Ultraviolet Patterned Calixarene-Derived Supramolecular Gels and

Mar 30, 2017 - Incorporating a photoreactive stilbene moiety, we show that the aggregation state of the material can be tuned by heating and UV exposu...
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Ultraviolet Patterned Calixarene-Derived Supramolecular Gels and Films with Spatially Resolved Mechanical and Fluorescent Properties Ji Ha Lee,†,‡ Sung Ho Jung,† Shim Sung Lee,† Ki-Young Kwon,*,† Kazuo Sakurai,*,‡ Justyn Jaworski,*,§ and Jong Hwa Jung*,† †

Department of Chemistry and Research Institute of National Sciences, Gyeongsang National University, Jinju, Korea Department of Chemistry and Biochemistry, The University of Kitakyushu, Hibikino, Kitakyushu 808-0135, Japan § Department of Bioengineering, University of Texas, Arlington, Arlington, Texas 76010, United States ‡

S Supporting Information *

ABSTRACT: Supramolecular assemblies have in the past been considered mechanically weak and in most cases unable to withstand their own weight. Calixarene-derived networks can, however, provide robust supramolecular gels. Incorporating a photoreactive stilbene moiety, we show that the aggregation state of the material can be tuned by heating and UV exposure in order to control the mechanical as well as the fluorescent properties. Regulating the extent of heating to control the proportion of H-aggregates and J-aggregates and further cross-linking of H-aggregates by control over UV exposure allows for adjustable photopatterning of the fluorescence as well as the material stiffness in the range from ∼100 to 450 kPa. We expect this straightforward supramolecular system will be suitable for advanced prototyping in applications where modulus and shape are important design criteria. KEYWORDS: supramolecular gel, calix[4]arenes, stilbene, cycloaddition, fluorescence

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their planar structure, certain stilbene aggregates, when in close face-to-face proximity, can result in photochemical dimerization at the double bonds upon UV irradiation to form a cyclobutane ring that significantly reduces the conjugation of the system.24 The resulting tetrafunctional cross-linking between neighboring stilbene moieties has previously been used, mostly in polymeric systems, for applications toward optical data storage and devices.25 The group of S. Y. Park has extensively reported on the fluorescence switching of stilbene crystal powders as a result of UV light-induced [2 + 2] cycloaddition.15,20,26 Among their reports, trifluormethyl-containing cyanostilbene crystalline compounds could be generated for tightly packed π-dimer systems which exhibit reversible [2 + 2] cycloaddition and a corresponding modulation in the characteristic fluorescence.15,20,26 In supramolecular gels, stilbene components have often been implemented to achieve responsive systems. Various stilbene

upramolecular gels represent a class of materials comprised of gelator components which can selfassemble into networked aggregates via noncovalent interactions including host−guest systems capable of selfhealing and the use of metallic cross-linkers to provide reversible sol−gel transition in response to stimuli including pH and temperature.1−10 A number of such interesting stimuli responsive properties have been demonstrated in supramolecular gels in the past, and research in this area continues to yield exciting results. Among these, supramolecular gels incorporating photosensitive elements have captured the attention of many researchers as a means for creating light responsive materials.11−14 Capabilities of such systems include gel−sol or sol−gel transitions,15 transition in optical properties like fluorescence,16,17 as well as switching of gelator fiber morphology/helicity,18 all of which can be tuned to respond to light. Stilbenes represent one class of photosensitive element that is widely implemented as a component in such functional self-assemblies in the solid state,19−21 as this moiety is wellknown for photoisomerization in addition to the possibility for [2 + 2] photocycloaddition in the presence of UV light depending on their aggregate conformation.22,23 Afforded by © 2017 American Chemical Society

Received: February 13, 2017 Accepted: March 30, 2017 Published: March 30, 2017 4155

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viscoelasticity and stiffness. In doing so, we demonstrate a gel system which succeeds in providing spatial mapping of tuned stiffness by photomasking and exposure to UV light. This provides our example of a system with correlation between mechanical properties and fluorescence properties of the gel by increasing temperature and/or UV irradiation. Specifically, the stiffness of the gel within a defined spatial area could be increased gradually by UV irradiation over 24 h, which is a rare example for soft supramolecular materials. By virtue of its fluorescent properties, this system also reveals the interplay between H-aggregates and J-aggregates as a function of heating which may be used to closely adjust the aggregation mode. The relationship between the mechanical and fluorescence properties via a cross-linking reaction with UV-light and/or heatinginduced aggregation modes changes had not been studied for such supramolecular gels. Thus, the following study holds value in controlling the H- and J-aggregation modes by heating and/ or UV irradiation while examining the correlation between the mechanical and photophysical properties of these supramolecular gels. We anticipate that the ability to control the stiffness of supramolecular gels within a spatially defined area by UV irradiation may be particularly applicable to tissue engineering and other biological fields.

