Use of a small particle solid‐core packing for improved efficiency and rapid measurement of sirolimus and everolimus by LC‐MS/MS

Measurement of whole blood sirolimus and everolimus is required in order to optimize patient treatment following solid organ transplant. Assay by LC‐MS/MS is increasingly preferred; however efficient use of the instrument and short turnaround times are crucial. Use of a 1.6 µm solid‐core packing HPLC column (Cortecs) gave significant increases in efficiency, sensitivity and throughput compared with an existing method, following simple protein precipitation of small‐volume (20 μL) whole blood samples. Sirolimus, everolimus and the stable isotopic internal standard (¹³C₂D₄ – everolimus) eluted at around 0.8 min, and total analytical run time was 2.2 min, saving almost 4 min per sample compared with an existing method. Within‐assay imprecision (CV) was 3.3–8.5%, and between‐assay imprecision was 2.2–10.8%. Retrospective assay of external quality assurance samples and comparison of patient samples assayed in parallel showed only small differences (between +6.8 and ?1.9%) in results using the Cortecs column when compared with the existing method. No significant interferences or ion suppression were observed. Copyright © 2015 John Wiley & Sons, Ltd.     

Ring-rearrangement metathesis of substituted dihydropyrans and dihydrofurans

The rearrangement of dihydropyrans and dihydrofurans featuring appending olefins has been studied. The rearranged products bear resemblance with polyunsaturated di- and trisaccharides. Examples of functionalization prior to, or following, rearrangement are provided suggesting that the method should be useful for the synthesis of nonclassical saccharides. This work also illustrates the power of cascade methatetic processes for increasing molecular complexity starting from relatively simple heterocycles.     

Detoxification of Chemical Warfare Agents Using a Zr6‐Based Metal–Organic Framework/Polymer Mixture

Owing to their high surface area, periodic distribution of metal sites, and water stability, zirconium‐based metal–organic frameworks (Zr₆‐MOFs) have shown promising activity for the hydrolysis of nerve agents GD and VX, as well as the simulant, dimethyl 4‐nitrophenylphosphate (DMNP), in buffered solutions. A hurdle to using MOFs for this application is the current need for a buffer solution. Here the destruction of the simulant DMNP, as well as the chemical warfare agents (GD and VX) through hydrolysis using a MOF catalyst mixed with a non‐volatile, water‐insoluble, heterogeneous buffer is reported. The hydrolysis of the simulant and nerve agents in the presence of the heterogeneous buffer was fast and effective.     

The standard double bubble is the unique stable double bubble in

We prove that the only equilibrium double bubble in which is stable for fixed areas is the standard double bubble. This uniqueness result also holds for small stable double bubbles in surfaces, where it is new even for perimeter-minimizing double bubbles.

     

Enantiodivergence in small-molecule catalysis of asymmetric phosphorylation: concise total syntheses of the enantiomeric D-myo-inositol-1-phosphate and D-myo-inositol-3-phosphate

Peptide-based catalysts have been found that catalyze the enantiodivergent phosphorylation of a meso myo-inositol-derived triol (1). The sequential screening of random peptide libraries, followed by the evaluation of a focused library, led to the identification of two peptides (2 and 24) that are complementary in producing enantiomeric D-myo-inositol-1-phosphate and D-myo-inositol-3-phosphate derivatives. The catalysts were then used to complete efficient total syntheses of both D-I-1P and D-I-3P in optically pure form. Additional information is gleaned from relative rate experiments that unambiguously show the catalysts to afford enantioselection through rate accelerative pathways with respect to simple achiral alkylimidazole catalysts. Furthermore, solvent effect studies show that the two enantiodivergent catalysts exhibit different tolerances of polar media. The systematic discovery of site-selective catalysts establishes a basis for future studies of chiral catalysts that differentiate unique functional groups in polyfunctional molecules.     

How to Make Drugs Orally Active: A Substrate Template for Peptide Transporter PepT1

By building key structural features into hydrophilic drugs, they can be recognized by the PepT1 transporter system of the small intestine and rendered orally active. The model shown provides, for the first time, a 3D template for all known substrates of PepT1.     

In situ preparation of a highly active N-heterocyclic carbene-coordinated olefin metathesis catalyst

Highly active N-heterocyclic carbene-coordinated catalysts may be synthesized and used in situ, without requiring prior isolation of the catalyst. Activation of this in situ catalyst with ethereal HCl dramatically reduces the reaction times required for high conversions. A variety of alpha,beta-unsaturated carbonyl-containing substrates participate readily in cross and ring-closing metathesis reactions using this preparation.     

MiniMax: What has been learned thus far

Summary A small experiment, ?MiniMax?, has been set up in the C0 intersection region of the Fermilab Tevatron to seek evidence for disoriented chiral condensates and to study other forward physics phenomena. The experiment consists of a proportional wire chamber telescope accompanied by scintillation (trigger) counters, a lead converter, and followed by an electromagnetic calorimeter. The solid angle accepted is a cone centered at pseudorapidity (η) of 4.1 and of radius (in η-ϕ space) of about 0.6. Over 2.5 million events thus far have demonstrated the successful operation of the apparatus, however to date the analysis has not progressed sufficiently to permit any conclusions concerning disoriented chiral condensates. presented byL. W. Jones Paper presented at the Special Session on very high-energy cosmic-ray interactions (superfamilies) of the XXIV International Cosmic-Ray Conference, Rome, August 28–September 8, 1995.     

Modelling flow over a backward–facing step using the F.E.M. and the two-equation model of turbulence

Flow over a downstream-facing step is predicted using the F.E.M. A two-equation model of turbulence is employed where the transport of turbulence kinetic energy and dissipation rate are depicted using transport-type equations, i.e. the two-equation model of turbulence. The results obtained are compared with other models and experimental results. Generally, the model was found to be under-predictive with regard to the reattachment length when previous empirical data was used in the transport equations.