Article pubs.acs.org/JPCB
Unusual Chiroptical Properties of the Cryptophane-222 Skeleton Delphine Pitrat,† Nicolas Daugey,‡ Marion Jean,§ Nicolas Vanthuyne,§ Frank Wien,∥ Laurent Ducasse,‡ Nathalie Calin,† Thierry Buffeteau,*,‡ and Thierry Brotin*,† †
Ecole Normale Supérieure de Lyon, CNRS UMR 5182, Laboratoire de Chimie, Lyon 1 University, 69364 Lyon, France Institut des Sciences Moléculaires, CNRS UMR 5255, Bordeaux University, 33405 Talence, France § Centrale Marseille, CNRS, iSm2, Aix-Marseille University, 13397 Marseille, France ∥ Synchrotron SOLEIL, L’Orme des Merisiers, 91192 Gif sur Yvette, France ‡
S Supporting Information *
ABSTRACT: Enantiopure cryptophane-222 derivative (1) devoid of substituents was obtained via high-performance liquid chromatography (HPLC) using chiral stationary phases. The chiroptical properties of 1 were determined from polarimetry, electronic circular dichroism (ECD), synchrotron radiation circular dichroism (SRCD), vibrational circular dichroism (VCD), and Raman optical activity (ROA) experiments and were compared to those of the cryptophane-A (2) derivative. Unusual polarimetric results were obtained for 1 in CHCl3 solvent as the sign of the optical rotation (OR) values changes in the nonresonance region above 365 nm, whereas no change was observed in the CH2Cl2 solvent. ECD spectra in the 1La and 1Lb regions were very similar for the two solutions and could not explain these unusual polarimetric properties. In contrast, SRCD spectra in the 1Bb region revealed spectral differences for the two solutions, which have been associated with conformational changes of the three linkers by time-dependent density functional theory (TDDFT) calculations. DFT calculations of the OR support that conformational changes may explain the polarimetric results obtained for the two solvents. Finally, TDDFT calculations of the ECD as well as DFT calculations of the VCD and ROA allowed the attribution of the (−)589-PP absolute configuration for 1 in solution, as determined from the X-ray structures of 1.
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Scheme 1. Chemical Structures of MM-1 and MM-218,19
INTRODUCTION Cryptophane derivatives are hollow molecules that possess remarkable molecular recognition properties.1,2 For instance, the ability of these derivatives to bind various substrates has been thoroughly studied in the past and more recently with xenon as a guest.3−7 They are composed of two cyclotribenzylene (CTB) units connected together by three aliphatic linkers whose length and nature can be varied. The spatial arrangement of the six benzene chromophores creates a cavity suitable for accommodating small guest molecules. Cryptophane molecules can be categorized into two classes of molecular hosts: inherently chiral cryptophanes and achiral cryptophanes. The inherently chiral cryptophanes possess different symmetries and their chirality usually comes from the helicoidal arrangement of the three aliphatic linkers. The anti-cryptophane-A (with three ethylenedioxy linkers as shown in Scheme 1) and its congeners belong to this class of derivatives. Cryptophanes possessing two different CTB caps are also inherently chiral molecules, regardless of the arrangement of the linkers. For instance, anti-cryptophane-C and syn-cryptophane-D are both chiral molecules.2 In contrast, cryptophanes with identical CTB units and a syn arrangement of its linkers possess a C3h-symmetry and are achiral molecules. In the mid-1980s, Collet and co-workers investigated for the first time the chiroptical properties of cryptophane derivatives. Six enantio-enriched cryptophanes were characterized via © 2016 American Chemical Society
