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Using combined computational methods, high-quality Raman optical activity spectra of model nucleotides are analyzed, revealing their molecular structure in solution.

It is generally assumed that hydrogen-bonded complexes are less stable in solvents than in the gas phase and that their stability decreases with increasing solvent polarity. This assumption is based on the size of the area available to the solvent, which is always smaller in the complex compared to the subsystems, thereby reducing the solvation energy. This reduction prevails over the amplification of the electrostatic hydrogen bond by the polar solvent. In this work, we show, using experimental IR spectroscopy and DFT calculations, that there are hydrogen-bonded complexes whose stability becomes greater with increasing solvent polarity. The explanation for this surprising stabilization is based on the analysis of the charge redistribution in the complex leading to increase of its dipole moment and solvation energy. Constrained DFT calculations have shown a dominant role of charge transfer over polarization effects for dipole moment and solvation energy.

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.

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.

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.

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., A strong influence of electronic circular dichroism on the measurement of resonance Raman optical activity of colorful chiral compounds is reported for a series of vitamin B12 derivatives. Neglecting this effect can lead to misinterpretation of recorded spectra, and seriously erroneous conclusions about molecular structure and chirality.

Vibrational frequencies of modes involving intermolecular motions in liquids are relatively small, in the Raman scattering close to the excitation frequency, and the bands may merge into a diverging uninterpretable signal. Raman optical activity (ROA) spectral shapes in this region, however, are structured more and may better reflect the nature of the studied systems. To understand the origin of the signal and its relation to the molecules, ROA spectra of six chiral neat liquids are recorded and analyzed on the basis of molecular dynamics and density functional theory computations. The theory of Raman scattering of liquids is discussed and adapted for modeling based on clusters and periodic boundary conditions. A plain cluster approach is compared to a crystal-like model. The results show that the low-frequency optical activity can be reliably modeled and related to the structure. However, momentary arrangement of molecules leads to large variations of optical activity, and a relatively large number of geometries need to be averaged for accurate simulations. The intermolecular modes are intertwined with intramolecular ones and start to dominate as the frequency goes down. The low-frequency ROA signal thus reflects the chemical composition and coupled with the modeling it provides a welcome means to study the structure and interactions of chiral liquids.

Helicenes are known to provide extremely strong optical activity. Prediction of the properties of helicenes may facilitate their design and synthesis for analytical or materials sciences. On a model 7,12,17-trioxa[11]helicene molecule, experimental results from multiple spectroscopic techniques are analyzed on the basis of density functional theory (DFT) simulations to test computational methodology and analyze the origins of chirality. Infrared (IR), vibrational circular dichroism (VCD), electronic circular dichroism (ECD), magnetic circular dichroism (MCD), and Raman optical activity (ROA, computations only) spectra are compared. Large dissymmetry factors are predicted both for vibrational (ROA/Raman ∼ VCD/IR ∼ 10-3) and electronic (ECD/Abs ∼10-2) optical activity, which could be verified experimentally except for ROA. Largest VCD signals come from a strong vibrational coupling of the C-H in-plane and out-of-plane bending modes in stacked helicene rings. The sum-over-states (SOS) approach appeared convenient for simulation of MCD spectra. Our results demonstrated that selected computational methods can be successfully used for reliable modeling of spectral and chiroptical properties of large helicenes. In particular, they can be used for guiding rational design of strongly chiral chromophores.

Combination of optical activity with surface-enhanced Raman scattering has been a dream of physical chemists for a long time. We report a measurement protocol based on silver colloids and aromatic linkers where chiral acids could be detected in concentrations of about 10-5 M. We explain the mechanism by binding and self-assembly of the linkers into chiral aggregates on the silver surface. Following the "sergeants-and-soldiers" principle, the chirality is determined by the relatively minor acidic component. Such detection of biologically relevant molecules may be useful when other methods, such as electronic circular dichroism, are not sensitive enough. In the future, variations of the chemical structure of the linker or other conditions are needed to provide a more specific signal allowing one to better discriminate among the optically active molecules.

