Thermo-Switchable de Novo Ionic Liquid-Based Gelators with Dye-Absorbing and Drug-Encapsulating Characteristics.

An ionic liquid-based surfactant with ester functionality self-aggregates in an aqueous medium and forms ionogels at 8.80% (w/v) concentration at physiological pH. The ionogel exhibited a remarkable change in its appearance with temperature from fibrillar opaque to transparent because of the dynamic changes within its supramolecular structure. This gel-to-gel phase transition occurs below the melting point of the solid ionic liquid. The ionogels were investigated using turbidity, differential scanning calorimetry, scanning electron microscopy (SEM), field emission SEM (FE-SEM), inverted microscopy, transmission electron microscopy imaging, Fourier transform infrared spectroscopy, and rheological measurements. The fibrillar opaque ionogel and transparent ionogel were studied for their ability to absorb dyes (methyl orange and crystal violet) and to encapsulate drugs (diclofenac sodium and imatinib mesylate).

Introduction

Hydrogels are water-swelled three-dimensional (3D) networks that exhibit extraordinary performance in various aspects, such as excellent biocompatibility, tunable mechanical strength, and multistimuli response to name a few.[1−4] Stimuli-responsive hydrogels are those which respond to various stimuli such as pH of the solution,[5−8] solvent,[9] ionic strength,[10−12] temperature,[13−15] and light[16−18] by an abrupt change in volume, accompanied by the intake or release of a large amount of water. Some amphiphilic molecules, for example, surfactants and hydrophilic copolymers, self-assemble in aqueous solutions with a large aspect ratio, leading to the formation of a 3D branched network. One of the prime requirements for the 3D network is to have multiple binding sites, which serves as the junction for the cross-linking, as reported in the case of the pillar[5]arene derivative with 10 hydrazide groups reacting with bis(p-formylphenyl)sebacate to form organogels, whose mechanical properties can be easily tuned by controlling the molar ratio of the components of the mixture.[5]arene Appended with Multiple Hydrazides. Macromol. Rapid Commun.. 2017 ">19] The 3D network may produce a physical hydrogel, the so-called “supramolecular structural entity” composed of fibrous aggregates connected through the noncovalent interactions, for example, hydrogen bonds,[20−25] π–π interactions,[26−28] lipophilic interactions,[28,29] host–guest interactions,[30] and dipole–dipole and donor–acceptor interactions.[31,32] Recently, a novel supramolecular fluorescent hydrogel with ATP/ATPase responsiveness was synthesized through the electrostatic interaction between poly(sodium p-styrene sulfonate) and tetraphenylethene derivatives with two quaternary ammonium cations.[33] These assemblies found applications in tissue engineering,[34] drug delivery,[35] optical field,[36] as injectable gels,[37,38] cell scaffolds,[39−41] self-healing materials,[42−44] and biosensors[45] to cite a few.

Among the various classes of hydrogels, thermo-responsive hydrogels[46−48] that are triggered by changing the gel temperature represent one of the most successful examples of these smart systems.[49] The mechanism responsible for gelation upon cooling is the formation of physical cross-links that denature at high temperatures.[50,51] In the case of heating, temperature-induced hydrogelation is due to dehydration of the hydrophobic moieties of the amphiphiles,[49,52,53] leading to the formation of 3D network gels.[52] The thermo-induced gel-to-gel transition in low-molecular-weight gelators (LMWGs) is limited to few cases.[54−56] Xie et al. reported a unique thermo-induced crystalline gel-to-transparent gel transition in a pH-sensitive LMWG.[54] Meister et al.[55] reported a temperature-induced gel-to-gel transition for bolaamphiphiles when the alkyl chain length exceeded 26 carbon atoms. Both the gel phases of the bolaamphiphiles were composites of fibers. Hard-to-soft organogel transitions from a discotic columnar to a plastic crystal to a crystalline phase were exhibited recently where the soft organogel only existed at a low temperature range (<5 °C).[56] Yan et al. designed metallohydrogels through the self-assembly of functionalized dicarboxylate ligands through intermolecular hydrophobic and π–π interactions that have potential as the functionalized soft materials.[28]

