Structural Variation in Homopolymers Bearing Zwitterionic and Ionic

Dec 12, 2017 - A series of monomers comprising units bearing both imidazolium bromide ionic liquid (IL) and zwitterionic imidazolium alkyl carboxylate...
0 downloads 13 Views 7MB Size
Download PDF
Article Cite This: Macromolecules XXXX, XXX, XXX−XXX

Structural Variation in Homopolymers Bearing Zwitterionic and Ionic Liquid Pendants for Achieving Tunable Multi-Stimuli Responsiveness and Hierarchical Nanoaggregates Yajnaseni Biswas and Tarun K. Mandal* Polymer Science Unit, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India S Supporting Information *

ABSTRACT: A series of monomers comprising units bearing both imidazolium bromide ionic liquid (IL) and zwitterionic imidazolium alkyl carboxylate moieties with different alkyl spacer groups are designed and synthesized. RAFT polymerization of these monomers produces a new class of ionic homopolymers, named poly(zwitterionic ionic liquid)s (PZILs), which behave like poly(ionic liquid)s as well as poly(zwitterion)s depending on the solution pH. Such PZILs exhibit an isoelectric point (pI) at pH 5.7, where they exist in their zwitterionic form, making them dual responsive to both pH and temperature. Above pH 5, the aqueous transparent solution of PZIL transforms into turbid suspension due to the formation of insoluble hierarchical nanoaggregates (NAs) of various morphologies such as small spheres, large spheres, flower-like, dendrite-shaped, and dendritic fibril-like depending upon the solution pH and PZILs’ structures. The dissolution of aggregates upon heating and reaggregation upon cooling suggests existence of reversible upper critical solution temperature (UCST)-type phase transition above pH 5. Below pH 5, owing to the presence of cationic IL moieties, aqueous PZIL solution exhibits transparent-to-turbid transition due to the formation of anioninduced NAs of various dendritic morphologies upon addition of various chaotropic anions within the Hofmeister series. Upon heating, this colloidal turbid suspension becomes transparent, showing a distinct UCST-type phase transition, and the process is reversible. It is easily possible to fine-tune the cloud point and morphologies of the NAs by changing various parameters such as molecular weight, concentrations, structure of PZILs, nature and concentration of anions, and solution pH.

■

(PZIs),26,34−37 along with a very limited number of nonionic polymers.32,33 In particular, poly(sulfobetaine)s (PSBs), a category of PZIs, are the most widely studied UCST-type ionic polymers.34,36,38,39 Among these PSBs, poly(sulfobetaine methacrylate)s are reported to have reversible pH- and salttunable UCST-type cloud points (Tcps).38,39 In contrast, PZIs, p o l y ( c a r b o x y b e t a i n e ) s ( P C B s ) , 3 6 , 4 0 , 4 1 a n d p o ly (phosphobetaine)s (PPBs)42 are reported to be only ionic strength and pH responsive but are not thermoresponsive. In fact, we have not found any PCBs that are responsive to temperature. Beside these polybetaines, a new class of amino acid-based zwitterionic homopolymers with both pH- and thermo-responsiveness has been synthesized recently from our laboratory.26,35 In addition to these stimuli-responsive properties, PZIs are interesting biocompatible antifouling materials with resistance to biofouling and potential for gene delivery application.35,38,39,43−45 Poly(ionic liquid)s (PILs), a special class of ionic polymers carrying ionic liquid (IL) species in each of the repeating units, have also gained huge attention due to their stimuli-responsive

INTRODUCTION Stimuli-responsive polymers undergo changes in chain conformation, solubility, and self-assembly behavior along with the external stimuli such as temperature,1−6 pH,7−10 light,11,12 redox,13,14 glucose,15 CO2,16 and specific ions.17−19 This class of smart polymeric materials has tremendous potential for a variety of interesting applications including drug delivery,20 catalysis,21 sensing/detection,22 and making responsive nanomaterials.17,23,24 Recent research in this area is, however, focused on the development of homopolymers/ copolymers that are responsive to dual11,17,25,26 or multiple15,27−29 stimuli rather than a single stimulus as they can provide greater flexibility in fabrication of smart materials and nanostructures with much more precise and sensitive applications.30 Of course, the major challenges are toward the designing of multi-responsive homopolymers with complex architectures rather than copolymers. Among various responsive polymers, thermoresponsive water-soluble nonionic polymers are the most widely investigated systems whose solutions exhibit either a lower critical solution temperature (LCST)-type1−3,5,11,31 or an upper critical solution temperature (UCST)-type32,33 phase transition. However, most of the reported UCST-type polymers are the charged ionic polymers, especially poly(zwitterion)s © XXXX American Chemical Society

Received: September 28, 2017 Revised: November 30, 2017

A

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 1. (A) Synthesis scheme for different ZIL monomers and their RAFT polymerization into PZILs. (B) GPC traces of different PZILs with their Mns and Đs (Table S1).

properties and other potential applications in different areas.14,23,24,46−49 However, only very few PILs are exhibiting thermoresponsive property with LCST-type phase behavior due to the presence of large hydrophobic counteranions24,48,50,51 along with the few exceptions that exhibited UCST-type phase behavior.17,52,53 Recently, we have reported a phosphonium PIL, synthesized by RAFT polymerization, exhibiting dual halide ion and tunable UCST-type phase transiiton.17 Tenhu et al.52 further reported imidazolium- and DMAEMA-based polycations with UCST-type thermoresponsiveness in the presence of both LiNTf2 and NaCl. Note that there are only very few examples of stimuli-responsive PIL systems, but those are mostly responsive to single54,55 or dual stimuli.17,52 Thus, it is always a challenging task to prepare new multi-stimuli-responsive IL-based polymers. Controlling the morphologies of self-assembled polymeric material in solution is a real challenge, and in this connection external stimuli always play an important role. There are several reports where the morphology tuning of most of the selfassembled block or graft copolymer systems is done by introducing various interacting stimuli such as pH,9,56,57 salt,57 CO2,58 etc. Therefore, besides copolymers, the design and synthesis of new homopolymers with desirable responsive properties and their related nanostructures with tunable morphologies have been of long-standing interest in materials

science, and their emerging applications open tremendous new directions in basic science and technology. So far, most of the reports are concerned with the synthesis of either PIL- or PZI-based ionic systems that are responsive to separate and different stimuli. Thus, in this paper, we take the challenge of developing novel ionic polymers containing both ionic liquid (IL) and zwitterionic (ZI) functionalities in order to have synergistic responsive properties toward many different stimuli. As shown in Figure 1A, we synthesize a series of zwitterionic ionic liquid (ZIL) monomers with both IL (imidazolium bromide) and ZI (imidazolium alkyl carboxylate of varying spacer length) moieties and their subsequent RAFT polymerization to produce poly(zwitterionic ionic liquid)s (PZILs). It is observed that variation in pH could induce reversible solubility phase transition, and subsequent temperature change could induce reversible and tunable UCST-type solubility phase transition in water due to the presence of ZI species in PZIL. Furthermore, the presence of IL moieties makes PZIL susceptible to Hofmeister anion-induced soluble− insoluble phase transition and temperature-induced UCST-type insoluble−soluble phase transition in aqueous solution. PZIL molecules can associate into hierarchical nanoaggregates (NAs) of various morphologies from sphere to flower-like to dendritelike depending upon the chemical structure, pH of the solution, and the nature of added salts. Such stimuli-responsive B