Intermolecular interactions sensitive to chirality occur in many biological events. We report a complex formation between a versatile vanadium-based probe and a chiral co-ligand monitored via the combination of electronic circular dichroism (ECD) and Raman scattering. This “ECD-Raman” effect was discovered relatively recently and can be measured using a Raman optical activity (ROA) spectrometer. Simulated spectra based on experimental ECD and degree of circularity (DOC) values agree with the observed ones. Sensitive recognition of the chiral enantiopure co-ligand is thus enabled by a combination of resonance of the excitation light with the diastereoisomeric complex, co-ligand complexation, circular dichroism, and polarized Raman scattering from the achiral solvent. Relatively dilute solutions could be detected (10−4 mol dm−3), about 1000× less than is necessary for conventional ROA detection of the pure co-ligand and comparable to concentrations needed for conventional ECD spectroscopy. The results thus show that differential ECD-Raman measurements can be conveniently used to monitor molecular interactions and molecular spectroscopic properties.

Raman optical activity (ROA) spectral features reliably indicate the structure of peptides and proteins, but the signal is often weak. However, we observed significantly enhanced low-frequency bands for α-helical poly-L-alanine (PLA) in solution. The biggest ROA signal at ∼100 cm−1 is about 10 times stronger than higher-frequency bands described previously, which facilitates the detection. The low-frequency bands of PLA were compared to those of α-helical proteins. For PLA, density functional simulations well reproduced the experimental spectra and revealed that about 12 alanine residues within two turns of the α-helix generate the strong ROA band. Averaging based on molecular dynamics (MD) provided an even more realistic spectrum compared to the static model. The low-frequency bands could be largely related to a collective motion of the α-helical backbone, partially modulated by the solvent. Helical and intermolecular vibrational coordinates have been introduced and the helical unwinding modes were assigned to the strongest ROA signal at 101–128 cm−1. Further analysis indicated that the helically arranged amide and methyl groups are important for the strong chiral signal of PLA, while the local chiral centers CαH contribute in a minor way only. The strong low-frequency ROA can thus provide precious information about the motions of the peptide backbone and facilitate future protein studies.

The histidine residue has an exceptional affinity for metals, but solution structure of its complexes are difficult to study. For zinc and nickel complexes, Raman and Raman optical activity (ROA) spectroscopy methods to investigate the link between spectral shapes and the geometry were used. The spectra were recorded and interpreted on the basis of ionic equilibria, molecular dynamics, ab initio molecular dynamics, and density functional theory. For zwitterionic histidine the dominant tautomer was determined by the decomposition of experimental spectra into calculated subspectra. An octahedral structure was found to prevail for the ZnHis

Amyloidal protein fibrils occur in many biological events, but their formation and structural variability are understood rather poorly. We systematically explore fibril polymorphism for polyglutamic acid (PGA), insulin and hen egg white lysozyme. The fibrils were grown in the presence of "seeds", that is fibrils of the same or different protein. The seeds in concentrations higher than about 5 % of the total protein amount fully determined the structure of the final fibrils. Fibril structure was monitored by vibrational circular dichroism (VCD) spectroscopy and other techniques. The VCD shapes significantly differ for different fibril samples. Infrared (IR) and VCD spectra of PGA were also simulated using density functional theory (DFT) and a periodic model. The simulation provides excellent basis for data interpretation and reveals that the spectral shapes and signs depend both on fibril length and twist. The understanding of fibril formation and interactions may facilitate medical treatment of protein misfolding diseases in the future.

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.

