Vibrational Circular Dichroism Spectra Research Articles

Separation of enantiomers of chiral fullerene derivatives through enantioselective encapsulation within an adaptable helical cavity of syndiotactic poly(methyl methacrylate) with helicity memory.

Optically active left (M)- and right (P)-handed helical syndiotactic poly(methyl methacrylate)s (M- and P-st-PMMAs) with a helicity memory enantioselectively encapsulated the racemic C60 derivatives, such as 3,4-fulleroproline tert-butyl ester (rac-1) and tetraallylated C60 (rac-2), as well as the C60-bound racemic 310-helical peptides (rac-3) within their helical cavities to form peapod-like inclusion complexes and a unique "helix-in-helix" superstructure, respectively. The enantiomeric excess (ee) and separation factor (enantioselectivity) (α) of the analyte 1 (ee = 23%-25% and α = 2.35-2.50) encapsulated within the helical cavities of the M- and P-st-PMMAs were higher than those of the analytes 2 and 3 (ee = 4.3%-6.0% and α = 1.28-1.50). The optically pure (S)- and (R)-1 were found to more efficiently induce an excess one-handed helical conformation in the st-PMMA backbone than the optically pure (S)- and (R)-1-phenylethylamine, resulting in intense mirror-image vibrational circular dichroism (VCD) spectra in the PMMA IR regions. The excess one-handed helices induced in the st-PMMAs complexed with (S)- and (R)-1 were memorized after replacement with the achiral C60, and the complexes exhibited induced electric CDs in the achiral C60 chromophore regions.

Vibrational Circular Dichroism Spectroscopy with a Classical Polarizable Force Field: Alanine in the Gas and Condensed Phases.

Polarizable force fields are an essential component for the chemically accurate modeling of complex molecular systems with a significant degree of fluxionality, beyond harmonic or perturbative approximations. In this contribution we examine the performance of such an approach for the vibrational spectroscopy of the alanine amino acid, in the gas and condensed phases, from the Fourier transform of appropriate time correlation functions generated along molecular dynamics (MD) trajectories. While the infrared (IR) spectrum only requires the electric dipole moment, the vibrational circular dichroism (VCD) spectrum further requires knowledge of the magnetic dipole moment, for which we provide relevant expressions to be used with polarizable force fields. The AMOEBA force field was employed here to model alanine in the neutral and zwitterionic isolated forms, solvated by water or nitrogen, and as a crystal. Within this framework, comparison of the electric and magnetic dipole moments to those obtained with nuclear velocity perturbation theory based on density-functional theory for the same MD trajectories are found to agree well with one another. The statistical convergence of the IR and VCD spectra is examined and found to be more demanding in the latter case. Comparisons with experimental frequencies are also provided for the condensed phases.

Multidimensional vibrational circular dichroism for insect wings: Comparison of species.

This study reports the microscopic measurements of vibrational circular dichroism (VCD) on four different insect wings using a quantum cascade laser VCD system equipped with microscopic scanning capabilities (named multi-dimensional VCD [MultiD-VCD]). Wing samples, including (i) beetle, Anomala albopilosa (female), (ii) European hornet, Verspa crabro flavofasciata Cameron, 1903 (female), (iii) tiny dragonfly, Nannophya pygmae Rambur, 1842 (male), and (iv) dragonfly, Symetrum gracile Oguma, 1915 (male), were used in this study. Two-dimensional patterns of VCD signals (~10 mm × 10mm) were obtained at a spatial resolution of 100 μm. Measurements covered the absorption peaks assigned to amides I and II in the range of 1500-1740 cm-1 . The measurements were based on the enhancement of VCD signals for the stereoregular linkage of peptide groups. The patterns were remarkably dependent on the species. In samples (i) and (ii), the wings comprised segregated domains of protein aggregates of different secondary structures. The size of each microdomain was approximately 100 μm. In contrast, no clear VCD spectra were detected in samples (iii) and (iv). One possible reason was that the chain of stereoregular polypeptides was too short to achieve VCD enhancement in samples (iii) and (iv). Notably, the unique features were only observed in the VCD spectra because the IR spectra were nearly the same among the species. The VCD results hinted at the connection of protein microscopic structures with the wing flapping mechanisms of each species.

Mid-IR and CH stretching vibrational circular dichroism spectroscopy to distinguish various sources of chirality: The case of quinophaneoxazoline based ruthenium(II) complexes.

