纳米孔道单分子电化学测量仪器的稳定性研究

纳米孔道分析技术是一种基于电化学空间限域效应的单分子检测技术。测量纳米孔道产生的单分子皮安级微弱电流信号对电化学测量仪器的电流分辨、时间分辨和抗噪音能力提出了挑战。Cube纳米孔道电化学测量仪器通过设计频率补偿电路、前置电流放大器测量系统和基于现场可编程逻辑门阵列(FPGA)的高速数字处理电路,实现了便携式超灵敏电化学测量仪器对微弱电流信号的高时间分辨、高电流分辨,以及低噪音的放大、采集和快速处理。稳定性是仪器能够应用于实际单分子测量分析的重要衡量指标之一。该文通过高阻值电阻对该仪器进行稳定性测试,在截止滤波频率为5、10、100 kHz条件下,Cube纳米孔道仪器获取的电流基线的噪音均方根(RMS)值分别比商品化仪器减小了80.0%、87.5%、48.2%,证明Cube纳米孔道仪器抑制噪音能力更强,电流分辨能力更好,仪器测量稳定性更佳。进一步通过统计比较施加电压值的实际值和标准偏差,结果显示该仪器施加电压误差小,其仪器施加电压标准偏差仅为施加电压变化量(10 mV)的0.14%。同时,通过Aerolysin纳米孔道检测Poly(dA)4的实验,对比Cube仪器和商品化仪器在不同施加电压下获取的单分子信号残余电流程度,得到两者误差均小于0.01,结果具有可重复性。因此,Cube纳米孔道仪器具有稳定性好、灵敏度高、便携性强的特点,可应用于纳米孔道单分子分析。     

基于双模检测仪器的大鼠神经放电和神经化学信号同步检测研究

研制了一种可同步检测神经电生理和化学信号的双模检测仪,并应用此仪器开展了双模同步检测实验。此仪器具有0.3μV电压分辨率的64通道神经电生理检测功能、pA级电流精度的4通道电化学检测功能,具备动作电位分离分类、计时电流法、循环伏安法等常用的检测功能,并且能实现对双模神经信号的同步观测和分析。在采用此仪器开展的单模实验中,完整地检测到了64通道的模拟神经信号,结合微电极阵列获得了信噪比( S/N)为6的神经动作电位发放;采用循环伏安法,获得了铁氰化钾在溶液浓度0.1~10 mmol/L范围内与电流响应的线性相关系数为0.9889;同时,采用计时电流法获得了抗坏血酸在溶液浓度10~800μmol/L 范围内与电流响应的线性相关系数为0.9841。结合大鼠脑缺血模型开展了双模检测实验,在该模型中成功地同步检测到了神经动作电位发放和抗坏血酸浓度变化引起的电流变化,并发现大鼠大脑初级感觉皮层抗坏血酸浓度与动作电位发放呈一定负相关关系。     

应用于神经通路研究的微机电系统探针与低功耗低噪声单集成芯片系统

针对神经内海马区谷氨酸化学递质与神经电生理信号的并行双模检测需要, 设计了8通道电化学递质与电生理双模并行检测传感芯片微系统, 系统组件包括:基于SOI(Silicon-on-insulator)工艺衬底制备的微机电系统MEMS(Micro-electro-mechanical system)神经信息检测探针、低噪声颅内神经电小信号放大器、低功耗中速SAR(Successive approximation register)-ADC(Analog/Digital Converter)模/数转换器、精简低能耗OOK(On-Off-Keying)/FSK(Frequency-Shift-Keying)调制射频发射器.本微型神经信息传感芯片系统具有体积小、抗干扰、化学递质与电生理信号并行检测、灵敏性好、线性度高等特点.对电生理裸探针的4个电生理位点表面沉积铂黑, 电极阻抗优化为35.0 kΩ;通过酶固定技术在谷氨酸检测位点上纳米定向修饰酶复膜结构(Pt-mPD-GluOx)以形成具有特异选择性的生物识别点, 实现神经化学递质谷氨酸的检测;在6～35 μmol/L谷氨酸浓度范围内线性度是0.97, 单位面积灵敏度是0.0069 pA/(μmol/L), 电流响应误差<3.0 pA, 表明此探针可以实现特异选择功能.同时, 基于数模混合180 nm的ASIC(Application specific integrated circuit)芯片制造工艺(SmicRF180 nm 1Poly6M)制造的神经电生理传感后端信息调理单芯片, 其内部关键测试指标:微弱小信号低噪系电压放大器(等效输入噪声电压≤0.7 μV rms, 增益>70 dB, 电源/共模抑制比>100 dB等)、SAR-ADC(有效量化位数是12 bits, 功耗1.2 mW, 最大转换速率1 Msps, 信噪比为60.9 dB)、ASK/FSK调制的射频发射器(功放PA 4～5 dBm, 输出功率满足10 m辐射距离).此微型神经信息感知处理芯片集成检测系统, 可为海马区神经通路的研究提供便携、普适性的无线可穿戴设备.     

