Helicity Inversion of Supramolecular Hydrogels Induced by Achiral

Nov 15, 2017 - The association–dissociation process of a chiral self-assembly is ..... by the National Natural Science Foundation of China (21628401...
10 downloads 0 Views 5MB Size
Download PDF
Helicity Inversion of Supramolecular Hydrogels Induced by Achiral Substituents Guofeng Liu,†,⊥ Xin Li,‡,⊥ Jianhui Sheng,†,§ Pei-Zhou Li,† Wee Kong Ong,† Soo Zeng Fiona Phua,† Hans Ågren,‡ Liangliang Zhu,§ and Yanli Zhao*,†,∥ †

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371 Singapore ‡ Division of Theoretical Chemistry and Biology, School of Biotechnology, KTH Royal Institute of Technology, SE-10691 Stockholm, Sweden § State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, P.R. China ∥ School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798 Singapore S Supporting Information *

ABSTRACT: Probing the supramolecular chirality of assemblies and controlling their handedness are closely related to the origin of chirality at the supramolecular level and the development of smart materials with desired handedness. However, it remains unclear how achiral residues covalently bonded to chiral amino acids can function in the chirality inversion of supramolecular assemblies. Herein, we report macroscopic chirality and dynamic manipulation of chiroptical activity of hydrogels self-assembled from phenylalanine derivatives, together with the inversion of their handedness achieved solely by exchanging achiral substituents between oligo(ethylene glycol) and carboxylic acid groups. This helicity inversion is mainly induced by distinct stacking mode of the self-assembled building blocks, as collectively confirmed by scanning electron microscopy, circular dichroism, crystallography, and molecular dynamics calculations. Through this straightforward approach, we were able to invert the handedness of helical assemblies by merely exchanging achiral substituents at the terminal of chiral gelators. This work not only presents a feasible strategy to achieve the handedness inversion of helical nanostructures for better understanding of chiral self-assembly process in supramolecular chemistry but also facilities the development of smart materials with controllable handedness in materials science. KEYWORDS: achiral substituent, helicity inversion, hydrogel, self-assembly, supramolecular chirality

T

nanostructures triggered by achiral factors during the selfassembly process,7,8,24 although many chirality inversions of supramolecular aggregates have been successfully achieved by changing the chiral structures of amphiphiles,25,26 tuning the sequence of nucleic acids or amino acids,27 and applying an external stimulus such as pH,28 light,29−31 temperature,32−34 solvent,35−40 and metal coordination.41−43 Thus, it is urgently in demand to explore the chirality transfer and handedness inversion of self-assemblies triggered by achiral factors to deepen the understanding of helicity inversion of supramolecular assemblies and the chirality transformation from molecular scale to supramolecular level in self-assembly systems.

he helical chirality of nanoscale architectures in polymer and supramolecular self-assembly systems is important not only for better understanding the role of chirality in medical and biological environments1−4 but also for extending their applications in areas of chiral recognition,5−7 chiroptical switches,8,9 asymmetric catalysis,10,11 and optoelectronics.12−17 To date, numerous right-handed and left-handed helical assemblies have been obtained by molecular selfassembly of either chiral or achiral small molecular building blocks, which are usually indispensable with the participation of chiral components.18−22 However, understanding how achiral factors or guests affect the chirality of supramolecular coassemblies is still in its early stage of study.23 In addition, the underlying mechanism and factors determining the twisting tendency and handedness development from molecular scale to supramolecular level and above have not yet been well understood. Moreover, it remains a great challenge to control the helical sense or even invert the macroscopic chirality of © 2017 American Chemical Society

Received: August 27, 2017 Accepted: November 15, 2017 Published: November 15, 2017 11880

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

www.acsnano.org

Article

ACS Nano

very rare example of the chirality inversion of supramolecular self-assemblies triggered by achiral substituents covalently bonded to phenylalanine acid-based hydrogelators.46

Inspired by appealing chirality features of supramolecular gels where the assemblies are collectively driven by various noncovalent interactions44,45 and the helical handedness of assemblies could be finely controlled, herein, we present an interesting chirality inversion of hydrogels self-assembled from phenylalanine-based gelators before (DPF, LPF, DCHF, and LCHF) and after (DPFEG, LPFEG, DCHFEG, and LCHFEG) modifications with achiral oligo(ethylene glycol) groups. D represents the gelators obtained from D-phenylalanine derivatives, whereas L stands for gelators originated from Lphenylalanine derivatives. As shown in Scheme 1, the

RESULTS AND DISCUSSION D/LPF and D/LCHF centered with 1,4-phenyldicarboxamide bear two L/D-helicogenic phenylalanine motifs and achiral COOH at each terminus of the phenylalanine arms. D/LPFEG and D/LCHFEG were synthesized through the esterification of D/LPF and D/LCHF with achiral diglycol, respectively, according to previously reported procedures.4,47,48 All the synthesized compounds were fully characterized by 1H and 13C NMR spectra as well as high-resolution mass spectrometry (Figures S1−S6). All of them can form self-supportive and homogeneous hydrogels by heating-to-cooling and inversion tests in vials (Figure S7). Circular dichroism (CD) spectra of these hydrogels were first measured at room temperature. As shown in Figure 1a, the CD spectrum of DPF hydrogel displayed an apparently negative dichroic signal at 237 nm and a strong positive CD peak at 268 nm corresponding to the absorption region of 225−300 nm. Compared with the molecular CD spectra (Figure 1c) of DPF and LPF in dilute aqueous solution, both DPF and LPF showed strong signals with positive and negative Cotton effects at 299 nm respectively, that is, at the absorption region of the aromatic unit, indicating the formation of helical superstructures with preferred handedness. Interestingly, the CD spectrum of DPFEG hydrogel showed a positive Cotton effect at 227 nm and a negative Cotton effect at 268 nm (Figure 1b), which revealed distinctly inverted helicity with respect to the one in DPF hydrogel. Thus, an apparent helix inversion occurred between DPF hydrogel and DPFEG hydrogel, although they possess the same helicogenic R-phenylalanine residue. Similarly, the CD spectrum of LPFEG hydrogel presented a strong negative Cotton effect at 227 nm and a positive CD signal at 268 nm, which was opposite to the case of LPF (positive maximum at 237 nm and negative minimum at 268 nm), indicating that the helical sense of the assemblies in LPF hydrogel switched to opposite handedness in LPFEG hydrogel. The contribution of linear dichroism (LD) on the CD signals of

