Mixed La-Li heterobimetallic complexes for tertiary nitroaldol resolution

A kinetic resolution of tertiary nitroaldols derived from simple ketones is described. Mixed BINOL/biphenol La-Li heterobimetallic complexes gave the best selectivity in retro-nitroaldol reactions of racemic tertiary nitroaldols. By using a mixture of La-Li3-(1a)3 complex (LLB 2a) and La-Li3-(1b)3 (LLB* 2b) complex in a ratio of 2/1, chiral tertiary nitroaldols were obtained in 80-97% ee and 30-47% recovery yield.     

Constituents of Holothuroidea, 17. Isolation and structure of biologically active monosialo-gangliosides from the sea cucumber Cucumaria echinata

Three new monosialo-gangliosides, CEG-3 (3), CEG-4 (4), and CEG-5 (5), were obtained, together with two known gangliosides, SJG-1 (1) and CG-1 (2), from the lipid fraction of the chloroform/methanol extract of the sea cucumber Cucumaria echinata. The structures of the new gangliosides were determined on the basis of chemical and spectroscopic evidence to be 1-O-[4-O-acetyl-alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3) and 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (4, 5). The ceramide moieties of each compound were composed of heterogeneous sphingosine or phytosphingosine bases, and 2-hydroxy or nonhydroxylated fatty acid units. These gangliosides showed neuritogenic activity toward the rat pheochromocytoma cell line PC-12 in the presence of nerve growth factor.     

Probing the structural requirements of peptoids that inhibit HDM2-p53 interactions

Many cellular processes are controlled by protein-protein interactions, and selective inhibition of these interactions could lead to the development of new therapies for several diseases. In the area of cancer, overexpression of the protein, human double minute 2 (HDM2), which binds to and inactivates the protein p53, has been linked to tumor aggressiveness and drug resistance. In general, inhibition of protein-protein interactions with synthetic molecules is challenging and currently remains a largely uncharted area for drug development. One strategy to create inhibitors of protein-protein interactions is to recreate the three-dimensional arrangement of side chains that are involved in the binding of one protein to another, using a nonnatural scaffold as the attachment point for the side chains. In this study, we used oligomeric peptoids as the scaffold to begin to develop a general strategy in which we could rationally design synthetic molecules that can be optimized for inhibition of protein-protein interactions. Structural information on the HDM2-p53 complex was used to design our first class of peptoid inhibitors, and we provide here, in detail, the strategy to modify peptoids with the appropriate side chains that are effective inhibitors of HDM2-p53 binding. While we initially tried to develop rigid, helical peptoids as HDM2 binders, the best inhibitors were surprisingly peptoids that lacked any helix-promoting groups. These results indicate that starting with rigid peptoid scaffolds may not always be optimal to develop new inhibitors.     

Raman spectroscopic study on solvation of diphenylcyclopropenone and phenol blue in room temperature ionic liquids

We investigated the solvation of several room temperature ionic liquids by Raman spectroscopy using diphenylcyclopropenone (DPCP) and phenol blue (PB) as probe molecules. We estimated acceptor numbers (AN) of room temperature ionic liquids by an empirical equation associated with the Raman band of DPCP assigned as a C=C stretching mode involving a significant C=O stretching character. According to the dependence of AN on cation and anion species, the Lewis acidity of ionic liquids is considered to come mainly from the cation charge. The frequencies and bandwidths of the C=O and C=N stretching modes of phenol blue are found to be close to those in conventional polar solvents such as methanol and dimethyl sulfoxide. The frequencies of these vibrational modes show similar dependence upon the electronic absorption band center as is observed in conventional liquid solvents. However, peculiar behavior was found in the Raman bandwidths and the excitation wavelength dependence of the C=N stretching mode in room temperature ionic liquids. Both the bandwidth of the C=N stretching mode and the extent of the excitation wavelength dependence of the Raman shift of the C=N stretching mode tend to decrease as the absorption band center decreases, in contrast to the case of conventional solvents. This anomaly is discussed in terms of the properties of room temperature ionic liquids.     