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

flasks (50 mL). CDP (21.19 mg, 0.052 mmol), ACVA (2.95 mg, 0.01 mmol), and 10 mL of water were then added in each of these three flasks (Table S1). The initial pHs of these solutions were acidic in nature and were adjusted to pH 5.5 for complete solubilization of CDP. These reaction mixtures were then purged with argon gas for 45 min, sealed with silicone rubber septum, and stirred in oil baths maintained at 70 °C for 24 h. After complete polymerization, PZILs were isolated by precipitation in acetone and were purified by redissolution/reprecipitation in water/acetone. PZILs were further purified by extensive dialysis from water to remove unreacted ZIL monomers. These aqueous solutions were then lyophilized, affording yellowish hygroscopic solid PZILs, which were designated as P[VBzImIBa][Br]-8.2K, P[VBzImAa][Br]-7.5K, and P[VBzImVa][Br]-7.9K with molecular weights (Mns) of 8.2, 7.5, and 7.9 kDa, respectively (Figure 1B and Table S1). Similarly, P[VBzImIBa][Br]6.5K and P[VBzImIBa][Br]-12.5K samples of two different Mns, 6.5 and 12.5 kDa, were also synthesized just by the variation of [[VBzImIBa][Br]]0/[CDP]0 ratio (Figure 1B and Table S1). pH Responsiveness of Aqueous PZILs Solutions. The pHs of aqueous PZILs solutions (1 wt %) were systematically adjusted between 2 and 11 by adding either HCl (1 M) and/or NaOH (1 M) as monitored by a pH meter (Oakton) at 25 °C. The pH-responsive soluble−insoluble phase transitions of these PZILs solutions were then investigated by monitoring its % transmittance (%T) (at λ = 600 nm) at different pHs in an UV−vis spectrophotometer and also by measuring the pH-dependent hydrodynamic diameter (Dh) via dynamic light scattering (DLS). Isoelectric Points (pIs) of ZIL Monomers and PZILs. The zeta potentials (ξs) of ZIL monomers and PZILs were measured at different pHs in a DLS instrument. The pIs were then determined from the plots of pH versus ξ, where ξs were zero. Determination of UCST-Type Cloud Point of Aqueous PZILs Solutions. Cloud points (Tcps) of aqueous solutions of different PZILs of varying alkyl spacer groups and of different Mns were determined at various solution pHs and at different added anion concentrations in an UV−vis spectrophotometer equipped with a temperature controller. In a typical procedure, a transparent aqueous solution of any PZIL (initial pH ∼ 2.7) was filtered through a membrane filter (D ∼ 0.45 μm). The pH was then adjusted to the desired value to obtain a turbid solution. The resultant turbid solution was then taken in a 3 mL quartz cuvette and placed into a UV−vis spectrophotometer. The Tcp was then measured by recording the %T (λ = 600 nm) in the temperature window of 2−90 °C with increasing/ decreasing temperature at a scan rate of 1 °C min−1 after equilibration for 2 min at the experimental temperature. Furthermore, aqueous solutions of PZILs (pH ∼ 2.7) were titrated with various inorganic salts (e.g., NaI, NaBF4, NaSCN, and NaClO4) to obtain turbid solutions at 25 °C. We also measured the Tcps of these anion-induced turbid PZILs solutions in a similar way as mentioned above. The Tcp was considered to be the point at which the solution transmittance reduced to half of its original value. Tcps of aqueous PZILs solutions at varying pHs and at different anion concentrations were also measured from the abrupt change of Dhs of PZILs nanoaggregates (NAs) against temperature in a DLS instrument. Characterizations. 1H and 13C NMR spectra of the VBzIm were acquired from CDCl 3 using a Bruker DPX 500/400 MHz spectrometer. The spectra of all the ZIL monomers and PZILs were recorded from D2O in the same instrument. ESI-MS spectra of the VBzIm and all the ZIL monomers were recorded from methanol solution (1 wt %) in a quadrupole time-offlight (Q-TOF) Micro YA263 mass spectrometer. Fourier transform infrared (FTIR) spectra of the VBzIm, ZIL monomers and PZILs were recorded from pellets prepared by mixing with KBr in a 1:100 (w/w) ratio in a PerkinElmer Spectrum 400 spectrometer. The number-average molecular weights (Mns) and dispersities (Đs) of PZILs were measured by size exclusion chromatography (SEC) using a Waters 1515 isocratic HPLC pump connected to three Ultrahydrogel columns (designated as 120, 250, and 500 with Mns

morphology transformations in the process of aggregation of responsive ionic polymers have not been previously reported.

■

EXPERIMENTAL SECTION

Materials. Imidazole (Im; 99%), α-bromoisobutyric acid (BIBa; 98%), bromoacetic acid (BAa; 97%), 5-bromovaleric acid (BVa; 97%), 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid (CDP; ≥97%), and (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO; 98%) were used as received from Aldrich. 4-Vinylbenzyl chloride (VBzCl) (Aldrich; 90%) was purified by passing through neutral alumina column to remove inhibitors prior to use. 4,4′-Azobis(4cyanovaleric acid) (ACVA) (Aldrich; ≥75%) was recrystallized twice from ethanol before use. Sodium bicarbonate (NaHCO3) and hydroquinone were purchased from E. Merck, India. Acetonitrile (ACN) was distilled with calcium hydride and collected over dried molecular sieves (3 Å) in a round-bottom (RB) flask prior to use. Acetone was pot-to-pot distilled prior to use. Ultrapure water retrieved from a Milli-Q Integral-3 System (Millipore) was used for making different aqueous solutions. Sodium iodide (NaI; 99.9%), sodium tetrafluoroborate (NaBF4; 98%), sodium thiocyanate (NaSCN; ≥98%), and sodium perchlorate (NaClO4; 98%) were used directly as obtained from Aldrich. Synthesis of 1-(4-Vinylbenzyl)imidazole (VBzIm). VBzIm was synthesized by slight modification of a previously reported protocol.59 Typically, a two-neck RB flask (250 mL) was charged with NaHCO3 (6.52 g, 77.6 mmol) and 124 mL of mixture of water/acetone (1:1, v/ v). Imidazole (16.9 g, 0.248 mol) and hydroquinone (62.33 mg, 0.56 mmol) were then added separately to this mixture and stirred at 25 °C for 1 h for complete dissolution under a nitrogen atmosphere. Finally, VBzCl (8.75 mL, 62.14 mmol) was added dropwise to the reaction mixture and was refluxed under a N2 atmosphere by placing in an oil bath (50 °C) and stirred for 20 h. After completion, the mixture was filtered through gauche funnel to remove unreacted salt. Acetone was evaporated in a rotary evaporator, and the entire liquid mass was then diluted with 350 mL of diethyl ether followed by washing with 35 mL of water for six times. VBzIm and the unreacted imidazole were extracted from organic phase by adding 100 mL of 2.0 M HCl for three times followed by its neutralization with 200 mL of 4.0 M NaOH. Finally, VBzIm was extracted from the obtained heterogeneous mixture by washing with (3 × 50 mL) diethyl ether in a separating funnel. VBzIm in diethyl ether was dried over anhydrous Na2SO4 for 30 min. Finally, the yellow viscous VBzIm liquid was isolated from the organic phase under reduced pressure affording a yield of 65%. Synthesis of Different Zwitterionic Ionic Liquid (ZIL) Monomers [3-(2-Carboxypropan-2-yl)-1-(4-vinylbenzyl)-1Himidazol-3-ium Bromide ([VBzImIBa][Br]), 3-(Carboxymethyl)1-(4-vinylbenzyl)-1H-imidazol-3-ium Bromide ([VBzImAa][Br]), and 3-(4-Carboxybutyl)-1-(4-vinylbenzyl)-1H-imidazol-3-ium Bromide ([VBzImVa][Br])]. Three different ZIL monomers were synthesized by nucleophilic substitution reactions between assynthesized VBzIm and bromoalkyl carboxylic acids of varying spacer length at a molar ratio of 2:1 (Figure 1A). The typical synthesis protocol was as follows: VBzIm (1.5 g, 8.14 mmol) was separately added to BIBa (679.8 mg, 4.07 mmol), BAa (565.62 mg, 4.07 mmol), and BVa (736.93 mg, 4.07 mmol) loaded in three RB flasks (100 mL) to prepare [VBzImIBa][Br], [VBzImAa][Br], and [VBzImVa][Br] monomers, respectively. The reaction vessels were then charged with TEMPO (radical quencher) (45 mg, 0.28 mmol) and 10 mL of dry ACN and were placed in a preheated oil bath at 60 °C. After 24 h of stirring, the products were isolated by precipitation in diethyl ether. Finally, the sticky solid ZIL monomers were obtained by three times purification in ACN/diethyl ether and were kept in a refrigerator under an argon atmosphere for subsequent polymerization. Synthesis of PZILs via RAFT Polymerization. The RAFT technique was used to polymerize above ZILs to prepare three different PZILs using CDP as a chain transfer agent (CTA) at a molar ratio of [ZIL monomer]0/[CDP]0/[ACVA]0 = 70:1:0.2 in water (Figure 1 and Table S1). For syntheses, [VBzImIBa][Br] (1 g, 3.68 mmol), [VBzImAa][Br] (0.895 g, 3.68 mmol), and [VBzImVa][Br] (1.05 g, 3.68 mmol) monomers were separately taken in three RB C

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules ranging from 0.1−5 kDa, 1−80 kDa, and 10−400 kDa at 40 °C and a Waters 2414 RI detector at 35 °C. The eluent was H2O−acetonitrile mixture (60:40, v/v) containing 0.1 (M) LiBr and 0.1 (M) NaNO3 and was passed with a flow rate of 0.8 mL min−1. The columns were calibrated against poly(ethylene glycol) standards having peak molecular weights (Mps) of 1500, 4450, 6240,10 680, 25 300, 44 000, and 69 100. Hydrodynamic diameter (Dh) and zeta potential (ξ) were measured in a DLS apparatus, Zetasizer NANO ZS 90, Malvern (Model 3690), equipped with a He−Ne laser (λ = 632.8 nm). PZILs solutions were filtered through a membrane filter (D ∼ 0.45 μm) prior to measurements. A field emission scanning electron microscope (FESEM) (Model JEOL JSM-6700F) was used to observe the morphologies of the aggregated PZILs in solution. Typically, for analysis, aqueous solution of PZIL (1 wt %) with initial pH ∼ 2.7 was adjusted to pH 5.5, 7, and 9 to obtained a turbid solution. However, for P[VBzImAa][Br], the solution was cooled down to below 10 °C to obtain turbidity at pH 5.5 as it did not show any turbidity at room temperature (25 °C) at this pH. In this context, it should be mentioned, that P[VBzImAa][Br] solution did not show any turbidity at pHs 7−9, even if the temperature was below 10 °C. Typically, 50 μL of an aqueous turbid PZIL solution was then injected into 500 μL of THF to freeze the asformed nanostructures (NAs). It should be noted that the FESEM image of NAs from 1 wt % PZIL solution was not very clear and distinctive because of its high concentration. Thus, we diluted the aqueous solution with THF as PZILs were insoluble in THF. The dispersed NAs in THF was then dropcast on small piece of glass, followed by quick drying with blotting paper, and finally dried overnight in air. The piece of glass containing the sample was then mounted on a metal stub followed by platinum coating to minimize charging, and the images were recorded from the microscope operated at an accelerating voltage of 5 kV. A similar procedure was used for acquiring FESEM images of NAs of PZILs in the presence of added anions. The %T of aqueous PZIL solution was measured in a HewlettPackard 8453 diode array UV−vis spectrophotometer (Agilent Technologies) equipped with a Peltier temperature controller. The measurements were performed in a temperature range from 2 to 90 °C with a heating/cooling ramp of 1 °C min−1. The glass transition temperatures (Tgs) and other thermal histories of all three PZILs were measured using a PerkinElmer diamond differential scanning calorimeter (DSC) equipped with an intercooler. For Tg measurement, samples were heated at a scan rate of 20 °C/min, and Tg values were taken in the second scan.

