Anomalous stereochemistry of pyrazolato-3,5-dicarboxylato-bridged dinuclear chromate(III) complexes containing ethylenediamine-N,N'-dicarboxylates with entrapped unstable conformations: X-ray structure of Na[Cr2(eddp)(mu-pzdc)].6H2O

Several new pyrazolato-3,5-dicarboxylato (pzdc) bridged dinuclear chromate(III) complexes containing linear tetradentate O-N-N-O type ligands were synthesized and structurally characterized. Among them, the X-ray structure of the eddp complex Na[Cr2(eddp)(mu-pzdc)].6H2O (eddp = ethylenediamine-N,N'-dipropionate) was determined to have a (sym-cis)-(unsym-cis) geometrical configuration with intramolecular three-center hydrogen bonds, entrapping the unfavored sym-cis configuration for the Cr(eddp) moiety as well as the favored unsym-cis one. As a pair of positional disorders, there were also found to be two conformational isomers with respect to the absolute configurations of the coordinated asymmetric nitrogen atom at the G (in-plane) ring for the unsym-cis moiety. Moreover, chiral pzdc-bridged dinuclear complexes with another type of O-N-N-O ligand, 1,2-cyclohexanediamine-N,N'-diacetate (cdda), were successfully synthesized, isolated, and characterized by column chromatographic behavior, elemental analysis, and chiroptical spectra. There were two diastereomers for Na[(R,R-cdda)Cr(mu-pzdc)Cr(S,S-cdda)] and only one isomer for Na[(R,R-cdda)Cr(mu-pzdc)Cr(R,S-cdda)] and Na[(R,R-cdda)Cr(mu-pzdc)Cr(edda)] (R,R- or S,S- and R,S-cdda = R,R-trans- or S,S-trans- and R,S-cis-1,2-cyclohexanediamine-N,N'-diacetate, and edda = ethylenediamine-N,N'-diacetate). From their circular dichroism (CD) spectra, these complexes could exhibit the delta-delta absolute configuration with ((sym-cis-R,R-cdda)-(unsym-cis-edda or S,S- or R,S-cdda)) geometrical configuration, indicating the abnormal eq-eq (N-Ceq) configuration for the R,R-cdda. The comparison among the CD spectra of the ((cdda)-(cdda)) complexes revealed that two diastereomers of the ((R,R-cdda)-(S,S-cdda)) complex correspond to the conformational isomers resulting from the difference in geometrical orientations of the secondary amine protons on two coordinated asymmetric nitrogen atoms with the opposite absolute configuration in the unsym-cis-S,S-cdda moiety. In a series of the pzdc-bridged Cr(III) complexes the anomalous conformations in two different geometrical configurations could be entrapped probably owing to stereognostic coordination through the intramolecular N-H...O hydrogen bond interaction.     

Preparation of biologically active and site specifically radioiodinated recombinant human insulin-like growth factor-I.

Recombinant human insulin-like growth factor-I (rhIGF-I) was iodinated using a lactoperoxidase-catalyzed labeling method. The labeled products were separated into more than five fractions by ion-paired reverse-phase high performance liquid chromatography (HPLC). A fraction (peak 1), which showed the highest yield and radioactivity, was found to be biologically active in the BALB/c 3T3 cell proliferating system. The site of the iodination was investigated by S-pyridylethylation followed by trypsinization and separation with HPLC using reverse phase columns. From the amino acid analysis of the peaks which were radioactive, the iodination site of peak 1 was revealed to be Tyr-24 and Tyr-60. This is the first report of the biological activity of radioactive peptide hormone with a defined labeled site.     

The basic research on physiological property of functionalized hyaluronan—I. Effect of hyaluronan and sulfated hyaluronan on cell proliferation of human epidermal keratinocytes

Hyaluronan (HA) is one of the polysaccharides that is found widely in connective tissue of mammals, and it has no sulfate group and high molecular weight in comparison with other glycosaminoglycans. Glycosaminoglycans are deeply concerned with the manifestation of biofunctions not only by their physical properties but also by physiological ones. In this study, sulfated HA (S‐HA) with various degrees of sulfate substitution and high molecular weight will be synthesized in order to give HA new biological functions. Moreover, the effect of HA and S‐HA on cell proliferation of human epidermal keratinocytes in vitro will be discussed. HA did not affect lag phase, but growth rate (metabolic turnover) of the cell in a logarithmic growth phase which was controlled by the molecular weight of HA. S‐HA stimulated the cell proliferation in the low concentration region under 1 μg/ml. While it inhibited the cell proliferation in the high concentration region over 10 μg/ml. It strongly suppressed the cell proliferation in the logarithmic growth metaphase. These facts were considered to be caused by the change of the cell‐matrix and/or cell–cell interactions. Copyright © 2004 John Wiley & Sons, Ltd.     