electronic circular dichroism (ECD), and their absolute configuration (AC) was established using an excitonic coupling mechanism.8 Then, chiral studies on these beautiful molecular objects were stopped probably because of the difficulty in synthesizing these molecules in their enantiopure form. More recently, new synthetic strategies developed by Brotin and coworkers have permitted the reproducible synthesis of enantiopure derivatives, allowing the study of their chiroptical Received: September 27, 2016 Revised: November 10, 2016 Published: November 10, 2016 12650
DOI: 10.1021/acs.jpcb.6b09771 J. Phys. Chem. B 2016, 120, 12650−12659
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The Journal of Physical Chemistry B
10 mm), thermostated at 25 °C using EtOH/CHCl3/CH2Cl2 (40/45/15) as the mobile phase. The flow rate of the mobile phase was 5 mL/min and the two enantiomers were detected by a UV−vis detector (at 240 nm) connected to a CD detector, giving the CD sign at 254 nm. A total of 1100 injections (90 μL) every 2.2 min allowed the separation of 320 mg of (rac)-1. The first eluted enantiomer, [CD(−)254]-1, was collected between 7.5 and 8.3 min and the second one, [CD(+)254]-1, between 8.6 and 9.2 min. X-ray Crystallography. X-ray structures of the two enantiomers of 1 were obtained from crystals mounted on a Kappa geometry diffractometer (Cu radiation) using the experimental procedure previously published.17 Compound [CD(−)254]-1 displayed solvent-accessible voids (intermolecular volume) of 707.4 Å3 per unit cell, where residual electronic density was present but the solvent molecule (pyridine) could not be refined. In contrast, one pyridine molecule per cryptophane was refined for compound [CD(+)254]-1. The contribution of the disordered solvent and the residual electronic density were removed using the SQUEEZE algorithm.20 The cryptophane cavity volume of [CD(+)254]-1 was calculated using the subroutine AVOIDS of the crystal structure visualization software, Mercury,21 with a probe radius of 1.4 Å and a grid spacing of 0.4 Å with the choice of the parameter Contact Surface to perform the calculation. CCDC 1452389 and 1452390 contain the crystallographic data of [CD(+)254]-1 (Supporting Information) and [CD(−)254]-1 Supporting Information, respectively. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif. Polarimetric, UV−Vis, and ECD Measurements. Optical rotations (ORs) at discrete wavelengths were measured at 25 °C in six solvents (CHCl3, CH2Cl2, dimethylsulfoxide (DMSO), dimethylformamide (DMF), acetone, and pyridine) using a 10 cm path length cell. Additional measurements were performed for (−)589-2 and (+)589-cryptophane(OAc)5 ((+)5893). Concentrations used for the polarimetric measurements were typically in the range of 0.1−0.3 g/100 mL. ECD spectra were recorded in four solvents (CHCl3, CH2Cl2, tetrahydrofuran (THF), and CH3CN) at 20 °C using a 2 mm path length quartz cell (concentrations were in the range of 5 × 10−5−1 × 10−4 M). Spectra were recorded in the wavelength ranges of 210−400 nm (THF and CH3CN) or 230−400 nm (CH2Cl2 and CHCl3) with a 0.5 nm increment and a 1 s integration time. UV−vis spectra were recorded in CH2Cl2 (230−400 nm) and THF (210−400 nm) at 20 °C using a 5 mm path length quartz cell. SRCD Measurements. SRCD measurements were carried out at the DISCO beamline, SOLEIL synchrotron.22,23 Samples of the two enantiomers of 1 were dissolved in CH2Cl2 and CHCl3. Serial dilutions of the concentrations in view of data collection in three spectral regions were chosen as 100, 10, and 2.5 g/L. Accurate concentrations