ring). These results collectively confirmed the successful synthesis of VBzIm. The second nucleophilic substitution reaction between the as-synthesized VBzIm with three different bromoalkyl carboxylic acids (BIBa, BAa, and BVa) resulted in three different ZIL monomers ([VBzImIBa][Br], [VBzImAa][Br], and [VBzImVa][Br], respectively) in the second step (Figure 1A). As expected, these ZIL monomers showed signals for vinyl protons (δ 5.2, 5.7, and 6.65 ppm) along with the characteristic signals for methyl, methylene, and benzylic protons (Figures S5−S7). 13C NMR spectra (Figures S8−S10) unambiguously revealed all the expected carbon signals for different alkyl carboxylic acid moieties, indicating successful attachment of these acids with VBzIm. The base peaks at m/z 271.2, 243.1, and 285.2 exactly matched with the molar masses of [VBzImIBa][Br], [VBzImAa][Br], and [VBzImVa][Br], respectively (Figure S11). Further, the appearance of a new band at 1727 cm−1 (⟩CO stretching of −COOH) for ZIL monomers compared to that of VBzIm along with other bands further confirmed the successful attachment of alkylcarboxylic acid with the nitrogen atom of imidazole group (Figure S4). Poly(zwitterionic ionic liquid)s (PZILs) via RAFT Polymerization. One of the important beautiful features of the RAFT process60 is the high tolerance toward different functional monomers. It is thus expected to be a suitable technique to polymerize ZIL monomers to obtain PZILs of varying and controllable Mns. The polymerizations using CDP as CTA and ACVA as radical initiator in H2O at pH 5.5 and at 70 °C produced three PZILs of varying alkyl spacer groups and two other P[VBzImIBa][Br]s of different Mns of 6.5 and 12.5 kDa (Figure 1A and Table S1). Figures S12−S14 showed 1H NMR spectra of PZILs exhibiting the absence of any signals corresponding to vinyl protons (δ 5.2, 5.7, and 6.65 ppm, Figures S5−S7) and the appearance of broad signals at δ 0.7− 2.0 ppm for the backbone methylene, methine and alkyl chain protons, indicating the successful polymerization of ZILs. FTIR spectra showed all the characteristics bands of ZIL monomers along with the intense polymeric ⟩CH2 bands at 2915 cm−1, indicating their successful polymerizations (Figure S4). The molecular weight analysis by SEC of charged PIL molecules is always tricky because of their strong interactions with the column materials leading to their aggregation in the column.61 This often results in either broad peak or absence of any peak in the SEC trace. Therefore, it is necessary to identify an eluant for optimization of SEC for measurements of Mns and Đs and to suppress the interactions between PZIL molecules and column materials. In this direction, our first attempt to measure Mns of PZILs using an eluent, aqueous 0.1 M LiBr solution, was ended up without any peak in the SEC traces. However, we found a mixture of water: acetonitrile (60:40, v/v) containing 0.1 M LiBr and 0.1 M NaNO3 was an ideal eluent for these PZILs and indeed exhibited unimodal SEC traces (Figure 1B) with narrow molecular weight distributions of Đs ranging from 1.11 to 1.18 (Table S1), which is a clear indication of very good control of this RAFT polymerization. For P[VBzImIBa][Br] samples, the lateral shifting of SEC traces toward higher elution time further clearly evidenced the formation of PZILs with increasing Mns due to the variation of [ZIL monomer]:[CDP] feed ratios (Figure 1B and Table S1). We found that the as-synthesized PZILs were completely soluble in water and the aqueous solutions exhibited a pH of ∼2.7. Thus, in solid state all the PZILs are mainly existed as

■

RESULTS AND DISCUSSION Zwitterionic Ionic Liquid (ZIL) Monomers. A two-step method was adopted to synthesize a series of ZIL monomers, each of which contained both an imidazolium IL moiety and a ZI moiety consisting of an imadazolium and carboxylate groups flanked by alkyl spacer groups of varying lengths (Figure 1A). The first step involved the synthesis of a precursor 1-(4vinylbenzyl)imidazole (VBzIm) monomer by reacting VBzCl with imidazole. The 1 H NMR spectrum (Figure S1) unambiguously confirmed the formation of VBzIm as it showed the characteristic signals of imidazolium (δ 7.54, 7, and 6.8 ppm), phenyl (δ 7.38 and 7.12 ppm), and vinyl protons (δ 5.2, 5.7, and 6.5 ppm). The 13C NMR spectrum (Figure S2) of VBzIm further revealed signals for vinylic and imidazolium ring carbons. The ESI-MS spectrum (Figure S3) exhibited only two sharp peaks: one at m/z 185 exactly matched with the mass of VBzIm and the other at m/z 117 for fragmented 4-vinylbenzyl cation, indicating the formation of monomer of high purity. FTIR spectra (Figure S4) showed all the characteristic bands at 1435 cm−1 (N−CH2− deformation), 1627 cm−1 (vinyl CC stretching), and 3110 cm−1 (CN deformation of imidazole D

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 2. Correlation between zeta potentials (ξs) and %T (at λ = 600 nm) of 1 wt % aqueous solutions of PZILs at different pHs. Inset showed the photographs of transparent and turbid solutions of PZILs at different pHs.

Scheme 1. Schematic Representation of (A) pH-Responsive Soluble-to-Insoluble and UCST-Type Insoluble-to-Soluble Phase Transitions of PZILs and (B) Anion-Induced Aggregates Formation of Cationic PZILs and Temperature-Induced Dissociation of Aggregates in Water

pH Responsiveness of Aqueous PZILs Solutions. The aqueous solutions of all three PZILs were transparent within the pH ranges from 2 to below 5 (inset of Figure 2) at 25 °C. Thus, it is expected that they would exhibit pH-responsive phase transitions as they contained zwitterionic imidazolium and carboxylate moieties (Scheme 1).40 We indeed found that transparent solution of P[VBzImVa][Br]-7.9K became turbid (two-phase) upon changing pH from 2 to anything between 5 and 8 and became less turbid at a pH > 8 (inset photographs of

cationic PILs. Notably, they were also soluble in various polar organic solvents such as MeOH, DMF, and DMSO. Thus, the solubility of these PZILs in both water and in organic solvents clearly differentiates them from a simple polyelectrolyte as questioned by one of the reviewer.49 Further, we also observed that P[VBzImVa][Br]-7.9K, P[VBzImIBa][Br]-8.2K, and P[VBzImAa][Br]-7.5K exhibited a broad (high transition breadth) and weak Tgs at 18.5, 4.6, and 28.6 °C, respectively (Figure S15), which further evident their PIL nature.49 E

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 3. FESEM images of different PZILs solutions at different pHs: (A) P[VBzImAa][Br]-7.5K (pH 5.5); (B) P[VBzImIBa][Br]-8.2K (pH 5.5); (C) P[VBzImVa][Br]-7.9K (pH 5.5); (D) enlarged view of flower-like aggregates in panel C; (E) P[VBzImIBa][Br]-8.2K (pH 7); (F) enlarged view of dendritic structures in panel E; (G) P[VBzImVa][Br]-7.9K (pH 7); (H) enlarged view of dendritic structures with fibers in panel G; (I) P[VBzImIBa][Br]-8.2K (pH 9); (J) enlarged view of dendritic structures with fibers in panel I; (K) P[VBzImVa][Br]-7.9K (pH 9); (L) enlarged view of dendritic structures with fibers in panel K.

