Selective N-Methylation of N-Methylaniline with CO_(2) and H_(2) over Cu/In_(2)O_(3) Catalyst

N-Methylation of amines with CO_(2) and H2 is a potential approach for CO_(2) utilization because N-methylated amines can be used as solvents and organic intermediates. In_(2)O_(3)-supported Cu (Cu/In_(2)O_(3)) acts as an effective heterogeneous catalyst for N-methylation reaction of N-methylaniline (MA) with CO_(2) and H_(2),showing higher N,N-dimethylaniline (DMA) selectivity than other supported Cu catalysts. On one hand,the dispersion of Cu can be improved by the defective In_(2)O_(3) support. On the other hand,In_(2)O_(3) support is active in the dissociative adsorption of CO_(2) through C—O bond breaking. In addition,the H_(2) dissociation ability of In_(2)O_(3) can also be enhanced by Cu. The combination of Cu and In_(2)O_(3) is effective in the activation of CO_(2),the adsorption of intermediate N-methylformanilide (MFA),the hydrogenation of MFA to DMA and the prohibition of C—N bond cleavage side reactions,thereby enhancing the reaction rate of MA conversion and the selectivity to DMA.

Zwitterionic cellular polymer enabled reductive fixation of CO_(2) for N-methylation of amines

Using heterogeneous catalysts to promote the construction of the C–N bond between amines and CO_(2) under mild conditions is a challenge yet.Herein,we synthesized a novel zwitterionic polymer(PDDC)with a cellular structure via self-complexation of copolymer bearing both quaternary ammonium cation and carboxylate anion.PDDC was employed as a recyclable catalyst for N-methylation of atmospheric CO_(2) and various amines with hydrosilane as a reductant,affording more than 17 N-methylamines in good to excellent yields(up to 99%)under mild conditions.The behavior of PDDC in the reaction medium was disclosed by using a dynamic light scattering study,revealing that the decreased hydraulic radius of particle size contributes to exposing more active sites and increasing reaction activity.Utilizing a series of designed experiments and density functional theory calculations uncovered the crucial role of the prepared zwitterionic polymer during the reaction procedure of CO_(2) conversion.

Scalable direct N-methylation of drug-like amines using 12CO2/13CO2 by simple inorganic base catalysis

With the growing urgency of potential catastrophic climate changes due to anthropogenic CO2 emissions,numerous efforts have been devoted to development of synthetic protocols using CO2 as a building block in organic reactions, but the general applicability to complex drug-like substrates remains a challenge.We develop a general protocol for scalable direct N-methylation of a wide-scope drug-like amines using CO2 and polymethylhydrosiloxane-a nontoxic, aerobically-stable hydrosilane considered as an industrial waste-via simple inorganic base catalysis. A rare application of the Sabatier principle in organic chemistry led to the discovery of cheap, nontoxic K3PO4 as an efficient catalyst. Preparations of a wide-scope drug-like amines with carbon-isotope label were also successfully achieved, enabling direct use of CO2 in studies of drug absorption, distribution, metabolism and excretion.

Air-tolerant direct reductive N-methylation of amines using formic acid via simple inorganic base catalysis

The construction of N-methyl amine moieties is an important reaction that has found numerous applications.Development of new methylation agents that are more environmentally benign than classical agents,such as iodomethane and methyl sulfate,is still highly desirable.Herein,we report a convenient protocol for direct reductive N-methylation of amines using formic acid as the methylation agent via simple inorganic base catalysis.The present protocol operates under transition-metal-free and air-tolerant conditions.Both the catalyst,K2 HPO4,and the reductant,polymethylhydrosiloxane(PMHS),are cheap and easily separable from the crude reaction product mixture.Mechanistic investigations suggest that the reaction occur through the formation of an acetal inte rmediate followed by the C-N bond formation.

