A one pot three-step process for the synthesis of an array of arylated benzimidazoribosyl nucleosides

A three-step one pot reaction/purification protocol was developed to facilitate rapid access to benzimidazole-based nucleosides, for which benzoylated benzimidazoribosyl nucleosides incorporating boronic esters were key reaction intermediates.

One-pot two-step mechanochemical synthesis: ligand and complex preparation without isolating intermediates

Although the use of ball milling to induce reactions between solids (mechanochemical synthesis) can provide lower-waste routes to chemical products by avoiding solvent during the reaction, there are further potential advantages in using one-pot multistep syntheses to avoid the use of bulk solvents for the purification of intermediates. We report here two-step syntheses involving formation of salen-type ligands from diamines and hydroxyaldehydes followed directly by reactions with metal salts to provide the corresponding metal complexes. Five salen-type ligands 2,2'-[1,2-ethanediylbis[(E)-nitrilomethylidyne]] bisphenol, ` salenH2', 1; 2,2'-[(+/-)-1,2-cyclohexanediylbis-[(E)-nitrilomethylidyne]] bis-phenol, 2; 2,2'-[1,2-phenylenebis( nitrilomethylidyne)]-bis-phenol, ` salphenH2' 3; 2-[[(2-aminophenyl) imino] methyl]-phenol, 4; 2,2'-[(+/-)-1,2-cyclohexanediylbis[(E)-nitrilomethylidyne]]-bis[4,6-bis(1,1-dimethylethyl)]-phenol, ` Jacobsen ligand', 5) were found to form readily in a shaker-type ball mill at 0.5 to 3 g scale from their corresponding diamine and aldehyde precursors. Although in some cases both starting materials were liquids, ball milling was still necessary to drive those reactions to completion because precipitation of the product and or intermediates rapidly gave in thick pastes which could not be stirred conventionally. The only ligand which required the addition of solvent was the Jacobsen ligand 5 which required 1.75 mol equivalents of methanol to go to completion. Ligands 1-5 were thus obtained directly in 30-60 minutes in their hydrated forms, due to the presence of water by-product, as free-flowing yellow powders which could be dried by heating to give analytically pure products. The one-armed salphen ligand 4 could also be obtained selectively by changing the reaction stoichiometry to 1 : 1. SalenH(2) 1 was explored for the onepot two-step synthesis of metal complexes. In particular, after in situ formation of the ligand by ball milling, metal salts (ZnO, Ni(OAc)2 center dot 4H(2)O or Cu(OAc)(2)center dot H2O) were added directly to the jar and milling continued for a further 30 minutes. Small amounts of methanol (0.4-1.1 mol equivalents) were needed for these reactions to run to completion. The corresponding metal complexes [M(salen)] (M = Zn, 6; Ni, 7; or Cu, 8) were thus obtained quantitatively after 30 minutes in hydrated form, and could be heated briefly to give analytically pure dehydrated products. The all-at-once ` tandem' synthesis of [Zn(salen)] 6 was also explored by milling ZnO, ethylene diamine and salicylaldehyde together in the appropriate mole ratio for 60 minutes. This approach also gave the target complex selectively with no solvent needing to be added. Overall, these syntheses were found to be highly efficient in terms of time and the in avoidance of bulk solvent both during the reaction and for the isolation of intermediates. The work demonstrates the applicability of mechanochemical synthesis to one-pot multi-step strategies.

