人尿中诺龙和炔诺酮代谢物的气相色谱—质谱分析

本文对合成的１９－去甲雄烷醇酮的四个差向异构体混合物进行气相色谱分离，对诺龙和炔诺酮用药后，留取的人尿样通过化学预处理，ＭＳＴＦＡ／ＴＭＳＩ衍生化反应，ＧＣ／ＭＳ分析，确证了尿样中诺龙的两个主要代谢产物为１９－去甲雄酮和１９－去甲原胆烷醇酮，炔诺酮的两个主要代谢物是四氢炔诺酮的两个形式，可能是３ａ－ＯＨ－５ａ－ＴＨＩＮＥ和３ａ－ＯＨ－５β－ＴＨＩＮＥ，在炔诺酮代谢前期，还发现有诺龙的上述两个代谢物     

2－芳酰氨基－5－［1－苯基－2－羟基－2－（对甲氧基苯）乙基］－1，3，4－噻二唑的合成

２－芳酰氨基－５－苄基－１，３，４－噻二唑１上５－位苄基在ＥｔＯＮａ／ＥｔＯＨ中生成负离子，再与对甲氧基苯甲醛亲核加成合成了一系列新的２－芳酰氨基－５－［１－苯基－２－羟基－２－（对甲氧基苯）乙基］－１．３，４－噻二唑２．化合物２的结构经元素分析，ＩＲ，￣ＨＮＭＲ和ＭＳ分析确证。初步观察了２抗菌活性。     

镉（Ⅱ）－1－苯基－3－甲基－4－苯甲酰基－吡唑啉酮－5配合物吸附波的研究

在ｐＨ４．８的ＨＡｃ－ＮＨ＿（４）Ａｃ介质中，Ｃｄ（Ⅱ）与１－苯基－３－甲基－４－苯甲酰基－吡唑啉酮－５（ＰＭＢＰ）生成配合物，于－０．６７Ｖ（ｖｓ．ＳＣＥ）出现一尖锐、灵敏的极谱波。镉含量在０．００１～１．μｇ／ｍＬ范围内与峰高成线性关系。用多种电化学方法研究了极谱波的性质及电极反应机理，证明－０．６７Ｖ处的极谱波为配合物吸附波，峰电流由中心离子Ｃｄ（Ⅱ）还原产生。配合物组成为Ｃｄ（Ⅱ）：ＰＭＢＰ＝１：１。试验了３０多种离子对峰电流的影响，用ＳｒＳＯ＿４共沉淀分离Ｐｂ（Ⅱ），再经巯基棉分离其它干扰离子。用于矿样中镉的测定，结果满意。     

Base－Catalyzed Rearrangement of 11－Isopropylidene－anti－4，5－Epoxyendo－Tricyclo［6．2．1．0~（2，7）］ Undeca－4，9－Diene－3，6－Dione

Ｂａｓｅ－ＣａｔａｌｙｚｅｄＲｅａｒｒａｎｇｅｍｅｎｔｏｆ１１－Ｉｓｏｐｒｏｐｙｌｉｄｅｎｅ－ａｎｔｉ－４，５－Ｅｐｏｘｙｅｎｄｏ－Ｔｒｉｃｙｃｌｏ［６．２．１．０~（２，７）］Ｕｎｄｅｃａ－４，９－Ｄｉｅｎｅ－３，６－ＤｉｏｎｅＸｉａｏＰｅｉＧＵＡ?..     

2－氯／2－甲磺酰基－5－（2－苯基－4－喹啉基）－1，3，4－噁二唑化合物的合成及其亲核取代的研究

借处理２－羟基－５－（２－苯基－４－喹啉基）－１，３，二唑同ＰＣｌ＿５／ＰＯＣｌ＿３之间的反应合成了２－氯－５－（２－苯基－４－喹啉基）－１，３，４－二唑（３）和通过２－基－５－（２－苯基－４－喹啉基）－１，３，４－二唑的甲基化，然后氧化制得２－甲磺酰基－５－（２－苯基－４－喹啉基）－１，３，４－二唑（６）．并分别研究了３和６同胺、叠氮及肼的反应，得到２，５－二取代的二唑新衍生物．初步观察了部分化合物的抗菌活性．     

