Amphiphilic Double-Brush Polymers Based on Itaconate Diesters

Jun 21, 2017 - Itaconic anhydride, a biosourced molecule, was readily transformed to polymerizable nonionic amphiphiles of the type R-Ita-R′; these ...
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Amphiphilic Double-Brush Polymers Based on Itaconate Diesters Saheli Chakraborty, S. G. Ramkumar, and S. Ramakrishnan* Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India S Supporting Information *

ABSTRACT: Itaconic anhydride, a biosourced molecule, was readily transformed to polymerizable nonionic amphiphiles of the type R-Ita-R′; these amphiphiles carry an exo-chain double bond, which upon polymerization yielded amphiphilic doublebrush polymers, especially when R and R′ are immiscible, and consequently exhibit a tendency to self-segregate. DSC, WAXS, SAXS, and variable temperature FT-IR studies of these amphiphilic double-brush polymers confirm the occurrence of self-segregation followed by crystallization of the cetyl segments; in most cases a lamellar morphology is seen wherein the two immiscible segments form the alternating lamellae and the polymer backbone presumably lie along their interface. C16-Ita-HEG, which carries a hydrophobic cetyl chain and a hydrophilic heptaethylene glycol monomethyl ether unit, forms a hydrogel upon polymerization at concentrations above 2.5 wt %; an interesting feature of this hydrogel is that it exhibits a reversible thermal and shear-induced transformation to a sol, a property that could be of interest for biomedical applications.

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INTRODUCTION Graft copolymers carry polymeric segments of one type grafted onto a backbone of another; immiscibility between the graft and the backbone segments has a strong bearing on their chain conformation and morphology. Although typical graft copolymers, wherein both the graft segment length and the periodicity of their placement along the backbone are statistically governed, do not develop well-defined microphase-separated morphologies, regulating these parameters, however, could result in precise and predictable morphologies.1,2 Brush polymers can be viewed as a special class of graft copolymers that have a high density of pendant graft segments; often the graft segments are located periodically and at very close distances along the backbone. Extensive studies have been done to examine the effect of graft segment length and grafting density on the conformation of the backbone.3 Dense grafting causes a considerable increase in the persistence length of the polymer backbone, and consequently block copolymers based on such brush polymers, that carry graft segment on every repeat unit, have recently been used to create periodic ordering at large enough length scales so as to realize photonic band gap structures.4 Cross-linked networks based on such dense brush polymers were shown to exhibit remarkably low compression modulus but with high strength; this is a direct consequence of the brush segments being able to preclude chain entanglements while retaining flexibility.5 Double-brush polymers are a special subclass wherein two different graft segments are anchored to a single point on every repeat unit along the polymer backbone;6 if the two segments are immiscible, then this could lead to the formation of facially amphiphilic (or Janus) brush polymers, as depicted in Figure 1. © XXXX American Chemical Society

Polymers that carry two immiscible pendant segments on every repeat unit have been examined in two distinct contexts: one has focused on their solution aggregation properties while the other on the microphase separation in bulk. In the former context, typically the pendant segments are relatively short whereas in the later both pendant segments are polymeric in nature. From the viewpoint of solution behavior, early studies by Thayumanavan et al.7 demonstrated the conformational adaptability of pendant amphiphilic polymers (Type I, Figure 1), which led to the formation of both micellar and reverse micellar aggregates in water and hydrocarbon solvents, respectively. Although most of the early designs utilized a hydrophobic alkyl segment and an ionizable hydrophilic unit, like −COOH, more recent reports have examined polymers that carry two different immiscible pendant segments on each repeat unit. Grayson et al., for instance, developed a nonionic analogue by polymerizing an acrylate derivative carrying pendant alkyl and PEG segments (Type I);8 these polymers also demonstrated the ability to undergo conformational reorganization to generate micellar and reverse micellar structures depending on the solvent used. Polymerizable amphiphiles (surfmers), that carry a polymerizable group at the junction of the hydrophobic and hydrophilic segments (Jsurfmers; for Junction-surfmers), on the other hand, have been used to prepare Type II amphiphilic polymers.9 Tsujii and coworkers were one of the first to study such J-surfmers based on amphiphilic itaconates; in a series of papers, they explored the Received: April 19, 2017 Revised: June 12, 2017

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Figure 1. Schematic depiction of the different architectures for amphiphilic polymers.

