Condensation products of 1‐aryl‐4‐carboxy‐ 2‐ pyrrolidinones with o‐diaminoarenes,o‐aminophenol,and their structural studies

A series of 2‐substituted benzimidazoles, benzoxazoles were synthesized by the condensation reactions of 1‐aryl‐4‐carboxy‐2‐pyrrolidinones and aromatic ortho‐diamines or ortho‐aminophenol. Alkylation of benzimidazoles with iodoalkanes led to 1‐aryl‐4‐(1‐alkyl‐1H‐benzimidazol‐2‐yl)‐2‐pyrrolidin‐ ones or 1,3‐dialkylbenzimidazolium iodides. N‐Subs‐ tituted γ‐amino acids were prepared by the hydrolysis of 1‐aryl‐4‐(1H‐benzimidazol‐2‐yl)‐2‐pyrrolidinones in sodium hydroxide solution, followed by treatment with acetic acid. The structure of the synthesized pro‐ ducts was investigated using IR and ¹H, ¹³C NMR spectra, MM2 molecular mechanics, and AM1 semi‐ empirical quantum mechanical methods. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:47–56, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20171     

Non-parametric estimation from simultaneous degradation and failure time dataEstimation non-paramétrique à partir de données de dégradation et de défaillances

The paper considers degradation and failure time models with multiple failure modes. Dependence of traumatic failure intensities on the degradation level are included into the models. Non-parametric estimators of various reliability characteristics are proposed. Theorems on simultaneous asymptotic distribution of random functions characterizing degradation and intensities of traumatic events are proposed. To cite this article: V. Bagdonavi?ius et al., C. R. Acad. Sci. Paris, Ser. I 335 (2002) 183–188.     

Switching the Inhibitor-Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII

A key part of the optimization of small molecules in pharmaceutical inhibitor development is to vary the molecular design to enhance complementarity of chemical features of the compound with the positioning of amino acids in the active site of a target enzyme. Typically this involves iterations of synthesis, to modify the compound, and biophysical assay, to assess the outcomes. Selective targeting of the anti-cancer carbonic anhydrase isoform XII (CA XII), this process is challenging because the overall fold is very similar across the twelve CA isoforms. To enhance drug development for CA XII we used a reverse engineering approach where mutation of the key six amino acids in the active site of human CA XII into the CA II isoform was performed to provide a protein chimera (chCA XII) which is amenable to structure-based compound optimization. Through determination of structural detail and affinity measurement of the interaction with over 60 compounds we observed that the compounds that bound CA XII more strongly than CA II, switched their preference and bound more strongly to the engineered chimera, chCA XII, based on CA II, but containing the 6 key amino acids from CA XII, behaved as CA XII in its compound recognition profile. The structures of the compounds in the chimeric active site also resembled those determined for complexes with CA XII, hence validating this protein engineering approach in the development of new inhibitors.     

Proton transfer in hydrogen-bonded pyridine/acid systems: the role of higher aggregation

In this work the role of higher molecular aggregation in the proton transfer processes within hydrogen bond (H-bond) is investigated. The H-bonded complex consisting of 4-cyanopyridine (CyPy) with trichloroacetic acid (TCA) has been studied in the solutions of acetonitrile, carbon tetrachloride, chloroform and dichloroethane as solvent by FTIR spectroscopy and quantum chemical DFT calculations. In order to illustrate the effect of increasing H-bond strength FTIR investigations have also been performed on solutions of CyPy with H(2)O, acetic-, trifluoroacetic- and methanesulfonic acids. Proton states in the H-bond have been monitored using vibrational CyPy ring modes in FTIR spectra. The stabilization of the CyPy/TCA complex in its protonated form upon increasing polarity of the solvent has been evidenced. It was shown that formation of the CyPy/(TCA)(2) aggregates in the solutions favors the proton transfer process. An X-ray diffraction study has been performed on a single 1 : 2 co-crystal of pyridine/3,5-dinitrobenzoic acid. The H-bond motif found in this system exhibits the same connectivity by strong hydrogen bonds N-H(+)[dot dot dot]O(-) and O-H[dot dot dot]O as that in the CyPy/(TCA)(2) complex predicted by DFT calculation. Certain discrepancies are observed in C-H[dot dot dot]O connectivity only. The networks of H-bonds in both assemblies differ from those usually pictured for 1 : 2 base/carboxylic acid complexes in the literature.     

