Formylation with "Supercritical” CO2: Efficient Ruthenium-Catalyzed Synthesis of N -Formylmorpholine

Formylation of morpholine with "supercritical” CO2 using the bidentate ruthenium catalyst RuCl2(dppe)2 affords high N-formylmorpholine production rate at almost 100% selectivity. The solventless reaction could be an interesting alternative to the present N-formylmorpholine synthesis routes, which are based on environmentally harmful formylation agents. Video monitoring of the reaction mixture during reaction revealed a complex phase behavior, including the formation of solid carbamate, which was most prominent at low conversion and gradually disappeared with higher conversion, i.e., with the formation of N-formylmorpholine and water as a by-product. Addition of water as an additive suppressed solid carbamate formation and enhanced the reaction rate. Infrared spectroscopy was applied to follow the changes in the liquid and dense gas phase. The ruthenium catalyst was confined to the liquid phase, containing morpholine, N-formylmorpholine, water, dissolved carbon dioxide and hydrogen. Although the solubility of the ruthenium catalyst in the liquid phase decreased with increasing conversion, good performance in the synthesis of N-formylmorpholine could be achieve

Catalytic Materials by Design

Recent activities of our group in the design of catalytic materials are briefly surveyed. Special attention is given to sol-gel-derived mixed oxide aerogels and organic-inorganic hybrid gels, and to supported noble metals with controlled particle size. Examples discussed embrace: organically modified titania-silica aerogels for the epoxidation of bulky olefins, Ru-containing silica hybrid gels for the synthesis of formic-acid derivatives, and colloid-derived supported gold catalysts with controlled metal particle size

Single photon emission and detection at the nanoscale utilizing semiconductor nanowires

We report recent progress toward on-chip single photon emission and detection in the near infrared utilizing semiconductor nanowires. Our single photon emitter is based on a single InAsP quantum dot embedded in a p-n junction defined along the growth axis of an InP nanowire. Under forward bias, light is emitted from the single quantum dot by electrical injection of electrons and holes. The optical quality of the quantum dot emission is shown to improve when surrounding the dot material by a small intrinsic section of InP. Finally, we report large multiplication factors in excess of 1000 from a single Si nanowire avalanche photodiode comprised of p-doped, intrinsic, and n-doped sections. The large multiplication factor obtained from a single Si nanowire opens up the possibility to detect a single photon at the nanoscale.Comment: 11 pages, 7 figure

A new reaction route for the synthesis of 2-methyl-5-ethyl-pyridine

In this work, a novel synthesis route to produce 2-methyl-5-ethyl-pyridine (MEP) from the cyclic acetaldehyde ammonia trimer (AAT) is explored. The reaction was studied in a semi-batch reactor in the presence of different promoters to adjust the pH of the reaction solution. Among various ammonium salts tested as promoters, ammonium acetate was identified as most suitable promoter for the reaction. By a Design of Experiments (DoE) approach temperature and concentration of reactants and promoter were identified as the most important/decisive parameters for influencing the course of the reaction. Additional mechanistic investigations were carried out to assess the effect of these parameters in detail and to clarify the by-product formation via oligomer formation

pH Effects in the acetaldehyde-ammonia reaction

The pH dependency of the reaction of acetaldehyde and ammonia to form the acetaldehyde-ammonia trimer has been studied in detail. Acetaldehyde-ammonia trimer is a molecule of interest in organic synthesis, since it can be used as substrate in many reactions involving acetaldehyde or ammonia. The trimer is well known in literature but no references are present so far to describe its formation from other ammonia sources than ammonium hydroxide. The focus of this study is on describing the course of reaction after addition of acetaldehyde to solutions of ammonia and various acids. Products have been analysed by means of 1H-NMR and IR spectroscopy and the complete range of pH values has been covered. Depending on pH, two reaction regimes can be distinguished: at high pH only trimer is formed. In contrast, at low pH only low quantities of trimer are produced and the nature of the applied acid has a distinct effect on the reaction outcome. Inorganic acids result in low trimer concentration and high quantity of unreacted ammonia. Polymer formation dominates with simple carboxylic acids. Complex organic acids, such as e.g. maleic or nicotinic acid, lead to comparable quantities of trimer and acetaldehyde. Based on our results, we propose some adjustments to the traditional reaction scheme developed for acetaldehyde-ammonia trimer formation at high pH

The BDSF quorum sensing receptor RpfR regulates Bep exopolysaccharide synthesis in Burkholderia cenocepacia via interaction with the transcriptional regulator BerB

