High-performance liquid chromatographic determination of Levetiracetam in human plasma: comparison of different sample clean-up procedures

An accurate and precise high-performance liquid chromatographic method using diode array detection for the determination of the novel antiepileptic, Levetiracetam, has been developed. Three clean-up procedures for the analysis of Levetiracetam in human plasma were implemented and evaluated, namely solid-phase extraction, deproteinization by addition of organic solvents and formation of insoluble salts. Adenosine was used as the internal standard for all three sample pretreatment procedures. Among the several cartridges used for solid-phase extraction, the hydrophilic-lypophilic balance (Oasis) HLB) phase provides the best extraction yield of Levetiracetam, together with high precision. With the two other clean-up procedures involving plasma deproteinization by addition of methanol or zinc sulphate, lower sensitivity and precision of the assays were obtained. However, they are cheaper and faster when compared with the solid-phase extraction procedure.     

On the reaction of isothiosemicarbazides with heterocumulenes. Part I

Isothiosemicarbazides 2 react with acyl isothiocyanates under addition-cyclization to yield 1,3,4-thiadiazoline-2-imines 3 as well as the isomeric 2-amino-substituted 1,3,4-thiadiazolium-5-acylaminides 3′ . In a similar manner the 2-hydrazino-substituted 1,3-thiazoline 4 adds ethoxycarbonyl isothiocyanate to give the thiosemicarbazide 5 , which undergoes a rearrangement to the 1,3,4-thiadiazoline-2-imine 5′. The [2+2] cycloreversion of 3d involving ethoxycarbonyl iso(thio)cyanate and the thermal induced Dimroth rearrangement of 3′f and h are also discussed.     

Solvothermal synthesis of new metal organic framework structures in the zinc-terephthalic acid-dimethyl formamide system

Two new metal organic framework (MOF) structures have been obtained from the Zn-terephthalic acid (H₂BDC)-dimethyl formamide (DMF) system and examined by single-crystal X-ray diffraction: Zn(C₈H₄O₄)(C₃H₇NO), 1, monoclinic C2/m, a=11.1369(5), b=14.0217(7), , β=106.316(1)°, , , Z=4, R₁=0.060, wR₂=0.169, S=1.27; Zn(HCO₂)₃(C₂H₈N), 2, trigonal , a=8.1818(1), , , , Z=6, R₁=0.014, wR₂=0.039, S=1.11. Contrary to previously published structures in the same system, the crystals were obtained by solvothermal synthesis at 381 K. Structure 1 consists of 2-D layers stacked in an offset manner to accommodate DMF moieties coordinated to Zn²⁺ within voids in adjacent layers. Structure 2 consists of a 3-D network constructed from Zn²⁺ ions bridged by deprotonated formic acid moieties. Over time, the structure of 1 rearranges to Zn(C₈H₄O₄)(C₃H₇NO)(H₂O) [monoclinic P2₁/n, a=6.6456(2), b=15.2232(5), , β=104.110(2)°, , , Z=4, R₁=0.048, wR₂=0.100, S=1.07], which is identical to the known MOF-2 structure, obtained by crystallization at ambient conditions. The three structures were determined from crystals with similar crystal habits picked from a single solvothermal synthesis batch. The study demonstrates that MOF syntheses can give not only multiple crystal structures under different conditions, but also that numerous different structures, including some that are metastable, can be formed under identical conditions.     

Purification of monoclonal antibodies from cell culture supernatants using a modified zirconia based cation-exchange support

A method suitable for the isolation of monoclonal antibodies (Mabs) is described. The protocol utilizes a zirconia based column modified with ethylenediamine-N,N'-tetra(methylenephosphonic) acid to create a novel cation-exchange chromatographic support. Initial experiments using a linear salt gradient demonstrate the ability of this support to efficiently separate Mab from transferrin and bovine serum albumin in a model matrix. Results of the purification of Mab from an actual cell culture supernatant over a range in protein concentrations are also shown. Analyses by enzyme-linked immunosorbent assay and gel electrophoresis demonstrate that Mabs can be recovered from a cell culture supernatant at high yield (92-98%) and high purity (> 95%) in a single chromatographic step.     

