Vibrational Circular Dichroism Experiments Research Articles

Quantum Cascade Laser-Based Vibrational Circular Dichroism Augmented by a Balanced Detection Scheme.

Vibrational circular dichroism (VCD) constitutes a powerful technique, enabling the determination of the absolute configuration of molecules without the need for specialized reagents. While delivering critical information, VCD signals commonly are several orders of magnitude weaker than classical absorbance signals, which so far necessitated long measurement times to achieve acceptable signal-to-noise ratios (SNRs) in VCD experiments. We present here an improved setup for the measurement of VCD in the range between 5.6 and 6.5 μm. Employing an external cavity quantum cascade laser (EC-QCL) as a high-power light source, we collected spectra with competitive noise levels in less than 5 min. The basis for this improvement was a balanced detection module combined with an optical path catered to VCD measurements. With the stabilization provided by the two-detector setup, noise originating from the laser source could be suppressed effectively. Noise level improvement up to a factor of 4 compared to the classical single detector EC-QCL-VCD could be reported. Compared to commercial Fourier transform infrared (FT-IR) instruments, the presented setup offers measurement time reductions of a factor of at least 6, with comparable noise levels. The applicability of the setup for qualitative and quantitative VCDs was proven. With the comparatively high temporal resolution provided, the monitoring of optically active processes will be possible in future applications.

Isolation and absolute configuration determination of alkaloids from Pandanus amaryllifolius

Seven new alkaloids belonging to three typical classes, isolated from an ethanolic extract of Pandanus amaryllifolius, were applied to establish the models in structural elucidation. The first type [pandanusines A and B (1 and 2)] was applied to alkaloids with a diazaspirocyclic ring system. The absolute stereochemistry of aminal carbon is determined by analysis of J-based configuration analysis and circular dichroism spectroscopy, which has never been revealed before. The second type [pandalizines C–E (3–5)], the stereochemistry of unusual indolizinone with chiral hydroxyl substitutions were determined by circular dichroism spectroscopy and vibrational circular dichroism experiments. The last type [norpandamarilactonines C and D (6 and 7)], a comparing model in determination of diastereomers of pyrrolidinyl α,β-unsaturated γ-lactone alkaloids was established. Our study provides solutions for a challenging subject in stereochemistry determination for three different types of Pandanus alkaloids.

ChemInform Abstract: Vibrational Circular Dichroism Absolute Configuration Determination of Natural Products

AbstractReview: 323 refs.

The Clusters-in-a-Liquid Approach for Solvation: New Insights from the Conformer Specific Gas Phase Spectroscopy and Vibrational Optical Activity Spectroscopy.

Vibrational optical activity spectroscopies, namely vibrational circular dichroism (VCD) and Raman optical activity (ROA), have been emerged in the past decade as powerful spectroscopic tools for stereochemical information of a wide range of chiral compounds in solution directly. More recently, their applications in unveiling solvent effects, especially those associated with water solvent, have been explored. In this review article, we first select a few examples to demonstrate the unique sensitivity of VCD spectral signatures to both bulk solvent effects and explicit hydrogen-bonding interactions in solution. Second, we discuss the induced solvent chirality, or chiral transfer, VCD spectral features observed in the water bending band region in detail. From these chirality transfer spectral data, the related conformer specific gas phase spectroscopic studies of small chiral hydration clusters, and the associated matrix isolation VCD experiments of hydrogen-bonded complexes in cold rare gas matrices, a general picture of solvation in aqueous solution emerges. In such an aqueous solution, some small chiral hydration clusters, rather than the chiral solutes themselves, are the dominant species and are the ones that contribute mainly to the experimentally observed VCD features. We then review a series of VCD studies of amino acids and their derivatives in aqueous solution under different pHs to emphasize the importance of the inclusion of the bulk solvent effects. These experimental data and the associated theoretical analyses are the foundation for the proposed “clusters-in-a-liquid” approach to account for solvent effects effectively. We present several approaches to identify and build such representative chiral hydration clusters. Recent studies which applied molecular dynamics simulations and the subsequent snapshot averaging approach to generate the ROA, VCD, electronic CD, and optical rotatory dispersion spectra are also reviewed. Challenges associated with the molecular dynamics snapshot approach are discussed and the successes of the seemingly random “ad hoc explicit solvation” reported before are also explained. To further test and improve the “clusters-in-a-liquid” model in practice, future work in terms of conformer specific gas phase spectroscopy of sequential solvation of a chiral solute, matrix isolation VCD measurements of small chiral hydration clusters, and more sophisticated models for the bulk solvent effects would be highly valuable.

Vibrational circular dichroism absolute configuration determination of natural products.