were reassessed by absorption measurements, allowing the scaling of spectral regions to each other. Samples were loaded in circular demountable CaF2 cells of 3.5 μm path lengths, using 2−4 μL.24 Two consecutive scans for each spectral region of the corresponding dilution were carried out for consistency and repeatability. CD spectral acquisitions of 1 nm steps at 1.2 s integration time, between 320−255, 260−216, and 232−170 nm, were performed for the samples. Averaged spectra were then subtracted from the corresponding averaged baselines collected three times. The
properties.9 In addition, the use of high-performance liquid chromatography (HPLC) on a chiral stationary phase has allowed easier access to these enantiopure derivatives. Thus, recent articles have shown that cryptophanes exhibit interesting chiroptical properties, which can be studied using several techniques such as ECD, vibrational circular dichroism (VCD), and Raman optical activity (ROA).10−17 The use of VCD or ROA spectroscopy associated with density functional theory (DFT) calculations allowed the unambiguous determination of the AC of these derivatives. These studies also provided important information on the conformation adopted by the host molecules in the presence or absence of guest molecules, especially when water was used as a solvent. However, the spectral modifications observed on the VCD and ROA spectra were difficult to interpret because the signals below 1500 cm−1 come from both the substituents and the backbone of cryptophane derivatives. Thus, there is an interest to study the chiroptical properties of model cryptophane derivatives possessing a simplified chemical structure. Cryptophane-222 (compound 1 in Scheme 1) is an example of such a molecule. The synthesis of racemic cryptophane-222 was reported in 2008,6 and this compound differs from cryptophane-A (compound 2 in Scheme 1) by the lack of six methoxy substituents. This molecule, composed of two CTB units connected by three ethylenedioxy linkers, possesses a D3symmetry because of the helicoidal arrangement of its linkers and represents the simplest molecule of cryptophane-A derivatives. This article reports the chiroptical properties of the two enantiomers of compound 1, measured in solution by polarimetry, ECD, VCD, ROA, and, for the first time, by synchrotron radiation circular dichroism (SRCD). The AC of the two enantiomers of 1 has been determined from ECD, VCD, and ROA experiments associated with DFT calculations, and in the solid state from their X-ray structures. Finally, the unusual polarimetric properties of 1 when using various solvents have been interpreted considering conformational changes in the three ethylenedioxy linkers.
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EXPERIMENTAL SECTION Synthesis of Cryptophane 1. The racemic mixture of cryptophane 1, (rac)-1, was prepared according to a known procedure.6 Enantiopure cryptophanes MM-1 and PP-1 were obtained and purified as described below. The 1H NMR and 13 C NMR of MM-1 and PP-1 are identical to those reported for (rac)-1. Compound [CD(−)254]-1: 1H NMR (500 MHz, CDCl3), δ: 7.09 (6H, d, J = 8.5 Hz), 6.66 (6H, s), 6.48 (6H, d, J = 8.5 Hz), 4.62 (6H, d, J = 13.5 Hz), 4.17 (12H, m), 3.48 (6H, d, J = 13.5 Hz). 13C NMR (126.7 MHz, CDCl3, 25 °C), δ: 156.9 (6C), 140.9 (6C), 131.6 (6C), 130.8 (6C), 117.0 (6C), 113.5 (6C), 65.5 (6C), 36.3 (6C). HRMS (ESI) calcd for C48H43O6 [M+], 715.3054; found, 715.3056. Compound [CD(+)254]-1: 1H NMR (500 MHz, CDCl3), δ: 7.09 (6H, d, J = 8.5 Hz), 6.66 (6H, s), 6.48 (6H, d, J = 8.5 Hz), 4.62 (6H, d, J = 13.5 Hz), 4.17 (12H, m), 3.48 (6H, d, J = 13.5 Hz). 13C NMR (126.7 MHz, CDCl3, 25 °C), δ: 156.9 (6C), 140.9 (6C), 131.6 (6C), 130.8 (6C), 117.0 (6C), 113.5 (6C), 65.5 (6C), 36.3 (6C). HRMS (ESI) calcd for C48H43O6 [M+], 715.3054; found, 715.3019. Chiral Separation of the Two Enantiomers of 1 via HPLC. Separation of the two enantiomers of compound 1 was carried out on a semipreparative Chiralpak ID column (250 × 12651
