Application of electronic circular dichroism in configurational and conformational analysis of organic compounds

This tutorial review is addressed to readers with a background in basic organic chemistry and spectroscopy, but without a specific knowledge of electronic circular dichroism. It describes the fundamental principles, instrumentation, data analysis, and different approaches for interpretation of ECD. The discussion focuses on the application of ECD, also in combination with other methods, in structural analysis of organic compounds, including host-guest complexes, and will emphasize the importance of the interplay between configurational and conformational factors. The tutorial also covers modern supramolecular aspects of ECD and recent developments in computational methods.     

Vibrational circular dichroism in the mid-infrared

Vibrational circular dichroism (VCD) has been measured for the First tune in the CH₂ bending region down to 1250 cm^?1. This advance in technique was facilitated by the addition of a carbon-rod light source, a cooled HgCdTe detector, and signal averaging to our instrument.     

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.     

Vibrational circular dichroism of matrix-isolated molecules

Vibrational circular dichroism (VCD) spectra are reported for (+), (?) and (±) α-pinene, and (?) ß-pinine, isolated in argon matrices at ≈ 18 K. These are the first observations of VCD of matrix-isolated molecules. Spectra are limited to the CH stretching region (2800–3100 cm^?1). In all cases, the VCD spectra are substantially more structured than the corresponding room-temperature spectra, as a result of much narrower linewidths. Further, VCD magnitudes are greater due to decreased cancellation of overlapping transitions with oppositely signed VCD. The largest anisotropy ratios observed are >5 × 10^?4 and are larger than any reported for room-temperature solutions of organic molecules. This technique will permit substantially more definitive evaluations of theoretical calculations of VCD.     

Vibrational circular dichroism of polypeptides and proteins

Vibrational circular dichroism spectra of poly-L-tyrosine, poly-L-phenylalanine, myoglobin and-lactoglobulin were measured in solution for the amide I region. These measurements are shown to be consistent with previous determinations of the secondary structures of these species.     

Synthesis, conformational analysis and biological studies of cyclic cationic antimicrobial peptides containing sugar amino acids

Sugar amino acid based 24-membered macrocyclic C2-symmetric cationic peptides were designed and synthesized. The cationic group was introduced in the sugar amino acids. The conformation of these cyclic compounds was ascertained through NMR techniques, which proved they were amphipathic in nature. All the compounds were bacteriolytic, showed good activity against the Gr(+ve) and Gr(-ve) bacteria, and exhibited low hemolytic activity.     

Vibrational circular dichroism of N-acetyl-l-cysteine protected gold nanoparticles

Vibrational circular dichroism is used to determine the conformation of a thiol adsorbed on gold nanoparticles.     

Theory of electronic circular dichroism lineshapes

A microscopic, quantum field theory of lineshapes for electronic circular dichroism spectra is presented. A simple, model Hamiltonian for a single impurity in a crystal is considered. In this formalism, electron-photon coupling terms contribute directly to the magnetic transition dipole moment. Lineshape functions for absorbance and circular dichroism spectra are derived. Electronic circular dichroism spectra contain vibronic contributions which do not appear in absorbance spectra. This treatment does not require perturbation theory to obtain the vibrational contribution to the circular dichroism lineshape.     

Vibrational circular dichroism study of optically pure cryptophane-A

Vibrational circular dichroism (VCD) measurements and density functional theory (DFT) calculations were used to obtain the absolute configuration of optically pure cryptophane-A molecule. This large molecule (120 atoms) that possess a globular shape, but no chiral centers, exceeds the molecular size of published structures for which VCD has been used to determine the absolute configuration. VCD spectra recorded in CDCl(3) solution for the two resolved enantiomers are near mirror images, and very good agreement between the observed IR and VCD spectra and intensity calculations performed at the DFT (B3PW91/6-31G) level establish, besides the absolute configuration, the preferential anti conformation of the aliphatic linkers of the chloroform-cryptophane-A complex. Experiments performed in CD(2)Cl(2) and C(2)D(2)Cl(4) solutions show no significant modifications in the IR and VCD spectra, indicating that the conformation of the aliphatic linkers is similar for empty (C(2)D(2)Cl(4) solution) and encaged (CDCl(3) and CD(2)Cl(2) solutions) cryptophane-A molecules.     

