Biomedical applications of two-dimensional electrophoresis using immobilized pH gradients: current status

There is currently much interest, as we enter the postgenome era, in studying gene expression at the protein level. Two-dimensional electrophoresis (2-DE) using immobilized pH gradients (IPG), coupled with mass spectrometry (MS), is currently the most widely utilized approach for the analysis of whole tissue proteins. The methodology for IPG-based 2-DE, since the introduction of the technique in the 1980s, is reviewed. In its present form the IPG methodology is mostly useful as a research tool. In general, high reproducibility and high resolution have been achieved. However, the lack of substantial automation and the limited sensitivity of the current overall methodology continue to represent drawbacks for biomedical applications. Further developments to increase throughput and to reduce sample requirement would substantially benefit the application of IPG-based 2-DE to biomedicine and would enhance the prospects for introducing the methodology into the clinical laboratory.     

Electrophoretic analysis of phospho and non-phospho protein mixtures extracted from zebrafish whole brain samples by immobilized metal affinity electrophoresis

Phosphoproteins are principle cellular protein components with diverse regulatory functions and phosphorylation is the most frequent post-translational modifications of proteins. Immobilized metal affinity electrophoresis (IMAEP) is a recently developed technique by which the phosphoprotein components of the cellular samples could be captured. We have made use of this new methodology to capture the whole phosphoproteins of zebrafish brain. Since the elution and resolution of captured phosphoproteins by this new methodology are not yet quite developed, we have tried to make this new methodology more efficient in (1) capturing phosphoproteins from biological samples and (2) elution and resolution of captured phosphoproteins. In this project, we first examined the captured phosphoproteins from zebrafish whole brain samples, as a mixture of phosphoproteins and non-phosphoproteins, examined and resolved the captured phosphoproteins by electrophoresis, and finally eluted them successfully from the gel. In this work, we provided an efficient methodology for the elution of captured phosphoproteins from the gel which is an important development in IMAEP in the analysis of phosphoprotein component of cellular samples and showed the possibility of elution of the captured phosphoproteins. The developed methodology will potentially have wide applications in profiling phosphoproteins from biological samples like zebrafish brain and also in studies about signal transduction systems.     

离子液体捕集二氧化碳非平衡热力学研究方法学探讨

介绍了应用非平衡热力学研究离子液体捕集二氧化碳（CO2）动力学的思路，分析了其成功应用需解决三大关键科学难题，即可靠的热力学模型，界面传递速率描述以及准确的通量数据．其中，准确通量数据的获得需要可靠的实验动力学数据和离子液体捕集CO2过程传递面积的有效考察．在此基础上系统地总结了该三大关键科学问题最新的研究进展和分析后续开展的工作，并对离子液体捕集二氧化碳非平衡热力学研究提出展望．     

Application of quantitative artificial neural network analysis to 2D NMR spectra of hydrocarbon mixtures

Understanding relationships between the structure and composition of molecular mixtures and their chemical properties is a main industrial aim. One central field of research is oil chemistry where the key question is how the molecular characteristics of composite hydrocarbon mixtures can be associated with the macroscopic properties of the oil products. Apparently these relationships are complex and often nonlinear and therefore call for advanced spectroscopic techniques. An informative and an increasingly used approach is two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy. In the case of composite hydrocarbons the application of 2D NMR methodologies in a quantitative manner pose many technical difficulties, and, in any case, the resulting spectra contain many overlapping resonances that challenge the analytical work. Here, we present a general methodology, based on quantitative artificial neural network (ANN) analysis, to resolve overlapping information in 2D NMR spectra and to simultaneously assess the relative importance of multiple spectral variables on the sample properties. The results in a set of 2D NMR spectra of oil samples illustrate, first, that use of ANN analysis for quantitative purposes is feasible also in 2D and, second, that this methodology offers an intrinsic opportunity to assess the complex and nonlinear relationships between the molecular composition and sample properties. The presented ANN methodology is not limited to the analysis of NMR spectra but can also be applied in a manner similar to other (multidimensional) spectroscopic data.     

