Optical Circular Dichroism Research Articles

Enantiomeric Mixtures in Natural Product Chemistry: Separation and Absolute Configuration Assignment.

Chiral natural product molecules are generally assumed to be biosynthesized in an enantiomerically pure or enriched fashion. Nevertheless, a significant amount of racemates or enantiomerically enriched mixtures has been reported from natural sources. This number is estimated to be even larger since the enantiomeric purity of secondary metabolites is rarely checked in the natural product isolation pipeline. This latter fact may have drastic effects on the evaluation of the biological activity of chiral natural products. A second bottleneck is the determination of their absolute configurations. Despite the widespread use of optical rotation and electronic circular dichroism, most of the stereochemical assignments are based on empirical correlations with similar compounds reported in the literature. As an alternative, the combination of vibrational circular dichroism and quantum chemical calculations has emerged as a powerful and reliable tool for both conformational and configurational analysis of natural products, even for those lacking UV-Vis chromophores. In this review, we aim to provide the reader with a critical overview of the occurrence of enantiomeric mixtures of secondary metabolites in nature as well the best practices for their detection, enantioselective separation using liquid chromatography, and determination of absolute configuration by means of vibrational circular dichroism and density functional theory calculations.

A natural variant of arylsulfatase from Kluyveromyces lactis shows no formylglycine modification and has no enzyme activity.

Kluyveromyces lactis is a common fungal microorganism used for the production of enzyme preparations such as β-galactosidases (native) or chymosin (recombinant). It is generally important that enzyme preparations have no unwanted side activities. In the case of β-galactosidase preparations produced from K. lactis, an unwanted side activity could be the presence of arylsulfatase (EC 3.1.6.1). Due to the action of arylsulfatase, an unpleasant "cowshed-like" off-flavor would occur in the final product. The best choice to avoid this is to use a yeast strain without this activity. Interestingly, we found that certain natural K. lactis strains express arylsulfatases, which only differ in one amino acid at position 139. The result of this difference is that K. lactis DSM 70799 (expressing R139 variant) shows no arylsulfatase activity, unlike K. lactis GG799 (expressing S139 variant). After recombinant production of both variants in Escherichia coli, the R139 variant remains inactive, whereas the S139 variant showed full activity. Mass spectrometric analyses showed that the important posttranslational modification of C56 to formylglycine was not found in the R139 variant. By contrast, the C56 residue of the S139 variant was modified. We further investigated the packing and secondary structure of the arylsulfatase variants using optical spectroscopy, including fluorescence and circular dichroism. We found out that the inactive R139 variant exhibits a different structure regarding folding and packing compared to the active S139 variant. The importance of the amino acid residue 139 was documented further by the construction of 18 more variants, whereof only ten showed activity but always reduced compared to the native S139 variant.

Magnetic and electric hotspots via fractal clusters of hollow silicon nanoparticles.

We show that fractal clusters of hollow Si nanoparticles provide both magnetic hotspots (MHs) and electric hotspots (EHs). The hollow size tailors the wavelength dependence of the field enhancement. In the wavelength window 400-750nm, magnetic field intensity enhancements of 10-3790 and electric field intensity enhancements of 10-400 are achievable. Wavelength-tuned MHs and EHs allow better enhancement of Raman optical activity, fluorescence and circular dichroism of molecules, and so on. Si nanoparticles overcome the limitations of metallic ones, which provide only EHs at the price of heat perturbations on a nearby quantum emitter due to metallic ohmic losses.

Optical Circular Conversion Dichroism via Heterogeneous Planar Nanoplasmonic Metasurface

Chirality as a physical phenomenon originating from lacking mirror symmetry in many natural substances exposes fascinating optical activities, including circular dichroism (CD) and optical circular conversion dichroism (O-CCD). While naturally occurring chiroptical properties are negligible in real substances, boosting these properties to significant levels is one of the main challenges for designing functional photonic and optoelectronic devices. Here, we introduce a new paradigm for the realization of planar metasurfaces with substantial O-CCD, reporting that considerable chiral effects of three-dimensional chiral structure are practically provided by feasible metasurfaces by picking out nanooscillators with strong near-field interaction, different optical properties including loss and radiation, and high overlap between their spectral positions. We apply this concept to heterogeneous nanoplasmonic structures, composed of L-pair of Au–Ag nanorods, as archetypical configurations for substantially raising dichroism compared to materially homogenous ones, i.e., Au–Au and Ag–Ag pairs with different length, respectively. The essential prerequisite for phase lag associated with the third dimension along lightwave propagation is compensated by proposed heterogeneity in metasurface design. Theoretical findings based on the simple hybridization model are adequately supported by the computational results.