[VBzImIBa][Br]-8.2K, when pHs was increased from anything below 5 to 5−8 and below 5.7 to 5.7−7.6, respectively (Figure S16). The decreasing trend of Dhs at high pHs (>8 and >7.6) for both of these PZILs can easily be correlated with increasing transmittance as mentioned above in Figure 2. Notably, Dhs of P[VBzImAa][Br]-7.5K was remained ∼5−7 nm in the pH ranges of 2−11 (Figure S16), which supported the 0% T in this pH range (Figure 2) at 25 °C. Such different phase behaviors for different PZILs can only be ascribed to their difference in pending zwitterionic moieties with different alkyl spacer groups. This interesting solution phase behavior of PZILs can be explained with the help of zeta potentials (ξs), which were +29 mV in pHs of 2−4 and then decreased sharply passing through pI (ξ = 0, at pH 5.7) to −7.8 mV at pH 8 and finally reached to a constant value of −10 mV at pH 11 (Figure 2). The positive ξ (+29 mV) at pH 2 revealed that the PZIL exists as cationic PIL with an imidazolium cation and a bromide counter anion along with a completely protonated carboxylate group (Scheme 1). The deprotonation of carboxylic acid group starts at pH 4 and is completed at pH 5.7 (pI, ξ = 0). Thus, PZILs chains are existed in complete zwitterionic form with equal number of imidazolium and carboxylate ions at pH 5.7. Therefore, at any

Figure 2). This change was accompanied by a sharp decrease of the %T of this solution from 100 (pH 2) to nearly 0 (pH 5−8) and further increased to %T ∼ 34 (pH > 8) (Figure 2). The P[VBzImIBa][Br]-8.2K solution also exhibited similar kind of pH-responsiveness showing transparency up to pHs < 5.7 and became turbid in the pH ranges of 5.7−7.6 with a decrease of % T from 100 to 0 and was further reached to ∼66 at pH > 7.6 (Figure 2). All these phase transitions were pH-reversible in nature. Interestingly, the solution of P[VBzImAa][Br]-7.5K, remained transparent (inset photographs of Figure 2) in the whole pH ranges of 2−11 at 25 °C. However, this solution transformed into a turbid two-phase system in the pH ranges of 5.15−5.85 upon cooling down the solution below 8 °C (inset of Figure 2). The turbidity at high pHs is due to the generation of colloidal suspension of nanogel aggregates, formed through the ionic cross-linking between the oppositely charged neighboring pendent groups of PZILs (Scheme 1), the details of which will be discussed later in this section. Such PZIL nanoaggregates (NAs) formation was further confirmed from DLS data, which showed that Dhs were increased abruptly from ∼7 to 2697 nm for P[VBzImVa][Br]-7.9K and ∼7 to 2330 nm for PF

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules Scheme 2. Schematic Representation for the Mechanism of Formation of PZIL Nanoaggregates (NAs) of Different Morphologies at Different Solution pHs (A) and in the Presence of Anions (B)

pH above 5.7, the ξ should be zero as it contains a permanent cationic imidazolium and anionic carboxylate moieties instead of negative ξ as observed above this pH (Figure 2). The negative ξ can be ascribed to the effective decrease of positive charge of imidazolium cation due to its screening by the associated OH− ions at higher pHs.40 Thus, below pH 5, P[VBzImVa][Br]-7.9K gives transparent solution (%T = 100) as there was no NA formation because of electrostatic repulsion between positive charged cationic PIL components (Scheme 1). Whereas, in pHs between 5 and 8, this solution became turbid (%T = 0) (Figure 2) due to the formation nanogel aggregates caused by the intra- and/or inter-chain electrostatic attractions between the oppositely charged imidazolium cation and carboxylate anion of neighboring PZIL chains (Scheme 1A).26 The P[VBzImIBa][Br]-8.2K solution was also transparent (%T = 100) below pH 5.7 and became turbid (%T = 0) in pHs 5.7−7.6 because of similar reason. However, the increase of %T from 0 to ∼34 and 66 for these two PZILs at high pHs (>8) can be ascribed to the partial dissolution of the NAs because of weakening of electrostatic interaction among PZIL chains (Scheme 1A). As mentioned above, the effective decrease of positive charge of imidazolium due to its screening by the associated OH− ions is responsible for such weakening of interactions. Further, the difference in solution transmittances for P[VBzImVa][Br]-7.9K (%T ∼ 34) and P[VBzImIBa][Br]-8.2K (%T ∼ 66) is due to the difference in hydrophobicity of valeric and isobutyric chains that separating the cation and anion of pendent zwitterionic moieties, respectively (Figure 1A). This indicates that in addition to intra- and/or interchain ionic interactions hydrophobic interactions among spacer groups also play an important role. This is also the reason why in spite of having ionic interaction, but of very less hydrophobic interactions among its acetic chains, P[VBzImAa][Br]-7.5K molecules did not undergo aggregation (%T ∼ 100) (Figure 2) in the pH ranges of 2− 11 at 25 °C. But, at low temperature (8 °C), these hydrophobic interactions in P[VBzImAa][Br]-7.5K become prominent enough to facilitate aggregation into nanogel beads in turbid solution although the electrostatic attraction is very weak in pHs of 5.15−5.85 (inset of Figure 2). The theoretical study of

zwitterionic poly(carboxybetaine) with varying spacer groups between the cation and anion also predicted similar type of phase behaviors.62 Kratzer et al. also observed similar phase behaviors in a series of poly(ammonioalkanesulfonate methacrylates).63 It is worth mentioning that ZIL monomers have the same pIs at pH 5.7 (Figure S17) and also exhibited pH- and thermoresponsiveness in water, the details of which are not included here for brevity and will be reported in the subsequent publication. Effect of pH on Morphology of Aggregates of PZILs. The morphologies of PZIL aggregates formed at different pHs were systematically examined by FESEM. As mentioned above, the aggregation of P[VBzImAa][Br]-7.5K occurred only at 8 °C but not at 25 °C, which showed nearly monodispersed spherical NAs of average diameter 18 ± 2 nm along with some prominent chain-like structures (red marked), formed by these NAs at pH 5.5 (Figure 3A). However, the image of P[VBzImIBa][Br]-8.2K showed mainly large spherical aggregates (D = 130 ± 10 nm) as well as some spherical NAs with very low contrast (D ∼ 20 nm) (Figure 3B) at this pH (5.5). Such large aggregates are probably formed by the secondary association of these NAs (D ∼ 20 nm), the detailed mechanism of which will be discussed later in this section. Whereas P[VBzImVa][Br]-7.9K at pH 5.5 aggregated mainly into flower-like structure (sperical diameter ∼830 ± 53 nm). The high-magnification image of one such flower clearly revealed that it was actually constituted with initially formed NAs (D ∼ 20 nm) (Figure 3D). Therefore, in each case, PZIL molecules initially associated through ionic interactions (Schemes 1A and 2A) to form NAs (D ∼ 20 nm), which act as building unit for large sphere or flower-like structures through secondary aggregation (Scheme 2A). When the solution pH was increased from 5.5 to 7 or 9, we observed mainly fractal type of aggregation in PZILs leading to the formation nanostructures of various morphologies (Figure 3).64 For example, at pH 7, P[VBzImIBa][Br]-8.2K molecules associated into dendritic structures (Figure 3E). At higher magnification (Figure 3F), it looked like that the branches were made up of spherical NAs (D ∼ 20 nm) as observed at pH 5.5 (Figure 3A). At this pH (7), the P[VBzImVa][Br]-7.9K also G

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 4. (A) Turbidity curves (at λ = 600 nm) of three PZILs solutions (1 wt %) at pH 5.45 in (- - -, heating)/(, cooling) cycles: (a) P[VBzImVa][Br]-7.9K; (b) P[VBzImIBa][Br]-8.2K; (c) P[VBzImAa][Br]-7.5K. (B) Variation of Dhs of PZILs in water (1 wt %) with temperature at pH 5.45 during cooling cycle. (C) Effect of pHs on Tcps of different PZILs solutions (1 wt %).

transformed into dendritic structures (Figure 3G), but the branches were fibrillar in nature with minimum diameter of ∼40 nm (Figure 3H). At pH 9, both P[VBzImIBa][Br]-8.2K (Figure 3I) and P[VBzImVa][Br]-7.9K (Figure 3K) again exhibited dendritic structure with fibrillar morphologies with average fiber diameters of ∼50 and 70 nm (Figures 3J and 3L), respectively, but all these patterns were different from each other. It seems that these fibers were formed by the linear association of spherical NAs (D ∼ 20 nm). We also observed thicker fibers, which probably formed by association of two or more thin fibers (Figures 3J and 3L). Form these results, it is very apparent that the building units for all such structures at different pHs are spherical NAs (D ∼ 20 nm). Thus, we may propose that initially at low pH the PZIL chains mainly selfassociate through ionic interactions (Schemes 1A and 2A) into spherical NAs (D ∼ 20 nm). With the increment of solution pH, the excess OH− ions adsorb on surface of these NAs, and they become unstable. It is known that fractal aggregation is common among destabilized colloidal particles.65 Thus, in order to stabilize and to reduce charge density, the spherical NAs (D ∼ 20 nm) merged into chain-like intermediates and eventually reorganize to form various fractal structures (dendrite, dendrite with fibrillar branching, etc.) (Scheme 2A). It should be mentioned that Dhs (DLS) of aggregated PZILs (Table S2) did not match with sizes measured from FESEM. Such a discrepancy is quite common as the DLS measures hydrated diameter of the aggregated particles.17 Also, Dhs of dendritic aggregates at higher pH are not well accepted as DLS generally measures the spherical diameter of particle no matter what the shape is. In this context, it should be mentioned that initially we tried to observe the formation of PZIL NAs of various morphologies directly by dropcasting and drying their 1 wt % turbid aqueous suspension. Figure S18 shows the generation of aggregated dendritic fibers and spherical nanostructured morphologies of 1 wt % P[VBzImVa][Br]-7.9K and P[VBzImIBa][Br]-8.2K at pH 9 and 5.5, respectively (see red marked area). However, these morphologies were not clearly identifiable because of high polymer concentration. To overcome this, FESEM specimens were prepared by diluting the 1 wt % solution via dropping aqueous PZIL solution into excess THF for freezing these formed NAs (see Experimental Section). As mentioned above, we observed high quality FESEM images of PZIL NAs of different morphologies (Figure 3). One reviewer questioned whether the formation of PZIL NAs with different

