Comparison of triple quadrupole,hybrid linear ion trap triple quadrupole,time‐of‐flight and LTQ‐Orbitrap mass spectrometers in drug discovery phase metabolite screening and identification in vitro – amitriptyline and verapamil as model compounds

Liquid chromatography in combination with mass spectrometry (LC/MS) is a superior analytical technique for metabolite profiling and identification studies performed in drug discovery and development laboratories. In the early phase of drug discovery the analytical approach should be both time‐ and cost‐effective, thus providing as much data as possible with only one visit to the laboratory, without the need for further experiments. Recent developments in mass spectrometers have created a situation where many different mass spectrometers are available for the task, each with their specific strengths and drawbacks. We compared the metabolite screening properties of four main types of mass spectrometers used in analytical laboratories, considering both the ability to detect the metabolites and provide structural information, as well as the issues related to time consumption in laboratory and thereafter in data processing. Human liver microsomal incubations with amitriptyline and verapamil were used as test samples, and early‐phase ‘one lab visit only’ approaches were used with all instruments. In total, 28 amitriptyline and 69 verapamil metabolites were found and tentatively identified. Time‐of‐flight mass spectrometry (TOFMS) was the only approach detecting all of them, shown to be the most suitable instrument for elucidating as comprehensive metabolite profile as possible leading also to lowest overall time consumption together with the LTQ‐Orbitrap approach. The latter however suffered from lower detection sensitivity and false negatives, and due to slow data acquisition rate required slower chromatography. Approaches with triple quadrupole mass spectrometry (QqQ) and hybrid linear ion trap triple quadrupole mass spectrometry (Q‐Trap) provided the highest amount of fragment ion data for structural elucidation, but, in addition to being unable to produce very high‐important accurate mass data, they suffered from many false negatives, and especially with the QqQ, from very high overall time consumption. Copyright © 2010 John Wiley & Sons, Ltd.     

Fluctuation Bounds in the Exponential Bricklayers Process

This paper is the continuation of our earlier paper (Balázs et al. in Ann. Inst. Henri Poincaré Probab. Stat. 48(1):151–187, 2012), where we proved t ^1/3-order of current fluctuations across the characteristics in a class of one dimensional interacting systems with one conserved quantity. We also claimed two models with concave hydrodynamic flux which satisfied the assumptions which made our proof work. In the present note we show that the totally asymmetric exponential bricklayers process also satisfies these assumptions. Hence this is the first example with convex hydrodynamics of a model with t ^1/3-order current fluctuations across the characteristics. As such, it further supports the idea of universality regarding this scaling.     

Layer-by-layer deposition of a polythiophene/Au nanoparticles multilayer with effective electrochemical properties

Multilayers consisting of a water soluble polythiophene derivative and Au nanoparticles have been deposited onto different electrode substrates by means of layer-by-layer deposition technique. The assembly of the films has been performed by taking advantage of the electrostatic interactions between the positively charged imidazolic moiety of the polythiophene chain and the negative charges of citrate ions surrounding Au nanoparticles, as well of the affinity of S to Au. The nanoparticles result stably grafted to the organic matrix. The resulting modified electrodes have been characterised through electrochemical, spectroelectrochemical and microscopic techniques. The results evidenced that a high number of individual nanoparticles is present inside the multilayer. The presence of nanoparticles is of chief importance for most effective charge percolation through the multilayer, as suggested by the responses to electroactive probe species in solution. The electrocatalytic performances of the modified electrodes have been tested with respect to the oxidation of ascorbic acid.

     

Synthesen und Strukturen der polymeren Silber‐Komplexe [Ag2Cl2(dppbp)3]∞, [Ag2(SPh)2(dppe)3]∞ und [Ag2(SPh)2(triphos)]∞ sowie der Silber‐Chalkogenido‐Cluster [Ag7(SPh)7(dppm)3], {[Ag7(TePh)7(dppp)3]2(dppp)} und [Ag22Cl(SPh)10(PhCOO)11(dmf)3]∞