A two-step approach for the analysis of hybrids in comparative social policy analysis: a nuanced typology of childcare policies

Typologies have represented an important tool for the development of comparative social policy research and continue to be widely used in spite of growing criticism of their ability to capture the complexity of welfare states and their internal heterogeneity. In particular, debates have focused on the presence of hybrid cases and the existence of distinct cross-national pattern of variation across areas of social policy. There is growing awareness around these issues, but empirical research often still relies on methodologies aimed at classifying countries in a limited number of unambiguous types. This article proposes a two-step approach based on fuzzy-set-ideal-type analysis for the systematic analysis of hybrids at the level of both policies (step 1) and policy configurations or combinations of policies (step 2). This approach is demonstrated by using the case of childcare policies in European economies. In the first step, parental leave policies are analysed using three methods – direct, indirect, and combinatory – to identify and describe specific hybrid forms at the level of policy analysis. In the second step, the analysis focus on the relationship between parental leave and childcare services in order to develop an overall typology of childcare policies, which clearly shows that many countries display characteristics normally associated with different types (hybrids and. Therefore, this two-step approach enhances our ability to account and make sense of hybrid welfare forms produced from tensions and contradictions within and between policies.

The vegetation and climate history of the last glacial cycle in a new pollen record from Lake Fimon (southern Alpine foreland, N-Italy)

The sediments of Like Fimon N Italy contain the first continuous archive of the Late Pleistocene environmental and climate history of the southern Alpine foreland We present here the detailed palynological record of the interval between Termination II and the List Glacial Maximum The age-depth model is obtained by radiocarbon dating in the uppermost part of the record Downward we con elated major forest expansion and contraction events to isotopic events in the Greenland Ice core records via a stepping-stone approach involving intermediate correlation to isotopic events dated by TIMS U/Th in Alpine and Apennine stalagmites and to pollen records from mime cores of the Iberian margin Modelled ages obtained by Bayesian analysis of deposition are thoroughly consistent with actual ages with maximum offset of +/- 1700 years Sharp expansion of broad-leaved temperate forest and of sudden water table rise mark the onset of the Last Interglacial after a treeless steppe phase at the end of penultimate glaciation This event is actually a two-step process which matches the two step rise observed in the isotopic record of the nearby Antro del Corchia stalagmite respectively dated to 132 5 +/- 2 5 and 129 +/- 1 5 ka At the interglacial decline mixed oak forests were replaced by oceanic mixed forests the latter persisting further for 7 ka till the end of the Eemian succession Warm-temperate woody species are still abundant at the Eemian end corroborating a steep gradient between central Europe and the Alpine divide at the inception of the last glacial After a stadial phase marked by moderate forest decline a new expansion of warm broad leaved forests interrupted by minor events and followed by mixed oceanic forests can be identified with the north-alpine Saint Germain I The spread of beech during the oceanic phase is a valuable circumalpine marker The subsequent stadial-interstadial succession lacking the telocratic oceanic phase is also consistent with the evidence at the north alpine foreland The Middle Wurmian (full glacial) is marked by persistence of mixed forests dominated by conifers but with significant lime and other broad leaved species A major Arboreal Pollen decrease is observed at modelled age of 38 7 +/- 0 5 ka (larch expansion and last occurrence of lime) which his been related to Heinrich Event 4 The evidence of afforestation persisting south of the Alps throughout most of MIS 3 contrasts with a boreal and continental landscape known for the northern alpine foreland pointing to a sharp rainfall boundary at the Alpine divide and to southern air circulation This is in agreement with the Alpine paleoglaciological record and is supported by the pressure and rainfall patterns designed by mesoscale paleoclimate simulations Strenghtening the continental high pressure during the full glacial triggered cyclogenesis in the middle latitude eastern Europe and orographic rainfall in the eastern Alps and the Balkanic mountains thus allowing forests development at current sea level altitudes (C) 2010 Elsevier Ltd All rights reserved

Simple method for the rapid simultaneous screening of photocatalytic activity over multiple positions of self-cleaning films