morphologies at different pHs were due to the excess amount of polar solvent (THF) added during FESEM specimen preparation. The following experiments were carried out to resolve the issue. As a control experiment, we further acquired the FESEM image of the PZIL solution at low pH ∼ 2 by diluting this clear solution in THF. The FESEM image did not show any such nanostructures (Figure S19A). Even the FESEM image of only NaOH solution in water/THF mixture (Figure S19B) did not show such dendritic PZIL nanostructures. This result confirmed that the formation of PZIL NAs of different morphologies were solely due to the aggregation of PZIL molecules at different pHs and not due to the addition of excess THF. Thermoresponsiveness of PZILs Solutions: Effect of pH. As mentioned above, below pH 5, PZILs solutions were transparent and did not exhibit any LCST-type transition. However, these solutions transformed into turbid system at a pH above 5 due to the formation of insoluble PZIL NAs in colloidal state, which disappeared upon heating and reappeared upon cooling indicating UCST-type phase behavior at these pHs (photographs in Figure 4A). Typically, the turbidity curve of P[VBzImIBa][Br]-8.2K showed that the %T gradually increased from 0 to 100 upon heating or visa versa on cooling showing a cloud point (Tcp) at 15.6 °C (cooling) with slight hysteresis (Table S3 and Figure 4A). P[VBzImVa][Br]-7.9K and P[VBzImAa][Br]-7.5K also exhibited a sharp UCST-type transition at 59.4 and 12.4 °C, respectively, at pH 5.45 (Table S3 and Figure 4A). DLS data (Figure 4B) in the cooling cycle revealed rapid increase of Dh from 17 to 2450 nm with decrease of temperature for P[VBzImIBa][Br]-8.2K further evidenced of a sharp UCSTtype transition at Tcp = 14.7 °C. Tcps of 56 and 10 °C for P[VBzImVa][Br]-7.9K and P[VBzImAa][Br]-7.5K, respectively (Figure 4B), were also found to be very close to those measured by turbidimetry (Table S3). Thus, these results substantiated that apparently a very small change in the spacer groups (acetic chain in P[VBzImAa][Br] to valeric chain in P[VBzImVa][Br]) of same Mns induced drastic effect with almost 4−5-fold increase in their Tcps (Table S3). Such increase of Tcp is due to the requirement of higher energy to disrupt additional higher hydrophobic interactions that caused by the valeric/isobutyric chains compared to that of acetic chain in addition to the ionic interactions. Similar increase in Tcp due change of spacer group in poly(sulfobetaine methacrylates) system has also been reported earlier.34 H

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 5. (A) Effect of molecular weight on Tcp of P[VBzImIBa][Br] samples of different Mns in water at pH 6.25. (B) Effect of P[VBzImVa][Br]7.9K concentration on Tcps at pH 4.7.

turbidity curves given in Figure S21A to check how molecular weight affected cloud points. Figure 5A clearly shows that that the Tcp increased almost linearly with increase of their Mns. Such observation is quite common for other thermoresponsive zwitterionic polymeric system.26 The high Mn means a higher length of the PZIL chains, which in turn increases the extent of interaction among the opposite charges of zwitterions within a coiled structure. Hence, higher energy, i.e., higher Tcp, is required to break such high interaction of nanogel aggregates to soluble PZIL chains of higher Mns. To study the effect of concentration of PZIL on its Tcp, we acquired the turbidity curves (Figure S21B) of a sample P[VBzImVa][Br]-7.9K at a fixed pH 4.7 with varying concentrations. The measured Tcps from these curves showed that they were linearly increased with PZIL concentration up to 3 wt % (Figure 5B). Notably, Tcp of this PZIL solution above this concentration was not measurable because of irreversible coagulation of PZIL chains and precipitation form the solution at this pH (4.7). These results again suggested that intra- and/ or interchain electrostatic interactions between the oppositely charged neighboring zwitterionic groups are responsible for showing such phase transition behavior. Anion Responsiveness of Aqueous PZILs Solutions. In the pH range of 2−4, a PZIL can be considered as a cationic PIL as it contained IL moieties composed of imidazolium cations and Br− counter anions along with undissociated neutral carboxylic acid groups (Scheme 1B). The transparent solutions of all three PZILs were transformed to turbid two phase solutions on addition of certain anions of Hofmeister series66 such as BF4−, I−, ClO4−, and SCN− (see photographs in Figure 6). We further titrated all PZILs solution (1 wt %) with these anions’ solution at pH 2.7. Turbidity curves (Figure S22) showed a sudden decrease of %T from 100 to 0 after addition of these anions with minimum concentrations. Figure 6 (constructed from Figure S22) revealed that the minimum concentration of anion ([anion]min) required to bring such phase transitions for all PZILs followed an order BF4− > I− > ClO4− > SCN−. That means the effectiveness of these anions toward such phase transition was as follows: SCN− > ClO4− > I− > BF4−. These anions are actually the chaotropic anions of Hofmeister series, and they are very efficient in salting-out proteins from their solution as they acquired positive charge at a pH below

As mentioned above, aqueous PZILs solutions showed pHinduced transparent to turbid transition, which further showed UCST-type transition due to the formation of NAs followed by their dissociation. To check the effect of pH, Tcps were determined from their corresponding turbidity cooling curves for three different PZILs at different pHs (Figure S20). Note that these UCST-type transitions are all reversible in nature. A dramatic linear increase of Tcp from 7.5 to 66.5 °C was initially noticed with a pH increase from 5.17 to 6.58 and then decreased to 38 °C upon further small increase of pH to 6.98 for P[VBzImIBa][Br]-8.2K (Figure 4C). For P[VBzImVa][Br]7.9K, Tcp also increased sharply in a linear fashion from 22 to 82 °C with increase of pH from 4.7 to 5.96. However, especially in the case of P[VBzImAa][Br]-7.5K, a very small linear increase in Tcp from 8 to 14.7 °C within a very small pH ranges of 5.15−5.63 and then decrease to 12.5 °C at pH 5.85 (Figure 4C) were registered. For each PZILs, we were unable to measure Tcps in water beyond the above-mentioned specified pH ranges due to the experimental limitation. In general, the high Tcp means the requirement of higher energy to dissociate PZIL aggregates that are formed by the intra- and/or interchain electrostatic attraction between the neighboring zwitterions of PZIL chains (Scheme 1A). At high pH, the degree of dissociation of carboxylic acid group of zwitterion is high. This increases the amount of charge difference between imidazolium cation and carboxylate anion, which resulting in the increase of electrostatic interactions between the opposite charges of zwitterions. Thus, the combined hydrophobic and high electrostatic interactions at higher pH is responsible for such dramatic increase of Tcps with very small increase in pHs for P[VBzImIBa][Br]-8.2K and P[VBzImVa][Br]-7.9K (Figure 4C). However, for P[VBzImAa][Br]-7.5K, such low increase in Tcp with pH can be ascribed to the requirement of less energy for dissociation of weakly interacted PZIL aggregates that are formed by strained intra- and/or interchain ionic intermediates of PZIL chains. As mentioned above, at high pH 6.58, the screening of imidazolium cations by excess OH− ions weaken the electrostatic attraction between the imidazolium and carboxylate ions of neighboring PZILs chains, resulting in the formation of weakly interacted aggregates, and require less energy to dissociate (Figure 1A). We further measured Tcps of three representative P[VBzImIBa][Br] samples of different Mns at pH 6.25 from I

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

the addition of various anions at pH 2.7 were then examined via FESEM for their morphology. As can be seen from Figure 7A,

Figure 6. Correlation between chemical structures and minimum concentration of anion required to bring transparent to turbid solution transition. Inset showed the photographs of anion-induced transparent to turbid phase transition of PZILs. Figure 7. FESEM images of (A) P[VBzImAa][Br]-7.5K, (B) P[VBzImIBa][Br]-8.2K, and (C) P[VBzImVa][Br]-7.9K at pH 2.7 in the presence of 10, 15, and 30 mM NaSCN, respectively. (D) Enlarged view of flower-like aggregates in panel C.

