分析化学的“昨天、今天和明天”

简述了分析化学的发展历史。分析化学的"昨天",从基于物理化学的溶液理论,以目视可见为工具的"化学分析",进入以物理方法为基础的仪器分析,因此有人提出"化学正在走出分析化学";分析化学的"今天",因为它的主体任务是解决物质的分子原子结构和成分,所以又回归化学领域;对分析化学的"明天"寄厚望,分析化学走出历来仅仅以"为他人报告提供数据"的技术支持者的角色,成为"实际问题解决者",利用分析化学中综合分析的"剖析技术",为新产品开发创制的"反工艺研究"做出独特的贡献。     

Novel α-Aminophosphonates and α-Aminophosphonic Acids: Synthesis,Molecular Docking and Evaluation of Antifungal Activity against Scedosporium Species

The Scedosporium genus is an emerging pathogen with worldwide prevalence and high mortality rates that gives multidrug resistance to antifungals; therefore, pharmacological alternatives must be sought for the treatment of diseases caused by this fungus. In the present project, six new α-aminophosphates were synthesized by the Kabachnik–Fields multicomponent reaction by vortex agitation, and six new monohydrolyzed α-aminophosphonic acids were synthesized by an alkaline hydrolysis reaction. Antifungal activity was evaluated using the agar diffusion method as an initial screening to determine the most active compound compared to voriconazole; then it was evaluated against 23 strains of the genus Scedosporium following the M38-A2 protocol from CLSI (activity range: 648.76–700 µg/mL). Results showed that compound 5f exhibited the highest antifungal activity according to the agar diffusion method (≤1 mg/mL). Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay and it was shown that compound 5f exhibits a lower toxicity in comparison to voriconazole at the same concentration (1000 µM). A docking study was conducted afterwards, showing that the possible mechanism of action of the compound is through the inhibition of allosteric 14-α-demethylase. Taking these results as a basis, 5f is presented as a compound with attractive properties for further studies.     

回归教育本源、以生发展为本、索行教学之道——结构化学课程教学研究与实践

努力将现代教育理念、理论、技术和方法融入到结构化学课程教学中。具体而言,就是将课程目标层次化、教学内容国际化、教学方法现代化、教学环境信息化、教学评价多元化、研究教学案例化等六"化"固化到结构化学课程教学的全过程中。通过长期的课程教学研究与实践,逐步构建并实施了一套适合结构化学课程的、以能力培养为导向的SC@O教学设计、过程与方法,探索践行以知识与技能的深度教学过程为载体,以培养学生LIC Thinking为核心的综合能力与STE@M素养的教学之道。     

Plant pathogen recognition as a natural, original and simple model for chemogenomics: a brief overview of cell-based assays to screen for peptides acting as plant defense activators

As plants lack a circulatory system and adaptive immune system, they have evolved their own defense systems distinct from animals, in which each plant cell is capable of defending itself from pathogens. Plants induce a number of defense responses, which are triggered by a variety of molecules derived from pathogenic microorganisms, referred to as microbe-associated molecular patterns (MAMPs), including peptides, proteins, lipopolysaccharide, beta-glucan, chitin, and ergosterol. The interaction between plants and chemicals in the context of plant defense represents a "natural" and simple model for chemogenomics, at the intersection between chemical and biological diversities. For protection of crop plants from diseases, it has been shown to be effective to stimulate the plant immunity by chemical compounds, the so-called "plant defense activators". Combinatorial chemistry techniques can be applied to the search for novel plant defense activators, but it is essential to establish an efficient and reliable screening system suitable for library screening. For studies of the plant immune system, it is difficult to use isolated proteins as biological targets because the receptors for MAMP recognition are largely unknown and even the receptors identified so far are transmembrane proteins. Therefore, screening for novel peptides acting on MAMP receptors from combinatorial libraries must rely on a solution-phase assay using cells as the biological targets. In this review, we introduce the cell-based lawn format assay for identification of peptides acting as plant defense activators from combinatorial peptide libraries. The requirements and limitations in constructing the screening system using combinatorial libraries in the studies of plant sciences are also discussed.     

Dramatic reduction of IR vibrational cross sections of molecules encapsulated in carbon nanotubes

Combined temperature-programmed desorption and IR studies suggest that absorption cross sections of IR-active vibrations of molecules "strongly" bound to single-wall carbon nanotubes (SWCNTs) are reduced at least by a factor of 10. Quantum chemical simulations show that IR intensities of endohedrally encapsulated molecules are dramatically reduced, and identify dielectric screening by highly polarizable SWCNT sidewalls as the origin of such "screening". The observed intensity reduction originates from a sizable cancellation of adsorbate dipole moments by mirror charges dynamically induced on the nanotube sidewalls. For exohedrally adsorbed molecules, the dielectric screening is found to be orientation-dependent with a smaller magnitude for adsorption in groove and interstitial sites. The presented results clearly demonstrate and quantify the screening effect of SWCNTs and unequivocally show that IR spectroscopy cannot be applied in a straightforward manner to the study of peapod systems.     

