Synthesis of Interlocked and Non-Interlocked Deca(para-phenylene) Derivatives by Ni-mediated Biaryl Coupling.

Oligo(para-phenylene) (PPn) is a compound composed of directly connected 1,4-phenylene moieties. The synthesis of PPn composed of six or more phenylene moieties with no substituent at the internal phenylene moiety has been challenging because of its low solubility. Herein we synthesized oligo(para-phenylene)[2]rotaxanes, including a deca(para-phenylene)[2]rotaxane, with a defined number of phenylene moieties. Biaryl coupling of iodoarenes mediated by macrocyclic dibenzodihydrophenanthroline-Ni complex was utilized for the first time to synthesize the [2]rotaxanes. Compared to the non-interlocked deca(para-phenylene), the deca(para-phenylene)[2]rotaxane showed higher solubility. The properties of the oligo(para-phenylene)[2]rotaxanes and non-interlocked oligo(para-phenylene)s were analyzed by spectroscopic methods.

Indoxyl Sulfate Promotes Metastatic Characteristics of Ovarian Cancer Cells via Aryl Hydrocarbon Receptor-Mediated Downregulation of the Mas Receptor.

Although platinum-combination chemotherapy shows a high response rate at the primary site, epithelial ovarian cancer (EOC) treatment remains challenging because of tumor recurrence and metastasis. Recent studies have revealed that chemotherapy paradoxically promotes cancer cell survival, proliferation, and metastasis, although the reason for this remains unclear. The underlying molecular mechanisms that contribute to chemotherapy-induced metastasis need to be elucidated to establish effective therapeutic strategies. Acute kidney injury is a known side effect of cisplatin treatment, and kidney dysfunction results in the accumulation of uremic toxins in the serum. The present study aimed to investigate whether indoxyl sulfate (IS), a representative uremic toxin, affects the pathophysiology of EOC. In this study, IS reduced the expression of Mas receptor (MasR) in cultured human EOC cells. Both knockdown of the aryl hydrocarbon receptor (AhR), which is an intracellular IS receptor, and inhibition of AhR function suppressed IS-mediated downregulation of MasR in SK-OV-3 cells. IS induced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in an AhR-dependent manner. Inhibition of the STAT3 pathway or reactive oxygen species production suppressed the IS-mediated reduction of MasR. IS stimulated cell migration and invasion of SK-OV-3 cells in an AhR-dependent manner. Cisplatin-nephropathy model mice exhibited elevated levels of serum IS accompanied by elevated levels of blood urea nitrogen and serum creatinine. Furthermore, intraperitoneal administration of IS in mice promoted tumor growth and metastasis. Finally, we found that the MasR agonist Ang-(1-7) suppressed the IS-mediated effects on cell proliferation, migration, and invasion of SK-OV-3 cells. However, the knockdown of MasR expression by specific small interfering RNA in the absence of IS resulted in only minimal promotion of cell migration and invasion. These findings demonstrate that IS promotes malignancy in ovarian cancer via AhR-mediated downregulation of MasR function, whereas Ang-(1-7) attenuates this effect, thereby suggesting that Ang-(1-7) could provide a future treatment strategy for this cancer type.

Conformational Control of [2]Rotaxane by Hydrogen Bond.

A series of [2]rotaxanes with various functional groups in the axle component was synthesized by the oxidative dimerization of alkynes, which is mediated by a macrocyclic phenanthroline-Cu complex. The rotaxanes were fully characterized by spectroscopic methods, and the structure of a rotaxane was determined by X-ray crystallographic analysis. The interaction between the ring component and the axle component was studied in detail to understand the conformation of the rotaxanes. The presence of the hydrogen bond between the phenanthroline moiety in the macrocyclic component and the acidic proton in the axle component influenced the conformation of rotaxane.

(Z)-Selective Hydrosilylation and Hydroboration of Terminal Alkynes Enabled by Ruthenium Complexes with an N-Heterocyclic Carbene Ligand.

