Optical Rotatory Dispersion Data Research Articles

Revisiting the Absolute Configuration of Peyssonnoside A Using Vibrational Circular Dichroism Spectroscopy

Peyssonnoside A is an unusual natural product consisting of a diterpene unit and a sulfonated monosaccharide. The experimental and theoretical comparison of Optical Rotatory Dispersion (ORD) and quantitative Nuclear Magnetic Resonance (NMR) data provided strong evidence for the stereochemistry of the diterpene unit. However, predicted Vibrational Circular Dichroism (VCD) spectra of Peyssonnoside A at the B3LYP/6-311++G(2d,2p) level showed poor correlation to the corresponding experimental spectra, preventing independent absolute configuration (AC) determination from VCD analysis. New calculations using the B3PW91 functional and the 6-311G(3df,2pd) basis set suggest that we can now independently and confidently assign the AC of Peyssonnoside A through VCD analyses. The use of f-polarization functions is responsible for the current successful assignment, compared to previously failed VCD analysis. This study highlights two important points: (a) the importance of using multiple levels of theories for satisfactorily reproducing the experimental spectra and (b) for quantitative comparisons using similarity indices, it is important to consider not only the VCD spectra but also the corresponding absorption spectra.

Aureobasidols A and B: New C11-Polyketides From an Endophytic Aureobasidium pullulans Isolate

Objective: The aim of this research was the isolation, structure elucidation and evaluation of the bioactivity of natural products produced by an Aureobasidium pullulans fungal endophyte of the medicinal plant Thuja occidentalis. Methods: The natural products were isolated from an extract of A. pullulans culture broth by reversed-phase chromatography and their structures were elucidated based on analysis of HRESIMS and 1D/2D NMR data. The absolute configurations of the compounds were assigned by comparison of their electronic circular dichroism (ECD) and optical rotatory dispersion (ORD) data with values obtained for Boltzmann-weighted conformer ensembles calculated by density functional theory. Results/Conclusion: Two new C11-polyketides, aureobasidol A (1) and B (2), were isolated from the A. pullulans extract. Both polyketides showed selective but weak inhibitory activity against Mycobacterium tuberculosis in vitro.

Lignan glycosides from the stems of Stephania cepharantha

Four new lignan glycosides (LGs) and four known analogues were isolated from the stems of Stephania cepharantha Hayata. Extensive spectroscopic analysis was used to study their structures, and electronic circular dichroism and optical rotatory dispersion data were used to establish their absolute configurations. These LG types were identified in Stephania cepharantha Hayata for the first time. Compounds 1 and 2 exhibited moderate inhibitory activity against nitric oxide production. Herein, we have also discussed their preliminary structure-activity relationship.

How important are the intermolecular hydrogen bonding interactions in methanol solvent for interpreting the chiroptical properties?

Two crispine A analogs and tetrahydrofuro[2,3-b]furan-3,3a(6aH)-diol, endowed with hydroxyl groups that can participate in intramolecular hydrogen bonding, have been synthesized and experimental vibrational circular dichroism (VCD) spectra and optical rotatory dispersion (ORD) data have been measured in CD3OD/CH3OH solvents. The absolute configurations (ACs) of these compounds have been determined using their synthetic schemes, supplemented wherever possible with X-ray diffraction data. The ACs are also analyzed with quantum chemical (QC) calculations of VCD and ORD utilizing implicit solvation as well as explicit solvation models, with the later employing classical molecular dynamics (MD) simulations. It is found that VCD calculations with implicit solvation model are adequate for determining the ACs, despite propensity of studied compounds for intermolecular hydrogen bonding between solute and solvent molecules. This observation is important because time-consuming MD simulations may not be necessary in the type of situations studied here. Additionally, it is found that the QC predicted VCD spectra provided enough diastereomer discrimination for determining the correct AC of studied compounds independently. The same observation did not apply to ORD.