DOI: 10.1021/acs.jpcb.6b09771 J. Phys. Chem. B 2016, 120, 12650−12659
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The Journal of Physical Chemistry B temperature was set to 20 °C with a Peltier controlled sample holder. Previously, (+)-camphor-10-sulfonic acid was used to calibrate the amplitudes and wavelength positions of the SRCD experiment. Data treatment including averaging, baseline subtraction, smoothing, scaling, and standardization were carried out with CDtool.25 IR and VCD Measurements. IR and VCD spectra were recorded on an FTIR spectrometer equipped with a VCD optical bench, 26 following the experimental procedure previously published.17 Samples were held in a 250 μm path length cell with BaF2 windows. The IR and VCD spectra of the two enantiomers of 1 were measured in CDCl3 and CD2Cl2 solvents at a concentration of 0.015 M. Raman and ROA Measurements. Raman and ROA spectra were recorded on a ChiralRAMAN spectrometer, following the experimental procedure previously published.15 The two enantiomers of 1 were dissolved in CDCl3 and CD2Cl2 solvents at a concentration of 0.1 M and filled into a fused silica microcell (4 × 3 × 10 mm3). The laser power was 200 mW (∼80 mW at the sample). The presented spectra in CDCl3 (CD2Cl2) are an average taken over about 16 (40) h. Theoretical Calculations. All DFT and time-dependent DFT (TDDFT) calculations were carried out using Gaussian 09.27 A preliminary conformer distribution search of 1 was performed at the molecular mechanics level of theory, utilizing MM+ and MMFF94 force fields incorporated in HyperChem 8 and ComputeVOA software packages, respectively. All conformers within roughly 8 kcal/mol of the lowest-energy conformer were kept and their geometries optimized at the DFT level using B3PW91 functional28 and 6-31G** basis set.29 Finally, six conformers were selected, corresponding to G−G−G−, G−G−G+, G−G+G+, G+G+G+, G−TT, and TTT conformations of the three ethylenedioxy linkers.30 Then, these six conformers were reoptimized with the use of the IEFPCM model of solvent (CH2Cl2 and CHCl3).31,32 Vibrational frequencies, IR and VCD intensities, and ROA intensity tensors (excitation at 532 nm) were calculated at the same level of theory. For comparison with the experiment, the calculated frequencies were scaled by 0.968 and the calculated intensities were converted to Lorentzian bands with a full width at halfmaximum (FWHM) of 14 cm−1. OR calculations have been carried out at several wavelengths (365, 435, 532, 546, 577, and 589 nm) by means of DFT methods (B3PW91 functional/6-31G** basis set) for the six conformers reoptimized with the use of the PCM solvent model. ECD spectra were calculated at the TDDFT level using the MPW1K functional33 and the 6-31+G* basis set. Calculations were performed for the six conformers reoptimized with the use of the PCM solvent model (IEFPCM = CH2Cl2), considering 120 excited states. For comparison with the experiment, the rotational strengths were converted to Gaussian bands with a FWHM of 0.05 eV.
mL/min) is shown in Figure 1. Enantiomer [CD(−)254]-1 was first eluted (t1 = 4.54 min), followed by enantiomer [CD(+)254]-1 (t2 = 5.39 min, α = 1.56).34
Figure 1. Separation of the two enantiomers of 1 using an analytical chiral HPLC column.
