Jana
Schiller
a,
Juan V.
Alegre-Requena
ab,
Eugenia
Marqués-López
b,
Raquel P.
Herrera
b,
Jordi
Casanovas
c,
Carlos
Alemán
d and
David
Díaz Díaz
*ae
aInstitut für Organische Chemie, Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany. E-mail: David.Diaz@chemie.uni-regensburg.de; Fax: +49 941 9434121; Tel: +49 941 9434373
bLaboratorio de Organocatálisis Asimétrica, Departamento de Química Orgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
cDepartament de Química, EPS, Universitat de Lleida, Jaume II 69, 25001 Lleida, Spain
dDepartament d'Enginyeria Química – ETSEIB and Center for Research in Nano-Engineering, Universitat Politècnica de Catalunya, Av. Diagonal 647, 08028 Barcelona, Spain
eIQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain
First published on 11th April 2016
Chiral N,N′-disubstituted squaramide 1 has been found to undergo self-assembly in a variety of alcoholic solvents at low concentrations leading to the formation of novel nanostructured supramolecular alcogels. The gels responded to thermal, mechanical, optical and chemical stimuli. Solubility studies, gelation ability tests and computer modeling of a series of structurally related squaramides proved the existence of a unique combination of non-covalent molecular interactions and favorable hydrophobic/hydrophilic balance in 1 that drive the anisotropic growth of alcogel networks. The results have also revealed a remarkable effect of ultrasound on both the gelation kinetics and the properties of the alcogels.
Within this context, hierarchical gel-based materials have received increasing attention over the last decades16–27 due to their unique architectures and potential for high-tech applications in numerous fields including, among others,28–32 the fabrication of sensors,33 liquid crystals,34 electrically conductive scaffolds,35,36 templates for the growth of cells and inorganic structures,37,38 chemical catalysis,39 as well as in cosmetic and food industries.16 In contrast to chemical gels40–42 that are based on covalent bonds, (e.g., cross-linked polymers), physical gels1,43–50 are typically made of low molecular weight compounds self-assembled through non-covalent interactions (e.g., hydrogen-bonding, van der Waals, charge-transfer, dipole–dipole, π–π stacking and coordination interactions), which usually provides reversible gel-to-sol phase transitions as response to environmental stimuli.51,52 Systems based on both types of connections are also known.53,54 The solid-like appearance and rheological properties of the gels result from the immobilization of the liquid (major component) into the interstices of a solid matrix (minor component) through capillary forces.51,55 The formation of the 3D-network with numerous junction zones56,57 is a consequence of the entanglement of 1D-polymeric strands of gelator molecules16 typically of nm diameters and μm lengths.58,59
Herein, we report the unprecedented self-assembly properties of a chiral squaramide in numerous alcoholic solvents leading to the formation of multistimuli-responsive supramolecular alcogels. The remarkable effect of ultrasound during the preparation of the gels as well as the plausible gelation mechanism supported by quantum mechanical calculations are also discussed. This work expands the applications of squaramides towards materials synthesis.
FTIR spectra were recorded using an Agilent Carry 630 spectrophotometer (Universität Regensburg) spectrophotometer.
Morphological characterization of the bulk samples was carried out by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). (a) FESEM: images were obtained with a Carl Zeiss Merlin field emission scanning electron microscope (0.8 nm resolution) equipped with a digital camera (SAI, Universidad de Zaragoza) and operating at 3 kV and 158 pA. Sample preparation: xerogel specimens were prepared by freeze-drying. Prior to imaging, a 5 nm sized Pt film was sputtered (40 mA, 30 seconds) on the samples placed on carbon tape. (b) TEM: images were recorded using a JEOL-2000 FXII transmission electron microscope (0.28 nm resolution) equipped with a CCD Gatan 694 digital camera (SAI, Universidad de Zaragoza) and operating at 200 kV (accelerating voltage). Sample preparation: 10 μL of the gel suspension was allowed to adsorb onto carbon-coated grids (300 mesh, from Aname). The grid was placed over a piece of filter paper in order to absorb the excess of solvent. (c) AFM: imaging was performed on a Multimode 8 (Bruker) instrument (LMA-INA, Zaragoza) in tapping mode at 0.5 Hz scanning rate using freshly cleaved mica surface as substrate and a single crystal silicon tip (TAP150A, 0.01–0.025 Ω cm, Antimony doped Si) at 128–152 kHz drive frequency. Drive amplitude ranged from 300 to 400 mV. Sample preparation: 10 μL of the alcogel suspension (ca. 5-fold dilution in MeOH) was placed on the substrate and homogeneously dispersed to form a thin layer that was allowed to dry in air overnight before measurement.