锆－7－碘－8－羟基喹啉－5－磺酸－EDTA－表面活性剂体系的荧光光度法研究

在ｐＨ６．２的ＨＡｃ－ＮａＡｃ缓冲溶液中，有溴化十六烷基三甲基铵（ＣＴＭＡ８）存在下，Ｚｒ（Ⅳ）与７－碘－８－羟基喹啉－５－磺酸（Ｈ＿２ＱＳＩ）及ＥＤＴＡ形成了四元荧光配合物。其组成为：Ｚｒ：Ｈ＿ＱＳＩ：ＥＤＴＡ：ＣＴＭＡＢ＝１：１：１：３。据此建立了错的选择性好、灵敏度高的荧光测定方法。方法检测限为１．２ｎｇ／ｍＬ。锆的线性范围为１．６ｎｇ～１．０μｇ／ｍＬ。用于铜合金中微量锆的测定，结果令人满意。     

1，12－烷基二胺－Na_2O－SiO_2－Al_2O_3－H_2O系统中ZSM

以硅溶胶为硅源．在０．３０１，１２－烷基二胺－ＸＮａ２Ｏ－ＹＡｌ２Ｏ３－ＳｉＯ２－ＺＨ２Ｏ体系中，研究ＺＳＭ—１１沸石于１６０～２００℃区间的水热结晶．用ＸＲＤ鉴定产物．合成纯相ＺＳＭ－１１的反应物配比是Ｘ＝０．０５；Ｙ＝０～０．０１１；Ｚ＝４０．其反应温度为１６０～１８０℃．加入ＺＳＭ－１１晶种或添加ＮａＦ可加快结晶速度，导致ＺＸＳ－１１（ｓｉｌｉｃａｌｉｔｅ－Ⅱ）柱状单晶的生成．该单晶的最大尺寸可达２０×２０×６０μｍ．     

手性氨基醇（R）－2－氨基－1，1－二苯基－3－（2－萘基）－1－丙醇：制备及其对前手性酮硼烷还原的对映选择性催化作用

用丙二酸酯法合成了Ｎ－乙酰基－３－（２－萘基）－ＤＬ－α－丙氨酸乙酯３．３经酶法拆分，得光学活性的Ｄ－３，后者经盐酸水解、酯化后再与苯基溴化镁作用，制得标题化合物６。在０．５ｍｍｏｌ６存在下，用过量硼烷对一系列前手性酮还原，得到了相应的光学活性二级醇。对映体过量（ｅ．ｅ值）５７．０～１００％。     

氧化物－NaZSM－5催化剂的研究 Ⅱ．ZnO－NaZSM－5的催化性能

研究了不同ＺｎＯ负载量的ＺｎＯ－ＮａＺＳＭ－５催化剂对甲醇、乙醇和王丙胺转化反应的催化行为．与ＮａＺＳＭ－５和ＺｎＯ相比，ＺｎＯ－ＮａＺＳＭ－５系列催化剂具有更高的催化活性和独特的产物选择性．ＺｎＯ高度分散的样品在甲醇、乙醇和正丙胺转化反应中表现出更有效的酸－碱双功能催化作用．还讨论了酸－碱对中心Ｚｎ－Ｏ在这些催化反应中的作用．     

左旋18—甲基炔诺酮—硅橡胶缓释体系小角激光散射法研究

以小角激光前向散射和背散射法研究了左旋１８－甲基炔诺酮－甲基乙烯基硅橡胶缓释体系的光散射时效行为，用紫外分光光度法测定释放过程，讨论药物释放过程中高分子链段运动和聚合物结构对药物释放的影响．     

Preparation and pharmaceutical evaluation of liposomes entrapping salicylic acid/gamma-cyclodextrin conjugate

