Vibrational Circular Dichroism Bands Research Articles

A vibrational circular dichroism approach to the determination of the absolute configuration of flexible and transparent molecules: fluorenone ketals of 1,n-diols

The infrared absorption (IR) and vibrational circular dichroism (VCD) spectra for five ketal molecules, three of which obtained from 1,2-diols and two from 1,3-diols, were recorded in the mid-IR region. The spectra have been satisfactorily reproduced by DFT calculations, even with not too large wavefunction basis sets, especially due to the low number of conformers to be considered. The mobility of some moieties provides a recognizable signature. A characteristic couplet of VCD bands attributed to normal modes involving the methine and a phenyl ring bonded to the stereogenic carbon atom is evidenced for two ketals of the series as a signature of the absolute configuration; due comparison with existing literature is made. A relation is discussed of the present VCD data with the literature VCD data of simple alcohols and diols.

Conformational equilibria of TADDOL‐s in solution investigated by vibrational circular dichroism

Six enantiomeric pairs of TADDOL-s gathered in two series with either methyl (series A) or phenyl (series B) substituent in 2-position of the dioxolane ring were studied by vibrational circular dichroism (VCD). Experimental IR and VCD spectra associated with density functional theory (DFT) calculations showed that the two series exhibit quite different conformations in solution. In series A, the conformer with anti C-O bonds and stabilized by intramolecular OH...OH hydrogen bonding prevails, whereas in series B the conformer with gauche C-O bonds and intramolecular OH...π hydrogen bonding is favored. The shape and sign of the VCD bands in the O-H stretching region revealing the nature of the intramolecular hydrogen bonding were clearly identified. Polarimetric measurements showed that, within the same absolute configuration, compounds in series A and in series B have opposite signs of optical rotation.

Direct calculations of vibrational absorption and circular dichroism spectra of alanine dipeptide analog in water: Quantum mechanical/molecular mechanical molecular dynamics simulations

The vibrational absorption (IR) and vibrational circular dichroism (VCD) spectra of alanine dipeptide analog in water are directly calculated by Fourier transforming the time correlation functions of the electric and magnetic dipole moments, which are calculated using the dynamic partial charges and trajectory of the peptide generated from the quantum mechanical/molecular mechanical molecular dynamics simulations. The alanine dipeptide analog is treated at the Hartree-Fock level with 3-21G, 4-31G, 6-31G, and 6-31G(*) basis sets and the solvent H(2)O is modeled with the TIP3P water. The atomic partial charges are obtained from the Lowdin population analysis, which gives consistent IR spectral profiles irrespective of the basis sets used. The simulated VCD spectrum by a polyproline II(P(II))-dominant trajectory is compatible with the previous experimental results of the polyproline peptides, where the amide I and II VCD bands are negative couplets with a weak positive peak to the high frequency region. The sampling efficiency of the P(II) conformer is much lower than the other ones at all basis levels used. The simulated VCD spectrum of alpha-helix averaged over five trajectories has the reverse sign pattern compared to the P(II) spectrum and is found to be consistent with the previously observed spectral features of alpha-helical polypeptides. The sign patterns of the beta-strand VCD spectrum are qualitatively similar to the experimental spectra of beta-sheet rich proteins. The VCD spectra obtained from the trajectories containing several extended conformers such as beta and P(II) are not clearly distinguishable from the beta-strand-dominant spectra. It is interesting that the P(II) and the coil VCD spectra coincide in sign pattern and relative intensity for all amide modes. This demonstrates that the negative couplet structures of the amide I and II VCD spectra do not necessarily prove the dominance of either P(II) or coil conformation. We anticipate that the present method can be used to directly simulate the IR and VCD spectra of structurally heterogeneous biomolecules in condensed phases.

