Theoretical VCD Research Articles

Solid-state Vibrational Circular Dichroism as Applied for Heterogenous Asymmetric Catalysis: Copper(II) Complexes Immobilized in Montmorillonite

Solid-state vibrational circular dichroism (SD-VCD) spectra were measured on the ion-exchange adducts of sodium montmorillonite and [Cu(RR- or SS-oxa)]2+ as prepared in the presence of a substrate in Michael additions, (E)-2-butenoyl-2-oxazolidinone. Here RR- or SS-oxa denotes RR- or SS-2,2′-isopropylidene-bis(4-phenyl-2-oxazoline), respectively. By comparing the observed and theoretical VCD spectra, it was deduced that the substrate was transformed to a chiral structure in association with the Cu(II) complex within a clay mineral.

Ferrocenes with simple chiral substituents: an in-depth theoretical and experimental VCD and ECD study.

Circular dichroism spectra in the IR range (VCD = vibrational circular dichroism) and in the UV range (ECD = electronic circular dichroism) have been recorded for both enantiomers of simple mono-substituted ferrocenes containing chiral pendants: 1-acetoxyethylferrocene, 1, 1-methoxyethylferrocene, 2, and 1-hydroxyethylferrocene, 3; the related disubstituted 1,1'-bis(1-hydroxyethyl)ferrocene, 4, was also considered. These two types of spectra, with the support of DFT calculations, concur to unequivocally confirm the absolute configuration for 1-4. In particular, our computational results point out the clear advantage of using an anharmonic oscillator model for the interpretation of VCD spectra of chiral ferrocenes. Interesting conformational properties are either confirmed or established by the technique, like the eclipsed conformation of the two cyclopentadienyl rings and an intra-molecular interaction involving the OH for 3. For 4, NMR, VCD and IR spectra are compatible with dimer formation and in this case a distorted conformation is predicted. Of utmost importance for the absolute configuration assignment in mono-substituted ferrocenes, we were able to identify a diagnostic VCD band at 950 cm-1 and a (low intensity) ECD band that clearly indicate the absolute configuration of the whole series.

Cocrystals of pyrazinamide with p-toluenesulfonic and ferulic acids: DFT investigations and molecular docking studies

Cocrystals of pyrazinamide with p-toluenesulfonic acid (PZTSA) and ferulic acid (PZFER) are investigated by density functional calculations to find geometrical parameters, wavenumbers and different molecular properties. The vibrational modes associated with the phenyl and pyrazine rings have small changes during the cocrystal formation, while changes are associated with the amide group of pyrazinamide, hydroxyl and carboxylic groups of ferulic acid and SO3 group of PZTSA. Using density functional theory method the molecular geometries of the co-crystals were optimized in the ground state and a comparison is made with the reported experimental data. The theoretically obtained wavenumbers are assigned by means of potential energy distribution. The downshift of different modes in the infrared spectrum is due to hydrogen bonding and this is supported by the strong hyper conjugative interactions given by natural bond orbital analysis. HOMO is delocalized over the entire molecule except phenyl ring and methyl group and LUMO is delocalized over the entire molecule except CONH2 group for PZTSA while for PZFER, HOMO and LUMO are delocalized over the ferulic acid. From the MEP plot, electron rich regions are mainly localized over CO and SO3 groups of PZTSA while for PZFER, all the oxygen atoms electron rich regions. The first hyperpolarizability of PZTSA and PZFER are 5.99 and 89.66 times that of urea. Different molecular properties like, global chemical descriptors, frontier molecular orbital analysis, nonlinear optical properties and natural bond orbital analysis are also discussed in the present work. The different functional groups in the title compounds are identified by configurations markers using the theoretical VCD spectra analysis. Light harvesting efficiency analysis shows that PZFER is suitable for photo sensitizers in DSSC's. Docking results suggest that the compounds might exhibit inhibitory activity against mycobacterium tuberculosis type II and the compounds can be developed as a new anti-TB drug.