To evaluate the potential use of a drug/cyclodextrin (CyD) conjugate for efficient entrapment in liposomes and prolonged residence of a drug in tissues, we synthesized a salicylic acid (SA) conjugate bound covalently with gamma-cyclodextrin (SA/gamma-CyD conjugate), a model drug/CyD conjugate, and then liposomes entrapping the conjugate (conjugate-in-liposome) were prepared by a freezing-thawing method. The chemical and physicochemical properties of the SA/gamma-CyD conjugate in solution and solid state were investigated and then the physicochemical properties of conjugate-in-liposome, in vitro cellular uptake/release and in vivo disposition of SA/gamma-CyD conjugate after intravenous administration of aqueous suspension containing conjugate-in-liposome in rats, were evaluated, comparing with those of the liposome-entrapped SA alone (SA-in-liposome) or the liposome-entrapped noncovalent SA/gamma-CyD complex (complex-in-liposome). As a result, it was found that the conjugate was amorphous powder and the release of SA from the conjugate in phosphate-buffered saline (PBS) was tolerated to chemical and enzymatic degradation. Meanwhile, the particle sizes and stability of these liposomes were almost identical, and the entrapment ratio of SA/gamma-CyD conjugate in liposomes was higher than those of SA alone and SA/gamma-CyD complex. The cellular uptake of these liposomes was almost equivalent, but the release of SA/gamma-CyD conjugate from RAW264.7 cells was markedly slower, compared with that of SA from cells following cellular uptake of the SA-in-liposome and complex-in-liposome. The disposition of SA or SA/gamma-CyD conjugate following intravenous administration of aqueous suspensions containing each liposome system in rats was comparable, but the residence time of the conjugate in tissues significantly prolonged, compared with that of the SA-in-liposome and complex-in-liposome systems. These results suggest the potential use of SA/gamma-CyD conjugate for efficient entrapment in liposomes as well as of liposomes containing SA/gamma-CyD conjugates for prolonged residence of drugs in tissues.     

Targeting of mitomycin C to the liver by the use of asialofetuin as a carrier.

Desialylated fetuin (asialofetuin) was adopted as a carrier for introducing drugs in parenchymal liver cells. Mitomycin C, as a model guest-compound, was covalently attached to asialofetuin through a spacer of the succinyl group. The asialofetuin-mitomycin C conjugate contained 4.4 w/w% of mitomycin C and liberated it gradually at physiological conditions (t1/2 = 37 h). The survival time of the conjugate in rat blood circulation was significantly smaller than that of the non-desialylated fetuin conjugate; the elimination half-life was 7.3 min after intravenous injection. At 30 min after injection of the conjugate in rats, 40% of the dose was present in the liver. Parenchymal cells in the liver selectively took up the conjugate, which was highly distributed to the lysosomal fraction in the cell. The greater uptake of the conjugate by hepatocytes reflected the increased excretion in the bile; totally 10.4% of the dose was recovered.     

Preparation of Monomeric Affinity-Purified Fab'-ß-D-Galactosidase Conjugate for Immunoenzymometric Assay

Abstract

A Simpler method for the preparation of monomeric affinity-purified Fab'-ß-D-galactosidase conjugate is described. Rabbit (anti-human IgG) serum was subjected to successive processes of pepsin digestion to convert IgG to F(ab')_2′ reduction with 2-mercaptoethy on a column of human IgG-Sepharose 4B. The affinity-purified Fab' thus obtained without using gel filtration was reacted with excess of maleimide groups introduced into ß-D-galactosidase from Escherichia coli. The monomeric Fab'-ß-D-galactosidase conjugate formed was separated from unconjugated Fab' by gel filtration and from unconjugated ß-D-galactosidase by affinity chromatography on a column of goat (anti-rabbit IgG) IgG-Sepharose 4B. By immunoenzymometric assay technique for human IgG, the monomeric conjugate was compared with a monomeric conjegate prepared by a previously reported complexmethod and non-monomeric conjugate which contained 3.7 Fab' molecules per ß-D-galactosidase molecule. The present monomeric conjugate provided as sensitive a dose-response curve as the previously reported monomeric conjugate and a more sensitive dose-response curve than the non-monomeric conjugate.     