Five diastereomers of ruthenium(II) complexes based on quinolinophaneoxazoline ligands were investigated by vibrational circular dichroism (VCD) in the mid-IR and CH stretching regions. Diastereomers differ in three sources of chirality: the planar chirality of the quinolinophane moiety, the central chirality of an asymmetric carbon atom of the oxazoline ring, and the chirality of the ruthenium atom. VCD, allied to DFT calculations, has been found to be effective in disentangling the various forms of chirality. In particular, a VCD band is identified in the CH stretching region directly connected to the chirality of the metal. The analysis of the calculated VCD spectra is carried out by partitioning the complexes into fragments. The anharmonic analysis is also performed with a recently proposed reduced-dimensionality approach: such treatment is particularly important when examining spectroscopic regions highly perturbed by resonances, like the CH stretching region.

Scaling-up VPT2: A feasible route to include anharmonic correction on large molecules

Vibrational analysis plays a crucial role in the investigation of molecular systems. Though methodologies like second-order vibrational perturbation theory (VPT2) have paved the way to more accurate simulations, the computational cost remains a difficult barrier to overcome when the molecular size increases. Building upon recent advances in the identification of resonances, we propose an approach making anharmonic simulations possible for large-size systems, typically unreachable by standard means. This relies on the fact that, often, only portions of the whole spectra are of actual interest. Therefore, the anharmonic corrections can be included selectively on subsets of normal modes directly related to the regions of interest. Starting from the VPT2 equations, we evaluate rigorously and systematically the impact of the truncated anharmonic treatment onto simulations. The limit and feasibility of the reduced-dimensionality approach are detailed, starting on a smaller model system. The methodology is then challenged on the IR absorption and vibrational circular dichroism spectra of an organometallic complex in three different spectral ranges.

Revisiting the Absolute Configuration of Peyssonnoside A Using Vibrational Circular Dichroism Spectroscopy

Peyssonnoside A is an unusual natural product consisting of a diterpene unit and a sulfonated monosaccharide. The experimental and theoretical comparison of Optical Rotatory Dispersion (ORD) and quantitative Nuclear Magnetic Resonance (NMR) data provided strong evidence for the stereochemistry of the diterpene unit. However, predicted Vibrational Circular Dichroism (VCD) spectra of Peyssonnoside A at the B3LYP/6-311++G(2d,2p) level showed poor correlation to the corresponding experimental spectra, preventing independent absolute configuration (AC) determination from VCD analysis. New calculations using the B3PW91 functional and the 6-311G(3df,2pd) basis set suggest that we can now independently and confidently assign the AC of Peyssonnoside A through VCD analyses. The use of f-polarization functions is responsible for the current successful assignment, compared to previously failed VCD analysis. This study highlights two important points: (a) the importance of using multiple levels of theories for satisfactorily reproducing the experimental spectra and (b) for quantitative comparisons using similarity indices, it is important to consider not only the VCD spectra but also the corresponding absorption spectra.

Differentiation of solvatomorphs of active pharmaceutical ingredients (API) by solid-state vibrational circular dichroism (VCD)

Here, we present the new application of solid-state Vibrational Circular Dichroism (VCD) spectroscopy to differentiate several dutasteride (DS) solvatomorphs – the model active pharmaceutical ingredient (API). Several crystalline DS hydrochloride hydrates solvated with methanol, ethanol, acetonitrile, acetone, and acetic acid were prepared. In contrast to almost identical IR spectra, the VCD ones were very sensitive to changes in the sample composition. We marked significant differences in the shape of VCD spectra of studied DS solvatomorphs, DS hydrates, and DS polymorphic forms. Our findings, supported by DFT calculations, show that VCD spectroscopy has the pronounced ability to distinguish their crystal arrangements. We believe that this contribution will extend the use of VCD in the pharmaceutical industry for developing and designing new chiral drug products for the identification, description, and in-depth probing of several pharmaceutical solvatomorphs in the future.

