4 mol) in ethanol (1.58 g) at 60 °C for 1 h (conversion = 38%; Mn = 3,200 g/mol; f ˜ 0.9). The hydrolysis was conducted by dissolving 1.5 g of the latter polymer in 15 mL of dichloromethane with addition of a 5-fold molar excess of TFA followed by stirring for 24 h at room temperature. The formed PAA[BOND]C=CH2 precipitated out of solution, was filtered, washed with further dichloromethane to remove excess TFA and dried in vacuo overnight at 50–60 °C. 1H NMR spectra revealed the hydrolysis of the tert-butyl group (˜1.3 ppm) to have occurred quantitatively, whilst less than 10% of the ω-ethyl ester end-group (3.97–4.15 ppm) had undergone hydrolysis.

Synthesis of Poly(methacrylic acid) Containing an Unsaturated ω-End Group (PMAA[BOND]C[DOUBLE BOND]CH2)

MAA (2.510 g, 2.92 × 10−2 mol) was polymerized in the presence of EBMA (0.197 g, 1.02 × 10−3 mol) and AIBN (16.4 mg, 1 × 10−4 mol) in water (1.53 mL) at 60 °C for 1 h (conversion = 17%; Mn = 3500 g/mol, Mw/Mn = 1.40; f ˜ 0.9). PMAA[BOND]C=CH2 was precipitated by the addition of the polymerization mixture to an excess of diethyl ether, with purification achieved by repeated precipitations. PMAA[BOND]C=CH2 was dried as earlier. Similar MAA polymerizations in the presence of various concentrations of EBMA (ranging from 0.11 to 0.25 M) were conducted to determine the chain transfer constant (CT) using the Mayo equation.13 The conversions of these polymerizations ranged from 17 to 24%.

Copolymerizations of PAA[BOND]C[DOUBLE BOND]CH2 with NIPAM

Ethanol (2.97 mL) solutions of NIPAM (0.4414 g, 3.9 × 10−3 mol), PAA[BOND]C=CH2 (0.1300 g; 6.5 × 10−5 mol based on Mn = 2000 g/mol), and AIBN (18.04 mg; 1.1 × 10−4 mol) were heated at 60 °C for 6, 12, 18, 24, and 30 min. The reactions were quenched on an ice-bath, and precipitated by addition of the polymerization mixtures to an excess of diethyl ether. Conversion of NIPAM was measured by the increase in weight of all polymeric material (both copolymer and unreacted macromonomer), after filtration and drying under vacuum. The decrease in macromonomer concentration was monitored from intensities of the 1H NMR resonances of the vinyl methylene (C=CH2) of the ω-end group (5.60 and 6.16 ppm) relative to the α[BOND]CH2Br end-group (3.49–3.69 ppm).

The graft copolymer was isolated free of unreacted poly(AA) homopolymer by the addition of water to a methanol solution of the polymer mixture at 41% conversion (originally isolated from diethyl ether). The precipitation was repeated twice, and resulted in isolation of the graft copolymer whilst unreacted poly(AA) (including macromonomer) remained in solution.

Homopolymerizations of NIPAM (Non-AFCT)

The conventional polymerizations of NIPAM were conducted by heating ethanol (2.97 mL) solutions of NIPAM (0.4414 g, 3.9 × 10−3 mol) and AIBN (18.04 mg, 1.1 × 10−4 mol) at 60 °C for 4, 9, 15, and 20 min. The polymer was precipitated from diethyl ether, filtered, and dried as earlier.

Polymerizations of NIPAM in the Presence of PMAA[BOND]C[DOUBLE BOND]CH2

Water (2.30 mL) and 1,4-dioxane (2.30 mL) solutions of NIPAM (0.316 g, 2.8 × 10−3 mol), PMAA[BOND]C=CH2 (0.350 g, 1 × 10−4 mol based on Mn = 3500 g/mol) and AIBN (27.9 mg, 1.7 × 10−4 mol) were heated at 60 °C for 9, 15, 21, 27, 50, 80, 110, and 140 min. The polymers were precipitated from diethyl ether, filtered, and dried as earlier. Conversion of NIPAM was measured by gravimetry as earlier.


