CHIRALITY 27:659–666 (2015)

Chiroptical Studies on Supramolecular Chirality of Molecular Aggregates 1

HISAKO SATO,1* TOMOKO YAJIMA,2 AND AKIHIKO YAMAGISHI3 Graduated of Science and Engineering, Ehime University, Matsuyama, Japan 2 Department of Chemistry, Ochanomizu University, Tokyo, Japan 3 Department of Chemistry, Toho University, Chiba, Japan

ABSTRACT The attempts of applying chiroptical spectroscopy to supramolecular chirality are reviewed with a focus on vibrational circular dichroism (VCD). Examples were taken from gels, solids, and monolayers formed by low-molecular mass weight chiral gelators. Particular attention was paid to a group of gelators with perfluoroalkyl chains. The effects of the helical conformation of the perfluoroalkyl chains on the formation of chiral architectures are reported. It is described how the conformation of a chiral gelator was determined by comparing the experimental and theoretical VCD spectra together with a model proposed for the molecular aggregation in fibrils. The results demonstrate the potential utility of the chiroptical method in analyzing organized chiral aggregates. Chirality 27:659–666, 2015. © 2015 Wiley Periodicals, Inc. KEY WORDS: vibrational circular dichroism; transformation; perfluoroalkyl A number of chiroptical methods such as electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and Raman optical activity (ROA) have been applied to reveal the static and dynamic features of chiral molecules.1–18 Among the methods, the VCD spectrum is an extension into the infrared and near-infrared regions of the circular dichroism spectrum.19–65 A main advantage of the method has been its utility in determining the absolute configuration of a chiral molecule in a solution. In addition to these aspects, VCD spectroscopy was recently applied to molecular aggregates.25–53 The attempts were motivated by the recent finding that the VCD signals are enhanced remarkably when chiral molecules aggregate.23,24 Self-assembly with low-molecular weight mass gelators provides an example of supramolecular architectures through the spontaneous aggregation of small molecules.66–93 Chiral gelators often give fibrils helically wound on a micrometer scale. An interesting aspect is that the helicity of a fibril is determined uniquely by the molecular chirality of a gelator. Thus, this raises an attractive issue to reveal the mechanism of chiral amplification from a microscopic scale to a mesoscopic or macroscopic scale. A fibril is proposed to be formed through the hierarchical self-assembling process. According to this mechanism, the primary, secondary, and higher-order configurations of a gelator should each play a role.66 There are two types of helical morphologies: one is a helical ribbon with plus curvature, the other a twisted saddle-like ribbon with minus curvature.69 For example, the alkanoyl derivatives of trans-1,2-diaminocyclohexane that form fibrils with right-handed helicity in the case of an RR-isomer belong to the latter case.92 It remains to be resolved, however, what the essential factor is in selecting either of these two types during the course of aggregation. The present review summarizes the recent results of chiroptical (VCD, ECD, and ROA) studies concerning supramolecular chirality. Examples are taken from the solids, films, and gels of chiral gelators.94–101 Among a variety of gelators, particular attention was paid to a group of gelators © 2015 Wiley Periodicals, Inc.

supramoelcular;

chiral

gelator;

sol-gel

with perfluoroalkyl chains. They are of practical utility for solidifying fluorous solvents. For example, Weiss et al. recently reported a work aiming at the development of new molecules with perfluoroalkanamides to gelate fluorous liquids.90,91 In the following, the structures and properties of gels as studied by the chiroptical method are reviewed.61,62,101,102 BASIC STRATEGY OF APPLYING VCD SPECTROSCOPY TO SUPRAMOLECULAR CHIRALITY Characteristics of the VCD Method

As stated above, the VCD spectrum covers the infrared and near-infrared regions of the circular dichroism spectrum.17 A large number of bands due to the normal modes are utilized to analyze the molecular vibrations of a given molecule in order to determine its detailed conformation. Another advantage of the method is that even a molecule with no electronic absorption in the UV-visible region can be a target. This property is particularly useful for analyzing a compound with perfluoroalkyl chains, since the chain with no electronic transition in the UV-vis region is reported to wind helically due to the steric interaction of bulky fluorine atoms.103 The simulation based on the Density Functional Theory (DFT) calculation is helpful in analyzing the observed VCD spectra. Since the theoretical calculation of VCD spectra includes the ground electronic state alone, except for the lowlying electronic transitions, the theory is thought to be more

[This article is part of the Special Issue: “Molecular Chirality Japan 2014 and Asia 2014.” See the first articles for this special issue previously published in Volume 27:8. More special articles will be found in this issue as well as in those to come.] *Correspondence to: Hisako Sato, Graduated of Science and Engineering, Ehime University, 2-5 Bunkyo-cho, Matsuyama, Japan. E-mail: sato.hisako. [email protected] Received for publication 29 January 2015; Accepted 8 June 2015 DOI: 10.1002/chir.22482 Published online 15 July 2015 in Wiley Online Library (wileyonlinelibrary.com).