Scheme 1. Schematic Illustration for the Chirality Inversion of Helical Assemblies Obtained between D/LPF and D/ LPFEG as Well as D/LCHF and D/LCHFEG

introduction of achiral oligo(ethylene glycol) groups can trigger apparent chirality inversion of helical nanostructures by either altering achiral substituents or changing absolute configuration of phenylalanine residues in both 1,4-phenyldicarboxamide(short as P) and 1,4-cyclohexanedicarboxamide (short as CH)based hydrogel systems. To the best of our knowledge, this is a

Figure 1. CD and corresponding UV absorption spectra of hydrogels of (a) D/LPF, (b) D/LPFEG, (e) D/LCHF, and (f) D/LCHFEG obtained by using a 0.1 mm path length of a quartz cuvette with a gelator concentration of 2.0 mg/mL. CD spectra of (c) D/LPF (0.02 mg/ mL), (d) D/LPFEG (0.02 mg/mL), (g) D/LCHF (0.05 mg/mL), and (h) D/LCHFEG (0.05 mg/mL) in molecularly aqueous solution obtained by using a 10 mm path length of quartz cuvette. 11881

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

ACS Nano

hydrogels, which is similar to the helicity inversion observed in 1,4-phenyldicarboxamide-based hydrogel systems. In addition, the supramolecular chirality inversion of gels was further confirmed by the molecular CD measurements of DCHF and DCHFEG (Figure 1g,h), both of which showed negative Cotton effects around 198 and 214 nm. The chirality inversion effect of the CD signals induced by achiral substituents could also be found between hydrogels of LCHF and LCHFEG. Thus, intriguing chirality inversion indeed occurs between the hydrogels assembled from gelators having carboxylic acid and oligo(ethylene glycol) units with the same chirality of the phenylalanine residue. Considering that the only difference between DPF and DPFEG as well as LPF and LPFEG is the achiral terminal substituents of carboxylic acid and oligo(ethylene glycol) units (similarly in a CH-based gel system), it is reasonably inferred that the helicity inversion of these hydrogels is induced by the alteration of achiral substituents in gelators. To visualize the chirality inversion of helical assemblies, scanning electron microscopy (SEM) experiments of the xerogels (Figure 2 and Figures S9−S16) were conducted.

all the four hydrogels was also studied. The intensity of LD signals (Figure S8) was obviously lower than that of corresponding CD signals, indicating that the LD contribution could be negligible in these hydrogels. To correlate the CD spectra between hydrogel and solution phases, all of the samples (D/LPF, D/LPFEG) were subjected to molecular CD measurements in their dilute aqueous solutions with the gelator concentration of 0.02 mg mL−1. For the CD spectrum of the DPF molecule in aqueous solution, negative, positive, and positive Cotton effects were observed at 218, 235, and 258 nm, respectively (Figure 1c). Consistent with our expectation, the CD spectrum of the DPFEG molecule in aqueous solution was very similar to the CD spectrum of DPF, in which a negative Cotton effect occurred at 217 nm and two positive Cotton effects appeared at 235 and 252 nm (Figure 1d). This observation means that there was almost no obvious difference of molecular chirality in CD spectra between DPFEG and DPF as the alteration between carboxylic acid and ester group did not induce observable changes of the UV absorption (both of them showed the same UV absorption peak around 250 nm with similar intensity). Similarly, the CD spectrum of the LPFEG molecule in aqueous solution displayed positive, negative, and negative Cotton effects at 217, 235, and 252 nm, respectively, which is also analogous with molecular CD signals of LPF, as illustrated in Figure 1c. There are obvious differences of the CD signals between hydrogel and solution phases. Taking DPFEG as an example (Figure 1b,d), the CD spectrum of the DPFEG molecule in dilute aqueous solution (0.02 mg mL−1) displayed negative, positive, and positive Cotton effects at 217, 235, and 252 nm, respectively, whereas the CD spectrum of the DPFEG hydrogel (2.0 mg mL−1) exhibited shifted positive and negative Cotton effects at 227 and 268 nm, respectively. Meanwhile, the CD signal intensity of the hydrogel is almost 100 times higher than the corresponding molecular signal intensity in the region of 220−300 nm. By contrast, the molecular CD spectrum of DPF in aqueous solution showing negative, positive, and positive Cotton effects at 218, 235, and 258 nm is similar to the CD spectrum of DPF hydrogel displaying negative and positive dichroic signals around 237 and 268 nm, except for an obvious difference in the signal intensity. These observations suggest that the chiroptical activity of monomers ended with carboxylic acid and oligo(ethylene glycol)ester groups is almost identical in molecular CD spectra when they possess the same chiral phenylalanine residue. However, after the gelation, the CD spectrum of DPFEG presented changes in both the intensity and property of the Cotton effects. To study if this interesting substituent effect is also applicable to other systems, hydrogels self-assembled from DCHF, LCHF, DCHFEG, and LCHFEG centered with the 1,4-cyclohexanedicarboxamide unit were also investigated in detail. As shown in Figure 1e, the CD spectrum of DCHF hydrogel displayed negative, negative, and positive Cotton effects around 199, 216, and 235 nm, respectively, related to the UV absorption region of 190−250 nm. Compared with the DCHF hydrogel, a perfect mirror-imaged CD curve was observed from the LCHF hydrogel. By contrast, the CD spectrum of the DCHFEG hydrogel showed positive, negative, and negative Cotton effects around 194, 202, and 250 nm, respectively (Figure 1f). Opposite to positive CD signals of DCHF above 225 nm, DCHFEG hydrogel showed well-defined negative Cotton effects. These observations indicate that supramolecular chirality inversion also occurs between DCHF and DCHFEG

Figure 2. SEM images of helical fibers obtained from xerogels. (a) Left-handed (M) helical nanofibers of DPF with a pitch of ∼100 nm (inset). (b) Right-handed (P) helical nanofibers assembled from LPF with a pitch of ∼85 nm (inset). (c) P helical nanofibers assembled from DPFEG with a pitch of ∼450 nm (inset). (d) M helical nanofibers assembled from LPFEG with a pitch of ∼500 nm (inset).