Figure 2. Structure and synthesis of itaconic acid-based nonionic J-surfmers.

immiscibility of PS and PLA segments. More recently, Johnson et al. examined the systematic evolution of bulk morphology in such double-brush systems (Type I), which they term Abranch-B; their systems were also based on polynorbornene derivatives carrying two immiscible pendant graft segments, namely polystyrene and polydimethylsiloxane, on every repeat unit.20 They too suggest that the backbone adopts a Janus comb structure, and consequently the polymers exhibited a range of well-defined morphologies in the bulk; from cylinders to gyroid to lamellae, depending upon the relative sizes of the pendant PS and PDMS segments. An important revelation of their work was the formation of domains at significantly smaller length scales than typically observed for block copolymers. Clearly, polymers prepared from J-surfmers are architecturally similar to amphiphilic double-brush polymers, except for the nature and size of the pendant segments; thus far, these have been examined from distinctly different contextsthe former in solution whereas the latter, primarily, in bulk. In the present study, a class of polymerizable amphiphiles was designed so as to be examined from both these perspectives; by appropriate choice of the two segments, we have been able to show that Type II amphiphilic double-brush polymers

formation and polymerization of expanded iridescent bilayers in water using n-dodecylglyceryl itaconate.10−13 Mathias and coworkers examined alternate systems based on an unsymmetrical diester of α-hydroxymethyl acrylate; they demonstrated that these J-surfmers were very effective in generating stable emulsions of acrylates with good control over particle size and their distribution.14 More recently, Dai and co-workers studied a maleate-based nonionic amphiphilic surfactants and utilized the maleate double bond to generate what they termed “waist cross-linked micelles” and analogous reverse micelles.15 However, none of these studies examine the bulk behavior of polymers. There are relatively fewer studies wherein two immiscible pendant polymeric segments are present on every repeat unit.16−20 Cheng et al. developed an interesting strategy wherein a norbornene derivative, carrying both a RAFT agent and a hydroxyl group, was used to simultaneously polymerize styrene and ring-open polymerize lactide; this was then polymerized by ROMP to yield Type I amphiphilic doublebrush polymers.19 The interesting feature of these polymers is that they underwent self-segregation and revealed Janus-type structures in the TEM images, presumably driven by the B

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melting point before the measurement. Rheology experiments were performed using an AR 1000 rheometer (TA Instruments). All the rheological studies were performed with hydrogels containing 4 wt % of the polymerized surfmer C16-Ita-HEG. Polymerization of C16-Ita-HEG in Water. A required amount of C16-Ita-HEG was dissolved in Millipore water and sonicated using a bath sonicator for 10 min to generate a uniform dispersion. N2 gas was purged through the solution for 10 min followed by addition of 1 wt % Irgacure 2959 as a water-soluble photoinitiator. The polymerization was performed in a Pyrex glass tube under 365 nm UV light for 2 h. After the reaction, if needed, water was removed by lyophilization to obtain sticky solid which was washed twice with cold MeOH to obtain the pure polymer. Yield = 70%. The hydrogel prepared at higher concentrations was directly used for all the studies, such as DSC, WAXS, and rheology; for TEM measurements, the as-prepared samples were suitably diluted before applying onto the grid. Mn = 3600. Polymerization of C16-Ita-Gly. 200 mg of C16-Ita-Gly was dissolved in 40 mL of Millipore water by heating at 55 °C for about 10 h. The polymerization was carried out following the same procedure as C16-Ita-HEG using Irgacure 2959 as the photoinitiator. After the polymerization, water was removed by lyophilization. Pure polymer was obtained by reprecipitating twice from MeOH. Yield = 65% and Mn = 3700. Polymerization of F8-Ita-HEG. 200 mg of the monomer was dissolved in 4 mL of Millipore water by sonication and was photopolymerized using Irgacure-2959 as initiator. After the polymerization, the solution was heated at 70 °C in the presence of small amount of NaCl; since the polymer exhibited an LCST, it precipitated out and was isolated. Yield = 75% and Mn = 3400. Polymerization of C16-Ita-F8. 200 mg of the monomer was dissolved in 200 μL of THF and degassed thoroughly. It was then polymerized thermally in the presence of 2 mol % AIBN as thermal initiator which was added in three batches during the course of polymerization. The polymerization was carried out for 48 h, and finally pure polymer was obtained by reprecipitating twice from MeOH. Yield = 60% and Mn = 3500; this polymer had a very low RI contrast, and hence the RI detector response was very weak. The NMR spectra of all the polymers along with those of the monomers can be found in the Supporting Information.

bearing relatively short segments can indeed form microphaseseparated morphologies and can also exhibit fairly interesting solution behavior; both these behaviors rely on the strong crystallization tendency of one or both the segments. This study was prompted by our recent observations of microphase separation in periodically grafted amphiphilic copolymers (PGACs),21,22 wherein lamellar morphologies at length scales as small as ∼5 nm was observed due to zigzag folding-induced self-segregation accompanied by crystallization of either one or both segments; crystallization, we believe, is a key driver for microphase separation at these length scales. Itaconic acid is an inexpensive biosourced molecule which is an aliphatic dicarboxylic acid containing an exo-chain double bond. Being a dicarboxylic acid, itaconic anhydride provides ample opportunities for hetero-functionalization and polymerization; some years ago we prepared simple long chain alkyl monoesters of itaconic acid and demonstrated that these can function as surfmers for the preparation of covalently stabilized polystyrene emulsions with controllable size.23 In an effort to develop other interesting amphiphilic polymerizable molecules based on itaconic acid, we explore here the heterofunctionalization of itaconic acidfirst, itaconic anhydride is functionalized with an alcohol, such as cetyl alcohol, to yield the monoesters, which can then be reacted with either a polar segment, such as poly(ethylene glycol) monomethyl ether (MPEG) and glycerol or with a perfluoroalkan-1-ol (Figure 2). Such hetero-diitconates would behave as J-surfmers and therefore would provide simple access to a variety of interesting double-brush polymers, wherein the two immiscible segments are small molecular fragments that can be readily varied. Despite the relatively small sizes of the pendant segments, the resulting amphiphilic double-brush polymers exhibit microphase separation as a consequence of adoption of Janus chain configuration.

