A computational study of halomethyllithium carbenoid mixed aggregates with lithium halides and lithium methoxide

Density functional theory calculations were used to examine the formation of lithium halide and lithium alkoxide mixed aggregates with halomethyllithium carbenoids. These mixed aggregates may be the important intermediates in carbenoid reactions where lithium halides are formed as byproducts, or when the mixture has been exposed to small amounts of air. The calculations showed that in the gas phase and in THF solution, mixed dimers, trimers, and tetramers may coexist with free lithium carbenoids, depending on the lithium salt. The calculations also indicated that mixed aggregates may influence the activation free energies of cyclopropanation reactions of lithium carbenoids.     

A mixed hard- and soft-modelling approach to study and monitor enzymatic systems in biological fluids

Mixed hard- and soft-modelling multivariate curve resolution (HS-MCR) is applied to study and to monitor complex enzymatic systems. Working under the basis of the soft-modelling technique multivariate curve resolution-alternating least squares (MCR-ALS), a hard constraint is introduced to force some or all concentration profiles to fulfil an enzymatic model. In this way, improvements to the application of pure hard- or pure soft-modelling are achieved.The enzymatic reactions of different mixtures of hypoxanthine, xanthine and uric acid with xanthine oxidase are studied. This is a complex enzymatic process, where uric acid acts as a linear competitive inhibitor. The reactions were monitored with UV-vis spectrophotometry coupled to a stopped-flow module.This work has two aims, both of them focusing on different aspects linked to modelling enzymatic systems using HS-MCR. The first goal is related to the elucidation of the real enzymatic mechanism when one of the chemical substances involved in the process apparently deviates from the mechanism found in the literature. The second one focuses on modelling the enzymatic reaction in the presence of a biological interference, such as human urine. The elucidation of the real mechanism of this enzymatic process and of the behaviour of the involved chemical species in a natural absorbing medium are good examples of situations that can benefit from mixed modelling approaches involving the best of hard- and soft-modelling methodologies.     

A facile chemoenzymatic approach to natural cytotoxic ellipsoidone A and natural ellipsoidone B

Starting from citraconic anhydride (3) a facile four-step synthesis of deoxyellipsoidone 8 has been reported with 37% overall yield. An elegant six-step access to naturally occurring cytotoxic ellipsoidone A (1) and ellipsoidone B (2) has been reported with good overall yields, via the conversion of itaconic anhydride (9) to the acetoxymethylmaleic anhydride (11), regioselective sodium borohydride reduction of anhydride 11 to acetoxymethylbutyrolactone 12, Knoevenagel condensation of lactone 12 with 5-methylfurfural, selenium dioxide induced oxidation of the formed butenolide 13 and an Amano PS catalyzed deacylation of the formed diacetoxybutenolide 14 as a pathway.     

Chemoselective addition of in situ prepared lithium alkynyl borates to aldehydes: a practical and transition metal free approach toward the synthesis of propargylic alcohols

A convenient synthesis of functionalized propargylic alcohols arising from the 1,2-addition of lithium alkynyl-trimethyl borate onto aldehydes under transition metal free mild conditions is reported. The reaction tolerates a wide range of functional groups, is highly chemoselective and the propargylic alcohols are isolated in good to excellent yields.     

A modified approach to 2-(N-aryl)-1,3-oxazoles: application to the synthesis of the IMPDH inhibitor BMS-337197 and analogues

[structure: see text] A modified approach to the synthesis of 2-(N-aryl)-1,3-oxazoles, employing an optimized iminophosphorane/heterocumulene-mediated methodology, and its application to the synthesis of BMS-337197, a potent inhibitor of IMPDH, are described.     

丁基锂与氯化铜存在条件下仲胺偶联形成N-N键的新方法

报道了以仲胺反应底物经丁基锂夺去活性质子,无水氯化铜氧化偶联形成N—N键的新方法.共完成了11种底物尝试,所得产物肼的产率在17％～76％之间.相关合成方法是一种从仲胺制备对称取代肼的高效合成方法.     

Capillary electrophoresis with contactless conductivity detection for the quantification of fluoride in lithium ion battery electrolytes and in ionic liquids—A comparison to the results gained with a fluoride ion‐selective electrode

In this study, an optimized method using capillary electrophoresis (CE) with a direct contactless conductivity detector (C⁴D) for a new application field is presented for the quantification of fluoride in common used lithium ion battery (LIB) electrolyte using LiPF₆ in organic carbonate solvents and in ionic liquids (ILs) after contacted to Li metal. The method development for finding the right buffer and the suitable CE conditions for the quantification of fluoride was investigated. The results of the concentration of fluoride in different LIB electrolyte samples were compared to the results from the ion‐selective electrode (ISE). The relative standard deviations (RSDs) and recovery rates for fluoride were obtained with a very high accuracy in both methods. The results of the fluoride concentration in the LIB electrolytes were in very good agreement for both methods. In addition, the limit of detection (LOD) and limit of quantification (LOQ) values were determined for the CE method. The CE method has been applied also for the quantification of fluoride in ILs. In the fresh IL sample, the concentration of fluoride was under the LOD. Another sample of the IL mixed with Li metal has been investigated as well. It was possible to quantify the fluoride concentration in this sample.     

