New sesquiterpene lactones from the aerial parts of Pseudoelephantopus spicatus

Two new sesquiterpene lactones, spicatolide C (1) and spicatocadinanolide A (2), have been isolated along with the known piptocarphol isomers (3, 4) and one eudismane type sesquiterpene (5) from the EtOAc extract of the aerial parts of Pseudoelephantopus spicatus. The structures and the relative stereochemistries of the new metabolites were determined by spectroscopic methods.     

Alternating droplet generation and controlled dynamic droplet fusion in microfluidic device for CdS nanoparticle synthesis

A multifunctional and high-efficiency microfluidic device for droplet generation and fusion is presented. Through unique design of the micro-channels, the device is able to alternately generate droplets, generating droplet ratios ranging from 1 ratio 5 to 5 ratio 1, and fuse droplets, enabling precise chemical reactions in several picoliters on a single chip. The controlled fusion is managed by passive control based on the channel geometry and liquid phase flow. The synthesis of CdS nanoparticles utilizing each fused droplet as a microreactor for rapid and efficient mixing of reagents is demonstrated in this paper. Following alternating droplet generation, the channel geometry allows the exclusive fusion of alternate droplets with concomitant rapid mixing and produces supersaturated solution of Cd2+ and S2- ions to form CdS nanoparticles in each fused droplet. The spectroscopic properties of the CdS nanoparticles produced by this method are compared with CdS prepared by bulk mixing.     

Chemically modified dansyl probes: a fluorescent diagnostic for ion and proton detection in solution and in polymers

[reaction: see text] The fluorescence emission intensity of the dansyl group is significantly diminished upon appending an ethyldimethylamino group to the N1 nitrogen substituent. Addition of acids and metal ions (i.e., Zn(2+)) to solutions of trimethylethylenediamine naphthalene sulfonamide (trinsyl) 2 produces a >25-fold increase in fluorescence intensity. Trinsyl probe 2 has been used as a diagnostic for the diffusion of protons and metal ions in a network polymer as well as an optical reporter for the glass transition temperature.     

A synthesis of the welwistatin core

[Structure: see text] An approach to the core structure of the microtubule-targeting agent welwistatin is described. The approach utilizes the type 2 intramolecular Diels-Alder reaction, with indole serving as the tether between diene and dienophile, to form the natural product's characteristic bicyclo[4.3.1]decane skeleton.     

Kuroshines A and B,new alkaloids from Zoanthus kuroshio

A chemical investigation of Zoanthus kuroshio has yielded two new alkaloids, kuroshines A (1) and B (2). The compounds possess a densely functionalized ring system on the basis of the zoanthamine frames. The structures of 1 and 2 were elucidated through interpretation of spectroscopic methods, especially 2D NMR techniques (COSY, HMQC, HMBC, and ROESY). The absolute stereochemistry of 1 was further confirmed by an X-ray single crystallographic analysis using a mirror Cu-Kα radiation.     

Discovery of the first non-planar flavonoid that can strongly inhibit xanthine oxidase: protoapigenone 1′-O-propargyl ether

Xanthine oxidase (XO) is a key enzyme in purine metabolism with an important role in various pathologies. Several flavonoids have been reported for their capacity to inhibit this enzyme, and, for these compounds, the ability to adopt a planar 3D structure has been accepted as fundamental prerequisite for such activity. Here we report the in vitro investigation of a series of non-planar protoflavone derivatives as XO inhibitors, among which protoapigenone 1′-O-propargyl ether was found to be an efficient competitive inhibitor of the enzyme with an IC₅₀ value of 3.61 μM, significantly (p <0.001) stronger than the anti-gout drug allopurinol (IC₅₀ = 8.72 μM). Methoxy substitution at C-7, however, resulted in complete loss of activity. In silico docking supported the observed structure–activity relationships, based on which a ‘planar structure’ itself can no longer be considered as a criterion for flavonoid-type inhibitors of XO.     

Structural study of adsorption of isonicotinic acid and related molecules on rutile TiO2(1 1 0) I: XAS and STM

X-ray absorption spectroscopy (XAS) and scanning tunneling microscopy (STM) have been used to study the absorption of monolayers of the pyridinecarboxylic acid monomers (isonicotinic acid, nicotinic acid, and picolinic acid) and benzoic acid on a rutile TiO₂(1 1 0) surface. We find that the pyridine and phenyl rings are oriented with their planes largely perpendicular to the surface. The azimuthal orientations are strongly influenced by adsorbate-adsorbate interactions, which in each case leads to at least two different molecular species. In order to reach this conclusion a detailed strategy has been developed for the interpretation of angle-dependent XAS data, which does not rely on any curve fitting procedures.     

The amyloid formation mechanism in human IAPP: dimers have β-strand monomer-monomer interfaces

Early oligomerization of human IAPP (hIAPP) is responsible for β-cell death in the pancreas and is increasingly considered a primary pathological process linked to Type II Diabetes (T2D). Yet, the assembly mechanism remains poorly understood, largely due to the inability of conventional techniques to probe distributions or detailed structures of early oligomeric species. Here, we describe the first experimental data on the isolated and unmodified dimers of human (hIAPP) and nonamyloidogenic rat IAPP (rIAPP). The experiments reveal that the human IAPP dimers are more extended than those formed by rat IAPP and likely descend from extended monomers. Independent all-atom molecular dynamics simulations show that rIAPP forms compact helix and coil rich dimers, whereas hIAPP forms β-strand rich dimers that are generally more extended. Also, the simulations reveal that the monomer-monomer interfaces of the hIAPP dimers are dominated by β-strands and that β-strands can recruit coil or helix structured regions during the dimerization process. Our β-rich interface contrasts with an N-terminal helix-to-helix interface proposed in the literature but is consistent with existing experimental data on the self-interaction pattern of hIAPP, mutation effects, and inhibition effects of the N-methylation in the mutation region.     

Flexible and stretchable electrodes for dielectric elastomer actuators

Dielectric elastomer actuators (DEAs) are flexible lightweight actuators that can generate strains of over 100 %. They are used in applications ranging from haptic feedback (mm-sized devices), to cm-scale soft robots, to meter-long blimps. DEAs consist of an electrode-elastomer-electrode stack, placed on a frame. Applying a voltage between the electrodes electrostatically compresses the elastomer, which deforms in-plane or out-of plane depending on design. Since the electrodes are bonded to the elastomer, they must reliably sustain repeated very large deformations while remaining conductive, and without significantly adding to the stiffness of the soft elastomer. The electrodes are required for electrostatic actuation, but also enable resistive and capacitive sensing of the strain, leading to self-sensing actuators. This review compares the different technologies used to make compliant electrodes for DEAs in terms of: impact on DEA device performance (speed, efficiency, maximum strain), manufacturability, miniaturization, the integration of self-sensing and self-switching, and compatibility with low-voltage operation. While graphite and carbon black have been the most widely used technique in research environments, alternative methods are emerging which combine compliance, conduction at over 100 % strain with better conductivity and/or ease of patternability, including microfabrication-based approaches for compliant metal thin-films, metal-polymer nano-composites, nanoparticle implantation, and reel-to-reel production of μm-scale patterned thin films on elastomers. Such electrodes are key to miniaturization, low-voltage operation, and widespread commercialization of DEAs.