Raman optical activity (ROA) becomes a standard method to monitor peptide conformation. However, the signal in the CH-stretching region is particularly difficult to measure and interpret. In order to understand the structural information contained in this part of the spectrum, data obtained on a custom-made ROA spectrometer have been analyzed for the model Ala-Ala molecule, with the help of molecular dynamics (MD) and density functional theory computations. The Ala-Ala enantiomers provided the "mirror image" spectra, which proves that the signal can be reliably measured, in spite of a rather low ROA/Raman intensity ratio (∼2 × 10-5). The theoretical modeling indicated that the most intense ROA bands can be attributed to locally asymmetric CH3 and αCH vibrations, whereas symmetric methyl CH-stretching modes contribute less. A simplified model made it possible to estimate the contribution of local chirality of the two alanine residues to the resultant ROA pattern. In spite of a significant frequency shift (over 100 cm-1) because of the anharmonic corrections, the harmonic level was able to explain the main spectral features. The anharmonic corrections were treated by second-order perturbation and limited vibrational configuration interaction procedures. This allowed for assignment of some weaker spectral features because of the combination and overtone vibrations. The results show that the peptide CH-stretching ROA signal contains rich structural information, reflecting also the peptide environment. The experimental data, however, need to be deciphered by relatively complex and time-consuming spectral simulations.

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.

Within harmonic approximations, molecular vibrational spectra are simulated in a standard way through force field diagonalization and following transformation of Cartesian to normal-mode tensor derivatives. This may become tedious for large systems of many thousands of atoms and also not necessary because of a limited resolution required to interpret an experiment. We developed an algorithm based on the real-time real-field molecular dynamics, effectively at zero temperature, invoked in a molecule by the electromagnetic field of light. The algorithm is simple to implement and suitable for parallel computing, and it can be potentially extended to more complicated molecular-light interaction modes. It circumvents the diagonalization and is suitable to model vibrational optical activity (vibrational circular dichroism and, to a lesser extent, Raman optical activity). For large molecules, it becomes faster than diagonalization, but it also enables the assignment of vibrational spectral bands to local molecular motions.

Oxidative stress may cause extended tyrosine posttranslational modifications of peptides and proteins. The 3-nitro-L-tyrosine (Nit), which is typically formed, affects protein behavior during neurodegenerative processes, such as Alzheimer's and Parkinson's diseases. Such metabolic products may be conveniently detected at very low concentrations by surface enhanced Raman spectroscopy (SERS). Previously, we have explored the SERS detection of the Nit NO

Arsenic of natural or industrial origin often occurs in water and makes it impotable. Due to its high toxicity, very sensitive detection is required. In the present study an ultra-sensitive arsenite (As

This Concept article summarizes recent work on the development of a new form of chiral Raman spectroscopy, eCP-Raman, which combines two spectroscopies: electronic circular dichroism (ECD) and circularly polarized Raman (CP-Raman). First, some puzzling observations while carrying out Raman optical activity (ROA) measurements of several transition metal complexes under resonance are described, as well as the search for the mechanisms responsible. Then an equation for quantifying the eCP-Raman contribution is presented, followed by several examples of how eCP-Raman influences the I

Intermolecular interactions sensitive to chirality occur in many biological events. We report a complex formation between a versatile vanadium-based probe and a chiral co-ligand monitored

α-Synuclein is a neuronal protein which adopts multiple conformations. These can be conveniently studied by the spectroscopy of vibrational optical activity (VOA). However, the interpretation of VOA spectra based on quantum-chemical simulations is difficult. To overcome the hampering of the computations by the protein size, we used the Cartesian tensor transfer technique to investigate links between the spectral shapes and protein structure. Vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra of α-synuclein in disordered, α-helical and β-sheet (fibril) forms were measured and analyzed on the basis of molecular dynamics and density functional theory computations. For the disordered and α-helical conformers, a high fidelity of the simulated spectra with a reasonable computational cost was achieved. Most experimental spectral features could be assigned to the structure. So far unreported ROA marker bands of the secondary structure were found for the lower-frequency and CH stretching vibrations. Fibril VCD spectra were simulated with a rigid periodic model of the geometry and the results are consistent with previous studies based on cryogenic electron microscopy. The fibrils also give a specific ROA signal, but unlike VCD it is currently not fully explicable by the simulations. In connection with the computational modeling the VOA spectroscopy thus appears as an extremely useful tool for monitoring α-synuclein and other proteins in solutions.

