Vibrational Raman Optical Activity Research Articles

Vibrational Optical Activity of Amyloid Fibrils.

Amyloid fibrils are supramolecular systems showing distinct chirality at different levels of their complex multilayered architectures. Due to the regular long-range chiral organization, amyloid fibrils exhibit the most intense Vibrational Optical Activity (VOA) signal observed up to now, making VOA techniques: Vibrational Circular Dichroism (VCD) and Raman Optical Activity (ROA) very promising tools to explore their structures, handedness and intricate polymorphism. This concept article reviews up-to-date experimental studies on VOA applications to investigate amyloid fibrils highlighting its future potential in analyzing of these unique supramolecular systems, in particular in the context of biomedicine and nanotechnology.

Pitfalls in the Optimization of Conformer Populations to Maximize the Similarity between Predicted and Experimental Chiroptical Spectra.

The conformational populations of pantolactone, epichlorohydrin, and N-acetyl-tryptophan methyl ester were investigated by using similarity analysis between their calculated and experimental chiroptical spectra. By performing the analysis on pantolactone using two different chiroptical methods, namely, vibrational circular dichroism and Raman optical activity, it was found that the optimal sets of conformers do not match between the two methods, indicating that the conformational populations obtained by optimizing the similarity between calculated and experimental spectra are unlikely to be more accurate than energy-based Boltzmann populations. Also, it was found for pantolactone, epichlorohydrin, and N-acetyl-tryptophan methyl ester that the similarity between calculated and experimental spectra would often not vary significantly if each of the populated conformers was discarded, one at a time. This observation indicates that more than one set of conformers can provide acceptable similarity between the predicted and experimental spectra. Therefore, the correct set of conformers cannot be accurately determined by similarity analysis.

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.

Molecular Properties of 3d and 4f Coordination Compounds Deciphered by Raman Optical Activity Spectroscopy.

Molecular properties of coordination compounds can be efficiently studied by vibrational spectroscopy. The scope of Raman spectroscopy has been greatly enhanced by the introduction of Raman optical activity (ROA) sensitive to chirality. The present review describes some of its recent applications to study the coordination compounds. 3d and 4f metal complexes often absorb the excitation light, or exhibit luminescence. Therefore, effects caused in ROA spectra by electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) must be taken into consideration.In 3d metal complexes ECD and circularly-polarized Raman scattering compete with the resonance ROA (RROA) signal. Pure RROA spectrum can thus be obtained by subtracting the so-called ECD-Raman component. CPL is frequently encountered in 4f systems. While it can mask the ROA spectra, it is useful to study molecular structure. These electronic effects can be reduced by using near-infrared excitation although vibrational ROA signal is much weaker compared to the usual green laser excitation scenario. The ROA methodology is thus complex, but capable of providing unique information about the molecules of interests and their interaction with light.

Chiral Spectroscopy of Nanostructures.

ConspectusChirality is ubiquitous in the universe and in living creatures over detectable length scales from the subatomic to the galactic, as exemplified in the two extremes by subatomic particles (neutrinos) and spiral galaxies. Between them are living creatures that display multiple levels of chirality emerging from hierarchically assembled asymmetric building blocks. Not too far from the bottom of this pyramid are the foundational building blocks with chiral atomic centers on sp3 carbon atoms exemplified by l-amino acids and d-sugars that are self-assembled into higher-order structures with increasing dimensions forming highly complex, amazingly functional, and energy-efficient living systems. The organization and materials employed in their construction inspired scientists to replicate complex living systems via the self-assembly of chiral components. Multiple studies pointed to unexpected and unique electromagnetic properties of chiral structures with nanoscale and microscale dimensions, including giant circular dichroism and collective circularly polarized scattering that their constituent units did not possess.To address the wide variety of chiral geometries observed in continuous materials, singular particles, and their complex systems, multiple analytic techniques are needed. Simultaneously, their spectroscopic properties create a pathway to multiple applications. For example, mirror-asymmetric vibrations at chiral centers formed by sp3 carbon atoms lead to optical activity for the infrared (IR) wavelength regions. At the same time, understanding the optical activity in, for example, the IR region enables biomedical applications because multiple modalities of biomedical imaging and vibrational optical activity (VOA) of biomolecules are known for IR range. In turn, VOA can be realized in both absorption and emission modalities due to large magnetic transition moments, as vibrational circular dichroism (VCD) or Raman optical activity (ROA) spectroscopy. In addition to the VOA, in the range of longer wavelengths, lattice vibrational mode or phononic behavior occurs in chiral crystals and nanoassemblies, which can be readily detected by terahertz circular dichroism (TCD) spectroscopy. Meanwhile, chiral self-assembly can induce circularly polarized light emission (CPLE) regardless of the existence of chirality in coassembled fluorophores. The CPLE from self-assembled chiral materials is particularly interesting because the CPLE can originate from both circularly polarized luminescence and circularly polarized scattering (CPS). Furthermore, because self-assembled nanostructures often exhibit stronger optical activity than their building blocks owing to dimension and resonance effects, the optical activity of single assembled nanostructures can be investigated by using microscopic technology combined with chiral optics. Here, we describe the state of the art for spectroscopic methods for the comprehensive analysis of chiral nanomaterials at various photon wavelengths, addressed with special attention given to new tools emerging both for materials with self-organized hierarchical chirality and single-particle spectroscopy.