Impact of novel screening technologies on ion channel drug discovery

Ion channels are a large superfamily of membrane proteins that pass ions across membranes. They are critical to diverse physiological functions in both excitable and nonexcitable cells and underlie many diseases. As a result, they are an important target class which is proven to be highly "druggable". However, for high throughput screening (HTS), ion channels are historically difficult as a target class due to their unique molecular properties and the limitations of assay technologies that are HTS-amendable. In this article, we describe the background of ion channels and current status and challenges for ion channel drug discovery, followed by an overview of both conventional and newly emerged ion channel screening technologies. The critical impact of such new technologies on current and future ion channel drug discovery is also discussed.     

发现化学之美感悟科学魅力

本文指出化学教学的关键,在于引导学生发现化学之美,感悟科学魅力,激发学生的学习兴趣及创造潜能。全文阐述了化学的外在美、揭示了化学的内在美———化学学科思想 (科学之美 )、崇尚化学家的人生之美及化学教师的人格之美。作者认为：化学教师的人格之美源自“以学生发展为本”的教育理念和对学生及化学教育事业的挚爱。本文旨在倡导广大教师更新教育观念,增强自身素质,升华崇高人格,真正实现化学教学中“教师快乐教学,学生享受学习”。     

"Black swan events" in organic synthesis

When a research area "goes viral", the event typically occurs in conjunction with a major change in "conventional wisdom". In retrospect, the literature often contains earlier hints that the original judgment was not correct. These antecedents are referred to as "Black Swan" events. The picture shows research on homogeneous gold catalysis "going viral".     

混合教学模式在有机化学课程教学中的应用

针对目前高职院校有机化学教学中面临的难题,本文以"羧酸"教学为例,探讨了混合教学模式在有机化学教学中的应用,采用在线学习和课堂教学相结合的方式实施翻转课堂教学,使课堂教学模式由"以教为主"转变为"以学为主",同时根据高职院校学生的特点,采用问题式学习任务单的方式和组长负责制的分组学习模式。实践证明,教学效果良好。     

Textural characteristics, surface chemistry and oxidation of activated carbon

Numerous researches were reviewed and interpreted to depict a comprehensive illustration of activated carbon and its behavior towards oxidation. Activated carbon as one of the most important adsorbents is tried to be described in this review paper by terms of its "Textural Characteristics" and "Surface Chemistry". These two terms, coupled with each other, are responsible for behavior of activated carbon in adsorption processes and in catalytic applications. Although as-prepared activated carbons are usually non-selective and their surfaces suffer from lack of enough reactive groups, their different aspects may be improved and developed by diverse types of modifications. Oxidation is one of the most conventional modifications used for activated carbons. It may be used as a final modification or as a pre-modification followed by further treatment. In this paper, methods of oxidation of activated carbon and other graphene-layer carbon materials are introduced and wet oxidation as an extensively-used category of oxidation is discussed in more detail.     

跨学科项目教学案例*——魔力沙

以魔术表演用的沙子为素材,开发了适用于高中选修课程“发展中的化学学科”的具有跨学科性的项目教学案例,该项目弱化理论分析环节后也可以用于初中科学实践活动课程。项目引导学生在更宽广的学科背景下认识物质及其变化的规律,帮助学生拓展视野和思路,综合运用化学、物理等学科的知识分析解决有关问题,发展“宏观辨识与微观探析”“科学探究与创新意识”“科学态度与社会责任”等化学学科核心素养。     

Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and liquid chromatography/atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discovery

This report addresses the continuing need for increased throughput in the evaluation of new chemical entities (NCEs) in terms of their pharmacokinetic (PK) parameters by describing an alternative procedure for increasing the throughput of the in vivo screening of NCEs in the oral rat PK model. The new approach is called "cassette-accelerated rapid rat screen" (CARRS). In this assay, NCEs are dosed individually (n = 2 rats/compound) in batches of six compounds per set. The assay makes use of a semi-automated protein precipitation procedure for sample preparation in a 96-well plate format. The liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/API-MS/MS) assay is also streamlined by analyzing the samples as "cassettes of six". Using this new approach, a threefold increase in throughput was achieved over the previously reported "rapid rat screen".     

A pseudo-ligand approach to virtual screening

A virtual screening method is presented that is grounded on a receptor-derived pharmacophore model termed "virtual ligand" or "pseudo-ligand". The model represents an idealized constellation of potential ligand sites that interact with residues of the binding pocket. For rapid virtual screening of compound libraries the potential pharmacophore points of the virtual ligand are encoded as an alignment-free correlation vector, avoiding spatial alignment of pharmacophore features between the pharmacophore query (i.e., the virtual ligand) and the candidate molecule. The method was successfully applied to retrieving factor Xa inhibitors from a Ugi three-component combinatorial library, and yielded high enrichment of actives in a retrospective search for cyclooxygenase-2 (COX-2) inhibitors. The approach provides a concept for "de-orphanizing" potential drug targets and identifying ligands for hitherto unexplored or allosteric binding pockets.     