We report extremely strong chirality transfer from a chiral nickel complex to solvent molecules detected as Raman optical activity (ROA). Electronic energies of the complex were in resonance with the excitation-laser light. The phenomenon was observed for a wide range of achiral and chiral solvents. For chiral 2-butanol, the induced ROA was even stronger than the natural one. The observations were related to so-called quantum (molecular) plasmons that enable a strong chiral Rayleigh scattering of the resonating complex. According to a model presented here, the maximal induced ROA intensity occurs at a certain distance from the solute, in a three-dimensional "ring of fire", even after rotational averaging. Most experimental ROA signs and relative intensities could be reproduced. The effect might significantly increase the potential of ROA spectroscopy in bioimaging and sensitive detection of chiral molecules.

Spectroscopy of vibrational optical activity has been established as a powerful tool to study molecular structures and interactions. In most cases, only fundamental molecular transitions are analyzed. In the present study, we analyze a broader range of vibrational frequencies (40-4000 cm

Cell imaging heavily depends on fluorescent labels typically incompatible with Raman microscopy. The europium(iii) complex based on dipicolinic acid (DPA) presented here is an exception from this rule. Although its luminescence bands are very narrow, their intensity is comparable to the background Raman bands. This makes it complementary to less luminous compounds referred to as Raman tags. Through several examples we show that the complex provides a morphological context in otherwise unstained cells, thus acting as a spectral-counterstaining agent.

Protein fibrils are involved in a number of biological processes. Because their structure is very complex and not completely understood, different spectroscopic methods are used to monitor different aspects of fibril structure. We have explored circularly polarized luminescence (CPL) induced in lanthanide compounds to indicate fibril growth and discriminate among fibril types. For hen egg-white lysozyme and polyglutamic acid-specific CPL, spectral patterns were obtained and could be correlated with vibrational circular dichroism (VCD) spectra and thioflavin T fluorescence. The CPL spectra were measured on a Raman optical activity spectrometer, and its various polarization modes are discussed. The experiments indicate that the induced CPL is sensitive to more local aspects of the fibril structure than VCD. For CPL, smaller amounts of the sample are required for the analysis, and thus this method appears to be a good candidate for future spectroscopic characterization of these peptide and protein aggregates.

The increase in resistant bacterial strains necessitates the identification of new antimicrobial molecules. Antimicrobial peptides (AMPs) are an attractive option because of evidence that bacteria cannot easily develop resistance to AMPs. The peptaibols, a class of naturally occurring AMPs, have shown particular promise as antimicrobial drugs, but their development has been hindered by their mechanism of action not being clearly understood. To explore how peptaibols might interact with membranes, circular dichroism, vibrational circular dichroism, linear dichroism, Raman spectroscopy, Raman optical activity, neutron reflectivity and molecular dynamics simulations have been used to study a small library of peptaibol mimics, the Aib‐rich peptides. All the peptides studied quickly partitioned and oriented in membranes, and we found evidence of chiral interactions between the phospholipids and membrane‐embedded peptides. The protocols presented in this paper open new ground by showing how chiro‐optical spectroscopies can throw light on the mechanism of action of AMPs., Sit up or lie down: Linear dichroism, circular dichroism and Raman spectroscopy, neutron reflectivity and molecular dynamics simulations have been used to explore how mimics of peptaibol antibiotics (Aib foldamers) interact with membranes. These studies revealed all peptides partitioned well into the bilayers, with orientation dependent upon peptide length, as well as chiral interactions between peptides and the phospholipids.

α-Synuclein is a neuronal protein involved in synaptic vesicle trafficking. During the course of Parkinson's disease, it aggregates, forming amyloid fibrils that accumulate in the midbrain. This pathological fibrillization process is strongly modulated by physiological interactions of α-synuclein with lipid membranes. However, the detailed mechanism of this effect remains unclear. In this work, we used environment-sensitive fluorescent dyes to study the influence of model lipid membranes on the kinetics of α-synuclein fibrillization. We observed that formation of the fibrils from α-synuclein monomers is strongly delayed even by small amounts of lipids. Furthermore, we found that membrane-bound α-synuclein monomers are not involved in fibril elongation. Hence, presence of lipids slows down fibril growth proportionally to the fraction of membrane-bound protein.