To obtain the two enantiomers in fair quantities, the chiral separation of 1 was first performed on a semipreparative Chiralpak ID column. The experimental conditions for the chiral separation are given in the Experimental. After this HPLC separation, the enantiomeric excess of the two collected enantiomers, [CD(−)254]-1 and [CD(+)254]-1, was measured using analytical HPLC (Figure S1). Thus, from 320 mg of racemic material, 135 mg of [CD(−)254]-1 (ee > 98%) and 135 mg of [CD(+)254]-1 (ee > 98%) were isolated. Then, the two enantiomers were purified using column chromatography on a silica gel (eluent: CH2Cl2/acetone 90/10) and recrystallized in a mixture of CHCl3 and EtOH. This overall procedure ensures an excellent chemical purity and very high enantiomeric excess for each enantiomer. The 1H NMR and 13C NMR for the two enantiomers are identical to those reported for (rac)-1 (Figures S2−S5). X-ray Crystallographic Structures. X-ray quality crystals of [CD(+)254]-1 and [CD(−)254]-1 were obtained in pyridine. The crystallographic data and the thermal ellipsoid plots of the two X-ray crystal structures are reported in Table S1 and Figure S6, respectively. Thanks to the determination of both Flack and Hooft parameters, the X-ray structures of the two enantiomers of 1 allow the assignment of the AC for these two compounds in the solid state. Thus, it was found that the first eluted compound [CD(−)254]-1 corresponds to the MM1 derivative. Similarly, the PP AC can be assigned to the second eluted compound [CD(+)254]-1. MM-1 and PP-1 crystallize in a trigonal P3121 and a trigonal P3221 space group, respectively. Three cryptophane molecules are present inside each unit cell (Z = 3). A strong disorder was observed for both structures, and the pyridine molecules present in the X-ray structure of MM-1 could not be refined. Disorder is also present in the alkyl chains connecting the two CTB caps. This suggests that in the solid state the ethylenedioxy linkers can adopt gauche (G+ or G−) or trans (T) conformations, as previously observed for cryptophane-A and its congeners.35 A closer examination of the X-ray structure of the PP-1 enantiomer in Figure 2 shows that the three ethylenedioxy linkers display dihedral angles of −54.8,
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RESULTS Synthesis and HPLC Separation of the Two Enantiomers of 1. The racemic mixture of cryptophane 1, (rac)-1, was prepared according to a known procedure (Scheme S1).6 As compound 1 does not possess any substituent to introduce a chiral substrate, HPLC on a chiral stationary phase has been used to separate the two enantiomers of 1. The separation of the two enantiomers of 1 using the analytical chiral HPLC column (Chiralpak IB, heptane/EtOH/CHCl3 20/40/40, 1 12652
DOI: 10.1021/acs.jpcb.6b09771 J. Phys. Chem. B 2016, 120, 12650−12659
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The Journal of Physical Chemistry B
Figure 3. SOR values (10−1 deg cm2 g−1) of [CD(+)254]-1 recorded at several wavelengths (365, 435, 546, 577, and 589 nm) in chloroform (c = 0.26), dichloromethane (c = 0.24), DMSO (c = 0.26), acetone (c = 0.17), DMF (c = 0.24), and pyridine (c = 0.1) solvents.
Figure 2. X-ray structure of the PP-1 enantiomer. The purple area represents the volume accessible (Vvdw = 73.5 Å3) for a guest molecule. The thermal ellipsoids are set to 50% probability. Hydrogen atoms have been removed for clarity.
−54.8, and −110.6°, which is characteristic of a mixture of the G−G−G− and G−G−T conformers. The unit cells of [CD(+)254]-1 and [CD(−)254]-1 exhibit large intermolecular volumes suitable for accommodating solvent molecules. For instance, [CD(−)254]-1 displays intermolecular voids of 707 Å3 per unit cell (i.e., 235 Å3 per cryptophane molecule). Finally, the intramolecular volume (cavity voids) has been measured to be 220.6 Å3 per unit cell (i.e., 73.5 Å3 per cryptophane molecule), which is a value between the estimated cavity volumes of the G−G−G− (65 Å3) and TTT (95 Å3) conformers. Polarimetry and ECD Spectroscopy. OR values for the two enantiomers of 1 have been measured in six solvents (DMSO, CH2Cl2, pyridine, acetone, CHCl3, and DMF) at various wavelengths. Compounds [CD(+)254]-1 and [CD(−)254]-1 are soluble in DMSO, CH2Cl2, CHCl3, and DMF but only sparingly soluble in pyridine and acetone. The specific optical rotation (SOR) values of the two enantiomers are reported in Tables S2 and S3, and the wavelength dependence of [CD(+)254]-1 is shown in Figure 3. The SOR values are strongly affected by the nature of the solvent. More importantly, a change of sign of the SOR values is observed in CHCl3, DMF, and acetone at short wavelengths. This effect is not observed in DMSO, CH2Cl2, and pyridine solvents. For instance, the second eluted enantiomer [CD(+)254]-1 shows a positive SOR value at 365 nm ([α]365 = +42.4) and a negative SOR value at 589 nm ([α]589 = −17.8) in CHCl3. In contrast, in CH2Cl2, the SOR values are negative regardless of the wavelength ([α]365 = −60.8 and [α]589 = −37.9). The first eluted enantiomer [CD(−)254]-1 shows a similar behavior but the sign of the SOR value is inverted. Polarimetric measurements were also performed in various solvents with (−)589-cryptophane-A ((−)589-2) and (+)589cryptophane-(OAc)5 ((+)589-3), and their SOR values at several wavelengths are reported in Tables S4 and S5, respectively. Cryptophane-A has been chosen because its chiroptical properties have been thoroughly studied in the past and it can be considered as a standard compound. This compound displays large SOR values ([α]365 = −1151.4 and [α]589 = −274.1; CHCl3, c = 0.13) regardless of the nature of the
solvent. Cryptophane-(OAc)5 presents lower SOR values ([α]365 = +160.8 and [α]589 = +20.9; CHCl3, c = 0.15). In both cases, a monotonous decrease in the magnitude of the SOR curves with the wavelength has been observed, regardless of the nature of the solvent. Generally, for cryptophane-A derivatives, the sign of the SOR value at 589 nm, taken as reference in the determination of the AC, is the same as that of the CD value at 254 nm. This study shows that this rule does not apply in the case of cryptophane-222. Consequently, attention must be paid to give the sign of the OR for the two enantiomers of 1 (mention of the wavelength and mention of the solvent at 365 nm). To complete this study, the UV−vis and ECD spectra of the two enantiomers of 1 have been recorded in different solvents. Unfortunately, DMSO, DMF, and acetone are not appropriate because these three solvents strongly adsorb light in the region of interest. Thus, UV−vis and ECD experiments for the two enantiomers of 1 have been performed in CH3CN, THF, CH2Cl2, and CHCl3 solvents. The ECD spectra were recorded down to 210 nm in CH3CN and THF solvents, and down to 230 (235) nm in CH2Cl2 (CHCl3). The UV−vis spectra of 1, measured in THF and CH2Cl2 solutions, reveal two broad bands in the 230−310 nm wavelength region (Figure S7). The band of moderate intensity (8000−9000 L mol−1 cm−1) located in the 260−300 nm wavelength region corresponds to the 1Lb transition of the phenyl rings. The second band located around 235 nm, with a larger intensity (∼35 000 L mol−1 cm−1), is related to the 1La transition. Finally, the UV−vis spectra recorded in THF solution exhibit a strong absorption band below 210 nm, corresponding to the 1Bb transition of the phenyl rings. The ECD spectra of the two enantiomers are reported in Figure S8 for the four solvents. In these solvents, the ECD spectra of [CD(+)254]-1 and [CD(−)254]-1 display four bands in the 230−320 cm−1 spectral range. For instance, in CHCl3 solution, the ECD spectrum of [CD(+)254]-1 presents a bisignate pattern in the 1Lb region with a positive contribution at longer wavelength. Similarly, in the 230−260 nm region, the ECD spectrum reveals a second bisignate pattern with a positive contribution at 250 nm and a negative one at 240 nm. 12653
DOI: 10.1021/acs.jpcb.6b09771 J. Phys. Chem. B 2016, 120, 12650−12659
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The Journal of Physical Chemistry B
Figure 4. Comparison of experimental (a) IR and (b) VCD spectra of [CD(+)254]-1 (black spectra) and (+)589-2 (red spectra) in CDCl3 solution (15 mM, 250 μm path length).
