VCD Signals Research Articles

Scope and limitations of absolute configuration determination of allenic natural products using the CCC stretching VCD signal.

The allene functional group in natural products isolated so far exists in a non-racemic form, but its axial chirality is difficult to elucidate. Allenes exhibit a characteristic antisymmetric CCC stretching mode at around 1950 cm-1, and their VCD properties have not been studied in detail. This work, for the first time, applied VCD spectroscopy to allenic natural products and allenic molecules with other asymmetric centers focusing on the antisymmetric CCC stretching mode. This vibrational mode yielded a negligibly weak VCD signal for several molecules, but in the presence of electron-withdrawing and/or conjugating substituents, it generated a stronger one. Its sign was found to be influenced by the nature of substituents. These findings should deepen the understanding of the VCD properties of the allene functional group and should be useful for future studies of chiral allenes.

Vibrational Circular Dichroism Spectroscopy toward Intercalation Compounds of Sodium Montmorillonite: Evidences for Molecular Packing of Enantiopure Monovalent Ir(III) Complexes within Interlayer Spaces

Solid state vibrational circular dichroism (SD-VCD) spectra were recorded on the intercalation compounds of sodium montmorillonite with a chiral iridium(III) complex. The complex used was Δ- (or Λ-)[Ir(bzq)2(phen)]+ (bzqH = benzo[h]quinoline; phen = 1,10-phenanthroline). The complex formed mono- or bi-molecular layers in interlayer spaces, depending on the adsorption amount to 50% or 100% cation exchange capacity (CEC), respectively. Notably, the VCD signals were sensitive enough to reveal the detailed molecular interactions in adsorption layers. Signal enhancement was achieved by the coherent delocalization of vibrational motions over tightly bound associates. Models of molecular packing were proposed with the help of theoretical simulations.

Stereoselective Enhancement of VCD Signals for Intercalation Compounds of Sodium Montmorillonite and Chiral Metal Complexes

Abstract Vibrational circular dichroism (VCD) spectra were recorded for the intercalation compounds of sodium montmorillonite co-adsorbing two kinds of metal complexes, Δ- (or Λ-)[Ru(phen)3]2+ and Λ- (or Δ-)[Ni(phen)3]2+. The complexes were chosen so as to form a pseudo racemate. Notably some of the VCD signals were enhanced in comparison to the samples adsorbing each complex separately. The results were rationalized in terms of the delocalization of vibrational motions over a tightly bound molecular pair in a coherent way. The model of racemic adsorption of [M(II)(phen)3]2+ (M(II) = a divalent metal ion) in the interlayer space of a clay mineral was proposed.

Exploration of chromophores for a VCD couplet in a spectrally transparent infrared region for biomolecules.

Interactions of two chromophores such as carbonyl groups yield a strong VCD couplet that reflects the molecular structures. The use of VCD couplets for biomacromolecular structural studies has been hampered by severe signal overlap caused by numerous functional groups that originally exist in biomacromolecules. Nitrile, isonitrile, alkyne, and azido groups show characteristic IR absorption in the 2300-2000 cm-1 region, where biomolecules do not strongly absorb. We herein examined the usefulness of these functional groups as chromophores to observe a strong VCD couplet that can be readily interpreted using theoretical calculations. Studies on a chiral binaphthyl scaffold possessing two identical chromophores showed that nitrile and isonitrile groups generate moderately-strong but complex VCD signals due to anharmonic contributions. The nature of their anharmonic VCD patterns is discussed by comparison with the VCD spectrum of a mono-chromophoric molecule and by anharmonic DFT calculations. On the other hand, through studies on diazido binaphthyl and diazido monosaccharide, we demonstrated that the azido group is more promising for structural analysis of larger molecules due to its simple, strong VCD couplet whose spectral patterns are readily predicted by harmonic DFT calculations.