their pI. It has reported that the effectiveness of these chaotropes in salting-out proteins is following the order of SCN− > ClO4− > I−, which exactly matched with our results in bringing soluble−insoluble transition of PZILs (Figure 6).66 There is an explanation that there should be some kind of charge screening effects depending on the polarizabilities of these chaotropes, which completely account for the hydrophobic collapse and aggregation of these proteins.66 This could reconcile the data with what is actually happening in this case. The positive charge of imidazolium cations of PZIL are effectively screened by thenegative charges of excess added anions resulting in an intra- and/or inter-chain ionic crosslinking and increase of hydrophobicity of PZIL chains which would facilitate their aggregation into insoluble nanogel beads (Scheme 1B). Thus, the more polarizable anion can effectively interact with large number of cations of PIL chains and more effective in bringing aggregation as mentioned in our previous report.17 In this case, as the order of decreasing polarizabilities of these anions is SCN− > ClO4− > I− > BF4−, therefore the same order is following in the agglomeration of the cationic PZILs chains into nanogel aggregates. The control experiments of kosmotropic anion (SO42−) and kosmotropic−chaotropic borderline anions (such as Cl−, NO3−, and Br−) with aqueous P[VBzImVa][Br]-7.9K (1 wt %) solution did not exhibit any turbidity up to a concentration of 3.0 M. Figure 6 further reveals that the effect of chaotropic anions on soluble−insoluble phase transition was minimum for P[VBzImVa][Br], maximum for P[VBzImAa][Br], and medium for P[VBzImIBa][Br]. For any anion, the minimum concentration required to bring such transition follows the order of P[VBzImAa][Br] < P[VBzImIBa][Br] < P[VBzImVa][Br] (Figure 6). The probable reason is that with increasing the steric hindrance or hydrophobicity of spacer group of zwitterions of cationic PZIL chain the foreign anions cannot effectively screen the positively charged imidazolium; hence, higher salt concentration is required to bring the sterically hindered PZILs chains closer for observing such phase transition. In this context, it is important to mention that ZIL monomers did not exhibit such phase transitions in the presence of these anions. Effect of Anions on Morphologies of PZIL Nanoaggregates. The PZIL NAs formed in turbid solutions due to

P[VBzImAa][Br]-7.5K with 10 mM SCN− exhibited only monodispersed spherical NAs of average diameter 20.6 ± 1.4 nm (red marked). Whereas in the case of P[VBzImIBa][Br]8.2K with 15 mM SCN−, the initially formed spherical NAs (D ∼ 20 ± 2 nm) tried to self-assemble into hierarchical dendritic NAs (Figure 7B). P[VBzImVa][Br]-7.9K in the presence of 30 mM SCN− showed a different type of flower-like fractal structures (Figure 7C). The enlarged view of these fractal structures (Figure 7D) again confirmed that spherical NAs (D ∼ 20 nm) were the main building unit to these flower-like aggregated structures. Thus, in order to explain such fractal morphologies in the presence of anions, it is envisaged that initially the PZILs chains agglomerate into spherical NAs (D ∼ 20 nm) through intra- and/or interchain ionic bridging interaction between the neighboring cationic PZIL chains (Scheme 2B). However, for P[VBzImIBa][Br]-8.2K and P[VBzImVa][Br]-7.9K, the required [SCN−]min (15 and 30 mM, respectively) were much higher than that (10 mM) for P[VBzImAa][Br]-7.5, and thus, it is expected that these excess anion are adsorbed on the surface of PZIL NAs. Therefore, in the case of the former two PZILS, in order to reduce surface negative charge density, the spherical NAs merged into various fractal structures (Scheme 2B). Furthermore, it was observed that upon addition of other chaotropic anions (BF4−, I−, and ClO4−) to an aqueous P[VBzImIBa][Br]-8.2K solution also exhibited similar type of spherical NAs (D ∼ 20 nm) along with some assembled fractal structures (Figure S23). As expected, the sizes of the aggregates (Dh = 167, 817, and 2248 nm) of different PZILs in the presence of [SCN−]min measured from DLS were much higher (Figure S24) than that obtained from FESEM analysis. UCST-Type Phase Behaviors of Cationic PZILs Solutions in the Presence of Hofmeister Anions. The aforementioned results confirmed formation of PZILs NAs, making the solutions turbid at pHs below their pIs in the presence of chaotropes (BF4−, I−, ClO4−, and SCN−). Thus, it is expected the ion-induced turbid solution became transparent upon heating above UCST. The photographs in Figure 8 indeed revealed that the turbid solution of P[VBzImIBa][Br]J

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

concentration. Thus, less energy (i.e., lower Tcp) is required to dissociate such ionic interactions in former PZIL than the latter two. The highest Tcp for P[VBzImIBa][Br] is probably due to the presence of two methyl spacer groups that favors more polymer−polymer hydrophobic interactions leading to increase in its Tcp. The turbidity curves of P[VBzImIBa][Br] solutions of three different Mns at fixed pH 2.7 and in the presence of fixed [BF4−] = 40 mM clearly revealed that the Tcps increased continuously with increase in their Mns (Figure S26). Such an increasing trend is quite common for other thermoresponsive cationic PIL systems in the presence of ions.17 With increasing Mn, the number of cationic centers in the PZIL/PIL chains also increases, resulting in more number of intra- and/or interchain ionic bridging in the nanogel at a fixed anion concentration. Hence, the disruption of such ionically cross-linked NAs of PZIL chains requires higher energy, which means higher Tcp. Further to check the effect of anion concentration on the UCST-type Tcp of PZIL, we monitored the temperaturedependent transmittances of P[VBzImVa][Br]-7.9K (1 wt %) solutions in the presence of varying amount of BF4−, I−, ClO4−, and SCN− anions, and the corresponding turbidity curves are given in Figure S27. The plot of T cps versus anion concentrations (Figure 9B) clearly revealed that there was a sharp and almost linear increase in Tcps with increasing concentrations for all anions up to a certain point and then with a slow increase for I− and BF4− ions. The slopes of the lines summarized that the rates of increase of Tcps of PZILs in the presence of these anions followed the order of SCN− > ClO4− > I− > BF4− (Figure 9B). As mentioned above, the effectiveness of these anions in bringing turbidity in PZIL solutions also followed the same order SCN− > ClO4− > I− > BF4− (Figure 6), which is actually the same order of their polarizabilities. The anion with higher polarizability interacts with the more number of imidazolium groups of the PZIL chains leading to higher number of NAs formation, meaning higher Tcp, which is actually reflected in the slopes of these lines in Figure 9B. Further, the concentration-dependent turbidity curves of a particular PZIL, P[VBzImVa][Br]-7.9K, at a fixed [ClO4−] = 50 mM and at pH 2.7 are depicted in Figure S28A. The plot of corresponding Tcps versus concentrations (Figure S28B) clearly revealed that the Tcp increased sharply and linearly with the PZIL concentration. These results again suggested that intra-

Figure 8. Variation of %T (heating/cooling cycles) and the Dhs of the aqueous P[VBzImIBa][Br]-8.2K solution (1 wt %) at pH 2.7 with 50 mM I− ion against temperature. The inset showed photographs of transition of turbid to transparent solution upon heating.

8.2K with 50 mM I− ion at pH 2.7 became transparent upon heating and turbid upon cooling. The turbidity curves in heating/cooling runs showed slight hysteresis with clear UCSTtype Tcps at 36 and 31 °C, respectively (Figure 8). The DLS data (Figure 8) in the cooling run further revealed a Tcp at 32.5 °C (very close to turbidity data) with the increase of Dh from 20 to 2436 nm upon decreasing the temperature. Such UCSTtype transition suggests that the ionically cross-linked nanogel aggregates of PZIL dissociates above its Tcp due to weakening of intrachain/interchain electrostatic bridging interactions between imidazolium cations and any chaotrope (Scheme 1B). To examine further the effect of structure of PZIL, we found that typically the Tcp increased heavily (∼32 °C) on going from P[VBzImVa][Br] to P[VBzImAa][Br] and then increased almost slightly (∼4 °C) for P[VBzImIBa][Br] at a fixed [I−] of 70 mM (Figure S25A and Figure 9A). A similar trend of change of Tcp (see turbidity curves in Figure S25) was also observed for other chaotropes (Figure 9A). These results again supported that the extent of aggregation of cationic P[VBzImVa][Br] at pH 2.7 (through anionic bridging) with long hydrophobic and sterically hindered valeric chain is less than those of P[VBzImAa][Br] and P[VBzImIBa][Br] with less sterically hindered acetic and isobutyric chains at a fixed anion

Figure 9. (A) Effect of the chemical structures of PZILs on the UCST-type cloud points at fixed concentrations of various anions. (B) Effect of different anions and their concentrations on Tcps of 1 wt % aqueous solutions of P[VBzImVa][Br]-7.9K at pH 2.7. K

