Structure and ion selectivity of the open potential-dependent potassium channel

The structure and ion selectivity of the potential-dependent potassium channel is investigated. It is shown that the channel constructed by joining the α-subunit with the β-subunit concave, when the axial symmetry axes coincide, is the potential-dependent potassium channel in the open state.     

Thermal degradation of phytate produces all four possible inositol pentakisphosphates as determined by ion chromatography and 1H and 31P NMR spectroscopy

Abstract

Decomposition of phytate has recently been shown to occur under mild conditions in the solid state, giving rise to a complex mixture of lower inositol phosphates. In this study, the reaction products of this thermal, abiotic degradation of phytate were separated using ion chromatography and the most highly phosphorylated products subsequently identified using 1D and 2D NMR spectroscopy. Two late eluting fractions were each shown to be a mixture of two specific inositol pentakisphosphate isomers. The peak with shorter retention time contained Ins(1,2,3,4,6)P₅ and DL-Ins(1,2,3,4,5)P₅, while the later eluting fraction contained Ins(1,3,4,5,6)P₅ and DL-Ins(1,2,4,5,6)P₅. The formation of all four possible inositol pentakisphosphate isomers by thermal degradation of phytate contrasts with the selective production of unique inositol pentakisphosphate isomers during enzymatic phytate degradation and therefore suggests a method for differentiating abiotic and biotic processes in environmental samples, including soils and decomposing plant biomass.     

Fluorescence emission control and switching of oxymethylcrowned spirobenzopyrans by metal ion

Oxymethylcrowned spirobenzopyran 1 and pyrenylspirobenzopyran 2 were synthesized, and fluorescence emission of their corresponding merocyanine form was examined in the presence of metal ions. For 2, fluorescence emission derived from the pyrene moiety was completely quenched by photoinduced electron transfer (PET) of the nitrogen atom when the merocyanine form was not produced, namely, without metal ions. However, when 2 was converted to the merocyanine form by the complexation of its crown ether with a metal ion, fluorescence resonance energy transfer (FRET) from the pyrene to the merocyanine moieties took place to produce fluorescence emission. This result demonstrates that the spirobenzopyran isomerization can function as a fluorescence emission switch. Fluorescence quantum yield measurement for 1 and 2 showed that fluorescence emission depends on the binding metal ion in which the fluorescence quantum yield generally increased with the increase of metal ion radius.     

含萘并呋喃基团冠醚的合成及离子选择性研究

以2-羟基-1-萘甲醛和2-羟甲基冠醚为原料,合成3种新的含萘并呋喃基团冠醚(3a-3c),并经1 H NMR,13C NMR,MS及元素分析确证.碱金属和碱土金属离子的加入对体系的最大吸收波长影响不大.Li+使3b摩尔吸光度变大,Ca2+和Ba2+引起3a-3c最大发射波长λem发生相对较大红移,同时使其荧光强度降低.     

Oxymethylcrowned chromene: photoswitchable stoichiometry of metal ion complex and ion-responsive photochromism

Chromene derivatives bearing oxymethyl-12-crown-4 (1), -15-crown-5 (2), -18-crown-6 (3) ether moieties, and non-cyclic analogue (4) were synthesized, and their metal ion binding properties and photochromism were examined. NMR titration with alkali metal ions revealed that 1 formed a 1:2 complex (metal ion: ligand) with Na⁺, while Li⁺ afforded a 1:1 complex of 1. In cases of K⁺ and Rb⁺, the complexes were a mixture of 1:1 and 1:2 complexes, but the formation of 1:1 complex was observed again with Cs⁺. Under UV irradiation, however, the complex stoichiometry of 1 with all alkali metal ions was 1:1. As a comparison of NMR spectra between the Li⁺ and Na⁺ complexes of 1 indicated considerable upfield shift for the chromene moiety of the Na⁺ complex, π-π stacking of the chromene moiety seems to induce formation of the 1:2 complex. These results indicate that the chromene moiety is not only to show photochromism but also to induce aggregation to form the 1:2 complex resulted in switching of the complex stoichiometry by UV irradiation. The formation of 1:2 complex appeared only with 1 because flexibility of the crown moieties for 2 and 3 interfered the formation of 1:2 complex. Studies on photochromism in the presence of a metal ion demonstrated that the chromene derivatives bearing crown ether moieties show ion-responsive photochromism depending on the metal ion binding ability of their crown ether moieties.     