Cyclization in situ of enose-/ynose-nitrilimines: an expedient approach to the synthesis of chiral glycopyrazoles and pyrazolonucleosides

Intramolecular [3+2] nitrilimine cycloaddition reactions on carbohydrate-derived substrates proceed in a regioselective fashion, affording structurally novel chiral glycopyrazoles (4-6 and 10a-c) in good yields. The products can be subsequently transformed to bicyclic pyrazoles (viz. 11 from 4) or nucleoside analogues (viz. 12 from 4).     

We the droplets: A constitutional approach to active and self-propelled emulsions

The field of active matter, and particularly active emulsions, is growing rapidly, with significant progress made recently on both theoretical and experimental fronts. Here, we summarize experimental research progress related to active droplets. The constitution of active droplets, in particular the chemical compositions and structure of interfaces, is critical. We discuss how emulsion properties such as mechanism of motion, speed, trajectory, interaction strength, and lifetime are related to the droplet composition. We consider not only traditional single emulsions but also more complex variants, such as Janus droplets, Pickering emulsions, and multiple emulsions. Active behavior of isolated droplets as well as pairwise and multibody interactions between droplets is described. The influence of physical barriers that shape the local chemical gradients and fluid flow is also highlighted. This review provides perspective on the past, current, and promising future experimental research directions in active droplet research.     

Combined microbial oxidation and reduction: a new approach to the highyield synthesis of homochiral unsaturated secondary alcohols from racemates

The oxidation of racemic secondary alcohols with Bacillus stearothermophilus followed by reduction of the mixture with Yarrowialipolytica to afford high yields of the enantiomerically pure R-alcohols 1a, b, d is described. Comparisons with Yarrowia lipolytica reduction, Bacillus stearothermophilus oxidation, and the contemporary use of the two microrganisms have been made.     

Solvent effectiveness factor: A new correlation to study the influence of solvent,temperature, and stirring rate on synthesis yield of Ionic Liquids

The main objective of this study is to investigate the effect of solvent, temperature, and stirring on synthesis yield of Ionic Liquids (ILs). A representative Ionic Liquid [BMIM][BF₄] is prepared using seven different solvents and their influence on percentage yield is explained using a new correlation; solvent effectiveness factor (SEF). The SEF of solvent is governed by nature of solvent, operating temperature and stirring rate. Acetone has the highest SEF 1.275 and affords maximum IL yield 88.11% while toluene has the least SEF 0.674 and produces minimum IL 63.21%. When synthesis temperature is increased from 50 to 80 °C, synthesis yield is substantially increased from 76.7 to 93.08% because rise in temperature increases the SEF from 1.234 to 1.333, mainly due to the decrease in solvent viscosity. Similarly, when stirring rate is increased from 80 to 200 RPM, IL yield slightly increased from 87.37 to 91.35% due to addition of mechanical energy in the reaction mixture which in turn reduced solvent viscosity and increased SEF from 1.278 to 1.297.     

Quinone-based molecular electrochemistry and their contributions to medicinal chemistry: A look at the present and future

Molecular electrochemistry is closely linked to life sciences. Electron transfers play important roles in the bioactivation of redox-active drugs, in their metabolism/catabolism, and in their targeted release at precise destinations and frequently promote their ligand–target interactions. Altogether, this rich chemistry and the complexity of cellular environments and biocompartmentation often impede full investigation in situ of the whole chain of processes that sustain their therapeutic applications. Conversely, electrochemical ex situ investigations of drug properties and interactions performed in aqueous/aprotic/micellar/membrane/cell-mimetic media, combined with in vitro and in vivo data, are expected to provide extremely useful information on these processes. Therein, considering the ubiquitous case of quinones, we exemplified how such strategies allow controlling their beneficial or negative impact on cellular environments.     

从二聚体到长链体系 I: 一种理解和获得-维能带的近似方法

将二聚体的分子轨道看作Bloch函数受微扰的结果, 对其能级作赝同相和赝反相分类, 获得的一维近似能带与晶体轨道计算得到的能带定性趋势完全一致. 以[Pt(CN)4^2^-]及聚乙炔为代表示范了应用, 表明从二聚体获得长链体系能带与性能的主要信息是可能的.     