Chiroptical spectroscopic methods are excellent tools to study structure and interactions of biomolecules. However, their sensitivity to different structural aspects varies. To understand the dependence of absorption, electronic and magnetic circular dichroism (ECD, MCD) intensities on the structure, dynamics and environment, we measured and simulated spectra of nucleosides and other nucleic acid model components. The conformation space was explored by molecular dynamics (MD), the electronic spectra were generated using time dependent density functional theory (TDDFT). The sum over state (SOS) method was employed for MCD. The results show that accounting for the dynamics is crucial for reproduction of the experiment. While unpolarized absorption spectroscopy is relatively indifferent, ECD reflects the conformation and geometry dispersion more. MCD spectra provide variable response dependent on the wavelength and structural change. In general, MCD samples the structure more locally than ECD. Simple computational tests suggest that the optical spectroscopies coupled with the computational tools provide useful information about nucleic acid components, including base pairing and stacking.

Oxidative stress can lead to various derivatives of the tyrosine residue in peptides and proteins. A typical product is 3-nitro-L-tyrosine residue (Nit), which can affect protein behavior during neurodegenerative processes, such as those associated with Alzheimer's and Parkinson's diseases. Surface enhanced Raman spectroscopy (SERS) is a technique with potential for detecting peptides and their metabolic products at very low concentrations. To explore the applicability to Nit, we use SERS to monitor tyrosine nitration in Met-Enkephalin, rev-Prion protein, and α-synuclein models. Useful nitration indicators were the intensity ratio of two tyrosine marker bands at 825 and 870 cm−1 and a bending vibration of the nitro group. During the SERS measurement, a conversion of nitrotyrosine to azobenzene containing peptides was observed. The interpretation of the spectra has been based on density functional theory (DFT) simulations. The CAM-B3LYP and ωB97XD functionals were found to be most suitable for modeling the measured data. The secondary structure of the α-synuclein models was monitored by electronic and vibrational circular dichroism (ECD and VCD) spectroscopies and modeled by molecular dynamics (MD) simulations. The results suggest that the nitration in these peptides has a limited effect on the secondary structure, but may trigger their aggregation.

A surface-enhanced Raman scattering-chiral anisotropy (SERS-ChA) effect is reported that combines chiral discrimination and surface Raman scattering enhancement on chiral nanostructured Au films (CNAFs) equipped in the normal Raman scattering Spectrometer. The CNAFs provided remarkably higher enhancement factors of Raman scattering (EFs) for particular enantiomers, and the SERS intensity was proportional to the enantiomeric excesses (ee) values. Except for molecules with mesomeric species, all of the tested enantiomers exhibited high SERS-ChA asymmetry factors (g), ranging between 1.34 and 1.99 regardless of polarities, sizes, chromophores, concentrations and ee. The effect might be attributed to selective resonance coupling between the induced electric and magnetic dipoles associated with enantiomers and chiral plasmonic modes of CNAFs.

Raman optical activity (ROA) is pursued as a promising method for structural analyses of sugars in aqueous solutions. In the present study, experimental Raman and ROA spectra of glucose and sorbose obtained in an extended range (50-4000 cm-1 ) are interpreted using molecular dynamics and density functional theory, with the emphasis on CH stretching modes. A reasonable theoretical basis for spectral interpretation was obtained already at the harmonic level. Anharmonic corrections led to minor shifts of band positions (up to 25 cm-1 ) below 2000 cm-1 , while the CH stretching bands shifted more, by ∼180 cm-1 , and better reproduced the experiment. However, the anharmonicities could be included on a relatively low approximation level only, and they did not always improve the harmonic band shapes. The dependence on the structure and conformation shows that the CH stretching ROA spectral pattern is a sensitive marker useful in saccharide structure studies.