Ultra performance liquid chromatography-tandem mass spectrometry for the determination of 5-nitroimidazoles and their metabolites in egg

An ultra performance liquid chromatography (UPLC) coupled to tandem mass spectrometry (MS/MS) procedure was developed for the determination of five 5-nitroimidazoles (dimetridazole, ipronidazole, metronidazole, ronidazole and ternidazole) and three of their metabolites (1-methyl-2-hydroxymethyl-5-nitroimidazole, 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 1-methyl-2-(2′-hydroxyisopropyl)-5-nitroimidazole) in egg matrices. Conditions for UPLC separation and electrospray ionization MS/MS in the positive ion mode were optimized. Samples were prepared by liquid-liquid extraction with buffered aqueous 2.5% trichloroacetic acid followed by solid-phase extraction on a Strata-X-C cartridge with reversed-phase and cation-exchange functionalities. The method’s performance was evaluated in accordance with Commission Decision 2002/657/EC, applying the alternative matrix-comprehensive in-house validation approach using specially designed InterVal software. The method was robust against different sample matrix and SPE cartridges, operator change, and changes in sample extract storage. Acceptable apparent recoveries (76 to 109%) were obtained for all analytes. The decision limits (CC_α) and detection capabilities (CC_α) were within the ranges of 0.19–2.62 and 0.26–4.29 μg kg⁻¹. For all compounds the calibration curve linearity was good with correlation coefficients greater than 0.99. Fifteen eggs and ten whole egg powder samples obtained commercially in Lithuania were analyzed by UPLC-MS/MS; none were found contaminated by 5-nitroimidazoles or their metabolites.     

Spatial Filters on Demand Based on Aperiodic Photonic Crystals

Photonic Crystal spatial filters, apart from stand‐alone spatial filtering function, can also suppress multi‐transverse‐mode operation in laser resonators. Here it is shown that such photonic crystals can be designed by solving the inverse problem: for a given spatial filtering profile. Optimized Photonic Crystal filters were fabricated in photosensitive glass. Experiments have shown that such filters provide a more pronounced filtering effect for total and partial transmissivity conditions.     

Synthesis of 1,2-Diphenylpyrazolidin-4-ol and its Derivatives

A synthesis of 1,2-diphenylpyrazolidin-4-ol via direct heterocyclization of 1,2-diphenylhydrazine with 1-chloro-2,3-epoxypropane, its O-epoxypropyl-, O-ethyl-, and O-benzylderivatives are described. Novel hydrazone derivatives with pyrazolidine units were also synthesized. The compounds were characterized by spectroscopic methods as well as elemental analyses.     

Synthesis of a Bifunctional 1,1′-Diphenyl-1,2,3,4-tetrahydroquinoline Derivative: 1,1′-Diphenyl-1,2,3,4,1′,2′,3′,4′-octahydro-6,6′-biquinolinyl-3,3′-diol

Summary. Intramolecular cyclization of N,N′-di(3-chloro-2-hydroxy)propyl-N,N′-diphenylbenzidine occurs to give bis-1,2,3,4-tetrahydroquinoline derivative 1,1′-diphenyl-1,2,3,4,1′,2′,3′,4′-octahydro-6,6′-biquinolinyl-3,3′-diol.     

Study on the influence of methyl groups and their location on properties of triphenylamino-based charge transporting hydrazones

Abstract  

Methyl substituent effects on the HOMO and LUMO energy levels, and the ability to transport charge and form stable molecular glasses of 4-(diphenylamino)benzaldehyde phenylhydrazones were investigated. Thermal properties, HOMO and LUMO energy levels, and hole mobility values are dependent on the number of methyl substituents and their position in the investigated transporting materials. Surprisingly, however, the presence of methyl groups at any position negatively affects the hole drift mobility of the molecularly doped polymers containing those hydrazones.