氟喹诺酮类C—5位及C—7位衍生物抑菌活性的QSAR研究

采用分子连接性指数法对文献报道的氟喹诺酮类Ｃ－５位及Ｃ－７位有不同取代基的４１个化合物的抑菌活性进行定量构效关系研究，首先编制了计算路径、簇项、路径／簇项和链项各阶分子连接性指标，并建立了这类化合物抑菌活性的定量构效关系（ＱＳＡＲ）方程，结果表明５位以简单取代基为宜。用建立的ＱＳＡＲ模型预测了Ｋｌｏｐｍａｎ组合设计的分子活性，结果表明对抑制革氏阳性菌活性不理想。     

胆甾—4,6—二烯—3—酮的合成

以胆固醇为原料，经二甲亚砜－二环己基碳二亚胺系统选择性氧化，生成胆甾－５－烯－３－酮，产率约３３％，胆甾５－烯－３酮经四氯苯酯进一步选择性脱氢生成胆甾－４，６－二烯－３－嘴化合物是合成１μ－羟基维生素Ｄ３的重要中间体。     

胆甾－4，6－二烯－3－酮的合成

以胆固醇为原料，经二甲亚砜－二环己基碳二亚胺（ＤＭＳＯ－ＤＣＣ）系统选择性氧化，生成胆甾－５－烯－３－酮，产率约３３％．胆甾－５－烯－３－酮经四氯苯醌进一步选择性脱氢生成胆甾－４，６－二烯－３－酮．此化合物是合成１ａ－羟基维生素Ｄ３的重要中间体．     

1,3-双(芳基丁二烯基酮)丙烷衍生物的合成及其在可见光诱导催化条件下的[4+4]和[2+2]环加成反应(英文)

合成了4种不同取代基的1,3-双(芳基丁二烯基酮)丙烷类新型双共轭链衍生物,并对其合成条件进行了优化,实施了其在可见光诱导Ru(bipy)3Cl2催化条件下发生的[4+4]和[2+2]环加成反应,合成得到了4个四环并五环及4个八环并五环双酮取代化合物.该结果为合成特殊八员环及四员环类药物分子和多共轭有机光电材料化合物,提供了很好的前体化合物.     

物理化学

正BODIPY快速可逆反应控制研究中国科学院化学研究所光化学重点实验室研究员杨国强课题组与国内外科学家合作,提出了三芳基硼化合物特异荧光性质的发光机理,设计制备了一系列特殊超分子结构荧光探针,应用于对细胞和生物体内的温度、酸碱性等微环境变化和多个活性物种的荧光检测。相关论文发表于《自然-通讯》。通过对meso-位无取代的BODIPY2,6-位取代基的选择性修饰,实现了在     

取代β-二酮镍络合物与格氏试剂反应中间体的研究

本文用ESR研究了乙酰丙酮镍、三氟乙酰丙酮镍和α-噻吩甲酰三氟丙酮镍分别与五种格民试剂反应形成的中间体——自由基负离子,并讨论了这类β-二酮的不同取代基对基寿命的影响。     

一类新型含炔基结构查尔酮的合成及表征

报道了一种新型含炔基查尔酮的合成方法,以邻溴苯甲醛和含取代基苯乙炔为原料,通过Sonogashira偶联反应,生成的炔基苯甲醛进一步与苯乙酮反应生成含炔基结构的查尔酮,此类查尔酮在过渡金属催化的串联反应研究领域有着重要的作用,该类化合物拓展了金、钯、铜等过渡金属参与催化的有机合成反应的底物范围,对进一步研究过渡金属参与的串联反应有一定的指导意义。该方法具有原料简单易得、反应过程操作容易、收率高等优点,产物经红外、核磁共振和质谱等分析手段确证结构。     

虎杖查尔酮合酶PcCHS1基因的克隆与功能分析

从中药虎杖中通过RACE等方法克隆到一个查尔酮合酶基因的全长cDNA,命名为PcCHS1.该cDNA全长1182 bp,编码一个含393个氨基酸的蛋白质.体外酶促活性研究表明,重组PcCHS1在pH 7～8时催化形成查尔酮为其单一产物,在pH 9时除催化形成查尔酮外,还产生一定量的苯亚甲基丙酮.对PcCHS1第216位和第333位氨基酸进行了定点突变研究,结果表明这些位点对PcCHS1的体外酶促活性影响较大.     