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EXPERIMENTAL SECTION

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Methods. NMR spectra were recorded using a Bruker AV400 MHz spectrometer in suitable deuterated solvents using tetramethylsilane (TMS) as internal standard. The polymerizations were carried out in a Luzchem photoreactor equipped with eight UV lamps that generate light of wavelength 365 nm, with a total intensity of 2.4 mW/cm2. The photoreactor is also equipped with a magnetic stirrer for gentle stirring. IR spectra were recorded in a PerkinElmer Spectrum One FTIR spectrometer. The homopolymers were lyophilized, dissolved in CHCl3, and drop-cast on either CaF2 window or KBr pellets and dried under vacuum before recording their IR spectra. Gel permeation chromatography (GPC) of all the samples was carried out using a Viscotek TDA model 300 system which is coupled with refractive index detector. The separation was achieved using two mixed-bed PLgel columns (5 μm, mixed-bed C) which were maintained at 35 °C. Tetrahydrofuran (THF) was used as the eluent. The molecular weights were determined using a standard calibration curve based on polystyrene standards. DSC measurements of the samples were carried out in a PerkinElmer DSC 8000 instrument using a heating rate of 10 deg/min, unless specified otherwise. Typically, about ∼5 mg of the sample was heated to a temperature above its melting to erase thermal history, followed by two heating/cooling cycles to ensure reproducibility. For the hydrogel samples, a larger 50 μL liquid sample pan was used, and the sample was hermetically crimped. The bright-field TEM images were recorded using a JEOL 2100F instrument at 200 kV voltages. The diluted as-prepared samples were drop-cast from water onto the carbon-coated Cu grids, which were rendered hydrophilic by plasma sputtering prior to the sample preparation. XRD experiments were performed in a PANalytical Empyrean machine operating at 45 kV and 30 mA, using Cu Kα radiation (λ = 1.5418 Å) equipped with a PIXcel 3D detector. All the samples were annealed around their

RESULTS AND DISCUSSION The two carboxylic acid groups of itaconic acid were functionalized sequentially using a simple two-step process; at first itaconic anhydride was ring opened by cetyl alcohol to obtain monocetyl itaconate, which was further esterified to add a polar segment, like heptaethylene glycol monomethyl ether or glyceryl, or a perfluoroalkyl unit to yield the desired heterofunctionalized diitaconates (Figure 2). As described in the Experimental Section (see Supporting Information for details), different approaches were required for the second step to access different diitaconates; some were prepared via the acid chloride approach whereas others were prepared under nucleophilic conditions using the tosylate. The polymerization of the itaconates-based J-surfmers carrying a hydrophobic and hydrophilic segment, such as C16-Ita-HEG and C16-Ita-Gly, were carried out in water above the CMC of the surfactant. Typically, the polymerization was photoinitiated using a watersoluble photoinitiator, Irgacure2959; as previously reported, when bulky substituents are present, itaconates are sluggish to polymerize.24 C16-Ita-HEG, C16-Ita-Gly, and F8-Ita-HEG polymerized only in the micellar state; the collocation of the double bonds within the aggregate enhanced the polymerizability of these amphiphilic itaconates. On the other hand, after several attempts under different conditions, C16-Ita-F8 was finally polymerized in a highly concentrated solution of THF. The C