An intelligent ink, previously shown to be capable of rapidly assessing photocatalytic activity, was simply applied via a felt-pen onto a commercially available piece of Activ (TM) self-cleaning glass. The ink, comprising of redox dye resazurin and the sacrificial electron donor glycerol within an aqueous hydroxy ethyl cellulose (HEC) polymer media, was photocatalytically degraded in a two-step process. The key initial stage was the photo-reductive conversion of resazurin to resorufin, whereby a colour change from blue to pink occurred. The latter stage was the subsequent photo-reduction of the resorufin, where a slower change from pink to colourless was seen. Red and green components of red-green-blue colour extracted from flat-bed scanner digital images of resazurin ink coated photocatalytic films at intervals during the photocatalysis reaction were inversely proportional to the changes seen via UV-visible absorption spectroscopy and indicative of reaction kinetics. A 3 x 3 grid of intelligent ink was drawn onto a piece of Activ (TM) and a glass blank. The photocatalysis reaction was monitored solely by flat-bed digital scanning. Red-green-blue values of respective positions on the grid were extracted using a custom-built program entitled RGB Extractor (c). The program was capable of extracting a number of 5 x 5 pixel averages of red-green-blue components simultaneously. Allocation of merely three coordinates allowed for the automatic generation of a grid, with scroll-bars controlling the number of positions to be extracted on the grid formed. No significant change in red and green components for any position on the glass blank was observed; however, the Activ (TM) film displayed a homogenous photo-reduction of the dye, reaching maxima in red and minima in green components in 23 +/- 3 and 14 +/- 2 min, respectively. A compositionally graded N-doped titania film synthesised in house via a combinatorial APCVD reaction was also photocatalytically tested by this method where 247 positions on a 13 x 19 grid were simultaneously analysed. The dramatic variation in photocatalysis observed was rapidly quantified for all positions (2-3 hours) allowing for correlations to be made between thicknesses and N : Ti% compositions attained from Swanepoel and WDX analysis, respectively. N incorporation within this system was found to be detrimental to film activity for the photocatalysis reaction of intelligent ink under 365 nm light.

Aza-annulation of enaminones with itaconic anhydride:kinetic preference for exocyclic enamide products

Enaminones react with itaconic anhydride in methylene chloride at room temperature to give exocyclic enamides sis the major products. These can be readily equilibrated to the thermodynamically more stable endocyclic enamides. In substrates where the exocyclic isomer could not be formed only intractable materials were produced from this reaction. An intermediate in this two step process was detected and identified by proton and C-13 NMR spectroscopy. In two cases chiral enaminones were employed and the relative stereochemistry at the new chiral centre in the product was established by a crystal structure of compound 27.

Safe fabrication of sharp gold tips for light emission in scanning tunnelling microscopy

Gold is the optimal tip metal for light emission in scanning tunnelling microscopy (LESTM) under ambient conditions. Sharp Au-tips of similar to 10nm radius were produced reliably using a safe, two-step etching method in 20% (w/w) CaCl2 solution. Previous CaCl2-based methods have tended to produce blunter tips, while other etching techniques that do produce sharp Au-tips, do so with the use of toxic or hazardous electrolytes. The tips are characterised using scanning electron microscopy and their efficacy in LESTM is evidenced by high-resolution, simultaneous topographic and photon mapping of Au(1 1 1)- and polycrystalline Au-surfaces. Spectra of the optical emission exhibit only one or two peaks with etched tips in contrast to the more complex spectra typical of cut tips; this feature, together with the highly symmetric geometry of the tips, facilitates a definitive analysis of the light emission process. (c) 2007 Elsevier B. V.. All rights reserved.

A comprehensive aerosol spray method for the rapid photocatalytic grid area analysis of semiconductor photocatalyst thin films

