具有除草活性的α-氧代膦酸衍生物研究进展

简要的总结了十三个系列的α-氧代膦酸衍生物的合成和生物活性的研究进展。为了获得具有较高除草活性及商品化潜力的新型膦酸脂,尝试采用生物合理设计的方法设计新型的丙酮酸脱氢酶系抑制剂,通过在合成、生物测定、机理及生物化学研究的基础上进行构效关系及结构优化的研究,发现α-(取代苯氧乙酰氧基)烃基膦酸酯为一类兼具有良好除草活性和植调活性的先导母体,研究证明该类化合物为丙酮酸脱氢酶系的强抑制剂。     

丙酮酸脱氢酶系：除草剂品种的新靶标

丙酮酸脱氢酶系抑制剂;综述;丙酮酸脱氢酶系：除草剂品种的新靶标     

脱氢酶电化学生物传感器的研究进展

自然界中超过400种脱氢酶使用辅酶-烟酰胺腺嘌呤二核苷酸(NAD+)或烟酰胺腺嘌呤二核苷酸磷酸(NADP+)作为生物催化反应中氢和电子的传递体,因此烟酰胺型辅酶的电化学氧化对构筑此类脱氢酶电化学生物传感器具有重要的意义.本文介绍了还原型辅酶在人工电子媒介体存在下的电化学氧化,以及脱氢酶电化学生物传感器的设计和应用.     

Pb-Pt/AC催化甘油一步法制备丙酮酸

生物质能具有绿色环保、可再生、来源广泛和安全性高等优点,成为当前的研究热点.作为生物柴油的主要副产物,甘油是一种重要的生物质平台化合物.甘油的高效利用,不仅能够获得重要的精细化学品及聚合物,也可以延长生物柴油的产业链,降低其生产成本,增加其市场竞争力.丙酮酸是一种弱有机酸,为生物体内葡萄糖分解代谢的中间产物,在生物能量代谢和物质代谢过程中起着重要的枢纽作用.同时,由于它同时含有羧基和酮羰基,具有很强的反应性,可参与多种化学反应,在化学工业中有广泛应用.目前,工业上主要采用酒石酸脱水脱羧法生产丙酮酸,丙酮酸收率可达50–55%,但生产过程需要消耗大量的KHSO4粉末,生产成本高,且高耗能高污染,不符合可持续发展的要求.因此,利用可再生资源甘油在温和条件下生产丙酮酸显现出良好的应用前景.目前,由甘油一步法获得丙酮酸仅可通过发酵法实现,但是其规模化生产存在效率低、废弃物污染等问题.因此,研究化学方法由甘油一步制备丙酮酸可行也十分必要.本课题组以Pt/AC或Cu-Pt/AC为催化剂进行甘油氧化制备乳酸的研究,所得产物中几乎未检出丙酮酸;当以Pb-Pt/C为催化剂进行乳酸脱氢氧化制备丙酮酸,可获得较高选择性的丙酮酸.因此,本文通过向Pt/AC催化剂中引入Pb助剂,以期调变甘油氧化的产物分布,从而获得相对高的丙酮酸选择性.通过浸渍-沉积沉淀法(Im-DP)制备了一系列不同Pb载量(1–7.0 wt%)的xPb-5Pt/AC-Im-DP催化剂,并采用不同方法制备了一系列5Pb-5Pt/AC催化剂,用于在温和条件下甘油选择性氧化制备丙酮酸反应中.结果表明,Pb载量和催化剂制备方法都对其催化活性有显著影响.当xPb-5Pt/AC-Im-DP催化剂中Pb载量为1%时,甘油转化率和丙酮酸选择性均较单金属5Pt/AC催化剂高,但当Pb载量继续升高至3%及以上时,甘油转化率明显下降.我们推测这与Pb3(CO3)2(OH)2物种的形成有关.采用该方法制备催化剂时,Pb载量宜为5.0 wt%.保持Pt和Pb载量均为5.0 wt%,采用共沉积沉淀(Co-DP)、共浸渍(Co-Im)、以及对催化剂进行500oC氩气焙烧等,制备了具有Pb3(CO3)2(OH)2物种、铂铅合金物种(PtPb和PtxPb)和两物种均没有的5Pb-5Pt/AC催化剂.通过评价它们的催化性能,进一步探究了Pb3(CO3)2(OH)2物种、铂铅合金物种、表面金属价态与催化剂活性的关系.实验表明,Pb3(CO3)2(OH)2和表面Pb0物种不利于甘油的转化,铂铅合金对甘油转化有一定的促进作用,对丙酮酸生成显现出明显促进作用.通过对Co-DP、Im-DP催化剂进行500oC氩气焙烧,能够除去Pb3(CO3)2(OH)2物种,同时形成铂铅合金.综上,本文在温和条件下,采用Pb-Pt/AC催化剂进行甘油选择性氧化制备丙酮酸反应.采用优化的方法制备的5Pb-5Pt/AC催化剂在90oC条件下反应10 h,丙酮酸收率可达18.4%,这是目前甘油一步法氧化制备丙酮酸的最高值.进一步优化反应条件、催化剂组成与结构,探索反应机理仍十分必要.     