The growth of crystals in the gel phase was monitored using a Wild Makroskop M420 optical microscope equipped with a Canon Power shot A640 digital camera (Universität Regensburg). A polarization filter was used to observe the birefringence of the gels under polarized light.
Temperature-dependent 1H-NMR studies were carried out on a 400 MHz Bruker Avance instrument (Universität Regensburg) equipped with a BVT 2000 heating system (Bruker BioSpin GmbH).
Powder X-ray diffraction (PXRD) patterns were collected on a STOE STADI P powder diffractometer (Universität Regensburg) (StartFragment Transmission mode, flat samples, Dectris MYTHEN 1k microstrip solid-state detector) with CuKα1 radiation operated at 40 kV and 40 mA. Conditions: (a) 0.015°, time 1200 s per step, 2 theta range 10–55° (short measurement); (b) StartFragment 0.015°, time 320 s per step, 2 theta range 2–90° (long measurement).
UV-vis spectra were recorded in a Varian Cary 50 Bio UV-visible spectrophotometer.
Critical gelation concentrations (CGC) were determined by adding solvent in several portions (0.1 mL each) into the vial until everything remained dissolved, precipitation and/or gelation took place upon heating–cooling (and/or ultrasound) treatment as described above. The initial concentration for gelation tests was 100 g L−1.
Gel-to-sol transition temperatures (Tgel) were determined by the inverse-flow method by placing the sealed vials containing the organogels into a thermoblock (Fig. S1, ESI†), which was heated up at the rate of 2 °C min−1. In this work, the temperature at which the gel started to break was defined as Tgel. The average values of at least two random experiments were given. These values were correlated with the first differential scanning calorimetry (DSC) endothermic transition of model using a DSC7 (Perkin Elmer) instrument (Universität Regensburg) at a scan rate of 2 °C min−1 under nitrogen atmosphere (gas flow rate = 20 mL min−1). For the measurements, an appropriate amount of gel was placed into a pre-weighted Al pan (Perkin-Elmer), which was sealed and weight on a six-decimal plate balance. The pans were weighted again after each measurement to check for possible leakage.
Entry | Solventa | Phaseb | Optical appearance | CGCe (g L−1) | Gelation timef | T gel (°C) | Procedureh | Temporal stabilityk |
---|---|---|---|---|---|---|---|---|
a Solvent volume = 1 mL. Systematic IUPAC name is provided for each case. b Abbreviations: G = gel; U = undissolved gelator; C = crystals. c Approximately 10% of the total volume remained ungelled. d Cluster of white needles are visible within the fresh gel sample, which turned into a transparent gel after 12 days (vide infra). e Values calculated by the inverse-flow method. Estimated error ± 0.5–1 g L−1. f Abbreviations: h = hour; min = minute; d = day. Unless otherwise noted, estimated error ± 1 min (for gelation times >1 min). g Estimated error ± 2 °C. h The heating–ultrasound treatment for the preparation of gels are highlighted in bold font. i To form this gel it was necessary to predissolve 1 in 20 μL of DMSO. j The sample was pretreated by heating–ultrasound as explain in the Experimental section. k The gels were stable at least for the indicated period. Symbol “>” indicates that the stability could possibly be much longer although it was not monitored. Abbreviation: nd = not determined due to unreliable variables; cryst = cyrstallization. | ||||||||