Metal-catalyzed trans-1,2-hydrosilylations and hydroborations of terminal alkynes that generate synthetically valuable (Z)-alkenylsilanes and (Z)-alkenylboranes remain challenging due to the (E)-selective nature of the reactions and the formation of the thermodynamically unfavorable (Z)-isomer. The development of new, efficient catalytic systems for the (Z)-selective hydrosilylation and hydroboration of terminal alkynes is thus highly desirable from a fundamental perspective as it would deepen our understanding of the metal-catalyzed (Z)-selective hydrosilylation and hydroboration of terminal alkynes. This personal account describes our research for developing a ruthenium complex that can efficiently catalyze the hydrosilylation and hydroboration of terminal alkynes, and for exploring the factors controlling (Z)-selectivity of the reactions. Our effort into the activation of B-protected boronic acids, R-B(dan) (dan=naphthalene-1,8-diaminato), that was believed not to participate in Suzuki-Miyaura cross-coupling, is also discussed.

The Aza-Prins Reaction of 1,2-Dicarbonyl Compounds with 3-Vinyltetrahydroquinolines: Application to the Synthesis of Polycyclic Spirooxindole Derivatives.

The aza-Prins reaction of 6,7-dimethoxy-3-vinyl-1,2,3,4-tetrahydroquinoline (1) with 1,2-dicarbonyl compounds proceeded smoothly in the presence of HCl, and the corresponding tricyclic benzazocines were isolated in yields of 20-86%. The reaction proceeded in a stereoselective manner, and the formation of the 2,4-trans isomer was observed. The reaction of 1 with an enantiopure ketoester gave the corresponding tricyclic benzazocine as a mixture of diastereomers. The diastereomers were easily separated and converted to enantiopure tricyclic benzazocines. The synthesis of spirooxindole derivatives was achieved by the reaction of 1 with isatin derivatives.

Direct observation of surface charge redistribution in active nanoscale conducting channels by Kelvin Probe Force Microscopy.

Surface-exposed uniformly doped silicon-on-insulator channels are fabricated to evaluate the accuracy of Kelvin Probe Force Microscopy (KPFM) measured surface potential and reveals the role of surface charge on the exposed channel operated in the ambient environment. First, the quality of the potential profile probed in the vacuum environment is assessed by the consistency of converted resistivity from KPFM result to the resistivity extracted by the other three methods. Second, in contrast to the simulated and vacuum surface potential profile and image, the ambient surface potential is bent excessively at the terminals of the channel. The excessive bending can be explained by the movement of surface charge under the drive of geometry induced strong local electric field from the channel and results in non-uniform distribution. The dynamic movement of surface charges is proved by the observation of time-dependent potential drift in the ambient measurement. The result suggests the surface charge effect should be taken into account of the measurement of the surface potential in the ambient environment and the design of charge sensitive devices whose surfaces are exposed to air or in ambient conditions in their operation.

Probing hole spin transport of disorder quantum dots via Pauli spin-blockade in standard silicon transistors.

Single hole transport and spin detection is achievable in standard p-type silicon transistors owing to the strong orbital quantization of disorder based quantum dots. Through the use of the well acting as a pseudo-gate, we discover the formation of a double-quantum dot system exhibiting Pauli spin-blockade and investigate the magnetic field dependence of the leakage current. This enables attributes that are key to hole spin state control to be determined, where we calculate a tunnel couplingtcof 57µeV and a short spin-orbit lengthlSOof 250 nm. The demonstrated strong spin-orbit interaction at the interface when using disorder based quantum dots supports electric-field mediated control. These results provide further motivation that a readily scalable platform such as industry standard silicon technology can be used to investigate interactions which are useful for quantum information processing.

Analytical approach for lubricant characterization of excipients using the surface replication method.

Lubricants are indispensable pharmaceutical ingredients for preventing tableting failure due to powder adhesion to the die wall. The impact of lubricants was evaluated with use of the Binding Identification for Net Detriment (BIND) surface replication method. Raloxifene hydrochloride (RH) was selected as a model chemical with high adhesion, and four commercially available tablet lubricants - stearic acid, sodium stearyl fumarate, calcium stearate, and magnesium stearate - were used for RH formulation. BIND was applied to the die wall to analyze the effect of various lubricants on binding properties. The preparations without lubricants showed poor tableting properties as evidenced by as much as 61.7% powder adhesion density. Lubricants significantly altered the binding properties, yielding powder adhesion densities of 40.2% (stearic acid), 29.7% (stearyl sodium fumarate), 23.0% (calcium stearate), and 13.6% (magnesium stearate). Evaluation of three grades of magnesium stearate resulted in a two-fold difference between the highest and the lowest powder adhesion density. Throughout the work, conventional methods including visual observations and measurement of ejection force were unable to provide qualitative/quantitative evaluations. The ejection process depends on both axial force and radial force; however, the ejection force show only the axial force. At the same time, visual observation could release significant qualitative results. However, BIND allowed qualitative and quantitative analysis of the binding properties. BIND is a promising assessment method for analyzing the impacts of various lubricants on binding properties and for optimizing RH formulations.