The most widely used physical methods for the chemical analysis of natural products are currently well established, although in the case of vibrational circular dichroism (VCD), this is not yet the case. The first VCD experiments were performed only about 40 years ago, and it took some 20 additional years for the development of sufficiently sensitive instrumentation for these types of measurements, since VCD signals are three to four orders of magnitude less sensitive than infrared bands. In addition, it is less than 20 years since chemists started to have routine access to computers that allowed adequate quantum chemical calculations for this type of study. Thus, most applications of VCD to the study of sesquiterpenes, diterpenes, and molecules of similar size have been performed in the present century. Consequently, the main objective of this chapter is to provide some background and to show the use of circularly polarized infrared radiation for the determination of absolute configuration, and in some cases of the configuration of a specific chiral center, in natural products. This is a task that, in some cases, has been almost impossible to complete using other spectroscopic methods. VCD relies mostly on the comparison of an experimental spectrum, obtained in the mid infrared region of the electromechanical spectrum, with a spectrum obtained by density functional theory calculations, a situation that requires a detailed knowledge of the lower energy conformers of the particular molecule being studied.

Chiroptical properties of nona- and dodecamethoxy cryptophanes.

Enantiopure cryptophane derivatives bearing nine (2, 3) and 12 (4) methoxy substituents attached on the six aromatic rings were separated by HPLC using chiral stationary phases. The chiroptical properties of compounds 2-4 were determined from polarimetry, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) experiments and were compared to those of cryptophane-A (1) derivative. ECD spectra of 1 and 4 were calculated by time-dependent density functional theory (TDDFT) to determine the absolute configuration (AC) of cryptophane derivatives. The (+)-PP absolute configuration was thus established for the anti-cryptophane-A (1) and its congeners 2 and 4. VCD experiments associated with DFT calculations confirmed the (+)-PP configuration of anti-compounds 2 and 4 and established the (+)-PM configuration of the syn-3 compound as well. This study revealed the preferential all-trans (TTT) conformation of the three ethylenedioxy linkers for the CHCl3@1, CHCl3@3, and CHCl3@4 complexes, whereas the GTT conformation was found the most favorable for the CHCl3@2 complex.

Diastereomeric preference of a triply axial chiral binaphthyl based molecule: a concentration dependent study by chiroptical spectroscopies.

We have examined the effects of environmental perturbations, specifically solvents and concentrations, on axial chirality of a recently synthesized axially chiral binaphthyl fluorene based salen ligand, named AFX-155, {[2,2'-(1E,1'E)-(R)-1,1'-binaphthyl-2,2'-diylbis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(4-((7-(diphenylamino)-9,9-dihexyl-9H-fluoren-2-l)ethynyl)-phenol)]}. Chirality and dominant conformations of AFX-155 in CDCl3 solvent have been characterized using vibrational absorption (VA) and vibrational circular dichroism (VCD) spectroscopy in combination with DFT calculations. AFX-155 exhibits triple axial chirality: one is at the binaphthyl ring and the other two are related to the axes of chirality along the -C-N bonds where Cs are part of the binaphthyl group. To evaluate solvent and concentration dependence, complementary VA and VCD experiments in both THF-d8 and CDCl3 have been performed, as well as the optical rotatory dispersion (ORD) and electronic CD (ECD) measurements in CDCl3 under much diluted conditions. While the binaphthyl chirality is determined by the synthetic route, the results show that the latter two axial chirality labels of the dominant diastereomers are concentration dependent. Under much diluted conditions, R-binaphthyl, R_intra_HB//R_extra_HB (R-RR) is favoured, whereas R-binaphthyl, S_intra_HB//S_extra_HB (R-SS) is the dominant species in a concentrated solution. This diastereomeric interconversion is found to be independent of the two solvents used. To provide insights into this interesting finding, conformational searches and the related spectral simulations have been carried out at the DFT/B3LYP/6-31G(d) level.

Isotope-assisted vibrational circular dichroism investigations of amyloid β peptide fragment, Aβ(16–22)

Isotope-assisted vibrational circular dichroism (VCD) investigations have been used to probe the site specific local structure of an amyloid peptide for the first time. A seven residue peptide, NH(2)-KLVFFAE-COOH, which represents the Aβ(16-22) fragment of the Alzheimer's amyloid β peptide, was used for these investigations. (13)C labels were introduced separately at the carbonyl group of leucine (residue 17), alanine (residue 21) and also at both sites together. Since VCD spectra provide structure dependent signs, band shapes and frequencies, the isotope-assisted VCD spectroscopy revealed information on site specific secondary structure of the polypeptide. Isotope dilution VCD experiments provided a means to distinguish between parallel and anti-parallel nature of the β-sheet structure formed by the Aβ(16-22) fragment. The current results establish the usefulness of isotope-assisted VCD analysis in determining the site specific secondary structure of amyloid peptides.

