Multivariate statistics for the differentiation of erythropoietin preparations based on intact glycoforms determined by CE-MS

Owing to the increasing number of erythropoietin biosimilars being approved, the comparison of different erythropoietin preparations in the pharmaceutical area is gaining in importance. Erythropoietin has a distinct natural heterogeneity arising from its glycosylation, which shows strong composition variations. This heterogeneity increases the complexity of the analysis of erythropoietin considerably, but may also be used to distinguish different preparations. Here, a method is presented for the differentiation of various erythropoietin preparations by capillary electrophoresis–mass spectrometry and the subsequent application of multivariate statistics. Relative peak areas of selected intact erythropoietin isoforms were used as variables in principal component analysis and hierarchical agglomerative clustering. Both of these strategies were suited for the clear differentiation of all erythropoietin preparations, including marketed products and preproduction preparations, which differ in the manufacturer, the production cell line, and the batch number. By this means, even closely related preparations were distinguished on the basis of the combined information on the antennarity, the sialoform, and the acetylation of the observed isoforms.     

Disordered carbon nanofibers/LiCoPO<Subscript>4</Subscript> composites as cathode materials for lithium ion batteries

LiCoPO₄-coated disordered carbon nanofibers (CNFs/LiCoPO₄) were obtained by a sol–gel method, using triethyl phosphite or triethyl phosphate as the phosphorous source. The crystal structure of the products was analyzed by X-ray powder diffraction, while morphology was studied using scanning electron microscopy, transmission electron microscopy, Auger electron spectroscopy and X-ray photoelectron spectroscopy. Optimal synthesis conditions for the CNFs/LiCoPO₄ in light of the best electrochemical performance are discussed. The best discharge capacity 105 mAh/g (or ca. 63% of the theoretical capacity) shows the material with 40% CNFs/LiCoPO₄ and addition coating by carbon black. This composition has a best purity of active materials and point coverage of CNFs. The X-ray photoelectron C1s spectra of the CNFs surface without and with sputter erosion show enhancement of C–O bonds at the fiber surface, which does not influence significantly electrochemical behavior of the composite materials.     

Target synthesis of bioactive thioglycolurils,based on QSAR predictions

Target synthesis of substituted thioglycolurils possessing sedative activity predicted by preliminary 3D-QSAR simulation of bioactive structures has been carried out.     

Development and validation of a fast isocratic liquid chromatography method for the simultaneous determination of norfloxacin,lomefloxacin and ciprofloxacin in human plasma

A simple and fast liquid chromatographic method coupled with fluorescence detection (LC‐FD) is reported, for the first time, for the simultaneous quantification of norfloxacin (NOR), ciprofloxacin (CIP) and lomefloxacin (LOM) in human plasma, using levofloxacin as internal standard (IS). Sample preparation consists of a single‐step precipitation of plasma proteins followed by vortex‐mixing and centrifugation. Chromatographic separation was achieved within 7 min on a reversed‐phase C₁₈ column with a mobile phase consisting of 0.1% aqueous formic acid (pH = 3.0, triethylamine)–methanol (82:18, v/v) pumped isocratically at 1.2 mL/min. The detector was set at excitation/emission wavelengths of 278/450 nm. Calibration curves were linear (r² ≥ 0.994) in the range of 0.02–5.0 µg/mL, and the limit of quantification was established at 0.02 µg/mL for all analytes (NOR, CIP and LOM). The overall precision did not exceed 8.19% and accuracy was within ±10.91%. NOR, CIP and LOM were extracted from human plasma with an overall mean recovery ranged from 90.1 to 111.5%. No interferences were observed at the retention times of the analytes and IS. This novel LC‐FD method enables the reliable determination of NOR, CIP and LOM in a single chromatographic run, which may be suitable to support human pharmacokinetic‐based studies with those antimicrobial agents. Copyright © 2010 John Wiley & Sons, Ltd.     

Lone pair···π interactions on the stabilization of intra and intermolecular arrangements of coordination compounds with 2-methyl imidazole and benzimidazole derivatives

Abstract

Spectroscopic and single crystal X-ray diffraction studies of coordination compounds of Co^II, Ni^II, Zn^II, and Pd^II with phenylsulfonyl imidazole and benzimidazole derivatives (2-mfsiz, 2-mfsbz) were performed. The relevance of non-covalent interactions on the stabilization of intra and intermolecular arrangements in the ligands and their coordination compounds was investigated. The imidazole 2-mfsiz ligand presents two enantiomeric conformers, where the ethylphenylsulfone moiety stabilizes intermolecular lone pair···π (S–O···π_(phe)) and H···π contacts, while its tetrahedral coordination compounds, [M(2-mfsiz)₂X₂] (M²⁺?=?Co, Ni, Zn; X?=?Cl, Br) showed intramolecular lone pair···π interactions (S–O···π_(iz)). On the other hand, compounds [Cu₂(2-mfsiz)₂(µ₂-AcO)₄] and trans-[Pd(2-mfsiz)₂Cl₂] do not present lone pair···π interactions due to the metal ion geometry (square base pyramidal or square planar), which leads to formation of π_(iz)···π_(phe) interactions. For the benzimidazole ligand 2-mfsbz, an intramolecular, H_(phe)···π_(bz) contact was observed, remaining in its tetrahedral and octahedral coordination compounds, [M(2-mfsbz)₂X₂] (M²⁺?=?Co, Zn; X?=?Cl, Br, NO₃). This interaction limits the free rotation of the ethylphenylsulfone moiety for stabilization of an intermolecular lone pair···π interaction (S–O···π_(iz)). The dimeric [Zn₂(2-mfsiz)₂(µ²-AcO)₄] compound has a π_(bz)···π_(phe) contact. Theoretical calculations confirmed the non-covalent interactions in the ligands and their coordination compounds.     

Atom based parametrization for a conformationally dependent hydrophobic index

An atomic parametrization for the determination of a hydrophobicity index that depends on the molecular conformation is presented. The hydrophobicity parameter was calculated in four alternative ways based on charge densities and atomic contributions to the total molecular surface area and depending on the approach, the molecular dipole moment. The geometries required for the computations were calculated using quantum mechanical semiempirical methods as well as molecular mechanics. The charges were computed using semiempirical methods as well as the Gasteiger method.     

Proteocubosomes: nanoporous vehicles with tertiary organized fluid interfaces

Proteocubosomes are nanostructured open-nanochannel hierarchical fluid vehicles characterized by a cubic lattice periodicity of the lipid/protein supramolecular assembly (protein-loaded cubosomes). They are obtained here at very high hydration levels by a three-dimensional (3D) self-assembly process, which exploits a protein-directed 3D patterning and fragmentation to create a new, tertiary-level structural order of fluid lipid/water interfaces. Our freeze-fracture electron microscopy study reveals that the proteocubosome structures are built up by patterned assemblies of nanocubosomes, which comprise 3D nanoporous fracture surfaces throughout. Complex cubosomic architectures, involving arrays of nanodroplets (larger than 20 nm) inside the proteocubosome particles, are established at high resolution. The soft-matter hierarchical nanocompartment formations display internal aqueous pores belonging to the D-type lipid cubic lattice nanochannel system that is proven by synchrotron X-ray diffraction. The reported nanostructured fluid may give rise to novel applications in nanofluidic biomimetic devices, porous protein drug delivery vehicles, nanoscale enzymatic bioreactors, and protein-encapsulating fluid nanomaterials.