Taming hazardous chemistry in flow: The continuous processing of diazo and diazonium compounds

The synthetic utilities of the diazo and diazonium groups are matched only by their reputation for explosive decomposition. Continuous processing technology offers new opportunities to make and use these versatile intermediates at a range of scales with improved safety over traditional batch processes. In this minireview, the state of the art in the continuous flow processing of reactive diazo and diazonium species is discussed

The impact of storage conditions upon gentamicin coated antimicrobial implants

A systematic approach was developed to investigate the stability of gentamicin sulfate (GS) and GS/poly (lactic-co-glycolic acid) (PLGA) coatings on hydroxyapatite surfaces. The influence of environmental factors (light, humidity, oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry. GS coated rods were found to be stable across the range of environments assessed, with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition. In contrast, rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C, 75% relative humidity or exposure to light. The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect. Finally, liquid chromatography–mass spectrometry analysis revealed that known gentamines C1, C1a and C2 were the major degradants formed. Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities

Novel co-crystals of the nutraceutical sinapic acid

Sinapic acid (SA) is a nutraceutical with known anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, and anti-anxiety properties. Novel co-crystals of SA were prepared with co-formers belonging to the category of GRAS [isonicotinic acid (INC), nicotinamide (NIA)], non-GRAS [4-pyridinecarbonitrile (PYC)], and active pharmaceutical ingredients (APIs) [6-propyl-2-thiouracil (PTU)] list of compounds. Structural study based on the X-ray crystal structures revealed the intermolecular hydrogen-bonded interactions and molecular packing. The crystal structure of sinapic acid shows the anticipated acid-acid homodimer along with discrete hydrogen bonds between the acid carbonyl and the phenolic moiety. The robust acid-acid homodimer appears to be very stable and is retained in the structures of two co-crystals (SA[middle dot]NIA and SA[middle dot]PYC). In these cases, co-crystallization occurs via intermolecular phenol O-H[three dots, centered]Naromatic hydrogen bonds between the co-formers. In the SA[middle dot]PTU[middle dot]2MeCN co-crystal the acid-acid homodimer gives way to the anticipated acid-amide heterodimer, with the phenolic moiety of SA hydrogen-bonded to acetonitrile. Attempts at obtaining the desolvated co-crystal led to lattice breakdown, thus highlighting the importance of acetonitrile in the formation of the co-crystal. Among the co-crystals examined, SA[middle dot]INC (5 weeks), SA[middle dot]NIA (8 weeks) and SA[middle dot]PYC (5 weeks) were found to be stable under accelerated humidity conditions (40 [degree]C, 75% RH), whereas SA[middle dot]PTU[middle dot]2MeCN decomposed after one week into individual components due to solvent loss

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

A continuous process strategy has been developed for the preparation of α-thio-β chloroacrylamides, a class of highly versatile synthetic intermediates. Flow platforms to generate the α-chloroamide and α-thioamide precursors were successfully adopted, progressing from the previously employed batch chemistry, and in both instances afford a readily scalable methodology. The implementation of the key α-thio-β-chloroacrylamide casade as a continuous flow reaction on a multi-gram scale is described, while the tuneable nature of the cascade, facilitated by continuous processing, is highlighted by selective generation of established intermediates and byproducts

Exposures of children in Canada to 60-Hz magnetic and electric fields

Objectives This study characterized personal exposures of Canadian children to 60-Hz magnetic and electric fields and explained the variability. Methods Altogether 382 Canadian children up to 15 years of age wore meters recording 60-Hz electric and magnetic fields over 2 days. Meter location was recorded. Thereafter, meters recorded fields in the center of the children's bedrooms for 24 h. Personal exposures were calculated for home, school or day care, outside the home, bedroom at night, and all categories combined (total). Results The arithmetic mean (AM) was 0.121 mT [geometric mean (GM): 0.085 mT), range 0.01-0.8 mT] for total magnetic fields. Fifteen percent of the total exposures exceeded 0.2 mT. The AM of the total electric fields was 14.4 (GM 12.3, range 0.82-64.7) V/m. By location category, the highest and lowest magnetic fields occurred at home during the day (0.142 mT) and during the night (0.112 mT), respectively. Measurements during sleep provided the highest correlation with total magnetic field exposure. Province of measurement explained 14.7% of the variation in the logarithms of total magnetic fields, and season accounted for an additional 1.5%. Electric heating, air conditioning, and housing type appeared to be useful predictors of magnetic field exposures. Conclusions In identifying differences in children's magnetic field exposures between provinces, measurements at night provided the best surrogate for predicting total magnetic field exposure, followed by at-home exposure and 24-h bedroom measurements. Electrical heating and air conditioning, wiring type, and type of housing appear to be promising indicators of magnetic field levels

An axisymmetric evolution code for the Einstein equations on hyperboloidal slices

We present the first stable dynamical numerical evolutions of the Einstein equations in terms of a conformally rescaled metric on hyperboloidal hypersurfaces extending to future null infinity. Axisymmetry is imposed in order to reduce the computational cost. The formulation is based on an earlier axisymmetric evolution scheme, adapted to time slices of constant mean curvature. Ideas from a previous study by Moncrief and the author are applied in order to regularize the formally singular evolution equations at future null infinity. Long-term stable and convergent evolutions of Schwarzschild spacetime are obtained, including a gravitational perturbation. The Bondi news function is evaluated at future null infinity.Comment: 21 pages, 4 figures. Minor additions, updated to agree with journal versio