Efficient total syntheses of phytoalexin and (+/-)-paniculidine B and C based on the novel methodology for the preparation of 1-methoxyindoles

A general route to 2-unsubstituted-1-methoxyindoles, based on our methodology for the synthesis of 1-methoxyindoles, is reported. This synthesis renders accessibility to a variety of natural products possessing the said skeleton. A direct synthesis of phytoalexin (1), (+/-)-paniculidine B (2), and (+/-)-paniculidine C (3) is disclosed based on the methodology. The synthesis of paniculidine B (2) has been achieved from aldehyde 10 in only two steps in 88% yield and in five steps from a methoxyindole compound 8 obtained using our earlier methodology.     

A Solid Phase Synthesis of Chalcones by Claisen-Schmidt Condensations

In previous papers1,2, we reported our recent findings that chalcone (l,3-dipheny1-2-propen-1-one) derivatives are novel potential antimalarials that are active against chloroquine-resistant strains of Plasmodium falciparum. According to our structure-activity relationships (SAR) and computer modeling data1,2, we expect the chalcone derivatives with hydroxyl functionality on one of the aromatic rings and with some other appropriate substitutions on the other ring will be even more potent as a…     

Solvent control of product diversity in palladium-catalyzed addition of arylboronic acid to aryl aldehydes

In Pd-catalyzed arylboronic acid addition to aryl aldehydes, the expected carbinol or asymmetrical ether can be obtained as the major product by altering aqueous solvent composition. Exploiting this methodology with 2-formylbiphenyls as reaction partner, a fluorene scaffold can be readily constructed in two steps.     

Evaluation of post-Cu CMP cleaning of organic residues using microfluidic device

The removal kinetics of organic residues remaining after chemical mechanical planarization (CMP) were studied using a microfluidic device that monitored the open circuit potential (OCP) response to rapid changes in electrolyte composition. Citric acid at various pH values, ranging from 2 to 9, was investigated as the cleaning solution. It is found that the optimized pH value of the citric-acid cleaning solution is 5. The in situ electrochemical methodology is effective for preliminary evaluation or optimization of cleaning solutions. In addition, the electrochemical methodology may be utilized in screening inhibitors used in CMP process for their susceptibility to post-process cleaning.     

Azomethine ylide mediated inversion of configuration of quaternary imidazoline carbon: converting trans- to its cis- imidazolines

An efficient synthetic methodology of converting trans-4,5-diaryl-2-imidazolines to the corresponding cis-4,5-diaryl-2-imidazolines has been developed. This methodology features mild reaction conditions and a simple one-pot two-step procedure.     

Palladium-catalyzed carbonylative annulation of o-alkynylphenols: syntheses of 2-substituted-3-aroyl-benzo[b]furans

We report here a general synthetic methodology for palladium-catalyzed carbonylative annulation of o-alkynylphenol to construct 2-substituted-3-aroyl-benzo[b]furan. On the basis of the results, this methodology could be applied to a wider selection of iodide substrates to generate desired products. In accordance with mechanistic studies, this process involves coordination of cationic and less hindered acyl palladium complexes with o-alkynylphenols to create a desired cascade triad (coordination, nucleophilic addition, and reductive elimination). Consistent with this mechanism, addition of 1 equiv of AgBF(4) to palladium catalyst Pd(Ph(3)P)(4) generates an ideal candidate for this unique transformation.     

Optimizing analytical methods using sequential response surface methodology. Application to the pararosaniline determination of formaldehyde

Sequential response surface methodology is a general procedure to re-optimize common analytical methods on the basis of the application of the response surface methodology and of a new approach to the steepest ascent method. This procedure, which is easy to apply, consists of estimating an analytical function relating the response with the experimental parameters by means of a second-degree polynomial. Thus, a 2nd order design covering the total experimental domain is used and when a maximum is obtained, the characteristics of the response surface are confirmed using a new design, which is obtained contracting the first one. In the proposed methodology, Box-Behnken designs are used because they offer advantages in comparison with second order designs more frequently used in the steepest ascent method (central composite designs), i.e. fewer experiments are needed, they are more efficient, they can be moved through the experimental domain and they can even be easily contracted or expanded.     