The images showed the formation of micrometer-long helical fibers with highly uniform diameters from these hydrogels. As shown in Figure 2a, nanofibers from the DPF gel revealed exclusively left-handed (M-type) twist with a diameter of 36 ± 1 nm and a helical pitch around 100 nm. By contrast, the LPF gel organized into uniformly right-handed (P-type) twist with a diameter of 36 ± 1 nm and a helical pitch of approximately 85 nm (Figure 2b). Interestingly, nanofibers with width of 60−70 nm and pitch of 450−500 nm obtained from DPFEG and LPFEG displayed exclusively right-handed and left-handed twists (Figure 2c,d), respectively, showing opposite handedness to corresponding chiral nanostructures in DPF and LPF (see more detailed morphologies of helical nanofibers in Figures S9−S12). For peptides and amino acid derivatives, the chirality of constituent amino acids is widely regarded as a key factor controlling the handedness of their supramolecular organiza11882

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

ACS Nano tions. According to previous reports,17 specific one-dimensional nanofibers self-assembled from L-phenylalanine-derived gelators normally show left-handedness. Specially, LPF exhibited exclusively right-handed nanofibers with uniform diameter and helical pitch, whereas DPF revealed exclusively left-handed nanofibers. More interestingly, apparently opposite handedness of helical assemblies was observed between DPF and DPFEG hydrogels, although their gelators possess the same R-type chiral center of phenylalanine residue. This helicity inversion was in good correlation with the chirality inversion of chiroptical activity observed in the CD spectra of hydrogels. It should be pointed out that the width and helical pitch of nanofibers between DPF and DPFEG are not the same because these two gelators are not exactly enantiomers. The helical inversion of chiral nanostructures was also found in the xerogels self-assembled from DCHF, LCHF, DCHFEG, and LCHFEG with a 1,4-cyclohexane center. As shown in Figure S13, the left-handed nanoribbons were observed in DCHF with widths varying between 30 and 45 nm and the pitch in the range of 110−130 nm, whereas helical nanoribbons from LCHF displayed completely opposite handedness (Figure S14) but with nearly the same width and pitch with respect to DCHF. To our delight, the handedness of assemblies in DCHF is the same as the one in DPF. More interestingly, right-handed helical nanofibers were observed from SEM images of the DCHFEG hydrogel (Figure S15), showing opposite handedness of helical nanostructures to DCHF. By contrast, LCHFEG presented left-handed helical nanofibers with a width around 50 nm and a helical pitch around 55 nm, as depicted in Figure S16. The results discussed above indicate how slight changes in the molecular structure of building blocks could obviously influence overall supramolecular chirality of corresponding aggregates in hydrogel systems. The chirality of aggregates presented here is not only controlled by the absolute configuration of the phenylalanine residue but also influenced by the achiral substituents covalently bonded at each terminus of gelator structures. These factors collectively play vital roles in guiding these gelators to organize into single-handed helical assemblies and show unexpected chirality inversion. Due to the same R-type phenylalanine stereocenter within DPF and DPFEG, it was reasonably anticipated that the achiral peripheral groups of oligo(ethylene glycol) and carboxylic acid are indispensable for the chirality inversion of selfassemblies between D/LPF and D/LPFEG. To obtain further insight into the helical inversion of hydrogels by the alteration of achiral peripheral groups, dynamic CD spectra of these samples were recorded with the concentration of gelators at 0.4 mg mL−1 in a quartz cuvette with a path length of 1 mm. Since gelators with low concentration can be completely dissolved in water, their CD signals are mainly attributed to the monomeric chirality. For solutions of gelators with higher concentration, gelators could self-assemble into dimers, unidirectional assemblies, or even helical nanofibers, which might present supramolecular chirality of helical assemblies with the chirality amplification.49 The conversion between gelators (monomers) and gels (nanofibers) and the chirality transition between monomeric chirality and supramolecular helicity are illustrated in Scheme 2. Two chiral monomers (m) could aggregate into a dimer (M2) via intermolecular noncovalent interactions, subsequently organize into supramolecular assemblies (Mn), and finally assemble into helical nanofibers displaying the supramolecular chirality. In addition, the heating run for DPFEG in water (0.5 mg mL−1)

Scheme 2. Schematic Representation for the Association− Dissociation Process of a Chiral Self-Assemblya

a

Where m represents monomer, n represents the number of monomers, and Mn represents assemblies aggregated by n monomers.

was carried out to obtain a plot of the fraction of aggregates (αagg) against temperature (Figure S17), where the heating curves (0.5 K min−1) could be fitted with a nucleation− elongation model proposed by van der Schoot, Schenning, and Meijer,50,51 and the elongation temperature (Te) and the enthalpy corresponding to the aggregation process (ΔHe) were calculated to be 337.1 K and −96.7 kJ mol−1, respectively. The association−dissociation process of a chiral self-assembly is reversible as the main driving forces are intermolecular noncovalent interactions (mainly constituted with hydrogen bond interaction here). Thus, the chirality transformation of gel-to-sol could be controlled dynamically by finely tuning the environmental temperature. As presented in Figure 3a, the CD spectrum of DPF sample at 20 °C showed the induction of a positive Cotton effect at higher wavelengths (around 260 and 296 nm) in spectral range of achiral aromatic moieties, indicating the formation of helical superstructures with a preferred handedness. Upon heating, the CD signal at 296 nm with the positive maximum gradually decreased up to 70 °C and completely disappeared upon further heating. The phenomenon demonstrates that the main driving force of helical supramolecular assembly is an intermolecular hydrogen bond interaction. The CD spectrum of the DPF sample at 20 °C is similar to the CD spectrum of the DPF hydrogel shown in Figure 1a. Both of CD curves displayed negative CD signs around 227 nm and positive CD signs at 260 nm. It should be noted that the signal intensity presents some differences because the concentration of the gelator and the path length of measurement cells were different. Interestingly, the Cotton effect bands of the DPF sample at 90 °C revealed obvious blue shifts to 218 and 258 nm, respectively, which are similar to those observed from molecularly dissolved DPF aqueous solution in Figure 1c. It should be mentioned that the CD spectrum of DPF sample at 90 °C still differs a little from that in Figure 1c because some dimers or fine assemblies may remain after the dissociation of most helical superstructures upon heating. This fact was further supported by the spectroscopic investigation shown in Figure 3a, where the negative Cotton effect of the DPF sample at 227 nm at 90 °C still red-shifted with respect to the negative CD signal of molecular DPF at 218 nm shown in Figure 1c. For the DPFEG sample shown in Figure 3c, the CD intensity around 225 and 266 nm weakened gradually upon heating from 20 to 70 °C. The maximum wavelength was blue-shifted, and the maximum intensity of the CD signal was decreased, indicating the gel-to-sol transition. Interestingly, the CD signal at 266 nm with the negative minimum decreased up to 50 °C and completely reversed to a positive Cotton effect of molecular CD signal upon further heating (Figures 3b and 11883

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

ACS Nano

Figure 3. Temperature-dependent CD spectra of (a) DPF, (b) LPF, (c) DPFEG, and (d) LPFEG samples obtained by using a 1 mm path length of a quartz cuvette with a gelator concentration of 0.4 mg/mL in aqueous solution.

