微波辅助组合合成的研究进展

微波辅助组合合成技术是近年来发展起来的一种新的制备化合物库的组合化学技术, 它不仅可以克服传统固相组合合成技术以及液相组合合成技术无法提高产物收率的不足, 而且利用该技术所制得的化合物库中对应的是高纯度的单一化合物, 采用高通量筛选技术可以快速直接地确定高活性结构, 极大地提高了新药开发的效率. 主要就近年来微波辅助组合合成技术的研究进展情况进行介绍, 内容包括固相组合合成、基于聚合物支载的催化剂的组合合成、液相组合合成、氟相组合合成以及组合平行合成等.     

固态组合化学及其在材料科学中的应用

概述了固态组合化学的概念及其在新材料开发中的应用 ,着重阐述了材料化合物薄膜库的组合制备方法和筛选技术的特点 ,简述了固态组合化学技术在超导、巨磁阻、磷光、催化剂、沸石等新材料开发中的应用以及固态组合化学现有技术中的困难和今后的发展方向     

天然产物衍生物化学库的组合合成

天然产物在药物化学和化学生物学中发挥着重要作用。目前,组合化学技术在合成天然产物衍生物化学库中的应用也越来越受到重视。本文综述了近5年来报道的组合合成天然产物衍生物化学库的一些例子。     

化合物库的组合技巧和组合合成

从化合物库的组合技巧和组合合成方法两个方面探讨了组合化学及其在药物开发中的应用。     

颜色指示法高通量筛选多相催化材料

介绍一种简单的组合化学技术, 用来筛选或优化多相催化反应中的催化剂. 在酯化反应中, 用甲基橙指示剂指示酯化反应的进程并对沸石的类型, 不同碳链的醇和酸的催化活性进行研究. 在光催化反应中, 选择甲基橙、罗丹明B作为反应物. 通过颜色变化, 对不同方法制备的TiO2进行高通量筛选.     

基于结构的组合库设计策略在新药创制中的应用

合理设计一些容量小的、针对特定靶标的化合物库(称为集中库,focused library),是当前组合库设计中的热点。当靶标的三维结构可以通过X射线衍射或NMR等手段确定后,人们就能采用几种不同的策略来进行组合库的设计。本文讨论了在靶标结合位点的约束下,进行组合库设计的主要方法及程序,同时强调了它们的优点与不足。通过这些方法的成功应用实例,显示了它们在新药创制中的广泛应用前景。     

动态组合化学最新进展*

动态组合化学是组合化学的一个新兴分支,在药物先导化合物的发现中有广阔的应用前景。在动态组合化学库中,利用靶标分子的诱导结合作用,通过可逆共价反应,能够选择性的筛选到与靶标分子存在强相互作用的优势化合物。本文按照动态组合化学方法简介、动态组合化学中的可逆共价化学、动态组合化学库的分类、动态组合化学库筛选方法的研究进展及动态组合化学在药物先导化合物发现过程中的应用等5个方面对动态组合化学进行了概述。     

催化不对称反应最新进展(Ⅱ)－组合化学方法之 应用

组合化学技术已经成为药物、新型固体材料和催化剂合成、评价和筛选的一种有力工具,最近它在催化不对称反应的手性催化剂高效率合成与筛选方面的应用也受到了重视,本文将综述组合化学技术在发展不对称合成新型催化剂方面的应用。第一部分主要介绍手性催化剂(或配体)库的固相平行合成;第二部分重点总结了所建立的手性催化剂库的高效率评价技术及其应用。     

吸附量热技术和多相催化微观动力学

本文介绍了多相催化研究中的吸附量热技术、多相催化微观动力学及其计算机模拟, 以及吸附量热技术在定量表征固体催化剂表面中心和在多相催化微观动力学分析中的重要作用。     

组合化学—一种新兴的化学领域

介绍了组合化学的起源，定义和组合库构建和鉴别方法。综述了组合化学的研究进展，并对其发展方向作一展望。     

Efficient Assays for Combinatorial Methods for the Discovery of Catalysts

The revolutionary developments in combinatorial approaches to pharmaceutical science are now being explored in such diverse areas as materials design and homogeneous and heterogeneous catalysis. The quest for more efficient and selective catalysts has created the desire to design parallel assays for catalytic activity in combinatorial studies. This contribution highlights some of the recent exciting developments in this area.     

The Application of Combinatorial Chemistry in Catalysis

In recent few years combinatorial methodology has been extensively used in material science research. Based on the desired properties of materials, various high throughput synthesizing and screening technologies were developed. These high throughput technologies can increase our speed to more than hundred folds for finding and optimizing materials. One of the most active areas is catalysis. Scientists are developing novel high throughput technologies to screen catalyst libraries to find and optimize new catalysts for chemical industry. In this area die key is combinatorial catalytic reactor design, catalyst library synthesis, and product detection. Systematic technologies for catalyst library synthesis and characterization were developed in our laboratory. In this work, catalyst in situ synthesis, parallel reactor design, and detection methods will be introduced. Combining with the powerful combinatorial methodology, good chemistry design will make our work even more efficient. Hence, as an example of combining combinatorial technologies with chemistry design, a successful catalyst design is also introduced.     