基于金属有机和元素有机化合物参与的新合成方法学 的研究

包括下列研究工作：碱催化形成碳-碳双键的合成方法学;双烯化反应的合成方法学;立体选择性地控制合成烯炔和丙烯类化合物的合成方法等;连串反应的合成方法学。     

A methodology for the synthesis of highly functionalized 2- and 4-aminoquinoline derivatives

A methodology for the synthesis of 2- and 4-aminoquinoline derivatives, which takes advantage of selective activation of 2- or 4-substituent of 2-methylsulfanyl-3-acyl-1H-quinolin-4-one 1, has been developed. Since a procedure for formation of 3-aminoquinolinones from the 4-quinolinone 1 was described previously, the new methodology comprises a general methodology for the selective syntheses of three isomeric 2-, 3- and 4-aminoquinoline derivatives starting with the common 4-quinolinone 1.     

Optimizing analytical methods using sequential response surface methodology. Application to the pararosaniline determination of formaldehyde

Sequential response surface methodology is a general procedure to re-optimize common analytical methods on the basis of the application of the response surface methodology and of a new approach to the steepest ascent method. This procedure, which is easy to apply, consists of estimating an analytical function relating the response with the experimental parameters by means of a second-degree polynomial. Thus, a 2nd order design covering the total experimental domain is used and when a maximum is obtained, the characteristics of the response surface are confirmed using a new design, which is obtained contracting the first one. In the proposed methodology, Box-Behnken designs are used because they offer advantages in comparison with second order designs more frequently used in the steepest ascent method (central composite designs), i.e. fewer experiments are needed, they are more efficient, they can be moved through the experimental domain and they can even be easily contracted or expanded.     

BF3·OEt2-promoted diastereoselective diacetoxylation of alkenes by PhI(OAc)2

Selective syn and anti diacetoxylations of alkenes have been achieved using a PhI(OAc)(2)/BF(3)·OEt(2) system in the presence and absence of water, respectively. A broad range of substrates including electron-deficient alkenes (such as α,β-unsaturated esters) could be elaborated efficiently at room temperature with this methodology, furnishing the desired products in good to excellent yields and diastereoselectivity. In particular, a multigram-scale diastereoselective diacetoxylation of methyl cinnamate (5.00 g) was also accomplished in a few hours, maintaining the same efficiency as small-scale reaction. This novel methodology provides an alternative approach for the preparation of various 1,2-diols.     

A novel oxidative transformation of alcohols to nitriles: an efficient utility of azides as a nitrogen source

An efficient methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been developed. This methodology employs DDQ as an oxidant and TMSN(3) as a source of nitrogen in the presence of a catalytic amount of Cu(ClO(4))(2)·6H(2)O.     

Multisyringe chromatography (MSC) using a monolithic column for the determination of sulphonated azo dyes

A methodology based on multisyringe chromatography with a monolithic column was developed to determine three sulphonated azo textile dyes: Acid Yellow 23, Acid Yellow 9 and Acid Red 97. An ion pair reagent was needed because of the low affinity between the monolithic column and the anionic dyes. The proposed analytical system is simple, versatile and low-cost and has great flexibility in manifold configuration.The method was optimized through experimentation based on experimental design methodology. For this purpose two blocks of full factorial 2³ were done sequentially. In the first experimental plan, the factors studied were: the % of acetonitrile in organic phase, the % of H₂O in the mobile phase and the kind of ion pair reagent. In this stage, a simple configuration was used which has only one syringe for the mobile phase.After the first experimentation, we added a second syringe with a second mobile phase to the multisyringe module and performed a second full factorial 2³. The factors studied in this case were: the % of acetonitrile in the second mobile phase, the pH and the concentration of ion pair reagent in both mobile phases. After this design, the optimal conditions were selected for obtaining a good resolution between the peaks of yellow dyes (1.47) and the elution of red dye in less than 8 min.The methodology was validated by spiking different amounts of each dye in real water samples, specifically, tap water, well water and water from a biological wastewater lagoon.     

碳-碳重键的新合成方法学研究

本研究工作包括下列8方面:(1)一种不同于Wittig反应的新的烯化方法,含氟β-酮基磷盐在有机合成中的应用。(2)"一锅"法的碳-碳双键形成反应。(3)一种新的叶立德阴离子的形成方法。(4)消去三苯基胂形成碳-碳双键的合成方法学。(5)立体选择性地控制合成(Z)或(E)-碳-碳双键化合物的新方法。(6)亲核试剂对全氟酰基膦酸酯进攻为基础的新合成方法学。(7)还原烯化反应的合成方法学。(8)含氟碳-碳叁键的合成方法学。