Synthesis and spectroscopic study of three new oxadiazole derivatives with detailed computational evaluation of their reactivity and pharmaceutical potential

Local reactivity properties and potential for application in new pharmaceutical compounds have been addressed for the three newly synthetized oxadiazole derivatives (2-(5-(2-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (ORTHONITRO), 2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (METANITRO) and 2-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (PARANITRO), by application of computational molecular modeling. Within the framework of density functional theory (DFT) this study encompassed calculations of molecular electrostatic potential (MEP), average local ionization energies (ALIE) and bond dissociation energies for hydrogen abstraction (H-BDE). MD simulations have been used in order to assess the influence of water and to identify the atoms of these molecules with preference towards the interaction with water molecules. Molecular docking procedure has been applied in order to check the binding activity of these derivatives against the Glucan endo-1.6-beta-glucosidase inhibitor, Acrocylindropepsin inhibitor and Chymosin inhibitor proteins. The pharmaceutical potential of these derivatives has been assessed by the calculations of the well-established drug likeness parameters. A strong out-of-plane CH mode of the phenyl rings are observed at 769 cm−1 for ORTHONITRO, 768 cm−1 for METANITRO and at 848 cm−1 for PARANITRO in the IR spectrum as expected for substituted benzenes. The VCD signals, corresponding to CN and NO2 modes of the title compounds are good markers for assigning of absolute configuration. In the title compounds, in ORTHONITRO, the oxadiazole ring is tilted from the phenyl and pyrazine ring while for METANITRO and PARANITRO, there is a planar orientation. The first hyperpolariazabilities of ORTHONITRO, METANITRO and PARANITRO are respectively, 34.83, 54.50 and 174.05 times that of urea. For all the compounds, HOMO is delocalized over the pyrazine and oxadiazole rings, while LUMO is delocalized over whole molecule, except pyrazine ring of ORTHONITRO, over phenyl ring and NO2 group of METANITRO and in the entire molecule of PARANITRO. The title compounds are docked with the proteins, Glucan endo-1.6-beta-glucosidase inhibitor, Acrocylindropepsin inhibitor and Chymosin inhibitor and METANITRO exhibits more inhibitory activity against the receptors than the other ligands. The results obtained from anti-TB activity are more promising as the compounds were found to be more potent than reference standard, ORTHONITRO (MIC = 1.6 μg/ml), METANITRO (MIC = 0.8 μg/ml), PARANITRO (MIC = 1.6 μg/ml), streptomycin (MIC = 6.2 μg/ml) and pyrazinamide (MIC = 3.1 μg/ml).

Helicity and Topological Chirality in Hydrogen-Bonded Supermolecules Characterized by Advanced Graph Set Analysis and Solid-State Vibrational Circular Dichroism Spectroscopy

The applicability of advanced graph set analysis and solid-state vibrational circular dichroism (SD-VCD) spectroscopy to the characterization of supramolecular chirality has been demonstrated. Recrystallization of R-(+)-1-phenylethylammonium 1-naphthoate affords two polymorphic crystals: one is composed of hydrogen-bonded (HB) 2-fold helices with helicity, while the other contains HB clusters with topological chirality. Handedness and origins of the chirality were crystallographically characterized by advanced graph set analysis. SD-VCD measurements were then recorded for these polymorphic crystals using the VCD spectrometer PRESTO-S-2007, which we developed. Unique VCD spectra were observed because of the difference in features of the chiral supramolecular structures. Enhancement of VCD signals depending on dimensionality of the supermolecules is especially noteworthy. Generality of 2-fold helices, demonstrated by statistics from the Cambridge Structural Database, and geometrical characteristics and theo...

Application of spectral analysis for differentiation between metals using signals from eddy-current transducers

The authors theoretically and experimentally substantiated the use of the spectral method for processing a signal of the vortex-current metal detector for dichotomous differentiation between metals. Results of experimental research that prove the possibility of using spectral analysis for differentiation between metals were presented. The vortex-current method for detection of hidden metal objects was analyzed. It was indicated that amplitude of output VCD signal is determined by electric conductivity of material of a hidden object and its magnetic permeability. It was shown that the spectral density of a signal can be an informative feature. The authors designed and fabricated a mockup of the vortex-current device, the special features of which include modularity, which, if necessary, makes it possible to replace quickly each of the modules. The developed algorithm of normalization of signals allows an operator to choose freely a scan mode and compare correctly VCD signals with reference signals. Research results show that it is possible to distinguish easily between the spectra of ferrous metals and those of non-ferrous metals. Spectral methods can be applied both for dichotomous analysis of hidden metal objects and for analysis of the type of metal in the subgroup of non-ferrous metals under condition of using highly sensitive spectroanalyzers with measurement error not exceeding 1 %. It was shown that advantage of the spectral method for analysis of signals of vortex-current transducer is identification of hidden objects by type of metal. The use of spectral methods for detection of hidden metals offers a new property – distant analysis of composition of detected metal objects.