Meroterpenoids from Ganoderma sinense protect hepatocytes and cardiomyocytes from oxidative stress induced injuries

Four meroterpenoids, applanatumols F (1), H (3), I (2), and lingzhiol (4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Their structures were established on the basis of NMR spectroscopic analyses, optical rotatory dispersion data, ECD spectra, and X-ray crystallography. Compounds 1, 2, 4 existed as racemic mixtures ((+) 1a, 2a, 4a; (−) 1b, 2b, 4b), while 3 as a single enantiomer. Base on the seperated enantiomers, we sought to explicit possible effects of compounds 1–4 on hydrogen peroxide (H2O2)-induced cell death and to determine their underlying molecular mechanisms in human normal liver LO2 cells. Among them, compound 2a treatment effectively protected LO2 cells against H2O2-induced cell damage and apoptosis. H2O2 exposure increased ROS, which was inhibited by 2a treatment. Mitochondrial membrane potential decrease, nuclear fragments, caspase-3 activation and PARP cleavage were also arrested by 2a. Further, increased levels of Nrf2, HO-1, phosphorylation Akt and up-regulation of antioxidant enzymes were detected in 2a treated cells, indicating that the anti-oxidative effects of 2a might protect LO2 cells against oxidative damage via PI3K/Akt-mediated activation of Nrf2/HO-1 pathway. In addition, compound 2a showed potential protective role of cardiomyocyte from ischemia/reperfusion injury, and pretreatment with 2a could decrease CK and LDH levels and increase GSH level.

Enantiopure, Monodisperse Alleno-acetylenic Cyclooligomers: Effect of Symmetry and Conformational Flexibility on the Chiroptical Properties of Carbon-Rich Compounds

A series of enantiopure, monodisperse alleno-acetylenic cyclooligomers were synthesized. The single-crystal X-ray structures of the cyclic trimer and hexamer were resolved, providing insights into the symmetry of these molecules. Electronic circular dichroism (ECD), optical rotatory dispersion (ORD), Raman spectroscopy, and vibrational circular dichroism (VCD) data were analyzed with the aid of theoretical calculations. This multidimensional approach ultimately provided general guidelines that are useful for designing carbon-rich compounds with intense chiroptical properties.

Determination of Absolute Configurations of 4-Hydroxyequilenin-Cytosine and -Adenine Adducts by Optical Rotatory Dispersion, Electronic Circular Dichroism, Density Functional Theory Calculations, and Mass Spectrometry

Estrogen components of some hormone replacement formulations have been implicated in the initiation of breast cancer. Some of these formulations contain equine estrogens such as equilin and equilenin that are metabolized to the genotoxic catechol 4-hydroxyequilenin (4-OHEN). Auto-oxidation generates the o-quinone form that reacts with dC and dA in oligodeoxynucleotides to form unusual stable cyclic bulky adducts, with four different stereoisomers identified for each base adduct. The dC and dA adducts have the same unsaturated bicyclo[3.3.1]nonane type linkage site with identical stereochemical characteristics. Stereochemical effects may play an important part in the biological consequences of the formation of 4-OHEN-DNA adducts, and the assignment of the absolute configurations of the stereoisomeric 4-OHEN-dC and -dA adducts is therefore needed to understand structure-function relationships. We used density functional theory (DFT) to compute the specific optical rotations and electronic circular dichroism (ECD) spectra of the four 4-OHEN-C stereoisomers, and the results were compared with experimentally measured optical rotatory dispersion (ORD) and ECD spectra. The predicted ORD curves for the four stereoisomeric base adducts reproduced the shapes and signs of experimental spectra in the transparent spectral region. The stereochemistry of the C3' atom was determined by comparison of the calculated and experimental ORD and ECD spectra, and the stereochemistry of C2' was determined by mass spectrometric methods. Combining the ORD and mass spectrometry data, the absolute configurations of the four 4-OHEN-C and the stereochemically identical -dC adducts have been identified. The molecular architecture of the linkage site at the 4-OHEN-C/A and 4-OHEN-dC/dA is identical, and it is shown that the deoxyribose group does not substantially contribute to the optical activities. The absolute configurations of the 4-OHEN-dA adducts were thus deduced by comparing the experimental ORD with computed ORD values of 4-OHEN-A adducts.

3β-Hydroxy-14β-androsta-5,15-dien-17-one

The steric structure of the title compound, C19H26O2, has been reported previously [Sondheimer et al. (1960). J. Am. Chem. Soc. 82, 3209–3214] as 14-isoandrosten by optical rotatory dispersion data. The X-ray data of the single crystal shows that ring A has a chair conformation and ring C has a boat conformation. An O—H⋯O hydrogen bond between the hydroxyl group and the carbonyl O atom of an adjacent molecule helps to establish infinite chains along the body diagonal of the unit cell.