Pb-Pt/AC催化甘油一步法制备丙酮酸（英文）

生物质能具有绿色环保、可再生、来源广泛和安全性高等优点,成为当前的研究热点.作为生物柴油的主要副产物甘油是一种重要的生物质平台化合物.甘油的高效利用,不仅能够获得重要的精细化学品及聚合物,也可以延长生物柴油的产业链,降低其生产成本,增加其市场竞争力.丙酮酸是一种弱有机酸,为生物体内葡萄糖分解代谢的中间产物,在生物能量代谢和物质代谢过程中起着重要的枢纽作用.同时,由于它同时含有羧基和酮羰基,具有很强的反应性,可参与多种化学反应,在化学工业中有广泛应用.目前,工业上主要采用酒石酸脱水脱羧法生产丙酮酸,丙酮酸收率可达50.55%,但生产过程需要消耗大量的KHSO4粉末,生产成本高,且高耗能高污染,不符合可持续发展的要求.因此,利用可再生资源甘油在温和条件下生产丙酮酸显现出良好的应用前景.目前,由甘油一步法获得丙酮酸仅可通过发酵法实现,但是其规模化生产存在效率低、废弃物污染等问题.因此,研究化学方法由甘油一步制备丙酮酸可行也十分必要.本课题组以Pt/AC或Cu-Pt/AC为催化剂进行甘油氧化制备乳酸的研究,所得产物中几乎未检出丙酮酸;当以Pb-Pt/C为催化剂进行乳酸脱氢氧化制备丙酮酸,可获得较高选择性的丙酮酸.因此,本文通过向Pt/AC催化剂中引入Pb助剂,以期调变甘油氧化的产物分布,从而获得相对高的丙酮酸选择性.通过浸渍-沉积沉淀法(Im-DP)制备了一系列不同Pb载量(1.7.0 wt%)的xPb-5Pt/AC-Im-DP催化剂,并采用不同方法制备了一系列5Pb-5Pt/AC催化剂,用于在温和条件下甘油选择性氧化制备丙酮酸反应中.结果表明,Pb载量和催化剂制备方法都对其催化活性有显著影响.当xPb-5Pt/AC-Im-DP催化剂中Pb载量为1%时,甘油转化率和丙酮酸选择性均较单金属5Pt/AC催化剂高,但当Pb载量继续升高至3%及以上时,甘油转化率明显下降.我们推测这与Pb3(CO3)2(OH)2物种的形成有关.采用该方法制备催化剂时,Pb载量宜为5.0 wt%.保持Pt和Pb载量均为5.0 wt%,采用共沉积沉淀(Co-DP)、共浸渍(Co-Im)、以及对催化剂进行500 oC氩气焙烧等,制备了具有Pb3(CO3)2(OH)2物种、铂铅合金物种(PtPb和PtxPb)和两物种均没有的5Pb-5Pt/AC催化剂.通过评价它们的催化性能,进一步探究了Pb3(CO3)2(OH)2物种、铂铅合金物种、表面金属价态与催化剂活性的关系.实验表明,Pb3(CO3)2(OH)2和表面Pb0物种不利于甘油的转化,铂铅合金对甘油转化有一定的促进作用,对丙酮酸生成显现出明显促进作用.通过对Co-DP、Im-DP催化剂进行500 oC氩气焙烧,能够除去Pb3(CO3)2(OH)2物种,同时形成铂铅合金.综上,本文在温和条件下,采用Pb-Pt/AC催化剂进行甘油选择性氧化制备丙酮酸反应.采用优化的方法制备的5Pb-5Pt/AC催化剂在90 oC条件下反应10 h,丙酮酸收率可达18.4%,这是目前甘油一步法氧化制备丙酮酸的最高值.进一步优化反应条件、催化剂组成与结构,探索反应机理仍十分必要     

通过三嗪荧光探针的多氢键作用识别胸腺嘧啶

发展新型光学受体分子, 研究其对核酸碱基的选择性识别不仅有助于了解生物体内分子作用和转化的机理, 同时对发展新的生物分子检测方法和研制新药等都具有重要意义. 然而, 由于核酸碱基的性质相近, 因此实现单一碱基的选择性识别较难[1]. 氢键是一种重要的分子间相互作用力, 在生物化学和分子药理学研究中, 尤其在生物大分子的三维结构中起着重要的作用[2,3].     

