Carbamohydrazonothioate derivative—experimental and theoretical explorations of the crystal and molecular structure

Structural Chemistry - The structural studies of carbamohydrazonothioate derivative and its hydrochloride solvate are the aim of hereunder presented research. The combination of the...     

Development of easy‐to‐use reverse‐phase liquid chromatographic methods for determining PRE‐084, RC‐33 and RC‐34 in biological matrices. The first step for in vivo analysis of sigma1 receptor agonists

Over the years there has been a growing interest in the therapeutic potential for central nervous system pathologies of sigma receptor modulators. The widely studied PRE‐084 and our compounds RC‐33 and RC‐34 are very potent and selective sigma 1 receptor agonists that could represent promising drug candidates for Amyotrophic Lateral Sclerosis (ALS). Herein, we develop and validate robust and easy‐to‐use reverse‐phase chromatographic methods suitable for detecting and quantifying PRE‐084, RC‐33 and RC‐34 in mouse blood, brain and spinal cord. An HPLC/UV/ESI‐MS system was employed for analyzing PRE‐084 and an HPLC/UV‐PDA system for determining RC‐33 and RC‐34. Chromatographic separations were achieved on Waters Symmetry RP₁₈ column (150 × 3.9 mm, 5 µm), eluting with water and acetonitrile (both containing 0.1% formic acid) in gradient conditions. The recovery of PRE‐084, RC‐33 and RC‐34 was >95% in all the considered matrices. Their limits of quantitation and detection were also determined. Validation proved the methods be suitable for separating tested compounds from endogenous interferences, being characterized by good sensitivity, linearity, precision and accuracy. A preliminary central nervous system distribution study showed a high distribution of RC‐33 in brain and spinal cord, with concentration values well above the determined limit of quantitation. The proposed methods will be used in future preclinical investigations. Copyright © 2015 John Wiley & Sons, Ltd.     

Trastuzumab quantification in serum: a new,rapid, robust ELISA assay based on a mimetic peptide that specifically recognizes trastuzumab

Trastuzumab, a humanized monoclonal antibody directed against the epidermal growth factor receptor 2 (HER2), is a milestone in the treatment of HER2-overexpressing breast cancer patients. An enzyme-linked immunosorbent assay (ELISA) for trastuzumab has been developed for routine use in the laboratory to support clinical and pharmacokinetic studies to optimize therapy. The method relies on an antigen peptide linked to a 96-well plate via the streptavidin/biotin system. The peptide sequence mimics the extracellular portion of the HER2 receptor that is recognized by trastuzumab. The calibration range of the assay is 10 to 360 ng/mL per well, corresponding to a trastuzumab serum concentration from 5 to 180 μg/mL with a lower limit of quantification of 10 μg/mL. Validation results demonstrate that trastuzumab can be accurately and precisely quantified in human serum using this assay. The procedure was also tested in sera obtained from breast cancer patients to evaluate trastuzumab serum levels, confirming the applicability of method that could be a valid assay to use in daily laboratory practice.     

Introducing an In Situ Capping Strategy in Systems Biocatalysis To Access 6‐Aminohexanoic acid

The combination of two cofactor self‐sufficient biocatalytic cascade modules allowed the successful transformation of cyclohexanol into the nylon‐6 monomer 6‐aminohexanoic acid at the expense of only oxygen and ammonia. A hitherto unprecedented carboxylic acid capping strategy was introduced to minimize the formation of the dead‐end intermediate 6‐hydroxyhexanoic acid. For this purpose, the precursor ε‐caprolactone was converted in aqueous medium in the presence of methanol into the corresponding methyl ester instead of the acid. Hence, it was shown for the first time that esterases—specifically horse liver esterase—can perform the selective ring‐opening of ε‐caprolactone with a clear preference for methanol over water as the nucleophile.     

Adsorption of 137Cs on titanium ferrocyanide and transformation of the sorbent to lithium titanate: a new method for long term immobilization of 137Cs

Dynamic adsorption of radiocesium on titanium ferrocyanide grains from reactor coolant simulating solution containing salts at moderate concentrations has been investigated. Effective decontamination of the neutral solutions has been achieved, in the amounts of a more than 20 thousand bed volumes. After adsorption the titanium ferrocyanide was transferred to titanates and calcined at 900 °C. The leaching test of the obtained lithium titanates indicates that the loaded adsorbent can serve as an effective primary barrier in nuclear waste repositories.     

Synthesis of picolinohydrazides and their evaluation as ligands in the zinc-catalyzed hydrosilylation of ketones

A set of picolinohydrazides was prepared by reaction between hydrazines and either 2-picolinic acid or ethyl pyridine-2-carboxylate, and characterized. These molecules were evaluated as ligands in the zinc-catalyzed hydrosilylation of ketones. Thus, several aromatic and aliphatic ketones were successfully reduced by diethoxymethylsilane as the hydride source in the presence of a catalytic system made of diethylzinc combined in situ to the picolinohydrazides described herein.     

Microwave-Assisted Synthesis of Aryl Amide Bonds on Solid Phase

A novel microwave-assisted synthesis of a library of triarylamides has been undertaken on the solid-phase.