derivatives have proven capable of altering the overall supramolecular assembly by local changes in their arrangement due to UV exposure23,27,28or other stimuli such as heating.26,29As a result, a number of research works implementing photoswitchable gelators have shown the ability to control the transition from gel−sol or sol−gel state for supramolecular systems,30−33 in some cases with implementation of a photomask for spatial patterning.34,35 Such research outcomes have promoted our understanding and engineering of supramolecular soft matter systems in a myriad of ways; however, in many cases, the practical applications of supramolecular gels remained limited due to their weak mechanical properties in contrast to their polymeric counterparts. To control mechanical properties and provide reversible sol−gel transitions, several supramolecular systems have employed host−guest interaction and metal coordination among other means for cross-linking, such as the work of the Hung group who reported a crown ether-based supramolecular polymer gel for controlling gel pore size as well as response to stimuli including temperature, cation concentration, and pH but was not photoresponsive.7−10 We recently also demonstrated that calixarene-based supramolecular organogels can be generated by hydrazone reaction to yield mechanically strong networked hydrogels by a simple solvent exchange process.36 In this prior work, the polymeric supramolecular gel induced by the hydrazone reaction was useful to prepare stable gels, and the mechanical properties could be tuned for the bulk gel as a whole by controlling the time of the reaction, but was not able to spatially control the mechanical properties. In contrast, compared with the stilbenebased self-assembled crystal powdered samples, the control of photoresponsive properties in multicomponent stilbene-containing supramolecular gels has not been reported. In order to improve the customizability and practical capabilities of such gels, we were motivated to control the gels mechanical properties by spatial photopatterning. To pursue this, we have implemented a stilbene derivative in the following work as a tunable cross-linking element (controlled via its isomerization). In addition, this approach could provide pattern defined mechanical properties as well as fluorescent properties of a supramolecular gel. The importance of tuning gel strength has value to a number of applications, particularly in the context of biomedical gel matrices wherein substrate stiffness can influence the fate/differentiation of certain progenitor cells and stiffness gradients dictate cellular migration.37−41 Controlling the spatial mechanical properties of possible biomedical gels is significant, since the stiffness of the cellular microenvironment can vary significantly for different tissue types, for example, 260 Pa for the brain, 640 Pa for the liver, 2.5 kPa for the kidney, and up to 12−100 kPa or even 950 kPa for skeletal muscle and cartilage, respectively.37−41 To briefly overview our approach, we utilize a gelator comprised of calixarene and photosensitive stilbene derivatives for regulating both the aggregation state (H- or J-aggregates) and the extent of cross-linking of the H-aggregates, by heating and photocycloaddition, respectively. The extent of H- and Jaggregations modes within supramolecular gels were controllable in relation to the temperature and affording distinct changes in their fluorescence properties. Because [2 + 2] cycloaddition of stilbene moieties can occur for stilbene Haggregates after UV exposure, this could affect the fluorescence by providing a strong green fluorescence emission, while the mechanical properties could be induced to have enhanced

RESULTS AND DISCUSSION Calix[4]arene-Based Polymeric Gel Formation by Hydrazone Reaction. In multicomponent gelator systems, the mixing of two different molecules is often used to dictate the final properties of the bulk gel. In contrast, we utilize the ability of a single calixarene-stilbene derived oligomer gelator to form two different aggregation states (H- and J-aggregates), thereby providing the means for locally tuning the mechanical and fluorescent properties by regulating the proportion of each aggregation state. To begin, we synthesized the hydrazinebearing calixarene derivative 1 and the aldehyde-bearing stilbene derivative 2 as gelator precursors. The gelator precursors were dissolved in DMSO in equimolar amounts with addition of HCl (and without HCl for enol formation) to control the resulting hydrazone reaction for oligomer formation as previously described.36 The oligomerization proceeded to result in stable gel formation after 2 days (Figure S1). The hydrazone reaction between 1 and 2 was monitored by 1H NMR (Figure S2). From the NMR data, the degree of hydrazone formation was determined to reach 65% completion. The morphology of the supramolecular gel formed by hydrazone reaction was observed using scanning electron microscopy (SEM) (Figure S3). Freeze-dried gels, which were formed in the presence of 2 μM HCl, showed very distinct network structures as revealed by SEM. Initially, the gels exhibited isolated, flake-like structures without a 3D network (Figure S3A). In contrast, increased aging times with UV irradiation (256 nm) of the gel resulted in the formation of a porous (pore diameter ∼150−300 nm) structure (Figure S3B), in which the 3D network structure could facilitate improved gel stability. The aging time and use of acid to catalyze the supramolecular gelation in this system followed the same trend as was explained in our earlier work.36 Aggregation Behavior for Stilbene Component of Calix[4]arene-Based Polymeric Gel. The stilbene components facilitated an observable blue fluorescence under 340− 380 nm light attributed to the stacking of favorable Haggregates (represented schematically within the yellow box of Scheme 1a) but had no fluorescence when exposed to 465−495 4156

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Scheme 1. Chemical Structure of Gelator Precursors (1 and 2) as well as (a−d) Schematic Representation of Proposed Network Structures: (a) Before and (b) after Heating for 1 h at 60 °C, (c) after UV Irradiation, and (d) after Immersion in DMSOa

The blue emission was observed from exposure to band pass filtered light of 340−380 nm, while the green emission was taken in response to band pass filtered light of 465−495 nm. a

Figure 1. (A) UV spectra of gel after UV irradiation for (a) 5 min, (b) 12 h, (c) 24 h, (d) 36 h, and (e) 48 h. (B) Fluorescence spectra of gel after UV irradiation at 256 nm. (C) Plot of peak fluorescence intensity vs UV irradiation time. (D) Photograph of gels before, during, and after spatially defined UV irradiation using a photomask (outside: UV blocked; inside: UV exposed): (a) initial state before irradiation, (b) after applying mask to outside, (c) under initial UV irradiation, (d) after UV irradiation under 256 nm and subsequent removal of mask.