Conformational Distributions of Phenyl β-D-Glucopyranoside and Gastrodin in Solution by Vibrational Optical Activity and Theoretical Calculations.

The conformational landscapes of two highly flexible monosaccharide derivatives, namely phenyl β-D-glucopyranoside (ph-β-glu) and 4-(hydroxymethyl)phenyl β-D-glucopyranoside, also commonly known as gastrodin, were explored using a combined experimental and theoretical approach. For the infrared, Raman, and the associated vibrational optical activity (VOA), i.e., vibrational circular dichroism and Raman optical activity, experiments of these two compounds in DMSO and in water were carried out. Extensive and systematic conformational searches were performed using a recently developed conformational searching tool called CREST (conformer-rotamer ensemble sampling tool) in the two solvents. Fourteen and twenty-four low-energy conformers were identified at the DFT level for ph-β-glu and gastrodin, respectively. The spectral simulations of individual conformers were done at the B3LYP-D3BJ/def2-TZVPD level with the polarizable continuum model of the solvents. The VOA spectral features exhibit much higher specificity to conformational differences than their parent infrared and Raman. The excellent agreements achieved between the experimental and simulated VOA spectra allow for the extraction of experimental conformational distributions of these two carbohydrates in solution directly. The experimental percentage abundances based on the hydroxymethyl (at the pyranose ring) conformations G+, G-, and T for ph-β-glu were obtained to be 15%, 75%, and 10% in DMSO and 53%, 40%, and 7% in water, respectively, in comparison to the previously reported gas phase values of 68%, 25%, and 7%, highlighting the important role of solvents in conformational preferences. The corresponding experimental distributions for gastrodin are 56%, 22%, and 22% in DMSO and 70%, 21%, and 9% in water.

Synthesis and Chiroptical Properties of a Chiral Isotopologue of syn-Cryptophane-B.

We report the synthesis and absolute configuration (AC) of a chiral isotopologue of syn-cryptophane-B. Low chiral signatures were measured by polarimetry and electronic circular dichroism, whereas most significant chiroptical effects were observed by vibrational circular dichroism (VCD) and Raman optical activity (ROA). The comparison of experimental VCD and ROA spectra with those predicted by DFT calculations allows the determination of the AC of the two enantiomers as (-)589-MP-syn-2 and (+)589-PM-syn-2.

Chirality induction and amplification in supramolecular systems exhibiting vibrational optical activity.

Vibrational optical activity (VOA) refers to two vibrational techniques: vibrational circular dichroism (VCD) and Raman optical activity (ROA) that are sensitive both to the chirality and the molecular structure, typically surpassing electronic optical activity (EOA) in recognition of fine structural details. However, the measurement of VOA is inherently obstructed as the intensity of the VOA signal is typically 10-4-10-5 of the intensity of the parent IR or Raman signals. This feature considerably limits the practical applications of VOA and is a fundamental reason why various strategies are currently developed to enhance the VOA intensity. This perspective review discusses up-to-date studies focusing on applications of VOA to analyse supramolecular, mostly biogenic, systems showing induction and amplification of chirality. Most attention is devoted to two types of biogenic supramolecular assemblies providing unique enhancement of VOA: amyloid fibrils showing enormous VCD and carotenoid aggregates exhibiting resonantly enhanced ROA.

