Raman Optical Activity Research Articles

Conformation of Retinal Schiff Base in Proteorhodopsin Based on Raman Optical Activity

Conformation of Retinal Schiff Base in Proteorhodopsin Based on Raman Optical Activity

New chiral ECD-Raman spectroscopy of atropisomeric naphthalenediimides.

In this study, we found that a recently discovered ECD-Raman effect dominated over the natural Raman optical activity in a series of atropisomeric naphthalenediimides, and we investigated the kind of information about the molecular structure that could be obtained from the spectra. The ECD-Raman effect is polarised Raman scattering modulated by electronic circular dichroism. We showed that the spectra significantly depended on the substitution of the solute and/or the change of the solvent. Moreover, the spectra could be well-predicted by the theory, thus providing an interesting tool to monitor the chirality of the binaphthyl compounds.

Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Measurement and Theory of Resonance Raman Optical Activity for Gases, Liquids, and Aggregates. What It Tells about Molecules.

Resonance Raman Optical Activity (RROA) appeared as a natural extension of the nonresonance branch. It combines the structural sensitivity of chiroptical spectroscopy with the signal enhancement coming from the resonance of molecular electronic transitions with the excitation laser light. However, the idea has been hampered by many technical and theoretical problems that are being clarified only in recent years. We provide the theoretical basis and several examples documenting the problems, achievements, and potential of RROA, in particular in biomolecular studies.

Potenciál spektroskopie v diagnostice hepatocelulárního karcinomu – pilotní studie

Summary: None of the bio­markers studied so far in the HCC area has yielded higher sensitivity and specificity in the early-stage dia­gnosis than the liver ultrasonography examination. There is an urgent clinical need for establishing a laboratory marker for HCC that meets the requirements for high sensitivity and specificity for the screening and early dia­gnosis of at-risk patients. As a variety of pathological processes, including carcinogenesis, may cause changes in both the concentration and the structure and spatial arrangement of body bio­molecules, the spectroscopic analysis of blood-based derivatives appears to be an appropriate tool for the early detection thereof. In our research, the focus is on the identification of novel bio­markers in blood plasma, which would exhibit sufficient sensitivity and specificity to detect early and potentially curable HCC stages, and which would be potentially useful for routine screening of this disease in well-defined at-risk groups. For this purpose, we utilised a unique combination of two chiroptical methods – electronic circular dichroism (ECD) and Raman optical activity (ROA) – supplemented by non-polarised variants – infrared (IR) absorption and Raman spectroscopy. Methods: Blood plasma of 18 selected patients with liver cirrhosis, 8 of which also suffered from HCC, was analysed by a combination of ECD, ROA, IR and Raman spectroscopy. Results: The obtained spectral data were processed by a multivariate statistical evaluation using principal component analysis (PCA) and linear discriminant analysis (LDA). The visualisation of the LDA results showed the separation of the two monitored groups with only a slight overlap. Based on the spectral analysis within this preliminary study, sensitivity and specificity for the discrimination between cirrhotic individuals with and without HCC reached 88% and 90% after leave-one-out cross validation, respectively. The area under the ROC curve of 0.975 proved high reliability of the established model. Conclusion: Based on our findings, the combination of advanced spectroscopic methods for the analysis of blood plasma might be a promising tool in HCC dia­gnosis and potentially in the screening thereof. Key words: hepatocellular carcinoma – blood plasma – spectroscopy – cirrhosis

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.

Engineering of inorganic nanostructures with hierarchy of chiral geometries at multiple scales

Engineering of inorganic nanostructures with hierarchy of chiral geometries at multiple scales

Non‐Covalent Interactions between Chiral Phosphate and Lanthanide Ion by Chiroptical Spectroscopy

AbstractChiroptical spectroscopy is instrumental in chiral recognition studies. Induced circularly polarized luminescence (CPL) of europium(III) aqua ion in optically active phosphate solution was observed on a standard Raman optical activity (ROA) spectrometer. The ROA‐CPL method displays characteristic CPL couplet of Eu‐phosphate interactions avoiding the participation of costly antenna chromophore. Similar CPL patterns pertaining 5D0→7F1 transition was also observed in other europium(III) complexes able to bind with phosphate. Titration data and simulations revealed the presence of hydrogen bond between the phosphate group and water molecules surrounding the metal core.