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Macromolecules GPC molecular weights (Mn) of the various polymers were found to be in the range of 3500−4000 (Figure S2), implying a DP of 8−12; bulky 1,1-disubstituted acrylates typically do not polymerize readily and yield polymers of relatively low molecular weight.14,18 The proton NMR spectra of all the polymers (Figure S1) confirmed their structure; the vinyl protons of the itaconate vanished, and all the other peaks were slightly broadened. Further, in order to examine the kinetics of polymerization, the FT-IR spectra of the polymerization mixture, in the case of C16-Ita-HEG, were recorded as a function of polymerization time (Figure S4); typically, an aliquot of the polymerization mixture was taken out after different time intervals and freeze-dried, and their spectra were directly recorded. It was clear that with increasing irradiation time the intensity of the peak at 1642 cm−1 due to the olefinic double bond decreased and almost completely disappeared within 60 min. Furthermore, whereas two closely separated CO stretching peaks are seen in the monomer, upon polymerization the shoulder at the lower wavenumber (∼1719 cm−1) corresponding to the α,β-unsaturated ester disappeared leading to a small apparent shift in the carbonyl peak to 1736 cm−1; this again reveals the expected loss of conjugation upon polymerization. All the polymerizations, therefore, were carried out for about 2 h to ensure completion. The polymers are labeled as monomer-P, for instance, C16-Ita-HEG-P. C16-Ita-HEG-P: Hydrogel Properties. The amphiphilic itaconate, C16-Ita-HEG, exhibited some unique behavior, and hence its polymerization was studied as a function of concentration. The critical micellar concentration (CMC) of C16-Ita-HEG was first determined using the pyrene encapsulation method,25 and it was found to be 0.057 mM (Figure S5); therefore, all the polymerizations were carried out above this concentration. It must be mentioned here that whereas the polymerization occurred at room temperature when a photoinitiator was used, thermal initiation using potassium persulfate at 60 °C failed to affect polymerization. This failure was attributed to the fact that C16-Ita-HEG exhibited a lower critical solution temperature (LCST) of 46 °C (Figure S6), and therefore it was effectively insoluble at the polymerization temperature of 60 °C and thereby inhibited polymerization. In an effort to understand the influence of the surfmer concentration, the polymerization was carried out at three different concentrations, namely, 0.02, 0.2, and 2.5 wt %all above the CMC. At the lowest concentration, TEM images (Figure 3) of the polymerized assemblies clearly reveal micellar aggregates having a fairly uniform size of about ∼4 nm (histogram shown in Figure S7); at 0.2 wt %, further aggregation into clustered micelles is evident. When the polymerization was carried out at 2.5 wt %, the solution gelled upon polymerization. Upon first examination, the sample obtained after freezedrying the hydrogel appeared insoluble in most common organic solvents; however, upon heating in toluene it dissolved completely ruling out the possibility of any inadvertent covalent cross-linking. Since the polymer bears long cetyl chains, it was hypothesized that crystallization of side-chains could lead to the formation of physically cross-linked gels. To examine this, DSC measurements of the aqueous surfmer solution, before and after polymerization, were carried out; from Figure 4, it is evident that melting/crystallization peaks are seen in both samples, suggesting the presence of some crystalline organization in both samples. First, it is noted that the melting temperature after polymerization is higher than that of the monomer (39 °C

Figure 3. TEM images of the polymerized C16-Ita-HEG solution at different initial concentrations. Note that the scale bars on the images are different.

Figure 4. DSC thermograms of 2.5 wt % C16-Ita-HEG solution before polymerization (upper panel) and of the hydrogel formed after polymerization (lower panel).

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Figure 5. (A) Frequency sweep (at 1 Pa), (B) stress sweep (at 1 Hz), and (C) time scans at different shear stress (at 1 and 100 Pa).

versus 30 °C); assuming that this peak is due to the crystallization of the cetyl segments, the peak area was normalized with respect to the weight fraction of the cetyl chains. It is seen that the normalized enthalpy is also significantly higher after polymerization (61 J/g versus 47 J/ g), suggesting an enhanced collocation/crystallization of the cetyl chains in the polymer. At first sight, this was little surprising given that polymerization would be expected to limit the freedom of cetyl segments; however, the stretching out of the pendant groups in such brush polymers20 could lead to such an enhancement. Reversibility of the melting/crystallization processes was confirmed by the overlap of multiple heating and cooling scans in both samples. WAXS data (Figure S8) of hydrogel revealed a sharp peak (2θ = 21.4°) corresponding to the formation of a paraffinic crystalline lattice, presumably due to the self-segregation and crystallization of the cetyl chains. These observations suggest that the gel formed upon polymerization of the C16-Ita-HEG at higher concentration is indeed due to physical gelation; visual observation suggested that upon heating above 40 °C the polymerized hydrogel turned to a free flowing sol, and upon cooling the gel was reformed. However, in an organic solvent, like toluene, although the freeze-dried sample of the polymerized gel was completely soluble upon heating, it did not form a gel upon cooling. As expected, in an organic solvent the driving motivation for aggregation/crystallization of the hydrophobic cetyl segments is not strong enough, unlike in an aqueous system. The TEM image of this gelled sample (Figure 3) also reveals the presence of elongated worm-like fibrils that are presumably generated by aggregation of individual micelles and upon polymerization forms an extended fibrillar network. Formation of such wormlike micelles in aqueous solutions of polymerizable amphiphiles has been observed earlier and was seen to be preserved upon polymerization, although detailed study of their properties was not carried out.26 In our amphiphilic brush polymers, the backbone could adopt a Janus configuration that segregates the cetyl and PEG segments on either side of the chain; the clustering of such Janus chains could then lead to cylindrical micelles. Since these aggregates in water would have the PEG segments on the outside, the formation of physical networks would require the collocation and crystallization of the cetyl core segments; this could happen by individual Janus chains serving as a bridge between two cylindrical micellar aggregates. This hypothesis that crystallization of the cetyl chains forms the basis for gelation is based on two observations: one is the visual observation that the gel turns to sol at ∼40 °C, which is where the endothermic peak is seen in the DSC of the hydrogel (Figure 4); second is the variable temperature FT-IR studies of