Vibrational Optical Activity Study of Four Antibiotic (Lipo)glycopeptides: Vancomycin, Oritavancin, Dalbavancin, and Teicoplanin.

The antibiotic glycopeptide class, of which vancomycin is the original compound, has received due attention over the past few decades in search of antibiotics to overcome resistances developed by bacteria. Crucial for the understanding and further development of glycopeptides that possess desired antibacterial effects is the determination of their conformational behavior, as this sheds light on the mechanism of action of the compound. Among others, vibrational optical activity (VOA) techniques (vibrational circular dichroism and Raman optical activity) can be deployed for this, but the question remains to what extent these spectroscopic techniques can provide information concerning the molecular class under investigation. This contribution takes the last hurdle in the search for the capabilities of the VOA techniques in the conformational analysis of the antibiotic glycopeptide class by extending research that was previously conducted for vancomycin toward its three derivatives: oritavancin, dalbavancin, and teicoplanin. The principal information that can be drawn from VOA spectra is the conformation of the rigid cyclic parts of the glycopeptides and the aromatic rings that are part hereof. The addition or removal of carbohydrates does not induce noticeable VOA spectral responses, preventing the determination of the conformation they adopt.

Anharmonic Vibrational Raman Optical Activity of Methyloxirane: Theory and Experiment Pushed to the Limits.

Combining Raman scattering and Raman optical activity (ROA) with computer simulations reveals fine structural and physicochemical properties of chiral molecules. Traditionally, the region of interest comprised fundamental transitions within 200–1800 cm–1. Only recently, nonfundamental bands could be observed as well. However, theoretical tools able to match the observed spectral features and thus assist their assignment are rather scarce. In this work, we present an accurate and simple protocol based on a three-quanta anharmonic perturbative approach that is fully fit to interpret the observed signals of methyloxirane within 150–4500 cm–1. An unprecedented agreement even for the low-intensity combination and overtone transitions has been achieved, showing that anharmonic Raman and ROA spectroscopies can be valuable tools to understand vibrations of chiral molecules or to calibrate computational models.

Comparative Study of Vibrational Raman Optical Activity with Different Time-Dependent Density Functional Approximations: The VROA36 Database.

A new database, VROA36, is introduced to investigate the performance of computational approaches for vibrational Raman optical activity (VROA) calculations. The database is composed of 36 molecules with known experimental VROA spectra. It includes 93 conformers. Normal modes calculated with B3LYP-D3(BJ)/def2-TZVP are used to compute the VROA spectra with four functionals, B3LYP-D3(BJ), ωB97X-D, M11, and optimally tuned LC-PBE, as well as several basis sets. SimROA indices and frequency scaling factors are used to compare calculated spectra with each other and with experimental data. The four functionals perform equally well independently of the basis set and usually achieve good agreement with the experimental data. For molecules in near- or at-resonance conditions, the inclusion of a complex (damped) linear response approach is important to obtain physically meaningful VROA intensities. The use of any of the tested functional approximations with the def2-SVPD Gaussian-type basis set, or a basis of similar flexibility, can be recommended for efficient and reliable theoretical VROA studies.

Vibrational Raman optical activity of diacetyl L‐tartaric acid and corresponding surfactants: Sodium salts and shorter analogs of surfactants simplify the interpretations

AbstractExperimental vibrational Raman and Raman optical activity (ROA) spectra for diacetyl L‐tartaric acid (DAT), two of its esters, namely, monomethyl and lauryl esters (T1OH and T12OH), and corresponding sodium salts (DATNa, T1ONa, and T12ONa), are measured. T12OH and T12ONa represent the first chiral surfactants investigated using ROA spectroscopy. The quantum chemical (QC) predictions using B3LYP functional and 6‐311++G(2d,2p) basis set are used to interpret the ROA spectra for DAT, DATNa, T1OH, and T1ONa. It is found that the use of implicit solvation, as represented in polarizable continuum model (PCM), for predicting the experimental ROA spectra in aqueous solutions is inadequate for DAT and T1OH. However, the same PCM predicts the experimental ROA spectra satisfactorily for the DATNa and T1ONa. This favorable observation for the latter is attributed to the absence of intra‐ and inter‐molecular hydrogen bonding interactions for sodium salts in aqueous solutions. The overwhelming number of conformations resulting from 12‐carbon alkyl chain, in T12OH and T12ONa, makes it impractical to undertake QC predictions for them. Nevertheless, it is found that the predictions made for shorter alkyl chain analogs, namely, T1OH and T1ONa, may be used to explain the experimental ROA spectra of T12OH and T12ONa. The current work highlights the importance of converting carboxylic acids to corresponding sodium salts and of QC predictions for shorter achiral alkyl chain analogs to interpret the ROA spectra of chiral surfactants that contain long achiral alkyl chains.

