Synthesis of P-chiral phosphines via chiral metal template promoted asymmetric furan Diels-Alder reaction

The organoplatinum complex containing ortho-metalated (S)-(1-(dimethylamino)ethyl)-naphthalene as the chiral auxiliary has been used to promote the asymmetric [4+2] Diels-Alder reaction between phenyldivinylphosphine and 2-diphenylphosphinofuran. The reaction was complete in 6 days at room temperature, with the formation of four isomeric diphosphino-substituted oxanorbornene metal complexes in the ratio of 4:2:2:1. Only the exo-cycloaddition products were formed. The formation of stereogenic carbon centers within the oxanorbornene skeleton are highly stereoselective, with all four cycloadducts adopting the same absolute configurations. However, the stereocontrol at the external phosphorus stereogenic center is less efficient (S_p:R_p = 2:1 for the template cycloadducts). The chiral naphthylamine auxiliary could be removed chemoselectively by treatment with concentrated hydrochloric acid, and further ligand liberation of the dichloro complexes with aqueous cyanide gave the diphosphino-substituted oxanorbornene ligands. Hydrogenation of the double bonds in the cycloadduct stabilizes the phosphorus stereogenic center of the free diphosphine ligand which otherwise undergoes inversion of absolute configuration.     

Expanded utility of the native chemical ligation reaction

The post-genomic era heralds a multitude of challenges for chemists and biologists alike, with the study of protein functions at the heart of much research. The elucidation of protein structure, localization, stability, post-translational modifications, and protein interactions will steadily unveil the role of each protein and its associated biological function in the cell. The push to develop new technologies has necessitated the integration of various disciplines in science. Consequently, the role of chemistry has never been so profound in the study of biological processes. By combining the strengths of recombinant DNA technology, protein splicing, organic chemistry, and the chemoselective chemistry of native chemical ligation, various strategies have been successfully developed and applied to chemoselectively label proteins, both in vitro and in live cells, with biotin, fluorescent, and other small molecule probes. The site-specific incorporation of molecular entities with unique chemical functionalities in proteins has many potential applications in chemical and biological studies of proteins. In this article, we highlight recent progress of these strategies in several areas related to proteomics and chemical biology, namely, in vitro and in vivo protein biotinylation, protein microarray technologies for large-scale protein analysis, and live-cell bioimaging.     

Calculation of mass spectra of some organic compounds undergoing two consecutive reactions from the molecular ions

The molecular ions of phenyl benzoate, methyl benzoate, t-butylbenzene, phthalic anhydride, p-dimethoxybenzene, o-dimethoxybenzene and acetophenone each undergo two consecutive reactions ([M]^+.→[A]⁺→[B]⁺). These unimolecular reactions are treated within the framework of the quasi-equilibrium theory (QET); a simple modification of the original equation relating the rate constant (k) with the internal energy (E) was used to calculate mass spectra of the above compounds from 12 to 20 eV. Good agreement between calculated and observed spectra is obtained.     

Evogliptin,a dipeptidyl peptidase-4 inhibitor,attenuates pathological retinal angiogenesis by suppressing vascular endothelial growth factor-induced Arf6 activation

Dipeptidyl peptidase-4 (DPP-4) inhibitors are used for the treatment of type 2 diabetes mellitus (DM). Recent studies have shown that beyond their effect in lowing glucose, DPP-4 inhibitors mitigate DM-related microvascular complications, such as diabetic retinopathy. However, the mechanism by which pathological retinal neovascularization, a major clinical manifestation of diabetic retinopathy, is inhibited is unclear. This study sought to examine the effects of evogliptin, a potent DPP-4 inhibitor, on pathological retinal neovascularization in mice and elucidate the mechanism by which evogliptin inhibits angiogenesis mediated by vascular endothelial growth factor (VEGF), a key factor in the vascular pathogenesis of proliferative diabetic retinopathy (PDR). In a murine model of PDR, an intravitreal injection of evogliptin significantly suppressed aberrant retinal neovascularization. In human endothelial cells, evogliptin reduced VEGF-induced angiogenesis. Western blot analysis showed that evogliptin inhibited the phosphorylation of signaling molecules associated with VEGF-induced cell adhesion and migration. Moreover, evogliptin substantially inhibited the VEGF-induced activation of adenosine 5′-diphosphate ribosylation factor 6 (Arf6), a small guanosine 5′-triphosphatase (GTPase) that regulates VEGF receptor 2 signal transduction. Direct activation of Arf6 using a chemical inhibitor of Arf-directed GTPase-activating protein completely abrogated the inhibitory effect of evogliptin on VEGF-induced activation of the angiogenic signaling pathway, which suggests that evogliptin suppresses VEGF-induced angiogenesis by blocking Arf6 activation. Our results provide insights into the molecular mechanism of the direct inhibitory effect of the DPP-4 inhibitor evogliptin on pathological retinal neovascularization. In addition to its glucose-lowering effect, the antiangiogenic effect of evogliptin could also render it beneficial for individuals with PDR.Subject terms: Vascular diseases, Growth factor signalling     

Comprehensive mathematical simulation of functional magnetic resonance imaging time series including motion-related image distortion and spin saturation effect