A mixed anhydride approach to the preparation of sulfinate esters and allylic sulfones: Trimethylacetic p-toluenesulfinic anhydride

A reagent combination of toluenesulfinic acid and trimethylacetyl chloride affords a putative trimethylacetic p-toluenesulfinic anhydride. This reagent has been used to prepare a series of sulfinate esters from primary and secondary alcohols. In addition, the reagent was used to convert Baylis-Hillman substrates into allylic sulfones. Attempts to use the reagent to convert amines to sulfinamides were unsuccessful. In contrast, the use of 2-pyrrolidinone afforded N-p-toluenesulfinyl pyrrolidinone in 64% yield. The use of a chiral 4-benzyl-1,3-oxazolidinone or 4-benzyl-1,3-oxazolidine-2-thione led to the isolation of S-p-tolyl p-toluenethiosulfonate.     

FluClass: A novel algorithm and approach to score and visualize the phylogeny of the influenza virus using mass spectrometry

A novel computer algorithm FluClass has been developed to facilitate the phylogenetic classification of influenza virus using mass spectral data. FluClass accepts a DNA or protein-based phylogenetic tree as input and generates theoretical peptide mass lists for each node. An experimental mass spectrum from an influenza virus protein digest is then placed onto the phylogenetic tree using a novel random resampling function (Z-score) that allows the scoring of spectrum against both internal and leaf nodes. Testing of the algorithm using hemagglutinin protein sequences from human-host influenza viruses showed that the Z-score performs comparably to the Profound scoring method for the scoring of leaf nodes and is substantially better at scoring internal nodes. Scoring of internal nodes allows colorizations of nodes of the phylogenetic tree enabling the classification of the query spectrum to be rapidly visualized. Finally we demonstrate the utility of FluClass on experimental spectra from six strains. Given that mass spectrometry data can be generated rapidly for influenza virus proteins, FluClass provides a fast and direct method for phylogenetic analysis of influenza proteins.     

A unified approach to the chromatography-FTIR interface: GC-FTIR,SFC-FTIR,and HPLC-FTIR with subnanogram detection limits

The results described in this paper demonstrate that Identifiable FTIR spectra of components separated by gas, supercritical fluid, and liquid chromatography can be measured in real time using a common approach. The sensitivity of each Interface is comparable with that obtained by interfacing the corresponding technique with a bench-top mass spectrometer. The combination of these two spectroscopic techniques should lead to an even more powerful means of Identification of volatile, semi-volatile, and non-volatile components of mixtures.     

A new hybrid algorithm for finding the lowest minima of potential surfaces: approach and application to peptides

A new algorithm is presented for finding the global minimum, and other low-lying minima, of a potential energy surface (PES) of biological molecules. The algorithm synergetically combines three well-known global optimization methods: the diffusion equation method (DEM), which involves smoothing the PES; a simulated annealing (SA) algorithm; and evolutionary programming (EP), whose population-oriented approach allows for a parallel search over different regions of the PES. Tests on five peptides having between 6 and 9 residues show that the code implementing the new combined algorithm is efficient and is found to outperform the constituent methods, DEM and SA. Results of the algorithm, in the gas phase and with the GBSA implicit solvent model, are compared with crystallographic data for the test peptides; good accord is found in all cases. Also, for all but one of the examples, our hybrid algorithm finds a minimum deeper than those obtained by a very extensive scan. TINKERs implementation of the OPLS-AA force field is employed for the structure prediction. The results show that the new algorithm is a powerful structure predictor, when a reliable potential function is available. Our implementation of the algorithm is time-efficient, and requires only modest computational resources. Work is underway on applications of the new algorithm to structural prediction of proteins and other biological macro-molecules.     

A novel approach to the qualitative and quantitative assay of HPTLC plates: Second and fourth derivative recording of spectrophotodensitograms

One of the limitations due to lack of resolution for a given pair of analytes in TLC or HPTLC is the need to optimize the system. In Practice this requires time, rerunning of the sample in different developing solvents, and a great deal of expertise on the part of the analyst. In our experience, application of first and second derivative recording techniques to HPTLC facilitates and speeds the whole process, permitting qualitative and quantitative assay of most unresolved spots. Consequently, we have now extended our instrumental capabilities to fourth derivative measurements. For this purpose, we have added a homemade electronic unit in series with the one previously used for first and second order derivatives. Thus, we have been able to evaluate the potential advantages of higher order derivatives for HPTLC analysis of unresolved components in various pharmaceutical products. A comparison of second and fourth order derivative measurements of seriously overlapping HPTLC components in a sample of preservatives used in the pharmaceutical industry suggests that the lower order derivatives might be a better choice in view of the higher accuracy and precision of the corresponding data. This is supported by the results of other applications, such as the assay of a commercial colorant, and a syrup formulation. The observed lack of precision of fourth order measurements stems from the fact that although the second and higher order derivatives produce narrower bandwidths, thus contributing to improved resolution, the signal to noise ratio decreases and satellite peak interactions increase, thus rendering correct discrimination of the fine structural detail of overlapping components more difficult.     

Ugi three-component reaction of alcohols,amines and isocyanides: A new approach to the synthesis of cyclic amidines

We have developed a novel, simple, efficient and one pot synthetic protocol for the synthesis of cyclic amidines via Ugi three-component reaction of alcohols, amines, and isocyanides.