Determination of Binding Selectivities by Electrospray lonization Mass Spectrometry

Electrospray ionization mass spectrometry is used for the measurement of binding selectivities of four model hosts, 18-crown-6, dibenzo-18-crown-6, dicyclohexano-18-crown-6, and 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane, for both alkali and transition metal ions. Based on the intensities of the metal complexes observed in the mass spectra, the relative binding selectivities can be directly estimated. Results are compared to theoretical selectivities obtained by solving simultaneous equilibria equations that define the competing complexation reactions in solution. Good agreement is found in most cases, thus allowing rapid determination of binding selectivities of hosts in a variety of solvents.     

The Lewis acidity of bismuth(III) halides: a DFT analysis

The Lewis acidity of BiX₃ (X=Cl, Br, I) is explored using density-functional theory (DFT) studies of simple complexes with various alcohol and carbonyl substrates. The calculated relative energies of the complexes follow the trend of hardness for BiX₃ (Cl>Br>I). The observed halogen exchange reaction of BiCl₃ with alcohols and alkyl halides is discussed in terms of the computational results as well as theories of hardness and carbocation stability. The DFT results predict similar activation of substrates by molecular BiI₃ relative to BiBr₃, which is inconsistent with experimental results, which show no reactivity for the iodide in nonpolar solvents. However, the molecular form is unlikely in these solvents as BiI₃ is an ionic salt in contrast to the chloride and bromide, which are covalent solids.     

Substrate binding and activation via pendant hydrogen-bonding groups as an approach to biomimetic homogeneous catalysis

In a biomimetic approach to organometallic catalysis, pendant hydrogen-bonding groups are shown to influence the chemistry of ligand binding and activation in an iridium complex. Such groups can bind a substrate by hydrogen bonding and so offer the possibility of a biomimetic approach to catalysis where binding is controlled via molecular recognition. Because catalyst design in this area may be challenging, combinatorial and rapid screening methods may be needed to assay potential catalysts and initial progress on developing these methods for hydrosilation of alkenes and imines is described. Catalysis of aldehyde imination and the origin of pK_a changes of bound H₂ are discussed.     

Gold-catalyzed rearrangement of substituted allyl aryl ethers

Triphenylphosphinegold(I) complexes catalyze the Claisen-type rearrangement of aryl allyl ethers to the corresponding branched and linear products. The product distribution depends on the olefin geometry of the allylic ether. Stereochemical transfer experiments support an ionic mechanism.     

Synthesis of nitrogen analogues of salacinol and their evaluation as glycosidase inhibitors.

The syntheses of two nitrogen analogues (11 and 12) of the naturally occurring sulfonium ion, salacinol (7) are described. The latter compound is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of a 1,4-dideoxy-1,4-imino-D- or L-arabinitol at the least hindered carbon of 2,4-O-benzylidene D- or L-erythritol-1,3-cyclic sulfate. The nitrogen analogues bear a permanent positive charge and serve as mimics of the sulfonium ion. We reasoned that these ammonium derivatives should function in a manner similar to that of known glycosidase inhibitors of the alkaloid class such as castanospermine (4) and deoxynojirimycin (5). Enzyme inhibition assays indicate that salacinol (7) is a weak (K(i) = 1.7 mM) inhibitor of glucoamylase, whereas compounds 11 and 12 inhibit glucoamylase with K(i) values in the range approximately 10-fold higher. The nitrogen analogues 11 and 12 showed no significant inhibitory effect of either barley alpha-amylase (AMY1) or porcine pancreatic alpha-amylase (PPA) at concentrations of 5 mM. In contrast, salacinol (7) inhibited AMY1 and PPA in the micromolar range, with K(i) values of 15 +/- 1 and 10 +/- 2 microM, respectively.     

Rapid analysis of tetracaine for a tape stripping pharmacokinetic study using short‐end capillary electrophoresis

A rapid and simple short‐end (reverse) capillary zone electrophoresis method was developed and validated for the separation and quantification of tetracaine in skin using tape samples. The separation was performed in a 485 mm (400 mm to window) × 50 µm internal diameter fused silica capillary using a background electrolyte of phosphoric acid–Tris pH2.5 at –25 kV. The extraction of tetracaine from tape samples was achieved using methanol diluted to 50% with water before injection. Procaine was the internal standard. The migration times for procaine and tetracaine were 1.25 and 1.36 min, respectively. The limit of quantification for tetracaine was 50 µg, with a signal‐to‐noise ratio greater than 10. The calibration curve was linear from 50 to 1200 µg with r² greater than 0.99. The CV for both within‐ and between‐assay imprecision and the percentage inaccuracy for the quality control samples including lower and upper limits of quantitation were <12.1% and <11%, respectively. The absolute mean recovery of tetracaine was >97%. The accuracy and selectivity of this method allowed the rapid measurement of tetracaine in tape samples obtained from a skin tape stripping study of local anaesthetics in healthy subjects. Copyright © 2008 John Wiley & Sons, Ltd.     

3,3-Di­phenyl-6-(p-toluene­sulfonyl)-6-aza-3-silabi­cyclo­[3.1.0]­hexane

The title compound, C₂₃H₂₃NO₂SSi, at 100 K adopts a boat conformation which brings the C—H bond of an axial phenyl substituent into proximity [C⃛N = 3.376 (1) Å] with the aziridine lone pair. The factors which favour this conformation for bi­cyclo­[3.1.0]­hexane systems are considered.     

Catalytic enantioselective Michael additions to unsaturated ester derivatives using chiral copper(II) Lewis acid complexes

[formula: see text] Chiral Cu(II) bisoxazoline (box) Lewis acids have been developed as catalysts of the Michael addition of enolsilanes to unsaturated ester derivatives. While enantioselection is stereoregular, the sense of diastereoselection is directly related to thioester enolsilane geometry: (E) enolsilanes give anti adducts and (Z) enolsilanes afford syn adducts. The size of the enolsilane alkylthio substituent directly impacts the magnitude of diastereoselection.     

Minimum Weight and Dimension Formulas for Some Geometric Codes

The geometric codes are the duals of the codes defined by the designs associated with finite geometries. The latter are generalized Reed–Muller codes, but the geometric codes are, in general, not. We obtain values for the minimum weight of these codes in the binary case, using geometric constructions in the associated geometries, and the BCH bound from coding theory. Using Hamada's formula, we also show that the dimension of the dual of the code of a projective geometry design is a polynomial function in the dimension of the geometry.