Vibrational circular dichroism analysis reveals a conformational change of the baccatin III ring of paclitaxel: visualization of conformations using a new code for structure-activity relationships

The comparison between measured and conformer-weighted calculated VCD spectra of the baccatin III ring of paclitaxel and visualization of the conformations using the new code for structure-activity relationships are reported for the first time. The VCD spectrum of paclitaxel closely resembles that of the baccatin III ring. The large characteristic nuCO VCD bands with bisignate signs (1732 cm-1, Deltaepsilon = -1.6 x 10(-1); 1715 cm(-1), Deltaepsilon = 2.4 x 10(-1)) strongly reflect the structural property of the family of conformations bacc-ABC32F defined using the new code. The comparison with the conformation of the baccatin III core in the electron micrograph of the crystal structure of tubulin-paclitaxel (1JFF) suggests a conformational change of paclitaxel corresponding to a switch through the binding with beta-tublin and the intermolecular interactions involving the hydroxyl group (D) and carbonyl of acetoxy group (E). The representation of conformational codes allows complicated conformations to be very easily compared and facilitates future computational analyses such as those for the large-molecule calculations as well as genome analysis.     

Vibrational circular dichroism in hydrogen bond systems: Part II. Vibrational circular dichroism of the OH stretching vibration in 2,2-dimethyl-1,3-dioxolane-4-methanol

Vibrational circular dichroism (VCD) of the OH stretching band in 2,2-dimethyl-1,3- dioxolane-4-methanol has been studied. The OH stretching vibration for the intramolecularly hydrogen-bonded species in the (R)-enantiomer gives rise to a positive VCD band but no VCD band for the hydrogen-bond free species. It is shown that the G⁻G⁺ conformation in the intramolecular hydrogen bond system

gives a positive VCD band for the OH stretching vibration. The thermodynamic parameters in equilibrium between the free and intramolecularly hydrogen-bonded species have been determined as ΔH =−7.8 kJ mol⁻¹ and ΔS = −18 kJ K⁻¹ mol⁻¹.     

Vibrational circular dichroism: a new spectroscopic tool for biomolecular structural determination

Vibrational circular dichroism (VCD) in the past two decades has developed into a powerful new structural tool. A concise review of the applications of VCD to determine the structures of various biological molecules, namely peptides and proteins, nucleic acids and carbohydrates, is provided.     

Vibrational circular dichroism: a new spectroscopic tool for biomolecular structural determination

Vibrational circular dichroism (VCD) in the past two decades has developed into a powerful new structural tool. A concise review of the applications of VCD to determine the structures of various biological molecules, namely peptides and proteins, nucleic acids and carbohydrates, is provided. Received: 31 August 1999 / Revised: 2 November 1999 / Accepted: 14 November 1999     

Vibrational circular dichroism study for natural bioactive schizandrin and reassignment of its absolute configuration

Bioactive natural product (+)-schizandrin was assigned as (7S,8S) using NMR. Recently, we obtained (+)-schizandrin from TCM Schisandra sphenanthera Rehd. et Wils. Its planar structure was well established using NMR and HR-MS including the reported references. Its absolute configuration is assigned using vibrational circular dichroism (VCD). By careful VCD investigation of (7S,8S) and (7S,8R) using B3LYP/6-311+G(d) methods, absolute configuration of (+)-schizandrin is assigned as (7S,8R). Electronic circular dichroism (ECD) was used for the discussion too and it gave the same conclusion.     

