A versatile protocol for the preparation of substituted 1- and 2-naphthyl piperazines from aminonaphthols

Aminonaphthols are easily transformed into a variety of 1- and 2-naphthyl piperazines using a sequence of diazotization, iodide substitution and Pd(0) catalyzed coupling reactions.     

Carbon fiber cylindrical microelectrode-based detector for the determination of antithyroid drugs

An amperometric flow-injection method for the determination of antithyroid drugs such as 6-methyl-2-thiouracil (MTU) using a carbon fiber cylindrical microelectrode-based detector is reported. A home-made flow-cell specially adapted for working with cylindrical microelectrodes ranging between 4 and 10 mm in length was used for this purpose. Methanol containing 0.05 mol l(-1) tetrabutylammonium perchlorate as the supporting electrolyte was employed, and a potential of +1.6 V was selected for the amperometric detection of MTU. No cleaning or electrode surface regeneration of the fiber was necessary during the whole working day. A limit of detection of 2.6x10(-7) mol l(-1) (37 mug MTU l(-1)) was achieved. The method was applied to the determination of MTU in spiked feed samples (peas and corn flour), at the 142 mug g(-1) level. The procedure involved the extraction of the drug in methanol, a clean-up step using Florisil cartridges and the use of the standard additions method. Recoveries of 81+/-6 and 85+/-8% were obtained for peas and corn flour, respectively.     

Second-generation mimics of ganglioside GM1 oligosaccharide: a three-dimensional view of their interactions with bacterial enterotoxins by NMR and computational methods

As a step to delineate a strategy of ligand design for cholera toxin (CT), NMR studies were performed on several mimics of the GM1 ganglioside oligosaccharide. The conformation of these analogues was investigated first in solution and then upon binding to cholera toxin by transferred nuclear Overhauser effect (TR-NOE) measurements. It was demonstrated that CT selects a conformation similar to the global minima of the free saccharides from the ensemble of presented conformations. No evidence of major conformational distortions was obtained, but one or two of the available conformers of the hydroxyacid side chain appear to be selected in the bound state. The NMR data were interpreted with the aid of computer models, generated and analyzed by using a combination of different approaches (MacroModels' MC/EM and MC/SD, Autodock, and GRID). Analysis of the NMR data supported by computational studies allowed us to interpret the experimental observations and to derive workable models of the ligand:toxin complexes. These models suggest that the higher affinity of the (R)-lactic acid derivative 3 may stem from lipophilic interactions with a hydrophobic area in the toxin binding site located in the vicinity of the sialic acid side chain binding region of the CT:GM1 complex, and formed by the side chain of Ile-58 and Lys-34. Thus, the models obtained have allowed us to make useful design suggestions for the improvement of ligand affinity.     

Semiempirical SCF/CI interpretation of the origin of the catalytic activity of transition metal-macrocycle complexes

Semiempirical self-consistent field (SCF) and configuration interaction (CI) calculations of the intermediate neglect of differential overlap (INDO) type are applied to the analysis of the electronic transitions of the hexaazacyclophane base and its Ni and Cu complexes. The ground states (¹A_g for the ligand and Ni complex, ²B_1g for the Cu complex) are planar structures of D₂h symmetry. The low-energy region of the UV-visible spectra, whose analysis may help to recognize the catalytic active sites of the complexes is associated with d → d transitions in the Ni complex, and M → L charge transfer in the Cu complex.     

On the validity of the BEBO method

The use of tha BEBO method proposed by Johnston and Parr is considered, taking into account the observations of Jordan and Kuafman. It is found that the original formulation is applicable even when the new values for noble gas pairs are employed,if an appropriate choice of the constant in Pauling's relation is made.     