Anharmonic effects on Vibrational circular dichroism and Raman optical activity spectra of medium‐size molecules: Alpha‐pinene and beta‐pinene

AbstractAn analysis of the vibrational circular dichoism (VCD) and Raman optical activity (ROA) of two medium‐sized molecules, alpha‐pinene and beta‐pinene, was performed using the second‐order perturbative PT2 method. We calculated the intensity (I in ) using the differential cross section. We reproduce mid‐IR spectra by generalized vibrational PT2 (GVPT2), where the GVPT2 approach has been applied to calculate both vibrational band wavenumbers and intensities to determine anharmonic effects on the spectral shape, adding combination bands to fundamental transition bands. Furthermore, the comparison with experimental spectra for both the band positions and the intensity pattern, our calculation, was evaluated.

Recent Progress in the Simulation of Chiral Systems with Real Time Propagation Methods

AbstractIn this brief review, an overview about recent efforts to simulate the spectroscopic signatures of chiral molecules is given with focus on real time propagation approaches to solve the time‐dependentSchrödingerequation. In particular the simulation of electric circular dichroism spectra and vibrationalRamanoptical activity is discussed. In comparison to linear absorption spectra, where only the response of the electric dipole moment is necessary, the response of the magnetic dipole moment and electric quadrupole moment is more intricate. Issues such as gauge origin dependence, basis set dependence, non‐local potentials and the dipole approximation are addressed.

Enantiopure cryptophane derivatives: Synthesis and chiroptical properties.

This review addresses the synthesis of enantiopure cryptophane and the study of their chiroptical properties. Cryptophane derivatives represent an important class of macrocyclic compounds that can bind a large range of species in solution under different conditions. The overwhelming majority of these host molecules is chiral, and their chiroptical properties have been thoroughly investigated. The first part of this review is dedicated to the optical resolution and the synthesis of enantiopure cryptophane derivatives. In a second part, the study of the chiroptical properties of these molecular hosts by different techniques such as electronic and vibrational circular dichroism and Raman optical activity is detailed. These techniques allow the determination of the absolute configuration of cryptophane derivatives and provide useful information about their conformation in different conditions.

Tackling Stereochemistry in Drug Molecules with Vibrational Optical Activity.

Chirality plays a crucial role in drug discovery and development. As a result, a significant number of commercially available drugs are structurally dissymmetric and enantiomerically pure. The determination of the exact 3D structure of drug candidates is, consequently, of paramount importance for the pharmaceutical industry in different stages of the discovery pipeline. Traditionally the assignment of the absolute configuration of druggable molecules has been carried out by means of X-ray crystallography. Nevertheless, not all molecules are suitable for single-crystal growing. Additionally, valuable information about the conformational dynamics of drug candidates is lost in the solid state. As an alternative, vibrational optical activity (VOA) methods have emerged as powerful tools to assess the stereochemistry of drug molecules directly in solution. These methods include vibrational circular dichroism (VCD) and Raman optical activity (ROA). Despite their potential, VCD and ROA are still unheard of to many organic and medicinal chemists. Therefore, the present review aims at highlighting the recent use of VOA methods for the assignment of the absolute configuration of chiral small-molecule drugs, as well as for the structural analysis of biologics of pharmaceutical interest. A brief introduction on VCD and ROA theory and the best experimental practices for using these methods will be provided along with selected representative examples over the last five years. As VCD and ROA are commonly used in combination with quantum calculations, some guidelines will also be presented for the reliable simulation of chiroptical spectra. Special attention will be paid to the complementarity of VCD and ROA to unambiguously assess the stereochemical properties of pharmaceuticals.

