High-throughput investigation and characterization of cobalt carboxy phosphonates

High-throughput methods have been employed to study the system Co(2+)/(H(2)O(3)PCH(2))(2)NCH(2)C(6)H(4)COOH/NaOH in detail. The use of the phosphonocarboxylic acid (H(2)O(3)PCH(2))(2)NCH(2)C(6)H(4)COOH has led to several new cobalt carboxyaryl phosphonates under hydrothermal conditions. In addition to the effect of the pH of the starting mixture, the influence of the counterions of the cobalt salts on the product formation was investigated. Thus, reaction trends as well as fields of formation could be identified. Four new compounds Co(2)[(O(3)PCH(2))(2)NCH(2)C(6)H(4)COOH].H(2)O (1), Co[(O(3)PCH(2))(OCH)NCH(2)C(6)H(4)COOH].H(2)O (2), Co[H(2)(O(3)PCH(2))(2)NCH(2)C(6)H(4)COOH] (3), and [Co(2)(O(3)PCH(2))(2)NCH(2)C(6)H(4)COOH].3.5H(2)O (4) were obtained, and compounds 1 and 2 could be isolated as single crystals suitable for single-crystal X-ray diffraction. The counterions of the cobalt salts have an influence on the structure of the resulting compounds. This is due to the effect on the initial pH as well as the possibility of the counterions to take part in redox reactions. Compounds 1 and 4 are formed under more basic conditions, and the phosphonic acid group is fully deprotonated. The structure of 1 is a rare example of the family of inorganic-organic hybrid materials with iminobis(methylphosphonic acid) units wherein the nitrogen coordinates to the metal center. Compound 2 is the result of an in situ oxidation of one of the P-C bonds; the organic building unit is stabilized by complexation of the cobalt ion. On the basis of spectroscopic, thermogravimetric, elemental chemical analysis, and EDX-analysis data, compound 3 has been characterized as Co[H(2)(O(3)PCH(2))(2)NCH(2)C(6)H(4)COOH] and compound 4 as [Co(2)(O(3)PCH(2))(2)NCH(2)C(6)H(4)COOH].3.5H(2)O. X-ray powder diffraction and IR-spectroscopic studies show that thermal treatment of 4 leads to the title compound 1. This transformation is accompanied by a change of color from pink to deep blue.     

High-throughput synthesis and characterization of bulk ceramics from dry powders

A high-throughput experimental (HTE) setup using conventional powders as raw materials was developed to synthesize and characterize ceramic bulk samples avoiding the customary liquid- or vapor-phase synthesis routes. Its functionality was verified using the well-known binary material system ZrO2-Y2O3. Libraries of 0.5 mol % yttria resolution were prepared using varying boundary systems as well as a number of liquid mixing aids. Automated powder X-ray diffraction (XRD) was applied to check the monoclinic phase content retained after heat-treatment on various positions for each sample. This phase information was used for comparison with a reference library comprising conventionally prepared samples by means of a regression analysis and mean deviation of monoclinic phase percentage. Out of the eight HTE libraries, three showed a significant comparability to the reference library.     

High-throughput parallel reactor system for propylene oxidation catalyst investigation

A high-throughput reactor system was designed for catalyst testing, which includes two important sections: the gas flow splitters and the parallel reactor. Each gas flow splitter could split one gas stream to 64 streams (8 x 8). The current system has two gas splitters that could feed two kinds of gases (from mass flow controllers) to a 64-channel (8 x 8) parallel fixed-bed reactor. The reactor is composed of tube connectors, a reactor tube array, a heating block, a product collector, and a temperature controller. The reactor system could test 64 catalysts simultaneously and give results, which are comparable with a regular single-channel microreactor. For the purpose of verifying the validity of the reactor system, propylene oxidation to prepare acrolein was used as the probing reaction. In order to analyze the reaction products, a high-throughput colorimetric diffusion-reflection imaging method was developed for the analysis of acrolein. By comparing the results from colorimetric diffusion-reflection imaging analysis with that from the traditional gas chromatography spectrometer with thermal conductivity detectors, a colorimetric diffusion-reflection imaging method was confirmed to be reliable and accurate in acrolein analysis.     