1 | Methanol | G | Transparent | 7 | 24 ± 2 h | 45 | Heating–cooling | >6 months |
2 | 2-Methylpentan-1-ol | G + U | nd | nd | nd | nd | Heating–cooling | nd |
3 | Butan-2-ol | G | Transparent | 20 | 24 ± 6 h | nd | Heating–coolingi | >4 months |
4 | Ethanol | G | Translucent | 5.8 | 10 min | 46 | Heating–ultrasound | Cryst. after 18 h |
5 | 2-Methylpropan-2-ol | G | Translucent | 3 | 5 min | 57 | Heating–ultrasound | >1 month |
6 | Butane-1,4-diol | G | Translucent | 5.5 | 10 min | 47 | Heating–ultrasound | >1 week |
7 | 2-Methylpropan-1-ol | G | Translucent | 4 | 1 min | 67 | Heating–ultrasound | >1 week |
8 | Phenylmethanol | G | Opaque | 21 | 8 min | 42 | Heating–ultrasound | >2 months |
9 | Acetone | G | Translucent | 7.1 | 1 min | 54 | Heating–ultrasound | >1 week |
10 | 2-Methylbutan-2-ol | G | Translucent | 3.3 | 5 min | 70 | Heating–ultrasound | >2 weeks |
11 | Propan-1-ol | G + C | Opaqued | 5.2 | 2 h | 64 | Heating–cooling | >6 months |
12 | Propan-1-ol | G | Translucent | 5.2 | 5 min | 56 | Heating–ultrasound | >4 months |
13 | Pentane-1,5-diol | G | Opaque | 10 | 15 min | 47 | Heating–cooling | >2 months |
14 | Pentane-1,5-diol | G | Translucent | 6.1 | 12 min | 36 | Heating–ultrasound | >1 week |
15 | Butan-1-ol | G | Transparent | 8.4 | 3.5 ± 0.25 h | 39 | Heating–cooling | >1 month |
16 | Butan-1-ol | G | Transparent | 8.4 | 6 min | 36 | Heating–ultrasound | >1 month |
17 | Hexan-1-ol | G + C | Transparent | 9.1 | 9 min | 35 | Heating–coolingj | >1 week |
18 | Hexan-1-ol | G | Transparent | 7 | 1 min | 75 | Heating–ultrasound | >2 months |
19 | 3-Methylbutan-2-ol | Gc | Transparent | 5 | 20 ± 4 h | nd | Heating–coolingj | >1 month |
20 | 3-Methylbutan-2-ol | G | Translucent | 3.7 | 2 min | 54 | Heating–ultrasound | >2 months |
21 | Pentan-2-ol | G | Transparent | 5.5 | 11 ± 1 d | 81 | Heating–cooling | >1 month |
22 | Pentan-2-ol | G | Transparent | 5.0 | 1 min | 65 | Heating–ultrasound | >2 months |
23 | 2-Methylbutan-1-ol | G + C | Transparent | 4.7 | 2.3 ± 0.15 h | 65 | Heating–cooling | Cryst. during gelation |
24 | 2-Methylbutan-1-ol | G | Translucent | 3.9 | 2 min | 53 | Heating–ultrasound | >1.5 months |
Complexes formed by two interacting molecules (dimers) were considered for model squaramides 1, 3, 7, 8 and 10. For this purpose, around 50 starting geometries were constructed for each dimer by varying the relative position between the two interacting molecules. Accordingly, the formation of different specific and non-specific intermolecular interactions, as well as different geometries for each of such interactions, were considered. All these starting arrangements were submitted to geometry optimization at the PCM-M06L/6-31+G(d,p) level. Interaction energies (ΔEi) were corrected with the basis set superposition error (BSSE) by means of the standard counterpoise (CP) method.69 Calculations were performed using the Gaussian 0970 computer package.
In this context, unsymmetrical substituted squaramide 1 was easily accessible following our own developed procedure in a one-pot synthesis using equimolar amounts of commercially available 3,4-dimethoxycyclobut-3-ene-1,2-dione (11), 4-tert-butylaniline (12a) and N-((1R,2R)-2-aminocyclohexyl)-4-methylbenzenesulfonamide (13a) in methanol at room temperature (Scheme 1). After 4 hours of reaction, squaramide 1 was obtained in very good yield (80%) after simple filtration as a powdered material with mesoscale ordering as indicated by PXRD analysis (Fig. S16, ESI†).