Syntheses and Structures of the Polymeric Silver Complexes [Ag₂Cl₂(dppbp)₃]_∞, [Ag₂(SPh)₂(dppe)₃]_∞ and [Ag₂(SPh)₂(triphos)]_∞ as well as the Silver Chalcogenido Clusters [Ag₇(SPh)₇(dppm)₃], {[Ag₇(TePh)₇(dppp)₃]₂(dppp)}, and [Ag₂₂Cl(SPh)₁₀(PhCOO)₁₁(dmf)₃]_∞ The reaction of silver carboxylate with silylated chalcogen compounds have been found to have a possibility for the synthesis of metal‐chalcogenide‐custers. Especially phosphine ligands have been found to be useful in stabilising the cluster cores. Some of the silver carboxylate phosphine complexes, which are formed in‐situ, ([Ag₂Cl₂(dppbp)₃]_∞ ( 1 )) and some silver chalcogen complexes ([Ag₂(SPh)₂(dppe)₃]_∞ ( 2 ) und [Ag₂(SPh)₂(triphos)]_∞ ( 3 )), could be isolated and characterised by X‐ray diffraction. Using special reaction conditions, it is possible to isolate cluster species like [Ag₇(SPh)₇(dppm)₃] ( 4 ), {[Ag₇(TePh)₇(dppp)₃]₂(dppp)} ( 5 ) and [Ag₂₂Cl(SPh)₁₀(PhCOO)₁₁(dmf)₃]_∞ ( 6 ) beside the complex compounds. 1: Space group P2₁/n (No. 14), Z = 2, a = 1336, 1(2), b = 2081, 2(5), c = 2015, 4(4) pm, β = 99, 87(2)°; 2: Space group P2₁/n (No. 14), Z = 2, a = 1416, 1(3), b = 1874, 7(4), c = 1444, 8(3) pm, β = 93, 26(3)°; 3: Space group P2₁/n (No. 14), Z = 4, a = 1456, 8(3, b = 1890, 2(4), c = 1916, 1(4) pm, β = 99, 11(3)°; 4: Space group P2₁/n (No. 14), Z = 4, a = 1570, 2(3), b = 2798, 5(6), c = 2752, 7(6) pm, β = 98, 02(3)°; 5: Space group P1 (No. 2), Z = 2, a = 2115, 5(4), b = 2553, 3(5), c = 3188, 7(6) pm, α = 68, 87(3)°, β = 74, 05(3)°, γ = 69, 70(3)°; 6: Space group P1 (No. 2), Z = 2, a = 1583, 0(3), b = 1709, 6(3), c = 2990, 0(6) pm, α = 80, 41(3)°, β = 88, 86(3)°, γ = 71, 10(3)°).     

Assessment of Agroeconomic Indicators of Sesamum indicum L. as Influenced by Application of Boron at Different Levels and Plant Growth Stages

To achieve the nutritional target of human food, boron (B) has been described as an essential mineral in determining seed and theoretical oil yield of Sesamum indicum L. The research to increase its cultivation is garnering attention due to its high oil content, quality and its utilization for various purposes, which include human nutrition as well as its use in the food industry. For this, a two-year field experiment was performed at PAU, Punjab, India to determine the effect of different concentrations of foliar-applied B (20, 30 and 40 mg L⁻¹) and different growth stages of crop, i.e., we measured the effects on agroeconomic indicators and certain quality parameters of sesame using different concentrations of B applied at the flowering and capsule formation stages as compared to using water spray and untreated plants. Water spray did not significantly affect the studied parameters. However, B application significantly increased the yield, uptake, antioxidant activity (AOA) and theoretical oil content (TOC) compared to those of untreated plants. The maximum increase in seed yield (26.75%), B seed and stover uptake (64.08% and 69.25%, respectively) as well as highest AOA (69.41%) and benefit to cost ratio (B:C ratio 2.63) was recorded when B was applied at 30 mg L⁻¹ at the flowering and capsule formation stages. However, the maximum sesame yield and B uptake were recorded when B was applied at a rate of 30 mg L⁻¹. A significant increase in TOC was also recorded with a B application rate of 30 mg L⁻¹. For efficiency indices, the higher values of boron agronomic efficiency (BAE) and boron crop recovery efficiency (BCRE) were recorded when B was applied at 20 mg L⁻¹ (5.25 and 30.56, respectively) and 30 mg L⁻¹ (4.96 and 26.11, respectively) at the flowering and capsule formation stages. In conclusion, application of B @ 30 mg L⁻¹ at the flowering and capsule formation stages seemed a viable technique to enhance yield, B uptake and economic returns of sesame.     