the gel (Figure S9) that also reveals that the symmetric and antisymmetric C−H stretching vibrations shift to higher wavenumbers 27 around the same temperature, thereby confirming that the DSC peak is indeed associated with the melting of the cetyl chains. Having said this, it is important to recognize that tacticity would play a crucial role in the aggregation process; it is evident that if the polymer is isotactic, the all-trans extended conformation would generate a Janus structure, whereas in the atactic case the Janus chain will have to adopt a random conformation to enable the two immiscible segments to lie above and below the chain. Thus, the role of tacticity in such amphiphilic double-brush polymers is clearly an interesting question that awaits detailed scrutiny. Rheological Properties of C16-Ita-HEG-P Hydrogel. Since the hydrogels formed at high concentrations exhibit a clear melting transition, above which it turns to a sol; we decided to examine the rheological properties of the gel to understand the effect of shear on the gel. Rheological studies of the gel samples were carried out using a parallel plate geometry rheometer under oscillatory shear; first, as evident from Figure 5A, a significantly higher value of the storage modulus G′ (almost 5 times greater) when compared to the loss modulus G″ confirmed the elastic nature of the hydrogel at RT. The frequency-sweep experiments (Figure 5A) indicate that both G′ and G″ varied weakly over a fairly wide range of frequencies, indicating that the relaxation times of the physically crosslinked network are significantly longer than the time scale of the experiments, and therefore the physical cross-links remain intact, thus retaining the elastic nature of the gel. The dynamic storage modulus of the hydrogel was ∼3 kPa, which is typical of hydrogels formed by hydrophobically modified hydrophilic polymers.28 The stress-sweep experiments (Figure 5B) revealed that the gel exhibited a yield stress of ∼30 Pa, beyond which it sharply transformed into a sol; both the values of G′ and G″ fell steeply, and importantly, the value of G″ exceeded that of G′, indicating the complete loss of elasticity due to the formation of sol. In order to examine the reversibility, the hydrogel was subjected to alternating low and high values of oscillatory stress (1 and 100 Pa) wherein the sample behaves as gel and liquid, respectively. It was observed that the sample almost completely recovers its gel state upon lowering the stress (Figure 5C); however, the magnitude of both G′ and G″ does not return to their original values, indicating that the state of the gel after the first transformation to a sol is slightly different. Such behavior is not uncommon and is generally attributed to the fact that rapid reaggregation happens only to a limited extent; and once the percolation threshold is crossed, the elastic nature is recovered. A relatively slower process of attaining the original state of E

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Macromolecules aggregation follows, which could be a lot slower, and hence the original values of G′ and G′′ are not immediately attained.29 Such reversible physical gelation has been extensively examined in the context of hydrophobically modified water-soluble polymers;28 the aggregation of the hydrophobic residues, which are typically long alkyl chains, leads to the generation of transient aggregates and consequently to the formation of hydrogels. Rheological studies of these systems also reveal a similar behavior of incomplete recovery of the gel strength upon lowering the strain rate below the threshold value. In most of these studies, however, the mole fraction of the pendant hydrophobic units is small and the backbone itself serves as the hydrophilic segment.28−31 Bulk Properties of Amphiphilic Double-Brush Poly(itaconates). Whereas C16-Ita-HEG-P formed a hydrogel, none of the other amphiphilc polyitaconates, namely C16-ItaGly-Pand F8-Ita-HEG-P, did so. Hence, their solution behavior was not examined; however, their solid state properties were investigated. As mentioned earlier, the self-segregation of immiscible segments in amphiphilic double-brush polymers to form Janus structures has been a topic of great interest both from a theoretical32 and an experimental point of view;19,20 recent experimental studies has revealed that various microphase-separated morphologies can result depending on the relative lengths of the two graft segments.20 However, as mentioned earlier, both previous studies have examined systems that carry long polymeric pendant segments. In order to explore the possibility of such self-segregation in our polymers, we first carried out DSC measurements; since C16 chains have a strong tendency to crystallize, it is expected that self-segregation would result in their crystallization. The DSC thermograms of the different amphiphilic polyitaconates are shown in Figure 6; it is evident that the cetyl chains in all the samples appear to crystallize and therefore exhibit clear melting/crystallization peaks. Assuming that the crystallization is primarily due to the cetyl chains, the enthalpies were normalized with respect to the weight percent of cetyl segment in the sample; these values along with the Tm are shown in the figure. The assumption that the melting peak is due to the crystallization of cetyl chains is supported both by variable temperature FT-IR studies (Figure S10) and by WAXS measurements; FT-IR spectra reveal a shift of the C−H symmetric and asymmetric stretching frequencies to high values upon melting, which is due to the transition from an all-trans conformation to a gauche-rich one upon melting.27 As observed previously,33 the presence of a crystallizable fluoroalkyl chains (F8) often leads to an increase in the melting point of the covalently linked hydrocarbon segment; comparing the thermograms of C16-Ita-HEG-P with that of C16-Ita-F8-P, we see a 10 deg increase in the melting temperature in the presence of the fluoroalkyl segment. Self-segregation in the case of C16-Ita-F8-P should lead to independent crystallization of both the C16 and F8 segments; however, since the enthalpy associated with the fluorocarbon is small,34,36 it is likely to be subsumed in the large peak due to the C16 chain. C16-Ita-GlyP showed a weak melting peak; the normalized enthalpy was significantly lower, suggesting that the glyceryl unit disturbs the packing of the cetyl chains. It is likely that the branched nature of the glyceryl unit and the possibility of H-bonding with the units in the adjacent layer adversely affect the ability of the cetyl segments to crystallize. Wide-angle X-ray scattering studies (WAXS) reveal the formation of a paraffinic lattice in all the samples carrying a