To correlate the structural functionalities of 1 with its gelation properties, we designed and synthesized the library of squaramides outlined in Fig. 1. Specifically, different analogous squaramides 7–10 were designed by incorporating substituents with different steric and electronic properties, following the same synthetic procedure.60,71 For this purpose, squaramides 7 and 9, with electron-withdrawing groups, or squaramide 8 with an electron-donating substituent in the aromatic ring, or 10 in the absence of the aromatic ring, were synthesized with the aim of modifying the basicity and/or conferring distinctive solvation properties to these organic compounds, which is believed to play a key role on the gelation phenomena.16–27 In all these cases (1, 7–10), the stereochemical configuration and the structural core were maintained. Moreover, squaramides 2 and 3 were included for comparison with 1, since we also observed that the viscosity of MeOH increased during their preparation. Additionally, and encouraged by our last work with urea-based compounds as efficient gelators,74 we also carried out the preparation of squaramide 4, which is the equivalent squaramide to the best urea compound used in our previous work.74 Related with compound 4, squaramide 5, lacking the substituent in the aromatic ring, or 6, bearing a methoxy group, were also explored.
All synthesized squaramides 1–10 were appropriately characterized after purification by a simple and straight filtration (see Experimental section).
The gel nature of the samples was initially confirmed by the absence of flow upon turning the vial upside-down and further confirmed by oscillatory rheological measurements in model solvents (vide infra). The critical gelation concentration (CGC) values estimated for the gels obtained with 1 ranged between 3 and 21 g L−1 (see the Experimental section for the procedure). These values indicate that hundreds or thousands of solvent molecules are immobilized per gelator molecule (e.g., the highest solvent/gelator ratio ∼ 1750:1 was obtained in methanol). As far as we are aware, the only precedent in the literature describing the formation of an organogel with squaramides corresponds to a recent report from Ohsedo and co-workers15 describing a series of squarylium monoalkylamides and dialkylamides. Therein, gelation was only observed in DMF (forming opaque gels) and in some cases only after cooling down the mixture to −15 °C.
Stable gels were classified in 3 different groups depending on the experimental protocol that was used for their preparation. The first group could only be formed by the classical heating–cooling protocol (entries 1–3), the second group could only be formed by applying heating and subsequent ultrasound treatment (entries 4–10) and the third group could be formed by any of these two methods (entries 11–24). Thus, ca. 47% of the obtained gels could be formed by heating–cooling, whereas ca. 82% could be prepared by a heating–ultrasound protocol (bold text). Although there is not an apparent correlation between the type of alcohol and the gel preparation method, heating followed by ultrasound was found to be a very convenient technique for the gelation of branched alcohols within minutes regardless the degree of substitution at the α-carbon. Based on these groups, we selected one model solvent of each group (i.e., methanol, phenyl methanol and hexan-1-ol) for further characterization and comparisons. So obtained alcogels displayed different degree of translucency (Fig. 2). Such optical differences indicate the formation of aggregates of different sizes.