Vibrational absorption and circular dichroism studies of (-)-camphanic acid

Vibrational absorption and circular dichroism (VCD) spectra of (-)-(1S,3R)-camphanic acid have been measured in deuterated chloroform solutions at different concentrations (0.005, 0.045, and 0.200 M) in the mid-infrared spectral range. Experimental spectra have been compared with the density functional theory (DFT) absorption and VCD spectra, calculated using the B3PW91 functional and cc-pVTZ basis set for three conformers of both the monomer and the dimer forms of (-)-(1S,3R)-camphanic acid. These calculations indicate that, in the dilute solution, the conformer with intramolecular hydrogen-bonding between the hydroxyl and lactone groups is of lowest energy and represents 70% of the different monomer conformers at room temperature, whereas, in concentrated solution, the dimer formed by intermolecular hydrogen-bonding of carboxyl groups of the two distinct monomer conformations is stabilized. The vibrational absorption and circular dichroism spectra calculated from the Boltzmann population of the individual monomer and dimer conformers are in very good overall agreement with the corresponding experimental spectra, allowing the absolute conformation and configuration of (-)-(1S,3R)-camphanic acid in dilute and concentrated solution, respectively. Experiments were also performed on (-)-(1S,3R)-camphanic chloride for which the populations predicted by DFT calculations are found to be in disagreement with those deduced from experimental spectra.     

Vibrational circular dichroism and ab initio structure elucidation of an aromatic foldamer

Ab initio calculations together with vibrational circular dichroism (VCD) are validated as very accurate tools for studying conformations and estimating conformational energies and helical handedness preferences of an entire, large (112 atoms), abiotic foldamer.     

Amplifying vibrational circular dichroism by manipulation of the electronic manifold

Vibrational circular dichroism is a powerful technique to study the stereochemistry of chiral molecules, but often suffers from small signal intensities. Electrochemical modulation of the energies of the electronically excited state manifold is now demonstrated to lead to an order of magnitude enhancement of the differential absorption. Quantum-chemical calculations show that increased mixing between ground and excited states is at the origin of this amplification.     

Vibrational circular dichroism and absolute configuration of chiral sulfoxides: tert-butyl methyl sulfoxide

Mid-infrared vibrational unpolarised absorption and vibrational circular dichroism (VCD) spectra of CCl4 solutions of tert-butyl methyl sulfoxide (1) are reported. The spectra are compared to ab initio density functional theory (DFT) calculations carried out using two functionals, B3PW91 and B3LYP, and two basis sets, 6-31G* and TZ2P. The VCD spectra are calculated using Gauge-invariant atomic orbitals (GIAOs). The analysis of the VCD spectrum confirms the R(-)/S(+) absolute configuration of 1. The advantages and disadvantages of VCD spectroscopy in determining the absolute configurations of chiral sulfoxides are discussed.     

Vibrational circular dichroism as a probe of fibrillogenesis: the origin of the anomalous intensity enhancement of amyloid-like fibrils

Amyloid fibrils are affiliated with various human pathologies. Knowledge of their molecular architecture is necessary for a detailed understanding of the mechanism of fibril formation. Vibrational circular dichroism (VCD) spectroscopy has recently shown sensitivity to amyloid fibrils [Ma et al. J. Am. Chem. Soc. 2007, 129, 12364 and Measey et al. J. Am. Chem. Soc. 2009, 131, 18218]. In particular, amyloid fibrils give rise to an intensity enhanced signal in the amide I band region of the corresponding VCD spectrum, offering promise of utilizing such a method for probing fibrillogenesis and the chiral structure of fibrils. Herein, we further investigate this phenomenon and demonstrate the use of VCD to probe the fibril formation kinetics of a short alanine-rich peptide. To elucidate the origin of the anomalous VCD intensity enhancement, we use an excitonic coupling model to simulate the VCD spectrum of stacked β-sheets containing one (Ising-like model) and two amide I oscillators per strand, as models for the underlying amyloid-fibril secondary structure. With this simple model, we show that the VCD intensity enhancement of amyloid-like fibrils results from intrasheet and, to a more limited extent, also from intersheet vibrational coupling between stacked β-sheets. The enhancement requires helically twisted sheets and is most pronounced for arrangements with parallel-oriented strands. Both the intersheet distance and the orientation of the amide I transition dipole moments of neighboring sheets are found to modulate the intensity enhancement of the amide I VCD signal. Moreover, our simulations suggest that, depending on the three-dimensional arrangement of the β-strands, 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 β-sheets. We compare the results of our simulation to experimental spectra of two short peptides, GNNQQNY, the N-terminal peptide fragment of the yeast prion protein Sup35, and an amyloidogenic alanine-rich peptide, AKY8. Our results demonstrate the advantages of using VCD spectroscopy to probe the kinetics of peptide and protein aggregation as well as the chirality of the resulting supramolecular structure.