Gamma-aminobutyric acid A receptor and N-methyl-D-aspartate receptor subunit expression in rat spiral ganglion neurons

BACKGROUND： Gamma-aminobutyric acid A （GABAA） and N-methyl-D-aspartate （NMDA） receptors are significant receptors in the central nervous system. An understanding of GABAA and NMDA receptor expression in spiral ganglion neurons （SGN） provides information for the functional role of these receptors in the auditory system. OBJECTIVE： To investigate mRNA expression of GABAA receptor （GABAAR） and NMDA receptor （NMDAR） subunits in the rat SGN. DESIGN, TIME AND SETTING： This in vitro, molecular biological study was performed at the Laboratory of Otolaryngology-Head and Neck Surgery, Guangxi Medical University, China from July 2007 to May 2008. MATERIALS： Reverse Transcriptase Kit and Taq DNA polymerase were purchased from Fermentas Burlington, ON, Canada; GABAAR and NMDAR primers were purchased from Shanghai Sangon, Shanghai, China. METHODS： SGN from 3-5 day postnatal Wistar rats was collected for primary cultures, mRNA expression of GABAAR and NMDAR subunits in the SGN was determined by reverse transcription polymerase chain reaction. MAIN OUTCOME MEASURES： Expression levels of GABAAR and NMDAR subunits were determined by quantitative analysis. RESULTS： GABAAR subunits （αl 6, β1 3, and y1 3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were detected in the SGN. In α subunit genes of GABAAR, α1 and α3 expression was similar （P 〉 0.05） and greater than the other subunits. Of the β subunit genes, β1 subunit mRNA levels were greater than β2 and β3. Of the y subunit genes, y2 subunit mRNA levels were greater than y1 and y3. NR1 mRNA expression was the greatest of NMDAR subunits. CONCLUSION： GABAAR subunits （α1 6, β1-3, and y1-3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were expressed in the rat SGN. Through comparison of GABAAR and NMDAR subunit expression, possible GABAAR combinations, as well as highly expressed subunit combinations, were estimated, which provided information for pharmacological and electrophysiological characteristics of GABAAR in the auditory system.

Dissolution Properties of 2-(Dinitromethylene)-5-methyl-1,3-diazacyclopentane in Dimethyl Sulfoxide and N-Methyl Pyrrolidone

The molar enthalpies of dissolution for 2-（dinitromethylene）-5-methyl-1,3-diazacyclopentane（DNMDZ） in dimethyl sulfoxide（DMSO） and N-methyl pyrrolidone（NMP） were measured using an RD496-2000 Calvet microcalorimeter at 298.15 K under atmospheric pressure.Empirical formulae for the calculation of the molar enthalpies of dissolution（Δ diss H） were obtained from the experimental data of the dissolution processes of DNMDZ in DMSO or NMP.The relationships between the rate constant（k） and the molality（b） and between the reaction order（n） and the molality（b） were determined.The corresponding kinetic equations describing the two dissolution processes were dα/dt=10^-2.16（1-α） ^1.01 for the dissolution of DNMDZ in DMSO,and dα/dt=10^-2.02（1-α）^ 0.85 for the dissolution of DNMDZ in NMP,respectively.

Synthesis and Structure Analysis of a Tripeptide Containing N-methyl Group Amino Acid

A convenient method of synthesizing a tripeptide-containing N-methyl group amino acid was developed using O-benzotriazole-N,N,N＇,N＇-tetramethyluronium-hexafluorophosphate as the condensing agent. The crystals of tripeptide had white needles belonging to the orthorhombic space group P2_12_12_1. The conformational preference for homochiral tripeptides with one N-methylated amide bond was also investigated. Crystal-structure analysis showed that homochiral tripeptides with an internal N-methylated amide bond preferred a trans-amide form, thereby giving the peptide β-fold characteristics. Intermolecular C-H···O and N-H···O hydrogen bonds linked the molecules into a one-dimensional chain and stabilized the structure.

Identification of N-Methyl Bis(2-(Alkyloxy-Alkylphosphoryloxy)Ethyl) Amines by LC-HRMS/MS

