Circular X-ray Research Articles

A Minimal Sequence for Left‐Handed G‐Quadruplex Formation

Recently, we observed the first example of a left-handed G-quadruplex structure formed by natural DNA, named Z-G4. We analysed the Z-G4 structure and inspected its primary 28-nt sequence in order to identify motifs that convey the unique left-handed twist. Using circular dichroism spectroscopy, NMR spectroscopy, and X-ray crystallography, we revealed a minimal sequence motif of 12 nt (GTGGTGGTGGTG) for formation of the left-handed DNA G-quadruplex, which is found to be highly abundant in the human genome. A systematic analysis of thymine loop mutations revealed a moderate sequence tolerance, which would further broaden the space of sequences prone to left-handed G-quadruplex formation.

Cholinesterase inhibitory isoquinoline alkaloids from Corydalis mucronifera

Eight previously undescribed isoquinoline alkaloids, mucroniferanines H-M, together with 16 known isoquinoline alkaloids, were isolated from Corydalis mucronifera Maxim.. The structures of the previously undescribed compounds were elucidated by interpretation of 1D and 2D NMR spectroscopic and HRMS data, and their absolute configurations were established by computational electronic circular dichroism (ECD) calculations and X-ray diffraction data. Mucroniferanine L is reported as the first natural amide bond linked isoquinoline alkaloid dimer. The isolated compounds were evaluated for AChE and BuChE inhibitory activities and mucroniferanine H showed significant activities with IC50 values of 2.31 μM and 36.71 μM, respectively.

New antiproliferative germacranolides from Carpesium divaricatum.

Six new highly oxygenated (2–7) and one known (1) germacranolides were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic analysis. The absolute configurations of 1 and 3 were established by circular dichroism (CD) and X-ray crystallographic analyses, and the stereochemistry of the new compounds 2 and 4–6 were determined by similar CD data to 1 and 3, respectively. All isolates were evaluated for their antiproliferative activities against three human tumor cell lines, and compounds 3 and 6 show antiproliferative activities against HeLa and Hep G2 cells with IC50 values of 4.13–8.37 μM. Intensive mechanism study showed that 3 caused cell-cycle arrest at the S/G2 phase and induced apoptosis in Hep G2 cells through a mitochondria-related pathway.

Stability of the two-dimensional lattice of bacteriorhodopsin reconstituted in partially fluorinated phosphatidylcholine bilayers

This study aims to investigate bacteriorhodopsin (bR) molecules reconstituted in lipid bilayers composed of di(nonafluorotetradecanoyl)-phosphatidylcholine (F4-DMPC), a partially fluorinated analogue of dimyristoyl-phosphatidylcholine (DMPC) to clarify the effects of partially fluorinated hydrophobic chains of lipids on protein's stability. Calorimetry measurements showed that the chain-melting transition of F4-DMPC/bR systems occurs at 3.5 °C, whereas visible circular dichroism (CD) and X-ray diffraction measurements showed that a two-dimensional (2D) hexagonal lattice formed by bR trimers in F4-DMPC bilayers remains intact even above 30 °C, similar to bR in a native purple membrane. Complete dissociation of the trimers into the monomers detected by visible CD almost coincides with the complete melting of 2D lattice observed by X-ray diffraction, in which both take place at around 65 °C (10 °C lower than that for bR in a native purple membrane). However, it is extremely high in comparison with the bR reconstituted in DMPC bilayers in which the dissociation of bR trimer in DMPC bilayers occurs near the chain-melting transition temperature of DMPC bilayers at approximately 18 °C. In order to explore the rationale behind the difference in stability, a further investigation of the detailed structural features of pure F4-DMPC bilayers was performed by analyzing the lamellar diffraction data using simple electron density models. The results suggested that the perfluoroalkyl groups do not exhibit any conformation change even if the chain-melting transition occurs, which is likely to contribute to the stability of the 2D hexagonal lattice formed by the bR trimers.