The sign of these two bands has been previously used to determine the AC of cryptophane-A,16,17 and hemicryptophane derivatives.36 As expected, the two enantiomers of 1 exhibit a perfect mirror image in the overall spectral region. Finally, the ECD spectra recorded in CHCl3, CH2Cl2, and THF solutions are very similar in shapes and intensities in the 1La and 1Lb regions (Figure S9). VCD and ROA Spectroscopy. The chiroptical properties of enantiopure cryptophane 1 have also been investigated using VCD in CDCl3 and CD2Cl2 solutions. IR and VCD spectra of the [CD(+)254]-1 enantiomer (black spectra), recorded in CDCl3 solution (15 mM), are reported in Figure 4a,b, respectively, and are compared with the IR and VCD spectra of the (+)589-2 enantiomer of cryptophane-A (red spectra). Comparison of the IR spectra of 1 and 2 reveals strong spectral differences (Figure 4a), indicating that the absence of the six methoxy substituents for compound 1 affects the intensities and frequencies of most of the bands of cryptophane-A drastically. For instance, the intensities of the bands due to the ν8bCC and ν8aCC stretching vibrations of the rings, observed at 1608 and 1577 cm−1, respectively, for 2, increase significantly in the IR spectra of 1. In contrast, the band observed at 1510 cm−1, due to the ν19bCC stretching vibrations of the rings, decreases significantly and shifts to lower wavenumbers (1497 cm−1) in the IR spectra of 1. The bands at 1466, 1445, and 1397 cm−1 associated with the δaCH3, δs′CH3, and δsCH3 bending vibrations of methyl groups, respectively, disappear in the IR spectrum of 1. Finally, the IR spectra of the two compounds are totally different at lower wavenumbers as the bands observed in this spectral range correspond to coupled modes; thus, the vibrations of the methoxy substituents are involved in most of the bands for 2. The IR spectra of the [CD(+)254]-1 enantiomer measured in CDCl3 and CD2Cl2 solvents are reported in Figure S10, which shows that these spectra are similar, except in the 1320−1240 cm−1 region where different relative intensities of the bands are observed. The VCD spectra of the two enantiomers of 1 measured in CDCl3 and CD2Cl2 solvents are reported in Figure S11, whereas the comparison of the experimental VCD spectra of [CD(+)254]-1 and (+)589-2 in CDCl3 solution is presented in Figure 4b. As shown in Figure S11a,b, the VCD spectra of 1 seem independent of the nature of the solvent, even though slight spectral differences are observed in the 1320−1240 cm−1
region (see Figure S11c). In contrast, the VCD spectrum of [CD(+)254]-1 differs significantly from that of (+)589-2 in the 1700−950 cm−1 spectral range (Figure 4b). In addition, the intensities of the VCD bands are significantly lower for [CD(+)254]-1. This feature is probably a consequence of the higher flexibility of the ethylenedioxy linkers, favored by the absence of the methoxy substituents for 1. Thus, the knowledge of the configuration of the cryptophane-A molecule,15,17 (+)589PP-2, cannot be used to determine, by analogy, that of [CD(+)254]-1. Finally, experimental Raman and ROA spectra measured for CDCl3 and CD2Cl2 solutions of 1 are shown in Figure S12a,b, respectively. The very low intensities of the cryptophane bands on the raw Raman spectra with respect to those of the solvents reveal the difficulty to perform experiments at moderate concentration (0.1 M). In addition, the Raman spectrum of the two enantiomers of 1 in CD2Cl2 solution exhibits a fluorescence background, making ROA experiments more difficult. Nevertheless, ROA spectra of the two enantiomers are nearly perfect mirror images, as expected for enantiopure materials. As already mentioned for the ECD and VCD experiments, the ROA spectra of 1 seem independent of the nature of the solvent. However, as shown in Figure S12c, slight differences between the two solvents are observed for the ROA spectra at 1485, 1205, and 1070 cm−1, whereas the spectral modifications at low wavenumbers (