Characterization of folded conformations in a tetrapeptide containing two tryptophan residues by vibrational circular dichroism

The intramolecularly hydrogen bonded conformations of the tetrapeptide Boc-Trp-Aib-Gly-Trp-OMe (WUGW) are investigated using experimental and quantum chemical predictions of vibrational circular dichroism (VCD) in the 1800-1550 cm(-1) region. The predicted VCD spectrum, for a conformation (conformer A) obtained from optimization of crystal structure, reproduced the dominant negative VCD band observed experimentally in CH(3)OH and CHCl(3) solvents. However, the predicted VCD spectrum of Conformation A also has an extra positive band which is not seen in the experimental spectra. This mismatch appears to be due to the lack of solvent influence in the quantum chemical geometry optimizations. However, Conformations I and II, obtained, respectively, from constrained optimization of crystal and NMR structures, mimic the solvent stabilized structures and are predicted to have dominant negative VCD band as found in the experimental spectra. It is noted that, for the peptide investigated here, unconstrained quantum chemical geometry optimizations in vacuum converged to structures that are not the realistic models of conformations found in solution. It is also noted that undertaking quantum chemical vibrational property calculations directly using geometries obtained from crystal data or NMR data resulted in unrealistic vibrational frequencies and descriptions. However, constraining the backbone dihedral angles to those found in condensed medium, and optimizing the remaining geometrical parameters resulted in a better reproduction of the observed VCD in condensed medium. The vibrational origins of bands in all of the predicted VCD spectra for the WUGW-tetrapeptide have also been presented.

Synthesis and Chiroptical Properties of Cryptophanes HavingC1-Symmetry

New enantiopure cryptophanes 3-7 having C(1)-symmetry have been synthesized. Electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) have been used to investigate their chiroptical properties, and the results are compared to those obtained for cryptophane-A (1) having D(3)-symmetry. The ECD spectra of compounds 3-7 show Cotton effects that differ from those of cryptophane-A. However, our results suggest that a confident determination of the absolute configuration of the monofunctionalized cryptophanes can be made using ECD spectroscopy. Interestingly, we have found that the ECD spectra of cryptophanes, especially the (1)L(b) transition, are very sensitive to the nature of the solvent. These spectral modifications are essentially due to bulk solvent properties rather than the ability of a particular solvent to insert into the cavity of cryptophanes. On the other hand, VCD spectra of the monofunctionalized cryptophanes have not revealed significant spectral modifications with respect to the VCD spectrum of the CHCl(3) at cryptophane-A complex, except for CHCl(3) at 7 and to a smaller extent for CHCl(3) at 6. These spectral modifications, which essentially consist in lower intensities of VCD bands associated with the cryptophane backbone, were perfectly reproduced by ab initio calculations performed at DFT (B3PW91/6-31G*) level. These results clearly demonstrate that VCD measurements associated with DFT calculations allow an easy determination of the absolute configuration of cryptophane-A derivatives.

A configurational and conformational study of aframodial and its diasteriomers via experimental and theoretical VA and VCD spectroscopies

