An alternative method to access diverse N,N′-diquaternised-3,3′-biquinoxalinium “biquinoxen” dications

An alternative synthetic route for the design of N,N′-diquaternised-3,3′-biquinoxalinium “biquinoxen” dications is reported, involving oxidative radical coupling of dithionite reduced quinoxaline quaternary salts. Although the reaction is not regioselective, leading to relatively modest yields (up to 32%), the advantages of this new synthetic protocol lie in a simple potentially gram scale synthesis using inexpensive easily accessible reagents with no metal catalysts and no purification steps. Thus whereas the method reported previously to access the N,N′-dimethyl-3,3′-biquinoxalinium, “methylbiquinoxen” precursor gave higher yield than the new method reported here, this new method avoids the limitation of using scarce oxonium reagents. Overall, the new protocol is a robust synthetic strategy which offers new design possibilities

Approaching the limit of CuII/CuImixed valency in a CuIBr2–N-methylquinoxalinium hybrid compound

A novel 1D hybrid salt (MQ)[CuBr2]∞ (MQ = N-methylquinoxalinium) is reported. Structural, spectroscopic and magnetic investigations reveal a minimal CuII doping of less than 0.1%. However it is not possible to distinguish CuI and CuII. The unusually close packing of the organic moieties and the dark brown colour of the crystals suggest a defect electronic structure

A fascinating multifaceted redox-active chelating ligand: introducing the N,N′-dimethyl-3,3′-biquinoxalinium “methylbiquinoxen” platform

To intimately combine a chelating ligand function with the numerous properties of a viologen-like redox-active centre would offer a rare possibility to design controllable multi-redox states, whose properties arise from strongly correlated phenomena between the organic ligand as well as with any metalloid coordinated centres. Such a concept previously proved to be feasible, however is not widely applicable owing to challenges in terms of synthesis, isolation, and aerial sensitivity of both the ligand and its metal complexes. Here we report the first stable example of such a redox-active molecule, N,N′-dimethyl-3,3′-biquinoxalinium2+/˙+/0 “methylbiquinoxen, MBqn2+/˙+/0”, which shows a rich redox chemistry and chelates a metal ion in the case of the metal complex [CdCl2(MBqn0)]. This goes beyond what is possible to achieve using viologens, which are limited by not providing chelation as well as having no accessible biradicaloid state, corresponding to the neutral direduced MBqn0 open-shell behaviour we observe here

Assessments of the Extent to which Health‐Care Providers Involve Patients in Decision Making: A Systematic Review of Studies Using the OPTION Instrument

Background: We have no clear overview of the extent to which health-care providers involve patients in the decision-making process during consultations. The Observing Patient Involvement in Decision Making instrument (OPTION) was designed to assess this. Objective: To systematically review studies that used the OPTION instrument to observe the extent to which health-care providers involve patients in decision making across a range of clinical contexts, including different health professions and lengths of consultation. We conducted online literature searches in multiple databases (2001-12) and gathered further data through networking

Caffeic Acid Phenethyl Ester and Its Amide Analogue Are Potent Inhibitors of Leukotriene Biosynthesis in Human Polymorphonuclear Leukocytes