Taking advantage of Co(ii) induced enhanced VCD for the fast and sensitive determination of enantiomeric excess.

Co(ii) induces a large VCD signal enhancement, which overcomes the low sensitivity of VCD and opens new perspectives in quantitative VCD. We used a stereodynamic system, where the analyte determines the chirality of the Co(ii) coordination sphere. The strong VCD signals stand out the baseline, which allows for their rapid and accurate quantitation. This lends itself to the first general method for the ee determination of α-amino acids based on vibrational circular dichroism and constitutes a model for the design of sensitive quantitative assays based on VCD.

Cyclopolymerization of Disiloxane-Tethered Divinyl Monomers To Synthesize Chirality-Responsive Helical Polymers

Synthetic polymers mimicking the stimuli-responsive coiled-coil structures of naturally occurring macromolecules such as motor proteins remain challenging. Here we report that chirality switchable quasi-double helical polymers can be synthesized by the free radical cyclopolymerization of the tetramethyldisiloxane-tethered divinyl monomers. Two cyclopolymers (pbSt and pbMA) are obtained in this work, which in solid state are helical polymers investigated by both ECD and VCD. According to VCD analysis, the C–H deformation modes including C–H bending (mode I) and C–H rocking (mode II) in the main-chain helix show strong signals in VCD spectra and the plots of the division of VCD by IR, which have different responses to solvation histories or thermal treatment compared with other vibrational signals arising from side rings (especially signals from tetramethyldisiloxane groups). After thermal treatment, all the side-ring VCD signals of both pbSt and pbMA are inverted, while the VCD signals from mode II of the ...

Revisiting an old concept: the coupled oscillator model for VCD. Part 1: the generalised coupled oscillator mechanism and its intrinsic connection to the strength of VCD signals.

Motivated by the renewed interest in the coupled oscillator (CO) model for VCD, in this work a generalised coupled oscillator (GCO) expression is derived by introducing the concept of a coupled oscillator origin. Unlike the standard CO expression, the GCO expression is exact within the harmonic approximation. Using two illustrative example molecules, the theoretical concepts introduced here are demonstrated by performing a GCO decomposition of the rotational strengths computed using DFT. This analysis shows that: (1) the contributions to the rotational strengths that are normally neglected in the standard CO model can be comparable to or larger than the CO contribution, and (2) the GCO mechanism introduced here can affect the VCD intensities of all types of modes in symmetric and asymmetric molecules.

Co(ii)-induced giant vibrational CD provides a new design of methods for rapid and sensitive chirality recognition.

We designed a stereodynamic system, where the chirality of the analyte serves as a template for the helicity of the first coordination sphere of Co(ii). Giant VCD bands induced by Co(ii) allow the measurement of a completely significant and conclusive VCD spectrum in only a few seconds and/or on minute quantities of the analyte. This paves the way for the development of similar protocols, overcoming the limitations due to weak VCD signals for the assignment of absolute configurations.

Theoretical investigations into spectral and non-linear optical properties of brucine and strychnine using density functional theory

The density functional theoretical (DFT) computations were performed at the B3LYP/6-311G++(d, p) level to calculate the equilibrium geometry, vibrational wave numbers, intensities, and various other molecular properties of brucine and strychnine, which were found in satisfactory agreement with the experimental data. The out-of-phase stretching modes of aromatic rings and carbonyl stretching modes in combination with CH stretching modes at stereogenic centers generate VCD signals, which are remarkably efficient configuration markers for these chiral molecular systems. NBOs analysis reveals that the large values of second order perturbation energy (47.24kcal/mol for brucine and 46.93kcal/mol for strychnine) confirms strong hyperconjugative interaction between the orbital containing the lone pair of electron of nitrogen and the neighboring CO antibonding orbital. The molecular electrostatic potential map of strychnine molecule, with no polar groups other than the lone keto group, shows less polarization, which accounts for its lower susceptibility towards electrophilic attack as compared to brucine.