High-throughput binding characterization of RNA aptamer selections using a microplate-based multiplex microcolumn device

We describe a versatile 96-well microplate-based device that utilizes affinity microcolumn chromatography to complement downstream plate-based processing in aptamer selections. This device is reconfigurable and is able to operate in serial and/or parallel mode with up to 96 microcolumns. We demonstrate the utility of this device by simultaneously performing characterizations of target binding using five RNA aptamers and a random library. This was accomplished through 96 total selection tests. Three sets of selections tested the effects of target concentration on aptamer binding compared to the random RNA library using aptamers to the proteins green fluorescent protein (GFP), human heat shock factor 1 (hHSF1), and negative elongation factor E (NELF-E). For all three targets, we found significant effects consistent with steric hindrance with optimum enrichments at predictable target concentrations. In a fourth selection set, we tested the partitioning efficiency and binding specificity of our three proteins’ aptamers, as well as two suspected background binding sequences, to eight targets running serially. The targets included an empty microcolumn, three affinity resins, three specific proteins, and a non-specific protein control. The aptamers showed significant enrichments only on their intended targets. Specifically, the hHSF1 and NELF-E aptamers enriched over 200-fold on their protein targets, and the GFP aptamer enriched 750-fold. By utilizing our device’s plate-based format with other complementary plate-based systems for all downstream biochemical processes and analysis, high-throughput selections, characterizations, and optimization were performed to significantly reduce the time and cost for completing large-scale aptamer selections.

Structure characterization and spectroscopic investigation of ciprofloxacin drug

Ciprofloxacin (CPF, C₁₇H₁₈FN₃O₃) drug is used in the treatment of some bacterial infectious diseases. The drug was investigated using thermal analysis (TA) measurements (TG/DTG) and electron impact mass spectral (EI-MS) fragmentation at 70 eV techniques. Furthermore, the drug was characterized and investigated by other spectroscopic tools as IR, UV–Vis, ¹H-, and ¹³C-NMR. Semi-empirical MO calculation using PM3 procedure has been carried out on neutral molecule and positively charged species. The calculations included, bond length, bond order, bond strain, partial charge distribution, ionization energy, and heat of formation (ΔH _f). The PM3 procedure provides a basis for fine distinction among sites of initial bond cleavage, which is crucial to the rationalization of subsequent fragmentation of the molecule. The mass spectra and thermal analysis fragmentation pathways were proposed and compared to each other to select the most suitable scheme representing the correct fragmentation of this drug. From EI-MS, the main primary cleavage site of the charged molecule is that due to C–COOH bond cleavage with H-rearrangement to skeleton and CO₂ loss which can further decompose by piperazine loss. Thermal analysis of the neutral form of the drug reveals the high response of the drug to the temperature variation with very fast rate. Thermal decomposition has carried out in several sequential steps in the temperature range 40–650 °C. The initial thermal decomposition is similar to that obtained by mass spectrometric fragmentation (C–COOH fragment) but differ in that a rearrangement occurs by OH and CO loss. Therefore, comparison between MS and TA helps in selection the proper pathway representing the fragmentation of this drug. This comparison successfully confirmed by MO calculation. Finally, the effect of fluorine atom on the stability of the drug was discussed.     

Synthesis,characterization and vibrational investigation of divinylborinic anhydride

The new molecule divinylborinic anhydride [(CH₂CH)₂B]₂O as been prepared by the limited hydrolysis of divinylchloroborane. Characterization of the compound has included the preparation of 1 : 1 adducts with trimethylphosphine, dimethylphosphine and trimethylamine. Born-11 and carbon-13 NMR spectra have been obtained and have been interpreted in terms of mesomeric interactions between the empty boron pπ orbital and unshared pairs of electrons on oxygen as well as the pi electron system of the vinyl moiety. The Raman spectra (3500–200 cm^-1) of liquid and solid [(C₂H₃)₂B]₂O and the infrared spectra (3500–200 cm^-1) of gaseous and solid [(C₂H₃)₂B]₂O ¹ have been investigated for both the ¹⁶O and ¹⁸O isotopic species. The vibrational data indicate that the molecule possesses C₁ symmetry and a linear BOB angle.     

High-throughput characterization for organic pollutants in environmental waters using a capillary electrophoresis chip.

To evaluate organic pollution in water, we did preliminarily studies on high-throughput characterization of organic pollution in water using microchip-based capillary electrophoresis (CE) with laseer-induced fluorescence (LIF) detection. The applied voltage was investigated to control the gated valve injection and CE separation for conventional cross type microchips using a self-made personal computer (PC)-based controller as the voltage supply. We obtained high-throughput data for the reproducible separation of fluorescein isothiocyanate (FITC)-labeled river-water samples using a zwitter-ion based buffer solution to avoid adsorption of the labeled sample onto the channel of a microchip made from quartz glass. We used real samples from the Hino River that flows into Lake Biwa, from ten sampling points and obtained several reproducible peaks in different separation patterns for each sample within 2 min. We successfully demonstrated high-throughput characterization of dissolved organic carbon (DOC) in environmental water using the microchip.     