Double Hydrogen Bonding Dimerization Propensity of Aqueous Hydroxy Acids Investigated Using Vibrational Optical Activity.

Lactic and malic acids are key substances in a number of biochemical processes in living cells and are also utilized in industry. Vibrational spectroscopy represents an efficient and sensitive way to study their structure and interactions. Since water is the natural environment, proper understanding of their molecular dynamics in aqueous solutions is of critical importance. To this end, we employed Raman spectroscopy and Raman optical activity (ROA) to study the conformation of l-lactic and l-malic acids in water (while varying pH, temperature, and concentration), with special emphasis on their double hydrogen bonding dimerization propensity. Raman and ROA experimental data were supported by extensive theoretical calculations of the vibrational properties and by additional experiments (IR absorption, vibrational circular dichroism, and NMR). Conformational behavior of the acids in water was described by molecular dynamics simulations. Reliability of the results was verified by calculating the vibrational properties of populated conformers and by comparing thus obtained spectral features with the experimental data. Calculations estimated the incidence of H-bonded dimers in water to be low in lactic acid and comparable to monomers in malic acid. The "hybrid" approach presented here reveals limitations of relying on the experimental spectra alone to study dimer formation.

Conformational Analysis of a Retinal Schiff Base Chromophore in Proteorhodopsin by Raman Optical Activity.

Raman optical activity (ROA) spectroscopy was used to study the conformation of the retinal Schiff base chromophore in green-light-absorbing proteorhodopsin, which is a globally distributed light-driven proton pump of aquatic bacteria. The ROA spectrum consisted mostly of the negative vibrational bands of the chromophore, while the hydrogen out-of-plane mode (at 960 cm-1) appeared as the sole positive band. This distinct spectral feature was not explained by the twisted structure of the retinal Schiff base but was reproduced by the structural model in which the polyene chain on the β-ionone ring side was bent out-of-plane. The bent chromophore structure potentially couples with proton pumping through the motion of the sixth helix in contact with the β-ionone ring.

Measurement of Raman Optical Activity with High-Frequency Polarization Modulation.

Many chiroptical spectroscopic techniques have been developed to detect chirality in molecular species and probe its role in biological processes. Raman optical activity (ROA) should be one of the most powerful methods, as ROA yields vibrational and chirality information simultaneously and can measure analytes in aqueous and biologically relevant solvents. However, despite its promise, the use of ROA has been limited, largely due to challenges in instrumentation. Here, we report a new approach to ROA that exploits high-frequency polarization modulation. High-frequency polarization modulation, usually implemented with a photoelastic modulator (PEM), has long been the standard technique in other chiroptical spectroscopies. Unfortunately, the need for simultaneous spectral and polarization resolution has precluded the use of PEMs in ROA instruments. We combine a specialized camera system (the Zurich imaging polarimeter, or ZIMPOL) with PEM modulation to perform ROA measurements. We demonstrate performance similar to the current standard in ROA instrumentation while reducing complexity and polarization artifacts. This development should aid researchers in exploiting the full potential of ROA for chemical and biological analysis.

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.

Can One Measure Resonance Raman Optical Activity?

Resonance Raman optical activity (RROA) is commonly measured as the difference in intensity of Raman scattered right and left circularly polarized light, IR -IL , when a randomly polarized light is in resonance with a chiral molecule. Strong and sometimes mono-signate experimental RROA spectra of several chiral solutes were reported previously, although their signs and relative intensities could not be reproduced theoretically. By examining multiple light-matter interaction events which can occur simultaneously under resonance, we show that a new form of chiral Raman spectroscopy, eCP-Raman, a combination of electronic circular dichroism and circularly polarized Raman, prevails. By incorporating the finite-lifetime approach for resonance, the experimental patterns of the model chiral solutes are captured theoretically by eCP-Raman, without any RROA contribution. The results open opportunity for applications of eCP-Raman spectroscopy and for extracting true RROA experimentally.