Syntheses and Crystal Structures of Rb2B2Se7, Tl2B2Se7, Cs3B3Se10, and Tl3B3Se10: New Perseleno‐selenoborates with Polymeric Anionic Chains

The perseleno‐selenoborates Rb₂B₂Se₇ and Cs₃B₃Se₁₀ were prepared from the metal selenides, amorphous boron and selenium, the thallium perseleno‐selenoborates Tl₂B₂Se₇ and Tl₃B₃Se₁₀ directly from the elements in evacuated carbon coated silica tubes by solid state reactions at temperatures between 920 K and 950 K. All structures were refined from single crystal X‐ray diffraction data. The isotypic perseleno‐selenoborates Rb₂B₂Se₇ and Tl₂B₂Se₇ crystallize in the monoclinic space group I 2/a (No. 15) with lattice parameters a = 12.414(3) Å, b = 7.314(2) Å, c = 14.092(3) Å, β = 107.30(3)°, and Z = 4 for Rb₂B₂Se₇ and a = 11.878(2) Å, b = 7.091(2) Å, c = 13.998(3) Å, β = 108.37(3)° with Z = 4 for Tl₂B₂Se₇. The isotypic perseleno‐selenoborates Cs₃B₃Se₁₀ and Tl₃B₃Se₁₀ crystallize in the triclinic space group P1 (Cs₃B₃Se₁₀: a = 7.583(2) Å, b = 8.464(2) Å, c = 15.276(3) Å, α = 107.03(3)°, β = 89.29(3)°, γ = 101.19(3)°, Z = 2, (non‐conventional setting); Tl₃B₃Se₁₀: a = 7.099(2) Å, b = 8.072(2) Å, c = 14.545(3) Å, α = 105.24(3)°, β = 95.82(3)°, γ = 92.79(3)°, and Z = 2). All crystal structures contain polymeric anionic chains of composition ([B₂Se₇]^2–)_n or ([B₃Se₁₀]^3–)_n formed by spirocyclically fused non‐planar five‐membered B₂Se₃ rings and six‐membered B₂Se₄ rings in a molar ratio of 1 : 1 or 2 : 1, respectively. All boron atoms have tetrahedral coordination with corner‐sharing BSe₄ tetrahedra additionally connected via Se–Se bridges. The cations are situated between three polymeric anionic chains leading to a nine‐fold coordination of the rubidium and thallium cations by selenium in M₂B₂Se₇ (M = Rb, Tl). Coordination numbers of Cs⁺ (Tl⁺) in Cs₃B₃Se₁₀ (Tl₃B₃Se₁₀) are 12(11) and 11(9).     

Bacillus cereus Toxin Repertoire: Diversity of (Iso)cereulide(s)

The emetic Bacillus cereus toxin cereulide (1) poses a significant safety risk in the food industry, causing emesis and nausea after consumption of contaminated foods. Analogously to cereulide, the structures of various isocereulides, namely, isocereulides A–G, have been recently reported and could also be identified in B. cereus-contaminated food samples. The HPLC fractionation of B. cereus extracts allows us to isolate additional isocereulides. By applying MSⁿ sequencing, post-hydrolytic dipeptide, amino acid and α-hydroxy acid analyses using UPLC-ESI-TOF-MS to purify the analytes, seven new isocereulides H–N (2–8) could be elucidated in their chemical structures. The structure elucidation was supported by one-dimensional and two-dimensional NMR spectra of the isocereulides H (2), K (5), L and N (6 + 8) and M (7). The toxicity of 2–8 was investigated in a HEp-2 cell assay to determine their respective 50% effective concentration (EC₅₀). Thus, 2–8 exhibited EC₅₀ values ranging from a 0.4- to 1.4-fold value compared to cereulide (1). Missing structure-activity correlations indicate the necessity to determine the toxic potential of all naturally present isocereulides as single compounds to be able to perform a thorough toxicity evaluation of B. cereus-contaminated foods in the future.