系列芳氧基取代酞菁锌荧光光谱及光敏氧化活性研究

酞菁类化合物具有高度共轭的π电子体系，在可见光区有强的跃迁，使酞菁化合物显示出独特的光、电、热、磁的性质，有着广阔的应用前景，在光动力治疗领域的应用尤其引人瞩目。本文在评述PDT用光敏剂研究现状的基础上，围绕具有一定应用前景的芳氧基取代酞菁锌进行了荧光光谱的研究及光敏氧化活性研究，其主要的工作内容和结果归纳如下：1、测定了标题配合物在8种溶剂中的荧光光谱；探讨了取代基、取代位置及溶剂等对光谱性质的影响。从荧光光谱数据看，芳氧基取代酞菁锌的荧光量子产率均低于无取代酞菁锌，其中氮杂芳氧基取代酞菁锌具有较高的荧光量子产率，有望开发成为光诊断剂。2、测定了喹啉氧基取代酞菁锌光敏氧化色氨酸速率常数，探讨了取代基、取代位置及取代基数目等对光敏氧化色氨酸速率常数的影响，结果表明α-（4-Q0）．PcZn具有良好的光敏氧化能力，有望开发成为抗癌光敏剂。     

新型糖肽类抗生素替考拉宁的产品特性与市场分析

替考拉宁为游动放线菌属发酵产生的一种糖肽类抗生素,对革兰氏阳性菌包括需氧菌和厌氧菌有良好的抗菌活性。本文分析了该品的产品特性、市场优势与国内外动态,预计发展前景看好。     

Effects of garlic extract treatment in normal and streptozotocin diabetic rats infected with <Emphasis Type="Italic">Candida albicans</Emphasis>

The anti-candidial effect of garlic extract (Allium sativum L.) was investigated in normal and streptozotocin-induced diabetic rats. Diabetes was induced after a single intraperitoneal injection of streptozotocin (60 mg/kg). Rats were divided into six groups with fifteen rats in each group: (1) Normal control rats (2) Control rats + C. albicans (3) Control rats + garlic extract + C. albicans (4) Diabetic control rats (5) Diabetic rats + C. albicans (6) Diabetic rats + garlic extract + C. albicans. The concerned groups were inoculated with C.albicans on the 15 th day. At the end of one month experiment, fasted rats were killed by cervical decapitation. Blood was collected for estimation of glucose and C. albicans concentrations were estimated in liver and kidneys homogenates. A significant increase was observed in serum glucose levels in diabetic rats. A loss of bodyweight, polydipsia and polyphagia were observed in diabetic rats. Administration of alcoholic extract of garlic (0.25 g/kg body weight) reduced the hyperglycemia, polydipsia, polyphagia and associated weight loss of streptozotocin-treated rats. Administration of garlic extract significantly reduced C. albicans concentrations in liver and kidneys homogenates in infected control and diabetic rats. It is concluded that garlic extract improves candidia infection in diabetic rats.     

The response of liver lipid peroxidative and antioxidant defense systems of protein undernourished rats to liver regeneration

The response of liver lipid peroxidative and antioxidant defense system of protein undernourished rats to liver regeneration induced by partial hepatectomy was examined in rats. Animals were divided into four groups; A,B,C and D of four animals each. Animals in group A were maintained on 16% casein diet while those in groups B, C and D were placed on low-protein diet (5% casein) for fourteen weeks and fed ad libitum. 72 hours before sacrifice, partial hepatectomy was carried out on animals in group D while animals in group C were sham-operated. The results show that protein undernutrition induced an increase in lipid peroxidation but reduced catalase activity, glutathione level and superoxide dismutase activity when compared with well-nourished rats. Liver regeneration however, resulted in significant increases in lipid peroxidation and catalase activity but significant reductions in glutathione level and superoxide dismutase activity in protein undernutrition rats when compared with their sham-operated counterparts. These results suggest that liver regeneration induced by partial hepatectomy exacerbates lipid peroxidation in protein undernutrition rats and that Catalase plays a major role in the mopping up of reactive oxygen species generated following liver regeneration in partially hepatectomised protein undernutrition rats.     