In this work we present the experimental and theoretical vibrational absorption (VA) and the theoretical vibrational circular dichroism (VCD) spectra for aframodial. In addition, we present the theoretical VA and VCD spectra for the diasteriomers of aframodial. Aframodial has four chiral centers and hence has 24 = 16 diasteriomers, which occur in eight pairs of enantiomers. In addition to the four chiral centers, there is an additional chirality due to the helicity of the entire molecule, which we show by presenting 12 configurations of the 5S,8S,9R,10S enantiomer of aframodial. The VCD spectra for the diasteriomers and the 12 configurations of one enantiomer are shown to be very sensitive not only to the local stereochemistry at each chiral center, but in addition, to the helicity of the entire molecule. Here one must be careful in analyzing the signs of the VCD bands due to the ‘non-chiral’ chromophores in the molecule, since one has two contributions; one due to the inherent chirality at the four chiral centers, and one due to the chirality of the side chain groups in specific conformers, that is, its helicity. Theoretical simulations for various levels of theory are compared to the experimental VA recorded to date. The VCD spectra simulations are presented, but no experimental VCD and Raman spectra have been reported to date, though some preliminary VCD measurements have been made in Stephens’ lab in Los Angeles. The flexible side chain is proposed to be responsible for the small size of the VCD spectra of this molecule, even though the chiral part of the molecule is very rigid and has four chiral centers. In addition to VCD and Raman measurements, Raman optical activity (ROA) measurements would be very enlightening, as in many cases bands which are weak in both the VA and VCD, may be large in the Raman and/or ROA spectra. The feasibility of using vibrational spectroscopy to monitor biological structure, function and activity is a worthy goal, but this work shows that a careful theoretical analysis is also required, if one is to fully utilize and understand the experimental results. The reliability, reproduceability and uniqueness of the vibrational spectroscopic experiments and the information which can be gained from them is discussed, as well as the details of the computation of VA, VCD and Raman (and ROA) spectroscopy for molecules of the complexity of aframodial, which have multiple chiral centers and flexible side chains.

Density Functional Theory Study on Vibrational Circular Dichroism as a Tool for Analysis of Intermolecular Systems: (1:1) Cysteine−Water Complex Conformations

This paper presents a discussion of the interaction energies for selected conformers of chiral l-cysteine and their (1:1) complexes with water at the B3LYP/aug-cc-pVDZ level. From among more than forty calculated 1:1 complexes three groups of complexes were singled out and examined by the B3LYP/aug-cc-pVDZ calculated vibrational circular dichroism (VCD) spectra. On the basis of analysis of the nu(OmicronEta) and nu(NuEta) and beta(OH2) and beta(NH2) ranges, the VCD spectra were found to be sensitive to conformational changes and water arrangement in cysteine complexes, and to be especially useful for discriminating between different chiral forms of intermolecular hydrogen-bonding complexes. In particular, we show that the VCD modes of an achiral water molecule after complex formation acquire significant rotational strengths whose signs change in line with the geometry of the complex. Moreover, for some water arrangements the VCD spectra can be sensitive to water-wagging conformers and, in temperatures low enough, the intensive nu(OmicronEtaWfree) and beta(H2O) VCD bands may be sufficiently separated to be splitted into pair of oppositely directed bands.

Observation and characterization of a specific vibrational circular dichroism band in phenyl glycosides

Application of vibrational circular dichroism (VCD) spectroscopy to structural analysis of carbohydrates has recently progressed. However, few studies on glycoconjugates VCD have thus far been reported, despite the fact that naturally occurring carbohydrates exist as various glycoconjugates. To further explore the application of the VCD technique, we have measured a series of aromatic glycosides and found that axial aromatic glycosides exhibited a negative band at around 1230 cm(-1) while equatorial ones showed flat features in this region. This is the first structure-spectra relationship on glycoconjugate VCD that distinguishes the stereochemistry of the sugar anomers. Several model compounds were prepared and their vibrational properties calculated by using the density functional theory (DFT) method, which assigned the vibrational mode of this band based on the stretching motion of the glycosidic oxygen and aromatic carbon. This concept that aglycan parts can reflect stereochemical information of sugar moieties may encourage further VCD studies on glycoconjugates to realize practical structural analysis of carbohydrates.