nm light. By heating at 60 °C for 1 h, the random nonaggregated stilbenes and partial H-aggregated stilbenes underwent J aggregation (as seen within the green box in Scheme 1b) in the gel resulting in green fluorescence under 340−380 nm light, while the mainly original blue fluorescence remained (represented by the H-aggregates found within the yellow box in Scheme 1b). This change of aggregation modes from H-aggregate to J-aggregate by increasing temperature may be due to encapsulated solvent molecules. The increasing temperature enhances solvent molecular movement, which in turn causes the aggregation mode to shift from H- to Jaggregates. This aggregation mode was changed to the gel state; thus, the photophysical property of supramolecular gel

composed stilbene moieties can also be controllable. Different molecular configuration for J-aggregates vs H-aggregates can afford different spectral responses, and it is also of interest that face-to-face associated stilbenes (i.e., H-aggregates) are known to be capable of photodimerization.42 After intense UV irradiation, a loss in blue fluorescence occurs from the [2 + 2] cycloaddition of stilbenes that were in close proximity, specifically former H-aggregates, providing a cyclobutane derivative (as represented within the red box of Scheme 1c) which had no blue fluorescence. Utilizing a photomask, the observed area exposed to UV light was found to have lost its blue fluorescence; however, the entire gel retained its green fluorescence indicating that the olefin 4157

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Figure 2. (A) UV spectra of gel by (a) before and after heating for (b) 1 h, (c) 6 h, (d) 12 h, (e) 24 h, and (f) 48 h. (B and C) Fluorescence spectra of gel (B: excitation wavelength: 380 nm; C: excitation wavelength: 450 nm) (a) before and after heating for (b) 1 h, (c) 6 h, (d) 12 h, and (e) 24 h. Increasing the length of heating time resulted in a decrease in the fluorescence intensity in (B), whereas the fluorescence intensity in (C) increased.

units of the J-aggregates were not sufficiently close for cycloaddition (Scheme 1c). The UV exposed gels were then once again treated with DMSO solvent, which eliminated the green fluorescence due to disassembly of the J-aggregates; however, the blue fluorescence remained unaffected by the presence of solvent (Scheme 1d, Figure S4 and Movie 1), presumably due to solvent-induced disruption of supramolecular interactions between only J-aggregates.43 As such, we find that the cycloaddition of H-aggregates in our gel system is not reversible, which is distinct from solid-state studies indicating thermally reversible cycloaddition of stilbene derivatives.20 Conversely for the J-aggregates, subsequent removal of the solvent followed by heating seems to indicate the J-aggregate formation is, in contrast, reversible. We believe this loss in J-aggregate structure to occur indirectly from the enhanced solvent encapsulation ability arising from the increased pore structures after photocyclization (Figure S3). The resulting swelling of the organogel after exposure to DMSO solvent could consequently have disrupted any existing J-aggregates. Furthermore, the gel before UV irradiation showed a reversible gel to sol transition at 100 °C (Figure S5). Photophysical Properties of Calix[4]arene-Based Polymeric Gel. From here, we explored these interesting photophysical properties in more detail, as related reports of nanofibril systems44 and solid-state systems20 have shown that changes in the supramolecular stacking modes (i.e., transitions from J- to H-aggregates or cycloaddition of H-aggregates) resulting from heating and UV exposure can significantly alter absorption and photoluminescence. Specifically, we find a significant decrease in the absorbance (A 400 nm) occurring with longer UV exposure times as shown in Figure 1A. Similarly, observing the blue fluorescence (λex = 380 nm) as a function of UV exposure time revealed a substantial decline in fluorescence within several hours (Figure 1B). The photocycloaddition of H-aggregates within the gel allows extraordinary fine-tuning over the extent of gel cross-linking, and moreover, the use of masking/UV exposure (256 nm) allows precise spatial patterning of the cross-linked regions. As shown in Figure 1C for a previously heated gel, a mask with a transparent heart shape was used to generate a nonfluorescent heart-shaped pattern on the gel after exposure to 256 nm UV light. While the bulk gel structure is maintained, the outside of the heart shape (wherein the H-aggregates had not undergone cycloaddition) was clearly more fluorescent than the UV exposed inner heart shape area where the cross-linked gel had formed.

