蒽醌衍生物的合成与光谱特性

合成了6个蒽醌衍生物(1a~1 f),其中2,3-二氢-9,10-二羟基-1,4-蒽醌(1d)和2,3,4,9-四氢-9-羟基-1,10-蒽醌(1 e)为新的蒽醌衍生物。1a~1 f的结构经UV,1H NMR,IR及MS确定。初步探讨了1a~1 f的荧光和燐光光谱特性。结果表明,1a~1 f都能发射荧光和室温燐光(RTP),尤其是SS-RTP具有较大的Stokes位移和较长的寿命。     

香豆素类肼荧光探针的合成及应用

以4-三氟甲基-7-羟基香豆素为荧光母体,4-溴丁酰基为识别基团,合成了一种基于分子内电荷转移机制的肼荧光探针XS-1,其结构经核磁共振氢谱(¹H NMR),核磁共振碳谱(¹³C NMR)和高分辨质谱(HRMS)确证,通过荧光发射光谱研究了探针对肼的响应性能。结果表明,在磷酸盐缓冲液(10 mmol,pH7.4)中,探针XS-1能通过荧光增强作用识别肼,并具有很好的选择性和抗干扰能力,检出限为0.11μmol/L。探针XS-1具有斯托克斯位移大(144 nm)、线性范围宽(0～400μmol/L)、合成简便以及能在水相中检测肼等优点,并已成功用于实际水样中肼的定量检测。     

1,5-二芳基-3-(2-羟基-4,6-二甲氧基苯基)-2-吡唑啉的合成及氟离子荧光探针行为

设计合成了8个1,5-二芳基-3-(2-羟基-4,6-二甲氧基苯基)-2-吡唑啉化合物4a~4h. 它们的结构经由IR、1H NMR、MS和元素分析确认. 测定了它们的紫外光谱和荧光光谱, 研究了它们对氟离子的选择性识别作用, 发现化合物4a,4c和4d均可选择性地识别氟离子, 其中4a和4c作为识别氟离子的荧光探针, 受常见离子干扰较小, 选择性较高.     

达格列净呋喃环杂质的合成

以5-溴-2-氯-4′-乙氧基二苯甲烷为原料，与2,3-二-O-叔丁基二甲基硅基-5,6-O-异亚丙基-D-葡糖醛酸-1,4-内酯缩合后，再经还原、脱保护、酯化及水解反应合成了达格列净呋喃环杂质--(1S)-1,4-脱水-1-(4-氯-3-(4-乙氧基苄基)苯基)-D-葡萄糖，总收率29.0%，纯度98.5%，其结构经¹H NMR，¹³C NMR， DEPT135，¹H-¹H COSY， HSQC， HMBC和MS(ESI)确证。     

叔胺催化的Sulfa-Michael-Aldol串联反应合成羟基取代的四氢噻吩类化合物

探究了叔胺1,4-二氮杂二环[2.2.2]辛烷(DABCO)催化的2,5-二羟基-1,4-二噻烷和羟基取代查尔酮的sulfa-Michael-aldol串联环化反应。考察了催化剂对反应收率的影响，以最高79%的收率合成了15个多取代的四氢噻吩化合物。 其代表产物的结构经X-ray单晶衍射实验确证，化合物结构经¹H NMR, ¹³C NMR, IR和HR-MS(ESI)表征。      

三种羟基蒽醌类药物与溶菌酶的作用及其构效关系研究

在模拟人体生理条件下,利用紫外光谱法、荧光光谱法和同步荧光光谱法结合研究三种羟基蒽醌类药物(1,2-二羟基蒽醌、1,4-二羟基蒽醌和1,8-二羟基蒽醌)与溶菌酶(LYSO)相互作用机制,并探讨其构效关系。紫外结果初步显示,三种羟基蒽醌类药物与LYSO发生相互作用。荧光结果进一步证实三种羟基蒽醌类药物均与LYSO发生结合,且对LYSO的荧光猝灭机制均为静态猝灭并伴随有非辐射能量转移。三种羟基蒽醌类药物与LYSO均存在一个结合位点,它们与LYSO形成1∶1复合物,在303K下,结合常数K分别为8.47×105、4.88×105和5.43×105L·mol-1,结合距离r分别为5.83、5.12和5.14nm,与溶菌酶作用后焓变分别为-41.2、-87.6和-39.0 kJ·mol-1,熵变分别为-22.4、-180和-19.1 J·mol-1·K-1。三种羟基蒽醌类药物与LYSO的作用力均为范德华力和氢键,且作用强弱不同,其顺序为:1,2-二羟基蒽醌1,8-二羟基蒽醌1,4-二羟基蒽醌。同步荧光法结果表明三种羟基蒽醌类药物与LYSO相互作用后均导致LYSO构象发生改变。研究结果表明,蒽醌环上羟基位置的不同对羟基蒽醌类药物与溶菌酶结合强弱有较大程度的影响。     