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

(3) Lutz, J.-F. Polymerization of Oligo(ethylene glycol) (meth)acrylates: Toward New Generations of Smart Biocompatible Materials. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 3459−3470. (4) Roy, D.; Brooks, W. L. A.; Sumerlin, B. S. New Directions in Thermoresponsive Polymers. Chem. Soc. Rev. 2013, 42, 7214−7243. (5) Schild, H. G. Poly(N-Isopropylacrylamide): Experiment, Theory and Application. Prog. Polym. Sci. 1992, 17, 163−249. (6) Seuring, J.; Agarwal, S. Polymers with Upper Critical Solution Temperature in Aqueous Solution. Macromol. Rapid Commun. 2012, 33, 1898−1920. (7) Banerjee, S.; Maji, T.; Paira, T. K.; Mandal, T. K. Amino-AcidBased Zwitterionic Polymer and Its Cu(II)-Induced Aggregation into Nanostructures: A Template for CuS and CuO Nanoparticles. Macromol. Rapid Commun. 2013, 34, 1480−1486. (8) Doncom, K. E. B.; Hansell, C. F.; Theato, P.; O’Reilly, R. K. pHSwitchable Polymer Nanostructures for Controlled Release. Polym. Chem. 2012, 3, 3007−3015. (9) Dule, M.; Biswas, M.; Paira, T. K.; Mandal, T. K. Hierarchical Nanostructures of Tunable Shapes Through Self-Aggregation of POSS End-Functional Polymer and Poly(ionic liquid) Hybrids. Polymer 2015, 77, 32−41. (10) Lee, C.-J.; Wu, H.; Tang, Q.; Cao, B.; Wang, H.; Cong, H.; Zhe, J.; Xu, F.; Cheng, G. Structure−Function Relationships of a Tertiary Amine-Based Polycarboxybetaine. Langmuir 2015, 31, 9965−9972. (11) Jana, S.; Bose, A.; Saha, A.; Mandal, T. K. Photocleavable and Tunable Thermoresponsive Amphiphilic Random Copolymer: SelfAssembly into Micelles, Dye Encapsulation, and Triggered Release. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 1714−1729. (12) Jiang, J.; Tong, X.; Morris, D.; Zhao, Y. Toward Photocontrolled Release Using Light-Dissociable Block Copolymer Micelles. Macromolecules 2006, 39, 4633−4640. (13) Feng, X.; Sui, X.; Hempenius, M. A.; Vancso, G. J. Electrografting of Stimuli-Responsive, Redox Active Organometallic Polymers to Gold from Ionic Liquids. J. Am. Chem. Soc. 2014, 136, 7865−7868. (14) Sui, X.; Hempenius, M. A.; Vancso, G. J. Redox-Active CrossLinkable Poly(ionic liquid)s. J. Am. Chem. Soc. 2012, 134, 4023−4025. (15) Vancoillie, G.; Brooks, W. L. A.; Mees, M. A.; Sumerlin, B. S.; Hoogenboom, R. Synthesis of Novel Boronic Acid-Decorated Poly(2oxazoline)s Showing Triple-Stimuli Responsive Behavior. Polym. Chem. 2016, 7, 6725−6734. (16) Yan, Q.; Zhou, R.; Fu, C.; Zhang, H.; Yin, Y.; Yuan, J. CO2Responsive Polymeric Vesicles that Breathe. Angew. Chem. 2011, 123, 5025−5029. (17) Biswas, Y.; Maji, T.; Dule, M.; Mandal, T. K. Tunable Doubly Responsive UCST-Type Phosphonium Poly(ionic liquid): a Thermosensitive Dispersant for Carbon Nanotubes. Polym. Chem. 2016, 7, 867−877. (18) Magnusson, J. P.; Khan, A.; Pasparakis, G.; Saeed, A. O.; Wang, W. X.; Alexander, C. Ion-sensitive “Isothermal” Responsive Polymers Prepared in Water. J. Am. Chem. Soc. 2008, 130, 10852−10853. (19) Zhang, Y.; Furyk, S.; Sagle, L. B.; Cho, Y.; Bergbreiter, D. E.; Cremer, P. S. Effects of Hofmeister Anions on the LCST of PNIPAM as a Function of Molecular Weight. J. Phys. Chem. C 2007, 111, 8916− 8924. (20) Schmaljohann, D. Thermo- and pH-Responsive Polymers in Drug Delivery. Adv. Drug Delivery Rev. 2006, 58, 1655−1670. (21) Doring, A.; Birnbaum, W.; Kuckling, D. Responsive Hydrogels− Structurally and Dimensionally Optimized Smart Frameworks for Applications in Catalysis, Micro-System Technology and Material Science. Chem. Soc. Rev. 2013, 42, 7391−7420. (22) Hu, J.; Liu, S. Responsive Polymers for Detection and Sensing Applications: Current Status and Future Developments. Macromolecules 2010, 43, 8315−8330. (23) Biswas, Y.; Dule, M.; Mandal, T. K. Poly(ionic liquid)-Promoted Solvent-Borne Efficient Exfoliation of MoS2/MoSe2 Nanosheets for Dual-Responsive Dispersion and Polymer Nanocomposites. J. Phys. Chem. C 2017, 121, 4747−4759.

and/or inter-chain ionic interactions among cationic PZIL chains through the anion bridging are responsible for such phase transition in water.

■

CONCLUSIONS A new class of zwitterionic ionic liquid (ZIL) monomers with coexisting IL and zwitterionic pendent moieties have been designed and synthesized. RAFT polymerization of these ZIL monomers produced a series of multi-stimuli-responsive poly(zwitterionic ionic liquid)s (PZILs) of controllable molecular weights and low dispersities in water. Unlike most of the single- or dual-stimuli-responsive poly(ionic liquid)s and poly(zwitterion)s, this new class of PZIL homopolymers exhibited triple-stimuli-responsiveness toward pH, temperature, and anions (SCN−, ClO4−, I−, BF4−) as demonstrated by solubility phase transition in aqueous solution. All these stimuliresponsive properties were strongly dependent on the chemical structures of PZILs. Compared to extensively studied LCSTtype nonionic and ionic polymers,1−3,5,24,48,50 we developed a series of novel UCST-type ionic PZILs whose cloud points can easily be tuned by solution pH, nature and concentration of anions, chemical structure, molecular weight, and concentration. Most of the nonionic or ionic thermoresponsive homopolymers transformed into insoluble spherical nano/ microgel aggregates during phase transition,11,17,26−28 whereas these PZIL chains gave hierarchical aggregated nanostructures of varying morphologies such as sphere, flower-like, and various dendritic structure depending upon the solution pH, nature of added anions, and structure of PZILs. In all, these PZILs open new opportunities for making emerging sensory, antifouling, and gene delivery materials.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b02106. NMR, ESI-MS, and FTIR spectroscopic data, DLS and zeta potential data, temperature-dependent transmittance data, Tg data, cloud points, FESEM images (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*Fax +91-33-24732805; e-mail [email protected] (T.K.M.). ORCID

Tarun K. Mandal: 0000-0003-1626-8637 Notes

The authors declare no competing financial interest.

■ ■

ACKNOWLEDGMENTS Y.B. thanks IACS for providing a fellowship. This research was supported by the grants from SERB, India. REFERENCES

(1) Confortini, O.; Du Prez, F. E. Functionalized ThermoResponsive Poly(vinyl ether) by Living Cationic Random Copolymerization of Methyl vinyl ether and 2-Chloroethyl vinyl ether. Macromol. Chem. Phys. 2007, 208, 1871−1882. (2) Hoogenboom, R. Poly(2-oxazoline)s: A Polymer Class with Numerous Potential Applications. Angew. Chem., Int. Ed. 2009, 48, 7978−7994. L