There has been vast interest in determining the feasibility of functional magnetic resonance imaging (fMRI) as an accurate method of imaging brain function for patient evaluations. The assessment of fMRI as an accurate tool for activation localization largely depends on the software used to process the time series data. The performance evaluation of different analysis tools is not reliable unless truths in motion and activation are known. Lack of valid truths has been the limiting factor for comparisons of different algorithms. Until now, currently available phantom data do not include comprehensive accounts of head motion. While most fMRI studies assume no interslice motion during the time series acquisition in fMRI data acquired using a multislice and single-shot echo-planar imaging sequence, each slice is subject to a different set of motion parameters. In this study, in addition to known three-dimensional motion parameters applied to each slice, included in the time series computation are geometric distortion from field inhomogeneity and spin saturation effect as a result of out-of-plane head motion. We investigated the effect of these head motion-related artifacts and present a validation of the mapping slice-to-volume (MSV) algorithm for motion correction and activation detection against the known truths. MSV was evaluated, and showed better performance in comparison with other widely used fMRI data processing software, which corrects for head motion with a volume-to-volume realignment method. Furthermore, improvement in signal detection was observed with the implementation of the geometric distortion correction and spin saturation effect compensation features in MSV.     

Microfluidic colloidal island formation and erasure induced by surface acoustic wave radiation

Spatiotemporal patterns form in many nonlinear physicochemical or biological systems. Although unusual, microfluidic systems are no exception. We observe such patterns to form by colloids along the free surface of a drop beneath which surface acoustic waves propagate, and propose fundamental mechanisms to elucidate their formation. With increasing excitation amplitude, the colloids first assemble into concentric rings and then cluster into islands due to a combination of capillarity and surface acceleration. As the excitation is further increased, fluid streaming commences within the drop, inducing a transient metastable state in which the system alternates between colloidal island formation on the quiescent drop surface and subsequent erasure due to local vortex generation.     

Enhanced Electroreduction of Carbon Dioxide to Methanol Using Zinc Dendrites Pulse‐Deposited on Silver Foam

The electrocatalytic CO₂ reduction reaction (CO₂RR) can dynamise the carbon cycle by lowering anthropogenic CO₂ emissions and sustainably producing valuable fuels and chemical feedstocks. Methanol is arguably the most desirable C₁ product of CO₂RR, although it typically forms in negligible amounts. In our search for efficient methanol‐producing CO₂RR catalysts, we have engineered Ag‐Zn catalysts by pulse‐depositing Zn dendrites onto Ag foams (PD‐Zn/Ag foam). By themselves, Zn and Ag cannot effectively reduce CO₂ to CH₃OH, while their alloys produce CH₃OH with Faradaic efficiencies of approximately 1 %. Interestingly, with nanostructuring PD‐Zn/Ag foam reduces CO₂ to CH₃OH with Faradaic efficiency and current density values reaching as high as 10.5 % and ?2.7 mA cm^?2, respectively. Control experiments and DFT calculations pinpoint strained undercoordinated Zn atoms as the active sites for CO₂RR to CH₃OH in a reaction pathway mediated by adsorbed CO and formaldehyde. Surprisingly, the stability of the *CHO intermediate does not influence the activity.     

Aerodynamic forces and flow fields of a two-dimensional hovering wing

This paper reports the results of an experimental investigation on a two-dimensional (2-D) wing undergoing symmetric simple harmonic flapping motion. The purpose of this investigation is to study how flapping frequency (or Reynolds number) and angular amplitude affect aerodynamic force generation and the associated flow field during flapping for Reynolds number (Re) ranging from 663 to 2652, and angular amplitudes (α _A) of 30°, 45° and 60°. Our results support the findings of earlier studies that fluid inertia and leading edge vortices play dominant roles in the generation of aerodynamic forces. More importantly, time-resolved force coefficients during flapping are found to be more sensitive to changes in α _A than in Re. In fact, a subtle change in α _A may lead to considerable changes in the lift and drag coefficients, and there appears to be an optimal mean lift coefficient around α _A = 45°, at least for the range of flow parameters considered here. This optimal condition coincides with the development a reverse Karman Vortex street in the wake, which has a higher jet stream than a vortex dipole at α _A = 30° and a neutral wake structure at α _A = 60°. Although Re has less effect on temporal force coefficients and the associated wake structures, increasing Re tends to equalize mean lift coefficients (and also mean drag coefficients) during downstroke and upstroke, thus suggesting an increasing symmetry in the mean force generation between these strokes. Although the current study deals with a 2-D hovering motion only, the unique force characteristics observed here, particularly their strong dependence on α _A, may also occur in a three-dimensional hovering motion, and flying insects may well have taken advantage of these characteristics to help them to stay aloft and maneuver. An erratum to this article can be found at     

New pregnane glycosides from Cynanchum ascyrifolium

Two new pregnane glycosides, cynascyrosides D and E, were isolated from the roots of Cynanchum ascyrifolium. The structures of these compounds were determined on the basis of spectroscopic and chemical evidence as cynajapogenin A 3-O-alpha-L-cymaropyranosyl-(1-->4)-beta-D-digitoxopyranosyl-(1-->4)-beta-L-cymaropyranoside and cynajapogenin A 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-diginopyranosyl-(1-->4)-beta-L-cymaropyranosyl-(1-->4)-beta-D-digitoxopyranoside.