Transient appearance of Ca2+ -permeable AMPA receptors is crucial for the production of repetitive LTP-induced synaptic enhancement (RISE) in cultured hippocampal slices.

We have previously shown that repetitive induction of long-term potentiation (LTP) by glutamate (100 µM, 3 min, three times at 24-hr intervals) provoked long-lasting synaptic enhancement accompanied by synaptogenesis in rat hippocampal slice cultures, a phenomenon termed RISE (repetitive LTP-induced synaptic enhancement). Here, we examined the role of Ca2+ -permeable (CP) AMPA receptors (AMPARs) in the establishment of RISE. We first found a component sensitive to the Joro-spider toxin (JSTX), a blocker of CP-AMPARs, in a field EPSP recorded from CA3-CA1 synapses at 2-3 days after stimulation, but this component was not found for 9-10 days. We also observed that rectification of AMPAR-mediated current appeared only 2-3 days after stimulation, using a whole-cell patch clamp recording from CA1 pyramidal neurons. These findings indicate that CP-AMPAR is transiently expressed in the developing phase of RISE. The blockade of CP-AMPARs by JSTX for 24 hr at this developing phase inhibited RISE establishment, accompanied by the loss of small synapses at the ultrastructural level. These results suggest that transiently induced CP-AMPARs play a critical role in synaptogenesis in the developing phase of long-lasting hippocampal synaptic plasticity, RISE.

Folate-appended cyclodextrin carrier targets ovarian cancer cells expressing the proton-coupled folate transporter.

Folate receptor alpha (FRα) is overexpressed in >80% of epithelial ovarian cancer (EOC). Accordingly, folate is attracting attention as a targeting ligand for EOC. For EOC patients, paclitaxel (PTX) is generally used as a first-line chemotherapeutic agent in combination with platinum-based drugs. Cyclodextrin (CyD) is a potential new formulation vehicle for PTX that could replace Cremophor-EL, a traditional formulation vehicle that causes significant side effects, including neutropenia. Several years ago, folate-appended ß-CyD (Fol-c1 -ß-CyD) was developed as an FRα-targeting drug carrier, but its efficacy as a treatment for EOC remains to be determined. In this study, we assessed the antitumor activity of PTX in Fol-c1 -ß-CyD (PTX/Fol-c1 -ß-CyD) in EOC-derived cell lines. We found that PTX/Fol-c1 -ß-CyD killed not only FRα-expressing cells but also FRα-negative cells. In the FRα-negative A2780 cells, knockdown of proton-coupled folate transporter (PCFT) significantly decreased the cytotoxicity of PTX/Fol-c1 -ß-CyD, whereas knockdown of FRα did not. By contrast, knockdown of either FRα or proton-coupled folate transporter (PCFT) decreased the cytotoxicity of PTX/Fol-c1 -ß-CyD in FRα-expressing SK-OV-3 cells. Furthermore, the cytotoxicity of PTX/Fol-c1 -ß-CyD in A2780 cells was increased at acidic pH, and this increase was suppressed by PCFT inhibitor. In mice intraperitoneally inoculated with FRα-expressing or PCFT-expressing EOC cells, intraperitoneal administration of PTX/Fol-c1 -ß-CyD significantly suppressed the growth of both types of EOC cells relative to PTX alone, without inducing a significant change in the neutrophil/white blood cell ratio. Our data suggest that Fol-c1 -ß-CyD targets not only FRα but also PCFT, and can efficiently deliver anticancer drugs to EOC cells in the peritoneal cavity.

Silicon erasable waveguides and directional couplers by germanium ion implantation for configurable photonic circuits.