The influence of the position of a chiral substituent on undecathiophene chain. A DFT study

Undecathiophenes substituted by chiral and achiral groups were studied using DFT method. The substituent shift from one end to the other was monitored for: relative energy, the SRCM chirality measure, the chiral Wiener index, the HOMO-LUMO gap, HOMA and NICS aromaticity indices, and theoretical VCD spectrum. For both, all-trans and one-cis conformations, structures substituted at the end were ca. 10 kJ/mol more stable than the other isomers. The SRCMs fluctuations with the conformation made this parameter not useful, but, the topological chiral Wiener index displayed regular yet non-linear changes with the substituent position enabling differentiation of the chiral systems. The HOMO-LUMO gap increased with the substituent shift towards the central ring. It varies regularly with the Wiener index for all-trans but irregularly for one-cis conformers, indicating strong response of the gap on slight conformational changes. The aromaticity indices adopted to linear systems indicated the all-trans to be a bit less delocalized than the one-cis isomers. Finally, the calculated VCD spectra were indicated possibility to monitor the position of the chiral substituent along the all-trans and one-cis structures.

Substituent effect in theoretical VCD spectra

A correlational study shows for the first time a quantitative substituent effect on Vibrational Circular Dichroism intensity.

Experimental and Theoretical Spectroscopic Study of 310 Helical Peptides using Isotopic Labeling

Experimental and theoretical studies of IR, VCD, and Raman spectra have been performed on synthesized peptides (iPrCO-Aib-L-Ala-Aib-L-Ala-L-Ala-Aib-NHiPr) having a 310-helical conformation. These sequences vary only due to isotopic labeling (13C=O) of the L-Ala on the relative (i , i +1), (i, i + 2), and(i, i + 3) positions. Di-alkyl substitution on the α-carbon of Aib restricts the rotational freedom of the backbone torsional angles (f, ψ) and favors the formation of 310-helices [1]. Theoretical IR, VCD and Raman simulations were performed on sequences identical to the synthesized ones but constrained (in terms of f, ψ torsional angles) to an ideal 310-helical geometry (−60, −30) and fully optimizing all the other coordinates. All calculations were performed for peptides in vacuum using the DFT BPW91/6-31G∗ level of theory. The simulations predicated the relative separations of 13C=O and 12C=O features and their dependence on conformation as seen experimentally, with the exception that end effects caused a change in diagonal force field not well represented in the theoretical modeling. Experimental spectra for longer sequences and singly labeled variants confirmed the source of deviation for the i,i+1 and i,i+3 models. Comparison of IR and VCD intensity patters helped sort out the vibrational coupling constants sensed in the 13C=O modes. The isotopic labeled group vibrations are coupled to each other most strongly when degenerate and are effectively uncoupled from those of the unlabeled groups.[1] Wang et al., Peptide Science, 2009, 92, 452-456.

Solvent effects on IR and VCD spectra of natural products: an experimental and theoretical VCD study of pulegone

The VCD spectra of pulegone, dissolved in CDCl3, CD2Cl2 and CS2 have been recorded in the frequency range from 1000 to 3000 cm(-1). The assignment of the absolute configuration was performed by comparing the experimental data with theoretical spectra computed at the B3LYP/6-311+G(d,p) level. Analysis of the agreement in several spectral regions revealed significant shortcomings when comparing with vacuum calculations. It is shown that the agreement improves when the solvent effects are taken into account by a continuum model. For the measurements in CDCl3 and CD2Cl2 further improvement was found when considering explicitly 1 : 1 complexes between a pulegone and a CDCl3 or CD2Cl2 solvent molecule in vacuo, while the best agreement was obtained when embedding these in a continuum model. The presence of the chiral solute was found to induce a VCD active C-D stretch band which could be modeled also at ab initio level.