Energy response characterization of InGaP X-ray detectors

Two custom-made In0.5Ga0.5P p+-i-n+ circular mesa spectroscopic X-ray photodiodes with different diameters (200 μm and 400 μm) and a 5 μm i layer have been characterized for their response to X-ray photons within the energy range 4.95 keV to 21.17 keV. The photodiodes, operating uncooled at 30 °C, were coupled, in turn, to the same custom-made charge-sensitive preamplifier. X-ray fluorescence spectra of high-purity calibration foils excited by a Mo target X-ray tube were accumulated. The energy resolution (Full Width at Half Maximum) increased from 0.79 ± 0.02 keV at 4.95 keV to 0.83 ± 0.02 keV at 21.17 keV, and from 1.12 ± 0.02 keV at 4.95 keV to 1.15 ± 0.02 keV at 21.17 keV, when using the 200 μm and 400 μm diameter devices, respectively. Energy resolution broadening with increasing energy was attributed to increasing Fano noise (negligible incomplete charge collection noise was suggested); for the first time, the Fano factor for In0.5Ga0.5P was experimentally determined to be 0.13, suggesting a Fano limited energy resolution of 145 eV at 5.9 keV. The charge output of each system had a linear relationship with photon energy, across the investigated energy range. The count rate of both spectroscopic systems increased linearly with varying X-ray tube current up to ∼105 photons s−1 cm−2 incident photon fluences. The development of In0.5Ga0.5P based spectrometers is particularly important for hard X/γ-ray astronomy, due to the material’s large linear X-ray and γ-ray absorption coefficients and the ability to operate uncooled at high temperatures.

Chiral Purity of Crystals Using Low-Frequency Raman Spectroscopy.

The pharmaceutical industry is in need of new techniques to identify the chirality of solids due to regulatory and safety concerns regarding the biological activity of enantiomers. In this study, we present for the first time the application of low-frequency Raman spectroscopy as a new and sensitive method for analyzing the chiral purity of crystals. Using this method, we were able to identify small amounts, as low as 1 % w/w, of an enantiomer in racemic crystals. To demonstrate the capabilities of the method, we used a model system based on chiral crystals of enantiopure, racemic crystals and their mixtures in various ratios. We found that the low-frequency Raman spectra of racemic and enantiopure crystals are significantly different, reflecting the different hydrogen bond networks. Moreover, a comparison of the sensitivity of enantiomeric excess in chiral crystals to that of circular dichroism and X-ray diffraction measurements showed that low-frequency Raman attains high sensitivity comparable to chiral optical methods used for solutions. Overall, our proposed approach of using Raman spectroscopy for determining enantiomeric excess in crystals is simple, fast, and offers a high degree of chiral sensitivity.

Crystal Chirality Identified by Circular Polarized X-rays in Resonant X-ray Diffraction

Crystal Chirality Identified by Circular Polarized X-rays in Resonant X-ray Diffraction

Isolation, Structure Elucidation, and Absolute Configuration of Germacrane Isomers from Carpesium divaricatum

Five sets of germacrane isomers (1/8/17, 2/7/10/11/13/16/18, 3/4/5/14/20, 6/12/15, and 9/19) with different skeletal types, including seven new ones (1–3, 8–9, and 15–16) were isolated from the whole plant of Carpesium divaricatum. Among them, there are six pairs of stereoisomers (1/8, 2/13, 4/14, 6/12, 7/11 and 10/11). The planar structures and relative configurations of the new compounds were elucidated by detailed spectroscopic analysis. The absolute configurations of 4, 10, 11, and 17 were established by circular dichroism (CD) spectra and X-ray crystallographic analyses, and the stereochemistry of the new compounds 1–3, 8–9, and 15–16 were determined by similar CD spectra with 4, 10, 11, and 17, respectively. The confusion in the literature about subtypes I and II of germacranolides was clarified in this paper. The NMR data of 10–11, and the absolute configurations of the known compounds 4–6, 13–14, and 17–20 were reported for the first time. Compounds 13, 17, and 18 showed cytotoxicity against human cervical (HeLa), colon (LoVo) and stomach cancer (BGC-823) cell lines with IC50 values in the range 4.72–13.68 μM compared with the control cis-platin (7.90–15.34 μM).