Amplified Vibrational Circular Dichroism as a Probe of Local Biomolecular Structure

We show that the VCD signal intensities of amino acids and oligopeptides can be enhanced by up to 2 orders of magnitude by coupling them to a paramagnetic metal ion. If the redox state of the metal ion is changed from paramagnetic to diamagnetic the VCD amplification vanishes completely. From this observation and from complementary quantum-chemical calculations we conclude that the observed VCD amplification finds its origin in vibronic coupling with low-lying electronic states. We find that the enhancement factor is strongly mode dependent and that it is determined by the distance between the oscillator and the paramagnetic metal ion. This localized character of the VCD amplification provides a unique tool to specifically probe the local structure surrounding a paramagnetic ion and to zoom in on such local structure within larger biomolecular systems.

Chiral Recognition of Amino Acid Enantiomers by a Crown Ether: Chiroptical IR-VCD Response and Computational Study

We report on a combined experimental and computational study of the chiral recognition of the amino acid serine in protonated form (L/D-SerH(+)), by the crown ether (all-S)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (S-18c6H4). Infrared and vibrational circular dichroism spectroscopies (IR-VCD) are employed to characterize the chiroptical response of the complexes formed by S-18c6H4 with the L-SerH(+) and D-SerH(+) enantiomers in dried thin films obtained from aqueous solutions. The study focuses on vibrational modes directly related to the intermolecular hydrogen bonds between the crown ether derivative and serine, responsible for crown-serine binding, namely, the C═O and C-O stretching modes, and on the C-O-H bending mode, which yield intense IR and VCD signals in the range of wavenumbers 900-2000 cm(-1). The experimental spectra are analyzed in combination with a computational structural survey and optimization at different levels of density functional theory. The conformational landscape of the complexes is found to be primarily governed by a bowl-like structure of the crown ether host and a tripodal coordination of the protonated R-NH3(+) group of serine with the oxygen atoms of the central ether ring. Additionally, one or two of the carboxylic side groups of the crown ether interact with the -COH and -COOH groups of serine. Chiral selectivity is probed by recording the IR and VCD spectra of dried thin films obtained from aqueous solutions with equimolar concentrations of the two serine enantiomers and the macrocycle. The results demonstrate a marked chiral recognition of L-SerH(+) relative to D-SerH(+) by the S-18c6H4 substrate, which arises from the favorable host-guest coordination through H-bonds at optimum distances and collinear orientations, also involving a limited distortion of the crown ether backbone.

Exciton Chirality Method in Vibrational Circular Dichroism

The interaction of two IR chromophores yields a strong vibrational circular dichroism couplet whose sign reflects the absolute configuration of the molecule. We present a method to determine absolute configuration of a chiral molecule based on this couplet without need of theoretical calculation. Not only can this method analyze various molecules whose absolute configuration is difficult to determine by other spectroscopic methods, but also it can significantly enhance VCD signals.

Conformational landscape of a chiral crown ether: a vibrational circular dichroism spectroscopy and computational study

Herein we report a study of the most stable conformers of the chiral crown ether (all-S)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (18c6H4), which constitutes a key building block for materials in asymmetric catalysis and enantiomeric separation. Infrared and vibrational circular dichroism spectroscopies are employed to characterize the vibrational modes of the 18c6H4 molecule in a low polarity solvent (CDCl3). The investigation covers a broad range of wavenumbers (800–4000cm−1) and focuses particularly on the O–H, C–H, CO and C–O stretching modes and on the C–O–H bending mode, which yield the most intense IR and VCD signals. The experimental results are combined with a computational conformational survey and structure optimization at the B3LYP/6-311++G(2d,2p) level. The conformational landscape of 18c6H4 is found to be governed by bowl-like structures sustained by various types of H-bonding arrangements of the carboxylic side chains with each other and with the central crown ether ring.

Comparison of mid‐infrared Fourier transform vibrational circular dichroism measurements with single and dual polarization modulations

Fourier transform infrared vibrational circular dichroism (FTIR-VCD) measurements have gone through major advances in the last decade. A major thrust in these advances was to find ways that can minimize the VCD spectral artifacts and obtain the VCD signals at enhanced signal quality. However, all these advances are not incorporated in FTIR-VCD instruments manufactured by some commercial manufacturers. In this article, we compare the measurements obtained with single and dual polarization modulations to seek the attention of the users of single polarization modulation method in minimizing the artifacts in such measurements. We also report that the VCD spectrum of a home-made collagen film can serve as a simple and convenient sample for routine verification of the correct functioning of the VCD spectrometers.