N-Methyl bis(2-(alkyloxy-alkylphosphoryloxy)ethyl)amines, which are abbreviated as PNPs, are a series of new skeleton chemicals belonging to schedule 2.B.04 chemicals of Chemical Weapons Convention (CWC). PNPs are important markers of chemical warfare agents because they are structurally relative to both nerve agents and N-mustards. In this study, fragmentation pathways of the most characteristic fragment ions in Q-TOF mass spectrometry were proposed based on the information from accurate mass and secondary fragmentations of product ions scan experiments. Results indicated that the base ion in LC/HRMS was the quasi-molecular ion [M+H]+. In LC-HRMS/MS, it was [M+H-CnH2n+1P(O)(OH)CmH2m+1O]+ fragment ion which was formed by losing an alkyloxy alkylphosphoryloxy group from the quasi-molecular ion. The diagnostic ion m/z84.0814 was identified as [C5H10N]+, which was the group of (CH2=CH)2N+(H)CH3. PNPs have two protonated centers. One is on the N atom, the other is on the O atom (P=O). O-n-propyl PNPs generally exhibited two fragmentation pathways. Firstly, the quasi-molecular ion [M+H]+ lost a propoxy alkylphosphoryloxy group to produce [R1P(OH+)(O-n-C3H7)OCH2CH2N(CH3)CH=CH2]+, which could be fragmented further to produce [C5H10N]+ ion. Secondly, [R1P(OH+)(O-n-C3H7) OCH=CH2]+ ions were produced from [M+H]+ and fragmented further to produce the abundant ions [R1P(OH+)(OH)OCH =CH2]. However, O-isopropyl PNPs characteristically produced weak fragment ions [M+H-C3H6]+, which were presumably formed via loss of CH3CH=CH2 from [M+H]+. Other PNPs showed similar fragmentation pathways as O-n-propyl PNPs. On the summarization of the MS fragmentation pathways of PNPs, LC-HRMS/MS quantitative and qualitative methods were developed and applied to analyze N-Methyl bis(2-(butoxy-methylphosphoryloxy)ethyl]amine in high background organic samples. The analytical results had successfully supported the sample preparation for the 33rd official proficiency test of Organization for Prohibition of Chemical Weapons (OPCW).

RE-DISTRIBUTION OF THE N-METHYL GROUP IN GELSEMINE

The N_(b)-bromomethyl derivative (2) of gelsemine,a quaternary ammonium salt,was found to be recalcitrant toward Hofmann type alkaline degradation which has been successful in other cases.Instead,a re-distribution of the N-methyl group took place,giving rise to 3a,1,3b and 3c,in descending order of R_f values.

Bifunctional flame retardant solid-state electrolyte toward safe Li metal batteries

Solid polymer electrolytes(SPEs)are one of the most promising alternatives to flammable liquid electrolytes for building safe Li metal batteries.Nevertheless,the poor ionic conductivity at room temperature(RT)and low resistance to Li dendrites seriously hinder the commercialization of SPEs.Herein,we design a bifunctional flame retardant SPE by combining hydroxyapatite(HAP)nanomaterials with Nmethyl pyrrolidone(NMP)in the PVDF-HFP matrix.The addition of HAP generates a hydrogen bond network with the PVDF-HFP matrix and cooperates with NMP to facilitate the dissociation of Li TFSI in the PVDF-HFP matrix.Consequently,the prepared SPE demonstrates superior ionic conductivity at RT,excellent fireproof properties,and strong resistance to Li dendrites.The assembled Li symmetric cell with prepared SPE exhibits a stable cycling performance of over 1200 h at 0.2 m A cm^(-2),and the solid-state LiFePO_4||Li cell shows excellent capacity retention of 85.3%over 600 cycles at 0.5 C.

海马长时程增强与26S蛋白酶复合体活性变化的关系

实验观察了大鼠海马脑片上突触传递长时程增强(long term potentiation,LTP)的产生和维持中26S蛋白酶复合体活性的动态变化过程,初步分析了介导其变化的受体途径。结果显示:强直刺激前,26S蛋白酶复合体活性为190±14.3 cpm/(100 μg·2 h),强直刺激诱导fEPSP斜率增加10 min时,其活性升为273±18.3 epm/(100μg·2 h),强直刺激诱导fEPSP斜率增加60 min时,26S蛋白酶复合体活性又降为210±12.8 cpm/(100μg·2 h)。NMDA受体特异阻断剂AP-5在损害L1P产生的同时,抑制26S蛋白酶复合体活性升高。实验结果提示:大鼠海马LTP产生过程中,26S蛋白酶复合体活性存在一个短时间的,依赖于N-methyl-D-aspartate(NMDA)受体的升高过程。