Fig. 2 Representative photographs of upside-down vials containing organogels made of gelator 1 in different alcohols prepared at the corresponding CGC (Table 1) via heating–cooling (H-C) or heating–ultrasound (H-U). |
Ultrasound-induced gelation (sonogelation), mainly by solvent cavitation, has attracted much attention over the last few years.75–78 During our work we found that the application of ultrasound after heating not only allowed the fabrication of stable gels that could otherwise (i.e., via heating–cooling) not be formed, but also decreased the gelation time drastically (e.g., entries 11, 15, 19, 21, 23 vs. entries 12, 16, 20, 22, 24, respectively). The most impressive case was pentan-2-ol that needed more than 10 days to be gelled by heating–cooling and only 1 min by heating–ultrasound even at lower concentration (entry 21 vs. entry 22). This is very appealing since the application of ultrasound to an already isotropic solution seems counterintuitive. However, sonication of the hot clear solution prior gelation may hinder the self-assembled system (non-entangled nanofibers) to fall into its lowest energy level making possible the formation of new gel networks. In addition, both the CGC was reduced in practically all cases in which the heating–ultrasound protocol was used instead of heating–cooling. This was also accompanied by certain reduction of the Tgel values. The case of hexan-1-ol should not be considered prematurely as an exception because the heating–cooling protocol gave a combination of gel and crystals (entry 17 vs. entry 18). Remarkably, the dynamic nature of the gels was evidenced by a gradual increase over time of the Tgel for the gel prepared by heating–ultrasound reaching eventually the same value obtained by heating–cooling (i.e., Tgel (fresh gel made in propan-1-ol) = 56 °C; Tgel (3-month old gel made in propan-1-ol) = 63 °C). As observed with the solid squaramide gelator 1, the xerogels obtained by freeze-drying the corresponding alcogels were found to have mesoscale ordering as demonstrated by PXRD analysis (Fig. S16 and Table S2, ESI†). However, clear differences were observed between both spectra. The peaks observed for the solid sample (i.e., as synthesized 1) are centered at 2θ = 4.41°, 6.71°, 11.51°, 16.35° and 17.90°, corresponding to lattice spacings d of 20 Å, 13.16 Å, 7.68 Å, 5.42 Å and 4.95 Å, respectively (calculated from Bragg's law). In contrast, the peaks centered at 11.51° and 17.90° disappeared completely in the xerogel sample, whereas all other peaks slightly shifted to low angles (i.e., 3.96°, 6.18° and 15.70°, respectively; these peaks correspond to d values of 22.28 Å, 14.3 Å and 5.64 Å, respectively). This suggests that the interactions of the solvent molecules with the gelator (or gelator-based aggregates) during gelation cause disorder and expansion of the potential crystal packing of the gelator, at least to some extent.
In addition, UV-vis analysis during the sol-to-gel transition did not show a shift of the absorption maximum (Fig. S17, ESI†), suggesting that the aggregation mode of 1 in solution (and probably in the solid state, vide infra) resembles that in the gel phase.
As usually observed in physical gels, Tgel values increased as the gelator concentration increased until reaching a plateau before visible crystal nucleation. For example, Tgel of the gel made in methanol increased ca. 23 °C upon increasing ca. 3-fold the concentration of 1 with respect to the CGC (7 g L−1). Crystal formation was observed over 22 g L−1 within 10 min (Fig. 4). Although these results might be in agreement with the formation of more entangled networks at higher gelator concentrations, the change in Tgel is likely due to solution thermodynamics where the phase boundary, or liquidus line, increases at low concentration and levels off at higher concentration.
Fig. 4 Phase diagram and variation of Tgel as a function of the concentration of gelator 1 in methanol. |
Very interestingly, in several cases we have observed an enhancement of both the gelation kinetics and the gel stability when the gels were reformed after being thermally destroyed for the first time. We believe that the gel-to-sol thermal transition could be controlled to avoid the complete dissociation of the supramolecular network (even when behaving as a fluid from the rheological standpoint). This could preserve the thermodynamically more stable aggregates through a self-sorting mechanism, thus providing a more robust starting platform for rebuilding the gel structure. We believe that such “preformation hypothesis” could be more general and become an important contribution to the gelation theory. We are currently studying this in detail and we will publish our results at due course.
On the other hand, gel-to-crystal transitions have been previously related to Ostwald rule of stages.80,81 The subtle equilibrium between the metastable gel phase and the thermodynamically stable crystalline phase82–85 could also be monitored in several of our alcogels. For instance, macroscopic crystallization in the form of long needles was observed first at the interface between air and the developing gel phase made of 1 in 2-methylbutan-1-ol, hexan-1-ol or propan-1-ol via heating–cooling (Fig. 5). Nevertheless, the robustness of the gel phase allowed in most of the cases the coexistence of crystalline and gel phases for at least one month supporting the inversion of the test tube. In general, the alcogels prepared via heating–ultrasound remained stable for several months without visible crystallization when stored in dark at room temperature.