Absolute Configuration and Conformation Analysis of 1-Phenylethanol by Matrix-Isolation Infrared and Vibrational Circular Dichroism Spectroscopy Combined with Density Functional Theory Calculation

The absolute configuration and conformation of 1-phenylethanol (1-PhEtOH) have been determined by matrix-isolation infrared (IR) and vibrational circular dichroism (VCD) spectroscopy combined with quantum chemical calculations. Quantum chemical calculations have identified that there are three conformers, namely, I, II, and III, in which characteristic intramolecular interactions are found. The IR spectrum-conformation correlation for 1-PhEtOH has been developed by the Ar matrix-isolation IR measurement and used for the assignments of the observed IR bands. In a dilute CCl(4) solution, 1-PhEtOH exists predominantly as conformer I along with a trace amount of conformer II. By considering conformations and intermolecular hydrogen-bonding in the spectral simulation for (S)-1-PhEtOH, we have successfully reproduced the VCD spectrum of (-)-1-PhEtOH observed in a dilute CS(2) solution. Thus, (-)-1-PhEtOH is of S-configuration and conformer I in the dilute solution. The same method has been applied to analyze the VCD spectra measured in the liquid state of (-)-1-PhEtOH. The absolute configuration of 1-PhEtOH in the condensed phase is enabled by identifying VCD bands that are insensitive to conformational changes and intermolecular interactions. The present work provides a combinatorial procedure for determination of both the absolute configuration and the conformation of chiral molecules in a dilute solution and condensed phase.

Harmonic and Anharmonic Features of IR and NIR Absorption and VCD Spectra of Chiral 4-X-[2.2]Paracyclophanes

The vibrational absorption spectra and vibrational circular dichroism (VCD) spectra of both enantiomers of 4-X-[2.2]paracyclophanes (X = COOCD3, Cl, I) have been recorded for a few regions in the range of 900-12000 cm(-1). The analysis of the VCD spectra for the two IR regions, 900-1600 cm(-1) and 2800-3200 cm(-1), is conducted by comparing with DFT calculations of the corresponding spectra; the latter region reveals common motifs of vibrational modes for the three molecules for aliphatic CH stretching fundamentals, whereas in the mid-IR region, one is able to identify specific signatures arising from the substituent groups X. In the CH stretching region between 2900 and 2800 cm(-1), we identify and interpret a group of three IR VCD bands due to HCH bending overtone transitions in Fermi resonance with CH stretching fundamental transitions. The analysis of the NIR region between approximately 8000 and approximately 9000 cm(-1) for X = COOCD3 reveals important features of the aromatic CH stretching overtones that are of value since the aromatic CH stretching fundamentals are almost silent. The intensifying of such overtones is attributed to electrical anharmonicity terms, which are evaluated here by ab initio methods and compared with literature data.

Analysis of Vibrational Circular Dichroism Spectra of (S)-(+)-2-Butanol by Rotational Strengths Expressed in Local Symmetry Coordinates

The vibrational circular dichroism (VCD) spectra of (S)-(+)-2-butanol have been observed in dilute CS(2) solutions. Two strong VCD bands are assigned mainly to the OH bending modes with the aid of quantum chemical calculations. The calculated VCD spectra corresponding to these bands are shown to depend on the conformation of the OH group. To understand this feature, we have calculated the contribution of each local vibrational mode to the rotational strengths and concluded that the coupling of the group vibrations between the in-plane and out-of-plane modes about the locally assumed symmetry planes play a significant role in VCD. This finding has provided a new scope of VCD in relation to molecular vibrations.

VCD spectroscopic investigation of enantiopure cyclic β‐lactams obtained through lipolase‐catalyzed enantioselective ring‐opening reaction

A direct enzymatic method for the preparation of cyclic beta-lactams and beta-amino acids was recently developed, involving the Lipolase-catalyzed enantioselective hydrolysis of racemic beta-lactams in an organic solvent. Vibrational circular dichroism (VCD) spectroscopy combined with quantum chemical calculations at ab initio (DFT) level of theory has now been applied to determine the absolute configuration and conformation of a series of cyclic beta-lactams (1-10). The absolute configuration of 8 was derived from X-ray crystallography. Only indirect evidence was available for 1, 2, 5, 6, and 7. The absolute configuration of the new lactams 3, 4, 9, and 10 was not known previously. The VCD analysis indicated the homochirality of the studied lactams. The conformation of the flexible beta-lactams was also predicted from the VCD data. Even in the cases where multiple conformers are allowed, the predominance of one conformer was found, with the exception of 2, being present as a mixture of four conformers. Beta-lactams tend to form H-bonded dimers. The fine structure of the amide I VCD band suggested that only a small population of H-bonded dimers is formed in deuterated chloroform.