Photochemical and photoelectrochemical behaviour of chlorophyll a-smectite conjugate

Chlorophyll a was adsorbed onto smectite to form chlorophyll-smectite conjugate, which became photostable against light illumination. The chlorophyll-smectite conjugate caused the photoreduction of nitro blue tetrazolium, NBT, through the formation of superoxide anion, and the conjugate retained the photosensitive activity even after 20 hour illumination. Furthermore, the conjugate deposited on SnO₂ electrode caused electron transfer under light illumination. The anodic photocurrent rose at ?200 mV versus Ag/AgCl electrode (KCl saturated) and reached a maximum level at approximately +100 mV. The photocurrent spectrum was in good agreement with the absorption spectrum of chlorophyll-smectite conjugate in an aqueous solution and the quantum efficiency was approximately 1% at 670 nm.     

Evaluation of the DNA Alkylation Properties of a Chlorambucil-Conjugated Cyclic Pyrrole-Imidazole Polyamide

Hairpin pyrrole-imidazole polyamides (hPIPs) and their chlorambucil (Chb) conjugates (hPIP-Chbs) can alkylate DNA in a sequence-specific manner, and have been studied as anticancer drugs. Here, we conjugated Chb to a cyclic PIP (cPIP), which is known to have a higher binding affinity than the corresponding hPIP, and investigated the DNA alkylation properties of the resulting cPIP-Chb using the optimized capillary electrophoresis method and conventional HPLC product analysis. cPIP-Chb conjugate 3 showed higher alkylation activity at its binding sites than did hPIP-Chb conjugates 1 and 2 . Subsequent HPLC analysis revealed that the alkylation site of conjugate 3 , which was identified by capillary electrophoresis, was reliable and that conjugate 3 alkylates the N3 position of adenine as do hPIP-Chbs. Moreover, conjugate 3 showed higher cytotoxicity against LNCaP prostate cancer cells than did conjugate 1 and cytotoxicity comparable to that of conjugate 2 . These results suggest that cPIP-Chbs could be novel DNA alkylating anticancer drugs.     

A helical flow, circular microreactor for separating and enriching "smart" polymer-antibody capture reagents

We report a mechanistic study of how flow and recirculation in a microreactor can be used to optimize the capture and release of stimuli-responsive polymer-protein reagents on stimuli-responsive polymer-grafted channel surfaces. Poly(N-isopropylacrylamide) (PNIPAAm) was grafted to polydimethylsiloxane (PDMS) channel walls, creating switchable surfaces where PNIPAAm-protein conjugates would adhere at temperatures above the lower critical solution temperature (LCST) and released below the LCST. A PNIPAAm-streptavidin conjugate that can capture biotinylated antibody-antigen targets was first characterized. The conjugate's immobilization and release were limited by mass transport to and from the functionalized PNIPAAm surface. Transport and adsorption efficiencies were dependent on the aggregate size of the PNIPAAm-streptavidin conjugate above the LCST and also were dependent on whether the conjugates were heated in the presence of the stimuli-responsive surface or pre-aggregated and then flowed across the surface. As conjugate size increased, through the addition of non-conjugated PNIPAAm, recirculation and mixing were shown to markedly improve conjugate immobilization compared to diffusion alone. Under optimized conditions of flow and reagent concentrations, approximately 60% of the streptavidin conjugate bolus could be captured at the surface and subsequently successfully released. The kinetic release profile sharpness was also strongly improved with recirculation and helical mixing. Finally, the concentration of protein-polymer conjugates could be achieved by continuous conjugate flow into the heated recirculator, allowing nearly linear enrichment of the conjugate reagent from larger volumes. This capability was shown with anti-p24 HIV monoclonal antibody reagents that were enriched over 5-fold using this protocol. These studies provide insight into the mechanism of smart polymer-protein conjugate capture and release in grafted channels and show the potential of this purification and enrichment module for processing diagnostic samples.     

