Mechanistic Aspects of Gas‐Phase Hydrogen‐Atom Transfer from Methane to [CO].+ and [SiO].+: Why Do They Differ?

The reactivity of the two diatomic congeneric systems [CO]^.+ and [SiO]^.+ towards methane has been investigated by means of mass spectrometry and quantum‐chemical calculations. While [CO]^.+ gives rise to three different reaction channels, [SiO]^.+ reacts only by hydrogen‐atom transfer (HAT) from methane under thermal conditions. A theoretical analysis of the respective HAT processes reveals two distinctly different mechanistic pathways for [CO]^.+ and [SiO]^.+, and a comparison to the higher metal oxides of Group 14 emphasizes the particular role of carbon as a second‐row p element.     

A New Easy Access to Enantiomerically Pure 2,2'-Dihydroxy-1,1'-Binaphthyl

Optically pure binaphthyl structures make up the most important family of auxiliaries, ligands and catalysts used in enantioselective reactions. Syntheses of 2,2'-disubstituted-1,1'-binaphtyl derivatives were carried out one pot in water by oxidative coupling with FeCl₃ in the presence of - and -cyclodextrin (CD) derivatives. A new efficient and inexpensive preparation of trihydroxyethyl- and tri-2-hydroxypropyl- - and -CD afforded these powerful solubilizing agents. The resolution of racemic 2,2'-dihydroxy-1,1'-binaphthyl was easily achieved by semipreparative HPLC separating diastereomers obtained from the reaction with (-)menthyl chloroformate. Final basic hydrolysis afforded the enantiomerically pure product.     

Simple and precise detection of lipid compounds present within liposomal formulations using a charged aerosol detector

In recent decades the use of liposomal preparations as drug delivery systems has become very attractive in pharmaceutical development. Therefore, thorough characterization and quantification of the lipids which form liposomes is wished from both investigators and regulatory authorities when the application in humans is being considered. In this study a new HPLC method for the detection of lipids in liposomal formulations was established using corona charged aerosol detection (CAD) which has the advantage to be independent of the chemical properties of the analytes. The superiority of this method over UV detection was demonstrated. Compared to UV detection no absorption effects of the organic solvent in the mobile phase interfering with the lipid signals were observed with CAD. CAD showed good linearity (R² > 0.990) for all liposomal compounds. The acceptance criteria for precision including repeatability were met. The average recovery for each of the excipients of the liposomal formulation was in the range of 90.0–110%.     

The disorder of perfluoroalkyl chains in crystals: Two case histories of interpretation and refinement

Perfluoroalkyl chains in solids are highly disordered in a wide range of temperatures. Poor attention is typically given to this problem in crystallographic studies to the point that no attempt is frequently made in order to model the collected data and disorder remains even unmentioned in a large number of single crystal reports. This paper presents a short analysis of the problems related with this disorder. Two simple crystal structures, namely the halogen bonded adducts between N,N,N′,N′-tetramethyl-1,4-phenylendiamine and α,ω-diiodoperfluorobutane or α,ω-diiodoperfluorohexane are discussed in details in order to suggest some simple and basic principles for the refinement of perfluoroalkyl chains in single crystal structural studies.     

A sensitive and specific precursor ion scanning approach in liquid chromatography/electrospray ionization tandem mass spectrometry to detect methylprednisolone acetate and its metabolites in rat urine

A new, simple, sensitive and specific liquid chromatography/electrospray ionization tandem mass spectrometric (LC/ESI‐MS/MS) method in precursor ion scanning (PIS) mode has been developed for the rapid detection of methylprednisolone acetate (MPA) and its metabolites in rat urine. A suitable product ion specific for methylprednisolone (MP) and MPA was selected after a fragmentation study on 20 (cortico)steroids at different collision energies (5–40 eV). Urine samples were simply treated with acetonitrile then dried in a SpeedVac system. The method was validated and compared with other PIS methods for detecting corticosteroids in human urine. It was more sensitive, with limit of detection (LOD) and lower limit of quantitation (LLOQ), respectively, of 5 and 10 ng mL^?1. The method was applied for the analysis of rat urine collected before and after (24, 48, 72 h) intra‐articular (IA) injection of a marketed formulation of MPA (Depo‐Medrol®). MS/MS acquisitions were taken at different collision energies for the precursor ions of interest, detected in PIS mode, to verify the MP‐related structure. Six different metabolites were detected in rat urine, and their chemical structures were assigned with a computational study. Copyright © 2010 John Wiley & Sons, Ltd.     