On the use of property-oriented basis sets for the simulation of vibrational chiroptical spectroscopies

We computed vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra for a test set of six chiral compounds using two standard density-functionals and an array of basis sets. We analysed the performance of property-oriented basis sets using a quadruple-zeta basis as a reference against four key metrics. We find little qualitative difference between the spectra produced by the larger basis sets (ORP, LPolX, aug-cc-pVTZ, and aug-cc-pVQZ), though their quantitative metrics exhibit wide variations. The smaller basis sets (rDPS, augD-3-21G, augT3-3-21G, Sadlej-pVTZ, and aug-cc-pVDZ) performed better for VCD rotatory strengths than for the corresponding ROA circular intensity differences (CIDs). However, this trend diminishes as the basis-set size is increased, lending validity to the conclusion that more robust property-oriented basis sets are required for ROA spectral generation than that of VCD. We observed improved performance in the mid-infrared region compared to the high-frequency regime, as well as overestimation of VCD rotatory strengths in the latter region as compared to the reference. We conclude that the ORP and LPol-ds basis sets are the most efficient and effective choices of basis set for the prediction of VCD and ROA spectra, as they provide both highly accurate results at reduced computational expense.

Exploring the Influence of the Phosphorus-Heteroatom Substitution in Nicotine on Its Electronic and Vibrational Spectroscopic Properties.

The influence of phosphorus substitution of nitrogen in heterocyclic compounds on the vibrational spectroscopy as well as frontier molecular orbitals are analyzed. Nicotine with two nitrogen atoms in its structure is taken as the sample system to be studied computationally. By replacing the nitrogen atom in one or both rings of this molecule with phosphorus, three nicotine derivatives are created. The vibrational circular dichroism and infrared spectra of these four molecules in their monomer state, as well as the assemblies up to trimers are determined. The aforementioned spectra are calculated using static quantum chemical calculations employing a cluster-weighted approach. The calculated gas phase spectra of nicotine are compared to their respective experimental spectra. It is observed that the nicotine derivatives with phosphorus in the methylpyrrolidine ring have considerably different gas phase and bulk phase vibrational circular dichroism spectra when compared to nicotine. The phosphorus substitution reduces the energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital as well as altering the polarizability and reactivity of the investigated molecules.

Efficient Prediction of Mole Fraction Related Vibrational Frequency Shifts.

While so far it has been possible to calculate vibrational spectra of mixtures at a particular composition, we present here a novel cluster approach for a fast and robust calculation of mole fraction dependent infrared and vibrational circular dichroism spectra at the example of acetonitrile/(R)-butan-2-ol mixtures. By assigning weights to a limited number of quantum chemically calculated clusters, vibrational spectra can be obtained at any desired composition by a weighted average of the single cluster spectra. In this way, peak positions carrying information about intermolecular interactions can be predicted. We show that mole fraction dependent peak shifts can be accurately modeled and, that experimentally recorded infrared spectra can be reproduced with high accuracy over the entire mixing range. Because only a very limited number of clusters is required, the presented approach is a valuable and computationally efficient tool to access mole fraction dependent spectra of mixtures on a routine basis.

Conformational distributions of tetrahydro-2-turoic acid in water at different pH values by their IR and vibrational circular dichroism spectra

Infrared (IR) and vibrational circular dichroism (VCD) spectra of tetrahydro-2-furoic acid (THFA) in aqueous solutions under several different pH conditions were recorded. To interpret the IR and VCD spectra of THFA obtained in highly acidic and basic aqueous solutions, extensive and systematic conformational searches were conducted to acquire the low-energy minima for both the neutral and deprotonated forms of THFA species, as well as their hydrated clusters. This was accomplished by using the conformer-rotamer ensemble sampling tool (CREST) with an implicit solvation model for water. The CREST candidates were further optimized at the B3LYP-D3BJ/def2-TZVP level of theory. The simulated VCD spectra of the neutral THFA conformers in the polarizable continuum model (PCM) of water alone exhibit little agreement with the experimental data under highly acidic conditions. Applying the clusters-in-a-liquid solvation model by considering the monohydrate THFA conformers in the PCM of water, significantly improved agreement with the experimental data. Similarly, the deprotonated THFA species solvated with one to four explicit water molecules in the PCM of water were considered. While the IR and VCD spectra of the deprotonated THFA monohydrate conformers offer the best agreement with the experimental data, other larger hydrated clusters, particularly the dihydrates, also contribute to the spectra. Through the synergistic combined experimental and theoretical approach used in the study, comprehensive conformational distributions of the predominant THFA species across various pH conditions were extracted.