The gelation ability and hence the applications can be customized by changing the structures of the amphiphilic LMWGs.[57,58] In this process, a new class of amphiphiles, ionic liquids (ILs)-based surfactants (ILBSs), are receiving increased attention. The inclusion of a functionality in the side chain of ILBSs allows the formation of ILBSs with tailor-made properties. For example, substituting a methyl group in 1-alkyl-3-methylimidazolium bromide ILBSs by a −CH2COOH group increased the surface activity.[57] Recently, we have investigated the surface active properties of the vinyl-functionalized imidazolium-based ILs and found that they possess better surface activity than the nonfunctionalized ILs.[58] Various surfactants were further tested in our laboratory for their ability to form various microstructural aggregates in the presence of solubilizates, including drugs.[59−62] Apart from the surface activity, the “green” credentials of ILBSs can be enhanced by introducing the functionality within the side chain. By introducing the ether or polyether side chain in imidazolium-based ILs, Morrissey et al. observed a clear reduction in their toxicity.[63] Further, the surface and biological activity of the imidazolium- and pyridinium-based ILs are improved significantly by introducing the ester functionality within the IL structure.[64] Introducing the cleavable ester functional group in the side chain significantly increased the biodegradability of the ILs as compared to the nonfunctionalized ILs. Such ester-functionalized ILBSs can be used as the LMWGs for various applications including drug delivery as of other biodegradable LMWGs.

Considering the above-mentioned favorable characteristics of ILBSs with ester functionality, we synthesized the ILBS 3-methyl-1-(hexadecyloxycarbonylmethyl)imidazolium bromide (CEMeImBr) and studied its self-assembly behavior in the aqueous medium. Among the halide counterions, the Br– anion possesses higher adsorption abilities as it adopts vertical orientation at the air–water interface as compared to the Cl– and I– anions.[65,66] CEMeImBr and CEMeImBr form gels at 25.20 and 22.60% w/v, respectively and hence were not further investigated. We found that CEMeImBr forms supramolecular ionic hydrogels in the aqueous medium at physiological pH at 8.80% w/v. An unusual, unprecedented reversible transition from the supramolecular fibrillary opaque ionic hydrogel into the supramolecular transparent ionic hydrogel was observed upon increasing the temperature from 25 to 50 °C. This gel-to-gel transition is due to the balance between gelator–gelator and gelator–water interactions. The morphology associated with the opaque fibrillar at 25 °C temperatures was studied using scanning electron microscopy (SEM), field emission SEM (FE-SEM), inverted microscopy, and transmission electron microscopy (TEM) imaging. The gel-to-gel transition was characterized by turbidity, differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. The dynamic mechanical analysis was assessed using rheological measurements. The temperature and dilution stability of the gels were also studied. Finally, the opaque and transparent ionogels were tested for their absorbing capacity of water-soluble dyes and drugs. The present work is a contribution to the use of functionalized, biodegradable ILBSs as LMWGs Scheme .

Scheme 1

Molecular Structures of (a) 3-Methyl-1-(hexadecyloxy carbonylmethyl)imidazolium Bromide (CEMeImBr), (b) IM, (c) CV, (d) DS, and (e) MO

Results and Discussion

Dependence of ILBS Aggregation in the Aqueous Medium on the Length of the Alkyl Chain and Effects of the Ester-Containing Side Chain

Figure shows the dependence of the surface tension (γ) on surfactant concentration for CEMeImBr at 25 °C, n = C, C, and C. The corresponding critical micelle concentrations (cmcs) are reported in Table . The values for the C and C members agree with literature values, and the value for CEMeImBr is reported for the first time. As expected, the value of cmc decreases as a function of the increasing length of the alkyl chain. Thus, the relative cmc values of these surfactants are 13.8:5: 1 for n = C, C, and C, respectively. For the ILBSs with the morpholinium head group containing ester functionality in the side chain, the relative cmc decreases from 11.07 to 1 by moving from C to C.[67] Note that the cmc of the ester-functionalized ILBS is lower than that of the nonfunctionalized (CMeImBr), vinyl-functionalized (CVnImBr), and conventional cationic surfactants (CTABr).[68,69] This may be due to hydration of the ester group that contributes to head-group repulsion at the micellar–water interface. Additionally, the ester group is localized close to the imidazolium ring, and this may favor electrostatic and H-bonding interactions among the alkyl chains of the ILBSs, favoring the aggregation at lower surfactant concentration. The surface activity of the ester-functionalized ILBSs is the result of the above factors and is discussed below in detail.

Figure 1

Surface tension versus logarithm of concentration of ILBS curves at 25 °C.