Spectroscopic analysis confirms that gelation resulting from photocycloaddition provides a powerful means to tune the network structure by UV irradiation. NMR spectroscopy, powder X-ray diffraction (XRD), and SAXS give evidence of [2 + 2] photocycloaddition within the stacked H-aggregation modes. NMR spectra confirmed breaking of the conjugation system for adjacent H-aggregated stilbenes after [2 + 2] photocycloaddition (Figure S6). Specifically, this was determined by the undisputable appearance of −CH peaks corresponding to cyclobutane in distinct chemical environments after UV irradiation. As a result, we find that the improvement in strength observed for the UV exposed gel is a factor of cross-linking between different stilbenes rather than isomerization which has also been known to occur in stilbene systems. Powder XRD similarly showed that after UV irradiation, the sample is less ordered, supporting the idea that stacked H-aggregates are lost to cycloaddition via their adjacent stilbenes (Figure S7). Before UV irradiation, the Bragg reflection pattern exhibited several sharp peaks at 2θ values of 10.5, 16.57, 19.76, 20.58, 24.35, and 26.15 and one broad peak centered at a 2θ value of 20.12. We measured additional powder XRD patterns of gels by increasing temperature. As shown in Figure S8, we can clearly see the distance at 3.656 Å originated from the interlayer center-to-center distance between stilbene moieties in H-aggregates. Interestingly, one small peak was observed at a 2θ value of 22 by heating. Furthermore, with increasing temperatures, the intensity of 3.656 Å relative to 4.092 Å decreased gradually, where 4.092 Å is the interlayer distance between the stilbene and stilbene moieties in J-aggregates. This decrease was due to the conversion of H-aggregates into J-aggregates. On the basis of the powder XRD patterns, the distance between double bonds in J-aggregates would be around 6−7 Å, as shown in Figure S8B, even though the interlayer center-to-center distance between double-bonds in J-aggregates cannot directly be obtained in powder XRD patterns. Correspondingly, the interlayer center-to-center distance of double bonds in Jaggregate would be too far for [2 + 2] cycloaddition. These findings indicate that partial H-aggregates were converted into J-aggregates. In addition, the powder XRD data support the view that [2 + 2] cycloaddition can occur in H-aggregation mode. On the other hand, after UV irradiation the gel exhibited one broad peak at the 2θ value of 15.99, indicating a more amorphous gel structure. SAXS experiments were accompanied to provide further support for the proposed structure of the gel. In general, SAXS is observed at very low angles (typically 0.1− 10°). This angle range provides information regarding the 4158

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Figure 3. Photograph of film state (DMSO 5 mL, PMMA, 0.5 mL, 10 wt %, compound 1 5 mg, 0.1 wt %, compound 2 1.34 mg, 0.41 wt %, HCl 10 μL) fluorescence change (a−d) under 340−380 nm and (e−h) under 465−496 nm. The images show the (a,e) initial state after spin coating, (b,f) after heating for 1 h at 60 °C, (c,g) after partial irradiation within the region of a heart-shaped cut out mask, and (d,h) after being immersed in DMSO.

455 nm) with increasing J-aggregate emission (λex = 450 nm, λem = 525 nm) (Figure 2B,C). Fortunately, these emission spectra offer a window into quantifying the proportion of Haggregates available in the gel for cross-linking by UV-induced cycloaddition. In doing so, we may monitor the relative peak heights to appropriately tune the mechanical properties which are not only affected by the proportion of H-aggregates but also are a function of UV exposure time. As shown in Figure S11, the absorption intensity at 380 nm corresponding to Haggregation and random nonaggregation decreased by increasing UV irradiation time indicating conversion into the cycloaddition form, but remained effectively constant at 450 nm, corresponding to J-aggregates which are unable to undergo cycloaddition. From this proof of concept, we can see that photomasked gel segments exposed to intense UV light could cause quenching of their blue fluorescence. This UV exposure results in crosslinked gel regions with improved mechanical properties by virtue of the stilbene cycloaddition as compared to unexposed (not cross-linked) adjacent regions which maintain blue fluorescence but are mechanically weak. Finally, we extend this idea of photopatterned fluorescence properties for use in solid-state films. By mixing the gelator precursors (10 wt %) with PMMA in DMSO, films were spin coated and subsequently heated to promote J-aggregation. By simple photomasking during UV exposure, the films fluorescent properties could be patterned by photocycloaddition of the stilbene H-aggregates within the film (Figure 3). As with the bulk gel, blue fluorescence disappeared due to UV irradiation at 256 nm in the open exposed region of a heart-shaped cut out mask as seen in Figure 3c,d, which was attributed to the [2 + 2] cycloaddition of stilbenes. In contrast, the green fluorescence still remained after UV irradiation (Figure 3g). This green fluorescence from the J-aggregate nonetheless did completely disappear in the film after exposure to solvent (Figure 3h), while the patterned blue fluorescence of H-aggregates that were not cross-linked remained unchanged. Once again, under the treatment with DMSO, J-aggregation is disturbed, which results in quenching of green emission without any impact on blue emission (Figure 3d,h). Spatially Resolved Mechanical Properties of Calix[4]arene-Based Polymeric Gel by UV Irradiation. After the gel was formed but prior to heating or UV irradiation, the storage and loss modulus of the gel was examined to show that the supramolecular gel remained very weak (Figure S12). Since the photocycloaddition between two adjacent stilbenes