The polysaccharide Bep is essential for in vitro biofilm formation of the opportunistic pathogen Burkholderia cenocepacia. We found that the Burkholderia diffusible signaling factor (BDSF) quorum sensing receptor RpfR is a negative regulator of the bep gene cluster in B. cenocepacia. An rpfR mutant formed wrinkled colonies, whereas additional mutations in the bep genes or known bep regulators like berA and berB restored the wild-type smooth colony morphology. We found that there is a good correlation between intracellular c-di-GMP levels and bep expression when the c-di-GMP level is increased or decreased through ectopic expression of a diguanylate cyclase or a c-di-GMP phosphodiesterase, respectively. However, when the intracellular c-di-GMP level is changed by site directed mutagenesis of the EAL or GGDEF domain of RpfR there is no correlation between intracellular c-di-GMP levels and bep expression. Except for rpfR, deletion mutants of all 25 c-di-GMP phosphodiesterase and diguanylate cyclase genes encoded by B. cenocepacia showed no change to berA and bep gene expression. Moreover, bacterial two-hybrid assays provided evidence that RpfR and BerB physically interact and give specificity to the regulation of the bep genes. We suggest a model where RpfR binds BerB at low c-di-GMP levels to sequester this RpoN-dependent activator to an RpfR/RpfF complex. If the c-di-GMP levels rise, possibly by the enzymatic action of RpfR, BerB binds c-di-GMP and is released from the RpfR/RpfF complex and associates with RpoN to activate transcription of berA, and the BerA protein subsequently activates transcription of the bep genes

Detection of primary melanoma in individuals at extreme high risk: a prospective 5-year follow-up study

IMPORTANCE: The clinical phenotype and certain predisposing genetic mutations that confer increased melanoma risk are established; however, no consensus exists regarding optimal screening for such individuals. Early identification remains the most important intervention in reducing melanoma mortality. OBJECTIVE: To evaluate the impact of full-body examinations every 6 months supported by dermoscopy and total-body photography (TBP) on all patients and sequential digital dermoscopy imaging (SDDI), when indicated, on detecting primary melanoma in an extreme-risk population. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study from February 2006 to February 2011, with patients recruited from Sydney Melanoma Diagnostic Centre and Melanoma Institute Australia who had a history of invasive melanoma and dysplastic nevus syndrome, history of invasive melanoma and at least 3 first-degree or second-degree relatives with prior melanoma, history of at least 2 primary invasive melanomas, or a CDKN2A or CDK4 gene mutation. EXPOSURES: Six-month full-body examination compared with TBP. For equivocal lesions, SDDI short term (approximately 3 months) or long term (≥6 months), following established criteria, was performed. Atypical lesions were excised. MAIN OUTCOMES AND MEASURES: New primary melanoma numbers, characteristics, and cumulative incidence in each patient subgroup; effect of diagnostic aids on new melanoma identification. RESULTS: In 311 patients with a median (interquartile range [IQR]) follow-up of 3.5 (2.4-4.2) years, 75 primary melanomas were detected, 14 at baseline visit. Median (IQR) Breslow thickness of postbaseline incident melanomas was in situ (in situ to 0.60 mm). Thirty-eight percent were detected using TBP and 39% with SDDI. Five melanomas were greater than 1 mm Breslow thickness, 3 of which were histologically desmoplastic; the other 2 had nodular components. The benign to malignant excision ratio was 1.6:1 for all lesions excised and 4.4:1 for melanocytic lesions. Cumulative risk of developing a novel primary melanoma was 12.7% by year 2, with new primary melanoma incidence during the final 3 years of follow-up half of that observed during the first 2 years (incidence density ratio, 0.43 [95% CI, 0.25-0.74]; P = .002). CONCLUSIONS AND RELEVANCE: Monitoring patients at extreme risk with TBP and SDDI assisted with early diagnosis of primary melanoma. Hypervigilance for difficult-to-detect thick melanoma subtypes is crucial. Copyright 2014 American Medical Association. All rights reserved

Orbital Kondo effect in carbon nanotubes

Progress in the fabrication of nanometer-scale electronic devices is opening new opportunities to uncover the deepest aspects of the Kondo effect, one of the paradigmatic phenomena in the physics of strongly correlated electrons. Artificial single-impurity Kondo systems have been realized in various nanostructures, including semiconductor quantum dots, carbon nanotubes and individual molecules. The Kondo effect is usually regarded as a spin-related phenomenon, namely the coherent exchange of the spin between a localized state and a Fermi sea of electrons. In principle, however, the role of the spin could be replaced by other degrees of freedom, such as an orbital quantum number. Here we demonstrate that the unique electronic structure of carbon nanotubes enables the observation of a purely orbital Kondo effect. We use a magnetic field to tune spin-polarized states into orbital degeneracy and conclude that the orbital quantum number is conserved during tunneling. When orbital and spin degeneracies are simultaneously present, we observe a strongly enhanced Kondo effect, with a multiple splitting of the Kondo resonance at finite field and predicted to obey a so-called SU(4) symmetry.Comment: 26 pages, including 4+2 figure

Rapid hierarchical assembly of medium-size DNA cassettes

Synthetic biology applications call for efficient methods to generate large gene cassettes that encode complex gene circuits in order to avoid simultaneous delivery of multiple plasmids encoding individual genes. Multiple methods have been proposed to achieve this goal. Here, we describe a novel protocol that allows one-step cloning of up to four gene-size DNA fragments, followed by a second assembly of these concatenated sequences into large circular DNA. The protocols described here comprise a simple, cheap and fast solution for routine construction of cassettes with up to 10 gene-size components