Biosynthesis of Indole Diterpene Lolitrems: Radical-Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome-editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical-induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.     

A Theoretical study on the charge and discharge states of Na-ion battery cathode material,Na1+xFePO4F

Na₂FePO₄F is a promising cathode material for a Na-ion battery because of its high electronic capacity and good cycle performance. In this work, first principle calculations combined with cluster expansion and the Monte Carlo method have been applied to analyze the charge and discharge processes of Na₂FePO₄F by examining the voltage curve and the phase diagram. As a result of the density functional theory calculation and experimental verification with structural analysis, we found that the most stable structure of Na_1.5FePO₄F has the P2₁/b11 space group, which has not been reported to date. The estimated voltage curve has two clear plateaus caused by the two-phase structure composed of P2₁/b11 Na_1.5FePO₄F and Pbcn Na₂FePO₄F or Na₁FePO₄F and separated along the c-axis direction. The phase diagram shows the stability of the phase-separated structure. Considering that Na₂FePO₄F has diffusion paths in the a- and c-axis directions, Na₂FePO₄F has both innerphase and interphase diffusion paths. We suggest that the stable two-phase structure and the diffusion paths to both the innerphase and interphases are a key for the very clear plateau. We challenge to simulate a nonequilibrium state at high rate discharge with high temperature by introducing a coordinate-dependent chemical potential. The simulation shows agreement with the experimental discharge curve on the disappearance of the two plateaus. © 2018 Wiley Periodicals, Inc.     

Iron–Oxalato Framework with One‐Dimensional Open Channels for Electrochemical Sodium‐Ion Intercalation

Discovery of a new class of ion intercalation compounds is highly desirable due to its relevance to various electrochemical devices, such as batteries. Herein, we present a new iron–oxalato open framework, which showed reversible Na⁺ intercalation/extraction. The hydrothermally synthesized K₄Na₂[Fe(C₂O₄)₂]₃ ? 2 H₂O possesses one‐dimensional open channels in the oxalato‐bridged network, providing ion accessibility up to two Na⁺ per the formula unit. The detailed studies on the structural and electronic states revealed that the framework exhibited a solid solution state almost entirely during Na⁺ intercalation/extraction associated with the reversible redox of Fe. The present work demonstrates possibilities of the oxalato frameworks as tunable and robust ion intercalation electrode materials for various device applications.     

Superstructure in the Metastable Intermediate‐Phase Li2/3FePO4 Accelerating the Lithium Battery Cathode Reaction

LiFePO₄ is an important cathode material for lithium‐ion batteries. Regardless of the biphasic reaction between the insulating end members, Li_xFePO₄, x≈0 and x≈1, optimization of the nanostructured architecture has substantially improved the power density of positive LiFePO₄ electrode. The charge transport that occurs in the interphase region across the biphasic boundary is the primary stage of solid‐state electrochemical reactions in which the Li concentrations and the valence state of Fe deviate significantly from the equilibrium end members. Complex interactions among Li ions and charges at the Fe sites have made understanding stability and transport properties of the intermediate domains difficult. Long‐range ordering at metastable intermediate eutectic composition of Li_2/3FePO₄ has now been discovered and its superstructure determined, which reflected predominant polaron crystallization at the Fe sites followed by Li⁺ redistribution to optimize the Li? Fe interactions.     

Biosynthesis of Indole Diterpene Lolitrems: Radical‐Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome‐editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical‐induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.     

X-ray characterisation of local molecular orientation in the electroclinic effect of surface-stabilised SmA liquid crystals

The local molecular orientation in the electroclinic effect of the chiral smectic A phase in a surface-stabilised cell has been determined using a time-resolved synchrotron X-ray microbeam diffraction technique. Space- and time-resolved X-ray wide-angle halo scattering under an electric field reveals the static and dynamic intralayer molecular orientation. The molecular orientation varies spatially in accordance with the stripe texture and is dependent on the applied voltage. It has been found that the deviation of the molecular orientation from the rubbing direction depends strongly on the sample history. The relation between the apparent molecular orientation and the layer structure is discussed.     

Ultrasonic-Combined Plasma Bubbling for Adherent Bacteria Disinfection on Medical Equipment

Plasma Chemistry and Plasma Processing - Atmospheric low-temperature plasma has received attention for application in disinfection methods. In this study, we develop a plasma bubbling method as a...     

N-Alkylation of carbamates and amides with alcohols catalyzed by a CpIr complex

New atom-economical catalytic systems consisting of [Cp^∗IrCl₂]₂/NaOAc (Cp^∗=pentamethylcyclopentadienyl) for the N-alkylation of carbamates and amides using alcohols as alkylating agents under solvent-free conditions have been developed. For example, the reaction of n-butyl carbamate with benzyl alcohol in the presence of [Cp^∗IrCl₂]₂ (5.0 mol % Ir) and NaOAc (5.0 mol %) at 130 °C under the absence of solvent gives n-butyl N-benzylcarbamate in the yield of 94%. The present catalytic system is applicable to not only carbamates but also amides, and only harmless water is produced as co-product.     

Sonoporation-mediated transduction of siRNA ameliorated experimental arthritis using 3 MHz pulsed ultrasound

The goal of this feasibility study was to examine whether sonoporation assisted transduction of siRNA could be used to ameliorate arthritis locally. If successful, such approach could provide an alternative treatment for the patients that have or gradually develop adverse response to chemical drugs. Tumor necrosis factor alpha (TNF-α) produced by synovial fibroblasts has an important role in the pathology of rheumatoid arthritis, inducing inflammation and bone destruction. In this study, we injected a mixture of microbubbles and siRNA targeting TNF-α (siTNF) into the articular joints of rats, and transduced siTNF into synovial tissue by exposure to a collimated ultrasound beam, applied through a probe 6 mm in diameter with an input frequency of 3.0 MHz, an output intensity of 2.0 W/cm² (spatial average temporary peak; SATP), a pulse duty ratio of 50%, and a duration of 1 min. Sonoporation increased skin temperature from 26.8 °C to 27.3 °C, but there were no adverse effect such as burns. The mean level of TNF-α expression in siTNF-treated knee joints was 55% of those in controls. Delivery of siTNF into the knee joints every 3 days (i.e., 7, 10, 13, and 16 days after immunization) by in vivo sonoporation significantly reduced paw swelling on days 20–23 after immunization. Radiographic scores in the siTNF group were 56% of those in the CIA group and 61% of those in the siNeg group. Histological examination showed that the number of TNF-α positive cells was significantly lower in areas of pannus invasion into the ankle joints of siTNF- than of siNeg-treated rats. These results indicate that transduction of siTNF into articular synovium using sonoporation may be an effective local therapy for arthritis.