Quantitative determination of d‐ and l‐threo enantiomers of methylphenidate in brain tissue by liquid chromatography–mass spectrometry

Methylphenidate, a psychostimulant used for the treatment of attention deficit hyperactivity disorder and narcolepsy, is administered as a 50:50 racemic mixture, despite the fact that d‐methylphenidate has been shown to have greater pharmacologic activity. This paper presents a validated LC‐MS/MS approach to separation and quantification of methylphenidate enantiomers using a vancomycin column and triethylammonium acetate to enhance the chiral separation. The method is applicable to the monitoring of these enantiomers in mouse brain, with a limit of detection of 0.5 ng/mL and a lower limit of quantification of 7.5 ng/mL. Copyright © 2013 John Wiley & Sons, Ltd.     

Discovery and characterization of a cell-permeable, small-molecule c-Abl kinase activator that binds to the myristoyl binding site

c-Abl kinase activity is regulated by a unique mechanism involving the formation of an autoinhibited conformation in which the N-terminal myristoyl group binds intramolecularly to the myristoyl binding site on the kinase domain and induces the bending of the αI helix that creates a docking surface for the SH2 domain. Here, we report a small-molecule c-Abl activator, DPH, that displays potent enzymatic and cellular activity in stimulating c-Abl activation. Structural analyses indicate that DPH binds to the myristoyl binding site and prevents the formation of the bent conformation of the αI helix through steric hindrance, a mode of action distinct from the previously identified allosteric c-Abl inhibitor, GNF-2, that also binds to the myristoyl binding site. DPH represents the first cell-permeable, small-molecule tool compound for c-Abl activation.     

Selection of enantioselective acyl transfer catalysts from a pooled peptide library through a fluorescence-based activity assay: an approach to kinetic resolution of secondary alcohols of broad structural scope.

An assay employing a fluorescently labeled split and pool peptide library has been applied to the discovery of a new class of octapeptide catalysts for the kinetic resolution of secondary alcohols. A highly diverse library of peptide-based catalysts was synthesized on solid-phase synthesis beads such that each individual bead was co-functionalized with (i) a uniform loading of a pH-sensitive fluorophore and (ii) a unique peptide-based catalyst. The library was then screened for activity in acylation reactions employing (+/-)-sec-phenylethanol as the substrate and acetic anhydride as the acylation agent. From the most active catalysts, a lead peptide (4) was identified that provides a selectivity-factor (k(rel)) of 8.2 upon resynthesis and evaluation under homogeneous conditions. A "directed" second-generation split and pool peptide library was synthesized such that the new peptide sequences in the library were biased toward the lead structure. Random samples of the second generation library were screened in single bead assays that revealed several new peptide-based catalysts that afford improved selectivities in kinetic resolutions. Peptide catalyst 13 proves effective for the kinetic resolution of sec-phenylethanol (k(rel) = 20), as well as eight other secondary alcohols of a broad substrate scope (k(rel) = 4 to >50).     

A Stability Analysis of an Electrostatic Precipitator Ionizer

An original study of wire oscillation in the ionizer unit of an electrostatic precipitator was made. The ionizer unit was modeled into a theoretical block diagram system, from which stability criteria were derived. Experimental measurements of the system parameters were devised. A comparison of an experimental single wire, double plate model and the theoretical system model resulted in close agreement.     

Massive particles in five dimensions

We consider a five-dimensional model of the universe with a dynamical extra dimension. Calculations of the ratio of the number density of Kolb and Slansky type pyrgons to that photons show the model to be uncacceptable. However by inserting N matter fields into the original action, it becomes possible to reduce the ratio below the observational bound.     

Sound radiation from Caribbean steelpans

Besides radiating sound from the note area being struck, a steelpan radiates from neighboring note areas that vibrate sympathetically, from the areas between notes, and from the skirt [Rossing et al., Phys. Today 49(3), 24-29 (1996)]. Measurements were taken in an anechoic chamber using a four-microphone intensity probe to visualize the acoustic radiation from selected notes on a double second and a low tenor steelpan. Swept sinusoidal excitation was effected using an electromagnet. Sound intensity maps were drawn for the first three harmonics.     

Session of the seminar “algebra i logika”

Session of the seminar algebra i logika