Spectroscopic Investigation of the Structures of Dialkyl Tartrates and Their Cyclodextrin Complexes

Structures of three dialkyl tartrates, namely, dimethyl tartrate, diethyl tartrate, and diisopropyl tartrate, in CCl4, dimethyl sulfoxide (DMSO)/DMSO-d6, and H2O/D2O solvents have been investigated using vibrational absorption (VA), vibrational circular dichroism (VCD), and optical rotatory dispersion (ORD). VA, VCD, and ORD spectra are found to be dependent on the solvent used. Density functional theory (DFT) calculations are used to interpret the experimental data in CCl4 and DMSO. The trans-COOR conformer with hydrogen bonding between the OH group and the C=O group attached to the same chiral carbon is dominant for dialkyl tartrates both in vacuum and in CCl4. The experimental VA, VCD, and ORD data of dialkyl-D-tartrates in CCl4 correlated well with those predicted for dimethyl-(S,S)-tartrate molecule as both isolated and solvated in CCl4. In DMSO solvent, dialkyl tartrate molecules favor formation of intermolecular hydrogen bonding with DMSO molecules. Clusters of dimethyl-(S,S)-tartrate, with one molecule of dimethyl-(S,S)-tartrate hydrogen bonded to two DMSO molecules, are used for the DFT calculations. A trans-COOR cluster and a trans-H cluster are needed to obtain a reasonable agreement between the predicted and experimental data of dimethyl tartrate in DMSO solvent. VA, VCD, and optical rotations are also measured for dialkyl tartrate-cyclodextrin complexes. It is noted that these properties are barely affected by complexation of dialkyl tartrates with cyclodextrins, indicating weak interaction between tartrates and cyclodextrin. Binding constants of alpha-CD and beta-CD with diethyl L-tartrate in both H2O and DMSO have been determined using isothermal titration calorimetry technique. The smaller binding constants (less than 100) confirmed the weak interaction between tartrates and cyclodextrin in the solution state.

Cotton Effect in Copper-Proline Complexes in the Visible Region

Optical rotatory dispersion (ORD) is an effective and relatively inexpensive method for probing both molecular structural and electronic properties. A typical ORD experimental setup in a student laboratory course utilizes the spectrally broad output of a tungsten lamp. Unfortunately its spectral output does not overlap with most of the electronic resonances in common molecular systems in a chemistry lab. Therefore it is difficult to demonstrate to students a representative Cotton effect. In this article we suggest taking advantage of the visible d–d electronic transition of Cu2+. This allows us to contrast the normal ORD response of d- and l-proline in aqueous solution with the strong Cotton effect observed when these amino acids are complexed with a metal cation. This experiment covers a number of topics in organic and inorganic chemistry and in optical spectroscopy. We provide the details of the complex preparation and discuss the instrumental basics for the ORD data measurements. This experiment is sui...

Verticillane Derivatives from Bursera suntui and Bursera kerberi

The stems of Bursera suntui afforded two new verticillane derivatives, (1S,3Z,7E,11S,12S)-(+)-verticilla-3,7-dien-12,20-diol (1) and (1S,3Z,7E,11S,12S)-(+)-verticilla-3,7-dien-12,20-diol 20-acetate (2), together with (1S,3E,7E,11R)-(+)-verticilla-3,7,12(18)-triene (3), (1R,3E,7E,11R,12Z)-(+)-verticilla-3,7,12-triene (4), (1R,7E,11Z)-(-)-verticilla-4(20),7,11-triene (5), and (1S,3E,7E,11S,12S)-(+)-verticilla-3,7-dien-12-ol (6). Compounds 3 and 4 are new enantiomerically pure natural products whose racemic mixtures, derived from synthetic approaches toward the taxane skeleton, were obtained previously. The stems of Bursera kerberi afforded the new (1S,3E,7E,11S,12R)-(+)-verticilla-3,7-dien-12-ol (7) together with 3-5. This is the first time that verticillane derivatives have been isolated from the genus Bursera. Their structures and stereochemistry were elucidated by 1D and 2D NMR data, including COSY, NOESY, HSQC, and HMBC experiments, while the absolute configuration was determined by comparison of the optical rotatory dispersion data with that of recently revised (1S,3E,7E,11S,12S)-(+)-verticilla-3,7-dien-12-ol (6), obtained from Sciadopitys verticillata, and those of (1R,3E,7E,11R,12R)-(-)-verticilla-3,7-dien-12-ol (8) and (1R,3E,7E,11R,12S)-(-)-verticilla-3,7-dien-12-ol (9), isolated from the liverwort Jackiella javanica. The conformational preferences of 1-7 were studied by molecular mechanics modeling employing the Monte Carlo protocol.

