Screening for library-assisted identification and fully validated quantification of 22 beta-blockers in blood plasma by liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization

A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization (LC-APCI-MS) is presented for screening for, library-assisted identification (both in scan mode) and quantification (selected-ion mode) of the beta-blockers acebutolol, diacetolol, alprenolol, atenolol, betaxolol, bisoprolol, bupranolol, carazolol, carteolol, carvedilol, celiprolol, esmolol, labetalol, metoprolol, nadolol, nebivolol, oxprenolol, penbutolol, propranolol, sotalol, talinolol and timolol in blood plasma after mixed-mode (HCX) solid-phase extraction (SPE) and separation by reverse-phase liquid chromatography with gradient elution. The validation data were within the required limits. The assay was successfully applied to authentic plasma samples allowing confirmation of diagnosis of overdose situations as well as monitoring of patients' compliance.     

Synthesis,Structure, and Optical Properties of Terminally Sulfur‐Functionalized Core‐Substituted Naphthalene‐Bisimide Dyes

The synthesis, characterization, and optical properties of a series of new 2,6‐disubstituted naphthalene‐bisimide dyes as molecular rods comprising terminal AcS groups is reported. The first series of dyes ( 1 – 3 ), comprising phenylhetero (Ph‐X) core substituents, cover a broad range of the VIS spectrum, ranging from yellow ( 2 ) over red ( 3 ) to blue ( 1 ). The second series of dyes contains benzylhetero (Bn‐X) core substituents ( 4 – 7 ). For the same heteroatom connecting the substituent to the naphthalene core, both series were found to display comparable colors. For the second series, the colors were blue ( 4 ), red ( 5 ), and violet ( 6, 7 ). The Ph‐X‐substituted dyes 1 – 3 are nonfluorescent, in contrast to the Bn‐X‐substituted compounds 4 – 7 . This rich variety of optical features that can be adjusted by rather small alterations of the core substituents makes these structurally very comparable molecular rods ideal candidates for optically triggered molecular‐transport investigations. Also, thanks to the terminal AcS groups, these compounds can be placed between nobel‐metal electrodes for optically triggered transport experiments.     

A molecular flytrap for the selective binding of citrate and other tricarboxylates in water

The synthesis and binding properties of a new tricationic guanidiniocarbonyl pyrrole receptor 7 are described. Receptor 7 binds citrate 9 and other tricarboxylates such as trimesic acid tricarboxylate 8 with unprecedented high association constants of K(assoc) > 10(5) M(-1) in water as determined by UV and fluorescence tritration studies. According to NOESY experiments and molecular modeling calculations, the tricarboxylates are bound within the inner cavity of receptor 7 by ion pairing between the carboxylate groups and the guanidiniocarbonyl pyrrole moieties, favored by the nonpolar microenvironment of the cavity. Hence, receptor 7 can be regarded as a molecular flytrap. In the case of the aromatic tricarboxylate 8, additional aromatic interactions further strengthen the complex. The complexes with the tricarboxylates are so strong that even the presence of a large excess of competing anions or buffer salts does not significantly affect the association constant. For example, the association constant for citrate changes only from K(assoc) = 1.6 x 10(5) M(-1) in pure water to K(assoc) = 8.6 x 10(4) M(-1) in the presence of a 170-fold excess of bis-tris buffer and a 1000-fold excess of chloride. This makes 7 one of the most efficient receptors for the binding of citrate in aqueous solvents reported thus far.     

Gas chromatographic/mass spectrometric determination of 3-methoxy-1,2-propanediol and cyclic diglycerols, by-products of technical glycerol, in wine: interlaboratory study

The aim of the present study was to provide the official wine control authorities with an internationally validated method for the determination of 3-methoxy-1,2-propanediol (3-MPD) and cyclic diglycerols (CycDs)-both of which are recognized as impurities of technical glycerol-in different types of wine. Because glycerol gives a sweet flavor to wine and contributes to its full-body taste, an economic incentive is to add glycerol to a wine to mask its poor quality. Furthermore, it is known that glycerol, depending on whether it is produced from triglycerides or petrochemicals, may contain considerable amounts of 3-MPD in the first case or CycDs in the second. However, because these compounds are not natural wine components, it is possible to detect glycerol added to wine illegally by determining the above-mentioned by-products. To this end, one of the published methods was adopted, modified, and tested in a collaborative study. The method is based on gas chromatographic/mass spectrometric analysis of diethyl ether extracts after salting out with potassium carbonate. The interlaboratory study for the determination of 3-MPD and CycDs in wine was performed in 11 laboratories in 4 countries. Wine samples were prepared and sent to participants as 5 blind duplicate test materials and 1 single test material. The concentrations covered ranges of 0.1-0.8 mg/L for 3-MPD and 0.5-1.5 mg/L for CycDs. The precision of the method was within the range predicted by the Horwitz equation. HORRAT values obtained for 3-MPD ranged from 0.8 to 1.7, and those obtained for CycDs ranged from 0.9 to 1.3. Average recoveries were 104 and 109%, respectively.     

The first example of a liquid crystalline side-chain polymer with bent-core mesogenic units: ferroelectric switching and spontaneous achiral symmetry breaking in an achiral polymer

A dimethylsiloxane diluted polysiloxane side chain co-polymer with non-chiral banana-shaped mesogenic units shows an optically isotropic ferroelectric switching polar smectic C phase (SmCPF) consisting of a conglomerate of homogeneously chiral domains with opposite handedness.     