Computational Spectroscopic Characterization of a Bistable Binuclear Complex [(CO)2(benzoate)FeII/III(terephthalate)CoIII/II(benzoate)(CO)2

Electric dipole moments, polarizabilities, and IR, Raman, optical rotatory dispersion, and electronic and vibrational circular dichroism spectra of the four cis–trans isomers of the proposed [(CO)2(benzoate)FeII/III(terephthalate)CoIII/II(benzoate)(CO)2]+ binuclear complex, having bistablity due to intramolecular charge transfer (IMCT), is investigated using the time-dependent density functional theory ((TD)DFT) B3LYP/6–31G(d,p)[LanL2DZ] method. Results show that the two FeII–CoIII and FeIII–CoII IMCT states of this binuclear complex have distinctly different spectroscopic, optical, and electric response properties, and are sensitive to the cis–trans arrangement of the ligands around the two metallic centres. Furthermore, intrinsic reaction coordinates inter-connecting the two IMCT states are identified using the Duschinsky matrix method. Only one or two of the normal coordinates remain almost (above 80 %) intact during the IMCT reaction which denotes global changes in the bonding strengths and potential energy hypersurface of this bistable binuclear complex. Analysis of the calculated spin densities characterizes the IMCT transition state structures of the trans–trans, cis–cis, and trans–cis isomers as early, early, and late transition states, respectively.

Magnetic properties of “doped” DNA

A series of double-stranded DNA samples, containing cholesteric liquid crystal droplets, were investigated. Binding of DNA molecules with Gd3+, La3+, Cu2+, ions was carried out. The samples were characterized by X-ray, optical circular dichroism and EPR techniques. Magnetic SQUID magnetometer research showed significant deviations of Gd3+ paramagnetism from the Curie-Weiss law. A possibility of spin-glass-like interactions was analyzed. The dispersion of magnetic parameters was claimed as a main reason of magnetic anomalies observed in the liquid crystal DNA-metal systems. Such systems can be useful in biomedical applications as low-toxic magnetic labels.

Optical absorption and magnetic circular dichroism spectra of thiouracils: a quantum mechanical study in solution.

The excited electronic states of 2-thiouracil, 4-thiouracil and 2,4-dithiouracil, the analogues of uracil where the carbonyl oxygens are substituted by sulphur atoms, have been investigated by computing the magnetic circular dichroism (MCD) and one-photon absorption (OPA) spectra at the time-dependent density functional theory level. Special attention has been paid to solvent effects, included by a mixed discrete/continuum model, and to determining how our results depend on the adopted DFT functional (CAM-B3LYP and B3LYP). Whereas including solvent effects does not dramatically impact the MCD and OPA spectra, though improving the agreement with the experimental spectra, the performances of CAM-B3LYP and B3LYP are remarkably different. CAM-B3LYP captures well the effect of thionation on the uracil excited states and provides spectra in good agreement with the experiments, whereas B3LYP shows some deficiency in describing 2-TU and 2,4-DTU spectra, despite being more accurate than CAM-B3LYP for 4-TU.

To Avoid Chasing Incorrect Chemical Structures of Chiral Compounds: Raman Optical Activity and Vibrational Circular Dichroism Spectroscopies.

A chemical structure (CS) identifies the connectivities between atoms, and the nature of those connections, for a given elemental composition. For chiral molecules, in addition to the identification of CS, the identification of the correct absolute configuration (AC) is also needed. Several chiral natural products are known whose CSs were initially misidentified and later corrected, and these errors were often discovered during the total synthesis of natural products. In this work, we present a new and convenient approach that can be used with Raman optical activity (ROA) and vibrational circular dichroism (VCD) spectroscopies, to distinguish between the correct and incorrect CSs of chiral compounds. This approach involves analyzing the spectral similarity overlap between experimental spectra and those predicted with advanced quantum chemical theories. Significant labor needed for establishing the correct CSs via chemical syntheses of chiral natural products can thus be avoided.

Photocontrol over Molecular Shape: Synthesis and Photochemical Evaluation of Glycoazobenzene Macrocycles.

