Conventional vs. Microwave- or Mechanically-Assisted Synthesis of Dihomooxacalix[4]arene Phthalimides: NMR,X-ray and Photophysical Analysis §

Direct O-alkylation of p-tert-butyldihomooxacalix[4]arene (1) with N-(bromopropyl)- or N-(bromoethyl)phthalimides and K₂CO₃ in acetonitrile was conducted under conventional heating (reflux) and using microwave irradiation and ball milling methodologies. The reactions afforded mono- and mainly distal di-substituted derivatives in the cone conformation, in a total of eight compounds. They were isolated by column chromatography, and their conformations and the substitution patterns were established by NMR spectroscopy (¹H, ¹³C, COSY and NOESY experiments). The X-ray structures of four dihomooxacalix[4]arene phthalimide derivatives (2a, 3a, 3b and 5a) are reported, as well as their photophysical properties. The microwave (MW)-assisted alkylations drastically reduced the reaction times (from days to less than 45 min) and produced higher yields of both 1,3-di-substituted phthalimides (3a and 6a) with higher selectivity. Ball milling did not reveal to be a good method for this kind of reaction.     

Selectivity Effects in Bimetallic Catalysis

An emerging area of homogeneous catalysis is the use of catalysts featuring two closely associated metal sites. This approach complements the traditional focus on single‐site catalysts and makes available new parameters with which to optimize catalytic behavior. Single‐site catalysts are optimized through changing 1) the identity of the metal, and 2) the steric and electronic properties of the ligands. Bimetallic catalysts introduce new optimization parameters such as 3) catalyst nuclearity (mononuclear vs. binuclear), and 4) bimetallic pairing (relative compatibility of two metal sites). In order to harness these new optimization parameters in developing systems, it is necessary to first understand the origin of bimetallic selectivity effects that already have been documented. This Concept article highlights bimetallic effects on the chemo‐, regio‐, and stereoselectivity of catalytic transformations, using selected case studies from the recent literature as illustrative examples.     

Spontaneous Reconstitution of Functional Transmembrane Proteins During Bioorthogonal Phospholipid Membrane Synthesis

Transmembrane proteins are critical for signaling, transport, and metabolism, yet their reconstitution in synthetic membranes is often challenging. Non‐enzymatic and chemoselective methods to generate phospholipid membranes in situ would be powerful tools for the incorporation of membrane proteins. Herein, the spontaneous reconstitution of functional integral membrane proteins during the de novo synthesis of biomimetic phospholipid bilayers is described. The approach takes advantage of bioorthogonal coupling reactions to generate proteoliposomes from micelle‐solubilized proteins. This method was successfully used to reconstitute three different transmembrane proteins into synthetic membranes. This is the first example of the use of non‐enzymatic chemical synthesis of phospholipids to prepare proteoliposomes.     

Integral equation formulation for buoyancy-driven convection problems

An integral equation formulation for buoyancy-driven convection problems is developed and illustrated. Buoyancy-driven convection in a bounded cylindrical geometry with a free surface is studied for a range of aspect ratios and Nusselt numbers. The critical Rayleigh number, the nature of the cellular motion, and the heat transfer enhancement are computed using linear theory. Green's functions are used to convert the linear problem into linear Fredholm integral equations. Theorems are proved which establish the properties of the eigenvalues and eigenfunctions of the linear integral operator which appears in these equations.     

Narrow band quantitative and multivariate electroencephalogram analysis of peri-adolescent period