S18), which clearly revealed the chirality transformation from the supramolecular level into molecular scale accompanied by the chirality inversion. The chirality inversion was also supported by the transformation of the CD signal at 212 nm from a positive sign to negative minimum upon heating (Figure 3c). Compared with the mere decrease of the CD intensity in the DPF sample, the chirality inversion during the gel-to-sol process in the DPFEG sample fully demonstrates supramolecular helicity inversion between DPFEG and DPF hydrogels, as illustrated in Figure 1a,b. Similarly, the CD signals of LPF at approximately 230, 260, and 296 nm dropped dramatically upon heating to 70 °C (Figures 3b and S18a), whereas for the LPFEG sample, not only the intensity of Cotton effects at 228 and 270 nm decreased gradually as the temperature increase, but also the chirality inversion occurred upon heating to 65 °C (Figures 3d and S18b). Thus, the molecular chirality could be transferred into the helicity of assemblies at supramolecular level accompanied by the chirality amplification during the self-assembly process. In addition, the observed chirality in CD spectra is the collective results of monomers, dimers, assemblies, and helical fibers, which can be reversibly regulated by tuning the system temperature due to the formation and destruction of hydrogen bond interaction. Based on the results discussed above, it was concluded that the intriguing chirality inversion of these assemblies could be undoubtedly attributed to the achiral substituents of carboxylic acid and oligo(ethylene glycol). The chiroptical activity and handedness inversions of helical assemblies might be due to the stacking propensity of gelators induced by these achiral substituents.

To explore the underlying mechanism of the helix inversion and better understand the molecular arrangement of selfassembly, single crystals of DPF and LPF were grown in tetrahydrofuran/para-xylene/H2O (3:5:0.1, v/v/v) solution at room temperature (Figure S19). As shown in Figure 4a, there are two water molecules, one para-xylene molecule, and one LPF molecule in each unit cell of LPF single crystal. The crystal structure and packing diagram of LPF suggest that the main driving forces for the self-assembly are four types of intermolecular hydrogen bond interactions according to the structural parameters (Figure 4b and Table S1). The crystal structure of LPF exhibited that two adjacent central phenyl rings of LPF molecules were perpendicular to each other (Figure S20a), and the two terminal phenyl groups were arranged in a trans fashion as the phenyl group in LPF was nearly parallel to an adjacent para-xylene molecule with the smallest intermolecular distance of about 3.9 Å and was simultaneously close to another adjacent para-xylene molecule with a dihedral angle of 60° (Figure 4b). Along the a−c plane, every two of the adjacent LPF molecules contacted with two water molecules via multiple hydrogen bond interactions. The detailed information on these multiple hydrogen bonds is as follows: each oxygen atom of the water molecule formed two hydrogen bonds with one hydrogen atom from the amide group of an adjacent LPF molecule (N−H···O−H, bond length: 2.975−2.997 Å, Table S1) and with another hydrogen atom from the carboxylic group of the other neighboring LPF molecule (CO−O-H···O−H, bond length: 2.605−2.613 Å, Table S1). The intermolecular hydrogen bonds show antiparallel conformation along the b axis. In addition, two 11884

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

ACS Nano

Figure 4. Single-crystal structures of (a) LPF and (c) DPF obtained from a mixture solution of tetrahydrofuran/para-xylene/H2O (v/v/v, 3:5:0.1) and corresponding packing structures of (b) LPF and (d) DPF stabilized by intermolecular hydrogen bonds (black dashed lines) in the single-crystal state.

hydrogen bond interactions. Since DPF and LPF are enantiomers, the crystal structure and packing diagram of DPF are almost the same as that of LPF (Figure S24b). Thus, exclusively right-handed helical assembly in LPF should result from a special stacking mode of LPF molecules, where they are perpendicular to each other and simultaneously linked by two water molecules via multiple hydrogen bonds. However, we did not obtain the single crystals of DPFEG and LPFEG, probably due to the flexible nature of oligo(ethylene glycol) groups located at the periphery. To further corroborate the chirality inversion triggered by achiral substituents, the general Amber force field (GAFF) was employed to simulate and optimize the dimer structures of LPF and LPFEG. The dimer structure of LPF was extracted from its crystal structure. For the LPFEG dimer, the structure was generated according to a report in the literature.23 Here, we focused our investigation on only the properties of LPF and LPFEG because of experimental mirror-imaged CD spectra between LPF and DPF, as well as DPFEG and LPFEG. The optimized structures of LPF and LPFEG dimers are shown in Figure 5a,b, respectively. In the LPF dimer, the central phenyl rings are nearly perpendicular to each other, and the peripheral phenyl rings are in a “trans” arrangement. In the LPFEG dimer, the two central phenyl rings are almost parallel to each other via a fully overlapped packing arrangement, and the two phenyl rings are in “cis” positions (Figure 5b). This structural difference may be attributed to their different side chains. In the LPF dimer, multiple hydrogen bond interactions are formed between OC of carboxylic acid and H−N of amide

other kinds of intermolecular hydrogen bonds formed between hydrogen atoms of a water molecule and an oxygen atom of the amide group on one side of LPF molecule (HN−CO···H− O−H, bond length: 2.683−2.696 Å) as well as an oxygen atom of the carboxylic group (OC−OH) on the other side of the same LPF molecule (HO−CO···H−O−H, bond length: 2.708−2.710 Å, Table S1). These four types of multiple intermolecular hydrogen bonds are the main driving forces to stabilize the single-crystal framework of LPF (Figures 4b and S21), which enable the stacking of LPF molecules to form a right-handed helix (Figure S20b). Similarly, the crystal structure of DPF is depicted in Figure 4c, which showed a similar unit cell of a single crystal with respect to LPF. The packing diagram of DPF was also stabilized by four kinds of intermolecular hydrogen bonds (N−H···O−H, bond length: 3.055−3.058 Å; CO−O−H···O−H, bond length: 2.619−2.627 Å; HN−C O···H−O−H, bond length: 2.721−2.726 Å; HO−CO···H− O−H, bond length: 2.718−2.728 Å, Figure 4d, Figures S22 and S23, and Table S2), which revealed a left-handed packing mode along the b axis in the single-crystal state (Figure S22b). Furthermore, the self-assembly mechanism of LPF was investigated in both xerogel and single-crystal states by using wide-angle X-ray diffraction (WAXD). Analogous WAXD patterns with peaks at 6.6, 14.6, 16.0, 18.4, 20.4, 21.4, 23.0, and 26.8° were obtained from single-crystal and xerogel states of LPF, although the intensity of signals in xerogel was lower than that of single crystal (Figure S24a). Therefore, a similar stacking mode was assumed for LPF in xerogel and singlecrystal states, which was mainly driven by intermolecular 11885