Structural basis for recognition of bacterial cell wall teichoic acid by pseudo-symmetric SH3b-like repeats of a viral peptidoglycan hydrolase

Endolysins are bacteriophage-encoded peptidoglycan hydrolases targeting the cell wall of host bacteria via their cell wall-binding domains (CBDs). The molecular basis for selective recognition of surface carbohydrate ligands by CBDs remains elusive. Here, we describe, in atomic detail, the interaction between the Listeria phage endolysin domain CBD500 and its cell wall teichoic acid (WTA) ligands. We show that 3′O-acetylated GlcNAc residues integrated into the WTA polymer chain are the key epitope recognized by a CBD binding cavity located at the interface of tandem copies of beta-barrel, pseudo-symmetric SH3b-like repeats. This cavity consists of multiple aromatic residues making extensive interactions with two GlcNAc acetyl groups via hydrogen bonds and van der Waals contacts, while permitting the docking of the diastereomorphic ligands. Our multidisciplinary approach tackled an extremely challenging protein–glycopolymer complex and delineated a previously unknown recognition mechanism by which a phage endolysin specifically recognizes and targets WTA, suggesting an adaptable model for regulation of endolysin specificity.

Combining genetic, biochemical and computational approaches, we elucidated the molecular mechanisms underlying the recognition of Listeria wall teichoic acid by bacteriophage-encoded SH3b repeats.     

Influence of medium and temperature on the hydrolysis kinetics of propacetamol hydrochloride: determination using derivative spectrophotometry

Propacetamol hydrochloride (PRO) is a water-soluble prodrug of paracetamol (PA) which can be parenterally administered as analgesic for the treatment of postoperative pain, acute trauma, and gastric and/or intestinal disorders where oral administration is not possible. In these circumstances, PRO can be administered in physiologic or glucose solutions since it is rapidly and quantitatively hydrolyzed into PA by plasma estearases. We have studied the degradation kinetics of PRO in 5% glucose and 0.9% saline solutions at 4 degrees C and 25 degrees C (storage and room temperatures, respectively). The analytic technique used to determine PRO and PA quantitatively was first-derivative spectrophotometry. The degradation process of PRO can be best fitted to a second-order kinetics with independence of the medium used (saline or glucose solution). The hydrolysis kinetics of PRO conversion into PA depends on the temperature but not on the assay medium (saline or glucose solution). The degradation rate constants obtained for PRO were approximately 4.5 times higher at 25 degrees C than at 4 degrees C. The values of t(90%) for PRO were 3.17 h and 3.61 h at 25 degrees C, and 13.42 h and 12.36 h at 4 degrees C when the tests were performed in 5% glucose and 0.9% saline solutions, respectively.     

Synthesis of 2,3,8,9-tetramethoxy-11-phenyl-5,6-dihydrodibenz[2,3;7,8]indolizine

2,3,8,9-Tetramethoxy-11-phenyldibenz[2,3;7,8]indolizine was obtainedinhighyieldfrom (6,7-dimethoxyisoquinolin-1-yl)-(3,4-dimethylphenyl)phenylcarbinol by cyclization in the presence of formic acid. The behavior of (6,7-dimethoxyisoquinolin-1-yl)-(3,4-dimethoxyphenyl)methylcarbinol and (6,7-dimethoxyisoquinolin-1-yl-(3,4-dimethoxyphenyl)carbinol was studied under these same conditions. 2,3,7,8-Tetramethoxy-11-phenyl-5,6-dihydrodibenz[2,3;7,8]indolizine was obtained by hydrogenation on rhenium heptasulfide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1233–1238, September, 1993.     

Electron-density topology in molecular systems: paired and unpaired densities

This work studies the partitioning of the electron density into two contributions which are interpreted as the paired and the effectively unpaired electron densities. The topological features of each density field as well as of the total density are described localizing the corresponding critical points in simple selected molecules (local formalism). The results show that unpaired electron-density concentrations occur out of the topological bonding regions whereas the paired electron densities present accumulations inside those regions. A comparison of these results with those arising from population analysis techniques (nonlocal or integrated formalisms) is reported.