Table 1

Calculated Parameters from Surface Tension Data for the Ester-Functionalized, Vinyl-Functionalized, and Nonfunctionalized ILBSs with Conventional Cationic Surfactants with Different Alkyl Chain Lengths at 25 °Ca

ILBS	cmc (mM)	γcmc (mN/m)	πcmc (mN/m)	pC20	Γmax × 106 (mol/m2)	Amin (Å2)	refs
C12EMeImBr	2.5	28.9	43.1	3.61	2.96	56.2	(64)
C14EMeImBr	0.90	24.8	47.2	4.31	3.61	46.1	(64)
C16EMeImBr	0.18	23.0	49.0	4.72	4.29	39.0	this work
C12VnImBr	7.0	34.1	38.4	2.80	2.03	81.8	(58)
C14VnImBr	1.85	33.8	38.6	3.40	2.18	76.2	(58)
C16VnImBr	0.48	33.5	39.1	4.00	2.53	65.7	(58)
C12MeImBr	10.9	39.4	33.6	2.67	1.91	86.8	(68)
C14MeImBr	2.61	39.1	33.7	3.33	1.98	84.0	(68)
C16MeImBr	0.66	38.7	34.2	3.78	2.09	79.0	(68)
C12TABr	15.8	33.0	39.0		1.40	118.0	(69)
C14TABr	3.45	40.0	32.5		2.18	80.0	(68)
C16TABr	0.92	40.8	31.4		2.30	72.0	(68)

The uncertainties in the calculated parameters are given as follows: γcmc = ±0.1 mN/m; πcmc = ±0.1 mN/m; Γmax = ±0.2 × 10–6 mol/m2; Amin = 0.5 Å2.

In addition to the values of cmc reported in Table , we discuss other parameters calculated from the plots of Figure . The discussion is based on the effect of (i) the alkyl chain length and (ii) presence of the ester group on the interfacial and micellar properties. Among the parameters calculated, surface tension at cmc (γcmc) decreases with an increase in the alkyl chain length of the ILBS. The values of γcmc for CEMeImBr are lower than those for CVnImBr, CMeImBr, and CTABr with an analogous alkyl chain, showing that introducing the ester functionality increases the surface activity of the ILBSs relative to the vinyl-functionalized and nonfunctionalized ILBSs and conventional cationic surfactants. That is, introducing the functionality increases the efficiency of the ILs to reduce the surface tension of water. Increasing the alkyl chain length increases the adsorption efficiency (pC20) and surface pressure at the cmc (πcmc), suggesting that the adsorption efficiency of the ILBSs increases because of the increased hydrophobic interactions. The values of pC20 and πcmc are in the order: CEMeImBr > CVnImBr > CMeImBr > CTABr. Similar to the nonfunctionalized ILBSs and conventional surfactants, the maximum surface excess concentration, Γmax, increases with the alkyl chain length, C, because of the increased hydrophobic interactions and tight packing among the monomers in the micelles.[70] The higher values of Γmax for the ester-functionalized ILBSs are larger than those of CMeImBr and CVnImBr as well as than those of the conventional cationic surfactants with an analogous alkyl chain length. These results indicate that ester-functionalized ILBSs accumulate more at the air–water interface than others.

Applications of these ester-functionalized ILBSs require knowledge of the geometry and size of their aggregates. We employed the well-known Israelachvilís ratio to predict the shape of the aggregates. Combining the experimentally determined values of Amin through surface tension data and using the Tanford formula,[70] we calculated the values for the packing parameter (P). For all three ILBSs with ester functionalization, the values of P were found to be less than 0.33, indicating that the aggregates of all ILBSs were spherical in shape near their cmc.

Formation of Ionogels with the Thermo-Induced Gel-to-Gel Transition

The spherically shaped ILBS micelles close to their cmc form isotropic solution in water. Upon increasing the concentration of CEmeImBr, CEmeImBr, and CEmeImBr beyond their cmc, the solutions go through the phase transition from isotropic to turbid because of the increased size of the aggregates. The ester-functionalized IL forms ionic hydrogels in an aqueous medium at physiological pH (i.e., pH 7.4) at higher concentrations. Experimentally, the solid CEMeImBr was weighed and mixed with 10 mL of water in a glass tube with the screw cap, and the mixture was heated in the water bath at 60 °C to yield a transparent solution. The latter was allowed to cool to room temperature using a specific cooling procedure [see scheme (a) of Figure ]. The formation of the fibrillar opaque ionic hydrogel, hereafter termed as ionogel, was observed visually. The critical concentration for gelation (CCG) was found to be 25.20, 22.60, and 8.80% (w/v) for CEmeImBr, CEmeImBr, and CEmeImBr, respectively. Below CCG, only a viscous gel or loose gel was observed. As CEmeImBr forms ionogels at much lower concentration than the other two ILBSs, we concentrated our studies on CEmeImBr. In the range of 8.80–10.40% (w/v) and at pH 7.4, a fibrillar opaque ionogel was observed at 25 °C for CEmeImBr, as shown in part (b) of Figure . Beyond 10.40% (w/v), precipitation occurs. The opaque gel showed good swelling and adhesive property, as shown in part (b,c) of Figure . Therefore, we carried out further gelation studies at 9.60% (w/v) and at pH 7.4 in the aqueous medium.