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

ACS Nano

Figure 5. Optimized structures of dimers of (a) LPF and (b) LPFEG. Both side view and top view are shown. Black dashed lines represent intermolecular hydrogen bonding formed from the self-assembly of LPF and LPFEG gelators. TDDFT calculated CD spectra of (c) LPF and (d) LPFEG dimers.

groups. In the case of LPFEG, more hydrogen bonds are formed between side chains and peripheral phenyl rings, forcing them to stay in the “cis” arrangement. The hydrogen bond interaction also leads to different twisting angles between the central phenyl rings, which are around 90° for the LPF dimer and 60° for the LPFEG dimer. In turn, molecules of LPF or LPFEG stack on top of each other with mutual rotation in a unidirectional mode to form helical fibers. Moreover, timedependent density functional theory (TDDFT) results suggested that such structural difference results in opposite signals in their CD spectra (Figure 5c,d). To gain insight into the electronic excitations occurred in the dimer systems, the participating molecular orbitals were plotted in Tables S3 and S4. In the LPF dimer, the CD signals are mainly contributed by the S2 and S10 states, which correspond to HOMO−2 → LUMO and HOMO−2 → LUMO+1 transitions, respectively. As shown in Table S3, the LUMO and LUMO+1 orbitals of the LPF dimer show significant mixing between the two monomers and exhibit opposite twisting patterns. The LUMO of the LPF dimer, which is lower in energy, shows left-hand twisting, while the LUMO+1 presents right-hand twisting. This different twisting leads to a pair of negative/positive CD signals from longer wavelength to shorter wavelength, which is consistent with the experimental CD spectrum of the LPF hydrogel shown in Figure 1a.

Differently in the LPFEG dimer, the most significant CD signals are contributed by the S6 and S8 states, corresponding to HOMO−1 → LUMO and HOMO−1 → LUMO+1, respectively (Table S4). In contrast to that in the LPF dimer, the LUMO and LUMO+1 of the LPFEG dimer show righthand and left-hand twisting, respectively, leading to a pair of positive/negative CD signals from longer wavelength to shorter wavelength. To our delight, the simulated results are in a good agreement with the experimental results of LPFEG hydrogel shown in Figure 1b. Thus, the calculations fully support experimentally observed helical inversion. What’s more, the calculations also illustrate how distinct CD signals of the assembled structures are arisen from a small change in the twisting angle of the central phenyl rings. Since both LPF and LPFEG possess the same S-type stereocenter within the L-configuration of phenylalanine units, distinctly opposite CD signals between dimers of LPF and LPFEG indicate that their supramolecular self-assembly could lead to the formation of helical aggregates with opposite handedness. According to our experimental results, LPF can assemble into right-handed helical nanofibers, while LPFEG aggregates into left-handed ones. Thus, the intriguing chirality inversion of these helical nanostructures was successfully achieved by the self-assembly of phenylalanine-based gelators with the same molecular chirality, indicating that the supra11886

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

ACS Nano

The gel-like precipitate was collected on a filter, washed with water, and dried in a vacuum oven to afford DCHFEG (2.6 g, 4.0 mmol, 66%). 1H NMR (300 MHz, DMSO-d6, ppm): δ = 1.17−1.25 (m, 4H, CH2), 1.52−1.68 (m, 4H, CH2), 2.06 (m, 2H, CH), 2.85−2.93 (m, 4H, CH2), 3.42−3.49 (m, 12H, CH2), 4.12−4.44 (m, 4H, CH2), 4.43−4.44 (m, 4H, CH2), 7.20−7.27 (m, 10H, Ar−H), 8.17−8.20 (d, J = 8.0 Hz, 2H, CO-NH). 13C NMR (75 MHz, DMSO-d6, ppm): δ = 175.51, 172.18, 137.82, 128.46−129.62, 126.93, 72.77, 68.59, 64.33, 60.65, 53.77, 43.27, 37.06, 28.54. EI-MS for C34H46O10N2 calcd 642.3152; found 643.3216 [M + H]+. LCHFEG. By using a similar procedure mentioned above, LCHFEG was obtained as a white solid (2.8 g, 4.3 mmol, 72%). 1H NMR (300 MHz, DMSO-d6, ppm): δ = 1.14−1.20 (m, 4H, CH2), 1.52−1.69 (m, 4H, CH2), 2.07 (m, 2H, CH), 2.85−2.93 (m, 4H, CH2), 3.43−3.48 (m, 12H, CH2), 4.13−4.14 (m, 4H, CH2), 4.43−4.44 (m, 4H, CH2), 7.20−7.27 (m, 10H, Ar−H), 8.16−8.19 (d, J = 8.0 Hz, 2H, CO-NH). 13 C NMR (75 MHz, DMSO-d6, ppm): δ = 174.63, 171.31, 136.93, 128.68, 127.75, 126.06, 71.90, 67.72, 63.45, 59.78, 52.89, 42.40, 36.20, 27.67. EI-MS for C34H46O10N2 calcd 642.3152; found 643.3254 [M + H]+. Hydrogel Preparation. The DCHFEG hydrogel formed from 0.2 wt % DCHFEG was employed as an example to describe the preparation procedure. DCHFEG (2.0 mg mL−1) was suspended in a septum-capped 4.0 mL glass vial and heated until a homogeneous solution was obtained. The solution was solidified into a hydrogel after standing for an hour at room temperature.

molecular chirality of helical nanostructures is not only controlled by the absolute configuration of phenylalanine residues but also highly influenced by peripherally achiral substituents. It was concluded from these experimental and computational results that the inversion of helical chirality in hydrogels is exclusively induced by the exchange of achiral substituents between carboxylic acid and oligo(ethylene glycol) groups.

