Neuroprotective effect from stem bark extracts of Knema laurina against H2O2- and Aβ1–42-induced cell death in human SH-SY5Y cells

The stem bark extracts of Knema laurina inhibited the hydrogen peroxide (H₂O₂)- and aggregated amyloid β-peptide 1–42 length (Aβ_1–42)-induced cell death in differentiated SH-SY5Y cells. Exposure of 250 μM H₂O₂ or 20 μM Aβ_1–42 to the cells for 24 h reduced 50% of cell viability. Pretreatment of cells with ethyl acetate extract (EAE) or n-butanol extract (BE) at 300 μg/mL and then exposure to H₂O₂ protected the cells against the neurotoxic effects of H₂O₂. Besides, methanolic extract (ME) at 1 and 10 μg/mL exerted neuroprotective effect on Aβ_1–42-induced toxicity to the cells. These results showed that EAE, BE and ME exhibited neuroprotective activities against H₂O₂- and Aβ_1–42-induced cell death. Flavonoids (3–6) and β-sitosterol glucoside (8) were isolated from the EAE. Compound 1 was isolated from hexane extract, and compounds 2 and 7 were isolated from dichloromethane extract. All these observations provide the possible evidence for contribution in the neuroprotective effects.     

Shear-induced crystallization in phase-separated blends of isotactic polypropylene with ethylene-propylene-diene terpolymer

The compatibility between isotactic polypropylene(i PP) and ethylene-propylene-diene terpolymer(EPDM) in the blends was studied. SAXS analysis indicates that i PP and EPDM phases in the binary blend are incompatible. Isothermal crystallization behaviors of i PP in phase-separated i PP/EPDM were studied by in situ POM equipped with a Linkam shear hot stage. It was found that typical spherulites of i PP were formed both in neat i PP and in i PP/EPDM blends. The radial growth rate(d R/dt) of spherulites of i PP in the blend was not influenced by EPDM phases. Further investigations on isothermal crystallization of i PP in i PP/EPDM after shear with a fixed shear time showed that the crystallization rate of i PP in the blends increased with increasing shear rates, whereas, the crystallization rate was much lower than that of neat i PP. WAXD results showed that ?-crystal i PP was formed in neat i PP as well as in i PP/EPDM blends after shearing and the percentage of ?-crystal bore a relationship to the applied shear rate. The presence of EPDM resulted in lower percentage of ?-crystal in the blends than that in neat i PP under the same constant shear conditions. SAXS experiments revealed that shear flow could induce formation of oriented lamellae in i PP and i PP in the blends, and the presence of EPDM led to a reduced fraction of oriented lamellae.     

以[β-Mo_8O_(26)]~(4-)阴离子为构筑块的有机-无机复合物的合成、结构及性质

以[(C4H9)4N]4Mo8O26·nH2O和[Cr3O(C6H5COO)6(H2O)3]NO3为原料,利用常规水溶液法合成了一种由同多阴离子[β-Mo8O26]4-和大阳离子[Cr3O(C6H5COO)6(H2O)3]+通过静电作用形成的有机-无机复合物[Cr3O(C6H5COO)6(H2O)3]4[Mo8O26]·11.5H2O(1).X射线单晶衍射结果表明,该晶体属三斜晶系,P-1空间群,晶胞参数:a=1.545 2(2)nm,b=2.035 1(3)nm,c=2.218 5(3)nm,α=63.097(3)°,β=72.545(3)°,γ=85.114(3)°.对化合物1的热稳定性进行了研究.热重分析表明化合物的失重分两步进行:第一步对应于11.5个结晶水和12个配位水的失去;第二步对应于24个C6H5COO-的失去.     

Extraction and Crystal Structure of β-Sitosterol

The title compound β-sitosterol(C29H50O), an active phytosterol in many medicinal and edible plants, was characterized by X-ray diffraction analysis and extensive nuclear magnetic resonance(NMR) data. It crystallizes in monoclinic system, space group P21 with C29H50O·1/2H2O, a = 9.4226(7), b = 7.4824(9), c = 36.889(3) , V = 2597.0(4) 3, Z = 4, Dx = 1.084 g/cm3, Mr = 423.70, F(000) = 948, and μ = 0.064 mm-1. The final R = 0.0886 and wR = 0.2234 for 10157 observed reflections(I 2σ(I)). The molecular crystal structure of β-sitosterol shows relative stereochemistry of 24R-ethylcholest-5-en-3β-ol. The molecule is composed of one steroid nucleus(3 six-membered rings and 1 five-membered ring) and one sidechain of 10 carbons. There are two C29H50O molecules and one H2O molecule in a symmetrical unit, and the title compound is stacked into a special laminated structure through hydrogen bonds and van der Waal forces. The special laminated structure was first reported.     