A parallel finite element simulator for ion transport through three‐dimensional ion channel systems

A parallel finite element simulator, ichannel, is developed for ion transport through three‐dimensional ion channel systems that consist of protein and membrane. The coordinates of heavy atoms of the protein are taken from the Protein Data Bank and the membrane is represented as a slab. The simulator contains two components: a parallel adaptive finite element solver for a set of Poisson–Nernst–Planck (PNP) equations that describe the electrodiffusion process of ion transport, and a mesh generation tool chain for ion channel systems, which is an essential component for the finite element computations. The finite element method has advantages in modeling irregular geometries and complex boundary conditions. We have built a tool chain to get the surface and volume mesh for ion channel systems, which consists of a set of mesh generation tools. The adaptive finite element solver in our simulator is implemented using the parallel adaptive finite element package Parallel Hierarchical Grid (PHG) developed by one of the authors, which provides the capability of doing large scale parallel computations with high parallel efficiency and the flexibility of choosing high order elements to achieve high order accuracy. The simulator is applied to a real transmembrane protein, the gramicidin A (gA) channel protein, to calculate the electrostatic potential, ion concentrations and I – V curve, with which both primitive and transformed PNP equations are studied and their numerical performances are compared. To further validate the method, we also apply the simulator to two other ion channel systems, the voltage dependent anion channel (VDAC) and α‐Hemolysin (α‐HL). The simulation results agree well with Brownian dynamics (BD) simulation results and experimental results. Moreover, because ionic finite size effects can be included in PNP model now, we also perform simulations using a size‐modified PNP (SMPNP) model on VDAC and α‐HL. It is shown that the size effects in SMPNP can effectively lead to reduced current in the channel, and the results are closer to BD simulation results. © 2013 Wiley Periodicals, Inc.     

反式-3-羟基-4-胺基苯并吡喃乙酰化物的合成及其血管舒张活性

以3-乙酰基-4-羟基苯腈为原料,经环合、还原、脱水、环氧化、氨基开环和乙酰化等反应合成了15种反式-3-羟基-4-胺基苯并吡喃及其乙酰化衍生物,其结构经IR1、H NMR、MS和元素分析测试技术确证。大鼠体外血管扩张实验研究表明,多数化合物在1.0μmol/L浓度下对30 mmol/L KC l诱导的大鼠主动脉条收缩具有一定程度的抑制作用,其中化合物7d的血管收缩抑制活性较强。初步构效关系研究表明,C-4位单乙酰化的衍生物的活性强于C-3和C-4位未乙酰化和双乙酰化的化合物。     

Study of the interaction of unaggregated and aggregated amyloid β protein (10-21) with outward potassium channel

Metal ion-induced aggregation of Aβinto insoluble plaques is a central factor in Alzheimer's disease. Zn2+ is the only physiologically available transition metal ion responsible for aggregating Aβ at pH 7.4. To make it clear that the neurotoxicity of Zn2+-induced aggregation of Aβ on neurons is the key to understand Aβ mechanism of action further. In this paper, we choose Aβ (10-21) as the model fragment to research hippocampal CA1 pyramidal neurons. For the first time, we adopt the combination of spectral analysis with patch-clamp technique for the preliminary study of the mutual relations of Zn2+, Aβ and ion channel from the cell level. The following expounds upon the effects and mode of action of two forms (unaggregated and aggregated) of Aβ (10-21) on hippocampus outward potassium channel three processes (activation, inactivation and reactivation). It also shows the molecular mechanics of AD from the channel level. These results are significant for the further study of Aβ nosogenesis and the development of new types of target drugs for the treatment of AD.     

Progress on Li3VO4 as a Promising Anode Material for Li‐ion Batteries

Vanadium oxide Li₃VO₄ has attracted much attention as anode material for Li‐ion batteries in recent years since it has a low and safe redox potential (vs. Li metal), high specific capacity and its cost is low. However, the poor electronic conductivity and initial low coulombic efficiency limit its practical application. In this mini‐review, the state‐of‐the‐art results associated with Li₃VO₄ are summarized including structure, lithium insertion mechanism, preparation, modification, and electrochemical properties. Finally, the challenges and prospects are also discussed.     

TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts

During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca²⁺ channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca²⁺-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca²⁺ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca²⁺-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without α1_SDHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in α1_SDHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or α1_SDHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca²⁺ content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes.     

Negative‐ion/positive‐ion coincidence spectroscopy as a tool to identify anionic fragments: The case of core‐excited CHF3

We have studied the dissociation of the trifluoromethane molecule, CHF₃, into negative ionic fragments at the C 1s and F 1s edges. The measurements were performed by detecting coincidences between negative and positive ions. We observed five different negative ions: F^?, H^?, C^?, CF^?, and F₂^?. Their production was confirmed by the analysis of triple coincidence events (negative‐ion/positive‐ion/positive‐ion or NIPIPI coincidences) that were recorded with cleaner signals than those of the negative‐ion/positive‐ion coincidences. The intensities of the most intense NIPIPI coincidence channels were recorded as a function of photon energy across the C 1s and F 1s excitations and ionization thresholds. We also observed dissociation channels involving the formation of one negative ion and three positive ions. Our results demonstrate that negative‐ion/positive‐ion coincidence spectroscopy is a very sensitive method to observe anions, which at inner‐shell edges are up to three orders of magnitude less probable dissociation products than cations.     

苄氧基甲基12—冠—3的合成与锂离子选择性电极研究

报道了苄氧基甲基－１２－冠－３－的合成，并以此化合物作载体研制成锂离子选择电极。用苄氧基甲基－１２冠－３－为载体的电极对锂离子响应拇性范围为１．０×１０＾－１－８．３×１０＾－５ｍｏｌ／Ｌ．检测限为４．２×１０＾－５ｍｏｌ／Ｌ，斜率为５７．４ｍＶ／ｐＬｉ。电极具有好的稳定性和重现性。     

Effect of N5+ ion implantation on optical and gas sensing properties of WO3 films

In this paper we report the optical and gas sensing behaviours of tungsten oxide (WO₃) films, implanted with 45‐keV N^{5 +} ions of different fluences in the range 1 × 10¹⁵ to 1 × 10¹⁷ cm^–2. The film with fluence 1 × 10¹⁵ cm^–2 shows the most intense PL spectrum with two prominent peaks near UV and blue regions. The morphological changes because of ion implantation are also investigated by atomic force microscopy. Because of implantation the gas sensitivity of the film, in exposure of methane, is found to increase with reasonably fast response and recovery times. With the increase of the concentration of methane, the sensors show better result. Present work also includes the effect of N^{5 +} ion implantation on the structural property of WO₃ films. Copyright © 2015 John Wiley & Sons, Ltd.     

Targeted biomarker detection via whole protein ion trap tandem mass spectrometry: thymosin beta4 in a human lung cancer cell line

N-Terminally acetylated thymosin beta4, a species implicated for use as a cancer biomarker, was identified in a human lung cancer cell line using ion trap tandem mass spectrometry at the whole protein level. Ion-ion proton transfer reactions were used for parent ion concentration/manipulation and to simplify interpretation of product ion spectra. Dissociation data for the +6 to +3 charge states are reported. As is usually the case, structural information available from the ion trap collisional activation of the protein is sensitive to parent ion charge state. Each parent ion charge state selected, however, provided sufficient information to make a confident identification. Furthermore, each charge state provided relatively rich fragmentation. Therefore, any of the charge states can be used to detect with high specificity thymosin beta(4) in a complex protein mixture. There are advantages associated with the rapid detection of protein biomarkers at the whole protein level, as opposed to the peptide level following protein digestion, particularly for relatively small protein and polypeptide biomarkers. Having identified and characterized the protein, product ion spectra obtained directly, without recourse to ion-ion proton transfer reactions, can be used for library matching. However, ion-ion proton transfer reactions for parent ion concentration and charge state purification are advantageous in addressing relatively complex mixtures.     

Synthesis of silica gel-bound acridino-18-crown-6 ether and preliminary studies on its metal ion selectivity

Starting from commercially available and relatively cheap chemicals a novel silica gel-bound acridino-18-crown-6 ether was prepared. Selectivity of the latter stationary phase toward different metal ions was studied. The stationary phase showed appreciable selectivity for Ag⁺, Cu²⁺, and Hg²⁺ ions.     