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules (24) Men, Y.; Li, X.-H.; Antonietti, M.; Yuan, J. Poly(tetrabutylphosphonium 4-styrenesulfonate): A Poly(ionic liquid) Stabilizer for Graphene Being Multi-Responsive. Polym. Chem. 2012, 3, 871−873. (25) Cui, W.; Lu, X.; Cui, K.; Niu, L.; Wei, Y.; Lu, Q. DualResponsive Controlled Drug Delivery Based on Ionically Assembled Nanoparticles. Langmuir 2012, 28, 9413−9420. (26) Maji, T.; Banerjee, S.; Biswas, Y.; Mandal, T. K. Dual-StimuliResponsive L-Serine-Based Zwitterionic UCST-Type Polymer with Tunable Thermosensitivity. Macromolecules 2015, 48, 4957−4966. (27) Jiang, X.; Li, R.; Feng, C.; Lu, G.; Huang, X. Triple-StimuliResponsive Ferrocene-Containing Homopolymers by RAFT Polymerization. Polym. Chem. 2017, 8, 2773−2784. (28) Klaikherd, A.; Nagamani, C.; Thayumanavan, S. Multi-Stimuli Sensitive Amphiphilic Block Copolymer Assemblies. J. Am. Chem. Soc. 2009, 131, 4830−4838. (29) Song, Z.; Wang, K.; Gao, C.; Wang, S.; Zhang, W. A New Thermo-, pH-, and CO2-Responsive Homopolymer of Poly[N-[2(diethylamino) ethyl] acrylamide]: Is the Diethylamino Group Underestimated? Macromolecules 2016, 49, 162−171. (30) Biswas, Y.; Jana, S.; Dule, M.; Mandal, T. K. Responsive Polymer Nanostructures. In Polymer-Engineered Nanostructures for Advanced Energy Applications; Lin, Z., Yang, Y., Zhang, A., Eds.; Springer: Cham, 2017; pp 173−304. (31) Niskanen, J.; Wu, C.; Ostrowski, M.; Fuller, G. G.; Hietala, S.; Tenhu, H. Thermoresponsiveness of PDMAEMA. Electrostatic and Stereochemical Effects. Macromolecules 2013, 46, 2331−2340. (32) Mishra, V.; Jung, S.-H.; Jeong, H. M.; Lee, H.-I. Thermoresponsive Ureido-Derivatized Polymers: The Effect of Quaternization on UCST Properties. Polym. Chem. 2014, 5, 2411−2416. (33) Seuring, J.; Agarwal, S. First Example of a Universal and CostEffective Approach: Polymers with Tunable Upper Critical Solution Temperature in Water and Electrolyte Solution. Macromolecules 2012, 45, 3910−3918. (34) Hildebrand, V.; Laschewsky, A.; Wischerhoff, E. Modulating the Solubility of Zwitterionic Poly((3-methacrylamidopropyl) ammonioalkane sulfonate)s in Water and Aqueous Salt Solutions Via the Spacer Group Separating the Cationic and the Anionic Moieties. Polym. Chem. 2016, 7, 731−740. (35) Maji, T.; Banerjee, S.; Bose, A.; Mandal, T. K. A StimuliResponsive Methionine-Based Zwitterionic Methacryloyl Sulfonium Sulfonate Monomer and the Corresponding Antifouling Polymer with Tunable Thermosensitivity. Polym. Chem. 2017, 8, 3164−3176. (36) Shao, Q.; Mi, L.; Han, X.; Bai, T.; Liu, S.; Li, Y.; Jiang, S. Differences in Cationic and Anionic Charge Densities Dictate Zwitterionic Associations and Stimuli Responses. J. Phys. Chem. B 2014, 118, 6956−6962. (37) Vasantha, V. A.; Jana, S.; Parthiban, A.; Vancso, J. G. Water Swelling, Brine Soluble Imidazole Based Zwitterionic Polymers Synthesis and Study of Reversible UCST Behaviour and Gel-Sol Transitions. Chem. Commun. 2014, 50, 46−48. (38) Chang, Y.; Chen, W.-Y.; Yandi, W.; Shih, Y.-J.; Chu, W.-L.; Liu, Y.-L.; Chu, C.-W.; Ruaan, R.-C.; Higuchi, A. Dual-Thermoresponsive Phase Behavior of Blood Compatible Zwitterionic Copolymers Containing Nonionic Poly(N-isopropyl acrylamide). Biomacromolecules 2009, 10, 2092−2100. (39) Shih, Y.-J.; Chang, Y. Tunable Blood Compatibility of Polysulfobetaine from Controllable Molecular-Weight Dependence of Zwitterionic Nonfouling Nature in Aqueous Solution. Langmuir 2010, 26, 17286−17294. (40) Ramireddy, R. R.; Prasad, P.; Finne, A.; Thayumanavan, S. Zwitterionic Amphiphilic Homopolymer Assemblies. Polym. Chem. 2015, 6, 6083−6087. (41) Thomas, D. B.; Vasilieva, Y. A.; Armentrout, R. S.; McCormick, C. L. Synthesis, Characterization, and Aqueous Solution Behavior of Electrolyte-and pH-Responsive Carboxybetaine-Containing Cyclocopolymers. Macromolecules 2003, 36, 9710−9715.

(42) Zhang, Z.; Moxey, M.; Alswieleh, A.; Morse, A. J.; Lewis, A. L.; Geoghegan, M.; Leggett, G. J. Effect of Salt on PhosphorylcholineBased Zwitterionic Polymer Brushes. Langmuir 2016, 32, 5048−5057. (43) Hu, G.; Emrick, T. Functional Choline Phosphate Polymers. J. Am. Chem. Soc. 2016, 138, 1828−1831. (44) Alswieleh, A. M.; Cheng, N.; Canton, I.; Ustbas, B.; Xue, X.; Ladmiral, V.; Xia, S.; Ducker, R. E.; El Zubir, O.; Cartron, M. L.; Hunter, C. N.; Leggett, G. J.; Armes, S. P. Zwitterionic Poly(amino acid methacrylate) Brushes. J. Am. Chem. Soc. 2014, 136, 9404−9413. (45) Dai, F.; Liu, W. Enhanced Gene Transfection and Serum Stability of Polyplexes by PDMAEMA-Polysulfobetaine Diblock Copolymers. Biomaterials 2011, 32, 628−638. (46) Grygiel, K.; Lee, J.-S.; Sakaushi, K.; Antonietti, M.; Yuan, J. Thiazolium Poly(ionic liquid)s: Synthesis and Application as Binder for Lithium-Ion Batteries. ACS Macro Lett. 2015, 4, 1312−1316. (47) Kohno, Y.; Saita, S.; Men, Y.; Yuan, J.; Ohno, H. Thermoresponsive Polyelectrolytes Derived from Ionic Liquids. Polym. Chem. 2015, 6, 2163−2178. (48) Men, Y.; Schlaad, H.; Yuan, J. Cationic Poly(ionic liquid) with Tunable Lower Critical Solution Temperature-Type Phase Transition. ACS Macro Lett. 2013, 2, 456−459. (49) Yuan, J.; Mecerreyes, D.; Antonietti, M. Poly(ionic liquid)s: An update. Prog. Polym. Sci. 2013, 38, 1009−1036. (50) Amajjahe, S.; Ritter, H. Supramolecular Controlled PseudoLCST Effects of Cyclodextrin-Complexed Poly(ionic liquids). Macromolecules 2008, 41, 3250−3253. (51) Kohno, Y.; Deguchi, Y.; Ohno, H. Ionic Liquid-Derived Charged Polymers to Show Highly Thermoresponsive LCST-type Transition with Water at Desired Temperatures. Chem. Commun. 2012, 48, 11883−11885. (52) Karjalainen, E.; Aseyev, V.; Tenhu, H. Counterion-Induced UCST for Polycations. Macromolecules 2014, 47, 7581−7587. (53) Niskanen, J.; Tenhu, H. How to Manipulate the Upper Critical Solution Temperature (UCST)? Polym. Chem. 2017, 8, 220−232. (54) Texter, J. Anion Responsive Imidazolium-Based Polymers. Macromol. Rapid Commun. 2012, 33, 1996−2014. (55) Vijayakrishna, K.; Jewrajka, S. K.; Ruiz, A.; Marcilla, R.; Pomposo, J. A.; Mecerreyes, D.; Taton, D.; Gnanou, Y. Synthesis by RAFT and Ionic Responsiveness of Double Hydrophilic Block Copolymers Based on Ionic Liquid Monomer Units. Macromolecules 2008, 41, 6299−6308. (56) Kocak, G.; Tuncer, C.; Butun, V. pH-Responsive Polymers. Polym. Chem. 2017, 8, 144−176. (57) Zhou, D.; Dong, S.; Kuchel, R. P.; Perrier, S.; Zetterlund, P. B. Polymerization Induced Self-Assembly: Tuning of Morphology Using Ionic Strength and pH. Polym. Chem. 2017, 8, 3082−3089. (58) Dong, S.; Zhao, W.; Lucien, F. P.; Perrier, S.; Zetterlund, P. B. Polymerization Induced Self-Assembly: Tuning of Nano-Object Morphology by Use of CO2. Polym. Chem. 2015, 6, 2249−2254. (59) Green, M. D.; Choi, J.-H.; Winey, K. I.; Long, T. E. Synthesis of Imidazolium-Containing ABA Triblock Copolymers: Role of Charge Placement, Charge Density, and Ionic Liquid Incorporation. Macromolecules 2012, 45, 4749−4757. (60) Moad, G.; Barner-Kowollik, C. Handbook of RAFT Polymerization; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2008. (61) He, H.; Zhong, M.; Adzima, B.; Luebke, D.; Nulwala, H.; Matyjaszewski, K. A Simple and Universal Gel Permeation Chromatography Technique for Precise Molecular Weight Characterization of Well-Defined Poly(ionic liquid)s. J. Am. Chem. Soc. 2013, 135, 4227−4230. (62) Du, H.; Qian, X. The Hydration Properties of Carboxybetaine Zwitterion Brushes. J. Comput. Chem. 2016, 37, 877−885. (63) Kratzer, D.; Barner, L.; Friedmann, C.; Brase, S.; Lahann, J. A Synthetic Route to Sulfobetaine Methacrylates with Varying Charge Distance. Eur. J. Org. Chem. 2014, 2014, 8064−8071. (64) Zhao, Q.; An, Q.; Qian, J.; Wang, X.; Zhou, Y. Insight into Fractal Self-Assembly of Poly(diallyldimethylammonium chloride)/ M

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules Sodium Carboxymethyl Cellulose Polyelectrolyte Complex Nanoparticles. J. Phys. Chem. B 2011, 115, 14901−14911. (65) Aubert, C.; Cannell, D. S. P. Restructuring of Colloidal Silica Aggregates. Phys. Rev. Lett. 1986, 56, 738. (66) Zhang, Y.; Cremer, P. S. The Inverse and Direct Hofmeister Series for Lysozyme. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 15249− 15253.

N

DOI: 10.1021/acs.macromol.7b02106 Macromolecules XXXX, XXX, XXX−XXX