CaL-B a highly selective biocatalyst for the kinetic resolution of furylbenzthiazole-2-yl-ethanols and acetates

A highly stereoselective enzymatic kinetic resolution of novel various substituted racemic furylbenzthiazole-2-yl-ethanols and their acetates has been developed. Both processes, the enzymatic acylation of the racemic alcohols and the enzymatic methanolysis of racemic acetates yielded highly enantiomerically enriched (ee >98%) resolution product, when CaL-B was used as a biocatalyst in acetonitrile. The absolute configuration of the obtained (R)-(+)-1-(5-(4-chlorobenzo[d]thiazol-2-yl)furan-2-yl)ethanol was determined by a detailed ¹H NMR study of rac- and (+)-1-(5-(4-chlorobenzo[d]thiazol-2-yl)furan-2-yl)ethanol Mosher derivatives.     

Qualitative and quantitative analysis of gallic acid in Alchemilla vulgaris, Allium ursinum, Acorus calamus and Solidago virga-aurea by chip-electrospray ionization mass spectrometry and high performance liquid chromatography

This study presents the results obtained from qualitative and quantitative analysis of gallic acid from hydro-alcoholic extracts (methanol, ethanol) of plants from Plantae regnum. Plant qualitative analysis was performed using a novel mass spectrometric (MS) method based on fully automated chip-nanoelectrospray ionization (nanoESI) high capacity ion trap (HCT) while quantitative analysis was carried out by high performance liquid chromatography (HPLC). These methods were applied to Alchemilla vulgaris — common lady’s-mantle (aerial part), Allium ursinum — bear’s garlic (leaves), Acorus calamus — common sweet flag (roots), Solidago virga-aurea — goldenrod (aerial part). Obtained results indicated that methanol extracts (96%, 80%) have a gallic acid content ranging between 0.0011–0.0576 mg mL⁻¹ extract while the ethanol extracts (96%, 60%) exhibit a gallic acid concentration that varies between 0.0010–0.0182 mg mL⁻¹ extract.      

Predicted binding rate of new cephalosporin antibiotics by a 3D-QSAR method: a new approach

Abstract  

Antibiotics are chemotherapeutic agents with activity against microorganisms, for example bacteria, fungi, or protozoa, used for the treatment of many types of diseases. Binding of antibiotics to serum proteins in human plasma is a major determinant of their pharmacodynamic and pharmacokinetic behavior and, consequently, can affect their systemic distribution in the body. Here, the predicted binding rates of ceftazidime and 13 other pharmacological agents classified as antibiotics to plasma proteins (percentage fraction bound; PFB) were evaluated by use of 3D-QSAR models. We attempted to establish the contribution of hydrogen bond donor/acceptor and hydrophobic properties supplied by electrostatic fields to the PFB. Significant cross-validated correlation q ² (0.5–0.7) and the fitted correlation r ² (0.7–0.97) coefficients revealed that these models have reasonable power to predict the design 19 new antibiotics using ceftazidime as template, these compounds being our suggestion for further studies.     

In vivo solid-phase microextraction for single rodent pharmacokinetics studies of carbamazepine and carbamazepine-10,11-epoxide in mice

The use of solid-phase microextraction (SPME) for in vivo sampling of drugs and metabolites in the bloodstream of freely moving animals eliminates the need for blood withdrawal in order to generate pharmacokinetics (PK) profiles in support of pharmaceutical drug discovery studies. In this study, SPME was applied for in vivo sampling in mice for the first time and enables the use of a single animal to construct the entire PK profile. In vivo SPME sampling procedure used commercial prototype single-use in vivo SPME probes with a biocompatible extractive coating and a polyurethane sampling interface designed to facilitate repeated sampling from the same animal. Pre-equilibrium in vivo SPME sampling, kinetic on-fibre standardization calibration and liquid chromatography–tandem mass spectrometry analysis (LC–MS/MS) were used to determine unbound and total circulating concentrations of carbamazepine (CBZ) and its active metabolite carbamazepine-10,11-epoxide (CBZEP) in mice (n = 7) after 2 mg/kg intravenous dosing. The method was linear in the range of 1–2000 ng/mL CBZ in whole blood with acceptable accuracy (93–97%) and precision (<17% RSD). The single dose PK results obtained using in vivo SPME sampling compare well to results obtained by serial automated blood sampling as well as by the more conventional method of terminal blood collection from multiple animals/time point. In vivo SPME offers the advantages of serial and repeated sampling from the same animal, speed, improved sample clean-up, decreased animal use and the ability to obtain both free and total drug concentrations from the same experiment.     

Supramolecular Structure - A Key Parameter for Cellulose Biodegradation

Summary: Three different cellulosic substrata, like microcrystalline cellulose, cotton cellulose and spruce dissolving pulp, were chosen for biodegradation. The kinetics of the enzymatic hydrolysis of these celluloses by Trichoderma reesei, has been investigated. The experiments proved the fact that both the morphological structure and the crystalline one are crucial to the process and the ratio of the reactions. In addition, in order to obtain the most accessible cellulose substratum it was studied the biodegradation of cellulose allomorphs of spruce dissolving pulp. The insoluble cellulose fraction remaining after enzymatic hydrolysis was examined by X-ray diffraction method and it was established the degree of crystallinity and the average crystallite size. The enzymatic degradation is also proved by the decrease in the degree of polymerization of hydrolyzed samples.     

Ink‐Jet Microdispensing for the Formation of Gradients of Immobilised Enzyme Activity

Summary: The integration of gradients of enzyme activity in microstructured biosensor arrays enables intrinsic on‐line quality control of biosensor performance. Multiple sensor elements with different compositions and hence varying responses for the same analyte are evaluated as a basis for improving data reliability. The formation of glucose oxidase/polymer microstructures using a piezo microdispenser and their examination by scanning electrochemical microscopy (SECM) are used to demonstrate the feasibility of this approach.

Optical microscope image of grids obtained by dispensing of 1 mg/mL GOx and 2 mg/mL Vinnapas® mixture.     

New N-aryloxy-phthalimide derivatives. Synthesis,physico-chemical properties,and QSPR studies

Starting from N-hydroxyphthalimide 1 and the reactive fluoro- or chloro-nitroaryl derivatives 2, 3 and 4a-e (2-chloro-3,5-dinitropyridine; 3, NBD-chloride; 4a, 1-fluoro-2,4-dinitrobenzene; 4b, picryl chloride; 4c, 4-chloro-3,5-dinitrobenzotrifluoride; 4d, 2-chloro-3,5- dinitrobenzotrifluoride; 4e, 4-chloro-3,5-dinitrobenzoic acid) the corresponding N-(2-nitroaryloxy)-phthalimide derivatives 5a-e, or 6 and 7 were obtained and characterized by IR, UV-Vis ¹H-NMR and ¹³C-NMR spectroscopy. The TLC behavior and the hydrophobicity of these derivatives have been experimentally evaluated by R_M0 parameters (using RP-TLC). The experimental R_M0 parameters were compared with the calculated partition coefficient, log P. A QSPR study was also performed to establish possible correlations between the structure and physical properties (λ_max and R_M0) of compounds 5a-e, 6, and 7.