shape and size of the structure. Initial slopes determine the general structure shape, such as a sphere (slope = 0), cylindrical particle (slope = −1), plate (slope = −2), and aggregate (slope = −3).45,46 In our case, the slope is −3. As shown in Figure S9, initial oligomerized gels included J- and H-aggregated stilbenes with highly ordered structures indicating intermolecular distances of 1.368 nm. On the other hand, the broad peak after [2 + 2] photocycloaddition of H-aggregated stilbenes suggests a less ordered structure; hence, photocycloaddition may disturb the prior ordered arrangement provided by Haggregation. In addition, the SAXS data support that the structure of the gel is similar to that which has been proposed. Since [2 + 2] cycloaddition proceeds selectively in Haggregates as opposed to J-aggregates due to the distance between stilbene olefin units, we could control the amount of cycloaddition-derived cross-links within the gel by tuning the extent of H-aggregates present before UV exposure. In order to clarify the individual components of the spectra, we have provided a curve-fitted spectra showing the distinct bands corresponding to H-aggregated structures, disorder structures, and J-aggregated structures. The lower wavelength band appearing in the spectra can be separated into two distinct peaks, wherein the shorter wavelength absorption peak appearing at 380 nm is due to H-aggregation, which was attributed to π−π stacking.20,47 In contrast, the UV−vis absorption peak appearing at the longer wavelength of 395 nm corresponds to nonaggregated or disordered stilbene (Figure S10).20,47 As shown in Figure 2B, the UV−vis absorption peak appearing at 385 nm still remained after heating at 60 °C, which showed blue emission. The nonaggregated and partial H-aggregated stilbene moieties would change into J-aggregation because the intermolecular interaction of nonaggregated and H-aggregated stilbene moieties was weaker than that of the J-aggregated stilbene moiety. Given that heating of the gel could alter the molecular stacking toward an increased proportion of J-aggregates for longer heating times, we could effectively control the mode of aggregation by regulating the extent of heating which we observed directly from the absorption and fluorescence spectra. The nonaggregated and partial H-aggregated stilbene moieties begin forming J-aggregates, and as the heating time is extended, a concomitant increase in J-aggregates (λmax = 450 nm) along with a proportional loss in H-aggregate regions (λmax = 380 nm) is observed (Figure 2A and Figure S10). From the fluorescence spectra, this was similarly demonstrated as loss in the H-aggregate emission (λex = 380 nm, λem = 4159

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UV irradiation, whereas at the site without UV irradiation as determined by the mask, it will be relatively weak. As seen in Figure S13 and Movie S2, we can observe that mechanical failure of a partially masked gel will occur predictably at the site without strengthening by UV irradiation. These results indicate that the dramatic enhancement in the mechanical property of the gel with UV exposure is due to cycloaddition of the stilbene moieties as we confirmed spectroscopically. This is the example of spatially controlling the mechanical properties of a single component supramolecular gel using UV irradiation. Thus, we examined the rheological properties of both heating and the UV exposed gels in detail. The gel without heating and UV exposure showed weak mechanical properties. On the other hand, the storage (G′) and loss (G″) moduli values of the gel increased with heating (Figures S14 and S15). After heating at 60 °C for 1 h, the storage (G′) and loss (G″) moduli values of the gel were nearly 2.2-fold larger than before heating (Figures S16 and S19). With increasing temperature, a portion of the random nonaggregates would be converted into J-aggregates. Thus, the main driving force for the enhanced mechanical properties by heating was due to random nonaggregates becoming J-aggregates. Indeed, UV exposure of the gels caused a dramatic enhancement in their mechanical properties with a >3 orders of magnitude increase (>1300-fold increase) in their storage and loss moduli as compared to the unexposed case (Figures S17−S20). For each of the gels, we found the elastic response, G′, to dominate across all frequencies, and each of the cross-linked gels exhibited immediate recovery of G′ and G″ upon repeated step strain tests alternating above/below their critical strain amplitudes. The mechanical properties of the gel with respect to UV irradiation time were obtained reproducibly in different batches. To demonstrate the UV irradiation time-dependent gel properties in a more complex photomasking process (Figure 5A), we prepared a gel in which we provided a gradation of increasing UV exposure times. The eight individual domains subjected to different amounts of UV irradiation could be easily distinguished by their resulting fluorescence (Figure 5B). In the initial stages of UV irradiation, we did not observe a linear correlation between the mechanical properties and fluorescence

provides a means for cross-linking of different oligomers, we examined the mechanical properties of the gels before and after UV exposure. As shown in Figure 4, the shape of the gel (5 wt

Figure 4. (A) Photograph of a gel before extensive UV irradiation that is destroyed by loading and (B) after UV irradiation that is able to sustain loads.

% gelator prepared with 2 mL of DMSO) was easily broken with 100 g of mass added in compression. In contrast, the shape of the gel (after UV exposure for 24 h) was maintained with 300 g of balance weight. In a related test, we show that the mechanical strength of the gel could be patterned by a masking technique to make a specific portion of the gel strengthened by

Figure 5. (A) Illustration of photomasking method. (B) Photograph of gel formed after masking process with increasing UV irradiation time for (a) 4 h, (b) 7 h, (c) 8 h, (d) 9 h, (e)10 h, (f) 11 h, (g) 12 h, and (h) 14 h. (C) Plots for rheology (black and red colors) and fluorescence spectra (blue color) vs UV irradiation time with masking process. These values were obtained over an average of five experiments. The results were reproducible for the different batches. 4160

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effective cross-linkable gelator. The amount of cross-linkable segments in the gel could be controlled by varying the aggregation mode of the stilbene units by altering the heating time. Moreover, the extent of photocycloaddition among the H-aggregates was tuned by the UV exposure time. By photomasking, we could afford spatially tuned stiffness in the gels and the fluorescent properties of the system allowed for observation of the aggregation mode. Future applications for bulk supramolecular gels or films that are capable of having custom patterned mechanical and fluorescent properties may be most evident in the areas of cellular scaffolds or actuated systems. Because substrate stiffness affects cell migration and differentiation, localized control of stiffness could provide a means for spatial regulation of cell fate in tissue scaffolds,48 or for the case of mechanical systems may allow tuning of the dynamic mechanical range of the actuator by altering the stiffness.49 As spatial patterning of gels by light is a highly desirable technology, related works have been heralded in recent reviews as being of immediate use in these areas of tissue engineering, microfluidics, or structured gel actuators.50,51 Beyond this, we hope that remote patterning of tunable material and fluorescent properties may offer greater customizability for a range of materials and devices.