Figure 2

(a) Schematic representation of the fibrillar opaque ionic hydrogel to transparent ionic hydrogel (9.6% w/v). (b) CEMeImBr-based ionic hydrogel at 25 °C. (c) Adhesion behavior of the water-swollen gel at 25 °C and (d) turbidity measurement of the ionogel as a function of temperature.

To assess whether the transition (fibrillary opaque → transparent gel) is a kinetic process or thermodynamic one, we employed different protocols for CEMeImBr solution cooling (9.60% w/v, pH = 7.4, and 60 → 25 °C): (1) fast cooling (ca. 4 min) by placing the hot surfactant solution in a constant-temperature water bath (25 °C) and (2) slow cooling by turning off the heat, thus allowing the system (CEMeImBr solution + water bath) to reach 25 °C (ca. 45 min). In both cases, fast and slow cooling, the solution produced a fibrillar opaque gel on cooling, as shown in Figure a. Consequently, the gelation of CEMeImBr is thermodynamically controlled; the entrapped water molecules between the hydrophobic alkyl side chains interact with the ester group, forming a fibrillar opaque ionic hydrogel.[71] For a dipeptide-based supramolecular gelator, a transparent gel was observed on fast cooling and a viscous turbid solution appeared upon slow cooling.[72]

The observed gel-to-gel transition (opaque to transparent) upon increasing the temperature from 25 to 50 °C was characterized using turbidity and DSC. As shown in Figure d, with an increase in the temperature, % transmittance of the ionogel increases. A sharp increase was observed between 42.5 and 48.5 °C, after which the value of % transmittance remained practically constant. The transition in the transmittance agrees with the opaque (25 °C) → transparent above 48.5 °C.

Turbidity data were further supported by the DSC thermogram. As observed in Figure , the temperature-induced gel-to-gel transition was observed at 46.6 °C (Tgel–gel) with one additional small endothermic peak at 71.5 °C, attributed to the melting point of solid CEMeImBr. The lower transition temperature than the melting temperature suggests that the gel-to-gel transition occurred below the melting point of CEMeImBr,[54] probably because of the disruption of the cross-linked fibrous network of the fibrillar opaque gel (vide infra FE-SEM results) to form the transparent gel at higher temperature.[55]

Figure 3

DSC thermogram of solid CEMeImBr and the opaque ionogel.

Gel Particle Morphology

We further probed the gel particle morphology by SEM, FE-SEM, inverted microscopy, and TEM. The SEM image (Figure a) revealed the formation of a 3D branched network composed of long entangled fibers. Here, the 3D filaments are made of tightly winded helical tubules. The gel is expected to be formed by encapsulating the water molecules within the network of the percolated gelator and inside the branched tubes.[73,74] The FE-SEM image (Figure b) showed an entangled 3D fibrillary network responsible for the gelation. The entangled thin fibers are 1 μm in width and several micrometers in length.[75,76] The gel contained a tubular-like structure, as observed in TEM images (Figure c).[77] The excellent quality of the micrographs shown in parts (a,b) of Figure indicates that the physical integrity of the gel was not disturbed by the drying step during sample preparation.

Figure 4

Morphology of the gel as revealed by SEM, part (a); FE-SEM, part (b); TEM, part (c); and inverted microscopy, part (d). All images were recorded at 25 °C.

The texture of the hydrogel was also studied using an inverted microscope. The fibrillar network can be observed (Figure d), confirming the formation of uniaxial structures in the hydrogel. Thus, the opaque hydrogel structure at 25 °C is made up of the tubes, which on interdigitating formed the 3D branched network.[78]

Mechanical Properties of the Ionogels

The mechanical properties of the fibrillar opaque and transparent supramolecular ionogel were studied using the angular frequency sweep and strain sweep dynamic rheology test. To determine the linear viscoelastic region for both gels, we performed the angular frequency sweep test up to the maximum frequency of 100 rad s–1. The elastic modulus (G′) and loss modulus (G″) were plotted as a function of oscillation frequency, and the results are shown in Figure a. At 5% fixed strain, for opaque and transparent gels, the storage modulus (G′) was higher than the loss modulus (G″) with increasing angular frequency (0–100 rad s–1). Furthermore, the values of G′ in the opaque gel were higher than the transparent gel, indicating branching of the former, which provides additional paths for the storage of energy. The loss modulus (G″)—indicative of how energy is dissipated in the system—showed a behavior similar to G′ for both types of gels. At the investigated angular frequency range, no cross-over frequency (ωc) was observed, indicating that the colloidal particles are unstable or form a 3D branched network.