Enantiomeric resolution of helicochiral paddlewheel complexes and their infrared, Raman, UV–vis and X-ray optical activity

Linear polynuclear paddlewheel complexes-extended atom chains or metal strings-have provided attractive models for the study of metal-metal bonding, magnetism and conductivity since their discovery in the 1990s [1]. Their helicoidal chirality, arising from mutual steric hindrance of the 3-pyridyl protons, resulting in the twisting of the equatorial ligand around the axis (see figure), has been less studied. Nonetheless, in one of the few examples of chiral resolution, the obtained enantiomers of a trinickel complex showed a remarkably high specific rotation of 5000 deg•mL•g −1 •dm −1 [2], motivating us to seek a general technique for the chiral resolution of such racemates. We have developed a procedure based on anion exchange for the chiral resolution of [M3(dpa)4] 2+ salts (M = Co(II) or Ni(II), Hdpa = 2,2'-dipyridylamine). Homochiral arsenyl tartrate (AsT) salts promoted the selective crystallization of [-M3(dpa)4(MeCN)2](NBu4)2[-AsT]2, or [-M3(dpa)4(MeCN)2](NBu4)2[-AsT]2 in the P4212 space group. The enantiopure compounds demonstrated surprisingly large optical activities using UV-vis, Raman and infrared spectroscopy in solution and, for the cobalt derivatives, in the X-ray range at the Co K-edge in single crystals. An intense X-ray linear dichroism was observed in the orthoaxial crystal orientation, whereas it vanished in the axial confirmation, while the angular dependence of the circular dichroism spectra followed the expected (3cos 2 − 1) function, thus spectroscopically confirming the D4 crystal symmetry. X-ray magnetic circular dichroism and X-ray magnetochiral dichroism signals at the Co K-edge were not detected, likely due to a strongly delocalized spin density on the metal-metal bonded tricobalt core. Nevertheless, these results establish that chiral polynuclear paddlewheel complexes can be cleanly resolved using selective crystallization and demonstrate considerable optical activity in the infrared, UV-vis and X-ray energy ranges, thus potentially offering future perspectives in non-linear optics and asymmetric synthesis [3].

Chiral effect on the self-assembly of chiral molecules synthesized from cholesterol

Abstract One predesigned chiral steroid base compound cholesteryl 4-(carbonyloxy) 4-(hexyloxyl) benzoate (CCH*) and two achiral compounds with various alkyl chain length oxalyl acid N',N'-di(4-(hexyloxy)benzoyl)-hydrazide (AG6) and oxalyl acid N',N'-di(4-(undecyloxy)benzoyl)-hydrazide (AG11) have been successfully synthesized. Formation of asymmetric self-assembled constructions via self-assembly of achiral molecules in chiral environment was investigated. Due to steric hindrance, CCH* could not form gel in any kind of organic solvents. On the other hand, AG6 and AG11 formed achiral gels in many kinds of solvent. The results suggest that polarity, side branch and intermolecular forces are the key factors for the gelation. Temperature-dependent 1H NMR analysis of the fabricated gels show that van der Waals forces and π-π interactions are key factors leading to self-assembly of molecules result in three-dimensional networks. In addition, CCH* was used as a chiral dopant added into achiral compounds forming asymmetric self-assembled constructions. The results indicate that doping of CCH* into achiral gelators giving a chiral environment leads to the formation of helical constructions. The fabricated asymmetric constructions were confirmed using circular dichroism (CD) spectroscopy and small angle X-ray scattering (SAXS).

Heliojatrones A and B, Two Jatrophane-Derived Diterpenoids with a 5/10 Fused-Ring Skeleton from Euphorbia helioscopia: Structural Elucidation and Biomimetic Conversion.

