An approach to computer-aided inhibitor design: Application to cathepsin L

Summary We have developed an approach to search for molecules that can be used as lead compounds in designing an inhibitor for a given proteolytic enzyme when the 3D structure of a homologous protein is known. This approach is based on taking the cast of the binding pocket of the protease and comparing its dimensions with that of the dimensions of small molecules. Herein the 3D structure of papain is used to model cathepsin L using the comparative modeling technique. The cast of the binding pocket is computed using the crystal structure of papain because the structures of papain and the model of cathepsin L are found to be similar at the binding site. The dimensions of the cast of the binding site of papain are used to screen for molecules from the Cambridge Structural Database (CSD) of small molecules. Twenty molecules out of the 80 000 small molecules in the CSD are found to have dimensions that are accommodated by the papain binding pocket. Visual comparison of the shapes of the cast and the 20 screened molecules resulted in identifying brevotoxin b, a toxin isolated from the red tide dinoflagellate Ptycho brevis (previously classified as Gymonodium breve), as the structure that best fits the binding pocket of papain. We tested the proteolytic activity of papain and cathepsin L in the presence of brevotoxin b and found inhibition of papain and cathepsin L with K_is of 25 M and 0.6 M, respectively. We also compare our method with a more elaborate method in the literature, by presenting our results on the computer search for inhibitors of the HIV-1 protease.     

Selective allylic oxidation of cyclohexene over a novel nanostructured CeO2–Sm2O3/SiO2 catalyst

Research on Chemical Intermediates - Selective allylic oxidation of cyclohexene was investigated over nanostructured CeO2/SiO2 and CeO2–Sm2O3/SiO2 catalysts synthesized by a feasible...     

Nonlinearly limited saturable-absorber mode locking of an erbium fiber laser

We describe an erbium fiber laser that is passively mode locked by a novel, precision antireflection-coated semiconductor saturable-absorber mirror that incorporates an additional two-photon absorber. It is shown that passive mode locking evolves from a Q-switching instability. The results are achieved by use of saturable absorbers that provide a large (15%) nonlinear (saturable) loss. Exploiting two-photon absorption can substantially reduce the peak power of the Q-switched pulses, which results in improved reliability of the laser. Moreover, two-photon absorption can be used to produce an optimal stability range for saturable-absorber mode locking.     

A novel transformation of 2-dichloracetamido-1-methyl-5-nitroimidazole to 5-dichloroacetylimino-tetrahydroimidazo (4,5-c) pyrazoles.

2-Dichloracetamido-1-methyl-5-nitroimidazole undergoes novel cycloaddition with diazomethane to form 5-dichloracetylimino-tetrahydroimidazopyrazoles via 2-dichloracetylimino-1,3-dimethyl-5-nitroimidazoline.     

Highly dispersed Mn2O3−Co3O4 nanostructures on carbon matrix as heterogeneous Fenton-like catalyst

This work reports the synthesis of various carbon (Vulcan XC-72 R) supported metal oxide nanostructures, such as Mn₂O₃, Co₃O₄ and Mn₂O₃−Co₃O₄ as heterogeneous Fenton-like catalysts for the degradation of organic dye pollutants, namely Rhodamine B (RB) and Congo Red (CR) in wastewater. The activity results showed that the bimetallic Mn₂O₃−Co₃O₄/C catalyst exhibits much higher activity than the monometallic Mn₂O₃/C and Co₃O₄/C catalysts for the degradation of both RB and CR pollutants, due to the synergistic properties induced by the Mn−Co and/or Mn (Co)−support interactions. The degradation efficiency of RB and CR was considerably increased with an increase of reaction temperature from 25 to 45°C. Importantly, the bimetallic Mn₂O₃−Co₃O₄/C catalyst could maintain its catalytic activity up to five successive cycles, revealing its catalytic durability for wastewater purification. The structure–activity correlations demonstrated a probable mechanism for the degradation of organic dye pollutants in wastewater, involving •OH radical as well as Mn²⁺/Mn³⁺ or Co²⁺/Co³⁺ redox couple of the Mn₂O₃−Co₃O₄/C catalyst.     