Myrrh, a resin derived from the damaged bark of Commiphora genus, has traditionally been used for treatment of various human diseases, such as amenorrhea, ache, tumors, fever, and stomach pains. In spite of this widespread use of the myrrh in Ethiopia, the pharmacological activity and chemical composition have not been studied in detail. A new tricyclic triterpene acid (3S,4S,14S,7E,17E,21Z)-3,30-dihydroxypodioda-7,17,21-trien-4-carboxylic acid (commafric A) has been isolated from a crude methanolic extract of Commiphora africana (A. Rich.) Engl. resin along with the known pentacyclic triterpene α-amyrin. The structure of commafric A was characterized using different spectroscopic techniques such as 1D and 2D NMR, IR, and VCD combined with computations. The anti-proliferative activity of both isolated compounds was evaluated using SRB based colorimetric cellular assay against four human cancer cell lines. Etoposide was used as a positive control. Commafric A showed significant anti-proliferative effects against non-small cell lung cancer (A549) with IC50 values of 4.52 μg/ml. The pentacyclic triterpene α-amyrin showed a weak anti-proliferative activity against A2780 (ovarian cancer), MIA-PaCa-2 (pancreatic cancer), and SNU638 (stomach cancer) cell lines tested with IC50 values ranging 9.28 to 28.22 μg/ml. Commafric A possessed anti-proliferative activity against non-small cell lung cancer (A549), which suggests that commafric A has potential to be further optimized being a lead compound in the search for new drugs against cancer diseases.

Binuclear lanthanide complexes of Eu(III) and Sm(III) were obtained in the presence of chiral ligand 1,2-(R,R+S,S)-N,N'-bis(2-pyridylmethylene),2-diamine. An unusual structure of the Eu(III) compound with two lanthanide atoms connected through two chlorines was determined by X-ray crystallography. In solution, the dimer coexists with a monomeric complex, and the stability of the binuclear form depends on the solvent and concentration. The dimer-monomer equilibrium was monitored by circularly polarized luminescence (CPL) measured on a Raman optical activity (ROA) spectrometer, where both forms provided large CPL anisotropic ratios of up to 5.6×10-2 . Monomer formation was favored in water, whereas the dimer was stabilized in methanol. When mixed with adenosine phosphates, AMP gave much smaller CPL than ADP and ATP, indicating a high affinity of the Eu (III) complex for the phosphate group, which in connection with the ROA/CPL technique can be developed into a bioanalytical probe.

Chiroptical spectroscopy exploring the interaction of matter with polarized light provides many tools for molecular structure and interaction studies. Here, some recent discoveries are reviewed, primarily in the field of vibrational optical activity. Technological advances results in the development of more sensitive vibrational circular dichroism (VCD), Raman optical activity (ROA) or circular polarized luminescence (CPL) spectrometers. Significant contributions to the field also come from the light scattering and electronic structure theories, and their implementation in computer systems. Finally, new chiroptical phenomena have been observed, such as enhanced circular dichroism of biopolymers (protein fibrils, nucleic acids), plasmonic and resonance chirality-transfer ROA experiments. Some of them are not yet understood or attributed to instrumental artifacts so far. Nevertheless, these unknown territories also indicate the vast potential of the chiroptical spectroscopy, and their investigation is even more challenging.

Structural studies of sugars in solution are challenging for most of the traditional analytical techniques. Raman and Raman optical activity (ROA) spectroscopies were found to be extremely convenient for this purpose. However, Raman and ROA spectra of saccharides are challenging to interpret and model due to saccharides' flexibility and polarity. In this study, we present an optimized computational protocol that enables the simulation of the spectra efficiently. Our protocol, which results in good agreement with experiments, combines molecular dynamics and density functional theory calculations. It further uses a smart optimization procedure and a novel adaptable scaling function. The numerical stability and accuracy of individual computational steps are evaluated by comparing simulated and experimental spectra of D-glucose, D-glucuronic acid, N-acetyl-D-glucosamine, methyl β-D-glucopyranoside, methyl β-D-glucuronide, and methyl β-N-acetyl-D-glucosaminide. Overall, our Raman and ROA simulation protocol allows one to routinely and reliably calculate the spectra of small saccharides and opens the door to advanced applications, such as complete 3-dimensional structural determination by direct interpretation of the experimental spectra.