一种吡啶-水杨醛类席夫碱的合成及对Zn2+的特异性识别

通过席夫碱反应将2-氨基4-甲基吡啶与4-(二乙氨基)水杨醛结合,设计并合成出一种新型的荧光探针L,该探针能特异性识别Zn²⁺。通过质谱、¹H NMR以及¹³C NMR表征其结构,并利用荧光光谱、紫外-可见吸收光谱研究了探针L在CH₃OH-H₂O(V:V=8:2,Tris-HCl缓冲液,pH=7.4)中对各种离子的选择识别能力。实验结果显示,向探针L中加入Zn2+之后,溶液从无荧光变成蓝色荧光,且457 nm处出现一发射峰。Job’s plot工作曲线结果和密度泛函理论(DFT)计算表明探针L与Zn2+结合计量比为1:1。荧光滴定结果表明探针L对Zn2+的检测极限可低至2.7×10^-8 mol·L^-1,结合常数为1.32×10⁴ L·mol^-1,pH应用范围4.0～10.0。对真实水样中的Zn2+进行检测,平均回收率大于98%,RSD小于1.61%,表明探针L能够检测真实水样中的Zn2+。     

新型蒽醌类拓扑异构酶II抑制剂的深度学习设计与合成

收集并整理了102个蒽醌化合物以及对应抗肿瘤活性和毒性,建立QSAR和分子对接模型。以1,4-二羟基蒽醌为基础,设计具有磺酰基和胺烷基结构的新型蒽醌衍生物。利用模型对所设计的衍生物进行筛选,经两步反应合成了11个潜在的拓扑异构酶II抑制剂（B1~B11）,其结构经¹H NMR, ¹³C NMR和HR-MS(ESI) 表征。药理实验结果表明：化合物对DU-145和HELA癌细胞均显现出良好的抗肿瘤活性。其中B6和B11对DU-145有显著抑制作用,IC₅₀分别为16.88 μM和5.48 μM。      

N,N-烃基-2-甲胺烃基酰胺的合成

以羧酸和环状仲胺为原料,二氯甲烷为溶剂,1-羟基-苯并-三氮唑（HOBT）和1-(3-二甲氨基丙基)-3-乙基碳化二亚胺盐酸盐(EDCI)为缩合剂,合成了一系列含咪唑环和吡嗪环的N-烷基酰胺衍生物,收率56%~73%,其结构经¹H NMR, ¹³C NMR和MS(ESI)确证。     

含缩氨基硫脲结构的新型6,7-二(2-甲氧乙氧基)-喹唑啉化合物的合成

以3,4-二羟基苯甲酸乙酯和2-氯乙基单甲醚为起始原料,经烷氧基化、硝化、还原、环化、氯化、胺化和缩合反应合成了一个含缩氨基硫脲结构的新型喹唑啉化合物,其结构经¹H NMR, ¹³C NMR和MS(ESI)表征。     

“黑洞型”缺电子联吡啶环蕃的合成

利用2,3,5,6-四氟-1,4-苯二甲酸为原料, 经过酯化、还原及溴代, 合成1,4-二溴甲基-2,3,5,6-四氟苯. 以其为原料在低温下利用模板效应合成高度缺电子的“黑洞型”缺电子联吡啶环蕃化合物, 经过连续液液萃取及离子交换得到“黑洞型”缺电子联吡啶环蕃单体. 产品经¹H NMR, ¹³C NMR, MS表征. 利用变温核磁共振技术研究“黑洞型”缺电子联吡啶环蕃与经典的双环(百草枯-对苯撑)型缺电子联吡啶环蕃在溶液中的变化.     

Drug impurity profiling by capillary electrophoresis/mass spectrometry using various ionization techniques