A novel technique for realization of configurable/one-time programmable (OTP) silicon photonic circuits is presented. Once the proposed photonic circuit is programmed, its signal routing is retained without the need for additional power consumption. This technology can potentially enable a multi-purpose design of photonic chips for a range of different applications and performance requirements, as it can be programmed for each specific application after chip fabrication. Therefore, the production costs per chip can be reduced because of the increase in production volume, and rapid prototyping of new photonic circuits is enabled. Essential building blocks for the configurable circuits in the form of erasable directional couplers (DCs) were designed and fabricated, using ion implanted waveguides. We demonstrate permanent switching of optical signals between the drop port and through the port of the DCs using a localized post-fabrication laser annealing process. Proof-of-principle demonstrators in the form of generic 1×4 and 2×2 programmable switching circuits were fabricated and subsequently programmed.

Synthesis and Systematic Structural Analysis of Cationic Half-Sandwich Ruthenium Chalcogenocarbonyl Complexes.

Although the chemistry of transition-metal complexes with carbonyl (CO) and thiocarbonyl (CS) ligands has been well developed, their heavier analogues, namely selenocarbonyl (CSe) and tellurocarbonyl (CTe) complexes remain scarce. The limited availability of such CSe and CTe complexes has so far hampered our understanding of the differences between such chalcogenocarbonyl (CE: E=O, S, Se, Te) ligands. Herein, we report the synthesis and properties of a series of cationic half-sandwich ruthenium CE complexes of the type [CpRu(CE)(H2 IMes)(CNCH2 Ts)][BArF 4 ] (Cp=η5 -C5 H5 - ; H2 IMes=1,3-dimesitylimidazolin-2-ylidene; ArF =3,5-(CF3 )2 C6 H3 ). A combination of X-ray diffraction analyses, NMR spectroscopic analyses, and DFT calculations revealed an increasing π-accepting ability of the CE ligands in the order O

Ruthenium-Catalyzed (Z)-Selective Hydroboration of Terminal Alkynes with Naphthalene-1,8-diaminatoborane.

The metal-catalyzed (Z)-selective hydroboration of terminal alkynes is synthetically challenging due to the usually (E)-selective nature of the hydroboration and the formation of the thermodynamically unstable (Z)-isomer. Herein, we report that N-heterocyclic-carbene-ligated ruthenium complexes catalyze the (Z)-selective hydroboration of terminal alkynes with H-B(dan) (dan = naphthalene-1,8-diaminato), which generates a diverse range of synthetically valuable (Z)-alkenylboranes. Mechanistic studies, particularly the isolation of a catalytically relevant borylruthenium complex, revealed a mechanism that involves the insertion of the alkyne into a Ru-B bond, which provides a catalytic cycle that is distinctly different from that of previously reported (Z)-selective hydroborations. The direct cross-coupling of the obtained (Z)-alkenyl-B(dan) enables the rapid synthesis of biologically active Combretastatin A-4 analogues.

Comparison of uniaxial and polyaxial suspended germanium bridges in terms of mechanical stress and thermal management towards a CMOS compatible light source.

Germanium (Ge) is a promising candidate for a CMOS compatible laser diode. This is due to its compatibility with Silicon (Si) and its ability to be converted into a direct band gap material by applying tensile strain. In particular uniaxial suspended Ge bridges have been extensively explored due to their ability to introduce high tensile strain. There have been two recent demonstrations of low-temperature optically-pumped lasing in these bridges but no room temperature operation accredit to insufficient strain and poor thermal management. In this paper we compare uniaxial bridges with polyaxial bridges in terms of mechanical stress and thermal management using finite element modelling (FEM). The stress simulations reveal that polyaxial bridges suffer from extremely large corner stresses which prevent larger strain from being introduced compared with uniaxial bridges. Thermal simulations however reveal that they are much less thermally sensitive than uniaxial bridges which may indicate lower optical losses. Bridges were fabricated and Raman spectroscopy was used to validate the results of the simulations. We postulate that polyaxial bridges could offer many advantages over their uniaxial counterparts as potential laser devices.

Synthesis of lactone-fused pyrroles by ruthenium-catalyzed 1,2-carbon migration-cycloisomerization.

A ruthenium-catalyzed cycloisomerization of 3-amino-4-alkynyl-2H-chromen-2-ones via 1,2-carbon migration was developed. Various 1-arylchromeno[3,4-b]pyrrol-4(3H)-ones were synthesized in good to excellent yields. The reaction was applied to the formal total synthesis of marine natural products Ningalin B and Lamellarin H. The efficient synthesis of γ-butyrolactone-fused pyrrole derivatives was also achieved.

Germanium vertically light-emitting micro-gears generating orbital angular momentum.