Can One Measure Resonance Raman Optical Activity?

AbstractResonance Raman optical activity (RROA) is commonly measured as the difference in intensity of Raman scattered right and left circularly polarized light, IR−IL, when a randomly polarized light is in resonance with a chiral molecule. Strong and sometimes mono‐signate experimental RROA spectra of several chiral solutes were reported previously, although their signs and relative intensities could not be reproduced theoretically. By examining multiple light‐matter interaction events which can occur simultaneously under resonance, we show that a new form of chiral Raman spectroscopy, eCP‐Raman, a combination of electronic circular dichroism and circularly polarized Raman, prevails. By incorporating the finite‐lifetime approach for resonance, the experimental patterns of the model chiral solutes are captured theoretically by eCP‐Raman, without any RROA contribution. The results open opportunity for applications of eCP‐Raman spectroscopy and for extracting true RROA experimentally.

Recognition of the True and False Resonance Raman Optical Activity

AbstractResonance Raman optical activity (RROA) possesses all aspects of a sensitive tool for molecular detection, but its measurement remains challenging. We demonstrate that reliable recording of RROA of chiral colorful compounds is possible, but only after considering the effect of the electronic circular dichroism (ECD) on the ROA spectra induced by the dissolved chiral compound. We show RROA for a number of model vitamin B12derivatives that are chemically similar but exhibit distinctively different spectroscopic behavior. The ECD/ROA effect is proportional to the concentration and dependent on the optical pathlength of the light propagating through the sample. It can severely alter relative band intensities and signs in the natural RROA spectra. The spectra analyses are supported by computational modeling based on density functional theory. Neglecting the ECD effect during ROA measurement can lead to misinterpretation of the recorded spectra and erroneous conclusions about the molecular structure.

Recognition of the True and False Resonance Raman Optical Activity.

Resonance Raman optical activity (RROA) possesses all aspects of a sensitive tool for molecular detection, but its measurement remains challenging. We demonstrate that reliable recording of RROA of chiral colorful compounds is possible, but only after considering the effect of the electronic circular dichroism (ECD) on the ROA spectra induced by the dissolved chiral compound. We show RROA for a number of model vitamin B12 derivatives that are chemically similar but exhibit distinctively different spectroscopic behavior. The ECD/ROA effect is proportional to the concentration and dependent on the optical pathlength of the light propagating through the sample. It can severely alter relative band intensities and signs in the natural RROA spectra. The spectra analyses are supported by computational modeling based on density functional theory. Neglecting the ECD effect during ROA measurement can lead to misinterpretation of the recorded spectra and erroneous conclusions about the molecular structure.

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.

All-dielectric chiral-field-enhanced Raman optical activity

Raman optical activity (ROA) is effective for studying the conformational structure and behavior of chiral molecules in aqueous solutions and is advantageous over X-ray crystallography and nuclear magnetic resonance spectroscopy in sample preparation and cost performance. However, ROA signals are inherently minuscule; 3–5 orders of magnitude weaker than spontaneous Raman scattering due to the weak chiral light–matter interaction. Localized surface plasmon resonance on metallic nanoparticles has been employed to enhance ROA signals, but suffers from detrimental spectral artifacts due to its photothermal heat generation and inability to efficiently transfer and enhance optical chirality from the far field to the near field. Here we demonstrate all-dielectric chiral-field-enhanced ROA by devising a silicon nanodisk array and exploiting its dark mode to overcome these limitations. Specifically, we use it with pairs of chemical and biological enantiomers to show >100x enhanced chiral light–molecule interaction with negligible artifacts for ROA measurements.