Quantitative analysis of transport process of cerium(III) ion through polymer inclusion membrane containing N,N,N′,N′-tetraoctyl-3-oxapentanediamide (TODGA) as carrier

The facilitated transport mechanism of cerium(III) ions through polymer inclusion membrane (PIM) consisting of cellulose triacetate (CTA) as a polymer matrix, 2-nitrophenyl n-octyl ether (NPOE) as a solvent and N,N,N′,N′-tetraoctyl-3-oxapentanediamide (TODGA) as a carrier was studied. In order to evaluate the mass transport phenomena in the PIM, a mathematical model was derived from the Fick's first law and the equations for the extraction and the material balance. Methods to determine the values of the transport parameters such as the diffusion coefficient are described, and the dependency of the flux on the experimental condition was calculated. The model is very useful as a design tool to analyze and optimize the concentration process of low level radioactive wastewater using the PIM.     

Thermal degradation of polyesters by simultaneous TG-DTA/FT-IR analysis

A combination system of thermogravimetric/differential thermal analysis (TG-DTA) and Fourier-transform infrared absorption spectroscopy (FT-IR) was described. This simultaneous TG-DTA/FT-IR technique gave spectroscopic and weight loss information about the thermal degradation process of engineering polyesters; poly(ethylene terephthalate)(PET) and poly(butylene terephthalate)(PBT). The evolved gases from PET were benzoic acid, carbon dioxide and carbon monoxide, while those from PBT were terephthalic acid esters and benzoic acid esters.

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Zusammenfassung Es wird ein kombiniertes System aus TG-DTA und FT-IR beschrieben. Mit dieser simultanen TG-DTA/FT-IR-Technik wurden spektroskopische und Massenverlustangaben über die thermische Zersetzung technisch wichtiger Polyester, namentlich von Poly(ethylenterephthalat) (PET) und Poly(Butylenterephthalat) (PBT) ermittelt. Die aus PET freigesetzten Gase waren Benzoesäure, Kohlendioxid und Kohlenmonoxid, die aus PBT freigesetzten Gase hingegen Terephthalsäureester und Benzoesäureester.

     

Inhibitory effects of bis(2-aminohexyl)disulfide and its analogues on polymorphonuclear leukocyte functions in vitro.

Water soluble analogues of the anti-inflammatory compound, bis(2-aminopropyl)disulfide dihydrochloride (compd. I) with a butyl (II), phenyl (III), benzyl (IV) or pyrrolidinyl group (V) instead of the methyl group were synthesized, and their effects on the functions of cells related to inflammation were studied in vitro. Compounds II, III and IV showed much higher inhibitory activity than compd. I on formyl Met-Leu-Phe (FMLP)-induced O2(-)-generation of polymorphonuclear leukocytes (PMNs) and platelet aggregation. Compound II showed the strongest activity among the compounds (IC50 values: 2.6 microM). The inhibition of O2(-)-generation of PMNs by compd. II was the most effective when FMLP was used as a stimulant rather than when phorbol myristate acetate, A-23187 and opsonized zymosan were used. However, compd. II was not an O2(-)-scavenger. Compounds II, III and IV significantly inhibited a series of activation processes in PMNs, chemotaxis, phagocytosis and lysosomal enzyme release at doses ranging from 10 to 100 microM. Under these doses, compds II, III and IV did not affect the histamine release from mast cells or the hemolysis of erythrocytes. These results strongly suggest that the anti-inflammatory action caused by compd. II and its analogues was at least partly due to inhibition of several functions of PMNs and platelets.     