铁离子促进过量多巴胺引起SH-SY5Y细胞儿茶酚异喹啉物质生成和氧化损伤

目的帕金森氏病(Pakinson’s disease,PD)中多巴胺能神经元选择性缺失与胞内铁水平升高有密切关系,提示铁可能通过参与氧化应激在PD发病机制中起重要作用。本研究使用一定浓度的Fe2+和多巴胺诱导人多巴胺能成神经细胞瘤SH-SY5Y细胞产生氧化应激状态,并且检测胞内是否有多巴胺衍生类的神经内毒素物质产生。方法多巴胺添加不同浓度的Fe2+诱导SH-SY5Y细胞,24h后用乳酸脱氢酶法、水杨酸捕获法、硫代巴比妥酸法、Hoechst 33258染色法和带有电化学检测器的高效液相色谱仪分别检测细胞存活率、羟自由基生成量、丙二醛含量、细胞凋亡和儿茶酚异喹啉物质的生成情况。结果(1)150μmol/L多巴胺添加40或80μmol/LFe2+后,胞内羟自由基和丙二醛含量较对照组显著增加;(2)单独多巴胺以及多巴胺加40或80μmol/LFe2+诱导后细胞发生凋亡;(3)在诱导后的胞内检测到Salsolinol和N-methylsalsolinol的含量高于对照组。结论一定浓度的Fe2+和多巴胺诱导SH-SY5Y细胞可模拟帕金森氏病人黑质区多巴胺能神经元所受到的氧化应激状态,胞内检测到的儿茶酚异喹啉物质,如去甲猪毛菜碱和N-methyl-salsolinol,可能作为一类潜在的神经毒性物质与帕金森氏病的发病有关。

Physicochemical properties of β-cyclodextrin solutions and precipitates prepared from injectable vehicles

β-Cyclodextrin( β-CyD) is cyclic oligosaccharide of a glucopyranose, containing a relatively hydrophobic central cavity and hydrophilic outer surface. However, the usefulness of β-CyD is limited owing to its low aqueous solubility whereas we found that its apparent high solubility was evident in some injectable solvents including 2-pyrrolidone(PYR), Nmethyl pyrrolidone(NMP) and dimethyl sulfoxide(DMSO). Therefore, in the present study, the physicochemical properties of the 30–60% w/w β-CyD in PYR, NMP and DMSO were investigated such as viscosity, water resistant, matrix formation rate and syringeability. The higher the concentration of β-CyD resulted in the increased viscosity and the higher force and energy of syringeability. β-CyD in PYR gave the highest viscosity which contributed to the lowest syringeability while β-CyD in DMSO exhibited the highest syringeability. The β-CyD in DMSO and NMP exhibited the higher rate of matrix formation. β-CyD in PYR showed the highest water resistant for phase separation while β-CyD in NMP gave the faster de-mixing rate compared to that from PYR. The difference in physicochemical properties of β-CyD dried ppts studied by scanning electron microscope(SEM), differential scanning calorimetry(DSC), X-ray diffraction(XRD), Fourier-transform infrared spectroscopy(FT-IR) and thermogravimetric analysis(TGA) revealed that there was partial complexation of β-CyD with respective solvents. Both solution and precipitate characteristic properties will be useful for using β-CyD in further investigation as matrix material dissolved in the injectable vehicles as the in situ forming gel for periodontitis treatment.

RESEARCH ON CONFORMATION OF CAPROLACTAM AND ITS ALKYL DERIVATIVES

Caprolactam is treated with dimethyl sulfate in benzene medium under conditions of various molar ratios to yield two different methylatcd products. The homogeneous reaction of caprolactam with dimethyl sulfate without any medium can only givc one methylated derivative. In a similar condition to that mentioned above, the reaction of caprolactam with diethylsulfate forms also one product, O-ethyl caprolactim. In this articlc NMR spectrum is applied to further identify the molecular structures of two methylated derivatives held by predecessors, and, applied the chemical shift reagent to induce the NMR and combined the field scanning and decoupling method to confirm the classification of signals, as a consequence the preferred conformation of caprolactam and its alkyl derivatives are proposed.