Molecular characterization of O-methyltransferases involved in isoquinoline alkaloid biosynthesis in Coptis japonica

O-Methyltransferases, which catalyze the production of small molecules in plants, play a crucial role in determining biosynthetic pathways in secondary metabolism because of their strict substrate specificity. Using three O-methyltransferase (OMT) cDNAs that are involved in berberine biosynthesis, we investigated the structure that was essential for this substrate specificity and the possibility of creating a chimeric enzyme with novel substrate specificity. Since each OMT has a relatively well-conserved C-terminal putative S-adenosyl-L-methionine-binding domain, we first exchanged the N-terminal halves of different OMTs. Among the 6 combinations that we tested for creating chimeric OMTs, 5 constructs produced detectable amounts of recombinant proteins, and only one of these with an N-terminal half of 6-OMT and a C-terminal half of 4′-OMT (64′-OMT) showed methylation activity with isoquinoline alkaloids as a substrate. Further enzymological analysis of 64′-OMT reaction product indicated that 64′-OMT retained the regio-specificity of 6-OMT. Further examination of the N-terminal region of 64′-OMT showed that about 90 amino acid residues in the N-terminal half were critical for reaction specificity. The creation of OMTs with novel reactivity is discussed.     

Superconducting properties of SmFeAsO1−x prepared under high-pressure condition

Synthetic conditions such as stoichiometries, temperature and pressure are optimized to achieve a high quality oxygen deficient SmFeAsO_0.6 superconductor. Both electric and magnetic measurements show a sharp superconducting transition at about 55 K. Several important physical parameters are deduced. The apparent superconducting gap observed in heat capacity with 2Δ_o/k_BT_c of 4.57 larger than that of previous fluorine replaced samples indicate that this superconductivity will not strongly conflict with the phonon-mediated BCS mechanism. The mean free length ?=18.8 nm and the coherent length ξ=2.3-3.3 nm show that the superconductivity is in the clean limit.     

Comparison between theoretical model and experimental calibrations and its inference for track formation in bubble detectors

Calculations on the formation of a linear track of a heavy ion in bubble detector have been carried out based on a theoretical model considering the minimum energy (including bubble surface energy, internal energy, evaporation energy, expansion energy, kinetic energy and viscous energy) required during the formation of a critical bubble at the cost of the ionization energy of the heavy ion. The calculated minimum energy is 8.99 keV for dichlorodifluoromethane (R-12) at 25 °C. The results of calculations have been combined with those of calibrations of bubble detectors with heavy ions at accelerator. The threshold (1.51±0.04) MeV mg^-1 cm² is obtained in the calibration with heavy ions for the above liquid and temperature. It shows that the distance over which the heavy ion traverses and transfers energy to the superheated liquid to produce a critical bubble is 4.67 times the radius of the seed bubble. The radius of the cylinder along which the heavy ion deposits energy to form a seed bubble is about 5.2 nm. This dimension indicates that the process of track formation in bubble detectors is consistent with the model of thermal spike.     

Observation of droplet motion during flame spread on three-fuel-droplet array with a pendulum suspender

Flame spread on a fuel droplet array has been studied as a simple model of spray combustion. A three-fuel-droplet array with a pendulum suspender was employed to investigate interactions between flame spread and droplet motion in the axial direction. Initial droplet diameter was 0.8 mm, and fuel was n-heptane. A silicon carbide pendulum suspender of 15 μm in diameter and 30 mm in length was used for the third droplet. The first fixed droplet was ignited by electric spark. Behavior of the flame and the third droplet was observed using a high-speed video camera with an image intensifier. Particle tracking velocimetry (PTV) measurements were performed to explain the behavior of the third movable droplet. The dimensionless droplet span, which is the average of droplet-to-droplet distances divided by the average initial diameter of the three droplets, was varied from 2.5 to 8 for observing flame spread, and fixed at 5.5 for PTV measurements. It was observed that the third droplet moved away from the second droplet before the flame spread to the third droplet. The displacement of the third droplet is remarkable when the dimensionless droplet span is close to the limit of flame spread. This implies that the movement of the droplet decreases the dimensionless span of the flame spread limit and the flame spread speed near the flame spread limit. Results of PTV measurements suggest that the heat expansion wave, caused by ignition of the premixture which was accumulated around the second droplet, and the burned gas flow from the second droplet pushed away the third droplet; then natural convection, induced by the flames of the first and second droplets, drew the third droplet to the second droplet. The heat expansion wave and the burned gas flow of the second droplet reached nearly 12 in dimensionless span.