1,2,4-三唑并［1,5-a］嘧啶-2-磺酰胺类除草剂的CoMFA研究

１,２,４－三唑并「１,５－ａ」嘧啶－２－磺酰胺类除草剂是继磺酰脲之后所开发出的又一类以ＡＬＳ为作用靶标的超高效除草剂,本文采用比较分子力场分析方法对该类除草剂进行了三维定量构效关系研究,,结果发现立体场和静电场对该类化合物的除草活性均有重要影响,其中以立体场搂主,根据我们所得的ＱＳＡＲ模型,可以对该类化合物的结构与活性关系进行很好的解释。     

氟喹诺酮类药物与牛血清白蛋白作用的研究

用荧光猝灭法研究了ＢＳＡ与ＮＦＬＸ及ＯＦＬＸ之间的相互作用，根据Ｆｏｒｓｔｅｒ的能量转移理论，确定了能量给体－受体间的距离，根据荧光猝灭谐绘制了猝灭曲线，确定其猝灭过程是静态猝灭，用Ｌｉｎｅｗｅａｖｅｒ－Ｂｕｒｋ双倒数曲线测定ＮＦＬＸ－ＢＳＡ和ＯＦＬＸ－ＢＳＡ络合物的离解常数，并详细研究了１０种阳离子，４种阴离子与药物对ＢＳＡ竞争结合的影响，推测了药物与蛋白的主要作用力。     

α-AMIDOALKYLATION VIA SULFONES:TOWARDS THE SYNTHESIS OF ANT VENOM ALKALOIDS

α－ＡＭＩＤＯＡＬＫＹＬＡＴＩＯＮ　ＶＩＡ　ＳＵＬＦＯＮＥＳ：ＴＯＷＡＲＤＳ　ＴＨＥ　ＳＹＮＴＨＥＳＩＳ　ＯＦ　ＡＮＴ　ＶＥＮＯＭ　ＡＬＫＡＬＯＩＤＳα－ＡＭＩＤＯＡＬＫＹＬＡＴＩＯＮＶＩＡＳＵＬＦＯＮＥＳ：ＴＯＷＡＲＤＳＴＨＥＳＹＮＴＨＥＳＩＳＯＦ...     

A NOVEL SYNTHESIS OF α－ARYLSELENO－α－ACYL PHOSPHORANES AND ITS INTRAMOLECULAR WITTIG REACTION

Ａ　ＮＯＶＥＬ　ＳＹＮＴＨＥＳＩＳ　ＯＦ　α－ＡＲＹＬＳＥＬＥＮＯ－α－ＡＣＹＬ　ＰＨＯＳＰＨＯＲＡＮＥＳ　ＡＮＤ　ＩＴＳ　ＩＮＴＲＡＭＯＬＥＣＵＬＡＲ　ＷＩＴＴＩＧ　ＲＥＡＣＴＩＯＮＡＮＯＶＥＬＳＹＮＴＨＥＳＩＳＯＦα－ＡＲＹＬＳＥＬＥＮＯ－α－Ａ...     

TOTAL SYNTHESIS OF CURVULARIN－TYPE MACROLIDES 12－OXOCURVULARIN AND CITREOFURAN

ＴＯＴＡＬ　ＳＹＮＴＨＥＳＩＳ　ＯＦ　ＣＵＲＶＵＬＡＲＩＮ－ＴＹＰＥ　ＭＡＣＲＯＬＩＤＥＳ　１２－ＯＸＯＣＵＲＶＵＬＡＲＩＮ　ＡＮＤ　ＣＩＴＲＥＯＦＵＲＡＮＴＯＴＡＬＳＹＮＴＨＥＳＩＳＯＦＣＵＲＶＵＬＡＲＩＮ－ＴＹＰＥＭＡＣＲＯＬＩＤＥＳ１２－ＯＸＯ...     

SUSTAINED RELEASE OF LEVONORGESTREL USING POLYPHOSPHATE AS DRUG CARRIER

ＳＵＳＴＡＩＮＥＤＲＥＬＥＡＳＥＯＦＬＥＶＯＮＯＲＧＥＳＴＲＥＬＵＳＩＮＧＰＯＬＹＰＨＯＳＰＨＡＴＥＡＳＤＲＵＧＣＡＲＲＩＥＲＳＵＳＴＡＩＮＥＤＲＥＬＥＡＳＥＯＦＬＥＶＯＮＯＲＧＥＳＴＲＥＬＵＳＩＮＧＰＯＬＹＰＨＯＳＰＨＡＴＥＡＳＤＲＵＧＣＡＲＲＩＥ...     

