Copper(II) Bromide–Catalyzed C-C/C-N Bond-Forming Reactions: Synthesis of Pyrrole-Incorporated Triarylmethanes

We have achieved a facile copper(II) bromide–catalyzed synthesis of 2,3,4-trisubtitued pyrrole incorporated into unsymmetrical triarylmethanes through direct replacement of hydroxyl group in the pyrrolyl phenyl methanol with electron-rich aromatic and heteroaromatic compounds. The newly developed method has been applied to a facile synthesis of a C2 symmetric bis-triarylmethane in which the two triarylmethanes were bridged through piperzine. The copper(II) bromide catalysis led to C-C bond formation at the C(5) position when the reacting partner was imidazole. In contrast, C-N bond formation took place with benzimdazole or 2-methylbenzimidazole.     

Ugi three-component coupling reaction for the synthesis of 2-(6-oxo-11-phenyl-7,8-dihydrobenzo[b]pyrrolo[1,2-d][1,4]diazocin-5(6H)-yl)-2-phenylacetamide derivatives

A three-component, four center Ugi reaction of 3-(1-(2-aminophenyl)-5-phenyl-1H-pyrrol-2-yl)propanoic acid with aromatic aldehyde and t-butyl isocyanide has been achieved to produce a novel class of N-tert-butyl-2-(6-oxo-11-phenyl-7,8-dihydrobenzo[b]pyrrolo[1,2-d][1,4]diazacine-5(6H)-yl)-2-phenylacetamides in moderate to good yields.     

Formation of Periodic γ‐Turns in α/β‐Hybrid Peptides: DFT and NMR Experimental Evidence

Hybrid peptidic oligomers comprising natural and unnatural amino acid residues that can exhibit biomolecular folding and hydrogen‐bonding mimicry have attracted considerable interest in recent years. While a variety of hybrid peptidic helices have been reported in the literature, other secondary structural patterns such as γ‐turns and ribbons have not been well explored so far. The present work reports the design of novel periodic γ‐turns in the oligomers of 1:1 natural‐α/unnatural trans‐β‐norborenene (TNAA) amino acid residues. Through DFT, NMR, and MD studies, it is convincingly shown that, in the mixed conformational pool, the heterogeneous backbone of the hybrid peptides preferentially adopt periodic 8‐membered (pseudo γ‐turn)/7‐membered (inverse γ‐turn) hydrogen bonds in both polar and non‐polar solvent media. It is observed that the stereochemistry and local conformational preference of the β‐amino acid building blocks have a profound influence on accessing the specific secondary fold. These findings may be of significant relevance for the development of molecular scaffolds that facilitate desired positioning of functional side‐chains.     

Self‐Assembly of DNA–Oligo(p‐phenylene‐ethynylene) Hybrid Amphiphiles into Surface‐Engineered Vesicles with Enhanced Emission

Surface‐addressable nanostructures of linearly π‐conjugated molecules play a crucial role in the emerging field of nanoelectronics. Herein, by using DNA as the hydrophilic segment, we demonstrate a solid‐phase “click” chemistry approach for the synthesis of a series of DNA–chromophore hybrid amphiphiles and report their reversible self‐assembly into surface‐engineered vesicles with enhanced emission. DNA‐directed surface addressability of the vesicles was demonstrated through the integration of gold nanoparticles onto the surface of the vesicles by sequence‐specific DNA hybridization. This system could be converted to a supramolecular light‐harvesting antenna by integrating suitable FRET acceptors onto the surface of the nanostructures. The general nature of the synthesis, surface addressability, and biocompatibility of the resulting nanostructures offer great promises for nanoelectronics, energy, and biomedical applications.     

Validation and clinical application of an LC‐ESI‐MS/MS method for simultaneous determination of tolmetin and MED5, the metabolites of amtolmetin guacil in human plasma

A highly sensitive, rapid assay method has been developed and validated for the simultaneous estimation of tolmetin (TMT) and MED5 in human plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. A simple solid‐phase extraction process was used to extract TMT and MED5 along with mycophenolic acid (internal standard, IS) from human plasma. Chromatographic separation was achieved with 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 0.50 mL/min on an X‐Terra RP₁₈ column with a total run time of 2.5 min. The MS/MS ion transitions monitored were 258.1 → 119.0 for TMT, 315.1 → 119.0 for MED5 and 321.2 → 207.0 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 20 ng/mL and the linearity was observed from 20 to 2000 ng/mL, for both the anlaytes. The intra‐day and inter‐day precisions were in the range 3.27–4.50 and 5.32–8.18%, respectively for TMT and 4.27–5.68 and 5.32–8.85%, respectively for MED5. This novel method has been applied to a clinical pharmacokinetic study. Copyright © 2010 John Wiley & Sons, Ltd.     

Gold,silver, and palladium nanoparticle/nano-agglomerate generation,collection, and characterization

Generation, collection, and characterization of gold, silver, and palladium nanoparticles and nano-agglomerates (collectively “nanoparticles”) have been explored. The nanoparticles were generated with a spark aerosol generator (Palas GFG-1000). They were collected using a deposition cell under diffusion and thermophoresis. The shapes and sizes of the deposited particles were measured using transmission electron microscopy (TEM). TEM images showed that the particles were in the range of 8–100 nm in diameter, and their shapes varied from nearly spherical to highly non-spherical. Thermophoresis enhanced the deposition of nanoparticles (over the diffusive or the isothermal deposition) in all cases. Further, the size distributions of the nanoparticles generated in the gas phase (aerosol) were measured using a scanning mobility particle sizer (SMPS 3080, TSI) spectrometer. The SMPS results show that an increase in the spark frequency of the generator shifted the size distributions of the nanoparticles to larger diameters, and the total particle mass production rate increased linearly with increase in the spark frequency. The computational fluid dynamics code Fluent (Ansys) was used to model the flow in the deposition cell, and the computed results conform to the observations.