Germanium (Ge) is capturing researchers' interest as a possible optical gain medium implementable on complementary metal-oxide-semiconductor (CMOS) chips. Band-gap engineering techniques, relying mainly on tensile strain, are required to overcome the indirect band-gap nature of bulk Ge and promote electron injection into the direct-gap valley. We used Ge on silicon on insulator (Ge-on-SOI) wafers with a high-crystalline-quality Ge layer to fabricate Ge micro-gears on silicon (Si) pillars. Micro-gears are created by etching a periodic grating-like pattern on the circumference of a conventional micro-disk, resulting in a gear shape. Thermal built-in stresses within the SiO2 layers that encapsulate the micro-gears were used to impose tensile strain on Ge. Biaxial tensile strain values ranging from 0.3-0.5% are estimated based on Raman spectroscopy measurements and finite-element method (FEM) simulations. Multiple sharp-peak resonances within the Ge direct-gap were detected at room temperature by photo-luminescence (PL) measurements. By investigating the micro-gears spectrum using finite-difference time-domain (FDTD) simulations, we identified vertically emitted optical modes with non-zero orbital angular momentum (OAM). To our best knowledge, this is the first demonstration of OAM generation within a Ge light source.

Real-time monitoring and gradient feedback enable accurate trimming of ion-implanted silicon photonic devices.

Fabrication errors pose significant challenges on silicon photonics, promoting post-fabrication trimming technologies to ensure device performance. Conventional approaches involve multiple trimming and characterization steps, impacting overall fabrication complexity. Here we demonstrate a highly accurate trimming method combining laser annealing of germanium implanted silicon waveguide and real-time monitoring of device performance. Direct feedback of the trimming process is facilitated by a differential spectroscopic technique based on photomodulation. The resonant wavelength trimming accuracy is better than 0.15 nm for ring resonators with 20-µm radius. We also realize operating point trimming of Mach-Zehnder interferometers with germanium implanted arms. A phase shift of 1.2π is achieved by annealing a 7-µm implanted segment.

Silicon slot fin waveguide on bonded double-SOI for a low-power accumulation modulator fabricated by an anisotropic wet etching technique.

We propose a new low VπL, fully-crystalline, accumulation modulator design based on a thin horizontal gate oxide slot fin waveguide, on bonded double Silicon-on-Insulator (SOI). A combination of anisotropic wet etching and the mirrored crystal alignment of the top and bottom SOI layers allows us for the first time to selectively pattern the bottom layer from above. Simulations presented herein show a VπL = 0.17Vcm. Fin-waveguides and passive Mach-Zehnder Interferometer (MZI) devices with fin-waveguide phase shifters have been fabricated, with the fin-waveguides having a transmission loss of 5.8dB/mm and a 13.5nm thick internal gate oxide slot.

Ruthenium-Catalyzed Cycloisomerization of 2-Alkynylstyrenes via 1,2-Carbon Migration That Leads to Substituted Naphthalenes.

A ruthenium-catalyzed carbocyclization of 2-alkynylstyrenes that involves a very rare 1,2-carbon migration of internal alkynes is reported. Various 1,2-di -and 1,4,7-trisubstituted naphthalenes are synthesized. Mechanistic studies revealed that this reaction proceeds via a disubstituted vinylidene complex as the key intermediate by 1,2-carbon migration of the 2-alkynylstyrenes.

Manipulation of random telegraph signals in a silicon nanowire transistor with a triple gate.

Manipulation of carrier densities at the single electron level is inevitable in modern silicon based transistors to ensure reliable circuit operation with sufficiently low threshold-voltage variations. However, previous methods required statistical analysis to identify devices which exhibit random telegraph signals (RTSs), caused by trapping and de-trapping of a single electron. Here, we show that we can deliberately introduce an RTS in a silicon nanowire transistor, with its probability distribution perfectly controlled by a triple gate. A quantum dot (QD) was electrically defined in a silicon nanowire transistor with a triple gate, and an RTS was observed when two barrier gates were negatively biased to form potential barriers, while the entire nanowire channel was weakly inverted by the top gate. We could successfully derive the energy levels in the QD from the quantum mechanical probability distributions and the average lifetimes of RTSs. This study reveals that we can manipulate individual electrons electrically, even at room temperature, and paves the way to use a charged state for quantum technologies in the future.