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reliable and straightforward than in the case of calculating ECD. Presently, the program for calculating VCD spectra is commercially available (Gaussian 09).104 In spite of these favorable features, however, the VCD method has one drawback: a signal is very small for a single molecule in a solution. The dissymmetry factor of circular dichroism (g-value) is given by g = ΔA/A, in which A and ΔA are absorbance and the difference of absorbance between leftand right-handed circularly polarized lights (or ΔA = Aleft A right ), respectively. The ΔA value for VCD is in the region of 10-5 ~ 10-4 for an isolated chiral molecule in a solution, which is two or three orders lower than those for ECD (10-3 ~ 10-2). In overcoming the difficulty arising from such small signals, the measurements of VCD spectra are usually carried out by repeating scans 104 ~ 105 times. Accordingly, a single measurement requires more than 1 h. Due to this limitation, it is difficult to apply the method to systems involving unstable species like reaction intermediates. Instrumental VCD Measurements

Conventional VCD instruments are now commercially available. Scheme 1 shows a VCD machine that was developed in our laboratory with the cooperation of JASCO Japan (a PRESTO-S-2007 VCD spectrometer).23 The machine was a concurrent system in combination with reflectionabsorption measurements using linearly polarized light. A shuttle system was introduced to replace a sample with a reference automatically in order to correct baseline continuously throughout the measurement. Recently, several improvements are reported for VCD instruments. Bürgi et al., for example, report the ATR-IR and VCD. They measured the VCD spectra on gold nanoparticles adsorbing chiral N-isobutyryl-cysteine.58 The method was the first successful example to investigate the self-assembled film of chiral thiols on a gold surface. In another attempt, Lüdeke et al. report the use of a quantum cascade laser VCD.59 The machine provides transient VCD spectra in the time range of 0–500 min. Kinetic parameters were determined by monitoring the reaction of (–)-sparteine to form nickel-(–)-sparteine in CDCl3. As for the measurements of time-dependent VCD spectra, Rhee et al. developed a machine based on linearly polarized coherent femtosecond light plus in order to follow the ultrafast structural changes in the time range of 10-15 sec.60 The technique of phase and amplitude measurements achieved extremely high time resolution. Strategy in Applying the VCD Method to Gels

When VCD spectra are recorded on gels or KBr-pellets, attention should be paid to confirm that the signals arise from the intrinsic chiral vibrational properties of a molecule. First, the mirror-imaged relation should be maintained between the samples of antipodal molecules. Next, no VCD signal is

Scheme 1. Instrument of concurrent VCD-RAS (PRESTO-S-2007).23 Chirality DOI 10.1002/chir

observed for the samples containing a racemic mixture. It is also needed to confirm that no change in the spectrum occurs when a cell rotates around the direction of monitoring to eliminate the dichroic effects in samples with anisotropic domains. To obtain the molecular conformation of an investigated chiral molecule in gels, the observed spectra are compared with the calculated VCD ones. Usually the calculation is performed for a single molecule under various conformations. The most probable conformation of a gelator in a gel is derived so as to reproduce the observed spectra over the whole wavenumber range. In this respect, the enhancement of signals is helpful to provide as many reliable peaks as possible. Presently, a theoretical work is in progress to explain the signal enhancement observed for the systems containing molecular aggregates. Preparation of Gels, KBr Pellets, and LB Films