Fig. 5 (A) Digital photograph showing crystal growth in the gel made of 1 in 2-methylbutan-1-ol (c = 4.7 g L−1) by heating–cooling. (B) Optical microscope picture of the crystals observed in (A). (C) Gradual crystal growth observed during the gelation of hexan-1-ol using 1 (c = 9.1 g L−1) and the heating–cooling protocol. The gelator concentration corresponds to the CGC (Table 1). |
Although gel-to-gel transitions have already been reported,86–89 it is still a rare phenomenon. The gels made in phenylmethanol showed an optical transition from transparent to opaque within 30 min at the CGC (Fig. 6A). This behavior is typically observed during the growth of fibrilar aggregates over time. Intriguingly, the uncommon opposite phenomenon was observed with the alcogel prepared in propan-1-ol by heating–cooling. In this case, initial macroscopic crystallization was observed during the gelation process leading to a transient opaque gel, which turned into a thermodynamically stable transparent gel within 12 days (Fig. 6B). However, additional detailed experimentation to determine the exact packing arrangement of the gelator molecules, and prove its gradual change, is still necessary in order to confirm the apparent gel-to-gel transition in this case.
Fig. 6 (A) Transparent-to-opaque transition recorded for the gel made of 1 in phenylmethanol (c = 21 g L−1) within 30 min after gel formation via heating–ultrasound. (B) Opaque-to-transparent transition observed in the gel made of 1 in propan-1-ol (c = 5.2 g L−1) within 12 days after gel formation via heating–cooling. The concentrations of gelator correspond to the CGC (Table 1). |
Fig. 7 Influence of enantiomeric purity of gelator 1 on its gelation ability in methanol (c = 7 g L−1) monitored over time. Enantiomeric excesses are given in percentages. |
On the other hand, temperature-dependent 1H-NMR experiments could provide additional information regarding phase interconversions. However, it should be noted that NMR signals of gelator molecules are unlikely to be observed in the gel phase due to long correlation times. Therefore, the observed signals are typically ascribed to small amounts of gelator molecules dissolved in the immobilized solvent.91,92 Preliminary NMR measurements of the alcogel made of 1 in d4-methanol with increasing temperature from 25 °C to 60 °C showed gradual chemical shifts (δ) of almost all protons of 1 suggesting at least conformational changes and/or expected modification in the aggregation pattern (e.g., through hydrogen bonding, π-stacking and/or electrostatic interactions) (Fig. S6, ESI†).
In contrast to the PXRD pattern of compound 1, non-gelators 2–10 showed additional peaks after 17° (Fig. S16 and Table S2, ESI†). Some of these compounds showed even higher crystallinity than the squaramide gelator 1 (e.g., compounds 5, 7). On the other hand, the two major peaks at low angle (around 4° and 6°) found in the xerogel of 1 do not appear in the other solid compounds, except compound 7 that also showed two peaks in the same region as well as the new additional peaks at higher angle. In other compounds (e.g., compounds 6, 8) only one of the two mentioned peaks was present together with the additional peaks at higher angle. Thus, although we can not provide a unique reason why squaramide 1 is the only one that forms gels, it seems that the complex gelation phenomenon, frequently defined as a “frustrated crystallization”, finds here a unique example, where both the structure of the gelator and the solvent must play a crucial and synergistic role in turning the phase balance towards gelation in the case of compound 1vs.2–10.
In order to gain a clearer insight into the potential aggregation mode of 1 and its unique gelation ability, comparative PCM-M06L/6-31+G(d,p) calculations in methanol were carried out on model dimers of 1, 3, 7, 8 and 10. It should be remarked that this methodology, which is not appropriated to evaluate why only alcohols and acetone give gels, is suitable to describe precisely specific interactions and evaluate differences among the interaction patterns in the different dimers. Moreover, 1, 3, 7, 8 and 10 are similar enough to represent the solvent using a polarized continuum dielectric medium, like the PCM one. Accordingly, these calculations do not intend to ascertain the role of the solvent in the gelation mechanism but differences among molecules in a given solvent. For simplicity, analyses of the results were restricted to the minima of lower relative energy, which correspond to those with more attractive interaction energies (ΔEi). Thus, 13 of the 22 minima obtained for 1 exhibit ΔEi values lower than −6 kcal mol−1. More specifically, ΔEi ranges from −26.1 to −6.1 kcal mol−1 (Fig. 8).