Ab Initio Calculation of Optical Rotation in (P)-(+)-[4]Triangulane

Optical rotation, the angle through which plane-polarized light rotates when passed through an enantiomerically pure medium, plays a vital role in the determination of the absolute configurations of chiral molecules such as natural products. We describe new quantum mechanical methodology designed to assist in this endeavor by providing high-accuracy computational optical rotatory dispersion data for matching to experimental results. Comparison between theory and experiment for the rigid, helical molecule trispiro[2.0.0.2.1.1]nonane [also known as (P)-(+)-[4]triangulane], recently synthesized with enantiomeric purity, shows that the coupled cluster quantum chemical model provides superb agreement for optical rotation across a wide range of wavelengths (589-365 nm), with errors averaging only 1%.

Determining absolute configuration in flexible molecules: a case study.

Assigning absolute configuration of molecules continues to be a major problem. Determining absolute configuration in conformationally flexible systems is challenging, even for experts. Here, we present a case study in which we use a combination of molecular modeling, solution NMR, and X-ray crystallography to illustrate why it is difficult to use solution methods alone for configuration assignment. For the case examined, a comparison of calculated and experimental optical rotatory dispersion (ORD) data provides the most straightforward way to assign the absolute configuration.

Amino acid sequence of Escherichia coli glutamine synthetase deduced from the DNA nucleotide sequence.

Glutamine synthetase is encoded by the glnA gene of Escherichia coli and catalyzes the formation of glutamine from ATP, glutamate, and ammonia. A 1922-base pair fragment from a cDNA containing the glnA structural gene for E. coli glutamine synthetase has been sequenced. An open reading frame of 1404 base pairs encodes a protein of 468 amino acid residues with a calculated molecular weight of 51,814. With few exceptions, the amino acid sequence deduced from the DNA sequence agreed very well with the amino acid sequences of several peptides reported previously. The secondary structure predicted for the E. coli enzyme has approximately 36% of the residues in alpha-helices which is in agreement with calculations of approximately 39% based on optical rotatory dispersion data. Comparison of the amino acid sequences of glutamine synthetase from E. coli (468 amino acids) and Anabaena (473 amino acids) (Turner, N. E., Robinson, S. T., and Haselkorn, R. (1983) Nature 306, 337-342) indicates that 260 amino acids are identical and 80 are of the same type (polar or nonpolar) when aligned for maximum homology. Several homologous regions of these two enzymes exist, including the sites of adenylylation and oxidative modification, but the regulation of each enzyme is different.

Optical rotation behavior of xanthan in mixtures of water and cadoxen

Optical rotatory dispersion (ORD) data were obtained for a sample of the sodium salt of xanthan gum dissolved in water-cadoxen mixtures at 25°C. The double-helical dimer of the polysaccharide was previously found to dissociate directly to single chains when w cad (the weight fraction of cadoxen in the mixed solvent) increases from 0·3 to 0·8. ORD data were also obtained for solutions prepared by diluting xathan solutions at low concentration in cadoxen with water to different w cad values. From previous work these were taken as those for single dissociated chains in the mixed solvent. These sets of data led to the finding that the specific rotation at 300 nm wavelength does not reflect the dissociation of the xanthan double helix in water-cadoxen mixtures, but the Moffitt parameter does. This parameter gave evidence that single coiling chains in cadoxen become intramolecularly ordered to a conformation similar to that of the individual chains in the double helix when the solution is diluted with water to w cad below 0·4.

Structural studies of a french bean storage protein: phaseolin

Molecular weights and sedimentation coefficients have been measured for different oligomeric forms of phaseolin, the major storage protein in seeds of Phaseolus vulgaris L. The results indicate that phaseolin is a trimer ( M r = 150000 ) at neutral pH which aggregates further to a dodecamer form ( M r = 596000 ) at pH 4.5. The subunit size is in good agreement with the recently determined sequence molecular weight, if allowance is made for bound oligosaccharide and phytic acid moieties. The trimeric nature at neutral pH has been confirmed by chemical crosslinking studies using dimethylsuberimidate and dithiobis(succinimidylpropionate). Analyses of optical rotatory dispersion and circular dichroism data have been used to examine the corformation of phaseolin. In common with other seed globulins, a low proportion of α-helix ( ∼ 10%) coupled with a high level of β-sheet ( ∼50%) is predicted. These data are compared with a structural analysis based on the amino acid sequence of a phaseolin subunit polypeptide. The predicted level of α-helix is increased ( ∼20%) when phaseolin is heated in sodium dodecyl sulphate, but not when the detergent is added at room temperature.