纳米通道单分子检测P53蛋白与DNA的弱相互作用

利用基于α-溶血素(α-HL)的纳米通道单分子检测技术在单分子水平上探测位于肿瘤抑制蛋白P53 DNA结合域的多肽分子(P53-P)与含有p21^waf1/cip1基因结合域的双链DNA (B40)之间弱相互作用. 在电场力的作用下, 单个P53-P/B40复合物被α-HL纳米通道捕获并限制在其前庭中. 通过空间限域作用, P53-P与B40之间的弱相互作用被放大为具有显著电压依赖性的复合物-α-HL间强烈的相互作用, 从而产生极易分辨的离子流特征阻断信号. 统计分析特征阻断信号显示P53-P与B40之间的弱相互作用使得B40产生微小的构型变化. 分子对接模拟进一步证明, P53-P能够插入B40的小沟并使得小沟间距变窄. 因此, 基于α-HL的纳米通道单分子检测技术可以作为研究单个生物大分子间弱相互作用的超灵敏分析方法.     

离子液体电解质对DNA穿过α-溶血素纳米孔的影响

不同碱基的DNA分子空间占位和带电状态存在差异,其通过单个纳米孔时可引起特征性的电流脉冲变化,有望成为新一代单分子测序方法。然而,常规条件下DNA分子穿过纳米孔的速度很快(10~(-2)s),引起的电流变化小(pA级),因此分子亚结构信息的准确获取对现有仪器设备的性能提出了极高要求。本研究在α-溶血素纳米孔的两端分别引入高粘度和离子导电性较好的离子液体支持电解质,以构建粘度梯度体系,并对溶液的酸度进行优化,以期对ss DNA穿孔行为进行调控。初步的研究结果表明,在trans端为纯离子液体Bmim PF_6,cis端为1 mol/L Bmim Cl、10 mmol/L Tris-HCl缓冲液(pH 5.5)的条件下,poly(dC)_(15)、poly(dC)_(20)、poly(dC)_(30)和poly(dC)_(50)均出现高抑制比的长阻断电流脉冲信号,长阻断事件的阻断深度达95%以上,持续时间达10~(-2)~10~(-1)s;同时,基线噪音峰峰值也降低约30%。对可能的机理进行了探讨。本研究结果表明,采用离子液体粘度梯度支持电解质体系可以有效调控ss DNA的迁移行为。     

基于金纳米棒-壳聚糖复合膜的葡萄糖生物传感器

本文采用金纳米棒-壳聚糖复合膜固定葡萄糖氧化酶构建电流型葡萄糖生物传感器.通过电化学交流阻抗法和循环伏安法对酶膜状态进行了表征,得到了相应的等效电路和动力学参数.实验结果表明,金纳米棒-壳聚糖复合膜可以辅助电子传递,提高电极的电流响应,并使生物传感器的使用温度范围有很大的扩展.此传感器表现出对葡萄糖溶液浓度的优良响应,线性范围在2.78×10^-5mol/L—2.22×10^-3mol/L,响应灵敏度约为7.819μA·cm^-2(mmol/L)^-1,表观米氏常数为10mmol/L.本工作还研究了温度和溶液pH值对电极电流响应的影响.     