A review on raw materials,commercial production and properties of lyocell fiber

As one of the regenerated cellulosic fibers,viscose fiber has the largest output.However,the wastes produced in the manufacturing process are difficult to eliminate,which restricts the de-velopment of viscose fiber.Lyocell fiber is claimed as“green and eco-friendly fiber”with a good application prospect in the 21st century.The preparation of lyocell fiber is based on the cellu-losic non-derivative solution system,i.e.,N-methylmorpholine-N-oxide system which is nontoxic and recyclable.In this review,firstly,the demands of dissolving pulp properties for regenerated-cellulosic fiber(RCF),especially for lyocell fiber,were introduced in detail.Next,the whole manu-facturing processes including pretreatment,preparation of spinning dope,spinning,posttreatment and efficient solvent recovery technologies were reviewed emphatically.Then,the properties and structural characteristics of lyocell fiber were illustrated.At last,some suggestions were proposed for lyocell fiber development in China.

Novel fibronectin-targeted nanodisk drug delivery system displayed superior efficacy against prostate cancer compared with nanospheres

Currently,prostate cancer is the most frequently diagnosed cancer in males and chemotherapy is often essential for treating advaneed prostate cancer.However,common chemotherapies for prostate cancer suffer from serious adverse effects due to poor drug targeting ability and tissue penetration,even with the help of conventional drug delivery systems.Here,encouraged by recent studies showing possible drug retention and tissue pen etration advan tages of unconventional non-spherical nan oparticles over conventional spherical nan oparticles,we design and construct a novel non-spherical nano disk drug delivery system for treating prostate cancer.norder to enhance tumor-targeting capability,these nanodisks are further modified with targeting peptide,Cys-Arg-Glu丄ys?Ala peptide with N-methylated Glu(CR(NMe)EKA),which recognizes extracellular matrix fibronectin and its complexes specifically expressed on the walls of tumor vessels and in tumor stroma.Compared with conventional nano spheres,the nano disks achieve much higher drug accumulati on at prostate tumor sites.When loaded with paclitaxel,the CR(NMe)EKA-modified nan odisks display superior an titumor efficacy to free paclitaxel,unmodified nan odisks and nano spheres.In summary,our study provides an attractive therapeutic strategy for targeted therapy against prostate cancer with simple preparation,high efficiency and low toxicity,and supplements a theoretical support for treatments realized by different shaped nano platforms.Our study also offers valuable data for understa nding biological effects of non-spherical nano disks and highlights the great pote ntial of unconventional nan oparticles in biomedical applicati ons.

Co-delivery of TRAIL and paclitaxel by fibronectin-targeting liposomal nanodisk for effective lung melanoma metastasis treatment

Melanoma is a highly aggressive cancer which often forms metastatic tumors in the lung,leading to sharply reduced patients'survival rate.Effectively treating these tumors thus could improve late stage melanoma with lung metastasis.In this study,we fabricated a Cys-Arg-Glu-Lys-Ala with N-methylated Glu(CR(NMe)EKA)decorated disk shaped nano vehicle to co-deliver tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and paclitaxel(PTX)to lung melanoma tumor sites(TRAIL-[ND-PTX]^(CR(NMe)EKA)).These nanodisks displayed better tumor-targeting and penetration capability than spherical nanoparticles,while the fibronectin-targeting CR(NMe)EKA motif also increased the tumor accumulation of loaded drugs.The combined usage of TRAIL and PTX both killed tumor cells and reduced local nutrition supply,leading to stronger overall anti-tumor effect.This TRAIL-[ND-PTX]^(CR(NMe)EKA)system performed remarkably better than free paclitaxel and also significantly elongated survival rate of melanoma lung metastasis bearing mice,without displaying significant toxicity.Hence,this designing strategy and the fabricated nanoplatform possess potential for further development.

N-甲基-D-天冬氨酸受体与水杨酸耳毒性

N-甲基-D-天冬氨酸受体属于离子型谷氨酸盐受体，是一种具有多种调控位点并对Ca2＋高度通透的双重门控通道，它可以通过不同亚基的选择性表达改变自身的结构和功能，影响突触的可塑性。水杨酸类药物是临床常用的解热、镇痛及抗风湿药物。国内外大量的研究证明水杨酸具有耳毒性，表现为可逆性的感音神经性聋和耳呜，但其具体的机制目前尚不明确。近年来研究认为，耳鸣与听觉中枢的可塑性有关。