Genes encoding enzymes responsible for biosynthesis of L-lyxose and attachment of eurekanate during avilamycin biosynthesis

The oligosaccharide antibiotic avilamycin A is composed of a polyketide-derived dichloroisoeverninic acid moiety attached to a heptasaccharide chain consisting of six hexoses and one unusual pentose moiety. We describe the generation of mutant strains of the avilamycin producer defective in different sugar biosynthetic genes. Inactivation of two genes (aviD and aviE2) resulted in the breakdown of the avilamycin biosynthesis. In contrast, avilamycin production was not influenced in an aviP mutant. Inactivation of aviGT4 resulted in a mutant that accumulated a novel avilamycin derivative lacking the terminal eurekanate residue. Finally, AviE2 was expressed in Escherichia coli and the gene product was characterized biochemically. AviE2 was shown to convert UDP-D-glucuronic acid to UDP-D-xylose, indicating that the pentose residue of avilamycin A is derived from D-glucose and not from D-ribose. Here we report a UDP-D-glucuronic acid decarboxylase in actinomycetes.     

Cyclization of Nitrospirobenzopyrans to Bridged Benzoxazepino[3,2-a]indoles

Condensation of 1-substituted 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with 5-nitrosalicylaldehyde afforded 1′-[(N-monosubstituted carbamoyl)methyl]indoline nitrospirobenzopyrans. Treatment of the latter with strong base led to the formation of a mixture of cis/trans-5a,13-methano-1,3-benzoxazepino[3,2-a]indoles. Results of semiempirical calculations gave evidence that such a transformation of nitrospirobenzopyrans to bicyclic indole derivatives could proceed via a single transition state, where the negatively charged carbon atom attacks the vinylic double bond of the spiropyran system.     

Laser-based detection of PAHs and BTXE-aromatics in oil polluted soil samples

Time-resolved laser-induced fluorescence spectroscopy and fiber optics are applied for the detection of aromatic hydrocarbons in oil contaminated water and soil samples. Time-integrated data accumulation of fluorescence intensities in an early and in a late time window with respect to the exciting laser pulse simplifies the method in such a way that it becomes very attractive for practical applications. For ultraviolet laser excitation at 337 nm and recording fluorescence signals at 400 nm, typical detection limits of the present set-up are 0.5 mg engine oil/L in water and 5 mg engine oil/kg in soil. A discrimination between BTXE-aromatics and PAHs in oil polluted soil or water samples is possible, when more than one laser wavelength in the ultraviolet is used for the excitation. The possibilities for a thermal discrimination between different aromatics are also discussed.     

Synthesis of Tricyclic (λ5)-Phosphoranes; unusual N-demethylation/N-alkylation reactions during the oxidative addition of hexafluoroacetone and tetrachloro-ortho-benzoquinone to benzodiaza-λ3-phosphorinones. Single crystal X-ray diffraction studies of various products

The reaction of methylisatoic acid anhydride 1 with benzylamines led to the N-benzyl-N′-methylanthranilamide derivatives 2 – 4 . Their reaction with phosphorus trichloride furnished the 2-chloro-1-halobenzyl/benzyl-3-methyl-4(1 H)-1,3,2-benzodiazaphosphorin-4-ones 5 – 7 which, upon reaction with bis-(2-chloroethyl)ammonium chloride/triethylamine, were converted into the P-bis-(2-chloroethyl)amino-1-halobenzyl/benzyl-3-methyl-4(1 H)-1,3,2-benzodiazaphosphorin-4-ones 8 – 10 and 12 . With 2-chloroethylammonium chloride/triethyl-amine the P? NHCH₂CH₂Cl-substituted compound 11 was obtained from the P^IIICl-species 6 . The reaction of 8 – 10 and 12 with hexafluoroacetone (HFA) took an unusual course: apart from the oxidative addition of HFA and formation of the perfluoropinacolyl ring system, one of the two CH₂CH₂Cl groups was found to alkylate the CH₃N atom with formation of a five-membered (diazaphospholane) ring in the tricyclic phosphoranes 13 – 16 . The reaction of 11 with HFA also produced a spirophosphorane 17 which involved a λ⁵-oxazaphosphetidine ring system. In the reaction of 8, 10 and 12 with tetrachloro-o-benzoquinone, an oxidative addition reaction with concomitant N-alkylation and formation of the tricyclic phosphoranes 18 – 20 was found to take place. Single crystal X-ray structure determinations are described for the phosphoranes 13, 14 and 16 , and for the precursor compound 9 . The following features are common to the isostructural compounds 13 and 16 and the diethyl ether hemisolvate of 14 : the (λ⁵)-spiro phosphorus atom lies out of the plane of the other atoms of the rings to which it is common, and the dioxaphospholane rings display a twist conformation. In the λ³P-compound 9 the phosphorus atom also lies out of the plane of the other ring atoms.     

Cu(OAc)2-catalyzed N-arylations of sulfoximines with aryl boronic acids

[reaction: see text] A simple and mild copper salt-catalyzed N-arylation of sulfoximines in high yields is reported. Cu(OAc)(2) activates aryl boronic acids for the reaction with NH-sulfoximines without additional base or heating. Furthermore, this new method allows the preparation of N-arylated sulfoximines, which have previously been more difficult to access.