For preparing a gel sample, a gelator was dissolved at 60 °C in solvents such as C6D6, CD3CN, and C6F6. The concentration was adjusted a little over the critical gel concentration (e.g., 10 mg mL-1). A 10–100 μl of the sample was sandwiched between two CaF2 plates with a spacing of 50 μm and cooled to room temperature. A gel sample should be transparent in order to avoid any scattering of incident light and dichroic effect.95–101 In the case of a solid sample, a KBr pellet was mounted into an assembled cell with a window of 5 mm ϕ or 3 mm ϕ.65 For preparing an LB film, a chloroform solution of chiral amphiphilic was spread onto an aqueous subphase in a trough. The surface of a trough was compressed until the surface pressure attained some value. A floating film thus prepared was transferred to a hydrophobic glass plate (2 x 2 cm2) at a constant surface pressure (e.g., 15 mNm-1). In order to obtain a reliable VCD spectrum, deposition was usually repeated to form a film of at least 50 layers.96 APPLICATION OF CHIROPTICAL METHODS TO GELS, FILMS, AND SOLID STATES Signal Enhancement in Gel States

VCD spectroscopy was first applied by analyzing the molecular structure of 12-hydroxyhexadecanoic acid (denoted by Ror S-12-HOA) in benzene-d6-gels.95,96 Before the work, ECD spectroscopy was the main method as chiroptical spectroscopy to study the molecular structures of gels. Helical structures of fibrils were reported by Tachibana et al.67 They established that the helicity of fibrils was determined uniquely by the molecular chirality of a gelator. The ECD spectra in CCl4 gels indicated that the mesophase of 12-HOA had a supramolecular helical structure.67 It was found that the gel gave strong VCD signals in comparison to the solution containing the same molecule. For example, no significant VCD signal was detected over the whole wavenumber range after 104 accumulations in the CD3OD solution of enantiomeric 12-HOA, while clear VCD peaks were recorded on the C6D6 gel samples under the same conditions. The main peaks were mirror-imaged between the antipodes in the wavenumber range of 1800–1000 cm-1.The strong peaks at 1078 cm-1 (negative for R-12-HOA), 1130 cm-1 (positive), 1220 cm-1 (positive), 1271 cm-1 (positive), and 1437 cm-1 (positive) cm-1 were all related to the vibrations involving the asymmetric center at carbon 12.

SUPRAMOLECULAR CHIRALITY OF MOLECULAR AGGREGATES

Fig. 1. The model of a bent-formed dimer proposed for R-12-HOA on the basis of the observed VCD spectra and the DFT calculation (modified from Ref. 95).

The enhancement of these VCD signals might be related to the aggregation of molecules by the zigzag chains of hydrogen-bonded hydroxyl groups at carbon 12. In particular, the intense C-O stretching of a carboxyl group appeared. This was interesting because the planar carboxyl group itself was achiral and VCD-inactive in a solution, while it was active in a gel. The results implied that the chiral nature at the hydroxylated carbon 12 transferred through a long alkyl chain to the carboxyl group in a gel. The model of a bent-formed dimer with the intermolecular hydrogen bonding was proposed on the basis of the conformation of a gelator molecule determined from the VCD spectra (Fig. 1). Chiroptical Application for Molecular Films

Some gelators are amphiphilic so that they form a wellordered molecular film. The structural study on such 2D films is helpful to understand the gelation mechanism. Motivated by this background, VCD studies were extended to the Langmuir-Blodgett (LB) films of R- and S-12-HOA. Their VCD spectra were recorded on the X-type 50 layered films deposited on glass substrates in the wavenumber region of 2700–3400 cm-1.96 This was the first report on the VCD spectra of LB films. By analyzing the peaks assigned to hydrogen bonds, it was concluded that no long sequence of intermolecular hydrogen bonding was formed in the LB films at carbon 12 position, in contrast to the gels. The results demonstrated the potential of VCD spectroscopy for the structural studies of 2D systems. A similar experiment was performed for the cast films of N-alkylated oligo(m-phenylurea)s that had helical conformations. The absolute configuration of the helices was determined from the CD and VCD spectra.94 Recently, Xu and colleagues reported the VCD and ECD spectra of the cast film to determine the absolute configurations and geometries of two Fráter Seebach alkylation reaction products with long hydrocarbon chains. They concluded that the compound was (2R,3R) with extended all trans-hydrocarbon chains.63 The strongly enhanced carbonyl stretching VCD vibrations indicated that the compounds in the film state existed predominantly as H-bonded dimers. The study showed that the combination of the film VCD and ECD techniques provided a straightforward method to determine the absolute configuration of a chiral molecule in a film. Chiroptical Application in Solid States and Gels

Low-molecular weight mass gelators based on trans-1, 2-diaminocyclohexane were first reported by Hanabusa et al.92 One of the outstanding properties of the gelators is that a fibril takes a helical structure, whose helicity depended