Figure 5

(a) Frequency sweep dynamic rheology data for the hydrogel (9.60%) at 25 and 50 °C (strain 5%). (b,c) Strain sweep dynamic rheological data for the hydrogel (9.6%) at (b) 25 and (c) 50 °C. The angular frequency is ω = 1 rad s–1).

The strain sweep test at the fixed angular frequency of 1 rad s–1 for both the opaque and transparent gels was carried out to characterize the mechanical properties of the fibrillar opaque and transparent ionogel. For the former, the values of (G′) and (G″) remain constant up to 5% strain, indicating that the gel is in the linear viscoelastic region in which the elasticity and viscosity are constant. Beyond 5% strain, G′ and G″ decrease rapidly, and the cross-over occurred at 9.5% strain (Figure b). This point is also known as the critical strain level (γc). γc is the characteristic boundary of the structured gel, below which the gel exhibits a viscoelastic character that hinders its flow. Above γc, the storage modulus starts decreasing because of the breaking up of the structured (fibrillar) network. The above results indicate that the opaque gel formed a stable continuous elastic network up to 5% strain.[79,80] For the transparent gel, G′ is higher than G″, and no cross-over is observed up to 100% strain sweep (Figure c), indicating the formation of a true gel in the entire strain sweep region.[81] Consequently, the hydrogel at 50 °C consists of an entangled temporally persistent network formed as a result of interactions because of topological constraints.[54]

Water–Surfactant Interactions in the Gels

To understand the water–surfactant interactions during gel-to-gel transition, we recorded the FT-IR spectra of the partially dried ionogel samples. As observed in Table , the −OH stretching frequency of water in the transparent gel is red-shifted from 3632 to 3529 cm–1 in the opaque gel because of stronger hydrogen bonding in the latter case.[82] The values of ν–C=O of the ester group, which is at 1749 cm–1 for the powder sample, are 1688 cm–1 for the opaque gel and 1708 cm–1 for the transparent counterpart. That is, the ester group is likely to be more hydrated in the gel that is formed at lower temperature (opaque gel).[83] The C–N stretching vibration in the cationic ring, which is located at −1575 cm–1 in powder CEMeImBr, is shifted to −1530 and −1540 cm–1 for the fibrillar opaque gel and the transparent ionic hydrogel gel, respectively. Thus, the hydrogen bonding plays a dominant role for the formation of the fibrillar opaque gel network at 25 °C, which got weaker at higher temperature, that is, at 50 °C forming the transparent gel. Increase in solubility of the ester group containing the hydrophobic alkyl chain at higher temperature also affects the physical appearance of the gel. Overall, for the transition of transparent ionogel → opaque ionogel, νOH, νC=O, and νC–N show a red shift, indicating stronger H-bonding.

Table 2

Bond Frequencies of Solid CEMeImBr, Opaque Ionogel, and Transparent Ionogel

bond, frequency, cm–1	solid C16EMeImBr	dried opaque ionogel	dried transparent ionogel
νOH of water-in-gel		3529	3632
νC=O of ILBS	1749	1688	1708
νC–N imidazolium ring	1575	1530	1540

Stability of the Ionogel with Respect to pH and Dilution

In order to utilize the opaque gel for various applications, it is important to evaluate its stability on dilution and toward pH changes. We performed the pH stability of the opaque gel in phosphate buffer pH (pH 5.0 and 7.4). After 12 days of incubation time (25 °C), no detectable gel was found at acidic pH versus 20% residual gel at 7.4 pH buffer solution. The degradation of the ionogel is due the presence of the ester group (β) to the quaternized nitrogen atom, which facilitates ester hydrolysis by its (−I) effect (Figure ).[84]

Figure 6

Degradation profile of the ionic hydrogel in two buffer solutions of pH 5.0 and 7.4 at room temperature.

Both ionogels were subjected to 100% volume dilution with water at 25 °C (opaque) and 50 °C (transparent) and were found to remain intact (see Figure ).

Figure 7

Dilution and temperature stability study.

Application of the Ionogel in Dye Absorption and Drug Encapsulation

Water pollution by (textile) dyes that are stable to thermal and light degradation is a major concern. Several gels were extensively explored as biosorbent for the removal of these dyes from the solution.[85−87] The characteristic feature of the crystalline-layered structures of the gels is responsible for the intercalation of the guest molecules.[88] We explored the ability of the opaque and transparent gels to absorb representative dye contaminants (methyl orange, MO, and crystal violet, CV) from the aqueous medium.