Indicator inks, previously shown to be capable of rapidly assessing photocatalytic activity via a novel photo-reductive mechanism, were simply applied via an aerosol spray onto commercially available pieces of Activ (TM) self-cleaning glass. Ink layers could be applied with high evenness of spread, with as little deviation as 5% upon UV-visible spectroscopic assessment of 25 equally distributed positions over a 10 cm x 10 cm glass cut. The inks were comprised of either a resazurin (Rz) or dichloroindophenol (DCIP) redox dye with a glycerol sacrificial electron donor in an aqueous hydroxyethyl cellulose (HEC) polymer media. The photo-reduction reaction under UVA light of a single spot was monitored by UV-vis spectroscopy and digital images attained from a flat-bed scanner in tandem for both inks. The photo-reduction of Rz ink underwent a two-step kinetic process, whereby the blue redox dye was initially reduced to a pink intermediate resorufin (Rf) and subsequently reduced to a bleached form of the dye. In contrast, a simple one-step kinetic process was observed for the reduction of the light blue redox dye DCIP to its bleached intermediates. Changes in red-green-blue colour extracted from digital images of the inks were inversely proportional to the changes seen at corresponding wavelengths via UV-visible absorption spectroscopy and wholly indicative of the reaction kinetics. The photocatalytic activity areas of cuts of Activ (TM) glass, 10 cm x 10 cm in size, were assessed using both Rz and DCIP indicator inks evenly sprayed over the films: firstly using UVA lamp light to activate the underlying Activ (TM) film (1.75 mW cm(-2)) and secondly under solar conditions (2.06 +/- 0.14 mW cm(-2)). The photo-reduction reactions were monitored solely by flat-bed digital scanning. Red-green-blue values of a generated 14 x 14 grid (196 positions) that covered the entire area of each film image were extracted using a Custom-built program entitled RGB Extractor(C). A homogenous degradation over the 196 positions analysed for both Rz (Red colour deviation = 19% UVA, 8% Solar: Green colour deviation = 17% UVA, 12% Solar) and DCIP (Red colour deviation = 22% UVA, 16% Solar) inks was seen in both UVA and solar experiments, demonstrating the consistency of the self-cleaning titania layer on Activ (TM). The method presented provides a good solution for the high-throughput photocatalytic screening of a number of homogenous photocatalytically active materials simultaneously or numerous positions on a single film; both useful in assessing the homogeneity of a film or determining the best combination of reaction components to produce the optimum performance photocatalytic film. (C) 2010 Elsevier B.V. All rights reserved.

Mechanistic Study of 1,3-Butadiene Formation in Acetylene Hydrogenation over the Pd-Based Catalysts Using Density Functional Calculations

Green oil, which leads to the deactivation of the catalysts used for the selective hydrogenation of acetylene, has long been observed but its formation mechanism is not fully understood. In this work, the formation of 1,3-butadiene, known to be the precursor of green oil, on both Pd(111) and Pd(211) surfaces is examined using density functional theory calculations. The pathways containing C-2 + C-2 coupling reactions as well as the corresponding hydrogenation reactions are studied in detail. Three pathways for 1,3-butadiene production, namely coupling plus hydrogenation and further hydrogenation, hydrogenation plus coupling plus hydrogenation, and a two step hydrogenation followed by coupling, are determined. By comparing the effective barriers, we identify the favored pathway on both surfaces. A general understanding toward the deactivation process of the industrial catalysts is also provided. In addition, the effects of the formation of subsurface carbon atoms as well as the Ag alloying on the 1,3-butadiene formation on Pd-based catalysts are also investigated and compared with experimental results.

Mechanism of Alizarin Red S and Methylene Blue Biosorption onto Olive Stone: Isotherm study in Single and Binary Systems

The biosorption process of anionic dye Alizarin Red S (ARS) and cationic dye methylene blue (MB) as a function of contact time, initial concentration and solution pH onto olive stone (OS) biomass has been investigated. Equilibrium biosorption isotherms in single and binary systems and kinetics in batch mode were also examined. The kinetic data of the two dyes were better described by the pseudo second-order model. At low concentration, ARS dye appeared to follow a two-step diffusion process, while MB dye followed a three-step diffusion process. The biosorption experimental data for ARS and MB dyes were well suited to the Redlich-Peterson isotherm. The maximum biosorption of ARS dye, qmax = 16.10 mg/g, was obtained at pH 3.28 and the maximum biosorption of MB dye, qmax = 13.20 mg/g, was observed at basic pH values. In the binary system, it was indicated that the MB dye diffuses firstly inside the biosorbent particle and occupies the biosorption sites forming a monodentate complex and then the ARS dye enters and can only bind to untaken sites; forms a tridentate complex with OS active sites.