The Utilization of the Anomalous Intensity Enhancement of the Amide I Couplet for Probing the Formation of Peptide Fibrils in Solution

Knowledge of the architecture of amyloid-like fibrils is necessary for understanding the mechanism of fibril formation. Some amyloid fibrils give rise to an intensity-enhanced amide I couplet in their VCD spectra [Ma et al. J. Am. Chem. Soc.2007, 129, 12364 and Measey et al. J. Am. Chem. Soc. 2009, 131, 18218]. An understanding of the structural basis for this enhancement would facilitate the use of VCD spectroscopy for the structural characterization of amyloid fibrils. To this end we developed a simplified model, which describes amide I modes in the fibrillar stacking of -sheets by a three-dimensional lattice of transition dipole moments. The lattice contains 2 dipoles per strand and variable numbers of sheets and strands per sheet. Thus, we showed that the VCD intensity enhancement requires either helically twisted sheets with parallel oriented strands or a special antiparallel arrangements of adjacent sheets with antiparallel strand orientation in a fibril, in which the strands in one sheet are rotated around their axes by 180o compared with a canonical antiparallel orientation. The sign of the VCD signal of amyloid-like fibrils can be used to distinguish between right and left handed helical twists of parallel oriented -sheets. We compare the results of our simulation to experimental spectra of GNNQQNY, a fragment of the yeast prion protein Sup35, and an alanine-rich peptide, AKY8. For the latter, we use IR, VCD and polarized Raman spectroscopy as well as atomic force microscopy to probe and analyze the nucleation phase as well as the fibril formation phase. Our results demonstrate the advantages of using vibrational spectroscopy to probe the kinetics of peptide and protein aggregation as well as the chirality of the resulting supramolecular structure.

The Self-Aggregation of A Polyalanine Octamer Promoted by its C-terminal Tyrosine and Probed by A Strongly Enhanced VCD Signal

The 8-residue alanine oligopeptide, Ac-A4KA2Y-NH2 (AKY8), was found to form amyloid-like fibrils upon incubation at room temperature in acidified aqueous solution, at peptide concentrations > 10 mM. The fibril solution exhibits an enhanced VCD couplet in the amide I’ band region, which is nearly 2 orders of magnitude larger than typical polypeptide/protein signals in this region. The UV-CD spectrum of the fibril solution shows circular dichroism in the region associated with the tyrosine side chain absorption. A similar peptide, Ac-A4KA2-NH2 (AK7), lacking in a terminal tyrosine residue, does not aggregate. These results suggest a pivotal role for the C-terminal tyrosine residue in stabilizing the aggregation state of this peptide. It is speculated that interactions between the lysine and tyrosine side chains of consecutive strands in an anti-parallel arrangement, e.g. via cation-π interactions, are responsible for the stabilization of the resulting fibrils. These results offer considerations and insight for the de novo design of self-assembling oligopeptides for biomedical and biotechnological applications, and highlight the usefulness of VCD as a tool to probe amyloid fibril formation.

Vibrational and electronic optical activity of the chiral disulphide group: Implications for disulphide bridge conformation

Using dihydrogendisulphide (H(2)S(2)), dimethyl- ((CH(3))(2)S(2)), and diethyldisulphide ((CH(3)CH(2))(2)S(2))as model molecules, theoretical ECD, VCD, and ROA spectra of nonplanar disulphides were calculated by DFT methods. Most of the calculated electronic and vibrational chiroptical features suffer an equivocal relation between calculatedsigns of ECD, VCD, or ROA and the sense of disulphide nonplanarity as noted earlier for low-lying ECD bands. This is a consequence of local C(2) symmetry of a disulphide group causing most electronic and vibrational transitions to occur as pairs falling to alternative A, B symmetry species, which become degenerate and switch their succession (and consequently the observed chiroptical sign pattern) at the energetically most favorable perpendicular conformation. According to present calculations, the key to resolving this ambiguity may involve the S-S stretching vibrational mode at approximately 500 cm(-1). The relation of signs of the relevant VCD and ROA features to sense of disulphide chirality seems simpler and less ambiguous. The right-handed arrangement of the S-S group (0 < chi(S-S) < 180 degrees) results in mostly negative VCD signals. Although relation to ROA still suffers some ambiguity, it gets clearer along the series H(2)S(2)-(CH(3))(2)S(2)-(CH(3)CH(2))(2)S(2). ROA is also attractive for the analysis of disulphide-containing peptides and proteins, because applying it to aqueous solutions is not problematic.