Fig. 8 For the most stable complexes of each family, representation of the interaction energy (ΔEi) of complexes calculated for 1, 3, 7, 8 and 10 with ΔEi ≤ 5.0 kcal mol−1. |
Inspection of the lowest energy dimer (Fig. 9A) revealed that the squaramide moiety of each molecule is involved in different intermolecular interactions. In addition to the conventional N–H⋯O hydrogen bond, which involves the squaramides of the two molecules, this dimer also exhibits stabilizing N–H⋯π and C–H⋯π intermolecular interactions. In addition to such interactions, the two molecules involved in this complex show intramolecular π⋯π stacking interactions, as is illustrated for one of the two monomers (Fig. 9A, right). These attractive interactions involve three aromatic rings forming a multiple phenyl⋯phenyl and squaramide⋯phenyl stacking, which provide extra stability to the complex. Moreover, careful inspection of the complexes ΔEi < −15 kcal mol−1 (9 of the 13 minima represented in Fig. 8) revealed that similar inter- and intramolecular interactions coexist in all cases. However, although in all cases intramolecular interactions involve the stacking of the three aromatic rings, intermolecular interactions typically consists of two CO⋯H–N hydrogen bonds involving the squaramides or a single SO⋯H–N hydrogen bond. This is illustrated in Fig. 9B and C, which display the second (ΔEi = −22.5 kcal mol−1) and third minima (ΔEi = −21.5 kcal mol−1) in the energy ranking, respectively.
Complexes of 3 tend to be stabilized by intermolecular N–H⋯O hydrogen bonds and N–H⋯π interactions, while intramolecular interactions consists of N–H⋯N hydrogen bonds (Fig. 10). It should be noted that, in comparison with 1, the lack of the third aromatic ring absence precludes the formation of intramolecular π⋯π stacking interactions. Comparison of complexes obtained for 1 and 3 suggests that both the lower number of intermolecular hydrogen bonds and the lack of intramolecular π⋯π stacking interactions are responsible for the relatively high ΔEi values and poor stability of the latter with respect to the former.
In comparison with 3, the interaction patterns of complexes derived from 7, 8 and 10 are more similar to those observed for 1, even though there are also some differences among the formers and the latter. Thus, the lower energy complexes calculated for 7 and 10 exhibited two N–H⋯O intermolecular hydrogen bonds (Fig. S19 and S20, ESI,† respectively), while those derived from 8 show only one of such interactions (Fig. S21, ESI†). Furthermore, no N–H⋯π and C–H⋯π intermolecular interactions were detected in 7, 8 and 10. Accordingly, intermolecular interactions seem to be weaker for 8 than for 7, 10 and, specially, 1.
Regarding to intramolecular interactions 7, 8 and 10 display π⋯π stacking, even though they also present some relevant differences. Specifically, such π⋯π interactions are apparently weaker for 7 and 10 than those obtained for 1 and 8. Thus, three aromatic rings participate in each π⋯π interaction identified in complexes of the two latter compounds (Fig. 9 and Fig. S21, ESI†), while only two aromatic rings are involved in those found in the complexes of the formers (Fig. S19 and S20, ESI†). The reduction in the intensity of π⋯π interactions for 7 and 10 has been attributed to the repulsive effects provoked by the fluoride substituents and to replacement of an aromatic ring by an aliphatic chain, respectively. These results clearly indicate that dimers calculated for 1 show a large and complex network of inter- and intramolecular interactions that provides an additional stability to the complex. This network of interactions becomes weaker and smaller for the complexes that involve the rest of compounds and, therefore, such extra stability disappears.