Figure 6. DSC thermograms of the different amphiphilic double-brush polymers done at a heating/cooling rate of 10 deg/min. C16-Ita-F8-P did not exhibit any peaks; however, upon annealing at ∼50 °C, a weak melting peak is visible in the inset, possibly due to the fluorocarbon. Subsequent runs did not reveal any peaks; clearly annealing was required to assist self-segregation.

cetyl segment; in all cases a peak at 21.4° confirms the formation of a hexagonally packed lattice with the d spacing of 4.1 Å; that is typical of a paraffinic crystalline lattice35 (Figure 7). The peak is significantly sharper in the case of C16-ItaHEG-P when compared to the other two samples indicating that both the microphase separation and crystallization is more effective in this case, possibly because HEG segment is amorphous and provides greater freedom for the crystallization of the cetyl segments. In the other two samples, namely C16Ita-Gly-P and C16-Ita-F8-P, the H-bonding network and the fluorocarbon crystallization, respectively, appear to impose a constraint on the crystallization of the cetyl segments. In the F

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Figure 7. WAXS profiles (left) of the amphiphilic double-brush polymers carried out at RT (∼25 °C). Sample F8-Ita-HEG-P was recorded after prolonged annealing at 50 °C for over 168 h. SAXS profiles (right) of the different samples at RT; as in the case of WAXS, the profile of F8-Ita-HEGP was recorded after the sample was annealed.

case of C16-Ita-F8-P, there are two clear peaks indicating the presence of crystalline organization of both the cetyl and fluoroalkyl segments; the additional peak at 18° corresponds to the packing of fluorocarbon chains into a crystalline lattice, with an interchain distance of 5.0 Å.36 SAXS profiles (Figure 7) of the samples confirm the formation of a lamellar morphology in all cases; in three of the samples the interlamellar spacing was over 5 nm, while in C16-Ita-Gly-P, as expected, it was significantly smaller at 3.9 nm. In an effort to rationalize the observed spacings, an estimate of the pendant segment lengths was obtained using molecular modeling; the cetyl chains in an all-trans extended conformation would account for ∼1.9 nm, whereas the perfluorooctyl segment would be about ∼1.0 nm in length. As shown in Figure 8, the lamellar morphology in these polymers would be generated by the formation of a bilayer assembly; consequently, the interlamellar spacing would reflect twice the length of the two pendant segments, along with a

contribution from the polymer backbone. In the case of C16Ita-HEG-P, the interlamellar spacing is 5.2 nm; an estimate of the thickness of the amorphous HEG layer was obtained from our previous studies on periodically grafted amphiphilic copolymers (PGACs),22 and the value of ∼0.85 nm was assigned to the HEG.37 It is clear that the sum total of two cetyl chains and two HEG segments (3.8 + 1.7 = 5.5 nm) exceeds the observed spacing, even without including contribution from the backbone itaconate repeat unit; this deviation could arise because of an incorrect assumption that the entire cetyl chain is in an extended all-trans conformation. It is well-known from studies of long chain alkyl (meth)acrylates that a significant fraction of the pendant alkyl segment lying close to the backbone do not adopt an extended all-trans conformation and consequently is not a part of the paraffinic crystalline lattice;38 it is suggested that a roughly constant number of methylenes (∼10−12) do not form a part of the crystalline lattice, which apparently is the minimum required number to decouple the G

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Figure 8. Structures of the different amphiphilic double-brush polymers, along with a pictorial depiction of their organization into a lamellar morphology; the observed interlamellar lattice spacing is also shown. The wiggly line (in red) depicts that the portion of the cetyl chains close to the backbone are not likely to form a part of the crystalline paraffinic lattice.