Reversible shape switching due to external stimuli is an attractive property for the control of molecular features. Hence, we aimed at macrocycles to investigate photoswitching of molecular shape. We prepared the first carbohydrate-based macrocycles comprising a photoresponsive azobenzene hinge. These macrocycles were readily obtained by cyclization of isothiocyanate-armed bis-azobenzene glycosides with piperazine. The unprotected macrocycles exhibit favorable photochromic properties in water and DMSO. Notably, the efficient trans→cis isomerization results in a remarkable shape transformation of the molecule. Additionally, the structure is characterized by restricted conformational freedom of the backbone, resulting in a single main conformer in each geometrical state (trans or cis). Measurement of optical rotation values and circular dichroism spectra revealed a tremendous change in chirality upon photoisomerization, with a strong helical induction in the cis state. These findings highlight the applicability of the new macrocycles as chiroptical molecular switches.

Natural occurrence of all eight stereoisomers of a neosecurinane structure from Flueggea virosa

All eight stereoisomers (1–8) of a neosecurinane-type Securinega alkaloid were isolated and identified from a Chinese medicinal plant, Flueggea virosa. Structures of the four pairs of enantiomers were characterized and differentiated from one another based on comprehensive spectroscopic analyses especially specific optical rotation and electronic circular dichroism measurements. While clarifying some historical ambiguities, the discovery of these molecules also brings new puzzles to the natural products community, which will be surely leading to further attention and studies. This case investigation also reminds that future researchers who work with natural products should pay more attention to the enantiomeric purity of their samples.

Tyrosine and hydantoin derivatives from the fungus Phoma herbarum PSU-H256 isolated from Hevea brasiliensis

Six new compounds including four tyrosine derivatives (1–4), and two hydantoin derivatives (5–6) were obtained from the investigation of the endophytic fungus Phoma herbarum PSU-H256, which was isolated from a leaf of Hevea brasiliensis. Their structures were determined by analysis of spectroscopic data, especially 1D and 2D NMR. The relative configurations were assigned using NOEDIFF data while the absolute configurations were established by comparison of the optical rotations and circular dichroism data with those of structurally related compounds.

Review on Polarization Selective Terahertz Metamaterials: from Chiral Metamaterials to Stereometamaterials

In this article, recent progress and development of terahertz chiral metamaterials including stereometamaterials are thoroughly reviewed. This review mainly focuses on the fundamental principles of design and arrangement of meta-atoms in metamaterials exhibiting chirality with various asymmetry and symmetry and 2D and 3D configuration. Related optical and propagation properties in chiral metamaterials, such as optical activity, circular dichroism, and negative refraction for each different chiral metamaterials, are compared and investigated. Finally, comparison between chiral metamaterials with stereometamaterials in terms of the polarization selective operation along with the similarity and the distinction is addressed as well.

Dimers and Trimers of Hollow Silicon Nanoparticles: Manipulating the Magnetic Hotspots

We study magnetic and electric hotspots in the gaps of nanoparticle dimers and trimers composed of hollow silicon nanoparticles. We find that the hollow size markedly influences the overall shape of the field enhancement, in particular, the peak magnitude and the peak position. The peak shifts about 100–200 nm as the hollow size varies. Tuned magnetic hotspots allow one to better enhance the Raman optical activity and circular dichroism of molecules, the interaction of light and nanomagnets, and so on.

Calculating Natural Optical Activity of Molecules from First Principles.

Computations of natural optical activity (OA) from first principles (ab initio) have become indispensable in chiroptical studies of molecular systems. Calculations are used to assign absolute configurations and to analyze chiroptical data, providing a basis for understanding their origin as well as for assigning and predicting experimental results. In this article, methodology for OA computations is outlined and accompanied by a review of selected, mainly recent (ca. 2010-2016) achievements in optical rotation, electronic and vibrational circular dichroism, and Raman OA calculations. We discuss some important aspects of the computational models and methodological developments, along with recently proposed approaches to analyze and interpret OA parameters. We highlight applications of chiroptical computational methods in studies of helicenes and chiral nanoparticles.

Tubakialactones A–E, new polyketides from the endophytic fungus Tubakia sp. ECN-111

Abstract Three new isocoumarins and two new phthalides, tubakialactones A–E ( 1 – 5 ), together with three known polyketides including ( R )-3,4-dihydro-4-hydroxyl-6,8-dimethoxy-4-methyl-3-methylene-1 H -2-benzopyran-1-one ( 6 ), (−)-5,7-dimethoxy-3-methyl-1(3 H )-isobenzofuranone ( 7 ), and isosclerone ( 8 ) were found in the endophytic fungus Tubakia sp. ECN-111 isolated from the leaves of Houttuynia cordata . The chemical structures of the new compounds were determined by spectroscopic analyses, including extensive 2D-NMR experiments. The absolute configuration of 3 and 7 was determined by optical rotation and circular dichroism.