IR, VCD, 1H and 13C NMR experimental and theoretical studies of a natural guaianolide: Unambiguous determination of its absolute configuration

7,10-Epoxy -1,5-guaia-3, 11-dien-8, 12-olide has been isolated from dried leaves of Hedyosmum arborescens Swartz. The structure, vibrational frequencies, infrared and VCD intensities, NMR 1H and 13C spectra have been calculated by the density functional theory (DFT) method at the B3LYP/6-31+G(d,p) levels for four stereoisomers of this natural guaianolide. This study shows that the comparison of the experimental and calculated 1H and 13C NMR spectra allows the determination of the most favorable diastereoisomers but is not sufficient to access to the absolute configuration of the 7,10-epoxy guaianolide since the two remaining enantiomers possess the same NMR spectra. The absolute configuration of this natural compound can be unambiguously established only by the comparison of the calculated and experimental VCD spectra. Indeed, a very good agreement between experimental and theoretical VCD spectra was obtained in the mid-infrared range for the 7 S, 10 R-epoxy-1 R,5 R-guaia-3,11-dien-8 S,12-olide stereoisomer.

Absolute Configuration of Chiral [2.2]Paracyclophanes with Intramolecular Charge-Transfer Interaction. Failure of the Exciton Chirality Method and Use of the Sector Rule Applied to the Cotton Effect of the CT Transition

Optically active 4,7-dicyano-12,15-dimethoxy[2.2]paracyclophanes have been separated by chiral HPLC and their absolute configurations determined by comparison of the experimental and the theoretical VCD spectra. X-ray crystallographic structures for both diastereomers are also reported. The electronic circular dichroism spectra of these enantiomeric pairs, as chiral intramolecular charge-transfer complexes, have been obtained for the first time. The exciton coupling method, usually used for determining the absolute configuration of chiral molecules, however, did not give a correct prediction for the present CT-paracyclophane system. Instead, empirical sector rules for the signs of the Cotton effects of the CT transition can be applied for the assignment of the absolute configuration.

Solvent Effects on IR and VCD Spectra of Helical Peptides: DFT-Based Static Spectral Simulations with Explicit Water

Simulations of IR and VCD spectra are carried out for model alpha-helical, 3(10)-helical, and 3(1)-helical (polyProII-like) oligopeptides, with up to 21 amide groups, and including explicit consideration of effects of directly hydrogen-bonded solvent (water). Parameters used were obtained from ab initio density functional theory (DFT) computations of force field, atomic polar and axial tensors for oligopeptides of 5 to 7 amides, whose structures were constrained in (phi,psi) to target the secondary structure type but otherwise fully optimized. By comparison with experimental data as well as with calculations for identical but isolated (gas phase) peptides, the computed effects of an inner shell of aqueous solvent on the vibrational spectra of helical oligopeptides are illustrated. The interaction with solvent causes significant frequency shifts of the amide bands, but only minor changes in the characteristic IR intensity distributions and splittings and the VCD band shapes. Better agreement with experimental band shapes is achieved for the alpha-helical amide I' (N-deuterated) VCD by inclusion of explicit solvent in the calculations. Some improvements are also observed in theoretical VCD predictions for 13C labeled alpha-helical peptides when solvated models are used. However, the qualitative isotopic splitting patterns are preserved and just shifted in frequency due to consistent, solvent independent interamide coupling constants. The critical match of experiment and theory for relative positions of transitions in peptides with specifically separated 13C=O labels, including and neglecting solvent, confirms the stability of the coupling interactions. Despite these solvation effects, the calculated VCD band shape of the amide I mode is shown to be a reliable conformational probe, since it remains basically insensitive to frequency shifts caused by environment. Thus theoretical VCD simulations, even vacuum calculations, are shown to provide useful spectral predictions for solution-phase peptides.