POTASSIUM FLUORIDE ON ALUMINA CATALYZED ALDOL CONDENSATION OF INDENE AND ACETOPHENONE

ＰＯＴＡＳＳＩＵＭ　ＦＬＵＯＲＩＤＥ　ＯＮ　ＡＬＵＭＩＮＡ　ＣＡＴＡＬＹＺＥＤ　ＡＬＤＯＬ　ＣＯＮＤＥＮＳＡＴＩＯＮ　ＯＦ　ＩＮＤＥＮＥ　ＡＮＤ　ＡＣＥＴＯＰＨＥＮＯＮＥＰＯＴＡＳＳＩＵＭＦＬＵＯＲＩＤＥＯＮＡＬＵＭＩＮＡＣＡＴＡＬＹＺＥＤＡＬＤＯＬ...     

THE STUDY ON EFFECT OF PARTICLE SIZE IN BOTANICAL STANDARD SAMPLE ANALYSIS BY SLURRY SAMPLING AND FLUORINATION ELECTROTHERMAL VAPORIZATION（ETV）－ICP－AES

ＴＨＥＳＴＵＤＹＯＮＥＦＦＥＣＴＯＦＰＡＲＴＩＣＬＥＳＩＺＥＩＮＢＯＴＡＮＩＣＡＬＳＴＡＮＤＡＲＤＳＡＭＰＬＥＡＮＡＬＹＳＩＳＢＹＳＬＵＲＲＹＳＡＭＰＬＩＮＧＡＮＤＦＬＵＯＲＩＮＡＴＩＯＮＥＬＥＣＴＲＯＴＨＥＲＭＡＬＶＡＰＯＲＩＺＡＴＩＯＮ（ＥＴＶ）...     

THE SUPPORTED GOLD CATALYSTS FOR CLOSED CYCLE CO_2 LASER

ＴＨＥ　ＳＵＰＰＯＲＴＥＤ　ＧＯＬＤ　ＣＡＴＡＬＹＳＴＳ　ＦＯＲ　ＣＬＯＳＥＤ　ＣＹＣＬＥ　ＣＯ_２　ＬＡＳＥＲＴＨＥＳＵＰＰＯＲＴＥＤＧＯＬＤＣＡＴＡＬＹＳＴＳＦＯＲＣＬＯＳＥＤＣＹＣＬＥＣＯ_２ＬＡＳＥＲ￥ＺｈｅｎｇＰｉｎｇＨＡＯ；ＬｉＤｕｎＡＮ；...     

SELF SUSTAINED SURFACE CHEMICAL OSCHLATION AND IT＇S MATHEMATICAL SIMULATION OF THE COMPLETE OXIDATION OF MATHANOL OVER Pt／Al_2o_3 CATALYST

ＳＥＬＦＳＵＳＴＡＩＮＥＤＳＵＲＦＡＣＥＣＨＥＭＩＣＡＬＯＳＣＨＬＡＴＩＯＮＡＮＤＩＴ’ＳＭＡＴＨＥＭＡＴＩＣＡＬＳＩＭＵＬＡＴＩＯＮＯＦＴＨＥＣＯＭＰＬＥＴＥＯＸＩＤＡＴＩＯＮＯＦＭＡＴＨＡＮＯＬＯＶＥＲＰｔ／Ａｌ_２ｏ_３ＣＡＴＡＬＹＳＴＣｏｎｇＱ...     

Fluorescence assay for monitoring Zn-deficient superoxide dismutase in vitro

A method has been developed for selective detection of the zinc-deficient form of Cu, Zn superoxide dismutase (SOD1) in vitro. Zinc-deficient SOD1 mutants have been implicated in the death of motor neurons leading in amyotrophic lateral sclerosis (ALS or Lou Gerhig's disease). Thus, this method may have applicability for detecting zinc-deficient SOD1 mutants in human ALS patients samples as well as in a transgenic mouse model of ALS and in cultured motor neurons. We determined previously that structural analogs of 1,10 phenanthroline, which react specifically with Cu(I), react with the active Cu(I) of SOD1 when zinc is absent, but not when zinc is also bound, as evidenced by the fact that the reaction is inhibited by pretreatment of the enzyme with zinc. We report herein that bathocuproine, or its water-soluble derivative bathocuproine disulfonate, react with zinc-deficient SOD1 to form a complex which fluoresces at 734 nm when excited at 482 nm. Fluorescent intensity is concentration dependent, thus we propose to use fluorescent confocal microscopy to measure intracellular levels of zinc-deficient SOD1 in situ.     

Sulfonylurea类ALS/AHAS抑制剂作用方式的分子对接研究和新抑制剂的虚拟筛选

采用Dock5和Autodock3的组合, 从乙酰乳酸合成酶(ALS)的晶体结构出发, 对五个磺酰脲分子和三个类磺酰脲分子与ALS的相互作用方式进行了详细的分子对接研究, 并结合对ALS与氯嘧磺隆(类磺酰脲)共结晶的复合物晶体结构的分析得出了一个简化的药效团模型, 与前人利用其它手段得到的药效团模型一致. 结合此药效团模型并根据sulfonylurea类分子与ALS的作用机理, 我们对425个具有不同除草和杀虫作用的已知农药和ALS进行了分子对接研究和筛选, 从中发现了一些可能对ALS有抑制作用的农药分子. 此结果可以很好地解释这类农药的结构和活性的关系, 对设计、开发新ALS抑制剂的先导化合物提供依据和指导.     