intensity but did so only after a period of several hours of UV exposure (Figure 5C). In contrast, the fluorescence intensity (under 340−380 nm light) was found to decrease for the domains subjected to longer UV irradiation times (Figure S21). An interesting observation after dissection and rheology of the eight patterned domains was that they exhibited distinctly increasing values for the storage and loss moduli for those subjected to increasing amounts of UV exposure (Figure S22) during patterning. Moreover, we could identify a correlation between the rheological properties and the fluorescence intensity for specific spatial location in the patterned gel as seen in Figure 5C. Atomic force microscopy (AFM) is a well-established tool to map the local mechanical properties of soft materials such as living cell, tissues, and gels with high spatial resolution.37−41 To directly determine the dependence of UV exposure time on the gel’s mechanical stiffness, the gel placed on a patterned silicon wafer and was irradiated with UV light over six different time periods by a photomasking technique (Figure 6A). Then,

EXPERIMENTAL SECTION Compound 3. p-tert-Butyl phenol (150 g, 1 mol) and NaOH (1.8 g, 45 mmol) were dissolved in 37% formaldehyde (100.7 g, 1.24 mol). The reaction mixture was refluxed at 120 °C for 12 h. After the solution was cooled to room temperature, H2O was eliminated in vacuo, and then diphenyl ether (450 mL) and toluene (150 mL) were added and refluxed at 250 °C. The color was changed to dark brown. Then, the crude product was recrystallized from ethyl acetate (300 mL) and was washed with acetic acid (100 mL) to give the white crystalline solid 3 in 57% yield. Mp 343−345 °C; IR (KBr pellet): 3176, 2958, 2866, 1603, 1482, 1361, 1242, 1200, 1042, 871, 816, 783 cm−1; 1H NMR (300 MHz, DMSO-d6) δ ppm 10.36 (s, 4H), 7.07 (s, 8H), 3.52 (s, 4H), 1.23 (s, 36H); 13C NMR (75 MHz DMSO-d6) δ ppm 147.62, 143.63, 126.96, 125.74, 34.52, 33.1, 31.2. ESI-MS: Calculated for C44H56O4 [M + H]+ 649.42, found 649.35; anal. calcd for C44H56O4: C, 81.44; H, 8.70; found: C, 81.75; H, 8.65. Compound 4. AlCl3 (24 g, 180 mmol) in toluene (150 mL) was stirred and poured into a suspension of compound 3 (20 g, 30.8 mmol), CH2Cl2 (200 mL), and toluene (50 mL). Then the reaction mixture was stirred for 0.5 h and was added to a CH2Cl2 (100 mL) and 10% aqueous HCl (400 mL) solution in an ice bath. Eventually, the reaction mixture was extracted with CH2Cl2 (3 × 200 mL), washed twice with water, and dried over anhydrous MgSO4, and the solvent was removed in vacuo. The crude product was recrystallized from CH2Cl2/ethyl ether (1:30, v/v) to give a beige crystalline solid 4 in 67% yield (8.7 g). Mp 314−315 °C; IR (KBr pellet): 3160, 2935, 2870, 1594, 1465, 1448, 1244, 752 cm−1; 1H NMR (300 MHz, DMSO-d6) d ppm 9.76 (br, 4H), 7.11 (d, J = 7.53 Hz, 8H), 6.64 (t, J = 7.50 Hz, 4H), 3.87 (s, 4H); 13C NMR (75 MHz DMSO-d6) δ ppm 149.8, 129.2, 129.0, 121.7, 31.1; ESI-MS: Calculated for C28H24O4 [M + H]+ 425.17, found 425.28; anal. calcd for C28H24O4: C, 79.22; H, 5.70; found: C, 79.25; H, 5.67. Compound 5. Compound 4 (5.00 g, 11.78 mmol), Cs2CO3 (38.4 g, 11.78 mmol), and ethyl 2-bromoacetate (11.81 g, 70.68 mmol) were suspended in dry acetone (300 mL). The reaction mixture was refluxed for 4 h. After cooling to room temperature, the salt was filtered, and acetone was removed in vacuo. To the resulting pale yellow oil, 10% aqueous HCl (100 mL) solution and CH2Cl2 (100 mL) were added, and the organic layer was separated and washed twice with water and dried over anhydrous MgSO4, and the solvent was removed in vacuo. The crude product was recrystallized from CH2Cl2/n-hexane (1:30, v/v) to give a white crystalline solid 5 in 46% yield (4.12 g). Mp 117−119 °C; IR (KBr pellet): 3062, 2980, 2938,

Figure 6. (A) Photograph of gel prepared by different UV irradiation time with photomask: (a) 6 h, (b) 9 h, (c) 12 h, (d) 15 h, (e) 18 h, and (f) 24 h. Scale bar is 2 mm. (The photo images of gel after exposure time more than 24 h are not shown because they are almost same.) (B) Plot of Young’s modulus vs UV irradiation time for 6−48 h. The Young’s moduli were obtained by 10 repeated measurements.