Conformational determination of [Leu]enkephalin based on theoretical and experimental VA and VCD spectral analyses

Conformational determination of [Leu]enkephalin in DMSO-d6 is carried out using VA and VCD spectral analyses. Conformational energies, vibrational frequencies and VA and VCD intensities are calculated using DFT at B3LYP/6-31G* level of theory. Comparison between the measured spectra and the spectral simulations of the low energy conformations of the neutral species enable conformational determination of the molecule. In an earlier study, based only on VA spectroscopy, the results led to the conclusion that [Leu]enkephalin had only a single β-bend conformation of the neutral species in DMSO-d6. The present work shows the importance of using VCD in addition to VA in determining the conformation of chiral molecules and which one of the examined three single β-bend structures is the most stable in DMSO-d6.

Chiral allenes: theoretical VCD and IR spectra

The theoretical geometries, rotational constants, VCD, and IR spectra for the chiral ( S)-HXCCCFH (X=F, Cl, Br) allene molecules were calculated at the B3PW91/aug-cc-pVTZ level. We have shown that there is plausible adequacy between IR spectrum of ( S)-1,3-difluoroallene molecule calculated at B3PW91/aug-cc-pVTZ level and experimental spectra of the racemate system. For the other molecules studied, the experimental spectra were not published, yet, although, some results reported earlier for alkilohalogenoallenes are in line with our findings. The halogen influence on the VCD and IR spectra of the studied molecules is discussed.

On theoretical VCD, IR, and Raman spectra of (+)-hexahelicene in the ν(C–H) region

The VCD, IR, and Raman spectra were calculated for the (+)-hexahelicene molecule at the B3PW91/6-31G** level. The geometry was also optimized at the B3PW91/6-311G** level. The assignment and the spectral pattern in the region of the stretching ν(C–H) vibrations is discussed for the three kinds of spectra. The (+)-hexahelicene chirality, connected with the helical twist, can be detected through the stretching ν(C–H) vibrations, however, some VCD bands can compensate the other. The bands of the largest VCD rotational strengths, IR intensity, and Raman activity in the spectra are also mentioned.

On theoretical VCD, IR and Raman spectra of model chiral right-hand trefoil knots

The theoretical VCD, IR and Raman spectra for two model carbyne right-hand trefoil knots of two sizes C 30 and C 60 were calculated and the CC stretching vibration modes were analysed. The molecules studied belonged to the D 3 point-group of symmetry and are topologically chiral: possess neither asymmetric carbon atom nor axis of chirality. Analysis of the VCD spectra of the model molecules shows that based solely on the CC stretching vibrations, the chirality of the molecules can be detected and that larger the trefoil molecule the weaker is its VCD spectrum. On the other hand intensity of some of the IR and Raman bands increase with the size of the molecules.

Conformational Spaces and Absolute Configurations of Chiral Fluorinated Inhalation Anaesthetics. A Theoretical Study

The results of an ab initio DFT study of the conformational spaces of the chiral fluorinated inhalation anaesthetics Isoflurane and Desflurane and their theoretical VCD spectra using the hybrid density functional B3LYP and 6-311++G** GIAO basis functions are reported. In each case six conformers were characterized by analytical frequencies. At room temperature conformers 1 and 2 of Isoflurane account for 71% and 27% of the population, respectively, and conformers 1 and 2 of Desflurane account for 82% and 16% of the population, respectively. Each of the six conformers of (R)-Isoflurane and (R)-Desflurane gives rise to a clearly distinct VCD spectrum with different vibrational frequencies and rotatory strengths. The less populated conformers 2 of (R)-Isoflurane and of (R)-Desflurane give rise to vibrational modes with much higher rotational strength than the corresponding conformers 1. In studies of conformational equilibria and absolute configurations based on VCD spectroscopy, Boltzmann weights rather than arbitrarily selected relative weights are recommended. In view of the ambiguities and shortcomings of the previous calculated and experimental VCD spectra of Isoflurane and Desflurane, the results of the present theoretical VCD study may serve together with future independent experimental VCD spectra as a basis for an unequivocal determination of the absolute configurations of Isoflurane and Desflurane.