A preliminary study indicates that the opaque ionogel very effectively absorbs MO and CV (see entries 1 and 2 of Table ). MO and CV are absorbed by 73.1 and 34.0% w/w, respectively (Figure S4a,b). The fibrillary ionogel absorbs 9.15 mg of MO per gram of the ionogel and 2.12 mg of CV per gram of the ionogel. The host–guest type of interactions and the electrostatic interactions are certainly responsible for the specific absorption of the anionic dyes rather than the cationic dyes in the opaque gel.[89] The absorption values of the present investigation are substantially higher than that of the tri-peptide-based gel but lower than that of the Ag(I)–melamine-based gel.[89,90] The ease of preparation as well as the ability to tune the properties of the ILBSs by merely changing the constituting cations and/or anions put these LMWGs ahead of the polymeric gels.

Table 3

Absorption of Various Substrates Using the Fibrillary Ionogel

entry	adsorbed substrate	relative conc. mg/g (adsorbate/ionogel)	λ, nm	adsorption time, h	adsorbate removal, %
1	MO	9.15	463	36	73.1
2	CV	2.12	590	36	34.0
3	DS	15.22	276	36	40.4
4	IM	27.62	255	36	72.3

As reported in entry nos 1 and 2 of Table , the transparent gel absorbs only 34.0 and 8.0% w/w of MO and CV, respectively (Figure S5a,b). The transparent gel absorbs 4.25 mg of MO per gram of the ionogel and 0.50 mg of CV per gram of the ionogel.

Table 4

Absorption of Various Substrates Using the Transparent Ionogel

entry	adsorbed substrate	relative conc. mg/g (adsorbate/ionogel)	λ, nm	adsorption time, h	adsorbate removal, %
1	MO	4.25	463	36	34.0
2	CV	0.50	590	36	8.0
3	DS	0.52	276	36	1.4
4	IM	17.75	255	36	53.59

Similarly, the encapsulation efficiency of the opaque and transparent gels was investigated for the two drugs, sodium salt of diclofenac (DS) and imatinibmesylate (IM). As reported in entry nos 3 and 4 of Table , the opaque crystalline gel encapsulates only 40.4% of DS, whereas 72.3% of IM was encapsulated (Figure S6). The transparent gel encapsulates only 1.4% of DS, whereas 53.59% of IM was encapsulated. The drug encapsulation efficiency for the opaque gel is calculated by measuring the absorbance of the drug through UV–vis data and is found to be 15.22 and 27.62 mg per gram of the ionic hydrogel molecule for DS and IM, respectively. For the transparent ionogel, 0.52 and 17.75 mg of DS and IM, respectively, were encapsulated per gram of the ionic hydrogel. Although both drugs are anionic, the latter is more hydrophobic (log P = 4.26 and 4.38), hence it is encapsulated more on the gel by hydrophobic interactions. The schematic representation of the absorption of dyes and drugs in the ionogel is given in Figure .

Figure 8

(a) Graphical representation of the percent absorption of dyes and drugs into the fibrillar gel matrix. (b) Schematic representation of the dye absorption and drug encapsulation by the gel fiber matrix.

Conclusions

Ester-functionalized ILBSs exhibited better surface-active properties than the nonfunctionalized and vinyl-functionalized ILBSs as well as than the conventional surfactants. These surface-active ILBSs form gels in water at higher concentration. Among the three ILBSs studied, CEMeImBr forms a gel in water with 8.80% w/v of CCG. The addition of CEMeImBr in an aqueous solution forms a unique gel-to-gel reversible transition with change in temperature: opaque at 25 °C and transparent at 50 °C. The transformation occurs below the melting point of the ILBS and is confirmed by turbidity and DSC measurements. The morphology of the gel at 25 °C temperature is further characterized through SEM, FE-SEM, inverted microscopy, and TEM imaging. The encapsulation of water among the 3D network of lamellar arrangement provides a microenvironment for the encapsulation of the hydrophobic moieties in protected manners. At high temperature, the fibrillar gel consisted of an entangled temporally persistent network is transformed into the transparent gel and is characterized by FT-IR spectroscopy. The mechanical properties of the ionogels were investigated by strain sweep and frequency sweep rheology measurements. The fibrillar gel exhibited excellent dye-absorbing and drug-encapsulating properties. The results show some potential applications of LMWGs.

Experimental Section

Materials

2-Bromoacetic acid (LOBA Chemie ≥98.0%), hexadecan-1-ol (SDFCL, 95.0%), toluene-4-sulfonic acid hydrate (LOBA Chemie ≥98.0%), 1-methylimidazole (Spectrochem ≥99.0%), IM (Sigma-Aldrich ≥98.0%), DS (Sigma-Aldrich ≥98.5%), MO (Acros, 95%)), and CV (Sigma-Aldrich ≥90.0%) were used without further purification. Other chemicals were of analytical grade, and water was triply distilled.