Prior to GPC analysis, poly(AA), poly(MAA) and graft copolymer in 3:2 mixtures of THF:methanol were reacted with a 2.0 M diethyl ether solution of (trimethylsilyl)diazomethane.17Mn of PAA[BOND]C=CH2, poly(t-BA)[BOND]CH2C(CO2Et)=CH2, and PMAA[BOND]C=CH2 were measured by a Viscotek GPC system equipped with Viscotek DM 400 data Manager, Viscotek VE 3580 refractive index (RI) detector, and two Viscotek Viscogel GMHHR-M columns using THF at a flow rate of 1 mL/min, which was used for estimation of f.13 Poly(styrene) standards (Mn = 376–2,570,000) were used for calibration. The same GPC system was used with DMF containing 0.01 M LiBr as the eluent at a flow rate of 1 mL/min at 60 °C for the GPC MWDs (macromonomer and copolymers) shown in Figures 1 and 5, as more conventional GPC solvents are not suitable for the analysis of NIPAM containing polymers.3, 18 Since linear standards are used to calibrate the latter (see earlier), Mn values are not quoted for branched/graft copolymers with the primary focus of GPC analysis instead being the shape and relative position of MWDs.

Figure 1.

MWDs (after methylation of acrylic acid moieties) of the polymers formed in the polymerization of NIPAM in the presence of PAA[BOND]C=CH2 (blue trace) in ethanol at 60 °C; [PAA[BOND]C=CH2] = 0.022 M, [NIPAM] = 1.31 M, [AIBN] = 0.037 M. MWD at different NIPAM conversions; thick black = 10%, dashed black = 19%, dotted black = 29%, thin black = 36%, dashed dotted black = 41%. The MWD of the purified graft copolymer (NIPAM conversion = 41%), with poly(AA) homopolymer removed by selective precipitation, is shown in red. The peak heights of the original macromonomer (blue) and the purified copolymer (red) MWDs are normalized to unity. All other MWDs are normalized to the crossover point between the macromonomer peak and the copolymer peak, with the height of this point selected arbitrarily (for best clarity) relative to the macromonomer and purified copolymer peaks. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

1H NMR spectra were recorded on a JEOL 400 MHz spectrometer, model ECX-400. Poly(t-BA) was measured in CDCl3, whereas poly(AA), poly(MAA), and graft copolymer were measured in CD3OD. Tetramethylsilane was used as internal standard.


Synthesis of Polymers Containing Unsaturated ω-End Groups

The preparation of PAA[BOND]C=CH2 has been previously achieved using AFCT by addition of the chain transfer agent, EBMA to the polymerization of AA.13 The macromonomer produced contains α-bromo (Br-) and ω-allyl [[BOND]CH2C(CO2Et)=CH2] end groups. However, an alternative two-step approach to this macromonomer involving selective TFA hydrolysis of tert-butyl groups of poly(t-BA)[BOND]CH2C(CO2Et)=CH2 was used in this study. This route was used because of the greater efficiency in ω-end-group preservation achieved in tBA polymerizations compared to AA polymerizations, as indicated by f (the number fraction of chains possessing an unsaturated ω-end group) being ∼ 0.9 (up to 50% conversion) irrespective of the chain transfer agent used.13 The latter is attributed to the overwhelming steric influence of the tert-butyl groups in the poly(t-BA) main chain preventing propagating radical addition onto unsaturated end-group and/or causing β-fragmentation to poly(t-BA) containing an unsaturated end group. Thus, PAA[BOND]C=CH2 prepared was highly functionalized with f ˜ 0.9.

In contrast, it was possible to prepare similar highly end-functionalized PMAA[BOND]C=CH2 by a direct polymerization of MAA in the presence of EBMA presumably because of analogous steric arguments that hold for AFCT polymerizations of tBA13 and MMA.19 The CT value obtained for EBMA in AFCT polymerizations of MAA was 0.49 at 60 °C. This value was smaller than that obtained for the same AFCT agent in the polymerization of AA (CT = 1.25).13

Synthesis of Graft Copolymer

The polymerization mechanisms discussed hence forth are depicted in Scheme 1. Upon propagating radical addition onto the ω-unsaturated end group of polymer (1) a tertiary adduct radical (2) is formed that undergoes either copolymerization (via monomer addition or coupling with further propagating radical) to give a branched or graft copolymer or, depending on the nature of the propagating radical and polymer main chain, β-fragmentation.13, 14, 19–21

Scheme 1.

Reactions of PAA[BOND]C=CH2 (R = H) and PMAA[BOND]C=CH (R = Me) in copolymerizations with excess NIPAM monomer. Graft copolymer is represented as • (AA) and ○ (NIPAM) units.