Heliojatrones A and B (1 and 2), two jatrophane-derived diterpenoids with an unprecedented trans-bicyclo[8.3.0]tridecane core, were isolated from the whole plants of Euphorbia helioscopia. Their structures and absolute configurations were unequivocally determined by a combination of spectroscopic data, electronic circular dichroism calculations, biomimetic conversion, and X-ray diffraction analyses. Their plausible biosynthetic pathways were also proposed. Compounds 1 and 2 were biomimetically synthesized from 3 and 4 through a photochemical rearrangement reaction of β,γ-unsaturated ketone, respectively. Compound 2 showed significant P-glycoprotein inhibitory activity compared with the positive control (cyclosporine A).

Three New Highly Oxygenated Germacranolides from Carpesium Divaricatum and Their Cytotoxic Activity.

Three new highly oxygenated (2–4), and two known (1 and 5) germacranolides, were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic analysis. The absolute configuration of 1 was established using the circular dichroism (CD) method and X-ray diffraction, and the stereochemistry of the new compounds 2–4 were determined using similar CD spectra with 1. The new compound 2 and the known compound 5 exhibited potent cytotoxicity against hepatocellular cancer (Hep G2) and human cervical cancer (HeLa) cells, superior to those of the positive control cis-platin.

Microscopic Investigation into the Electric Field Effect on Proximity-Induced Magnetism in Pt.

Electric field effects on magnetism in metals have attracted widespread attention, but the microscopic mechanism is still controversial. We experimentally show the relevancy between the electric field effect on magnetism and on the electronic structure in Pt in a ferromagnetic state using element-specific measurements: x-ray magnetic circular dichroism (XMCD) and x-ray absorption spectroscopy (XAS). Electric fields are applied to the surface of ultrathin metallic Pt, in which a magnetic moment is induced by the ferromagnetic proximity effect resulting from a Co underlayer. XMCD and XAS measurements performed under the application of electric fields reveal that both the spin and orbital magnetic moments of Pt atoms are electrically modulated, which can be explained not only by the electric-field-induced shift of the Fermi level but also by the change in the orbital hybridizations.

Redox responsive curcumin-loaded human serum albumin nanoparticles: Preparation, characterization and in vitro evaluation

The purpose of this study was to fabricate redox-responsive human serum albumin (HSA) nanoparticles (NPs) through self-assembly of HSA molecules for incorporation of curcumin (CCM) as a hydrophobic drug molecule. The structural changes of HSA in self-assembly process of nanoparticle formation were investigated using fluorescence, UV–vis, circular dichroism spectroscopy and X-ray diffraction. Spectroscopy data show changes in secondary and tertiary structures of HSA in the process of nanoparticle formation, which can be indicative of the interaction of the hydrophobic drug with HSA molecules. Unlike free CCM, nanoparticulate curcumin is readily dispersed in aqueous medium. Furthermore, self-assembled HSA-CCM NPs release CCM in an environment imitating the intracellular environment with the trigger of acidic pH and redox potential. The in vitro release studies showed that at pH7.4 only 26% CCM was released from CCM-loaded HSA NPs in 48h. However, the release of CCM was significantly accelerated in the presence of 10mM glutathione (GSH) at pH7.4 or pH5.5, in which 57% and 70% of CCM was released, respectively. The incorporation of CCM in HSA nanoparticles enhanced the cellular uptake of CCM in comparison with free CCM results in higher anticancer efficacy against MCF-7 cells.

Mollebenzylanols A and B, Highly Modified and Functionalized Diterpenoids with a 9-Benzyl-8,10-dioxatricyclo[5.2.1.01,5]decane Core from Rhododendron molle.