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uniquely on their RR/SS molecular chirality. As the application of chiroptical spectroscopy to gels, the ECD spectra of acetonitrile gels were reported. Strong peaks were observed in the wavelength region of 190–240 nm. The signs of the peaks were correlated with the absolute configuration of the used gelators. The absorption was assigned to the n-π* transition of the peptide moieties, reflecting the helical stacking of the aggregates of gelators in fibrils. No further structural information was difficult to obtain from the ECD spectra alone. The compounds attracted extensive attention due to their highly gelating capability towards a wide range of organic solvents. Recently, the gelators based on diaminocyclohexane with various alkyl chains was reported, revealing the role of weak van der Waals interactions among the alkyl chains.93 To investigate the effects of alkyl chain length on gel structures, we applied VCD spectroscopy on the benzene-d6 gels formed by trans(RR)- or trans(SS)-N, N’-alkanoyl-1,2-diaminocyclohexane (Chart 1a) (denoted by RR-Cn or SS-Cn, respectively; n = the number of carbon atoms in an introduced alkanoyl group).97 Figure 2 compares the VCD and IR spectra among the solution (CDCl3), solid (KBr), and gel (benzene-d6) states for C8. In the case of the CDCl3 solution (upper), the couplet peaks around 1524 cm-1, which are assigned to symmetric and asymmetric N-H bending vibrations from the higher to lower wavenumber, respectively, showed the opposite signs between the RR-C8 and SS-C8. No VCD peak arising from the C = O stretching of a carboxyl group was observed around 1650 cm-1, although the corresponding band was observed in the IR spectra. In the case of the KBr pellet (middle), the clear VCD peaks assigned to C = O stretches appeared around 1640 cm-1. The couplet signal around 1640 cm-1 gave plus and minus signs from the lower to higher wavenumber for RR-C8. In the case of the benzene-d6 gels (lower), the strong couplet was observed around 1640 cm-1, where the signs of the couplet were plus at 1643 cm-1 and minus at 1632 cm-1. It should be noted that the signs of the couplet were opposite between the solids and gels.

Chart 1. (a) The examples of chiral gelators: The molecular structure of RR-Cn. C7 and C8 correspond to a compound with n = 6 and 7, respectively. (b) The examples of chiral gelators: The molecular structure of RR-CnBr. C7Br and C8Br correspond to a compound with n = 6 and 7, respectively. (c) The examples of chiral gelators: The molecular structure of RR-CFn. CF7 and CF8 correspond to a compound with n = 6 and 7, respectively. Chirality DOI 10.1002/chir

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Fig. 2. The IR and VCD spectra of RR- (solid) and SS-C8 (broken) for the samples of a CDCl3 solution (upper), a KBr pellet (middle), and a benzene-d6 gel (lower) (modified from Ref. 97).

Figure 3 shows the results of similar measurements in the cases of the solids (upper) and the gels (lower) for C7. In this case, the signs of the couplets assigned to C = O vibrations were the same between the gels and the solid states. The DFT calculation was performed under the various conformations of Cn.97 The calculated results depended little on the variation of n, while the signs of the couplet due to the stretching vibration of C = O bond were affected delicately by the mode of hydrogen bond. It was concluded that the VCD results for the gels by C8 (Fig. 2, lower) corresponded to the formation of the double antiparallel chains of intermolecular hydrogen bonds using two pairs of > NH and > C = O

Fig. 3. The IR and VCD spectra of RR- (solid) and SS-C7 (broken) for the samples of a KBr pellet (upper) and a benzene-d6 gel (lower) (modified from Ref. 97). Chirality DOI 10.1002/chir