Structures of plant viruses from vibrational circular dichroism

Vibrational circular dichroism (VCD) spectra in the amide I and II regions have been measured for viruses for the first time. VCD spectra were recorded for films prepared from aqueous buffer solutions and also for solutions using D(2)O buffers at pH 8. Investigations of four filamentous plant viruses, Tobacco mosaic virus (TMV), Papaya mosaic virus, Narcissus mosaic virus (NMV) and Potato virus X (PVX), as well as a deletion mutant of PVX, are described in this paper. The film VCD spectra of the viruses clearly revealed helical structures in the virus coat proteins; the nucleic acid bases present in the single-stranded RNA could also be characterized. In contrast, the solution VCD spectra showed the characteristic VCD bands for alpha-helical structures in the coat proteins but not for RNA. Both sets of results clearly indicated that the coat protein conformations are dominated by helical structures, in agreement with earlier reports. VCD results also indicated that the coat protein structures in PVX and NMV are similar to each other and somewhat different from that of TMV. The present study demonstrates the feasibility of measuring VCD spectra for viruses and extracting structural information from these spectra.

Isotope‐labeled vibrational circular dichroism studies of calmodulin and its interactions with ligands

In this work we have studied ligand-induced secondary structure changes in the small calcium regulatory protein calmodulin (CaM) using vibrational circular dichroism (VCD) spectroscopy. We find that, due to its chiral sensitivity, VCD spectroscopy has increased ability over IR spectroscopy to detect changes in the structure and flexibility of secondary structure elements upon ligand binding. Moreover, we demonstrate that the uniform isotope labeling of CaM with (13)C shifts its amide I' VCD band by about approximately 43 cm(-1) to lower wavenumbers, which opens up a spectral window to simultaneously visualize a bound target protein. Therefore this study also provides the first example of how isotope labeling enables protein-protein interactions to be studied by VCD with good separation of the signals for both isotope-labeled and unlabeled proteins.

Film Techniques for Vibrational Circular Dichroism Measurements

Vibrational circular dichroism (VCD) spectra in the 1800-900 cm(-1) region have been measured recently for protein films and for carbohydrate films prepared from aqueous solutions. In addition to the advantages of avoiding the interference from strong infrared absorption of water at 1650 cm(-1) and requiring a two-orders-of-magnitude-smaller amount of sample for film measurements (than those required for the same in water solutions), the VCD bands in film measurements are found to be the same as those in solution measurements and to be independent of film orientation. This latter observation indicated the possibility for routine VCD measurements in the film state. In this manuscript we report different film techniques for VCD measurements. These techniques include preparation of supported films, free-standing films, film-on-film, and facilitation of film formation for substances that otherwise do not form amorphous films. The experimental data for films prepared by each of these techniques are presented and the relative merits of these different methods are discussed.

Determining the Conformer Populations of (R)-(+)-3-Methylcyclopentanone Using Vibrational Absorption, Vibrational Circular Dichroism, and Specific Rotation