Synthesis of Ester-Functionalized ILBSs

Ester-functionalized IL CEMeImBr (molecular formula C22H41BrN2O2 and molecular weight 445.48 g/mol) was synthesized in a two-step procedure. Other two ILBSs of the series were synthesized by the same method except for the length of alkyl bromides, dodecyl, and tetradecyl. In the first step, hexadecyl-2-bromoacetate was synthesized by the procedure reported elsewhere.[91] Briefly, in the first step, hexadecyl-2-bromoacetate was synthesized by mixing cetyl alcohol (2.43 g, 10 mmol) and bromoacetic acid (12 mmol, 8.63 mL) at a volume ratio of 1:1.2. In the mixture, p-toluene sulfonic acid monohydrate (10%, 1 mmol, 192 mg) was added as the catalyst, and the reaction mixture was heated at 80 °C in the magnetic stirrer for 4 h. The completion of the reaction was monitored through thin-layer chromatography (n-hexane/ethyl acetate, 9:1). The reaction mass was dissolved in CHCl3 and then washed with 100 mL of water (10 mL aliquots). The product was phase-separated, and the reaction mass was transferred to a rotary evaporator to remove the solvents and water at 40 °C. Then, the crude product was washed with warm aqueous methanol (methanol/water, 98:2) at room temperature. The phase-separated product (lower layer) was again taken in a rotary evaporator to remove excess methanol and water.

In the second step, hexadecyl-2-bromoacetate (3.63 g, 10 mmol) was reacted with N-methyl imidazole (0.80 g, 10 mmol) at 90 °C for 2–3 h. After cooling to room temperature, the product was repeatedly washed with diethyl ether and then precipitated in cold acetone. The white solid product was separated using a separating funnel, and the product was dried under a vacuum dryer at 50 °C overnight (yield 76.35%, mp 71.5 °C).

1H NMR (Bruker ADVANCE 300 spectrometer (400 MHz). CDCl3, δ in ppm, Figure S1): 10.03 (s, 1H), 7.6 (s, 1H), 7.5 (s, 1H), 5.46 (s, 2H), 4.1 (t, 2H), 4.0 (s, 3H), 1.6 (m, 2H), 1.25–1.30 (m, 26H), 0.89 (t, 3H).

FT-IR (Shimadzu, KBr pallets, 400–4000 cm–1Figure S2): 2916 cm–1 (Ar (C–H)str/b), 2850 cm–1 (aliphatic (C–H) str), 1749 cm–1 (ester C=O), 1633 cm–1 (Ar (C–C)), 1575 cm–1 (imidazole ring), 1471 cm–1 (Ar, str/deform), 1361 cm–1 (Me (C–H), b, asym), 1080 cm–1 (C–O, str).

Methods

Surface Tension Measurements

Surface tension of the ILBSs solution was determined using a K9 tensiometer (Krüss) with a platinum–iridium ring at 25.0 ± 0.1 °C. The instrument was calibrated using triple-distilled water.

Thermal Gravimetric Analysis

The thermal stability of the representative CEMeImBr ILBS was determined using an SDT Q600 instrument between the temperature range of 25 and 500 °C at a heating rate of 10 °C/min in a N2 atmosphere. The start temperature (Tstart) is the temperature at which the decomposition of the sample starts, and the onset temperature (Tonset) is the intersection point of the baseline weight, either from the beginning of the experiment or the tangent of the weight versus temperature curve as decomposition arises. The onset temperature of the ILBS is 230 °C (Figure S3).

DSC Measurements

The DSC measurements were performed using a METTLER TOLEDO DSC 1 STARe instrument. The DSC cell was calibrated by using indium (mp 156.6 °C; ΔHfusion = 28.42 J/g) and zinc (mp 419.6 °C; ΔHfusion = 112.0 J/g). An amount of 20–30 mg of the opaque gel samples was introduced into the equipment aluminum “pan” that was heated in the temperature range of 20–70 °C at the heating rate of 2 °C min–1 under a N2 atmosphere. To check reproducibility, this cycle was repeated three times. The third scan was used to judge the transition of the gel from opaque to transparent.

FT-IR Spectroscopy

FT-IR spectra of the solid LMWG at 25 °C and gel at 25 and 50 °C were recorded on a Shimadzu FT-IR-8400S spectrophotometer with KBr pellets (1 wt % sample) in the 400–4000 cm–1 region. Both gel samples were allowed to dry for 2 days under identical conditions (room temperature) before recording their spectra.