Additional PCM-M06L/6-31+G(d,p) calculations were performed for dimers of 1 in water and chloroform (ε = 4.7 and 78.4, respectively). Results were similar to those obtained in methanol suggesting that the influence of the solvent on the gelation ability of this compound is not due to simple electrostatic effects induced by the polarization of the solvent but to the role of the first solvation shell in the network of inter- and intramolecular interactions discussed above. Unfortunately, continuum models, like PCM, are unable to describe the effects associated to solute⋯solvent interactions in the first solvation shell. Therefore, considering the remarkable selectivity of the gelator for alcoholic solvents, the differences in PXRD patterns (e.g., as synthesized gelator vs. xerogel) and the standard gelation mechanism associated to supramolecular gels,1,43–50 we should not dismiss the potential role of at least some solvent molecules acting, for instance, as bridges between gelator molecules. This has been proved by additional PCM-M06L/6-31+G(d,p) calculations on complexes formed by two interacting molecules of 1 and two methanol molecules positioned between them (Fig. S22, ESI†). It is worth noting that each molecule of 1 interacts simultaneously with methanol and with the second molecule of 1. Unfortunately, the theoretical methodology used in this work is suitable to examine the ability of the different compounds to form intermolecular interactions but it is not appropriated for a systematic exploration of this bridge-like gelation mechanism. Thus, due to the huge number of possibilities, other theoretical approaches based on statistical sampling procedures would be more appropriated for such purpose.
Fig. 11 Representative FESEM images of the xerogels prepared by freeze-drying of the corresponding organogels made of 1 in different solvents at their CGC (Table 1). (A) Methanol (heating–cooling, c = 7 g L−1), (B) phenylmethanol (heating–ultrasound, c = 21 g L−1), (C) hexan-1-ol (heating–ultrasound, c = 7 g L−1) and (D) hexan-1-ol (heating–cooling, c = 9.1 g L−1). Note: the selected images are representative of the bulk material. For additional images see ESI.† |
Fig. 12 Representative TEM images of xerogels of the corresponding organogels made of 1 in different solvents at the CGC (Table 1): (A) methanol (heating–cooling, c = 7 g L−1), (B) hexan-1-ol (heating–ultrasound, c = 7 g L−1). Note: the selected images are representative of the bulk material. For additional images see ESI.† |
As expected, complementary fibril structures with average heights between ca. 4 nm and 10 nm were also observed by atomic force microscopy (AFM) (Fig. 13). Certain fiber helicity was detected by FESEM and AFM imaging (Fig. S10, ESI†). Although we have recorded images of the nanostructures by different techniques in order to identify any possible artifact, it should be emphasized that important changes in the structures could occur during preparation of the samples and, therefore, the interpretation of the images should always be done carefully without overselling.
Fig. 13 Representative AFM images of the gel made of 1 in methanol (heating–cooling) at the CGC (c = 7 g L−1). Note: the selected images are representative of the bulk material. For additional images see ESI.† |
In addition, the anisotropic and thermoreversible features of the alcogels allowed turning on/off their birefringence under polarized light (Fig. S11, ESI†). The ability to control the refractive index of soft materials constitutes an important property for applications in optical devices.93
Fig. 14 Representative oscillatory rheological plots of the model gel made of 1 in methanol at CGC (c = 7 g L−1). Top: DFS experiment. Bottom: DSS experiment. |
Furthermore, these gels were also found to be thixotropic,94 a key property for real-life applications of many gel-based materials.95 This behavior was confirmed by a three-steep rheological loop test consisting of (1) application of shear strain as defined by DTS experiments (G′ > G′′), (2) subsequent increase of the strain until the gel collapses (G′ < G′′) and (3) return to the starting strain value (G′ > G′′). Full recovery of the gel strength was observed within seconds after each cycle (Fig. 15). This self-healing behavior was also macroscopically observed upon vigorous shaking of the vial containing the bulk gel followed by a resting period (Fig. S18F, ESI†).
This work opens new possibilities for the use of squaramides in materials synthesis beyond their classical applications in catalysis, sensors and medicine. However, additional examples of other squaramide-based gelators with broader gelation abilities and higher mechanical stabilities are still necessary in order to establish the real potential of this building block for the preparation of supramolecular gels. Investigations related to the described “preformation hypothesis” within the overall gelation theory for similar systems, as well as the study of the apparent gel-to-gel transitions are currently underway in our laboratories and the results will be published at due course.
Footnote |
† Electronic supplementary information (ESI) available: Spectroscopy, rheology, additional experimental and calculation details, pictures and tables. See DOI: 10.1039/c5sm02997j |
This journal is © The Royal Society of Chemistry 2016 |