groups, while the VCD results for the gels by C7 (Fig. 3, lower) corresponded to the formation of a single chain of intermolecular hydrogen bonds using a pair of > NH and > C = O groups. The remaining pair of > NH and > C = O groups formed an intramolecular hydrogen bond. We also studied the terminal effects of alkyl chains for the alkanoyl derivatives of trans-1,2-diaminocyclohexane.98 The replacement of a single bromine atom with a hydrogen atom at the terminal of an alkyl chain was found to give a crucial influence on gel formation. To study the terminal effect of the alkyl chain toward gel formation by low molecular mass gelators, VCD was applied for (R,R)- or (S,S)-N, N’-nbromoalkanoyl-1,2-diaminocyclohexane (denoted RR-CnBr or SS-CnBr, respectively; n = the number of carbon atoms in an alkanoyl group) (Chart 1b) When n was varied from 5 to 12, the gelators formed transparent or opaque or turbid gels in benzene except for n = 8. C8Br was unable to form a gel, while C7Br formed the clear gel in benzene. In the case of a C8Br crystal, both alkyl chains are straight in all-trans conformation. They eject oppositely or the one upward and the other downward from the cyclohexyl plane. As a result, the intermolecular Br-Br chain is formed, connecting the terminal bromine atoms in a helical way. Its helicity is determined by the SS/RR configuration of a cyclohexyl part. The highly crystallizing tendency of C8Br might be caused by such interactions among bromine atoms. In the VCD spectra of the benzene-d6 gels formed by C7Br, the signs of the coupled peaks around 1640 cm-1 were the same as those of C7. Based on the present models, the lower gelation capability by CnBr might be related to the weaker binding (or a single chain of hydrogen bonds) in the molecular aggregation. In fact, from the molecular packing structures in the crystals of these molecules as determined by X-ray analyses, it was found that the packing modes depended remarkably on the length of a mono-brominated alkyl chain.98 VCD Application to Chiral Gelators With Perfluoroalkyl Chains

The VCD application to gels has recently been extended to the low-molecular mass gelators with perfluoroalkyl chains.99,100 The analyses of the spectra led to determining the detailed conformation of a gelator molecule including the helicity of the perfluoroalkyl chains. As an example of applying the VCD method to perfluoroalkyl compounds, Monde et al. recently reported the helical properties of a perfluoroalkyl chain in a solution by means of VCD.54 The work showed the utility of VCD to determine the absolute configuration with no absorbance in the UV-vis spectra. The formation of gels was studied in detail in the case of CF7 (Chart 1c). Comparing the thermodynamic behavior between CF7 and C7 for CH3CN as a solvent, the former gave higher enthalpy of gelation by 7.7 kJmole-1.99 This was ascribed to the higher cohesive energy of a perfluoroalkyl chain than an alkyl chain.105 Figure 4 shows the VCD spectra recorded on the CD3CN gels of CF7. A mirror-imaged relation was confirmed over the whole wavenumber region between the samples of RR-CF7 and SS-CF7. First, attention was paid to the multiple peaks in the region of 1238–1170 cm-1. They were assigned to the stretching vibrations of C-F bonds in the perfluoroalkyl chains. In order to investigate the contribution of the perfluoroalkyl chains to VCD spectrum, a DFT calculation

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SUPRAMOLECULAR CHIRALITY OF MOLECULAR AGGREGATES

TABLE 1. The sign of C-O and C-F stretching for RR-CF7 gel (modified from Ref. 101) Solvent (units) C-O couplet Low/ high wavenumber C-F stretching

Fig. 4. VCD (upper) and IR spectra (lower) of RR- and SS-CF7 in CD3CN (modified from Ref. 99).

was performed for a perfluorohexyl group. Figure 5 shows the results of such calculations when it was assumed to wind with right or left-handed helicity. Comparing the observed spectra with the calculated ones, the perfluoroalkyl carbon chains in RR-CF7 were concluded to take a right-handed helix along the C-C skeletons. Most probably, the helicity was determined by the interaction of the hydrogen atom in the –NH-C = O moiety with the fluorine atom in the perfluoroalkyl chain. When the VCD spectrum of the same molecule was recorded in a solution, the very low VCD peaks were observed around 1680 cm-1 with no peak observed in the region of 1238–1170 cm-1. Thus, the chain was thought to interconvert rapidly between the right- and lefthanded helixes. As another aspect, the strong couplet was observed around 1688 cm-1, which was assigned to the stretching vibration of C = O bonds. In summarizing the results, it was proposed that the minus and plus signs from low to high wavenumber for the RR-CF7 indicated that a fibril took a stable structure with two antiparallel intermolecular hydrogen bonds between > NH and > C = O. Under such an aggregation mode, the helically wound perfluoroalkyl chains might be stacked closely to enhance stability.99 To study the solvent effect, VCD spectra were compared between the CD3CN and C6F6 gels.101 As a result, the sign of the couplet due to the C = O stretching and perfluoroalkyl chains was opposite between these two solvents even for the same enantiomers of CF7 (Table 1). In other words, the gelators formed a stable structure with two antiparallel

Fig. 5. A model for the helical winding of a perfluorohexyl chain (right) and the calculated VCD spectra (left).