Evidence of Optical Circular Dichroism in GaAs‐Based Nanowires Partially Covered with Gold

Semiconductor nanostructures hybridized with metals have been known to offer new opportunities in nonlinear optics, plasmonics, lasing, biosensors; among them GaAs‐based nanowires (NWs) hybridized with gold can offer new functionalities, as chiral sensing and light manipulation, as well as circular polarization sources. This study investigates GaAs–AlGaAs–GaAs NWs fabricated by self‐catalyzed growth on Si substrates, and partially covered with gold, thus inducing the symmetry breaking and a potential chiral response. Three different samples are investigated, each of them with a different morphology, as the length and the overall diameter ranging from 4.6 to 5.19 µm and from 138 up to 165 nm, respectively. The samples are first characterized by measuring the absorption spectra by using a scattering‐free photoacoustic (PA) technique. Then, the circular dichroism (CD) is investigated by measuring PA absorption for circularly polarized light under different incident angles at 532 and 980 nm. An efficient CD is found for proper configurations, and results are in good agreement with extrinsic chiral theory predictions and numerical simulations. It is therefore proven that these samples exhibit chiral behavior, and can be further optimized. Moreover, PA technique can be used as an extremely sensitive and efficient technique to characterize their “extrinsic” chirality.

Chiral exploration of 6,12-diphenyldibenzo[b,f][1,5]diazocine with stable conformation.

A first optical resolution of 6,12-diphenyldibenzo[b,f][1,5]diazocine with stable boat conformation was achieved by chiral supercritical fluid chromatography (SFC). The absolute configurations of enantiomers were first assigned and determined by X-ray crystal structure based on CIP-rules. The high optical rotation and circular dichroism spectrum were well explained by electronic helix theory. Owing to the high stabilization of boat conformation, the chiral configuration could be maintained at very high temperature, more than 200°C, which was proved by Density Functional Theory calculations.

Helical screw sense bias in chiral polyfluorene stimulated by solvent.

Conjugated homopolymer poly(9,9-bis(3-((S)-2-methylbutylpropanoate))fluorene) (PSF) with chiral pendants was synthesized and characterized. Dissolution experiments show that PSF is well dissolved in racemic limonene at high temperature and begins aggregating upon sequential cooling treatment. The corresponding assemblies were transferred to quartz plate by the spin-coating method. Comparably, film casting from chloroform solution was also prepared. Upon annealing thermal treatments, these PSF films exhibited perfect mirror circular dichroism (CD) Cotton effects and dissymmetry ratios. Optical absorption spectroscopy (UV-vis), CD, and fluorescence spectroscopy results reveal that chiral side chains successfully induced M- and P-helical structures in aggregates and films, and this significant difference was ascribed to their differential supramolecular conformations.

Synthesis of Optically Pure Helicene Metallocenes.

Two types of ruthenocenes and a ferrocene coordinated by rac-9H-cyclopenta[1,2-c:4,3-c']diphenanthrenyl anion(s), a [7]helicene with a cyclopentadienyl moiety at the center of its skeleton, were successfully synthesized: mono-helicene ruthenocene 1 and its iron analogue 1Fe with one [7]helicene ligand bound to the central metal, and bis-helicene ruthenocene 2 with two [7]helicenes. Starting from a racemic mixture of the ligand precursor, rac-2 and meso-2 were obtained in a 7:3 ratio. Since the [7]helicene has a high racemization barrier, enantiomers of the complexes were isolated in their pure forms; they showed large optical rotations and intense circular dichroism (CD) responses.

Synthesis of Optically Pure Helicene Metallocenes

AbstractTwo types of ruthenocenes and a ferrocene coordinated by rac‐9H‐cyclopenta[1,2‐c:4,3‐c′]diphenanthrenyl anion(s), a [7]helicene with a cyclopentadienyl moiety at the center of its skeleton, were successfully synthesized: mono‐helicene ruthenocene 1 and its iron analogue 1Fe with one [7]helicene ligand bound to the central metal, and bis‐helicene ruthenocene 2 with two [7]helicenes. Starting from a racemic mixture of the ligand precursor, rac‐2 and meso‐2 were obtained in a 7:3 ratio. Since the [7]helicene has a high racemization barrier, enantiomers of the complexes were isolated in their pure forms; they showed large optical rotations and intense circular dichroism (CD) responses.