Bootstrap-based consensus scoring method for protein-ligand docking

To improve the performance of a single scoring function used in a protein-ligand docking program, we developed a bootstrap-based consensus scoring (BBCS) method, which is based on ensemble learning. BBCS combines multiple scorings, each of which has the same function form but different energy-parameter sets. These multiple energy-parameter sets are generated in two steps: (1) generation of training sets by a bootstrap method and (2) optimization of energy-parameter set by a Z-score approach, which is based on energy landscape theory as used in protein folding, against each training set. In this study, we applied BBCS to the FlexX scoring function. Using given 50 complexes, we generated 100 training sets and obtained 100 optimized energy-parameter sets. These parameter sets were tested against 48 complexes different from the training sets. BBCS was shown to be an improvement over single scoring when using a parameter set optimized by the same Z-score approach. Comparing BBCS with the original FlexX scoring function, we found that (1) the success rate of recognizing the crystal structure at the top relative to decoys increased from 33.3% to 52.1% and that (2) the rank of the crystal structure improved for 54.2% of the complexes and worsened for none. We also found that BBCS performed better than conventional consensus scoring (CS).     

Hidden active information in a random compound library: extraction using a pseudo-structure-activity relationship model

We propose a hypothesis that "a model of active compound can be provided by integrating information of compounds high-ranked by docking simulation of a random compound library". In our hypothesis, the inclusion of true active compounds in the high-ranked compound is not necessary. We regard the high-ranked compounds as being pseudo-active compounds. As a method to embody our hypothesis, we introduce a pseudo-structure-activity relationship (PSAR) model. Although the PSAR model is the same as a quantitative structure activity relationship (QSAR) model, in terms of statistical methodology, the implications of the training data are different. Known active compounds (ligands) are used as training data in the QSAR model, whereas the pseudo-active compounds are used in the PSAR model. In this study, Random Forest was used as a machine-learning algorithm. From tests for four functionally different targets, estrogen receptor antagonist (ER), thymidine kinase (TK), thrombin, and acetylcholine esterase (AChE), using five scoring functions, we obtained three conclusions: (1) the PSAR models significantly gave higher percentages of known ligands found than random sampling, and these results are sufficient to support our hypothesis; (2) the PSAR models gave higher percentages of known ligands found than normal scoring by scoring function, and these results demonstrate the practical usefulness of the PSAR model; and (3) the PSAR model can assess compounds failed in the docking simulation. Note that PSAR and QSAR models are used in different situations; the advantage of the PSAR model emerges when no ligand is available as training data or when one wants to find novel types of ligands, whereas the QSAR model is effective for finding compounds similar to known ligands when the ligands are already known.     

Indirect Synthesis System for Ammonia from Nitrogen and Water Using Nonthermal Plasma Under Ambient Conditions

The indirect synthesis of NH₃ from N₂ and H₂O through plasma processing is proposed and demonstrated. NH₃ is a promising hydrogen storage material because of its high hydrogen storage density. Mg₃N₂ is a key material for indirect NH₃ synthesis, because the reaction of Mg₃N₂ with water easily generates NH₃ at room temperature. In this paper, therefore, we focus on generating Mg₃N₂ by nitridation of MgO with nonthermal atmospheric-pressure dielectric barrier discharge (DBD) plasma in a N₂ atmosphere. By intermittent DBD nitridation treatment while the reaction device was cooled in a water bath, a maximum Mg₃N₂ generation efficiency of 93 mg/kWh was estimated. Because NH₃ is generated through a simple chemical reaction, our scheme does not cause NH₃ decomposition by plasma, which is one of the greatest concerns associated with plasma synthesis. Contrary to the conventional NH₃ generation process, which emits CO₂ and requires high temperature and pressure, our scheme enables NH₃ synthesis from N₂ and H₂O without CO₂ emissions. This allows for an onsite small-scale NH₃ synthesis system to be realized under mild conditions, which is necessary for a future low-carbon society.     

Inhomogeneity of currents in a wire array during its explodingphase

The current in a wire array during its exploding phase has been studied. The wire array consisting of many thin wires is used as a plasma source in a z-pinch X-ray radiation system. The current distribution in the exploding wire array plays an important role in producing an initial symmetrical plasma. In the present experiment, four tungsten wires of 0.1 mm in diameter were exploded in a vacuum. The experiment was carried out with an inductive voltage adder pulsed power generator providing a current of 160 kA at quarter period of 1.8 μs The currents through and the voltage across the wires were measured simultaneously. It was found that the currents in the wires were inhomogeneous, especially after the wires became plasma. Once the currents became inhomogeneous, the inhomogeneity remained throughout the discharge. It was also studied how the dimensions of the wires affected the homogeneity of the currents. Wires of different lengths or different cross sectional areas resulted in strong inhomogeneities of the currents. The wires with shorter length or smaller cross-sectional area became plasmas earlier than other wires. Thus, the resistances of the wires were not equal. These differences in the resistance caused the inhomogeneity of the currents