Induced Chiroptical Changes of a Water‐Soluble Cryptophane by Encapsulation of Guest Molecules and Counterion Effects

We report the synthesis of the water-soluble cryptophanol derivative 1 and the study of the chiroptical properties of its two enantiomers (>99 % ee) by polarimetry, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD). We show that cryptophanol 1 exhibits unusual chiroptical properties in water under basic conditions (pH>12). For instance, the shapes of the ECD and VCD spectra of 1 in water were strongly dependent on the nature of the alkali metal ions (Li(+), Na(+), K(+), Cs(+)) surrounding the cryptophane and whether or not a guest molecule is present inside the cavity of the host. To the best of our knowledge, this is the first example in which the nature of these counterions governs the chiroptical properties of a host molecule. Moreover, specific ECD spectra were obtained depending on the size of the guest molecules. This makes 1 a good sensor for small neutral molecules in aqueous solvent. Finally, VCD experiments associated with DFT calculations show that the chiroptical changes can be directly correlated to the presence of charges close to the aromatic rings and with a conformational change of the alkyl chains upon encapsulation.

Molecular and supramolecular chirality in gemini‐tartrate amphiphiles studied by electronic and vibrational circular dichroisms

This contribution presents an application of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) to study the molecular and supramolecular chirality in assemblies of gemini-tartrate amphiphiles. Nonchiral dicationic n-2-n amphiphiles (n = 14-20) can self-organize into right- or left-handed structures upon interacting with chiral tartrate counterions. Micellar solutions can also be obtained for shorter alkyl chains (n = 12). First, the conformation of tartrate counterions has been investigated in various environments (micellar solutions and chiral ribbons). ECD and VCD spectra recorded in micellar solutions are independent from the solvent and from the nature of the cations (sodium, cetyl-trimethylammonium, or dimeric surfactant 12-2-12) used and are representative of the anticonformation of the tartrate dianions. On the other hand, drastic changes in the ECD and VCD spectra have been observed in multilayered chiral assemblies of 16-2-16 tartrate. These strong spectral modifications are associated with the chiral arrangement of the tartrate molecules at the surface of the bilayers. Moreover, chirality transfer from counterions to achiral amphiphiles has been clearly evidenced by VCD since circular dichroism has been observed on vibrations related to alkyl chains and gemini headgroups. Finally, ECD and VCD experiments were performed varying the enantiomeric excess of the tartrate. The ECD and VCD intensities do not vary linearly with the enantiomeric excess of the anion and different behaviors have been observed from the two spectroscopic methods: ECD intensities are correlated to the pitch of the ribbons, whereas the VCD intensities are correlated to the dimension of the chiral ribbons.

Chromatographic and spectroscopic studies on the chiral recognition of sulfated β-cyclodextrin as chiral mobile phase additive: Enantiomeric separation of a chiral amine

A fast enantiomeric separation of a chiral aromatic amine was achieved, using ultra high pressure liquid chromatography and highly sulfated beta-cyclodextrin (S-β-CD) as a chiral additive in the mobile phase. The stationary phase consisted of a core–shell support with a particle size of 2.7 μm. Under these conditions the base-line separation was obtained within 2.5 min. The influence of the concentration of the additive, along with the thermodynamics of the separation, was studied. Vibrational circular dichroism (VCD) spectroscopy was applied to assess the absolute configuration of the two enantiomeric analytes, as well as the interaction of these enantiomers with the S-β-CD. The VCD results revealed that S-β-CD undergoes a temperature-induced conformational change. Further, VCD experiments indicate that the interactions of the two enantiomers with the S-β-CD occur through an inclusion of the aromatic part of the analyte, as well as through electrostatic interaction between the protonated amine and the sulfate groups located at the narrow part of the S-β-CD. Molecular mechanics calculations performed according to the VCD results are consistent with experimental data, providing further evidence of these interactions.

Assessment of configurational and conformational properties of naringenin by vibrational circular dichroism

The electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra of both enantiomers of naringenin (4',5,7-trihydroxyflavanone) in acetonitrile solution have been measured. The enantiomers were obtained by chiral HPLC separation of the racemic sample. DFT calculations have been performed for relevant conformers and subsequent evaluations of VCD spectra are compared with VCD experiments: safe assignment of the absolute configuration is provided, based in particular on the VCD data. The relevance of the rotational conformers of the hydroxyl groups and of the mobility of phenol moiety is studied: based on this, we provide a first interpretation of the observed intense and broad couplet at 1325/1350 cm(-1). Four conformers contribute to this pattern with different sign and amplitude as shown by DFT calculations. Time dependent DFT calculations have been performed and compared with ECD experimental data, under the same assumption of conformational properties and mobilities investigated by VCD.