54] Optical activity measurements for elucidating structure—Function relationships in muscle protein systems

Publisher Summary This chapter presents circular dichroism (CD) and occasional optical rotatory dispersion (ORD) data obtained from several representative muscle protein systems. The proteins considered are restricted to the structural or regulatory ones that make up the myofibril. The chapter outlines novel ways ORD and CD methodologies that can be applied to solving various problems in the muscle protein area. The complete three dimensional positioning of the polypeptide backbone as well as all the side chains in muscle proteins can now analyzed by technique of ORD, or almost exclusively replaced by the more powerful sister technique of CD. Small quantities suffice for a rapid, and usually fairly accurate, estimate of the amounts of the various conformational forms present in dilute solution. Perhaps of more interest and utility than the establishment of the amount of these conformers present in any particular protein is an understanding of any changes in these values when— for example, the protein interacts with a metal, another protein, a variety of solvent systems, a substrate or inhibitor (if the protein displays any enzymic activity), or when the protein undergoes changes in temperature. This sensitivity of ORD and CD to conformational changes has led to its widespread satisfactory use.

Electron Spin Resonance Study of the Correlation Times and Rotational Motions of Spin-Labeled Poly(α-L-glutamic acid) in Aqueous Solutions with Reference to the Optical Rotatory Dispersion Data of the pH-Induced Helix-Coil Transition

Electron Spin Resonance Study of the Correlation Times and Rotational Motions of Spin-Labeled Poly(α-L-glutamic acid) in Aqueous Solutions with Reference to the Optical Rotatory Dispersion Data of the pH-Induced Helix-Coil Transition

Solution Properties of Synthetic Polypeptides. XXII. Helix–Coil Transition of Poly(Nγ-carbobenzoxy-L-α,γ-diaminobutyric acid)

The helix–coil transition of poly(Nγ-carbobenzoxy-L-α,γ-diaminobutyric acid) (PCLB) in mixtures of dichloroacetic acid (DCA) and 1,2-dichloroethane (EDC) was studied by optical rotatory dispersion (ORD) measurement. At DCA contents between 55 and 58 vol%, the Moffitt parameter b0 increased with increasing temperature, passed through a maximum, and gradually decreased above 40°C. This result indicates that in mixtures of DCA and EDC of appropriate compositions, PCLB undergoes a dual transition: one which is normal (helix to coil) at lower temperatures and one which is inverse (coil to helix) at higher temperatures. The ORD data were analyzed theoretically to evaluate the equilibrium constant s for the helix formation as a function of temperature T and solvent composition. A plot of In s at a fixed solvent composition against 1/T followed a curve convex downward, corresponding to the dual transition. The conformation of PCLB in a helicogenic solvent, dimethyl sulfoxide, was investigated by light scattering and viscometry, and it was found from the observed relation between the mean-square radius of gyration ‹S2› and molecular weight that PCLB takes on the form of an interrupted helix in this solvent. The molecular weight dependence of ‹S2› and intrinsic viscosity indicates that the helix of PCLB is as stable as those of poly(Nε-carbobenzoxy-L-lysine) and poly(Nδ-carbobenzoxy-L-ornithine), but less stable than that of poly(γ-benzyl L-glutamate).

Asymmetric induction radical copolymerization of optically active l‐menthyl vinyl ether with vinylene carbonate and indene

AbstractThe copolymerizations of l‐menthyl vinyl ether (l‐MVE) with the monomers vinylene carbonate (VCA) and indene (IN) were carried out in benzene with azobisisobutyronitrile (AIBN) as an initiator to obtain optically active copolymers. The optically active l‐menthyl residue from the copolymer main chain was removed using dry hydrogen bromide gas. After the ether cleavage reaction, the copolymers prepared (VA–VCA and VA–IN) were still optically active, and hence it was found that asymmetric induction had taken place in the copolymer main chain. The optical rotatory dispersion (ORD) and circular dichroism (CD) data of the original and ether‐cloven copolymers were also determined.