Combinatorial Chemistry in Heterogeneous Catalysis: A New Scientific Approach or “the King's New Clothes”?

The spectacular success in materials science of the application of combinatorial chemistry has raised the hope that it may eventually lead to a new scientific approach to catalyst development. This method is, within the constraints of heterogeneous catalysis, merely a potentially efficient tool to be used in rational catalyst development and should not be considered an independent novel strategy towards rational catalyst design.     

Combinatorial synthesis of bimetallic complexes with three halogeno bridges

Methods for the synthesis of bimetallic complexes in which two different metal fragments are connected by three chloro or bromo bridges are reported. The reactions are general, fast, and give rise to structurally defined products in quantitative yields. Therefore, they are ideally suited for generating a library of homo- and heterobimetallic complexes in a combinatorial fashion. This is of special interest for applications in homogeneous catalysis. Selected members of this library were synthesized and comprehensively characterized; single-crystal X-ray analyses were performed for 15 new bimetallic compounds.     

Screening of a combinatorial library reveals peptide-based catalysts for phosphorester cleavage in water

A combinatorial library of 625 octapeptides was screened for their efficiency to catalyze phosphorester cleavage in water. Octapeptides such as 1c, which contains a catalytically active histidine and two cationic residues (Gua) as potential anion-binding sites, show substrate hydrolysis in water. Metal-free catalysis with a rate enhancement of up to a factor of 175 over the uncatalyzed background reaction is observed.     

Detection of Catalytic Activity in Combinatorial Libraries of Heterogeneous Catalysts by IR Thermography

Only about 200 μg of catalyst are required to identify the catalytically active materials on a combinatorial library of heterogeneous catalysts by IR thermography. The procedure is highly sensitive, and temperature differences arising from catalytic activity of hydrogenations and oxidations have been reliably detected down to 0.1 K.     

A general method for designing combinatorial peptide libraries decodable by amino acid analysis

Herein we describe an algorithm for designing combinatorial peptide libraries for split-and-mix synthesis on solid support that are decodable by amino acid analysis (AAA) of the beads. AAA is a standard service analysis available in most biochemical laboratories, and it allows one to control the quality of the peptide on each bead, an important feature that is missing from most library decoding protocols. In the algorithm, each AA is assigned to two variable positions in the sequence grouped in a "unique pair". This arrangement limits sequence design because both the number of unique pairs U (setting the maximum number of variable AA) and the maximum number S of different AA per variable position depend on the peptide length N (U=N(N-1)/2), S=N-1). The method is therefore only suitable for focused libraries. An application example is shown for the selection of peptides with N-terminal proline or hydroxyproline catalyzing an aldol reaction from a combinatorial library of 65536 octapeptides. A simple enumeration program is available to help design combinatorial libraries decodable by amino acid analysis. The method applies to linear and cyclic peptides, can be used for nonnatural building blocks, including beta-amino acids, and should help to explore the vast chemistry of linear and cyclic peptide for catalysis and bioactivity.     

超分子双膦配体的构筑及应用研究进展

超分子双膦配体是一类新兴起的基于非共价键作用构筑的双膦配体,近年来引起人们的重视.与传统的共价键连接的双膦配体相比,利用非共价相互作用的可逆性和选择性,超分子双膦配体具有合成简便,组合灵活,易于合成超分子配体库,并利用组合化学的方法对催化体系进行优化和筛选等优点.详细综述了近几年发展的基于氢键、配位键、主客体作用和静电作用等弱相互作用的超分子双膦配体,重点讨论了它们的构建方法以及在不对称催化反应中的应用,并对其发展前景进行了展望.     

How hard is mechanism elucidation in catalysis? Combinatorial analysis of C1 chemistry

Most chemical reactions occur over multiple steps whose identity is elucidated by experiment, yielding a reaction mechanism. Knowledge of cognitive science suggests that mechanism elucidation can be viewed as a knowledge-guided search within a combinatorial space. The MECHEM computer program searches this space comprehensively for the simplest plausible mechanisms. We use MECHEM to find mechanisms for Fischer-Tropsch chemistry and CO2 re-forming of methane, both heterogeneous catalytic reactions of current importance. The results reveal hundreds of equally simple mechanisms consistent with evidence. Hence, mechanism elucidation in catalysis is a much harder problem than is ordinarily realized.     

Affinity Capillary Electrophoresis: From Binding Measurement to Combinatorial Library Screening

Affinity capillary electrophoresis is a new procedure for receptor-ligand binding studies. Since its introduction in the early 1990s, this method has proved valuable in chiral separation of racemates, the measurement of binding constants, the estimation of kinetic rate constants, the determination of stoichiometries, the investigation of electrostatic interactions, the estimation of effective charges and molecular weights of biomolecules, the characterization of enzymatic catalysis, and, most recently, combinatorial library screening in solutions. This technique demands small amounts of samples, involves no radiolabeled materials or chemically immobilized ligands, and does not require changes in spectroscopic characteristics upon binding. This paper reviews the most recent applications of affinity capillary electrophoresis in binding measurement and combinatorial library screening.