Reaktionen an komplexgebundenen liganden: XXIX. Ein einfacher weg zu azomethin-komplexen: Kondensation von chrom—, molybdän—, wolfram—, mangan— und eisen—ammoniak-komplexen und ketonen zu ketimin-komplexen

Treatment of transition-metal—ammonia complexes with ketones yields complexes with RR′CNH ligands. Of particular interest is the stabilization of dialkylketimines such as e.g. (CH₃)₂CNH and C₆H₁₀NH in [M(CO)₅{NHC(CH₃)₂}] or [M(CO)₅ {NHC₆H₁₀}] (M = Cr, Mo, W). The principle of synthesis may be applied to a wide range of different metals and types of complexes, as can be shown by the synthesis of [C₅H₅Mn(CO)₂ {NHC(CH₃)₂}], [C₅H₅Fe(CO)₂{NHC(CH₃)₂}]PF₆, [M(CO)₄L₂] (M = Cr, Mo, W; L = (CH₃)₂CNH, C₆H₁₀NH) and [W(CO)₃(diphos){NHC(CH₃)}₂]. Treatment of [Cr(CO)₅NH₃] with urotropine gives [Cr(CO)₅ {N₄(CH₂)₆}] which is also obtained from [Cr(CO)₅THF] and urotropine. The methods of preparation, reactions and spectroscopic properties of the complexes are reported.     

PEG based resins for protease drug discovery synthesis, screening and analysis of combinatorial on-bead libraries

This review will cover the entire hit identification process performed with biocompatible, aqueous solvated, poly[ethylene glycol] (PEG) based resins - from synthesis, through screening, to analysis. The different types of resins (including their preparation) will be discussed and compared individually. Examples of one-bead-one-compound substrate libraries will be presented, as will one-bead-two-compounds libraries used for the discovery of enzyme inhibitors. The review includes a section covering organic and bio-organic reactions performed on all-PEG resins and discusses on-bead screening of the libraries with biomolecules. Finally, analysis of compounds on single beads, either via investigation by on-bead NMR or by ladder-coding of the combinatorial compound is covered. In general, the review will focus on chemistry, libraries, synthesis, screening, and analysis, using all-PEG based resins.     

Reactions of Ru3(CO)12 with Diphosphenes — A New Route to 50‐Electron Ru3P2 nido‐Clusters

The reaction of the symmetric diphosphene 2, 4, 6‐(CF₃)₃‐C₆H₂‐P=P‐C₆H₂‐2, 4, 6‐(CF₃)₃ 4 with Ru₃(CO)₁₂ led to the 50‐electron Ru₃P₂ nido‐cluster Ru₃(CO)₉[μ‐P‐C₆H₂‐2, 4, 6‐(CF₃)₃]₂ 5 , which in solution at room temperature displays hindered rotation of the aromatic rings about the C(aryl)—P bonds. The structure of 5 was determined by X‐ray crystal structure analysis; its Ru₃P₂ centre forms a distorted square pyramid with one ruthenium atom at the apex. One of the two C₆H₂(CF₃)₃ groups is also appreciably distorted. Temperature‐dependent ¹⁹F NMR studies of the [A₃M₃X]₂ spin system (A = M = CF₃, X = ³¹P) of 5 indicated a rotational barrier ΔG^≠ of 82.3 kJ mol^‐1 at 141 °C. The same Ru₃P₂ core was obtained by the reaction of the unsymmetric diphosphene Mes*‐P=P‐Mes 11 with Ru₃(CO)₁₂; hindered rotation about the C(aryl)—P bonds was also observed, in this case.     

Stoffwechselprodukte von Mikroorganismen. 177. Mitteilung. Avilamycin C

From cultures of the Avilamycin (Avilamycin A) producing organism, Streptomyces viridochromogenes, strain ETH 23575, a second antibiotic, Avilamycin C, C₆₁H₉₀Cl₂O₃₂ could be isolated in crystalline form. Both Avilamycins belong to the group of the Orthosomycins. By IR., ¹H- and ¹³C-NMR. spectroscopy and by transformation to a common derivative it could be proven that Avilamycin A is a methyl ketone, Avilamycin C the corresponding methyl carbinol.