亚精胺诱导λ-DNA凝聚现象的AFM研究

生物体内DNA的紧密堆积存在方式与基因表达的自我调控机制有关 ,因此研究体内凝聚诱导物对DNA凝聚所起的作用具有重要意义 .采用原子力显微镜(AFM )研究了这一体系 .研究表明 :亚精胺可直接诱导λ DNA形成一种特殊的结构———环形凝聚体 ;环形凝聚体的形成受动力学因素 (时间 ,浓度 )影响较大 ;环形凝聚体由纳米级小颗粒紧密排列而成 ;凝聚机制可能是以这些颗粒为组成单元的螺旋盘绕过程 .所得结论对生物体内DNA凝聚过程的理论研究具有重要意义     

血红蛋白在纳米金修饰电极上的电化学研究

氧化还原蛋白在电极上的直接电化学研究不但能获得有关蛋白质和酶的热力学和动力学性质等重要信息,为开发新型生物传感器和生物反应器提供理论指导,而且对了解它们在生命体内的电子转移机理和生理作用机制具有重要意义。血红蛋白(Hb)是以血红素为辅基的蛋白质,在生物体中的主要     

固定在硬脂酸Langmuir-Blodgett膜中的辣根过氧化酶修饰电极的直接电化学行为

近年来,氧化还原蛋白质的直接电子转移反应引起了越来越多研究者的兴趣~([1]),研究氧化还原蛋白质的直接电子转移反应,不仅对于探索生命体内的生理作用机理等理论研究具有重要意义,而且为制备基于氧化还原蛋白质直接电化学行为的第三代生物传感器奠定了技术基础.本文研究了硬脂酸(SA)Langmuir-Blodgett(LB)膜固定的辣根过氧化物酶(HRP)在金电极(Au)上的直接电化学行为.     

类二十烷酸分析方法及应用的研究进展

类二十烷酸是一大类由二十碳多不饱和脂肪酸氧化产生的具有生物活性的不饱和脂肪酸,是重要的炎症因子,广泛存在于体液和组织中,调节体内众多生理和病理过程。类二十烷酸在生物体内种类众多,含量较低,并且存在大量同分异构体,因此生物体内类二十烷酸的分离和分析具有较大的挑战。本文对近5年来类二十烷酸的分析方法和其在生物样品分析中的应用进行归纳总结,重点介绍了不同分析方法的特点及其在生物样品分析中的最新进展,旨在为类二十烷酸的体内药物分析及应用研究提供参考。     

Application of high-performance liquid chromatography to the purification, disintegration and molecular mass determination of pyruvate dehydrogenase multi-enzyme complexes from different sources

The pyruvate dehydrogenase complex is associated with the inner mitochondrial membrane. A gentle and rapid purification procedure, especially for the very unstable pyruvate dehydrogenase complex from the extremely thermophilic organism Thermus aquaticus, is described. This procedure is based essentially on a combination of hydrophobic interaction and of adsorption chromatography by the rapid fast protein liquid chromatographic technique. Applying the same method, a relative molecular mass of 9.1 . 10(6) daltons was obtained by gel filtration on Superose 6 HR 10/30 for the pyruvate dehydrogenase complex from T. aquaticus. The same column served to resolve the pyruvate dehydrogenase complex into its enzyme components.     

The Pyruvate Dehydrogenase Multienzyme Complex

The three enzymes pyruvate dehydrogenase, dihydrolipoamide transacetylase, and dihydrolipoamide dehydrogenase constitute the pyruvate dehydrogenase multienzyme complex of E. coli; in mammals the complex also contains a kinase and a phosphatase. Multienzyme complexes are structural, functional, and regulatory units enabling the organism to operate more economically than with single enzymes. The pyruvate dehydrogenase multienzyme complex may stand at the switch-point between energy metabolism and gluconeogenesis.     