2002年有机化学闪光点

介绍了全球有机化学领域在2002年所取得的重大进展,包括“在钯膜上实现由 苯到苯酚的直接转化”等13个闪光点。     

Is Universal,Simple Melting Point Prediction Possible?

An investigation of the melting points of 520 organic 1:1 salts is presented with the aim of developing a universal, simple, physically well-founded prediction scheme. The general reliability and reproducibility of the recorded experimental data are discussed with respect to purity, phase behavior, disorder and thermal history of a given substance. Additionally, mistakes, systematic errors, or lack of conventions can lead to considerable differences in the experimental measurements. A rough error bar for the reproducibility of the melting points of organic salts of ±5 to ±15 °C can be assigned. With this restraint, we developed two simple, semiempirical, five- and nine-parameter schemes with easy-to-calculate quantities. With these, we could predict the melting temperature of a given organic salt in the temperature range of -25 to +300 °C with an average error of 33.5 °C and a relative error of 9.3%. All calculated quantities are assessed with the help of conventional DFT, COSMO and COSMO-RS calculations, and are currently implemented into the IL-Prop module of the upcoming version of COSMOtherm. These prediction schemes are suitable for high-throughput computational screening of substances in the context of "computer-aided synthesis". Therefore, they are valuable tools to find a compound with a suitable melting point before its first synthesis.     

Helicate extension as a route to molecular wires

We describe the preparation of a helicate containing four closely spaced, linearly arrayed copper(I) ions. This product may be prepared either directly by mixing copper(I) with a set of precursor amine and aldehyde subcomponents, or indirectly through the dimerization of a dicopper(I) helicate upon addition of 1,2-phenylenediamine. A notable feature of this helicate is that its length is not limited by the lengths of its precursor subcomponents: each of the two ligands wrapped around the four copper(I) centers contains one diamine, two dialdehyde, and two monoamine residues. This work thus paves the way for the preparation of longer oligo- and polymeric structures. DFT calculations and electrochemical measurements indicate a high degree of electronic delocalization among the metal ions forming the cores of the structures described herein, which may therefore be described as "molecular wires".     

Enantioselective enzymes for organic synthesis created by directed evolution

A new concept for the creation of enzymes displaying improved enantioselectivity in a given reaction is described; it is based on "evolution in the test tube". Accordingly, proper molecular biological methods for random mutagenesis, gene expression, and high-throughput screening systems for the rapid assay of enantioselectivity are combined. Several rounds of mutagenesis and screening are generally necessary in order to create mutant enzymes that show high degrees of enantioselectivity, as in the case of the lipase-catalyzed hydrolytic kinetic resolution of a chiral ester in which the original enantioselectivity of 2 % ee (E = 1) increases to > 90% ee (E = 25).     

中学化学建构主义课堂环境量表的编制与应用研究

基于弗雷泽建构主义课堂环境理论构架,采用量化研究与质化研究相结合的方法,编制了中学化学建构主义课堂环境量表(SCCLES),并运用SCCLES测量了625名中学生对建构主义化学课堂环境的感知状况。研究结果表明:SCCLES具有良好的效度和信度,是较为经济、实用、有效的过程性课堂评价工具;中学化学课堂环境存在“传统型”“中间型”和“建构型”等3种类型;不同课堂环境类型的学生在“学生声音”“个人相关”“合作”“任务取向”等维度的感知存在显著差异。     

金(Ⅰ)化合物中的亲金相互作用

In the 1980s, interaction between gold atoms in gold (Ⅰ) species was discovered, which is afterwards named "aurophilicity". Based on in-depth researches conducted on these compounds, chemists are able to explain the reason for formation, the interacting mechanism and the theoretical foundation of them. This article reviews on the discovery of "aurophilicity", its historical development with typical examples, and its fresh applications in branches of physics and chemistry.     

Drug-like index: a new approach to measure drug-like compounds and their diversity

Combinatorial organic synthesis (combinatorial chemistry or CC) and ultrahigh-throughput screening (UHTS) are speeding up drug discovery by increasing capacity for making and screening large numbers of compounds. However, a key problem is to select the smaller set of "representative" compounds from a virtual library to make or screen. Our approach is to select drug-like as well as structurally diverse compounds. The compounds, which are not very drug-like, are less taken into account or excluded even if they contribute to the diversity of the collection. Hence, the first step in the compound selection is to rank compounds in drug-like "degree". To quantify the drug-like "degree", drug-like index (DLI) is introduced in this paper. A compound's DLI is calculated based upon the knowledge derived from known drugs selected from Comprehensive Medicinal Chemistry (CMC) database. The paper describes the way of this knowledge base is formed and the procedure for selecting drug-like compounds.