噻吩-2-甲醛缩L-半胱氨酸席夫碱的合成、晶体结构及量子化学研究

采用噻吩-2-甲醛分别与邻氨基苯硫酚和硫代氨基脲合成了2种噻吩-2-甲醛杂环席夫碱.利用红外光谱、紫外-可见光谱、荧光光谱、X-射线单晶衍射分析、热重分析和核磁共振氢谱等检测方法对2种目标新型杂环类席夫碱产物的结构和性质进行了表征与分析.采用量子化学中常用的密度泛函方法(DFT)对2种新席夫碱化合物进行几何优化,采用单激发组态相互作用(CIS)和含时密度泛函方法(TD-DFT)进一步优化,比较计算光谱与实际测试光谱之间的误差,探究了2种席夫碱化合物荧光发光机制,为这类席夫碱分子结构设计提供了理论依据.     

淫羊藿多糖的分子特征及免疫活性研究

用超声复合酶提取、离子交换凝胶分离、分子筛凝胶纯化得到3个淫羊藿叶多糖组分(EPs-1,EPs-2和EPs-3).3个多糖组分的分子特征通过气相色谱、高效凝胶渗透色谱进行了表征,并采用体外淋巴细胞增殖和巨噬细胞吞噬活性实验对多糖的免疫活性进行了评价.3个多糖组分EPs-1,EPs-2和EPs-3的总糖含量分别为90.36%,94.51%和89.19%.EPs-1,EPs-2和EPs-3主要由半乳糖醛酸(GalA)、半乳糖(Gal)、鼠李糖(Rha)、木糖(Xyl)、阿拉伯糖(Ara)和甘露糖(Man)组成,其平均相对分子质量分别为81.64×10~3,60.53×10~3,21.85×103;3个多糖都能够促进脾淋巴细胞增殖和激活巨噬细胞活性.这些结果说明淫羊藿多糖可以作为天然的免疫活性调节剂应用于医药和功能食品.     

High-throughput synthesis and screening of hydrogen-storage alloys

Libraries of mixed-metal hydride materials are synthesized on a silicon microfabricated array of "hot-plate" MEMS devices, which allow high-throughput screening using temperature programmed desorption and infrared thermography. The heating plate of the MEMS device is a membrane with low heat capacity, allowing fast and localized temperature control and the extraction of calorimetric data from thermography. The combination of the synthetic method and screening chip allows a fast determination of the desorption temperature and hydrogen content of the materials. Mixed metal hydrides are synthesized directly. The potential of the method is exemplified by presenting results for the sorption properties of Mg xNi 1- x hydride thin-film materials. The results are consistent with the literature, showing the highest hydrogen capacity and desorption temperature for the MgH 2 phase in Mg-rich compositions and the promotion of a lower temperature desorption from the Mg 2NiH 4 phase, with a concomitant reduction in hydrogen capacity.     

High-throughput purification of single compounds and libraries

The need for increasing productivity in medicinal chemistry and associated improvements in automated synthesis technologies for compound library production during the past few years have resulted in a major challenge for compound purification technology and its organization. To meet this challenge, we have recently set up three full-service chromatography units with the aid of in-house engineers, different HPLC suppliers, and several companies specializing in custom laboratory automation technologies. Our goal was to combine high-throughput purification with the high attention to detail which would be afforded by a dedicated purification service. The resulting final purification laboratory can purify up to 1000 compounds/week in amounts ranging from 5 to 300 mg, whereas the two service intermediate purification units take 100 samples per week from 0.3 to 100 g. The technologies consist of normal-phase and reversed-phase chromatography, robotic fraction pooling and reformatting, a bottling system, an automated external solvent supply and removal system, and a customized, high-capacity freeze-dryer. All work processes are linked by an electronic sample registration and tracking system.     

Synthesis, characterization and antimicrobial investigation of some moxifloxacin metal complexes

The new complexes of moxifloxacin (MOX), with Ti(IV), Y(III), Pd(II) and Ce(IV) have been synthesized. These complexes were then characterized by melting point, magnetic studies and spectroscopic techniques involving infrared spectra (IR), UV-Vis, (1)H NMR. C, H, N and halogen elemental analysis and thermal behavior of complexes also investigated. The results suggested that the molar ratio for all complexes is M: MOX=1:2 where moxifloxacin acts as a bidentate via one of the oxygen atoms of the carboxylate group and through the ring carbonyl group and the complexes have the following formula [Ti(MOX)(2)](SO(4))(2)·7H(2)O, [Y(MOX)(2)Cl(2)]Cl·12H(2)O, [Pd(MOX)(2)(H(2)O)(2)]Cl(2)·6H(2)O and [Ce(MOX)(2)](SO(4))(2)·2H(2)O. The activation energies, E*, enthalpies, ΔH*, entropies, ΔS* and Gibbs free energies, ΔG*, of the thermal decomposition reactions have been derived from thermogravimetric (TGA) and differential thermogravimetric (DrTG) curves, using Coats-Redfern (CR) and Horowitz-Metzger (HM) methods. The antimicrobial activity of these complexes has been evaluated against three Gram-positive and three Gram-negative bacteria and compared with the reference drug moxifloxacin. The antibacterial activity of Ti(IV) complex is significant for E. coli K32 and highly significant for S. aureus K1, B. subtilis K22, Br. otitidis K76, P. aeruginosa SW1 and K. oxytoca K42 compared with free moxifloxacin.     