could drive the formation of Janus-type chains that further organize to form lamellar morphologies in the bulk. It was shown that self-segregation occurs effectively in polymer brushes bearing cetyl and PEG, cetyl and perfluoroalkyl chains, perfluoroalkyl and PEG, and also between cetyl and glyceryl segments; the crystallization of one or both of the pendant segments appears to reinforce the self-segregation process and in turn enables the formation of microphase-separated morphologies. DSC thermograms of all polymers with pendant cetyl chains exhibit a melting peak reflecting the microphase separation and crystallization of the cetyl chains, which was confirmed by WAXS and variable temperature IR measurements. In C16-Ita-F8-P, carrying cetyl and perfluoroooctyl chains, WAXS data show that both the segments are organized in independent crystalline lattices. SAXS studies revealed the formation of a lamellar morphology in all cases; the interlamellar spacing in three of the samples fall in the range of 5−6 nm, whereas in C16-Ita-Gly-P, which carries a smaller polar glyceryl unit, the value is smaller, ∼3.9 nm. These interlamellar spacings reflect a bilayer arrangement of Janus chains, wherein alternate lamellae are populated by the two immiscible pendant segments and the polymer backbone straddles the interfacial domains. C16-Ita-HEG-P exhibited an interesting behavior in aqueous solution; at concentration above 2.5 wt %, polymerization leads to the formation of a hydrogel. As is typical of hydrophobically associating polymers, here too the hydrogel is formed by the association and crystallization of the cetyl chains that leads to

backbone conformation from the crystalline organization of the side chains. If one takes this into consideration, the smaller value of the interlamellar spacing may be rationalized; this is also consistent with the significantly lower value of the cetyl segment normalized melting enthalpy, which also suggests that only a small section of the cetyl chains (∼6 methylene units) contribute to the crystalline lattice.39 One other possibility for the lower value of the spacing could be some level of interdigitation of the alkyl segments within the bilayer; a combination of both these factors is likely to operate in reality. Similar arguments could be used to rationalize the smaller than expected d-spacing in all other samples (see Figure S11), except in the case of F8-Ita-HEG-P; here the observed spacing of 5.2 nm is significantly larger than that estimated for amorphous HEG and perfluorooctyl (1.7 + 2.0 = 3.7 nm). This observation appears to suggest that in this case the HEG chains could be adopting a slightly more extended conformation due to constraints imposed by the crystallization of the fluoroalkyl segments; the WAXS data clearly show that the perfluorooctyl chains are in a crystalline lattice, although no separate melting peak is seen in the DSC thermogram.

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CONCLUSIONS Using a series of amphiphilic double-brush polymers prepared by free-radical polymerization of heterodiesters of itaconic acid, we have shown that even relatively short but dissimilar pendant segments emanating from each repeat unit along the backbone H