force−distance (FD) curves were applied to measure the stiffness by AFM (Figures S23). In AFM experiments to measure the stiffness of the nonirradiated gel, the gel was too sticky to obtain reproducible data even when a large spring constant cantilever was used. Among the 10 patterned positions on the surface of the gel sample, the slope of the FD curve for the gel surface irradiated by UV for 48 h was largest, indicating the highest stiffness. In contrast, the slope of the FD curve for the gel exposed to UV for only 6 h was the smallest. Based on the FD curves, we determined the Young’s modulus (E) as a function of different spatially patterned locations having undergone times of UV irradiation (Figure 6B). The Young’s modulus increased linearly from ∼100 to 450 kPa upon increasing UV irradiation time. The tendency for the Young’s modulus of the gel to increase showed the same trend as the macro-rheology measurement. In contrast, the Young ’s modulus for the gel exposed to UV after 24 h remained almost constant. The AFM measurements of gel stiffness provide a clear demonstration that the mechanical properties of our gel system can be spatially controlled by patterning with external light stimuli.

CONCLUSION In conclusion, we have found that an oligomer comprised of calixarene and photosensitive stilbene units could serve as an 4161

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ACS Nano 1758, 1453, 1180, 1095, 1060, 769 cm−1; 1H NMR (300 MHz, DMSO-d6) d ppm 7.07 (d, J = 7.57 Hz, 8H), 6.65 (t, J = 7.49 Hz, 4H), 4.13 (q, J = 7.12, 7.11 Hz, 8H), 3.95 (s, 8H), 3.79 (s, 8H), 1.22 (t, J = 7.12 Hz, 12H); 13C NMR (75 MHz DMSO-d6) δ ppm 169.9, 158.2, 133.8, 130.6, 122.7, 69.8, 60.7, 35.7, 14.5; ESI-MS: Calculated for C44H48O12 [M + Na]+ 791.30, found 791.25; anal. calcd for C44H48O12: C, 68.74; H, 6.29; found: C, 68.72; H, 6.30. Compound 1. A solution of compound 5 (3.5 g, 4.5 mmol) in EtOH (80 mL) was stirred for 12 h at room temperature. The hydrazine monohydrate (4.5 g, 90 mmol) was added to the reaction mixture. The reaction mixture was refluxed for 12 h. The organic solvents were evaporated in vacuo. The crude product was recrystallized in MeOH/ethyl ether (1:1, v/v) to give a white solid 1 as a product in 90% yield (2.91 g). Mp 285−286 °C; FT-IR (KBr): v = 3414, 3397, 3373, 3255, 3019, 2916, 1685, 1617, 1570, 1528, 1459, 1445, 1353, 1323, 1249, 1209, 1191, 1161, 1096, 1060, 1012, 976, 922, 856, 772, 691, 629, 570, 555, 513, 435 cm−1; 1H NMR (300 MHz, DMSO-d6) δ ppm 7.29 (s, 4H), 7.04 (d, J = 7.55 Hz, 4H), 6.81 (t, J = 7.46 Hz, 4H), 4.14 (d, J = 3.81 Hz, 8H), 4.03 (s, 8H), 3.89 (s, 8H); 13 C NMR (75 MHz, DMSO-d6) 167.04, 155.27, 133.85, 129.25, 123.44, 69.15, 36.61; ESI-MS: Calculated for C36H40N8O8 [M + H]+ 713.30 [M + Na]+ 735.29, found 713.25, 735,33; anal. calcd for C36H40N8O8: C, 60.66; H, 5.66; N, 15.72; found: C, 60.64; H, 5.63; N, 15.74. Compound 6. Compound 6 was purchased by Sigma-Aldrich. Compound 2. trans-4,4′-Stilbenedicarboxylic acid (3 g, 11.1 mmol) in SOCl2 (13.3 mL, 111.0 mmol) was refluxed for 1 day at 80 °C. The unreacted SOCl2 was removed in vacuo. Then a solution of 4-hydroxybenzaldehyde (3.41 g, 27.75 mmol) in THF (20 mL) and TEA (4.0 mL) was added and refluxed for 5 h. After filtration of the reaction mixture, the crude product was recrystallized in MeOH to give a yellow solid 2 as a product in 70% yield. FT-IR (KBr): v = 3073, 2827, 2745, 1758, 1681, 1596, 1585, 1500, 1455, 1424, 1391, 1320, 1305, 1247, 1122, 1072, 970, 961, 904, 763, 693, 525 cm−1; 1H NMR (300 MHz, DMSO-d6) δ ppm 10.047 (s, 2H), 8.19 (d, J = 8.1 Hz, 4H), 8.053 (d, J = 8.40 Hz, 4H), 7.927 (d, J = 8.4 Hz, 4H), 7.611(s, 2H), 7.584 (d, J = 8.4 Hz, 4H); 13C NMR (75 MHz, DMSO-d6) 190, 164, 158, 140, 133, 130, 129, 126, 125, 121; ESI-MS: Calculated for C30H20O6: [M + H]+ 477.09, [M + Na]+ 499.17, found 477.11, 499.18; anal. calcd for C30H20O6: C, 75.62; H, 4.23; found: C, 75.64; H, 4.20. General Characterization. 1H and 13C NMR spectra of the samples were gained by using a Bruker ARX 300. IR spectra were carried out with a Shimadzu FTIR 8400S instrument. A Hitachi U2900 was used to determine the optical absorption spectra. A JEOL JMS-700 mass spectrometer was used to get the mass spectra. All fluorescence spectra were measured in a RF-5301PC spectrophotometer. The X-ray powder diffraction (XRPD) experiments were performed in transmission mode with a Bruker GADDS diffractometer equipped with graphite monochromatic Cu Kα radiation (λ = 1.54073 Å). Rheological Properties. Rheological tests were carried out by using an AR-2000ex (TA Instruments Ltd., New Castle, DE, USA). Plate type was implemented with a 40 mm diameter parallel plate that was attached to a transducer. The gap was 1.0 mm. Strain sweep tests were performed with increasing amplitude oscillation up to 1000%. Frequency sweeps were measured from 5 to 1000 Hz. The recovery properties of the gels in response to applied shear force were investigated with the following 1500 s procedure: 0.1% (300 s) → 100% (300 s − 600 s) → 0.1% (600 s − 900 s) → 100% (900 s − 1200 s) → 0.1% (1200 s − 1500 s). SAXS Measurement. SAXS experiments were carried out at the BL40B2 station at SPring-8 in Japan. At BL40B2 station, the camera length and the X-ray wavelength were adjusted to 125 cm and 1.0 Å, respectively. The scattering intensity was accumulated for 300s in the range of q = 0.12−10 nm−1 with Rigaku R-AXIS IV++ system (30 cm × 30 cm imaging plate). The samples were loaded between peek film, and then the cell sealed with epoxy adhesive. Characterization of Gel Stiffness by AFM. We characterized the gel stiffness by the Young’s modulus (E). Values of the spatiallydependent moduli of the stiffness-gradient gels were measured by