Catalyst screening: Refinement of the origin of the volcano curve and its implication in heterogeneous catalysis

Understanding the overall catalytic activity trend for rational catalyst design is one of the core goals in heterogeneous catalysis. In the past two decades, the development of density functional theory (DFT) and surface kinetics make it feasible to theoretically evaluate and predict the catalytic activity variation of catalysts within a descriptor-based framework. Thereinto, the concept of the volcano curve, which reveals the general activity trend, usually constitutes the basic foundation of catalyst screening. However, although it is a widely accepted concept in heterogeneous catalysis, its origin lacks a clear physical picture and definite interpretation. Herein, starting with a brief review of the development of the catalyst screening framework, we use a two-step kinetic model to refine and clarify the origin of the volcano curve with a full analytical analysis by integrating the surface kinetics and the results of first-principles calculations. It is mathematically demonstrated that the volcano curve is an essential property in catalysis, which results from the self-poisoning effect accompanying the catalytic adsorption process. Specifically, when adsorption is strong, it is the rapid decrease of surface free sites rather than the augmentation of energy barriers that inhibits the overall reaction rate and results in the volcano curve. Some interesting points and implications in assisting catalyst screening are also discussed based on the kinetic derivation. Moreover, recent applications of the volcano curve for catalyst design in two important photoelectrocatalytic processes (the hydrogen evolution reaction and dye-sensitized solar cells) are also briefly discussed.

Differences in mitochondrial and nuclear DNA status of high-density and low-density sperm fractions after density centrifugation preparation

Background: In order to isolate the â??bestâ?? sperm for assisted conception a discontinuous two-step density gradient centrifugation is usually employed. This technique is known to isolate a subpopulation with good motility, morphology and nuclear DNA (nDNA) integrity. As yet its ability to isolate sperm with unfragmented mitochondrial DNA (mtDNA) is unknown. Methods: Semen was obtained from men (n=28) attending our Regional Fertility Centre for infertility investigations. We employed a modified long polymerase chain reaction to study mtDNA and a modified alkaline Comet assay to determine nDNA fragmentation. Results: The high- density fraction displayed significantly more wild type mtDNA (75% of samples) than that of the low- density fraction (25% of samples). In the high-density fraction, there was a higher incidence of single, rather than double or multiple deletions and the deletions were predominantly small scale (0.1-4.0kb). There was a strong correlation between nDNA fragmentation, the number of mtDNA deletions (r=0.7, p

Effect of eucaloric high- and low-sucrose diets with identical macronutrient profile on insulin resistance and vascular risk - A randomized controlled trial

The long-term impact of dietary carbohydrate type, in particular sucrose, on insulin resistance and the development of diabetes and atherosclerosis is not established. Current guidelines for the healthy population advise restriction of sucrose intake. We investigated the effect of high- versus low-sucrose diet (25 vs. 10%, respectively, of total energy intake) in 13 healthy subjects aged 33 +/- 3 years (mean +/- SE), BMI 26.6 +/- 0.9 kg/m(2), in a randomized crossover design with sequential 6-week dietary interventions separated by a 4-week washout. Weight maintenance, eucaloric diets with identical macronutrient profiles and fiber content were designed. All food was weighed and distributed. Insulin action was assessed using a two-step euglycemic clamp; glycemic profiles were assessed by the continuous glucose monitoring system and vascular compliance by pulse-wave analysis. There was no change in weight across the study. Peripheral glucose uptake and suppression of endogenous glucose production were similar after each diet. Glycemic profiles and measures of vascular compliance did not change. A rise in total and LDL cholesterol was observed. In this study, a high-sucrose intake as part of an eucaloric, weight-maintaining diet had no detrimental effect on insulin sensitivity, glycemic profiles, or measures of vascular compliance in healthy nondiabetic subjects.