High throughput screening in agrochemical research

The demand for new herbicides, insecticides and fungicides led to a steady increase in the number of compounds being tested to find novel market products. To keep pace with the rising workload, high throughput screening (HTS) technologies have been introduced. In agrochemical research miniaturised in vivo tests on whole real target organisms are now possible and are an integral part of the screening cascade. A complementary target based in vitro HTS has also been established in agrochemical research. Target based HTS allows a directed approach towards untouched market shares by novel modes of action. Selection of the best suited targets is the most crucial issue in this approach. Genomic methods thereby deliver many essential genes as candidate targets. Consideration of further criteria such as druggability notably narrows down the number of promising targets. Though target to hit to lead progression still is as in pharmaceutical research a complex and therefore risky process, the implementation of novel bioscience technologies has entailed the transition to an integrated innovative agrochemical research perspective.     

Metabolic Inertia in Contracting Skeletal Muscle: The Expanding Role of the Carnitine Pool

The ability of the muscular carnitine pool to accept and temporally donate acetyl groups (from and towards the coenzyme A pool) is an important functional role of carnitine within biological systems that is often overlooked within the scientific literature. The present review will discuss recent research demonstrating the existence of a period of inadequate acetyl-CoA delivery towards the tricarboxylic acid cycle (the so-called ‘acetyl group deficit’), which occurs as a consequence of the impaired integration of cytosolic (glycolysis) and mitochondrial energy producing pathways at the onset of muscular contraction; due to a lag in the activation of the pyruvate dehydrogenase complex. During this period of inadequate acetyl-CoA delivery, acetyl groups can be sequestered from the limited muscular acetylcarnitine reserve in an attempt to sustain continued tricarboxylic acid cycle flux. Following on from this, the present review will highlight the metabolic and functional benefits to be gained by overcoming this period of metabolic inertia, through elevating the concentration of acetylcarnitine prior to physical exercise; in the presence and absence of pyruvate dehydrogenase complex activation and through appropriately timed ‘warm-up’ exercise.     

Metabolic Inertia in Contracting Skeletal Muscle: The Expanding Role of the Carnitine Pool

Summary. The ability of the muscular carnitine pool to accept and temporally donate acetyl groups (from and towards the coenzyme A pool) is an important functional role of carnitine within biological systems that is often overlooked within the scientific literature. The present review will discuss recent research demonstrating the existence of a period of inadequate acetyl-CoA delivery towards the tricarboxylic acid cycle (the so-called ‘acetyl group deficit’), which occurs as a consequence of the impaired integration of cytosolic (glycolysis) and mitochondrial energy producing pathways at the onset of muscular contraction; due to a lag in the activation of the pyruvate dehydrogenase complex. During this period of inadequate acetyl-CoA delivery, acetyl groups can be sequestered from the limited muscular acetylcarnitine reserve in an attempt to sustain continued tricarboxylic acid cycle flux. Following on from this, the present review will highlight the metabolic and functional benefits to be gained by overcoming this period of metabolic inertia, through elevating the concentration of acetylcarnitine prior to physical exercise; in the presence and absence of pyruvate dehydrogenase complex activation and through appropriately timed ‘warm-up’ exercise.     

Strecker reaction and α-amino nitriles: Recent advances in their chemistry,synthesis, and biological properties

α-Amino nitrile compounds have a profound impact on bio-chemical sciences, as they have been prepared from inexpensive starting materials and have become valuable intermediates in the chemical synthesis of vitally important heterocyclic and carbocyclic molecules, which serve as suitable models in pharmacological and biological research. The α-amino nitrile moiety has been found in the structure of different alkaloids, while the α-amidoacetonitrile group is an essential fragment of new anti-hyperglycemic drugs and promising pharmacological and agrochemical agents. Due to their synthetic, biological and practical importance, this review highlights the recent information about the preparation of α-amino nitriles through the Strecker-type and α-cyanation reactions, their chemical and biological properties, as well as their synthetic application, paying attention on the wonderful capacity for generating novel molecular diversity for pharmacological, biological and agrochemical researches, which ends with the total synthesis of complex alkaloids, preparation of new N-heterocycles and α-aminonitrile-containing drugs. Analyzing modern synthetic protocols for the Strecker-type reactions and cyanation reactions based on cross-dehydrogenative coupling (CDD) process, the advantages and disadvantages of new catalysts and green reaction conditions are also discussed. In addition, remarkable biological properties of α-amidoacetonitrile derivatives as potent and selective protease inhibitors as well as promising pesticidal agents were briefly reviewed. The bibliography includes 461 references.     