CONCLUSIONS In conclusion, the helix inversion of assemblies based on phenylalanine derivatives has been successfully achieved by altering the peripherally achiral groups. The chiral inversion is mainly attributed to the stacking mode of the self-assembled building blocks exclusively triggered by achiral substituents of carboxylic acid and oligo(ethylene glycol), as collectively confirmed by electron microscopy, optical spectroscopy, crystallography, and computational calculations. This study discloses a straightforward approach through the self-assembly of small-molecule-based hydrogelators into helical nanoassemblies together with helical inversion of their handedness and provides a compelling self-assembly mechanism for the development of helical nanostructures with desirable chirality. Having the generality of this approach demonstrated for both 1,4-phenyl- and 1,4-cyclohexane-centered building blocks, it is expected that this approach could be applicable to various building blocks for constructing chiral nanostructures with desired helical topologies. Further investigations using this strategy to design chiral materials would not only bring insights into better understanding of chiral assembly processes in supramolecular chemistry but also be in favor of applying these chiral materials in the fields of asymmetric catalysis and chiroptical switches.

ASSOCIATED CONTENT S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.7b06097. Experimental procedures, characterization spectra, CD and LD spectra, SEM images, crystal structures, PXRD, and computational details (PDF) X-ray data for LPF (CIF) X-ray data for DPF (CIF)

EXPERIMENTAL SECTION DCHF. 1,4-Cyclohexanedicarboxylic acid (1.73 g, 10.00 mmol) was added to dry dichloromethane containing thionyl chloride (20 mL). The reaction mixture was stirred at 100 °C for 4 h. The solvent was evaporated under vacuum, and the residue liquid was collected to give 1,4-cyclohexanedicarbonyl dichloride. 1,4-Cyclohexanedicarbonyl dichloride (2.0 g, 9.66 mmol) in dry dichloromethane (100 mL) was added dropwise to a dichloromethane solution (100 mL) containing Dphenylalaninemethyl ester hydrochloride (5.0 g, 23.18 mmol) and trimethylamine (3.6 mL, 26.00 mmol) in an ice−water bath. After the addition was finished, the solution was stirred at room temperature overnight. The solvent was evaporated under vacuum, and the residue was subsequently dissolved in dichloromethane (100 mL). After being washed with water, the organic phase was dried by anhydrous MgSO4. The organic solvent was removed to give the dimethyl ester of DCHF. For the hydrolysis, aqueous NaOH (10 mL, 2.0 M) was added to a cooled suspension of dimethyl ester having DCHF (5.43 g, 6.14 mmol) in MeOH (20 mL). The mixture was gradually heated to room temperature and stirred for 24 h. A clear solution was then obtained. The solution was acidified with 3.0 M HCl until the pH value was less than 3.0, and gel-like precipitate was formed. The gel phase was filtered, washed with deionized water, and finally dried in a vacuum oven to afford DCHF (2.8 g, 6.0 mmol, 64.4%). 1H NMR (300 MHz, DMSO-d6, ppm): δ = 12.62 (s, 2H, COOH), 8.03 (d, 2H, CONH), 7.22 (m, 10H, Ar−H), 4.40 (s, 2H, CH), 3.05 (m, 2H, CH2), 2.84 (m, 2H, CH2), 2.06 (s, 2H, CH), 1.59 (d, 4H, CH2), 1.19 (d, 4H, CH2). 13 C NMR (75 MHz, DMSO-d6, ppm): δ = 178.52, 175.30, 138.28, 129.57, 128.52, 126.77, 53.57, 43.34, 37.16, 28.50−28.66. EI-MS for C26H30O6N2 calcd 466.2104; found 467.2163 [M + H]+. DCHFEG. DCHF in diglycol (60 mL) was added to concentrated HCl (0.5 mL). The mixture was stirred at 130 °C for 3.5 h, and the achieved clear solution was poured into a water/ice mixture (300 mL).

AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]. ORCID

Guofeng Liu: 0000-0003-1911-8546 Hans Ågren: 0000-0002-1763-9383 Liangliang Zhu: 0000-0001-6268-3351 Yanli Zhao: 0000-0002-9231-8360 Author Contributions ⊥

G.L. and X.L. contributed equally to this work.

Notes

The authors declare no competing financial interest.

ACKNOWLEDGMENTS This research is supported by the Singapore Academic Research Fund (RG112/15, RG19/16, and RG121/16) and partially supported by the National Natural Science Foundation of China (21628401). REFERENCES (1) Aida, T.; Meijer, E. W.; Stupp, S. I. Functional Supramolecular Polymers. Science 2012, 335, 813−817. (2) Roche, C.; Sun, H. J.; Leowanawat, P.; Araoka, F.; Partridge, B. E.; Peterca, M.; Wilson, D. A.; Prendergast, M. E.; Heiney, P. A.; Graf, R.; Spiess, H. W.; Zeng, X. B.; Ungar, G.; Percec, V. A Supramolecular Helix That Disregards Chirality. Nat. Chem. 2015, 8, 80−89. 11887