AFM, using a Bioscope Catalyst NanoScope V device (Bruker, Santa Barbara, CA) attached to an inverted optical microscope (LX71, Olympus, Japan). The gels were probed with a V-shaped cantilever (MSCT, pyramidal tipped, nominal k = 0.05 N/m; Bruker) whose spring constant was calibrated by the thermal fluctuations method.52,53 The relationship between photodiode signal and cantilever deflection was computed from the slope of the force displacement curve obtained at bare region of the coverslip. For each gel point, we acquired ten force−distance (FD) curves (where F = kd, where d is the deflection of the cantilever) by monitoring F and D while the piezo translator was ramped forward and backward at constant speed (5 μm amplitude, 1 Hz and ∼500 nm of indentation, less than the tip height which was 2.5 μm). The Young’s modulus was calculated as reported previously in literature.37 Preparation of Supramolecular Gels. Compounds 1 (15 mg, 42 mmol) and 2 (13 mg, 42 mmol) were dissolved in DMSO (0.5 mL). The samples were then prepared in the presence of 5 μL of 12 M HCl. The supramolecular gels were formed after simple mixing and incubation at room temperature. Irradiation of Supramolecular Gels. Cross-linked gels were placed onto a circular quartz dish with a radius of 1 cm. The dish was covered with a quartz lid to prevent the gel from drying out. A wavelength of 256 nm was used to irradiate the gel samples by a handheld UV lamp. When a mask was used, the shape of the mask was cut out a sheet of black paper and placed over the sample prior to irradiation. Preparation of Film. Compounds 1 (5 mg, 0.1 wt %) and 2 (1.34 mg, 0.1 wt %) were dissolved in DMSO (300 μL). HCl (10 μL of 12M) was added to the reaction mixture. Next, poly(methyl methacrylate) (0.5 g, 10 wt %, Mw 960,000) in DMSO (5 mL) was prepared and added to the reaction mixture at 60 °C for 30 min on the slide glass (10 cm × 5 cm). This glass was dried for 5 h by vacuum condition. Then, the opaque film was obtained. Preparation of Gel Sample for AFM Measurement. Compounds 1 (15 mg, 42 mmol) and 2 (13 mg, 42 mmol) were dissolved in DMSO (0.5 mL). The reaction mixture was dropped (50 μL) onto a silicon wafer (1 cm × 1 cm). After 24 h, the gel formed on the silicon wafer was exposed to UV light for different times (6 h, 9 h, 12 h, 15 h, 18 h, and to 24 h) with a photomasking technique.

ASSOCIATED CONTENT S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.7b00997. 1 NMR, SEM, XRPD, SAXS, and rheology measurements of calix[4]arene-based gel (PDF) Movie S1: UV exposed gels treated with DMSO solvent, which eliminated the green fluorescence due to disassembly of the J-aggregates; however, the blue fluorescence remained unaffected by the presence of solvent (AVI) Movie S2: Shape changes and resulting cleavage of the gel at the site that had not undergone UV irradiation (AVI)

AUTHOR INFORMATION Corresponding Authors

*E-mail: *E-mail: *E-mail: *E-mail:

[email protected]. [email protected]. [email protected]. [email protected].

ORCID

Ji Ha Lee: 0000-0002-4456-0128 Shim Sung Lee: 0000-0002-4638-5466 Jong Hwa Jung: 0000-0002-8936-2272 4162

DOI: 10.1021/acsnano.7b00997 ACS Nano 2017, 11, 4155−4164

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ACS Nano Author Contributions

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J.H.L. contributed to the project design and performed the preparation of gel, UV and fluorescence property, rheology properties, and SEM images. S.H.J. performed the film state experiment. S.S.L. contributed to the NMR experiment. K-.Y.K. carried out AFM measurement. K.S. contributed to the SAXS experiment. J.H.J. and J.J. conceived the methodology and supervised the project. Notes

The authors declare no competing financial interest.

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