Symmetry and Chirality: Where Physics Shakes Hands with Chemistry and Biology

AbstractIn reflecting the author's personal perspective, this review demonstrates how chirality is a unifying theme in modern science. Using the discrete symmetries of parity P, time reversal T and charge conjugation C to characterize chiral systems, the concepts of true and false chirality that emerge provide an extension of Lord Kelvin's definition to dynamic situations This clarifies the nature of physical influences able to induce absolute enantioselection, emphasizing the distinct behaviour of processes under thermodynamic and kinetic control. Parity violation and CP violation are suggested to be manifestations of true and false cosmic chirality, respectively, with possible roles in abiotic enantioselection. Truly chiral systems support time‐even pseudoscalar observables which endows chiroptical spectroscopies with a special sensitivity to absolute stereochemistry, exemplified by the application of vibrational Raman optical activity to small chiral organic molecules and intact viruses.

Recent research progress on surface-enhanced spectra ofchiral molecules

Chiral molecules are ubiquitous in natural world. Molecular chirality determines their physical and chemical properties. Detection and characterization of these chiral enantiomers are of considerable importance for biochemical and pharmaceutical industries. Conventional chiroptical spectroscopy techniques nowadays can not meet the needs in practical applications, with the disadvantages of small signal and large noise, etc. It is necessary to solve these problems and characterize chiral enantiomers fast and sensitively. Surface-enhanced spectroscopic techniques delivered through specifically designed nanostructures have been proved to be highly successful for ultrasensitive chiral detection, with dramatic enhanced interactions between light and chiral molecules induced by nanostructures. There are considerable researches on surface-enhanced spectroscopic techniques in recent years, and the enhancement effect on the circular dichroism (CD), vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectrum is excellent. In this review, we present a survey of the recent work about surface-enhanced spectroscopic techniques in the two aspects of metal and dielectric nanostructures, respectively. Plasmonic nanostructures based on metallic elements can provide highly enhanced electric fields, which ensures the generation of strong chiral near fields, showing promise for the enhancement of detection sensitivities of chiral spectroscopies. The dielectric nanostructures exhibit strong enhancement of the electric near-field while simultaneously providing intense magnetic resonances, which can generate uniform-sign superchiral field, ensuring the untrasensitive chiral sensing. Besides, dielectric nanostructures show extremely low optical losses, which is very beneficial for the detection of enhanced chiroptical spectroscopy. With surface-enhanced spectroscopic method, it is promising to solve the problems in the chirality characterization techniques nowadays and lead to unprecedented levels of chiroptical sensitivity.

Theoretical study of the Raman optical activity spectra of with M=Co, Rh.

Vibrational Raman optical activity (ROA) spectra were calculated under off-resonance, near-resonance, and at-resonance conditions for (A) and under off-resonance conditions for (B) using a new driver software for calculating the ROA intensities from complex (damped) time-dependent linear response Kohn-Sham theory. The off-resonance spectra of A and B show many similarities. At an incident laser wavelength of 532nm, used in commercial ROA spectrometers, the spectrum of A is enhanced by near-resonance with the ligand-field transitions of the complex. The near-resonance spectrum exhibits many qualitative differences compared with the off-resonance case, but it remains bi-signate. Even under full resonance with the ligand-field electronic transitions, the ROA spectrum of A remains bi-signate when the electronic transitions are broadened such as to yield absorption line widths that are comparable with those in the experimental UV-vis absorption and electronic circular dichroism spectra.

Pressure dependence of vibrational optical activity of model biomolecules. A computational study.

Change of molecular properties with pressure is an attracting means to regulate molecular reactivity or biological activity. However, the effect is usually small and so far explored rather scarcely. To obtain a deeper insight and estimate the sensitivity of vibrational optical activity spectra to pressure-induced conformational changes, we investigate small model molecules. The Ala-Ala dipeptide, isomaltose disaccharide and adenine-uracil dinucleotide were chosen to represent three different biomolecular classes. The pressure effects were modeled by molecular dynamics and density functional theory simulations. The dinucleotide was found to be the most sensitive to the pressure, whereas for the disaccharide the smallest changes are predicted. Pressure-induced relative intensity changes in vibrational circular dichroism and Raman optical activity spectra are predicted to be 2-3-times larger than for non-polarized IR and Raman techniques.