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

ACS Nano

Assembly with Achiral Molecules. Angew. Chem., Int. Ed. 2016, 55, 2411−2415. (24) Liu, G.; Liu, J.; Feng, C.; Zhao, Y. Unexpected Right-Handed Helical Nanostructures Co-assembled from L-phenylalanine Derivatives and Achiral Bipyridines. Chem. Sci. 2017, 8, 1769−1775. (25) Zhu, X.; Duan, P.; Zhang, L.; Liu, M. Regulation of the Chiral Twist and Supramolecular Chirality in Co-assemblies of Amphiphilic L-glutamic acid with Bipyridines. Chem. - Eur. J. 2011, 17, 3429−3437. (26) Aparicio, F.; Nieto-Ortega, B.; Najera, F.; Ramirez, F. J.; Lopez Navarrete, J. T.; Casado, J.; Sanchez, L. Inversion of Supramolecular Helicity in Oligo-p-Phenylene-Based Supramolecular Polymers: Influence of Molecular Atropisomerism. Angew. Chem., Int. Ed. 2014, 53, 1373−1377. (27) Kashida, H.; Murayama, K.; Toda, T.; Asanuma, H. Control of the Chirality and Helicity of Oligomers of Serinol Nucleic Acid (SNA) by Sequence Design. Angew. Chem., Int. Ed. 2011, 50, 1285−1288. (28) Lin, R.; Zhang, H.; Li, S.; Chen, L.; Zhang, W.; Wen, T. B.; Zhang, H.; Xia, H. pH-Switchable Inversion of the Metal-Centered Chirality of Metallabenzenes: Opposite Stereodynamics in Reactions of Ruthenabenzene with L- and D-Cysteine. Chem. - Eur. J. 2011, 17, 2420−2427. (29) Pijper, D.; Feringa, B. L. Molecular Transmission: Controlling the Twist Sense of a Helical Polymer with a Single Light-Driven Molecular Motor. Angew. Chem., Int. Ed. 2007, 46, 3693−3696. (30) Pijper, D.; Jongejan, M. G. M.; Meetsma, A.; Feringa, B. L. Light-Controlled Supramolecular Helicity of a Liquid Crystalline Phase Using a Helical Polymer Functionalized with a Single Chiroptical Molecular Switch. J. Am. Chem. Soc. 2008, 130, 4541− 4552. (31) Kim, J.; Lee, J.; Kim, W. Y.; Kim, H.; Lee, S.; Lee, H. C.; Lee, Y. S.; Seo, M.; Kim, S. Y. Induction and Control of Supramolecular Chirality by Light in Self-assembled Helical Nanostructures. Nat. Commun. 2015, 6, 6959−6966. (32) Zhang, L.; Liu, M. Supramolecular Chirality and Chiral Inversion of Tetraphenylsulfonato Porphyrin Assemblies on Optically Active Polylysine. J. Phys. Chem. B 2009, 113, 14015−14020. (33) Gopal, A.; Hifsudheen, M.; Furumi, S.; Takeuchi, M.; Ajayaghosh, A. Thermally Assisted Photonic Inversion of Supramolecular Handedness. Angew. Chem., Int. Ed. 2012, 51, 10505− 10509. (34) Huang, Z.; Kang, S.-K.; Banno, M.; Yamaguchi, T.; Lee, D.; Seok, C.; Yashima, E.; Lee, M. Pulsating Tubules from Noncovalent Macrocycles. Science 2012, 337, 1521−1526. (35) de Jong, J. J. D.; van Rijn, P.; Tiemersma-Wegeman, T. D.; Lucas, L. N.; Browne, W. R.; Kellogg, R. M.; Uchida, K.; van Esch, J. H.; Feringa, B. L. Dynamic Chirality, Chirality Transfer and Aggregation Behavior of Dithienylethene Switches. Tetrahedron 2008, 64, 8324−8335. (36) Johnson, R. S.; Yamazaki, T.; Kovalenko, A.; Fenniri, H. Molecular Basis for Water-Promoted Supramolecular Chirality Inversion in Helical Rosette Nanotubes. J. Am. Chem. Soc. 2007, 129, 5735−5743. (37) Ogoshi, T.; Akutsu, T.; Yamafuji, D.; Aoki, T.; Yamagishi, T. A. Solvent- and Achiral-Guest-Triggered Chiral Inversion in a Planar Chiral Pseudo[1]catenane. Angew. Chem., Int. Ed. 2013, 52, 8111− 8115. (38) Kubota, R.; Tashiro, S.; Shionoya, M. Chiral Metal-Macrocycle Frameworks: Supramolecular Chirality Induction and Helicity Inversion of the Helical Macrocyclic Structures. Chem. Sci. 2016, 7, 2217−2221. (39) Qing, G. Y.; Shan, X. X.; Chen, W. R.; Lv, Z. Y.; Xiong, P.; Sun, T. L. Solvent-Driven Chiral-Interaction Reversion for Organogel Formation. Angew. Chem., Int. Ed. 2014, 53, 2124−2129. (40) Huang, Y.; Wang, J.; Wei, Z. Modulating Supramolecular Helicity and Electrical Conductivity of Perylene Dyes through an Achiral Alkyl Chain. Chem. Commun. 2014, 50, 8343−8345. (41) Miyake, H.; Tsukube, H. Coordination Chemistry Strategies for Dynamic Helicates: Time-Programmable Chirality Switching with