Determining the nanostructure and main axis of gly-his-gly fibrils using the amide I’ bands in FTIR, VCD, and Raman spectra

The zwitterionic tripeptide glycyl-histidine-glycine (GHG) has been shown to self-assemble into visible crystalline fibrils that form a gel-supporting network with a very high storage modulus. Here we elaborate on the theory and experimental setup behind our novel approach employed to determining the main fibril axis for these gel-forming fibrils by simulating the amide I band profile for infrared absorption (IR), vibrational circular dichroism (VCD), and visible Raman scattering. We also highlight that combining these three vibrational spectroscopies can help in validating structures that are solved using powder x-ray diffraction analysis (PXRD). The PXRD analysis yielded a GHG fibril unit cell with P21 symmetry containing two peptide monomers and two water molecules. The monomers adopt a conformation reminiscent of the distorted polyproline II conformation obtained for tri-lysine in aqueous solution. Stabilization occurs primarily through peptide-peptide intermolecular hydrogen bond interactions, while the role of water in peptide hydration is minimal. The comparison of simulated and experimental amide I’ band profiles suggests that the xz plane of the crystal unit cell is being predominantly probed in the experimental IR and VCD spectra, with the x axis of the unit cell pointing in the direction of the main fibril axis. The monomer peptide in the unit cell interacts with six adjacent peptides forming hydrophobic channels by edge-to-face and parallel-displaced ππstacking in the y direction. These cores are further stabilized by a plethora of intermolecular interactions in the x and z directions. Our result suggests that the hydrophobic xz-surfaces would be a good target for the adsorption of hydrophobic drugs.

Quantitative evaluation of IR and corresponding VCD spectra

Classical electromagnetic theory applied to infrared (IR) and vibrational circular dichroism (VCD) spectra of chiral compounds can provide useful insights, such as the fact that the area of all bands of wavenumber-normalized absorbance above zero must be the same as the area below zero. Additionally, dispersion analysis based on wave optics and dispersion theory, which was extended by Born and Kuhn to include chiral substances, can be used to quantitatively describe the dielectric function and the chiral admittance functions that shape IR and VCD spectra. For dispersion analysis, pairs of coupled oscillators, with five different kinds of parameters, namely oscillator strength, damping, oscillator position, vertical distance between coupled oscillators, and the coupling constant are used to model the dielectric functions and chiral admittance functions. We report the results of such an analysis for α-Pinene and Propylene oxide. For most bands, the oscillator model using two coupled oscillators is sufficient to achieve a good correspondence between experimental and modelled data.

Solid-state vibrational circular dichroism: Methodology and application for amphetamine derivatives

Amphetamine derivatives are considered most seized substances worldwide. In this study, solid-state vibrational circular dichroism (VCD) measurements of enantiomerically pure substances were performed for spectroscopic discrimination between (S)- and (R)-enantiomers. First, we have developed a universal experimental approach to obtain reliable and reproducible solid-state VCD spectra. First, the samples were prepared as pellets composed of mixtures of camphor as a model compound and a crystalline matrix powder. In order to obtain the best results without artifacts and with a maximum signal-to-noise ratio, the following experimental conditions were optimized: pellet thickness and diameter and sample rotation speed. The optimized parameters were then used for the analysis of amphetamine and its derivatives (methamphetamine and 3,4-methylendioxymethamphetamine). Our high-quality spectra and results suggest that solid-state VCD spectroscopy represents a cost-effective and easy-to-use method for the analysis of conformation changes and molecular packing in solid-state with potential applications in pharmaceutical and forensic practice.

Selective Chirality Transfer to the Bis(trifluoromethylsulfonyl)imide Anion of an Ionic Liquid.

Chirality transfer from the chiral molecule (R)-1,2-propylene oxide to the achiral anion of the 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquid is observed. The chiral probe selectively affects one part of the binary ionic liquid, i. e., it has previously been shown experimentally and theoretically that this particular imidazolium cation can be affected by chirality transfer, but in the present system chirality is almost exclusively transferred to the anion and not to both parts of the solvent (anion and cation). This observation is of high relevance because of its selectivity and because anion effects are usually much more important in ionic liquid research than cation effects. From ab initio molecular dynamics simulations, a conformational analysis and dissected vibrational circular dichroism spectra are obtained to study the chirality transfer. While in the neat ionic liquid two mirror imaged trans conformers of the anion occur almost equally, we observe an excess of one of these conformers in the presence of the chiral solute, causing optical activity of the anion. Although the cis conformers are not tremendously affected by the chirality transfer, they gain in total population when (R)-1,2-propylene oxide is dissolved in the ionic liquid.