Capillary electrophoresis/mass spectrometry (CE/MS) is predominantly carried out using electrospray ionization (ESI). Recently, atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) have become available for CE/MS. With the VUV lamp turned off, the APPI source may also be used for CE/MS by thermospray ionization (TSI). In the present study the suitability of ESI, APCI, APPI and TSI for drug impurity profiling by CE/MS in the positive ion mode is evaluated. The drugs carbachol, lidocaine and proguanil and their potential impurities were used as test compounds, representing different molecular polarities. A background electrolyte of 100 mM acetic acid (pH 4.5) provided baseline separation of nearly all impurities from the respective drugs. APPI yielded both even‐ and odd‐electron ions, whereas the other ionization techniques produced even‐electron ions only. In‐source fragmentation was more pronounced with APCI and APPI than with ESI and TSI, which was most obvious for proguanil and its impurities. In general, ESI and TSI appeared the most efficient ionization techniques for impurities that are charged in solution achieving detection limits of 100 ng/mL (full‐scan mode). APPI and APCI showed a lower efficiency, but allowed ionization of low and high polarity analytes, although quaternary ammonium compounds (e.g. carbachol) could not be detected. Largely neutral compounds, such as the lidocaine impurity 2,6‐dimethylaniline, could not be detected by TSI, and yielded similar detection limits (500 ng/mL) for ESI, APPI and APCI. In many cases, impurity detection at the 0.1% (w/w) level was possible when 1 mg/mL of parent drug was injected with at least one of the CE/MS systems. Overall, the tested CE/MS systems provide complementary information as illustrated by the detection and identification of an unknown impurity in carbachol. Copyright © 2009 John Wiley & Sons, Ltd.     

A study of the direct spectrophotometric determination of fluoride ion with the cerium(3)-alizarin fluorine blue complex

Several workers have observed that the sensitivity of the cerium (ItII)-alizarin fluorine blue method for the spectrophotometric determination of microgram amounts of fluoride may be enhanced by addition of certain solvents. The present study proves that the use of an aqueous 25% v/v solution of dimethylsulfoxide, the most polar aprotic solvent, enhances to a maximum the sensitivity of the reaction and increases its speed. Two procedures, allowing the determination of 1–25 μg fluoride ion, are described: the best pH value is 4.1 and the spectrophtotometric measurements are carried out at 625 or 630 nm. The interferences of 12 ions were studied.     

Potentiometric determination of ultratrace amounts of fluoride enriched by zirconia in a flow system

A satisfactory method was described for separation and preconcentration of ultratrace amounts of fluoride ions enriched by zirconia (ZrO₂) as an inorganic ion exchanger. Fluoride ions can be adsorbed rapidly and selectively on zirconia from an acidic solution (pH 4.8) then reversibly desorbed by increasing pH up to 13. A flow system consisting of a column packed with zirconia impregnated on cellulose fibers and an ion-selective electrode was used for the determination of fluoride. The RSD was found to be 1.6% and the detection limit defined by S/N = 3 was 3 × 10⁻⁹ mol L⁻¹. The interference effects of various ions, such as nitrate, sulfate, halides, alkaline, and alkaline earth ions, which may be found in the environmental water, were studied, and it was found that they were tolerated even at high concentrations. The method was applied to determine fluoride in drinking water, which contains ultratrace amounts of fluoride. The concentration of fluoride was found to be 42 μg L⁻¹, which is confirmed by spiking 2 μmol fluoride to the drinking water with a recovery of 99%. Published in Russian in Zhurnal Analiticheskoi Khimii, 2006, Vol. 61, No. 2, pp. 179–183. The text was submitted by the authors in English.     

Identification of ilaprazole metabolites in human urine by HPLC‐ESI‐MS/MS and HPLC‐NMR experiments

Ilaprazole is a new proton pump inhibitor designed for the treatment of gastric ulcers, and limited data is available on the metabolism of the drug. In this article, the structural elucidation of urinary metabolites of ilaprazole in human was described by HPLC‐ESI‐MS/MS and stopped‐flow HPLC‐NMR experiments. Urinary samples were precipitated by sodium carbonate solution, and then extracted by liquid–liquid extraction after adding ammonium acetate buffer solution. The enriched sample was separated using a C₁₈ reversed‐phase column with the mobile phase composed of acetonitrile and 0.05 mol/L ammonium acetate buffer solution in a gradient solution, and then directly coupled to ESI‐MS/MS detection in an on‐line mode or ¹H‐NMR (500 MHz) spectroscopic detection in a stopped‐flow mode. As a result, four sulfide metabolites, ilaprazole sulfide (M1), 12‐hydroxy‐ilaprazole sulfide (M2), 11,12‐dihydroxy‐ilaprazole sulfide (M3) and ilaprazole sulfide A (M4), were identified by comparing their MS/MS and NMR data with those of the parent drug and available standard compounds. The main biotransformation reactions of ilaprazole were reduction and the aromatic hydroxylation of the parent drug and its relative metabolites. The result testified that HPLC‐ESI‐MS/MS and HPLC‐NMR could be widely applied in detection and identification of novel metabolites. Copyright © 2010 John Wiley & Sons, Ltd.     