Regularities in data from factorial experiments

This article documents a meta‐analysis of 113 data sets from published factorial experiments. The study quantifies regularities observed among factor effects and multifactor interactions. Such regularities are known to be critical to efficient planning and analysis of experiments and to robust design of engineering systems. Three previously observed properties are analyzed: effect sparsity, hierarchy, and heredity. A new regularity is introduced and shown to be statistically significant. It is shown that a preponderance of active two‐factor interaction effects are synergistic, meaning that when main effects are used to increase the system response, the interaction provides an additional increase and that when main effects are used to decrease the response, the interactions generally counteract the main effects. © 2006 Wiley Periodicals, Inc. Complexity 11: 32–45, 2006     

Condensed pyrrole compounds-I 3H-pyrrolo(2,3,-c)quinolines

The synthesis of a number of 3H-pyrrolo(2,3-c)quinolines by the Fischer method is reported.     

Sampling of Atmospheric Carbonyls with Small DNPH-Coated C18 Cartridges and Liquid Chromatography Analysis with Diode Array Detection

Abstract

Carbonyls in air are sampled using small DNPH-coated C18 cartridges and analyzed by liquid chromatography with diode array detection. Carbonyl structure confirmation is obtained by comparing diode array spectral scans of samples to the uv-visible spectra (190–600 nm) of some 20 carbonyl hydrazones recorded in the CH₃CN—H₂O eluent used for LC analysis. Analytical detection limits are 0.09–3.4 nanograms carbonyl and correspond to 0.14–1.24ppb in 60 L air samples. Accuracy was ±5% as measured for independently prepared hydrazone standards. The precision was 1–5% for multiple injections of hydrazone standards and 2–10% for replicate analysis of indoor and outdoor air samples. Excellent agreement was obtained in an interlaboratory comparison that included hydrazone standards as well as indoor air samples.

Cartridge collection efficiency has been tested over a range of conditions (sampling flow rate, volume of air sampled, presence of co-pollutants including photochemical oxidants) and is >0.95 for monofunctional carbonyls, unsaturated carbonyls, and alpha dicarbonyls. Carbonyl recovery by cartridge elution is >0.99 for all carbonyls tested. Examples of applications are given in the fields of atmospheric chemistry, indoor air pollution in museums, and outdoor air quality.     

A facile synthesis of structurally novel 1-aryl-2-arylamino-4-alkyl/phenyl-5-aroyl-1H-imidazoles from amidinothioureas

We report here a convenient and efficient two-step synthesis of 1-aryl-2-arylamino-4-alkyl/phenyl-5-aroyl-1H-imidazoles from easily available amidinothioureas. Guanylation of amidinothioureas 1 using mercury(II) chloride as a thiophile yielded amidinoguanidines 2, which reacted with various phenacyl bromides under mild conditions to afford the corresponding diversely functionalized imidazoles 3 in moderate to good yields.     

Nonlinear phenomena in A2MX4 type crystals with incommensurate phases

Investigations of the nonlinear phenomena in A₂MX₄ type crystals (A, organic cation or alkaline metal ion; M, metal ion; X, halogen ion) with incommensurate phases are very interesting from both a scientific and a practical point of view. In the crystals many interesting nonlinear phenomena are observed, e.g., thermal hysteresis of birefringence and absorption coefficient, piezooptic effect, electrooptic effect. Different anomalies (e.g., a discontinuity or change of sign of the briefringence coefficient, a distinct increase of the value of piezooptic and electrooptic coefficients) exist in the phase transition regions. They are especially distinct for a transition from the incommensurate phase to the commensurate phase. Some possibilities of detection and recognition of the existence of incommensurate phases by optical methods are suggested.