BACKGROUND: 5-lipoxygenase (5-LO) catalyses the transformation of arachidonic acid (AA) into leukotrienes (LTs), which are important lipid mediators of inflammation. LTs have been directly implicated in inflammatory diseases like asthma, atherosclerosis and rheumatoid arthritis; therefore inhibition of LT biosynthesis is a strategy for the treatment of these chronic diseases. METHODOLOGY/PRINCIPAL FINDINGS: Analogues of caffeic acid, including the naturally-occurring caffeic acid phenethyl ester (CAPE), were synthesized and evaluated for their capacity to inhibit 5-LO and LTs biosynthesis in human polymorphonuclear leukocytes (PMNL) and whole blood. Anti-free radical and anti-oxidant activities of the compounds were also measured. Caffeic acid did not inhibit 5-LO activity or LT biosynthesis at concentrations up to 10 µM. CAPE inhibited 5-LO activity (IC(50) 0.13 µM, 95% CI 0.08-0.23 µM) more effectively than the clinically-approved 5-LO inhibitor zileuton (IC(50) 3.5 µM, 95% CI 2.3-5.4 µM). CAPE was also more effective than zileuton for the inhibition of LT biosynthesis in PMNL but the compounds were equipotent in whole blood. The activity of the amide analogue of CAPE was similar to that of zileuton. Inhibition of LT biosynthesis by CAPE was the result of the inhibition of 5-LO and of AA release. Caffeic acid, CAPE and its amide analog were free radical scavengers and antioxidants with IC(50) values in the low µM range; however, the phenethyl moiety of CAPE was required for effective inhibition of 5-LO and LT biosynthesis. CONCLUSIONS: CAPE is a potent LT biosynthesis inhibitor that blocks 5-LO activity and AA release. The CAPE structure can be used as a framework for the rational design of stable and potent inhibitors of LT biosynthesis

Breaking Symmetry Relaxes Structural and Magnetic Restraints, Suppressing QTM in Enantiopure Butterfly Fe2_{2}Dy2_{2} SMMs**

These 2 coordination clusters are similar but different both in the fine details of their structures as well as their magnetic behaviour. [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{6}$], which normally forms with the racemic version of Me-teaH3 by using enantiopure ligand, allows access to the S-version, but for the R-version there is significant racemisation. Surprisingly, by using the synthesis of [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{4}$(NO$_{3}$)$_{2}$] both enantiopure R- and S-compounds were obtained. In both cases breaking the symmetry of the parent compounds leads to enhanced SMM behaviour. The {Fe$_{2}$Dy$_{2}$} butterfly systems can show single molecule magnet (SMM) behaviour, the nature of which depends on details of the electronic structure, as previously demonstrated for the [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{6}$] compound, where the [N,N-bis-(2-hydroxyethyl)-amino]-2-propanol (Me-teaH$_{3}$) ligand is usually used in its racemic form. Here, we describe the consequences for the SMM properties by using enantiopure versions of this ligand and present the first homochiral 3d/4 f SMM, which could only be obtained for the S enantiomer of the ligand for [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{6}$] since the R enantiomer underwent significant racemisation. To investigate this further, we prepared the [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{4}$(NO$_{3}$)$_{2}$] version, which could be obtained as the RS-, R- and S-compounds. Remarkably, the enantiopure versions show enhanced slow relaxation of magnetisation. The use of the enantiomerically pure ligand suppresses QTM, leading to the conclusion that use of enantiopure ligands is a “gamechanger” by breaking the cluster symmetry and altering the intimate details of the coordination cluster\u27s molecular structure

Compositional meta-analysis of the nutrient profile of potato cultivars

While several potato (Solanum tuberosum L.) cultivars of different maturity groups (e.g. early, mid-season, late) are being selected each year as a result of successful breeding for disease resistance and market requirements, their nutrient management is based on past experience and few experiments. Nutrient profiles from leaf analysis can guide fertilization and liming programs of potato cultivars. Since leaf analytical data are strictly positive and compositional, nutrient profiling using raw data is spoiled by non normal distribution, resonance and spurious correlations. Compositional data analysis provides log ratio transformations that avoid such problems. Our objective was to derive nutrient profiles from tissue analysis using isometric log ratio (ilr) coordinates and meta-analysis for classification of cultivars into uniform nutrient management groups. The dataset comprised 678 potato fields producing more than 28.5 Mg marketable tuber ha-1, i.e. above Quebec average, of the early-, mid-, and late-season cultivars. The first mature leaf from top was sampled at the beginning of flowering for N, P, K, Ca, and Mg analysis. Anionic (N, P) and cationic (K, Ca, Mg) nutrients were arranged into binary partitions representing positive and negative nutrient interactions. Groups of cultivars were compared to ‘Superior’ using ilr mean and standard deviation in the mixed model of meta-analysis. We minimized the within-group heterogeneity (I2 value) by allocating cultivars iteratively between ilr groups. We derived group-specific ilr norms to compute the Aitchison distance. The critical value for nutrient imbalance was 0.38. To guide correcting nutrient deficiencies with appropriate nutrient management techniques, nutrient composition can be altered numerically by a perturbation vector on nutrients that lead to the largest and most negative ilr differences from ilr norms until the Aitchison distance falls below critical value