合成4-巯基-1-丁醇的新方法

报道了一种合成4-巯基-1-丁醇（1）的新方法。以1,4-丁二醇为原料,经磺酰化反应及亲核取代反应制得1,总收率达75%,纯度98%（GC）,其结构经¹H NMR和MS（ESI）确证。     

A coumarin-based fluorescent and colorimetric chemosensor for rapid detection of fluoride ion

A novel coumarin-based compound 1 featuring thiosemicarbazone as binding unit, was reported as a colorimetric and fluorescent probe for the detection of fluoride anion. The addition of F^? to a solution of probe 1 in tetrahydrofuran resulted in evident naked-eye color change from green-yellow to orange-red under daylight and obvious fluorescence quenching within 3 s. And the detection limit toward F^? was calculated to be as low as 2.16 × 10^?7 mol/L. ¹H NMR titrations proved that the interaction between 1 and fluoride ion: hydrogen bond at low fluoride ion concentration, deprotonation at high fluoride ion concentration. Besides, it exhibited highly sensitivity and selectivity for F^? over other examined ions (Cl^?, Br^?, I^?, AcO^?, NO₃^?, HSO₄^?, H₂PO₄^?) in tetrahydrofuran solution.     

A novel HPQ-based turn-on fluorescent probe for detection of fluoride ions in living cells

2-(2′-Hydroxyphenyl)-4(3H)-quinazolinone (HPQ) has been reported as a precipitating fluorescent molecule with excellent optical properties, such as large Stokes shift and strong fluorescence intensity. HPQF, a novel HPQ-based turn-on probe for localizable detection of fluoride ions, was designed, synthesized and fully characterized by ¹H NMR, ¹³C NMR and HRMS. As a chemogenic fluoride probe, the tert-butyldiphenylsilane moiety of HPQF can be easily cleaved by fluoride. After spontaneous 1,6-elimination, HPQ molecule was generated to emit fluorescence under the excitation light. Further study shows that HPQF exhibited high selectivity and sensitivity for detection of fluoride. In addition, HPQF was utilized for the detection of fluoride in living cells.     

Hydrogen evolution from aliphatic alcohols and 1,4-selective hydrogenation of NAD+ catalyzed by a [C,N] and a [C,C] cyclometalated organoiridium complex at room temperature in water

A [C,N] cyclometalated Ir complex, [Ir(III)(Cp*)(4-(1H-pyrazol-1-yl-κN(2))benzoic acid-κC(3))(H(2)O)](2)SO(4) [1](2)·SO(4), was reduced by aliphatic alcohols to produce the corresponding hydride complex [Ir(III)(Cp*)(4-(1H-pyrazol-1-yl-κN(2))-benzoate-κC(3))H](-)4 at room temperature in a basic aqueous solution (pH 13.6). Formation of the hydride complex 4 was confirmed by (1)H and (13)C NMR, ESI MS, and UV-vis spectra. The [C,N] cyclometalated Ir-hydride complex 4 reacts with proton to generate a stoichiometric amount of hydrogen when the pH was decreased to pH 0.8 by the addition of diluted sulfuric acid. Photoirradiation (λ > 330 nm) of an aqueous solution of the [C,N] cyclometalated Ir-hydride complex 4 resulted in the quantitative conversion to a unique [C,C] cyclometalated Ir-hydride complex 5 with no byproduct. The complex 5 catalyzed hydrogen evolution from ethanol in a basic aqueous solution (pH 11.9) under ambient conditions. The 1,4-selective catalytic hydrogenation of β-nicotinamide adenine dinucleotide (NAD(+)) by ethanol was also made possible by the complex 1 to produce 1,4-dihydro-β-nicotinamide adenine dinucleotide (1,4-NADH) at room temperature. The overall catalytic mechanism of hydrogenation of NAD(+), accompanied by the oxidation of ethanol, was revealed on the basis of the kinetic analysis and detection of the reaction intermediates.     

A near-infrared large Stokes shift probe based enhanced ICT strategy for F- detection in real samples and cell imaging

In view of the few reports of the near-infrared emissive probe for fluorine ions, we herein designed and synthesized a new easy-to-get colorimetric and near-infrared emissive fluorescent probe (IS-NR-F) with a large Stokes shift (>127 nm). Based on specific F^? triggered desilylation reaction induced enhanced ICT strategy involving the donor phenolate anion and the acceptor malononitrile, the probe exhibited dual colorimetric and fluorescent turn-on responses, and provided excellent selectivity for fluoride ions. The fluorescent response at 665 nm displayed very good linear relationship in the wide concentration range and deduced a low detection limit of 0.09 ppm. The detection mechanism was confirmed by ¹H NMR, ESI-MS, and TLC calculation. Moreover, probe IS-NR-F has been successfully employed to detect F^? in tap water, toothpaste samples, and fluorescent imaging of F^? in HeLa cells.