Synthesis,characterization, and biological investigation of new mixed-ligand complexes

A novel series of mixed-ligand complexes of 5,5′-{(1E,1E′)-1,4-phenelynebis(diazene-2,1-diyl)}bis(quinolin-8-ol) (H₂L₁) as a primary ligand and 4-aminoantipyrine(L₂) as a secondary ligand with Mn(II) ion were prepared using two general formulae: [Mn₂(H₂L₁)₂(L₂)₂X₄].4Cl (X = OH₂( 1 ), ONO₂⁻( 2 ), Cl=nil; OAc( 3 ), Cl = nil) and [Mn₂(H₂L₁)(L₂)₂(O₂SO₂)₂]( 4 ). Free ligands and their complexes were characterized. Electronic absorption spectra of the mixed-ligand complexes indicate a distorted octahedral geometry around the central metal ion, and the anions X⁻ are in the axial positions for all compounds. The ligands behave in a neutral bidentate manner, through nitrogen atoms and oxygen atoms of the carbonyl group (L₂), whereas H₂L₁ coordinated through nitrogen and OH groups as a neutral bidentate ligand. All complexes do not contain coordinated water molecules, but complex ( 1 ) contains four water molecules. The water molecules are removed in a single step. The complexes exhibited magnetic susceptibility corresponding to five unpaired electrons. The antimicrobial activity of the Mn(II) mixed-ligand complexes ( 1–4 ) against two gram-positive bacteria, three local gram-negative bacteria, and three fungi species was tested. Mn(II) mixed-ligand complex ( 2 ) exhibited significant antibacterial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas sp. Mixed-ligand complex ( 2 ) exhibited a high potential cytotoxicity against the growth of human lung cancer cells.     

High-throughput synthesis and analysis of acylated cyanohydrins

The yields and optical purities of products obtained from chiral Lewis acid/Lewis base-catalysed additions of alpha-ketonitriles to prochiral aldehydes could be accurately determined by an enzymatic method. The amount of remaining aldehyde was determined after its reduction to an alcohol, whilst the two product enantiomers were analysed after subsequent hydrolysis first by the (S)-selective Candida antarctica lipase B and then by the unselective pig liver esterase. The method could be used for analysis of products obtained from a number of aromatic aldehydes and aliphatic ketonitriles. Microreactor technology was successfully combined with high-throughput analysis for efficient catalyst optimization.     

High-throughput protein crystallography and drug discovery

Single crystal X-ray diffraction is the technique of choice for studying the interactions of small organic molecules with proteins by determining their three-dimensional structures; however the requirement for highly purified protein and lack of process automation have traditionally limited its use in this field. Despite these shortcomings, the use of crystal structures of therapeutically relevant drug targets in pharmaceutical research has increased significantly over the last decade. The application of structure-based drug design has resulted in several marketed drugs and is now an established discipline in most pharmaceutical companies. Furthermore, the recently published full genome sequences of Homo sapiens and a number of micro-organisms have provided a plethora of new potential drug targets that could be utilised in structure-based drug design programs. In order to take maximum advantage of this explosion of information, techniques have been developed to automate and speed up the various procedures required to obtain protein crystals of suitable quality, to collect and process the raw X-ray diffraction data into usable structural information, and to use three-dimensional protein structure as a basis for drug discovery and lead optimisation.This tutorial review covers the various technologies involved in the process pipeline for high-throughput protein crystallography as it is currently being applied to drug discovery. It is aimed at synthetic and computational chemists, as well as structural biologists, in both academia and industry, who are interested in structure-based drug design.     

High-throughput heterogeneous catalytic science

High-throughput experimentation in heterogeneous catalysis has recently experienced nearly exponential growth. Initial qualitative screening has evolved into quantitative high-throughput experimentation, characterization, and analysis. This allows high-throughput catalysis now to rise above simple screening to the level of fundamental understanding of reaction mechanisms, which will lead on a faster path to the Holy Grail of catalysis: rational catalyst design.