The evolution of the MWDs with conversion for the polymerization of NIPAM in the presence of PAA[BOND]C=CH2 is shown in Figure 1. A clear depreciation in the macromonomer peak with conversion, at the expense of a higher molecular weight peak, indicated the formation of the new graft copolymer possessing poly(NIPAM) main chain and poly(AA) branches.

NIPAM polymerization conducted in the absence of PAA[BOND]C=CH2 proceeded ∼ 2.4 times faster than the copolymerization that gave the graft copolymer (Fig. 2). This is rationalized by the persistence of the tertiary adduct radical (2, R = H) (Scheme 1). However, adduct radical (2, R = H) adds onto NIPAM faster than β-fragmentation allowing the copolymerization to prevail.

Figure 2.

Polymerizations of NIPAM in the absence (▴, [NIPAM] = 1.31 M, [AIBN] = 0.037 M) and in the presence (▪) of PAA[BOND]C=CH2 in ethanol at 60 °C. Copolymerization of PAA[BOND]C=CH2 with NIPAM; [PAA[BOND]C=CH2 = 0.022 M, [NIPAM] = 131 M, [AIBN] = 0.037 M.

The reactivity ratio (k1/k2) of poly(NIPAM) propagating radical towards macromonomer and monomer double bonds is given by eq 1 (which is valid when macromonomer concentration is low), and was estimated from the slope of the line of best fit through the origin of the decrease in unsaturated end group (C=C) of the macromonomer (trans and cis-H to carboethoxy substituent of ω-end group appeared at 5.60 and 6.16 ppm, respectively13) as a function of NIPAM conversion (Fig. 3).13, 19

equation image(1)

where k1 and k2 refer to the rate constants for addition of poly(NIPAM) propagating radical onto macromonomer unsaturated ω-end group and NIPAM double bond, respectively (and [C=C]0 denotes the initial concentration). The slope of 2.1 obtained from Figure 3 indicated that the macromonomer was more than two times more reactive towards poly(NIPAM) propagating radical than NIPAM monomer. This leads to the macromonomer concentration decreasing more than two times faster than that of the monomer (thus decreasing the rate of incorporation the macromonomer into the graft copolymer relative to that of the monomer with conversion). The level of macromonomer incorporation at specific NIPAM concentrations (conversions) can be obtained using eq 1. This is used to estimate the relative number of macromonomer units incorporated relative to monomer, i.e. the graft density. Using the reactivity ratio of 2.1, the average number of NIPAM units between poly(AA) branches is 32 at 1% monomer conversion, which increases to 40 NIPAM units between poly(AA) branches at 41% conversion.

Figure 3.

Reactivity of PAA[BOND]C=CH2 and NIPAM monomer double bonds towards poly(NIPAM) propagating radical in copolymerizations in ethanol at 60 °C: [PAA[BOND]C=CH2] = 0.022 M, [NIPAM] = 1.31 M, [AIBN] = 0.037 M.

Isolation of the graft copolymer free of unreacted macromonomer and any nonfunctionalized poly(AA) homopolymer was achieved using a selective precipitation process by the addition of water to a methanol solution of the polymer mixture at 41% monomer conversion (originally isolated by precipitation in diethyl ether) (See Fig. 4 for 1H NMR of the graft copolymer). Comparison of the 1H NMR resonances due to the NCH of the isopropyl groups of the poly(NIPAM) backbone (˜ 3.90 ppm) with that of the CH2[BOND]Br (3.49–3.69 ppm) of the α-end structure of the poly(AA) yielded a graft density of one poly(AA) branch occurring approximately every 42 NIPAM units along the main chain. This latter value is found to be in excellent agreement with the average graft density calculated using eq 1 at the same conversion, where one branch was estimated to occur every 40 NIPAM units.

Figure 4.

1H NMR spectrum (with assignments) of purified graft copolymer (NIPAM conversion = 41%) containing poly(NIPAM) main chain and poly(AA) branches. Resonance with asterisk is due to MeOH (NMR solvent).