Experimental mid-infrared absorption and vibrational circular dichroism (VCD) spectra of (R)-(+)-3-methylcyclopentanone were measured in CCl4 solution. Theoretical absorption and VCD spectra were obtained with B3LYP functional and large basis sets, namely aug-cc-pVDZ, 6-311++G(2d,2p), and aug-cc-pVTZ. From the temperature dependent absorption spectra, ΔH° for equatorial ↔ axial equilibrium was determined to be 4.84 kJ/mol, and the ratio of percent populations of equatorial-methyl:axial-methyl conformers, to be 87:13. The populations of equatorial-methyl and axial-methyl conformers were also determined using the experimental and predicted vibrational intensities. However, the errors associated with the populations determined from infrared absorption and VCD band intensities are fairly large. Optical rotation of (+)-3-methylcyclopentanone at 589 nm was measured as a function of concentration in CCl4, CH3OH, and CH3CN solvents, and intrinsic rotation was extracted therefrom. Theoretical specific rotations were predicted using the B3LYP functional and the same basis sets as those used for infrared absorption and VCD. The populations determined from predicted specific rotations and experimental intrinsic rotation are within the error ranges of those determined from infrared absorption and VCD intensities. Using the populations determined from temperature dependent absorption spectra, the predicted population weighted specific rotation for an isolated molecule is found to be larger than the observed intrinsic rotation. The incorporation of solvent influence in specific rotation calculation increased the deviation of predicted value from experimental value, indicating the need for improved models for solvent influence.

A characteristic CH band in VCD of methyl glycosidic carbohydrates

Novel vibrational circular dichroism (VCD) studies in the CH region of a series of methyl glycosidic carbohydrates were examined. The specific CH stretching VCD band predicts absolute stereochemistries of their anomeric positions. The C-1 chiral information was extracted to the methoxy substituent as a probe. The concept of the vibrational chirality probe from a single chiral center in the presence of numerous such centers might be useful in determining the absolute configuration, when a multiplicity of chiral centers is present in a molecule such as a carbohydrate.

Vibrational circular dichroism of protein films.

Vibrational circular dichroism (VCD) spectra in the 1800-1400 cm(-)(1) region have been measured for the first time for protein films prepared from aqueous buffer solutions. These measurements demonstrate several advantages of significant importance. First, the interference from infrared absorption of water in the amide I region, which is a serious limitation for measurements in water solutions, is eliminated. Second, the amounts of protein samples required for VCD measurements on films are approximately 2 orders of magnitude smaller than those required for the same in water solutions. In addition, the amide I absorption and VCD bands of protein films are found to be independent of film orientation. Furthermore, characteristic VCD patterns have been observed for protein films whose secondary structure is dominated by alpha-helix, beta-sheet, and alpha + beta combinations. These results demonstrate that VCD can be used to study the structure of proteins in the film state.

Specific band observed in VCD predicts the anomeric configuration of carbohydrates.

The vibrational circular dichroism (VCD) technique was applied to carbohydrates and produced a glycoside characteristic VCD band, which was named the "glycoside band." It confirmed that this vibration was related to anomeric configurations of carbohydrates in the case of the d-series by means of isotope substitution. This band is defined as a negative, sharp, and intense VCD band at around 1145 cm-1, exhibited by d-sugars with an axial alpha-glycosidic linkage in the 4C1 conformation. As applications of this band, the VCD studies of the maltose-cellobiose mixture and the monitoring of the amyloglucosidase reaction were examined.

RNA Structural Forms Studied by Vibrational Circular Dichroism: Ab Initio Interpretation of the Spectra

Infrared (IR) and vibrational circular dichroism (VCD) spectra of single-stranded poly(rA) and poly(rU) RNA polynucleotides and double- and triple-stranded RNA helices were recorded and interpreted on the basis of density functional theory (DFT) at the BPW91/6-31G** level. Ab initio computations were performed for smaller fragments and extended to longer oligomers via transfer of atomic property tensors. The normal mode partial optimization method developed lately was found convenient for relaxation of the fragment geometries. Most of observed spectral features could be assigned to vibrations of the adenine, uracil, and sugar−phosphate chromophores; in particular, the VCD band shapes could be explained on the basis of specific spatial interactions. Thus, the VCD technique proved to be sensitive to various RNA conformational types (random coil, single strand, duplex, and triplex) in solution, spectra of which could be reliably modeled. The effect of the solvent could be only partially included, and ambiguity remains in the model structure used for the triplex RNA form.