Coordinating properties of C2-symmetric chiral bis(oxazolinylpyridinyl)dioxolane ligands

Metal complexes of general formula M(L)X₂ and M(L)X₃ [L = (4S,5S)-2,2-dimethyl-4,5-bis{6-[(4,5-dihydro-4-(S)-(1-methylethyl)oxazol-2-yl)pyridin-2-yl]}-1,3-dioxolane] were obtained by reacting, respectively, Co^II, Cu^II, Ni^II, and Zn^II nitrate salts and the Rh^III chloride salt, with a chiral C₂-symmetric bis(oxazolinylpyridinyl)dioxolane (L) ligand, in MeOH/CHCl₃ solution. A single crystal X-ray analysis was carried out on [Ni(L)(OH₂)₂](NO₃)₂ · 2H₂O and the molecular structure of L was also determined. In the free ligand the two symmetric arms are essentially planar and oriented nearly perpendicular to the dioxolane average plane. In the Ni complex one seven-membered and two five-membered chelation rings are formed. The metal atom also lies on the C₂ axis, and two symmetry-related water molecules complete the octahedral coordination environment. Both compounds crystallize in chiral space groups; the ligand crystallizes in orthorhombic system, space group C 2 2 2₁, Z = 4; the nickel complex crystallizes in tetragonal system, space group P 4₃ 2₁ 2, Z = 4.     

Stereochemical effects in supramolecular self-assembly at surfaces: 1-D versus 2-D enantiomorphic ordering for PVBA and PEBA on Ag(111)

We present investigations on noncovalent bonding and supramolecular self-assembly of two related molecular building blocks at a noble metal surface: 4-[trans-2-(pyrid-4-yl-vinyl)]benzoic acid (PVBA) and 4-[(pyrid-4-yl-ethynyl)]benzoic acid (PEBA). These rigid, rodlike molecules comprising the same complementary moieties for hydrogen bond formation are comparable in shape and size. For PVBA, the ethenylene moiety accounts for two-dimensional (2-D) chirality upon confinement to a surface; PEBA is linear and thus 2-D achiral. Molecular films were deposited on a Ag(111) surface by organic molecular beam epitaxy and characterized by scanning tunneling microscopy. At low temperatures (around 150 K), both species form irregular networks of flat lying molecules linked via their endgroups in a diffusion-limited aggregation process. In the absence of kinetic limitations (adsorption or annealing at room temperature), hydrogen-bonded supramolecular assemblies form which are markedly different. With PVBA, enantiomorphic twin chains in two mirror-symmetric species running along a high-symmetry direction of the substrate lattice form by diastereoselective self-assembly of one enantiomer. The chirality signature is strictly correlated between neighboring twin chains. Enantiopure one-dimensional (1-D) supramolecular nanogratings with tunable periodicity evolve at intermediate coverages, reflecting chiral resolution in micrometer domains. In contrast, PEBA assembles in 2-D hydrogen-bonded islands, which are enantiomorphic because of the orientation of the supramolecular arrangements along low-symmetry directions of the substrate. Thus, for PVBA, chiral molecules form 1-D enantiomorphic supramolecular structures because of mesoscopic resolution of a 2-D chiral species, whereas with PEBA, the packing of an achiral species causes 2-D enantiomorphic arrangements. Model simulations of supramolecular ordering provide a deeper understanding of the stability of these systems.     

Asymmetric Synthesis in the Presence of Cyclodextrins

Oxidative couplings of 2-naphthol, 6-bromo-2-naphthol and2-naphthylamine were achieved at room temperature in the presence of H₂O₂, horseradish peroxidase and a suitable cyclodextrin.2-Thionaphthol behaved differently, yielding the corresponding disulfide. Yields of binaphthyl derivatives were generally excellent, and a fairly good enantiomeric excess was observed. Under similar reaction conditions methyl 2-(6-methoxy-2-naphthyl) propanoate, when treated with esterase in the presence of cyclodextrin, yielded naproxen (a well-known anti-inflammatory drug) with a good enantiomeric excess. No reaction product was detected in the absence of cyclodextrin. Cyclodextrins do not act as simple transfer agents.     

Electrophilic cyclization of o-acetoxy- and o-benzyloxyalkynylpyridines: an easy entry into 2,3-disubstituted furopyridines

[reaction: see text] 2,3-Disubstituted furo[3,2-b]pyridines, 2,3-disubstituted furo[2,3-b]pyridines, and 2,3-disubstituted furo[2,3-c]pyridines are readily prepared under mild conditions via the palladium-catalyzed cross-coupling of 1-alkynes with o-iodoacetoxy- or o-iodobenzyloxypyridines, followed by electrophilic cyclization by I(2) or by PdCl(2) under a balloon of carbon monoxide.     

12-Acylindolo[1,2-c]quinazolines by palladium-catalyzed cyclocarbonylation of o-alkynyltrifluoroacetanilides

6-Trifluoromethyl-12-acylindolo[1,2-c]quinazolines are prepared in high yield through the palladium-catalyzed reaction of bis(o-trifluoroacetamidophenyl)acetylene with aryl or vinyl halides and triflates. The reaction, which tolerates a variety of important functional groups, probably involves the formation of a 3-acyl-2-(o-trifluoroacetamidophenyl)indole intermediate, followed by its cyclization to the indoloquinazoline product. [reaction: see text]