新型双β-环糊精键合SBA-15液相手性固定相的制备及评价

由于桥联双β-环糊精的协同包结作用和独特的多重识别功能已被广泛地用作人工模拟酶,本文尝试用桥联双β-环糊精作固定相配体,开发其手性分离功能.采用3-异氰酸丙基三乙氧基硅烷偶联剂连续反应法,首先将（6-氧-对甲苯磺酰）-β-环糊精键合到有序介孔SBA-15硅胶表面,然后与（6-乙二胺-6-去氧）-β-环糊精反应,制备一种新型的乙二胺桥联双β-环糊精键合SBA-15液相色谱手性固定相（BCDSP）.采用质谱、红外光谱、元素分析、热重分析和透射电镜等进行结构表征.在极性有机溶剂模式下,评价了新固定相的基本色谱性能,并用于β-受体阻滞剂对映体的拆分.考察了流动相中有机溶剂、三乙胺、冰醋酸改性剂用量和柱温对手性分离的影响.基于优化的色谱条件,采用双β-环糊精键合固定相成功地拆分了常用的14种β-受体阻滞剂药物对映体,其中普萘洛尔的分离度可达到2.18,卡维地洛的分离度可达到2.01,分析时间一般为10～20 min,取得了较高的分离效率.为比较研究,还制备了一种单β-环糊精固定相（CDSP）,结果发现双β-环糊精键合相可拆分14种β-受体阻滞剂,而在优化的条件下单β-环糊精键合相仅能部分拆分4种β-受体阻滞剂,且前者的分离度明显优于后者.基于实验数据对双β-环糊精和单β-环糊精固定相的分离机理的异同点展开讨论.一方面包结作用和氢键作用在桥联双β-环糊精键合相的手性分离中占重要地位,与常见的单β-环糊精固定相相似;另一方面桥联双β-环糊精固定相拥有自身的特点,两个β-环糊精腔体存在协同作用,相应于它的模拟酶功能,协同作用不仅扩大了空间识别域,还提高了立体选择性,基于双腔体的包结作用和乙二胺桥键的氢键作用等增强了固定相的手性识别能力,加上有序的SBA-15能加快传质,使得BCDSP具有较好的手性色谱性能,拥有更广泛的拆分对象、更高的分离度和更短的分析时间.新固定相的制备方法简便,手性分离功能强,色谱性能稳定,且制备成本较低.这类桥联双β-环糊精键合有序介孔SBA-15新型的快速分离材料在手性药物质量监控和药代动力学研究中存在良好的应用前景.     

Isoquinolin-1(2H)-ones and 1,6-naphthyridin-5(6H)-ones by an N-acylation-SNAr sequence

A new synthesis of 2,3-dialkyl-4-carbomethoxyisoquinolin-1(2H)-ones and 6,7-dialkyl-8-carbomethoxy-1,6-naphthyridin-5(6H)-ones is reported. The process involves treatment of a β-enaminoester with 2-fluoro-5-nitrobenzoyl chloride, 2-fluorobenzoyl chloride or 2-chloronicotinoyl chloride followed by heating in the presence of base. The conversion, which proceeds by an N-acylation-S_NAr reaction sequence, affords 50–86% yields when R¹ is n-alkyl but ≤30% yields when R¹ is α-branched.     

New cyclic RGD peptides: synthesis,characterization, and theoretical activity towards αvβ3 integrin

Two new cyclic RGD peptides were prepared using a click chemistry approach. The linear RGDfV peptide was synthesized by solid-phase peptide synthesis using a 9-fluorenylmetoxicarbonyl (Fmoc) strategy and a 2-chlorotrityl chloride resin. After coupling 5-hexynoic acid the peptide was cleaved from the resin and linked to propargylamine. The bis-alkynyl RGDfV peptide was then reacted with two different bis-azides by treatment with copper iodide and triethylamine. These two cyclic RGD peptides were characterized by NMR and HRMS. In order to evaluate the interaction of these new compounds with integrin α_vβ₃ docking experiments were carried out and the results compared with those obtained with cyclo(RGDf[N–Me]V) (Cilengitide). The two new cyclic RGD peptides showed a higher affinity to the α_vβ₃ integrin when compared with Cilengitide thus representing two new potential integrin α_vβ₃ antagonists.     

Detection and quantification of plasma amyloid-β by selected reaction monitoring mass spectrometry

Amyloid-β (Aβ) in human plasma was detected and quantified by an antibody-free method, selected reaction monitoring mass spectrometry (SRM-MS) in the current study. Due to its low abundance, SRM-based quantification in 10 μL plasma was a challenge. Prior to SRM analysis, human plasma proteins as a whole were digested by trypsin and high pH reversed-phase liquid chromatography (RPLC) was used to fractionate the tryptic digests and to collect peptides, Aβ_1–5, Aβ_6–16, Aβ_17–28 and Aβ_29–40(42) of either Aβ_1–40 or Aβ_1–42. Among those peptides, Aβ_17–28 was selected as a surrogate to measure the total Aβ level. Human plasma samples obtained from triplicate sample preparations were analyzed, obtaining 4.20 ng mL⁻¹ with a CV of 25.3%. Triplicate measurements for each sample preparation showed CV of <5%. Limit of quantification was obtained as 132 pM, which corresponded to 570 pg mL⁻¹ of Aβ_1–40. Until now, most quantitative measurements of Aβ in plasma or cerebrospinal fluid have required antibody-based immunoassays. Since quantification of Aβ by immunoassays is highly dependent on the extent of epitope exposure due to aggregation or plasma protein binding, it is difficult to accurately measure the actual concentration of Aβ in plasma. Our diagnostic method based on SRM using a surrogate peptide of Aβ is promising in that actual amounts of total Aβ can be measured regardless of the conformational status of the biomarker.     

Operationally convenient method for preparation of sulfonamides containing α,α-difluoro-β-amino carbonyl moiety

We report here that the reactions of in situ generated unprotected α,α-difluoroenolates with various N-sulfonyl imines take place under operationally convenient conditions affording a novel type of fluorinated sulfonamides of high pharmaceutical potential. The reactions feature structural generality, excellent yields and can be easily scaled up for practical preparation of the target fluorine-containing sulfonamides.