Taming tosyl azide: the development of a scalable continuous diazo transfer process

Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. Small quantities of tosyl azide were accessed in a 'one pot' batch procedure using shelf stable, readily available reagents. For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including beta-ketoesters, beta-ketoamides, malonate esters and beta-ketosulfones. An effective in-line quench of sulfonyl azides was also developed, whereby a sacrificial acceptor molecule ensured complete consumption of any residual hazardous diazo transfer reagent. The telescoped diazo transfer process with in-line quenching was used to safely prepare over 21 g of an alpha-diazocarbonyl in > 98% purity without any column chromatography

In-vivo visualisation of the anatomical structures related to the acupuncture points Dai mai and Shen mai by MRI: A single-case pilot study

BACKGROUND: The concept of acupuncture point localisation in Traditional Chinese Medicine (TCM) is based on millenary practical experience. Modern imaging methods such as PET, MRI and SPECT have been used primary for the investigation of the mechanisms of action of acupuncture. In this pilot single-case study we have evaluated the technical possibilities for in-vivo imaging of the anatomical relations of acupuncture points using state of the art MRI. METHODS: Preliminary experiments relating to the quality of acupuncture needles under the setting of MRI were done both with stainless steel and gold needles. In a second step, in-vivo imaging was carried out. A licensed acupuncture practitioner (RM) chose two points belonging to the so-called extraordinary vessels. In 2 sequential, separate procedures, he inserted himself gold acupuncture needles using a neutral technique (known as Ping Bu Ping Xie) into the Dai mai and Shen mai points, i.e. gall bladder 26 and bladder 62. Imaging was done on a Siemens Magnetom Avanto MR scanner using a head array and body coil. Mainly T1-weighted imaging sequences, as routinely used for patient exams, were used to obtain multi-slice images. RESULTS: In the preliminary experiments only acupuncture needles made of gold showed enough stability in order to be used for further imaging procedures. Using an onion and a banana as an object, further studies showed that the gold needles produced a void defect that corresponds to the tip of the inserted needle, while at the same time an artefactually increased diameter was observed. The in-vivo experiments showed that the Dai mai point was in relation to the abdominal internal oblique muscle. The Shen mai point artefact showed up close to the longus and brevis peroneal tendons at the fibular malleolus. Side effects related to heating or burning were not observed. Improved anatomical recognition was obtained using 3D-volume rendering techniques. CONCLUSION: Through an adequate choice of acupuncture material (gold needles) as well as of ideal MRI imaging sequences it has been possible to visualize the anatomical characteristics at the acupuncture points Dai mai and Shen mai in-vivo. At the selected sites the needles showed a relation to tendino-fascial and muscular structures. These anatomical structures fit well into the recently described WOMED concept of lateral tension in which these acupuncture points play a regulatory role

The XMM Cluster Survey: The Stellar Mass Assembly of Fossil Galaxies

This paper presents both the result of a search for fossil systems (FSs) within the XMM Cluster Survey and the Sloan Digital Sky Survey and the results of a study of the stellar mass assembly and stellar populations of their fossil galaxies. In total, 17 groups and clusters are identified at z < 0.25 with large magnitude gaps between the first and fourth brightest galaxies. All the information necessary to classify these systems as fossils is provided. For both groups and clusters, the total and fractional luminosity of the brightest galaxy is positively correlated with the magnitude gap. The brightest galaxies in FSs (called fossil galaxies) have stellar populations and star formation histories which are similar to normal brightest cluster galaxies (BCGs). However, at fixed group/cluster mass, the stellar masses of the fossil galaxies are larger compared to normal BCGs, a fact that holds true over a wide range of group/cluster masses. Moreover, the fossil galaxies are found to contain a significant fraction of the total optical luminosity of the group/cluster within 0.5R200, as much as 85%, compared to the non-fossils, which can have as little as 10%. Our results suggest that FSs formed early and in the highest density regions of the universe and that fossil galaxies represent the end products of galaxy mergers in groups and clusters. The online FS catalog can be found at http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.html.Comment: 30 pages, 50 figures. ApJ published version, online FS catalog added: http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.htm

Knowledge and attitudes to prescription charges in New Zealand and England

Prescription charge regimes vary between countries but there is little research on how much people know about these or support values underlying them. To explore, in New Zealand (NZ) and England, the public's knowledge of, and attitudes to, charges and whether knowledge and attitudes varied by demographic characteristics or by values about entitlement to public goods. A questionnaire was developed and administered to people over 18 recruited in public places in NZ and England. 451 people in NZ and 300 people in England participated. Less than half in each country knew the current prescription charge. In each country 62% of people were unaware of arrangements to protect people from excessive annual charges. Support for free or lower cost medicines for children, people over 65, people on low incomes, people on benefits, and people with chronic health problems was higher in England than in NZ. Support varied by participants' demographic characteristics and, in the case of people on low incomes and people on benefits, by values about universal entitlements. Gaps in knowledge, particularly about mechanisms to protect people from high costs, are concerning and may lead to people paying excessive charges. There was consensus about the elderly, children and the chronically ill being "deserving" of lower prescription charges, but people who did not believe in universal access to public goods appeared to see people on low incomes or benefits as less "deserving". In general, public views resembled those underlying the prescription charge regime in their country. [Abstract copyright: Copyright © 2017 Elsevier Inc. All rights reserved.