Inhibition by methylated organoarsenicals of the respiratory 2-oxo-acid dehydrogenases

Inorganic arsenic that is ingested through drinking water or inhalation is metabolized by biological methylation pathways into organoarsenical metabolites. It is now becoming understood that this metabolism that was formerly considered to be detoxification may contribute as much or more to increasing the toxicity of arsenic. One proposed mode of the toxic action of arsenic and its organoarsenic metabolites is through its binding to proteins and inactivating their enzymatic activity. The classic case has been considered the affinity of the proximal 1,3 sulfhydryl groups of the lipoic acid cofactor of the pyruvate dehydrogenase complex for arsenic. A 2:1 stoichiometry of sulfhydryl to arsenic groups has been measured in proteins and arsenical complexes can be synthesized using free d,l-lipoic acid. The relative importance of this site for arsenic binding has come in to question through the use of methylating bifunctional arsenic complexes, and the suggestion that arsenic inhibits the pyruvate dehydrogenase complex indirectly by elevating mitochondrial hydrogen peroxide generation. In order to separate the effects of direct trivalent arsenite toxicity from that of hydrogen peroxide and activated oxygen, we studied the inhibition of the PDH complex under conditions that did not generate hydrogen peroxide but did expose the lipoic acid group in its reduced state to arsenicals. We also studied the effects of arsenicals in the inhibition of the α-ketoglutarate dehydrogenase complex. We found that only trivalent arsenical compounds inhibited the activity of both dehydrogenase complexes and only when the lipoic acid was in its reduced form. Arsenite inhibited both enzyme complexes approximately equivalently while monomethylarsenite inhibited the PDH complex to a greater extent than the KGDH complex - although both complexes were very sensitive to inhibition by this complex. Dimethylarsenite inhibition of both complexes was only observed with longer pre-incubation periods. Cumulative inhibition by the reduced arsenical was observed for all complexes indicating a binding mode of inhibition that is dependent upon lipoic acid being in its reduced state.     

Applications of combinatorial chemistry in the agrosciences

During the past ten years combinatorial chemistry developed from a powerful synthetic methodology, providing large libraries of usually simple new chemical entities, to a comprehensive strategy presently covering a multitude of technologies across the whole workflow from hit generation to lead optimization. Thus combinatorial chemistry had a major impact not only on the pharmaceutical research but also with some delay on the agrochemical research. The agrochemical discovery environment is different from that of the pharmaceutical research in that it relies mainly on whole organism screenings. This review summarizes some recent applications of combinatorial chemistry in the agrosciences, covering all the three major fields of research: fungicides, herbicides, and insecticides. The article focuses on libraries with published biological activities and thus highlights some characteristic features of successful agrochemical libraries, which may be fundamentally different from pharmaceutical libraries.     

In Vivo Regulation of Alcohol Dehydrogenase and Lactate Dehydrogenase in <Emphasis Type="Italic">Rhizopus Oryzae</Emphasis> to Improve <Emphasis Type="SmallCaps">l</Emphasis>-Lactic Acid Fermentation

Rhizopus oryzae is becoming more important due to its ability to produce an optically pure l-lactic acid. However, fermentation by Rhizopus usually suffers from low yield because of production of ethanol as a byproduct. Limiting ethanol production in living immobilized R. oryzae by inhibition of alcohol dehydrogenase (ADH) was observed in shake flask fermentation. The effects of ADH inhibitors added into the medium on the regulation of ADH and lactate dehydrogenase (LDH) as well as the production of cell biomass, lactic acid, and ethanol were elucidated. 1,2-diazole and 2,2,2-trifluroethanol were found to be the effective inhibitors used in this study. The highest lactic acid yield of 0.47 g/g glucose was obtained when 0.01 mM 2,2,2-trifluoroethanol was present during the production phase of the pregrown R. oryzae. This represents about 38% increase in yield as compared with that from the simple glucose fermentation. Fungal metabolism was suppressed when iodoacetic acid, N-ethylmaleimide, 4,4′-dithiodipyridine, or 4-hydroxymercury benzoic acid were present. Dramatic increase in ADH and LDH activities but slight change in product yields might be explained by the inhibitors controlling enzyme activities at the pyruvate branch point. This showed that in living R. oryzae, the inhibitors regulated the flux through the related pathways.