镧、钆、镱三种稀土离子诱导背根神经元凋亡及膜上钾电流的比较研究

运用流式细胞仪和膜片钳技术研究La3+,Gd3+,Yb3+三种稀土离子诱导大鼠背根神经元DRG凋亡以及膜上钾离子通道的影响。结果表明:10,100,1000μmol.L-1LaCl3和GdCl3处理DRG神经元96 h,细胞不出现凋亡;YbCl3处理96 h,细胞的凋亡率明显递增。胞外La3+,Gd3+,Yb3+抑制瞬间外向钾电流IA,使IA的激活和失活过程都显著右移,抑制和右移的程度La3+最弱,Gd3+次之,Yb3+最强;胞内的La3+,Gd3+,Yb3+抑制延迟整流钾电流IK,抑制的程度也呈增长趋势。稀土离子在胞内外的结合位点不同;Yb3+较La3+和Gd3+的神经毒性强。     

A ternary phased SnO2-Fe2O3/SWCNTs nanocomposite as a high performance anode material for lithium ion batteries

A new SnO_2-Fe_2O_3/SWCNTs(single-walled carbon nanotubes) ternary nanocomposite was first synthesized by a facile hydrothermal approach.SnO_2 and Fe_2O_3 nanoparticles(NPs) were homogeneously located on the surface of SWCNTs,as confirmed by X-ray diffraction(XRD),transmission electron microscope(TEM) and energy dispersive X-ray spectroscopy(EDX).Due to the synergistic effect of different components,the as synthesized SnO_2-Fe_2O_3/SWCNTs composite as an anode material for lithium-ion batteries exhibited excellent electrochemical performance with a high capacity of 692 mAh·g~(-1) which could be maintained after 50 cycles at 200 mA·g~(-1).Even at a high rate of2000 mA·g~(-1),the capacity was still remained at 656 mAh·g~(-1).     

Design and synthesis of type-III mimetics of ShK toxin

ShK toxin is a structurally defined, 35-residue polypeptide which blocks the voltage-gated Kv1.3 potassium channel in T-lymphocytes and has been identified as a possible immunosuppressant. Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. ShK toxin is a challenging target for mimetic design as its binding epitope consists of relatively weakly binding residues, some of which are discontinuous. We discuss here our investigations into the design and synthesis of 1st generation, small molecule mimetics of ShK toxin and highlight any principles relevant to the generic design of type-III mimetics of continuous and discontinuous binding epitopes. We complement our approach with attempted pharmacophore-based database mining.     

离子色谱法测定甘油磷酸制剂中的β-甘油磷酸根和L-苹果酸根

建立了离子色谱等度洗脱检测甘油磷酸制剂中的β-甘油磷酸根和L-苹果酸根的分析方法。实验采用Metro sep A Supp7离子色谱柱(250 m m×4.0 m m,5μm)分离,3.6 m m o l/L碳酸钠(Na_2CO_3)溶液等度洗脱,流速为0.7 m L/min,柱温为35℃,电导检测器测定,外标法定量。该方法可将甘油磷酸制剂中的α-甘油磷酸根与β-甘油磷酸根完全分离。β-甘油磷酸根和L-苹果酸根的加标回收率为90.73%~106.27%。该方法简单、快速、灵敏,适用于甘油磷酸制剂中β-甘油磷酸根和L-苹果酸根的检测。     

Synthesis and biological characterization of clicked chloroquine copolymers as macromolecular inhibitors of cancer cell migration

We report synthesis of nondegradable chloroquine (CQ)‐containing N‐(2‐hydroxyethyl)methacrylamide (HPMA) copolymers (pCQ2) by a combination of reversible addition‐fragmentation chain‐transfer (RAFT) polymerization and click chemistry. The ability of the copolymers to inhibit cancer cell migration was compared to our previously reported degradable pCQ1 in breast cancer cells utilizing transwell and wound healing assays. Both cleavable and noncleavable pCQ demonstrated enhanced inhibitory activity when compared with small‐molecule CQ. This study validates that pCQ2 functions as a macromolecular inhibitor of cancer cell migration without the need for CQ release and provides support for pCQ as a new class of antimetastatic polymer agents with a possibly unique mechanism of action. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2235–2242