Polymerization of NIPAM with PMAA[BOND]C[DOUBLE BOND]CH2

The MAA analogue of the poly(AA) macromonomer, PMAA[BOND]C=CH2, was found to behave differently in polymerizations with NIPAM (Fig. 5). The MWD for the original PMAA[BOND]C=CH2 was found to be very similar to polymerization mixtures up to ∼25% NIPAM conversion, indicating negligible copolymerization and significant β-fragmentation of adduct radical (2, R = Me) to give poly(MAA) propagating radical (3, R = Me) and new macromonomer of NIPAM (4) (Scheme 1). This was supported by 1H NMR spectra of polymerization mixtures showing a change in the vinylic peak pattern with conversion (new signals appeared at 5.58 and 6.15 ppm, respectively, for the trans and cis-H to the ω-carboethoxy substituent of 4 [Fig. 6(b)], but of similar overall intensity. The OCH2 quartet resonance of the ω-end group (˜4.2 ppm) undergoes slight deformation up to 25% conversion, further supporting the generation of a new macromonomer. Therefore, PMAA[BOND]C=CH2 cannot act as an effective macromonomer because of its inability to copolymerize. Copolymerization or β-fragmentation of tertiary adduct radicals is dictated by relief of internal strain, with the bulkier main chain of poly(MAA) favoring β-fragmentation in an analogous fashion to AFCT superiority in polymerizations of MA with poly(MMA) containing an ω-unsaturated 2-carbomethoxy-2-propenyl [[BOND]CH2C(CO2Me)=CH2] end group.19

Figure 5.

MWDs (after methylation of methacrylic acid moieties of the polymers formed in the polymerization of NIPAM in the presence of PMAA[BOND]C=CH2: (blue trace) in 50:50 (v/v) mixture of water and l,4-dioxane at 60 °C: [PMAA[BOND]C=CH2] = 0.022 M, [NIPAM] = 0.61 M: [AIBN] = 0.037 M: MWD at different NIPAM conversions; black (hidden) = 8%, pink = 13%, green = 20%, cyan = 25%, dashed black = 63%, dotted black = 78%, dashed dotted black = 83%, red = 92%. The peak heights are all normalized to unity.

Figure 6.

Part of the 1H NMR spectra of (a) PMAA[BOND]C=CH2, and polymerizations of the latter with NIPAM at (b) 25%, (c) 63%, (d) 92% conversion. Resonance with asterisk is due to the [BOND]OH of the poly(MAA) repeat unit.

However, when the polymerization of PMAA[BOND]C=CH2 was taken to high conversion (>63%), a shift of the MWD to higher molecular weight was clearly observed (Fig. 5) indicating copolymerizations of poly(MAA) propagating radicals (3, R = Me) with NIPAM and of newly formed in situ macromonomer (4) with poly(NIPAM) propagating radicals to give undefined branched polymers. Bimodality evident here, especially in the MWD at 63% conversion, is presumably attributable to the presence of all polymeric species at the same time, i.e. macromonomers and undefined branched polymers. At higher conversion (92%) the MWD was shifted almost entirely to higher molecular weight relative to the original PMAA[BOND]C=CH2 indicating the vast majority of the original poly(MAA) homopolymer was now incorporated into new copolymer. The disappearance of the unsaturated methylene signals and the shift of the OCH2 resonance (˜ 4.2 ppm) to a lower chemical shift (presumed to be hidden by the emerging NCH resonance of the isopropyl groups of the poly(NIPAM) backbone (˜ 3.9 ppm)) in the 1H NMR spectra at these very high conversions indicated the disappearance of all traces of 1 (R = Me) and 4 by copolymerization [Fig. 6(d)].


NIPAM copolymerizes with poly(AA) macromonomer to give a novel graft copolymer. This is the first report of a graft copolymer containing poly(NIPAM) main chain and poly(AA) side chains. A novel selective precipitation was successfully used to remove unreacted macromonomer (poly(AA) homopolymer) resulting in pure graft copolymer. An average graft density of one poly(AA) branch every 42 NIPAM units was calculated for the latter copolymer sample at 41% conversion of NIPAM using 1H NMR, whilst the radical reactivity ratio indicated a very similar average graft density of one poly(AA) every 40 NIPAM units.

AFCT occurs with the methacrylic analogue of poly(AA) macromonomer in polymerizations with NIPAM at low conversion, presumably due to the steric hindrance associated with the polymer main chain. This was followed by copolymerizations of the in situ formed NIPAM macromonomer, and polymerizations of NIPAM initiated by poly(MAA) radicals, at higher conversions.


Authors thank Science Foundation Ireland for an E.T.S. Walton Visitor Award for Professor Bunichiro Yamada and The Irish Research Council for Science, Engineering, and Technology: funded by the National Development Plan, for an Embark Postgraduate Scholarship for Ronan McHale.