Determination of memantine in human plasma by GC using negative ion chemical ionization MS detection after derivatization with a new reagent

We describe a method for the determination of memantine in plasma by use of the derivatization reagent o-(pentafluorobenzyloxycarbonyl)-benzoyl chloride. Memantine can be quantitatively analyzed down to 49?pg per mL of plasma using a 250?μL sample and negative ion chemical ionisation mass spectrometry (GC-NICI-MS). Plasma samples were made alkaline with carbonate buffer and extracted with n-hexane. The extracts were treated with reagent solution for 20?min, concentrated, and submitted to GC-NICI-MS. The method is rapid because extraction and derivatization occur in one single step. Amantadine is used as an internal standard. The utility and robustness of the assay is demonstrated by giving data on specificity, linearity, accuracy and precision, benchtop stability, freeze–thaw stability, autosampler stability, aliquot analysis, and prospective analytical batch size accuracy.

Komplexe von Acetylaceton und Acetonylaceton mit Alkali- und Erdalkaliionen. MO-SCF-Berechnungen und UV-Spektroskopie

In analogy to previous investigations on main group metal ion complexes with diacetyl², model calculations within the LCGO MO SCF framework using minimal basis sets are used in combination with UV spectrocopy in order to investigate complex formation tendencies, eventual ion specifities and ion binding energies of Li, Na, K, Mg and Ca ions with dicarbonyl ligands. The influence of the separation of the coordinative centers by methylene groups on the interaction with these metal ions is discussed. The simple quantum chemical models seem to work in the case of diacetyl and acetylacetone, whereas they fail in the prediction of the experimentally observed interaction of acetonylacetone with the metal ions.

     

Enantioseparation of citalopram analogues with sulfated β‐cyclodextrin by capillary electrophoresis

Capillary electrophoresis methods were developed for the enantiomeric separation of 27 citalopram analogues. Sulfated β‐cyclodextrin was the most broadly selective and useful chiral selector. The separations of most of the citalopram analogue compounds reported in this work have not been reported previously. Excellent enantiomeric separations were obtained for 26 out of 27 compounds, and most of the separations were achieved within 10 min. The effects of chemical parameters such as chiral selector types, buffer types, chiral selector and buffer concentrations, buffer pH and organic modifiers on the separation were investigated. The influence of analyte structure on separation also was examined and discussed.     

Nonspecific protein adsorption at the single molecule level studied by atomic force microscopy

Liquid tapping atomic force microscopy was used to study the nonspecific adsorption of horse spleen ferritin at a bare gold surface at single molecule resolution. The majority of ferritin molecules adsorbed irreversible on gold surfaces in accordance with the random sequential adsorption (RSA) mechanism frequently used to describe irreversible adsorption processes. However, the time-resolved data also reveal events that go beyond the RSA model, i.e., lateral mobility and fragility of some molecules, resulting in desorption, chain formation, and subunit dissociation. Scanning effects of the AFM tip were observed, resulting in diminished protein coverage in the scanned area.     

Syntheses of Diamino-dideoxylyxose Derivatives using Acylnitroso Dienophiles

N-Acylnitroso derivatives 6 which were prepared by in-situ oxidation of the corresponding hydroxamic acids 5 reacted instantaneously and in high yields with dihydropyridine 4 . The Diels-Alder adducts 8 were formed regiospecifically with the acylnitroso dienophiles 6a–c , whereas the dienophiles 6d–f gave mixtures of both regioisomers 7 and 8 . These and some other results [2] were best explained by the FMO theory. The Diels-Alder adducts 7 and 8 gave the corresponding ‘anti’-cis-glycols when reacted with OsO₄/N-methylmorpholine N-oxide. Hydrogenolysis of the N–O bond followed by peracetylation led to the expected aminolyxose derivatives 14 and 16 . A similar sequence, using 4 and the hydroxamic-acid derivative 18 of (+)-D-mandelic acid led, with a poor asymmetric induction, to a mixture of the expected optically active aminolyxose compounds 19A / 19B .     

Stereoselective synthesis of optically active bicyclic beta-lactam carboxylic acids that target pilus biogenesis in pathogenic bacteria

Optically active bicyclic beta-lactams were synthesized, starting from 2-H-delta 2-thiazolines and Meldrum's acid derivatives. Several methods to accomplish an ester hydrolysis without damaging the beta-lactam framework were investigated. A rapid CsOH saponification of the beta-lactam methyl esters was developed and protonation of the Cs-carboxylates by Amberlite (IR-120 H+) afforded a series of bicyclic beta-lactam carboxylic acids. Moreover, a convenient method for the synthesis of 2-H-delta 2-thiazolinecarboxylic acid methyl ester 2 was developed. Bicyclic beta-lactam carboxylic acids 7a-g and aldehydes 4a-d were screened for their affinity to the bacterial periplasmic chaperone PapD using a surface plasmon resonance technique. beta-Lactams substituted with large acyl substitutents showed better binding to the chaperone than the native C-terminal peptide PapG 8, demonstrating that bicyclic beta-lactams constitute a new class of potential bacterial chaperone inhibitors.