靶向抗肿瘤药物甲氨喋呤-琥珀酰壳聚糖缀合物的制备及其体外稳定性的初步探讨

报道了甲氨喋呤-琥珀酰壳聚糖缀合物的合成方法,并通过紫外光谱、红外光谱及核磁共振谱进行了结构验证.流式细胞仪的检测结果表明,N-琥珀酰壳聚糖对K562白血病肿瘤细胞具有较强的亲和性;溶解性实验结果表明,甲氨喋呤-琥珀酰壳聚糖缀合物的水溶性较好(pH=1～14);体外释放实验结果表明,缀合物性质稳定,能明显延缓甲氨喋呤的释放,为抗肿瘤药物的靶向及缓控释给药体系的研究提供了初步参考.     

Simulation of the bioadhesive gelatin‐alginate conjugate loaded with antibiotic drugs

In the present research, molecular modeling methods were used to study a novel bioadhesive composed of gelatin (protein) and alginate (polysaccharides), crosslinked with N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride (EDC) and N‐hydroxysuccinimide (NHS). Three antibiotic drugs were added to the bioadhesive: Vancomycin, Ofloxacin, and Clindamycin. Computational tools were applied to estimate the crosslinking degree and compare the effect of the antibiotics on the physical properties of the gelatin‐alginate conjugate. The crosslinking degree was estimated by calculating the enthalpy of mixing of gelatin with alginate and their interaction with the crosslinking agents. The calculations revealed that gelatin mixes well with alginate, which enables their crosslinking. Various ratios between EDC and NHS were examined, and an optimal ratio was found. The interaction of alginate‐gelatin conjugate with the antibiotics was correlated to the experimental results of bonding strength. The most significant interaction of the conjugate is with clindamycin. The gelatin part is responsible for the strong interaction with clindamycin, and alginate forms strong interaction with ofloxacin. Thus, the interaction of alginate‐gelatin conjugate with the antibiotics is governed by the proportion between gelatin and alginate in the conjugate. The degradation rate of gelatin‐alginate was related to its interaction with water. It was found that the conjugate is highly hydrophilic. Gelatin is more soluble in water than both alginate and alginate‐gelatin and is probably the part in the conjugate that governs the solubility and degradation rate. Therefore, the degradation rate of the conjugate can be controlled by changing the proportion between gelatin and alginate.     

Synthesis and antitumor activities of mitomycin C (1----3)-beta-D-glucan conjugate.

The conjugate of mitomycin C (MMC) with linear (1----3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 was synthesized and its antitumor activities investigated. The conjugate (MMC-carboxymethylated linear (1----3)-beta-D-glucan (CMPS)) was obtained by treatment of CMPS with MMC in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. In vitro cytotoxicity of MMC-CMPS against L1210 leukemia cells was similar to that of MMC. In i.p.-i.p. system in vivo against P388 leukemia in mice, the maximum increase of MMC-CMPS conjugate in life span (ILSmax) was higher than that of MMC but the therapeutic index was reduced. However, the antitumor activity of MMC-CMPS conjugate against subcutaneously implanted sarcoma 180 solid tumor in mice by i.p. administration was similar to that of MMC at a dose of 1.5 mg eq MMC/kg/d x 7 and the reduction of the number of leukocytes caused by MMC was suppressed by attaching MMC to CMPS. In addition, on assay using serum of sarcoma 180 solid tumor-bearing mice with injection of MMC-CMPS conjugate, a drastic loss of tumor cells and an increase in polymorphonuclear leukocytes (PMN) were observed. This result suggested that MMC-CMPS conjugate induced tumor-regressing factor similar to CMPS.     

A Facile Procedure for Conjugate Addition of Amines to Electron Deficient Alkenes with Metal Oxide as Catalyst

A novel efficient procedure has been developed for the conjugate addition of amines to electron deficient alkenes. A series of metal oxides was synthesized for catalyzing the conjugate addition of amines and alkenes. After optimizing the reaction conditions, SrO was chosen as the most efficient catalyst for the reactions. The results show that the catalyst is very efficient for the conjugate addition of amines to electron deficient alkenes with the excellent yields in several minutes. Operational simplicity...