Two highly modified and functionalized diterpenoids, mollebenzylanols A (1) and B (2), and a known grayanane diterpenoid rhodojaponin III (3) were isolated from Rhododendron molle. Their structures were determined by spectroscopic data analysis, an electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis of the p-bromobenzoate ester of 1 (1a). Compounds 1 and 2 possess an unprecedented diterpene carbon skeleton featuring a unique 9-benzyl-8,10-dioxatricyclo[5.2.1.01,5]decane core, and their plausible biosynthetic pathways are proposed. Their PTP1B inhibitory activity and modes of action were investigated.

Selective Interaction of Colistin with Lipid Model Membranes

Although colistin’s clinical use is limited due to its nephrotoxicity, colistin is considered to be an antibiotic of last resort because it is used to treat patients infected with multidrug-resistant bacteria. In an effort to provide molecular details about colistin’s ability to kill Gram-negative (G(−)) but not Gram-positive (G(+)) bacteria, we investigated the biophysics of the interaction between colistin and lipid mixtures mimicking the cytoplasmic membrane of G(+), G(−) bacteria as well as eukaryotic cells. Two different models of the G(−) outer membrane (OM) were assayed: lipid A with two deoxy-manno-octulosonyl sugar residues, and Escherichia coli lipopolysaccharide mixed with dilaurylphosphatidylglycerol. We used circular dichroism and x-ray diffuse scattering at low and wide angle in stacked multilayered samples, and neutron reflectivity of single, tethered bilayers mixed with colistin. We found no differences in secondary structure when colistin was bound to G(−) versus G(+) membrane mimics, ruling out a protein conformational change as the cause of this difference. However, bending modulus KC perturbation was quite irregular for the G(−) inner membrane, where colistin produced a softening of the membranes at an intermediate lipid/peptide molar ratio but stiffening at lower and higher peptide concentrations, whereas in G(+) and eukaryotic mimics there was only a slight softening. Acyl chain order in G(−) was perturbed similarly to KC. In G(+), there was only a slight softening and disordering effect, whereas in OM mimics, there was a slight stiffening and ordering of both membranes with increasing colistin. X-ray and neutron reflectivity structural results reveal colistin partitions deepest to reach the hydrocarbon interior in G(−) membranes, but remains in the headgroup region in G(+), OM, and eukaryotic mimics. It is possible that domain formation is responsible for the erratic response of G(−) inner membranes to colistin and for its deeper penetration, which could increase membrane permeability.

Selective Interaction of Colistin with Lipid Model Membranes

Although colistin's clinical use is limited due to nephrotoxicity, colistin is considered an antibiotic of last resort since it is used to treat patients infected with multi-drug resistant bacteria. In an effort to provide molecular details about colistin's ability to kill Gram-negative (G(-)) but not Gram-positive (G(+)) bacteria, we investigated the biophysics of interaction between colistin and lipid mixtures mimicking the cytoplasmic membrane of G(+), G(-) bacteria as well as eukaryotic cells. Two different models of G(-) outer membrane (OM) were assayed: lipid A with two deoxy-manno-octulosonyl sugar residues (KDO2) and Escherichia coli lipopolysaccharide (LPS) mixed with dilaurylphosphatidylglycerol. We used circular dichroism and X-ray diffuse scattering at low and wide angle in stacked multilayered samples, and neutron reflectivity (NR) of single, tethered bilayers mixed with colistin. We found no differences in secondary structure when colistin was bound to G(-) vs G(+) membrane mimics, ruling out a protein conformational change as the cause of this difference. However, bending modulus KC perturbation was quite irregular for G(-) IM, where colistin produced a softening of membranes at intermediate lipid:peptide molar ratio but stiffening at lower and higher peptide concentrations, while in G(+) and eukaryotic mimics there was only a slight softening. Acyl chain order in G(-) was perturbed similarly to KC. In G(+) there was only a slight softening and disordering effect, while in OM mimics, there was a slight stiffening and ordering of both membranes with increasing colistin. X-ray and NR structural results reveal colistin partitions deepest into the hydrocarbon interior in G(-) membranes, but remains in the headgroup region in G(+), OM and eukaryotic mimics. It is possible that domain formation is responsible for the erratic response of G(-) inner membranes to colistin and for its deeper penetration, which could increase membrane permeability.