Influence of microsolvation on vibrational circular dichroism spectra in dimethyl sulfoxide solvent: A Bottom-Up approach using Quantum cluster growth

Chiroptical spectroscopic measurements serve as routine methods to assign the absolute configuration of chiral compounds and interpret their conformational behavior in solution. One common challenge is the use of strongly hydrogen-bonding solvents, which can significantly bias the conformational ensemble and affect the vibrational circular dichroism (VCD) active bands in solution. One such solvent is dimethyl sulfoxide (DMSO)—an excellent solvent for stubborn compounds—that must be explicitly considered in VCD analysis. Explicit consideration of solvent remains a critical challenge in chiroptical spectroscopy due to the need to explore solute–solvent conformational space and the computational expense in modeling these clusters. Interested in the recent development of the Quantum Cluster Growth (QCG) program by the Grimme lab, we set out to model and interpret previously reported VCD spectra for several molecules using their efficient program. Our purposes are two-fold: (1) to investigate the applicability of the QCG program to the problem of reproducing VCD spectra in DMSO solvent and (2) to identify limitations in using this approach. We find that we can conveniently model and analyze the VCD spectra of investigated molecules in DMSO. However, the final set of conformers used for VCD calculations are functional dependent and different sets of conformers can provide satisfactory quantitative agreement between experimental and predicted VCD spectra. We hope that this study provides guidance for future chiroptical studies in the challenging DMSO solvent.

Impact of conformation and intramolecular interactions on vibrational circular dichroism spectra identified with machine learning

Vibrational Circular Dichroism (VCD) spectra often differ strongly from one conformer to another, even within the same absolute configuration of a molecule. Simulated molecular VCD spectra typically require expensive quantum chemical calculations for all conformers to generate a Boltzmann averaged total spectrum. This paper reports whether machine learning (ML) can partly replace these quantum chemical calculations by capturing the intricate connection between a conformer geometry and its VCD spectrum. Three hypotheses concerning the added value of ML are tested. First, it is shown that for a single stereoisomer, ML can predict the VCD spectrum of a conformer from solely the conformer geometry. Second, it is found that the ML approach results in important time savings. Third, the ML model produced is unfortunately hardly transferable from one stereoisomer to another.

Impact of conformation and intramolecular interactions on vibrational circular dichroism spectra identified with machine learning

Impact of conformation and intramolecular interactions on vibrational circular dichroism spectra identified with machine learning

Comparison of different density functional theory methods for the calculation of vibrational circular dichroism spectra.

The determination of the absolute configuration (AC) of an organic molecule is still a challenging task for which the combination of spectroscopic with quantum-mechanical methods has become a promising approach. In this study, we investigated the accuracy of DFT methods (480 overall combinations of 15 functionals, 16 basis sets, and 2 solvation models) to calculate the VCD spectra of six chiral organic molecules in order to benchmark their capability to facilitate the determination of the AC.

Infrared and vibrational circular dichroism spectra of methyl β-D-glucopyranose in water: The application of the quantum cluster growth and clusters-in-a-liquid solvation models.

The infrared (IR) and vibrational circular dichroism (VCD) spectra of methyl β-D-glucopyranose in water were measured. Both implicit and explicit solvation models were utilized to explain the observed spectra. The vast body of existing experimental and theoretical data suggested that about eight explicit water molecules are needed to account for the solvent effects, supported by the current Quantum Cluster Growth (QCG) analysis. Extensive manual and systematic conformational searches of the molecular target and its water clusters were carried out by using a recently developed conformational searching tool, conformer-rotamer ensemble sampling tool (CREST), and the microsolvation model in the associated QCG code. The Boltzmann averaged IR and VCD spectra of the methyl β-D-glucopyranose-(water)n (n = 8) conformers in the PCM of water provide better agreement with the experimental ones than those with n = 0, 1, and 2. The explicit solvation with eight water molecules was shown to greatly modify the conformational preference of methyl β-D-glucopyranose from its monomeric form. Further analyses show that the result is consistent with the existence of long-lived methyl β-D-glucopyranose monohydrates with the additional explicit water effects being accounted for with the quantum mechanical treatment of the other seven close-by water molecules in the PCM of water.