高效液相色谱法检测细胞能量代谢物质的方法建立与应用

建立高效液相色谱法(HPLC)测定细胞中ATP、ADP和AMP含量的方法,以比较高糖培养的MRC-5细胞和D-半乳糖诱导的拟衰老MRC-5细胞能量代谢水平。体外培养的细胞经高氯酸裂解后,用反向HPLC法检测两组细胞ATP、ADP和AMP的含量。HPLC系统采用Ecosil C18反相柱(4.6*250mm 5μm pH 2～8),流动相为15mM磷酸二氢钾缓冲液和10%甲醇,流速0.5mL/min,紫外检测波长为254nm;检测温度为25℃,进样量20μL。以标准曲线法计算ATP、ADP和AMP含量,并计算腺苷酸能荷(EC)。结果显示拟衰老细胞的ATP含量及EC较对照组显著降低,而AMP含量明显升高,差异具有统计学意义(p<0.05),但两组之间的ADP含量没有明显差别。结果表明高效液相色谱法可检测出不同状态细胞能量物质的差异,其具有操作简便、快速、重现性好等特点,可以作为线粒体能量代谢功能的评估方法之一。     

Assessment of oxidative stress and effect of antioxidant supplementation during radiotherapy in carcinoma of upper digestive tract

Oxidative stress was studied by estimating plasma levels of malondialdehyde (MDA), beta carotene, vitamin E and erythrocytic superoxide dismutase(E-SOD) activity in 50 cases of carcinoma of upper digestive tract which included carcinoma of oral cavity, pharynx and oesophagus. While plasma MDA level was found to be increased (3.5±1.0 nmole/ml), a significant decrease in beta carotene (81.2±14.5mg%), vitamin E (8.5±1.1 mg/L) level and E-SOD activity (657.0±80.6 U/G Hb) were observed in carcinoma of upper digestive tract. Patients were treated with radiotherapy which itself was toxic enough and produced its deleterious effects by generation of reactive oxygen species (ROS). As antioxdiants can detoxify ROS, beneficial effect if any, of antioxidant administration during radiotherapy was studied in two groups of patients, group A (n=5, supplemented with antioxidants) and group B (n=5, without antioxidant supplementation). Plasma MDA level was found to be elevated in both the groups but the increase in group B was significant, compared to pretreatment level. Further, body weight was found to be significantly decreased in group B patients, which was maintained in group A patients. Moreover, group A patients showed significant elevation in beta carotene concentration, thus showing beneficial effect of administration of antioxidants during radiotherapy without disturbing the desirable therapeutic effect of radiotherapy.     

取代芳烃对蝌蚪毒性的定量构效关系研究

对24种取代芳烃化合物进行DFT-B3LYP/6-311G**水平全优化计算,据所得量子化学参数建立取代芳烃对蝌蚪12h暴露急性半致死毒性(lg1/LC50,mol·L-1)的定量构效关系(QSAR)模型.对训练集样本经逐步多元回归分析后,所建QSAR模型的相关系数R及去一法(LOO)交互检验复相关系数R2cv分别为0.950和0.875,用预测集样本进行了外部预测,所得外部预测样本复相关系数R2ext和外部预测集交互检验Q2ext分别为0.880和0.856,表明所建立的QSAR方程具有较好的稳定性和预测能力.模型结果表明:分子的体积愈大,化合物毒性愈强;最负的原子净电荷愈负,毒性愈弱.对模型应用域(AD)进行了表征,所建模型可以应用于应用域内化合物的毒性预测,具有潜在应用价值.     

