VCD spectroscopy reveals conformational changes of chiral crown ethers upon complexation of potassium and ammonium cations.

Two chiral derivatives of 18-crown-6, namely the host molecules 2,3-diphenyl- and 2-phenyl-18c6, serve as model systems to investigate whether VCD spectroscopy can be used to monitor conformational changes occurring upon complexation of guests. Host-guest complexes of both crown ethers were prepared by addition of KNO3. The more bulky 2,3-diphenyl-18c6 is found to undergo major conformational changes upon encapsulation of K+, which are revealed as characteristic changes of the VCD spectral signatures. In contrast, while 2-phenyl-18c6 also incorporates K+ into the macrocycle, strong conformational changes are not occurring and thus spectral changes are negligible. With an octyl ammonium cation as guest molecule, 2,3-diphenyl-18c6 shows the same conformational and spectral changes that were observed for K+-complexes. In addition, the asymmetric NH3-deformation modes are found to gain VCD intensity through an induced VCD process. An analysis of the vibrational spectra enables a differentiation of VCD active and inactive guest modes: There appears to be a correlation between the symmetry of the vibrational mode and the induced VCD intensity. While this finding makes the host-guest complexes interesting systems for future theoretical studies on the origin of induced VCD signatures, the observations described in this study demonstrate that VCD spectroscopy is indeed a suitable technique for the characterization of supramolecular host-guest complexes.

Induced VCD and conformational chirality in host-guest complexes of a chiral ammonium salt with crown ethers.

The hydrogen bonded complexes of the chiral ammonium salt α-methylbenzyl ammonium chloride (MBA-H+Cl-) and the achiral crown ethers 18c6 and 15c5 serve as model systems to investigate the effect of host-guest complex formation on the conformational preferences of the macrocycles. We demonstrate that the intermolecular interactions result in new VCD signatures, that can be assigned to vibrational modes of the crown ethers. Based on a detailed conformational analysis, we investigate the origin of these signatures and discuss induced VCD (iVCD) and conformational chirality as possible sources of VCD intensity. The macrocycle in the MBA-H+/18c6 complex prefers either an achiral D3d-symmetric conformation, which gives rise to iVCD, or chiral conformations, that feature individual contributions to the VCD spectrum. For the MBA-H+/15c5 complex, the contributions of the macrocycle to the VCD signatures are less pronounced and found to arise solely from conformational chirality. Therefore, analysis of the VCD signatures confirms that the small chiral guest molecule is able to affect the conformational preferences of a macrocyclic host. The study thus demonstrates the suitability of VCD spectroscopy for the characterization of analogous supramolecular host-guest complexes.

More complex, less complicated? Explicit solvation of hydroxyl groups for the analysis of VCD spectra.

Solute-solvent interactions and in particular hydrogen bonding can significantly influence the appearance of vibrational spectra due to band shifts, intensity changes and band broadening. In VCD spectroscopy, solvation may also lead to sign changes and thus an overall drastic change in the spectral pattern. As the VCD spectral analysis relies heavily on the comparison with computed spectra, such solvent effects have to be accounted for in the calculations. For simple model systems with one stereocenter, we have previously shown for carboxylic acids and hydroxyl groups that considering solvation explicitly improves the match substantially. In the present study we evaluate if explicit solvation is always necessary and if larger, more complex molecules featuring several stereocenters show the same susceptibility to H-bonding induced spectral changes as the previously investigated model systems. We analyse the spectra of the diastereomeric pairs menthol/neomenthol and borneol/isoborneol and study both experimentally and computationally the influence of hydrogen bonding to dimethylsulfoxide-d6 (DMSO-d6) and acetonitrile-d3 (ACN-d3) on their VCD spectral signatures. Further chiral alcohols with tertiary hydroxyl group (terpinen-4-ol and cedrol) and more complex structures with multiple stereocenters (cholesterol) are investigated to show that solvent effects on the spectra become less pronounced. We related this to the increasing number of vibrational bands that are insensitive to solvation and thus overlap with actually affected modes. As a consequence, the analysis of the spectra does not require consideration of explicit solvation and in this respect becomes less complicated.

How many solvent molecules are required to solvate chiral 1,2-diols with hydrogen bonding solvents? A VCD spectroscopic study.

Strong solute-solvent interactions have been shown to have a significant influence on the vibrational circular dichroism (VCD) spectral signatures of chiral solutes. In order to use VCD spectroscopy to determine absolute configurations, these intermolecular interactions thus need to be accounted for in spectra simulations. For hydrogen bond donating functional groups such as carboxylic acids or hydroxy groups, it has been shown that micro-solvation with a single solvent molecule is usually sufficient to model the effect of the solvent on the vibrational spectra. In the case of diols, however, solvent molecules are competing against the intramolecular hydrogen bond. Therefore, this study investigates the influence of solute-solvent interactions on the conformational preferences and VCD spectroscopic features of chiral 1,2-diols with the aim to answer the title question. We show that both mono- and twofold solvation lead to unique spectral features that can be distinguished experimentally. Furthermore, in the context of absolute configuration determinations, the results of the study suggest that it will not be possible to derive a general rule that is able to tell whether one or two solvent molecules need to be considered explicitly in the simulation of VCD spectra.

Solvation and self-aggregation of chiral alcohols: how hydrogen bonding affects their VCD spectral signatures.

In infrared spectra, intermolecular hydrogen bonds give rise to band shifts of OH-stretching vibrations and intensity enhancements of the hydrogen bonded OH-stretching vibration. The fingerprint region of IR spectra is often not considered in the analysis of hydrogen bonds as the effects are rather weak and often masked by other overlapping vibrational modes. For VCD spectra, however, the fingerprint region is the most important spectral range as it typically contains the strongest and most characteristic VCD patterns. As solute-solvent interactions might significantly alter the observed VCD spectral signatures, it is therefore important to understand which vibrational modes are affected by a hydrogen bond to the solvent and how this solute-solvent interaction is best modeled in the theoretical prediction of IR and VCD spectra. For this study, four structurally related primary and secondary chiral alcohols serve as model compounds for our investigations on the effect of solvation of the OH-group in dimethylsulfoxide-d6 and acetonitrile-d3 and of its self-aggregation in chloroform-d1. The analysis of the experimental and computational data allows us to provide first benchmarked guidelines for explicit consideration of solvent molecules in DFT-based spectra calculations of chiral alcohols. In the typical concentration range for VCD measurements, self-aggregation of secondary alcohols is found to be partially negligible, while explicit solvation with DMSO-d6 and ACN-d3 is almost indispensible.