Rapid and concomitant gut microbiota and endocannabinoidome response to diet-induced obesity in mice

The intestinal microbiota and the expanded endocannabinoid (eCB) system, or endocannabinoidome (eCBome), have both been implicated in diet-induced obesity and dysmetabolism. These systems were recently suggested to interact during the development of obesity. We aimed at identifying the potential interactions between gut microbiota composition and the eCBome during the establishment of diet-induced obesity and metabolic complications. Male mice were fed a high-fat, high-sucrose (HFHS) diet for 56 days to assess jejunum, ileum, and cecum microbiomes by 16S rRNA gene metataxonomics as well as ileum and plasma eCBome by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). The HFHS diet induced early (3 days) and persistent glucose intolerance followed by weight gain and hyperinsulinemia. Concomitantly, it induced the elevation of the two eCBs, anandamide, in both ileum and plasma, and 2-arachidonoyl-glycerol, in plasma, as well as alterations in several other N-acylethanolamines and 2-acylglycerols. It also promoted segment-specific changes in the relative abundance of several genera in intestinal microbiota, some of which were observed as early as 3 days following HFHS diet. Weight-independent correlations were found between the relative abundances of, among others, Barnesiella, Eubacterium, Adlercreutzia, Parasutterella, Propionibacterium, Enterococcus, and Methylobacterium and the concentrations of anandamide and the anti-inflammatory eCBome mediator N-docosahexaenoyl-ethanolamine. This study highlights for the first time the existence of potential interactions between the eCBome, an endogenous system of multifunctional signaling lipids, and several intestinal genera during early and late HFHS-induced dysmetabolic events, with potential impact on the host capability of adapting to increased intake of fat and sucrose

Tracking ultrafast solid-state dynamics using high harmonic spectroscopy

WWe establish time-resolved high harmonic generation (tr-HHG) as a powerful spectroscopy method for tracking photoinduced dynamics in strongly correlated materials through a detailed investigation of the insulator-to-metal phase transitions in vanadium dioxide. We benchmark the technique by comparing our measurements to established momentum-resolved ultrafast electron diffraction, and theoretical density functional calculations. Tr-HHG allows distinguishing of individual dynamic channels, including a transition to a thermodynamically hidden phase. In addition, the HHG yield is shown to be modulated at a frequency characteristic of a coherent phonon of the equilibrium monoclinic phase over a wide range of excitation fluences. These results demonstrate that tr-HHG is capable of tracking complex dynamics in solids through its sensitivity to the band structure

Tracking ultrafast solid-state dynamics using high harmonic spectroscopy

We establish time-resolved high harmonic generation (tr-HHG) as a powerful spectroscopy for photoinduced dynamics in strongly correlated materials through a detailed investigation of the insulator-to-metal transitions in vanadium dioxide. We benchmark our technique by comparing our measurements to established momentum-resolved ultrafast electron diffraction, and theoretical density functional calculations. Tr-HHG allows distinguishing of individual dynamic channels, including a transition to a thermodynamically hidden phase. In addition, the HHG yield is shown to be modulated at a frequency characteristic of a coherent phonon in the equilibrium monoclinic phase over a wide range of excitation fluences. These results demonstrate that tr-HHG is capable of tracking complex dynamics in solids through its sensitivity to the band structure.Comment: 20 pages and 4 figures main text, 8 pages and 4 figures supplementary informatio