DOI: 10.1021/acs.macromol.7b00815 Macromolecules XXXX, XXX, XXX−XXX

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(2) Beyer, F. L.; Gido, S. P.; Büschl, C.; Iatrou, H.; Uhrig, D.; Mays, J. W.; Chang, M. Y.; Garetz, B. A.; Balsara, N. P.; Tan, N. B.; Hadjichristidis, N. Graft Copolymers with Regularly Spaced, Tetrafunctional Branch Points: Morphology and Grain Structure. Macromolecules 2000, 33, 2039−2048. (3) Potemkin, I. I.; Palyulin, V. V. Comb-like Macromolecules. Polym. Sci., Ser. A 2009, 51, 123−149. (4) Sveinbjörnsson, B. R.; Weitekamp, R. A.; Miyake, G. M.; Xia, Y.; Atwater, H. A.; Grubbs, R. H. Rapid Self-assembly of Brush Block Copolymers to Photonic Crystals. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 14332−14336. (5) Daniel, W. F. M.; Burdyńska, J.; Varnoosfaderani, M. V.; Matyjaszewski, K.; Paturej, J.; Rubinstein, M.; Dobrynin, A. V.; Sheiko, S. S. Solvent free, Supersoft and Superelastic Bottle Brush Melts and Networks. Nat. Mater. 2015, 15, 183−189. (6) Zhu, Y.; Weidisch, R.; Gido, S. P.; Velis, G.; Hadjichristidis, N. Morphologies and Mechanical Properties of a Series of Block-DoubleGraft Copolymers and Terpolymers. Macromolecules 2002, 35, 5903− 5909. (7) Kale, T. S.; Klaikherd, A.; Popere, B.; Thayumanavan, S. Supramolecular Assemblies of Amphiphilic Homopolymers. Langmuir 2009, 25, 9660−9670. (8) Wang, Y.; Alb, A. M.; He, J.; Grayson, C. M. Neutral Linear Amphiphilic Homopolymers Prepared by Atom Transfer Radical Polymerization. Polym. Chem. 2014, 5, 622−629. (9) Mueller, A.; O’Brien, D. F. Supramolecular Materials via Polymerization of Mesophases of Hydrated Amphiphiles. Chem. Rev. 2002, 102, 727−757. (10) Naitoh, K.; Ishii, Y.; Tsujii, K. Iridescent Phenomena and Polymerization Behaviors of Amphiphiiic Monomers in Lamellar Liquid Crystalline Phase. J. Phys. Chem. 1991, 95, 7915−7918. (11) Hayakawa, M.; Onda, T.; Tanaka, T.; Tsujii, K. Hydrogels Containing Immobilized Bilayer Membranes. Langmuir 1997, 13, 3595−3597. (12) Tsujii, K.; Hayakawa, M.; Onda, T.; Tanaka, T. A Novel Hybrid Material of Polymer Gels and Bilayer Membranes. Macromolecules 1997, 30, 7397−7402. (13) Ozawa, J.; Matsuo, G.; Kamo, N.; Tsujii, K. Separated Organized Polymerization of an Amphiphilic Monomer and Acrylamide in One-Pot Reaction. Macromolecules 2006, 39, 7998− 8002. (14) Morizur, J. F.; Irvine, D. J.; Rawlins, J. J.; Mathias, L. J. Synthesis of New Acrylate-Based Nonionic Surfmers and Their Use in Heterophase Polymerization. Macromolecules 2007, 40, 8938−8946. (15) Yuan, C.; Xu, Y.; Deng, Y.; Chen, J.; Liu, Y.; Dai, L. Waist CrossLinked Micelles Synthesized via Self-Assembly Guiding Radical Polymerization. Soft Matter 2009, 5, 4642−4646. (16) Gu, L.; Shen, Z.; Zhang, S.; Lu, G.; Zhang, X.; Huang, X. Novel Amphiphilic Centipede-Like Copolymer Bearing Polyacrylate Backbone and Poly(ethylene glycol) and Polystyrene Side Chains. Macromolecules 2007, 40, 4486−4493. (17) Lian, X.; Wu, D.; Song, X.; Zhao, H. Synthesis and SelfAssembly of Amphiphilic Asymmetric Macromolecular Brushes. Macromolecules 2010, 43, 7434−7445. (18) Li, H.; Miao, H.; Gao, Y.; Li, H.; Chen, D. Effective Synthesis of Narrowly Dispersed Amphiphilic Double-Brush Copolymers Through the Polymerization Reaction of Macromonomer Micelle Emulsifiers at the Oil-water Interface. Polym. Chem. 2016, 7, 4476−4485. (19) Li, Y.; Themistou, E.; Zou, J.; Das, B. P.; Tsianou, M.; Cheng, C. Facile Synthesis and Visualization of Janus Double-Brush Copolymers. ACS Macro Lett. 2012, 1, 52−56. (20) Kawamoto, K.; Zhong, M.; Gadelrab, K. R.; Cheng, L. C.; Ross, C. A.; Katz, A. A.; Johnson, J. A. Graft-through Synthesis and Assembly of Janus Bottlebrush Polymers from A-Branch-B Diblock Macromonomers. J. Am. Chem. Soc. 2016, 138, 11501−11504. (21) Mandal, J.; Prasad, S. K.; Rao, D. S. S.; Ramakrishnan, S. Periodically Clickable Polyesters: Study of Intra-chain Self-segregation Induced Folding, Crystallization and Mesophase Formation. J. Am. Chem. Soc. 2014, 136, 2538−2545.

physical cross-links; the hydrogel exhibits a clear melting peak in the DSC and a scattering peak in WAXS reflecting the formation of a paraffinic crystalline lattice. Furthermore, heating the hydrogel beyond the melting temperature transformed it into a sol, reaffirming the role of cetyl chain crystallization in gel formation. The gel also exhibited a shear-induced transformation to a sol; rheological studies showed that beyond a critical shear stress of 30 Pa the gel became liquid-like. Both thermal and shear-induced transformation of the hydrogel to a sol were fully reversible; the gel state is quickly recovered after the shear-induced transformation, whereas the recovery was relatively slower in the thermally induced case. In summary, the most important outcomes of the study are (a) development of a simple and potentially scalable route to hetero-diitaconates, which upon polymerization provides an easy access to amphiphilic double-brush polymers; (b) despite the relatively small sizes of the pendant segments, we have shown that the resulting amphiphilic double-brush polymers exhibit microphase separation as a consequence of adoption of Janus chain configuration; crystallization of either one or both the pendant segments appears to drive the formation of ultrasmall lamellar ordering, apparently breeching the lower χN limit 40 for microphase separation predicted for block copolymers; and (c) the demonstration that the polymer bearing cetyl and HEG segments, namely C16-Ita-HEG-P, forms a soft hydrogel that exhibits both thermal and shearinduced gel-to-sol transition; the low melting temperature of the gel would permit the easy inclusion of thermally sensitive therapeutics in this potentially injectable and benign hydrogel. Work to explore the biological applications of this itaconatebased hydrogel is currently underway.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b00815. Detailed synthetic methods, additional NMR and IR spectral data, GPC chromatograms, and WAXS data (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (S.R.). ORCID

S. Ramakrishnan: 0000-0001-9161-0848 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank Dr. Bhoje Gowd, NIIST, Thiruvananthapuram, for valuable assistance with the SAXS measurements. We also thank the Department of Science and Technology, New Delhi, for the research grant (SR/S1/OC-84/2012) and for the award of J C Bose fellowship (2011-2016 and 2016-2021) to S.R. S.C. acknowledges MHRD for the fellowship.

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