CD3CN

C6F6

A 4:1 (v/v) mixture of CD3CN and C6F6

-/ +

+/ -

Initial +/- Final -/+

-

+

Initial + final -

hydrogen bonds in CD3CN, while they formed an unstable structure with one single intermolecular and one single intramolecular hydrogen bond. In this sense, solvent molecules participated directly in the formation of molecular aggregates, but did not play simply a guest role in the cavities of a gel. Gelation was studied in the case of CF8 to see the effect of the length of perfluoroalkyl chains. As a result, the elongation of a single –CF2- unit resulted in a drastic change of gel formation. In contrast to CF7, for example, a CH3CN gel was most stable at the racemic mixture in the case of CF8. Its stability lowered with the increase in the optical purity of the gelator.100 Dynamics of Sol-Gel Transformation as Observed by Chiroptical Spectroscopy

The method was extended to reveal the dynamic aspects of gelation processes.101 For this purpose, a mixture of CD3CN and C6F6 containing CF7 at a little over the critical gel concentration was prepared at 60 °C and sandwiched between two CaF2 plates. The sample was cooled to room temperature. When the sample was observed with a crossed Nicols microscope, the isotropic liquid changed into a gel within 10 min. The same process was monitored by the VCD measurement. When the data were stored for 1 min of accumulation, a clear VCD signal was obtained. Figures 6 and 7 show the initial, intermediate, and stable VCD spectra. It was noted that some peaks inverted their signs before the appearance of the final spectrum. By comparing the observed spectra with the theoretically simulated ones, it was deduced that the observed reversal of the signs of the VCD couplets around 1700 cm-1 was thought to reflect the structural transition from an unstable conformation (half-intramolecular and half-intermolecular hydrogen bonding in a tape-like fibril) to a stable conformation (two antiparallel intermolecular hydrogen bonding in a fiber-like fibril). Accompanying this change, the perfluoroalkyl chains inverted their helicity. One reason for the appearance of such an unstable intermediate might be that the perfluoroalkyl gelator showed higher affinity toward C6F6 than CD3CN. Accordingly, C6F6 molecules were included dominantly at the initial step. The results are summarized in Table 1. The results demonstrated the potential utility of the VCD method to reveal the formation mechanism of organized chiral aggregates. As one of the recent applications of chiroptical spectroscopy to dynamic processes, Sánchez and colleagues reported the temperature-dependent VCD spectra on a solution of oligo-p-phenylene polymers. They applied time-dependent VCD, VT-CD, and ROA methods. The sign of VCD couplet single assigned to the amide I groups inverted after 24 h.61 The observed change reflected the helical inversion of a p-phenylene chain. It was concluded that the inversion of a biphenyl core induced the inversion of the supramolecular helicity at higher temperature. Oda and colleagues reported Chirality DOI 10.1002/chir

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chiral low-molecular mass weight gelator, a derivative of trans-1,2-diaminocyclohexane derivatives. The influence of the chain length, the terminal effects, the perfluoroalkyl chains of a gelator and solvents on gelation behavior was investigated from the change of VCD spectra. This review demonstrates that chiroptical spectroscopy provides a powerful tool to reveal the molecular packing in the chiral supramolecular aggregates and sol-gel transformation. As a future application, it will be interesting if the same methods are applied to other supramolecuar systems including biomolecules. ACKNOWLEDGEMENTS

This work was supported by JSPS KAKENHI Grant Number 26620068. LITERATURE CITED

Fig. 6. The initial (upper) and intermediate (lower) VCD spectra of RRCF7 in 4:1(v/v)CD3CN/C6F6 (modified from Ref. 101).

Fig. 7. The final VCD spectra of RR-CF7 in 4:1(v/v) CD3CN/C6F6 (modified from Ref. 101).

the in-situ observation of the helicity inversion for L-tartarate gels by ROA.62 The handedness of helices was inverted when these helices were in contact with a solution containing an excess amount of chiral anions with opposite enantiomers. CONCLUSION

The present article reviews the recent results of applying chiroptical spectroscopy (ECD, VCD, and ROA) to investigating the chiral structures of gels, monolayer films, and solid samples. The main attention was on the gels formed by a Chirality DOI 10.1002/chir

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