基于二硫化钼/纳米金和硫堇/纳米金信号放大的雌二醇电化学适配体传感器

构建了一种新型的基于二硫化钼/纳米金和硫堇/纳米金信号放大的检测17β-雌二醇的电化学适配体传感器. 利用巯基自组装技术将17β-雌二醇的适配体探针DNA固定在二硫化钼/纳米金修饰玻碳电极表面, 与末端带巯基的部分互补DNA链杂交, 将硫堇/纳米金电化学指示剂自组装在杂交后的双链DNA上, 制备了17β-雌二醇电化学适配体传感器. 二硫化钼/纳米金复合材料增加了电极的有效表面积和DNA探针的固定量. 纳米金作为信号物质载体负载硫堇, 实现了电化学指示剂的信号放大. 加入目标物17β-雌二醇后, 目标物与适配体DNA特异性结合, 导致互补DNA链脱落, 双链上结合的硫堇/纳米金电化学指示剂数量减少, 电化学信号降低. 实验结果表明, 在1.0×10 ^-14~5.0×10 ^-12 mol/L范围内17β-雌二醇浓度与峰电流的线性关系良好, 检出限为4.2×10 ^-15 mol/L(S/N=3). 该传感器可望用于其它环境激素类物质的检测.     

含氧酸根及4-硝基苯酚在氧化钨/聚苯胺修饰电极上的电催化还原

采用循环伏安(CV)、方波脉冲伏安(SWV)和计时电流(CA)技术研究了含氧酸根离子 , , 和4-硝基苯酚(4-NP)在WO₃/PANI修饰电极上的电催化还原. 实验结果表明, WO₃/PANI对 , , 以及4-NP电化学还原都具有良好的催化活性. 恒电位时, WO₃/PANI对相应底物有快速的电流响应, 在40 mmol/L～1.2 mmol/L ( ), 0.12～20 mmol/L ( ), 40 mmol/L～2.50 mmol/L ( ), 50～400 mmol/L (4-NP)浓度范围内, 响应电流与底物浓度呈线性关系, 检测灵敏度及检测限(S/N＝3)分别为0.202 mA/(mmol/L), 4.8 mmol/L ( )|0.035 mA/(mmol/L), 23 mmol/L ( )|0.120 mA/(mmol/L), 5.9 mmol/L ( )|0.443 mA/(mmol/L), 8.8 mmol/L (4-NP).     

微芯片毛细管电泳电化学/电化学发光同时检测药物分子

提出了基于毛细管电泳芯片的电化学和电化学发光同时检测技术.在此芯片系统中,三联吡啶钌Ru(bpy)₃²⁺[Tris(2,2'-bypiridyl) ruthenium(Ⅱ)]既作为电化学发光(ECL)检测所需的发光试剂与被分析物反应,生成激发态的Ru(bpy)₃^2+*,从而产生电化学发光信号;又具有催化作用参与电极表面的电化学反应,从而得到增强的电流响应.电化学信号与电化学发光信号同时产生并被分别纪录,从而实现了电化学和电化学发光的同时检测.这种芯片由两部分构成,分别是带有分离和进样通道的聚二甲基硅氧烷(PDMS)层和ITO(Indium tin oxide)工作电极底片.PDMS层与ITO电极底片采用可逆键合的方式组成芯片,该芯片大大简化了操作过程,提髙了发光信号的采集效率.在整个实验过程中,ITO电极表现出良好的稳定性,可长时间多次使用.选用山莨菪碱和氧氟沙星两种药物分子作为被分析物,对芯片系统性能进行了表征.     

功能化氧化锌纳米棒放大电化学免疫分析乳制品中大肠杆菌的研究

将检测抗体(dAb)和二茂铁甲酸(FCA)固载于二氧化硅修饰的氧化锌(Zn O@Si O2)表面制备纳米复合材料标记物({dAb-Zn O-FCA}),并将其用于放大电化学免疫分析乳制品中的大肠杆菌(E.coli)。在{dAbZn O-FCA}中,检测抗体用于免疫结合大肠杆菌,二茂铁甲酸作为电活性物质产生电流信号。采用"三明治"免疫分析模式,基于二茂铁甲酸产生的电流信号与大肠杆菌浓度之间的线性关系实现了对大肠杆菌的检测。实验结果表明,二茂铁甲酸产生的电流信号与大肠杆菌浓度的对数在2.0×102~2.0×106cfu/m L范围内呈良好线性关系,检出限(S/N=3)为100 cfu/m L。利用该电化学免疫分析方法对乳制品进行了大肠杆菌的加标回收实验,回收率为95.8%~105%。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.