Rheology

Rheological measurements were carried out using a Physica MCR 301 rheometer (Anton Paar). A plate–plate geometry of 49.973 mm diameter and a default gap of 0.4 mm were used. Frequency scans were performed at 1–100 rad s–1 under a strain of 5% (linear viscoelastic region). These measurements were done within the viscoelastic region where G′ and G″ are independent of strain amplitude. Strain scans were performed from 0.1 to 100% with a constant frequency of 1 rad s–1. The critical strain was quoted as the point that G′ starts to deviate for linearity and ultimately crosses over G″, resulting in gel breakdown.

Transmission Electron Microscopy

TEM images were recorded with a Philips CM-200 electron microscope at a working voltage of 200 kV. The sample (20 μL) was dispersed in 2 mL of water, and then solutions were spread on a copper grid (200 mesh) coated with a carbon Formvar. After 10 min, the excess solution was wiped away with a filter paper. Gel samples were stained with 1% sodium phosphotungstate solution. Excess liquid was also wiped with a filter paper after 5 min.

Scanning Electron Microscopy

The supramolecular crystalline opaque gel was analyzed on a Hitachi S-3400N scanning electron microscope operating at 15 kV, after drying at the ambient atmosphere. The gel samples were gold-coated.

Field Emission Scanning Electron Microscopy

The FE-SEM experiment was performed by placing a 20–30 mg gel sample on a microscope cover glass. The opaque gel sample was dried under reduced pressure and coated with platinum for at least 90 s at 5 kV voltages. The average thickness of the coating layer of platinum was 2–3 nm. The micrographs were taken using a FE-SEM (S-4800, Hitachi).

Inverted Optical Microscope

Phase behavior was investigated using a Nikon Eclipse TS 100 inverted optical microscope with the high-intensity light-emitting diode eco-illumination system. Opaque gels were placed between two glass slides at room temperature, and the gel texture was recorded with a Nikon camera.

Turbidity and UV–Vis Absorption Study

The gel-to-gel transition of opaque to transparent gel was confirmed upon increasing the temperature from 25 to 50 °C, and UV–vis absorption spectra (dyes, drugs, and gels) were recorded with a Varian Cary 50 UV spectrophotometer at 25 °C.

Gel Preparation

The respective amount of CEMeImBr powder was weighed into a glass vial and then water was added in a fixed amount (10 mL). The pH of the solution was adjusted by phosphate buffer solution. The mixture was agitated (vortex mixer), and the homogeneous solution was heated to 60 °C. Upon heating, the solution became isotropic and transparent at 50 °C. The glass vials were then left to equilibrate at room temperature for 24 h to obtain the opaque gel (Web-Enhanced Objects). It is to be noted here that we had cropped the video (57 s) in order to save the size and for better attention of the reader.

Stability of the Gel

pH Stability

The degradation study of the ionogel was performed in phosphate buffer solutions at pH = 5 and 7.4. A weighed amount of the ionogel was added to the appropriate buffer, and the solution was magnetically stirred at 50–70 rpm at room temperature. The beakers containing the gel samples were incubated for 12 days at controlled conditions of temperature and pressure (25 °C, atmospheric pressure). The change in weight of the gel was observed at regular intervals to observe the degradation of the gel in different buffer solutions. Degradation was calculated by the following equation:where ma is the dry mass of the sample and mb is the dry mass of the sample after the certain time of degradation.

Dilution Stability

Two different gel samples of 2 mL volume (opaque and transparent) at 9.60% w/v of each were prepared in two different vials. To this, 2 mL of water (25 °C in first and 50 °C in another) was carefully added from the top of the vial. The vials were shaken carefully for 30 min in 5 min interval to observe the breakage of the gel on dilution.

Absorption of Dye and Encapsulation of Drug

The dye absorption was carried out in the opaque and transparent gel (9.60% w/v, 216 mM). The process is monitored by recording the absorption bands at 463 and 590 nm λmax for MO and CV, respectively, with a time interval, and the final spectra were collected after 36 h.

The encapsulation of DS (0.148 mM) and IM (0.152 mM) in the fibrillar opaque crystalline gel and transparent gel (9.60% w/v, 216 mM) was monitored by measuring the UV-absorption spectra at the respective λmax 276 and 255 for DS and IM, respectively. The process is monitored by recording the absorption band λmax with a time interval, and the final spectra were collected after 36 h. The temperature for the fibrillar opaque crystalline gel and transparent gel was controlled by a Peltier temperature controller with 0.1 °C accuracy.