Elemental imbalance studies by INAA on extraneural tissues from amyotrophic lateral sclerosis patients

Human kidney and liver tissues were studied for generalized elemental imbalances in amyotrophic lateral sclerosis (ALS) by instrumental neutron activation analysis (INAA). Iron was significantly increased (p<0.05) in ALS kidneys and Co and Fe (marginal, p<0.10) were increased in ALS liver compared with their respective controls. Mercury values were almost two-fold higher for ALS kidney and 17% higher for ALS liver as compared with their respective controls. However, the Hg data exhibited large variations and ALS-control differences were not significant. Data from the present study are discussed with reference to the role of metallothioneins (MT) in ALS, and a possible linkage between a free radical mediated mechanism and degeneration of cells in ALS is also explored.     

ALS抑制剂合理分子设计的研究进展

以乙酰乳酸合成酶为靶标合理设计开发新型超高效除草剂是当前除草剂化学研究中的重要领域。结合本课题组的研究工作,从ALS抑制剂的结构特征、分子力学与量子化学研究、定量构效关系(QSAR)与三维定量构效关系(3D-QSAR)研究、非线性QSAR研究以及新型除草剂的分子设计等几个方面对该领域的研究现状进行了总结报道,并对该领域的发展前景及存在的问题进行了展望。     

咪唑啉酮类除草剂的三维构效关系研究

从三维角度出发,采取不同的构象搜索方法得到了咪唑酮类化合物分子的活性构象。利用比较分子场分析方法进一步证实了模板分子构象的正确性。并从静电场、立体场及活性关系等方面进行了三维定量构效关系研究,得到了具有较强预测能力的QSAR模型。     

Comments on a recently published paper ‘some surprising properties of multivariate curve resolution‐alternating least squares (MCR‐ALS) algorithms’

Some of the results given in a recently published paper in this journal concerning some surprising properties of the multivariate curve resolution‐alternating least squares (MCR‐ALS) method are discussed. My results showed that the surprising properties of MCR‐ALS refer only to the slow linear convergence properties of ALS algorithms and to rounding error computer calculations. Results obtained by MCR‐ALS for the first data example were correct and no significant differences were observed in the resolved profiles. In the second more complex data example, large rotation ambiguities were present for the spectrum profile of the very minor second component which was not correctly estimated by MCR‐ALS. However, even in this case, the subspaces spanned by the MCR‐ALS solutions were also very close to the correct ones apart from slow convergence properties of the MCR‐ALS algorithm in this case. Copyright © 2009 John Wiley & Sons, Ltd.     

新型含二甲氧基甲基嘧啶基磺酰脲衍生物的合成及生物活性

将二甲氧基甲基引入到嘧啶环的4位, 设计并合成了15个结构新颖的磺酰脲类衍生物. 初步生物活性测试结果表明, 目标化合物具有较好的除草活性. 在75 g/ha的剂量下, 化合物6a和6g对油菜的芽前除草活性为100%, 与对照药单嘧磺隆和氯磺隆相当; 在50 mg/L的浓度下, 化合物6i和6o对3种病菌的离体抑制率都超过80%, 与对照药百菌清和多菌灵接近.     

三唑并嘧啶磺酰胺类除草剂的比较分子场法分析

用比较分子场分析方法,分析了三唑并嘧啶类化合物对乙酰乳酸合成酶(ALS)抑制活性的构效关系,推测其与ALs的空间结合模式.     

以ALS为靶标的新型除草剂的分子设计、合成及生物活性研究(Ⅵ)——嘧啶(硫)醚类除草剂的电子结构研究及新型除草剂的分子设计

从量子药理学的角度,对嘧啶(硫)醚类化合物的电子结构进行了量子化学研究.结果表明,在高活性分子的嘧啶环周围存在一个大的电负性区域,其除草活性与杂环部分的电荷转移能力有关.在上述结果的基础上,设计并合成了一类结构新颖的除草剂.生测结果表明,所设计的化合物具有很好的除草活性,其中化合物b的pI_C50达到7以上.     

距离比较法(DISCO)构建ALS抑制剂药效团模型

在乙酰乳酸合成酶（ALS）三维结构未知的情况下,利用距离比较法（DISCO） ,将10 个结构特征具有代表性的ALS抑制剂的分子构象进行叠合,建立了可能的 药效团模型,并初步验证了模型的可靠性。