ABSTRACT: BACKGROUND: The peri-adolescent period is a crucial developmental moment of transition from childhood to emergent adulthood. The present report analyses the differences in Power Spectrum (PS) of the Electroencephalogram (EEG) between late childhood (24 children between 8 and 13 years old) and young adulthood (24 young adults between 18 and 23 years old). RESULTS: The narrow band analysis of the Electroencephalogram was computed in the frequency range of 0--20 Hz. The analysis of mean and variance suggested that six frequency ranges presented a different rate of maturation at these ages, namely: low delta, delta-theta, low alpha, high alpha, low beta and high beta. For most of these bands the maturation seems to occur later in anterior sites than posterior sites. Correlational analysis showed a lower pattern of correlation between different frequencies in children than in young adults, suggesting a certain asynchrony in the maturation of different rhythms. The topographical analysis revealed similar topographies of the different rhythms in children and young adults. Principal Component Analysis (PCA) demonstrated the same internal structure for the Electroencephalogram of both age groups. Principal Component Analysis allowed to separate four subcomponents in the alpha range. All these subcomponents peaked at a lower frequency in children than in young adults. CONCLUSIONS: The present approaches complement and solve some of the incertitudes when the classical brain broad rhythm analysis is applied. Children have a higher absolute power than young adults for frequency ranges between 0-20 Hz, the correlation of Power Spectrum (PS) with age and the variance age comparison showed that there are six ranges of frequencies that can distinguish the level of EEG maturation in children and adults. The establishment of maturational order of different frequencies and its possible maturational interdependence would require a complete series including all the different ages.     

Chiral analytical method development of liquiritigenin with application to a pharmacokinetic study

Pharmacometric characterization studies of liquiritigenin have historically overlooked its chiral nature. To achieve complete characterization, an analytical method enabling the detection and quantification of the individual enantiomers of racemic (±) liquiritigenin is necessary. Resolution of the enantiomers of liquiritigenin was achieved using a simple high‐performance liquid chromatographic method. A Chiralpak® ADRH column was employed to perform baseline separation with UV detection at 210 nm.The standard curves were linear ranging from 0.5 to 100 µg/mL for each enantiomer. Limit of quantification was 0.5 µg/mL. The assay was applied successfully to stereoselective serum disposition of liquiritigenin enantiomers in rats. Liquiritigenin enantiomers were detected in serum as both aglycones and glucuronidated conjugates. Both unconjugated enantiomers had a serum half‐life of ~15 min in rats. The volume of distribution (V_d) for S‐ and R‐liquiritigenin was 1.49 and 2.21 L/kg, respectively. Total clearance (Cl_total) was 5.12 L/h/kg for S‐liquiritigenin and 4.79 L/h/kg for R‐liquiritigenin, and area under the curve (AUC_0‐inf) was 3.95 µg h/mL for S‐liquiritigenin and 4.23 µg h/mL for R‐liquiritigenin. The large volume of distribution coupled with the short serum half‐life suggests extensive distribution of liquiritigenin into tissues. Copyright © 2012 John Wiley & Sons, Ltd.     

Chiral analytical method development and application to pre‐clinical pharmacokinetics of pinocembrin

An analytical method enabling the detection and quantification of the individual enantiomers of racemic (±) pinocembrin is required to fully characterize its pharmacokinetic disposition. Direct resolution of the enantiomers of pinocembrin was achieved using a novel and simple reversed‐phase high‐performance liquid chromatography method with electrospray ionization and detection by mass spectrometry in rat serum. A Chiralcel® AD‐RH column was employed to perform baseline separation with electrospray positive‐mode ionization with selected ion monitoring detection. The standard curves were linear from 0.5 to 100 µg/mL for each enantiomer. The limit of quantification was 0.5 µg/mL. The assay was applied successfully to stereoselective serum disposition of pinocembrin enantiomers in rats. Pinocembrin enantiomers were detected in serum. Both enantiomers had a serum half‐life of ~15 min in rats. Similar values of volume of distribution between the enantiomers were also observed: 1.76 L/kg for S‐pinocembrin and 1.79 L/kg for R‐pinocembrin. Total clearance was 5.527 L//h/kg for S‐pinocembrin and 5.535 L/h/kg for R‐pinocembrin, and the area under the curve was 1.821 µg h/mL for S‐pinocembrin and 1.876 µg h/mL for R‐pinocembrin. The large volume of distribution coupled with the short serum half‐life suggests extensive distribution of pinocembrin into the tissues. Copyright © 2012 John Wiley & Sons, Ltd.