(3) Kim, Y.; Li, H.; He, Y.; Chen, X.; Ma, X.; Lee, M. Collective Helicity Switching of a DNA−Coat Assembly. Nat. Nanotechnol. 2017, 12, 551−556. (4) Liu, G.-F.; Zhang, D.; Feng, C.-L. Control of Three-Dimensional Cell Adhesion by the Chirality of Nanofibers in Hydrogels. Angew. Chem., Int. Ed. 2014, 53, 7789−7793. (5) de Loos, M.; van Esch, J.; Kellogg, R. M.; Feringa, B. L. Chiral Recognition in Bis-Urea-Based Aggregates and Organogels through Cooperative Interactions. Angew. Chem. 2001, 113, 633−636. (6) Freire, F.; Seco, J. M.; Quinoa, E.; Riguera, R. Chiral Amplification and Helical-Sense Tuning by Mono- and Divalent Metals on Dynamic Helical Polymers. Angew. Chem., Int. Ed. 2011, 50, 11692−11696. (7) Liu, M.; Zhang, L.; Wang, T. Supramolecular Chirality in SelfAssembled Systems. Chem. Rev. 2015, 115, 7304−7397. (8) de Jong, J. J. D.; Lucas, L. N.; Kellogg, R. M.; van Esch, J. H.; Feringa, B. L. Reversible Optical Transcription of Supramolecular Chirality into Molecular Chirality. Science 2004, 304, 278−281. (9) Miao, W.; Qin, L.; Yang, D.; Jin, X.; Liu, M. Multiple-StimulusResponsive Supramolecular Gels of Two Components and Dual Chiroptical Switches. Chem. - Eur. J. 2015, 21, 1064−1072. (10) Jiang, J.; Meng, Y.; Zhang, L.; Liu, M. Self-Assembled SingleWalled Metal-Helical Nanotube (M-HN): Creation of Efficient Supramolecular Catalysts for Asymmetric Reaction. J. Am. Chem. Soc. 2016, 138, 15629−15635. (11) Liu, G.; Sheng, J.; Zhao, Y. Chiral Covalent Organic Frameworks for Asymmetric Catalysis and Chiral Separation. Sci. China: Chem. 2017, 60, 1015−1022. (12) Shen, Z. C.; Wang, T. Y.; Shi, L.; Tang, Z. Y.; Liu, M. Strong Circularly Polarized Luminescence from the Supramolecular Gels of an Achiral Gelator: Tunable Intensity and Handedness. Chem. Sci. 2015, 6, 4267−4272. (13) Liu, C.; Yang, D.; Jin, Q.; Zhang, L.; Liu, M. A Chiroptical Logic Circuit Based on Self-Assembled Soft Materials Containing Amphiphilic Spiropyran. Adv. Mater. 2016, 28, 1644−1649. (14) Han, J.; You, J.; Li, X.; Duan, P.; Liu, M. Full-Color Tunable Circularly Polarized Luminescent Nanoassemblies of Achiral AIEgens in Confined Chiral Nanotubes. Adv. Mater. 2017, 29, 1606503. (15) Wu, H.; Zhou, Y.; Yin, L.; Hang, C.; Li, X.; Ågren, H.; Yi, T.; Zhang, Q.; Zhu, L. Helical Self-Assembly-Induced Singlet−Triplet Emissive Switching in a Mechanically Sensitive System. J. Am. Chem. Soc. 2017, 139, 785−791. (16) Zhu, L.; Li, X.; Wu, S.; Nguyen, K. T.; Yan, H.; Ågren, H.; Zhao, Y. Chirality Control for in Situ Preparation of Gold Nanoparticle Superstructures Directed by a Coordinatable Organogelator. J. Am. Chem. Soc. 2013, 135, 9174−9180. (17) Liu, G.; Zhao, Y. Switching between Phosphorescence and Fluorescence Controlled by Chiral Self-Assembly. Adv. Sci. 2017, 4, 1700021. (18) Lara, C.; Reynolds, N. P.; Berryman, J. T.; Xu, A.; Zhang, A.; Mezzenga, R. ILQINS Hexapeptide, Identified in Lysozyme LeftHanded Helical Ribbons and Nanotubes, Forms Right-Handed Helical Ribbons and Crystals. J. Am. Chem. Soc. 2014, 136, 4732−4739. (19) Edwards, W.; Smith, D. K. Enantioselective Component Selection in Multicomponent Supramolecular Gels. J. Am. Chem. Soc. 2014, 136, 1116−1124. (20) Cao, J.; Yan, X.; He, W.; Li, X.; Li, Z.; Mo, Y.; Liu, M.; Jiang, Y.B. C−I···π Halogen Bonding Driven Supramolecular Helix of Bilateral N-Amidothioureas Bearing β-Turns. J. Am. Chem. Soc. 2017, 139, 6605−6610. (21) Liu, Y.; Chen, C.; Wang, T.; Liu, M. Supramolecular Chirality of the Two-Component Supramolecular Copolymer Gels: Who Determines the Handedness? Langmuir 2016, 32, 322−328. (22) Ajayaghosh, A.; Varghese, R.; George, S. J.; Vijayakumar, C. Transcription and Amplification of Molecular Chirality to Oppositely Biased Supramolecular π Helices. Angew. Chem., Int. Ed. 2006, 45, 1141−1144. (23) Liu, G.-F.; Zhu, L.-Y.; Ji, W.; Feng, C.-L.; Wei, Z.-X. Inversion of the Supramolecular Chirality of Nanofibrous Structures through Co11888

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889

Article

ACS Nano Labile and Inert Metal Helicates. Chem. Soc. Rev. 2012, 41, 6977− 6991. (42) Park, S. H.; Jung, S. H.; Ahn, J.; Lee, J. H.; Kwon, K.-Y.; Jeon, J.; Kim, H.; Jaworski, J.; Jung, J. H. Reversibly Tunable Helix Inversion in Supramolecular Gels Trigged by Co2+. Chem. Commun. 2014, 50, 13495−13498. (43) Kokan, Z.; Peric, B.; Vazdar, M.; Marinic, Z.; Vikic-Topic, D.; Mestrovic, E.; Kirin, S. I. Metal-Induced Supramolecular Chirality Inversion of Small Self-Assembled Molecules in Solution. Chem. Commun. 2017, 53, 1945−1948. (44) Zhang, M.; Xu, D.; Yan, X.; Chen, J.; Dong, S.; Zheng, B.; Huang, F. Self-Healing Supramolecular Gels Formed by Crown Ether Based Host−Guest Interactions. Angew. Chem., Int. Ed. 2012, 51, 7011−7015. (45) Yan, X.; Xu, D.; Chi, X.; Chen, J.; Dong, S.; Ding, X.; Yu, Y.; Huang, F. A Multiresponsive, Shape-Persistent, and Elastic Supramolecular Polymer Network Gel Constructed by Orthogonal SelfAssembly. Adv. Mater. 2012, 24, 362−369. (46) Cui, J.; Zheng, Y.; Shen, Z.; Wan, X. Alkoxy Tail Length Dependence of Gelation Ability and Supramolecular Chirality of Sugar-Appended Organogelators. Langmuir 2010, 26, 15508−15515. (47) Liu, G.-F.; Ji, W.; Wang, W.-L.; Feng, C.-L. Multiresponsive Hydrogel Coassembled from Phenylalanine and Azobenzene Derivatives as 3D Scaffolds for Photoguiding Cell Adhesion and Release. ACS Appl. Mater. Interfaces 2015, 7, 301−307. (48) Liu, G.-F.; Ji, W.; Feng, C.-L. Installing Logic Gates to Multiresponsive Supramolecular Hydrogel Co-assembled from Phenylalanine Amphiphile and Bis(Pyridinyl) Derivative. Langmuir 2015, 31, 7122−7128. (49) Korevaar, P. A.; George, S. J.; Markvoort, A. J.; Smulders, M. M. J.; Hilbers, P. A. J.; Schenning, A. P. H. J.; De Greef, T. F. A.; Meijer, E. W. Pathway Complexity in Supramolecular Polymerization. Nature 2012, 481, 492−496. (50) Jonkheijm, P.; van der Schoot, P.; Schenning, A. P. H. J.; Meijer, E. W. Probing the Solvent-Assisted Nucleation Pathway in Chemical Self-Assembly. Science 2006, 313, 80−83. (51) Smulders, M. M. J.; Schenning, A. P. H. J.; Meijer, E. W. Insight into the Mechanisms of Cooperative Self-Assembly: The “Sergeantsand-Soldiers” Principle of Chiral and Achiral C3-Symmetrical Discotic Triamides. J. Am. Chem. Soc. 2008, 130, 606−611.

11889

DOI: 10.1021/acsnano.7b06097 ACS Nano 2017, 11, 11880−11889