Effect of nitrogen,carbon sources and agitation speed on acetoin production of Bacillus subtilis SF4-3

BackgroundCurrently, microbial fermentation method has become the research hotspot for acetoin production. In our previous work, an acetoin-producing strain, Bacillus subtilis SF4-3, was isolated from Japanese traditional fermented food natto. However, its conversion of glucose to acetoin was relatively low. In order to achieve a high-efficient accumulation of acetoin in B. subtilis SF4-3, main medium components and fermentation conditions were evaluated in this work.ResultsThe by-products analysis showed that there existed reversible transformation between acetoin and 2,3-butanediol that was strictly responsible for acetoin production in B. subtilis SF4-3. The carbon sources, nitrogen sources and agitation speed were determined to play crucial role in the acetoin production. The optimal media (glucose·H₂O 150 g/L, yeast extract 10 g/L, corn steep dry 5 g/L, urea 2 g/L, K₂HPO₄ 0.5 g/L, MgSO₄ 0.5 g/L) were obtained. Furthermore, the low agitation speed of 300 r/min was found to be beneficial to the reversible transformation of 2,3-butanediol for acetoin production in B. subtilis SF4-3. Eventually, 48.9 g/L of acetoin and 5.5 g/L of 2,3-butanediol were obtained in a 5-L fermenter, and the specific production of acetoin was 39.12% (g/g), which accounted for 79.90% of the theoretical conversion.ConclusionsThe results indicated acetoin production of B. subtilis SF4-3 was closely related to the medium components and dissolved oxygen concentrations. It also provided a method for acetoin production via the reversible transformation of acetoin and 2,3-butanediol.     

流式细胞术分析五味子乙素促进阿霉素内化的实验研究

[目的]建立流式细胞术分析肿瘤细胞内阿霉素分布的方法,并研究低浓度五味子乙素对K562细胞内化阿霉素的影响。[方法]体外培养猪内皮细胞(pEC),以20μmol/L阿霉素处理2、4和6小时;或加入不同浓度阿霉素(0、10、20、40、80和100μmol/L)处理4小时。培养K562细胞,以5μmol/L阿霉素处理2、4和6小时;或加入不同浓度阿霉素(0、2.5、5、10和20μmol/L)处理4小时。采用不同浓度(0、25、50和100μmol/L)五味子乙素(Sch B)与阿霉素联合处理K562细胞4小时。收集细胞,采用流式细胞术分析阿霉素的特异荧光。[结果]固定浓度处理pEC(20μmol/L)和K562(5μmol/L)后检测,发现细胞内荧光强度随时间延长而增加,两种细胞4小时组荧光强度分别达到6小时组的96.93%和95.23%/。在直方图上,阴性和阳性细胞群界限分明。阿霉素(2.5、5和10μmol/L)单独处理细胞的荧光强度分别为26.78±3.34、64.70±6.24和118.35±9.67;添加25μmol/L Sch B实验后荧光强度增加到43.45±4.25、103.74±7.36和146.69±8.32,Sch B显著增加了K562细胞内阿霉素的分布(p<0.05)。[结论]建立的方案可快速测定细胞内的阿霉素分布;低浓度Sch B促进肿瘤细胞内化阿霉素。     

辐射防护手套的初步模拟研究

利用MCNP程序对防护手套的布料进行模拟研究。防护布料材质、密度及与源的距离的差异,对射线的阻止本领是有不同的。本次研究的防护布料成分主要包含氧、氢、铅、碳,研究内容是模拟不同成分组成及不同密度的布料对射线的阻止能力。     

RAPID DETERMINATION OF GUANINE BY HIGH PERFORMANCE CAPILLARY ELECTROPHORESIS

A simple and reproduciable method for determining guanine by high performance capillary electrophoresis is presented. The method involved the use of 2-amino-5-mercapto-3,4-dithiazole as internal standard and 40mmol/L borax-H3PO4 (pH2)-5% EtOH as.the background electrolyte. The result showed that the linear range for guanine is 5-300 mg/L with the recovery of 94%-98% , the detection limit of 2. 80 mg/L and the RSD of 3. 1%. The satisfactory result was obtained when it was used to detect the concentration of guanine in acyclovir product.