Electronic structure and magnetic properties of the half-metallic ferrimagnetMn2VAlprobed by soft x-ray spectroscopies

We have studied the electronic structure of ferrimagnetic Mn2VAl single crystal by means of soft X-ray absorption spectroscopy (XAS), X-ray absorption magnetic circular dichroism (XMCD) and resonant soft X-ray inelastic scattering (RIXS). We have successfully observed the XMCD signals for all constitute elements, supporting the spin polarized states at the Fermi level. The Mn $L_{2,3}$ XAS and XMCD spectra are reproduced by the spectral simulation based on density-functional theory (DFT), indicating itinerant character of the Mn 3d states. On the other hand, V $3d$ electrons are rather localized since the ionic model can qualitatively explain the V $L_{2,3}$ XAS and XMCD spectra as well as the local dd excitation revealed by V $L_3$ RIXS.

Ni and CoO spin cantings induced by Fe layer in Ni/CoO/Fe/vicinal MgO(001)

Using element-resolved x-ray magnetic circular dichroism and x-ray magnetic linear dichroism measurements, we studied Ni/CoO/vicinal MgO(001) and Ni/CoO/Fe/vicinal MgO(001) systems at 350 and 78 K. Above the CoO N\'eel temperature, the Ni magnetization is fully in plane and parallel to the atomic steps in both systems due to step-induced magnetic anisotropy. Below the CoO N\'eel temperature, the CoO spins in Ni/CoO/vicinal MgO(001) are fully in plane and parallel to the atomic steps and the Ni magnetization is fully in plane and perpendicular to the atomic steps due to the 90\ifmmode^\circ\else\textdegree\fi{} Ni/CoO magnetic coupling. The CoO spins in Ni/CoO/Fe/vicinal MgO(001), however, develop an out-of-plane canted spin component in addition to the in-plane component parallel to the atomic steps. Consequently, the Ni magnetization is canted towards the out-of-plane direction by an appreciable angle. Photoemission electron microscopy imaging shows a 90\ifmmode^\circ\else\textdegree\fi{} interfacial magnetic coupling at both the Ni/CoO and the CoO/Fe interfaces and an absence of a direct interlayer coupling, showing that the Ni spin canting is due to its coupling to the canted CoO spin components which is caused by the underlying ferromagnetic Fe layer in Ni/CoO/Fe/vicinal MgO(001).

Magnetism, X-rays and accretion rates in WD 1145+017 and other polluted white dwarf systems

This paper reports circular spectropolarimetry and X-ray observations of several polluted white dwarfs including WD 1145+017, with the aim to constrain the behavior of disk material and instantaneous accretion rates in these evolved planetary systems. Two stars with previously observed Zeeman splitting, WD 0322-019 and WD 2105-820, are detected above 5 sigma and <Bz> > 1 kG, while WD 1145+017, WD 1929+011, and WD 2326+049 yield (null) detections below this minimum level of confidence. For these latter three stars, high-resolution spectra and atmospheric modeling are used to obtain limits on magnetic field strengths via the absence of Zeeman splitting, finding B* < 20 kG based on data with resolving power R near 40 000. An analytical framework is presented for bulk Earth composition material falling onto the magnetic polar regions of white dwarfs, where X-rays and cyclotron radiation may contribute to accretion luminosity. This analysis is applied to X-ray data for WD 1145+017, WD 1729+371, and WD 2326+049, and the upper bound count rates are modeled with spectra for a range of plasma kT = 1 - 10 keV in both the magnetic and non-magnetic accretion regimes. The results for all three stars are consistent with a typical dusty white dwarf in a steady-state at 1e8 - 1e9 g/s. In particular, the non-magnetic limits for WD 1145+017 are found to be well below previous estimates of up to 1e12 g/s, and likely below 1e10 g/s, thus suggesting the star-disk system may be average in its evolutionary state, and only special in viewing geometry.