Methods of vibrational optical activity (VOA) traditionally include Raman optical activity and vibrational circular dichroism. They combine structural sensitivity of chiroptical spectroscopy with the richness of vibrational spectra. Different peptide and protein conformations usually provide quite distinct VOA patterns. For spectra interpretation, it is desirable to understand the underlying physical principles. Quantum-chemical simulations of spectral shapes can also be very helpful. At present, they are implemented in common software, usually within the density functional theory. However, simulations of VOA spectra of even small molecules may be complicated by interactions with the solvent and molecular flexibility. For large molecules, direct quantum-chemical methods can be combined with or replaced by molecular dynamic simulations or semiempirical approaches. We present several examples of calculations used for small and large systems, with a bias to our previous results. Nevertheless, we tried to document general possibilities of contemporary computational chemistry.

Helical α-aminoisobutyric acid (Aib) foldamers show great potential as devices for the communication of conformational information across phospholipid bilayers, but determining their conformation in bilayers remains a challenge. In the present study, Raman, Raman optical activity (ROA), infrared (IR) and vibrational circular dichroism (VCD) spectroscopies have been used to analyze the conformational preferences of Aib foldamers in solution and when interacting with bilayers. A 310 -helix marker band at 1665-1668 cm-1 in Raman spectra was used to show that net helical content increased strongly with oligomer length. ROA and VCD spectra of chiral Aib foldamers provided the chiroptical signature for both left- and right-handed 310 -helices in organic solvents, with VCD establishing that foldamer screw-sense was preserved when the foldamers became embedded within bilayers. However, the population distribution between different secondary structures was perturbed by the chiral phospholipid. These studies indicate that ROA and VCD spectroscopies are valuable tools for the study of biomimetic structures, such as artificial signal transduction molecules, in phospholipid bilayers.

Lanthanide complexes are used as convenient spectroscopic probes for many biomolecules. Their binding to proteins is believed to be enhanced by the presence of histidine, but the strength of the interaction significantly varies across different systems. To understand the role of peptide length and sequence, short histidine-containing peptides have been synthesized (His-Gly, His-Gly-Gly, His-Gly-Gly-Gly, Gly-His, Gly-His-Gly, His-His, and Gly-Gly-His) and circularly polarized luminescence (CPL) induced at the [Eu(dpa)3 ]3- complex has been measured by means of a Raman optical activity (ROA) spectrometer. The obtained data indicate relatively weak binding of the histidine residue to the complex, with a strong participation of other parts of the peptide. Longer peptides, low pH, and a histidine residue close to the N-peptide terminus favor the binding. The binding strengths are approximately proportional to the CPL intensity and roughly correlate with predictions based on molecular dynamics (MD) simulations. The specificity of lanthanide binding to the peptide structure and its intense luminescence and high optical activity make the ROA/CPL technique suitable for probing secondary and tertiary structures of peptides and proteins.

Biomolecular aggregation is omnipresent in nature and important for metabolic processes or in medical treatment; however, the phenomenon is rather difficult to predict or understand on the basis of computational models. Recently, we found that electronic circular dichroism (ECD) spectroscopy and closely related resonance Raman optical activity (RROA) are extremely sensitive to the aggregation mechanism and structure of the astaxanthin dye. In the present study, molecular dynamics (MD) and quantum chemical (QC) computations (ZIndo/S, TDDFT) are used to link the aggregate structure with ECD spectral shapes. Realistic absorption and ECD intensities were obtained and the simulations reproduced many trends observed experimentally, such as the prevalent sign pattern and dependence of the aggregate structure on the solvent type. The computationally cheaper ZIndo/S method provided results very similar to those obtained by TDDFT. In the future, the accuracy of the combined MD/QC methodology of spectra interpretation should be improved to provide more detailed information on astaxanthin aggregates and similar macromolecular systems.