Synthesis of a base-stabilized silanone-coordinated complex by oxygenation of a (silyl)(silylene)tungsten complex

Base-stabilized silanone complex Cp*(OC)(2)W(SiMe(3)){O═SiMes(2)(DMAP)} (2) was synthesized by the reaction of (silyl)(silylene)tungsten complex Cp*(OC)(2)W(SiMe(3))(═SiMes(2)) (1) with 1 equiv of pyridine-N-oxide (PNO) in the presence of 4-(dimethylamino)pyridine (DMAP). Further oxygenation of 2 with 3 equiv of PNO at 80 °C resulted in the formation of a W-O-Si-O-Si framework to give disiloxanoxy complex Cp*(O)(2)W{OSiMes(2)(OSiMe(3))} (3). Complex 3 was also obtained by the direct reaction of complex 1 with 4 equiv of PNO at 80 °C.     

Sulfonyl-bridged oligo(benzoic acid)s: synthesis, X-ray structures, and properties as metal extractants

Sulfonyl-bridged oligo(benzoic acid)s 7 _n (n = 2–4) are prepared from the corresponding triflate esters (8 _n ) of sulfur-bridged oligophenols by palladium-catalyzed methoxycarbonylation of the triflate moieties, followed by hydrolysis of the resulting methyl esters, and subsequent oxidation of the sulfur bridges. X-ray analysis reveals that dimer 7 ₂ forms supramolecular zig-zag chains through intermolecular hydrogen bonds between the carboxy groups. As for the crystal of trimer 7 ₃ , two molecules are associated through two couples of intermolecular hydrogen bonds between terminal and central carboxy groups to form a cyclic dimer, which connects with two adjacent dimers with the remaining carboxy groups to construct an infinite columnar structure. Tetramer 7 ₄ adopts a monomolecular cyclic structure through intramolecular hydrogen bonds between the terminal carboxy groups, and a molecule connects with each of two adjacent molecules through two couples of intermolecular hydrogen bonds between inner carboxy and sulfonyl groups. Solvent extraction experiments reveal that the oligo(benzoic acid)s exhibit high extractability toward lanthanoid ions (Ln³⁺); the performance follows the order 7 ₄  ≈ 7 ₃  > 7 ₂ . Moderate extraction selectivity is observed for the extraction of Pr³⁺, Gd³⁺, and Yb³⁺ with 7 ₂ . X-ray crystallographic analysis of cluster [Tb₄L₄(H₂O)₆](Et₃NH)₄, which was prepared from 7 ₄ (H₄L) and Tb(NO₃)₃·6H₂O in the presence of Et₃N, reveals that no sulfonyl oxygens coordinate to the metal centers. This indicates that the high extractability of 7 ₄ originates from the electron-withdrawing nature of the sulfonyl function, which increases the acidity of two adjacent carboxy groups.     

Genetic and expression analysis of SNPs in the human deoxyribonuclease II: SNPs in the promoter region reduce its in vivo activity through decreased promoter activity

Five SNPs in the human DNase II gene have been reported to be associated with rheumatoid arthritis (RA). Genotype and haplotype analysis of 14 SNPs, nine SNPs of which reported in the NCBI dbSNP database in addition to these five SNPs, was performed in healthy subjects. The enzymatic activities of the amino acid substituted DNase II corresponding to each SNP and serum DNase II in healthy Japanese, and promoter activities derived from each haplotype of the RA‐related SNPs were measured. Significant correlations between genotype in each RA‐related SNP and enzymatic activity levels were found; alleles associated with RA exhibited a reduction in serum DNase II activity. Furthermore, the promoter activities of each reporter construct corresponding to predominant haplotypes in three SNPs in the promoter region of the gene exhibited significant correlation with levels of serum DNase II activity. These findings indicate these three SNPs could alter the promoter activity of DNASE2, leading to a decline in DNase II activity in the serum through gene expression. Since the three SNPs in the promoter region of the DNase II gene could affect in vivo DNase II activity through reduction of the promoter activity, it is feasible to identify these SNPs susceptible to RA.     

Asymmetric synthesis of the carbon-14-labeled selective glucocorticoid receptor modulator using cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate

We describe in this study the asymmetric synthesis of radioisotope (RI)-labeled selective glucocorticoid receptor modulator. This synthesis is based on optimization of the cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate and Negishi coupling of zinc cyanide to the 6-bromoindole moiety. [1?C] Labeled (-)-{4-[(1-{2-[6-cyano-1-(cyclohexylmethyl)-1H-indol-3-yl]-3,3,3-trifluoro-2-hydroxypropyl}piperidin-4-yl)oxy]-3-methoxyphenyl}acetic acid (-)-1 was synthesized successfully with high enantioselectivity (>99% ee) and sufficient radiochemical purity.     

Promotion effects of optical antipodes on the formation of helical fibrils: chiral perfluorinated gelators

A chiral gelator, RR- or SS-N,N'-diperfluorooctanoyl-1,2-diaminocyclohexane, gelated racemic 2-butanol. The gel was most stable at the racemic mixture, its stability lowered with the increase in the optical purity of the gelator. Notably, characteristic helically coiled fibrils were formed in the narrow region of enantiomer excess (ee = 0.2-0.4). Promotion effects of the antipodal enantiomers are proposed.     

Comprehensive study of proteins that interact with microcystin-LR

We carried out a comprehensive study of proteins that exhibit specific interactions with a naturally occurring toxin, microcystin (MC)-LR, in order to gain insight into the unknown underlying mechanism of MC virulence. This audacious study employed a simple affinity test that used MC-LR immobilized on an original ethylene oxide based monolithic solid phase (Moli-gel), and swine liver lysate. Some of the proteins that interacted with MC-LR on this original affinity resin were separated by SDS-PAGE, measured by nano-LC/MS/MS after trypsin digestion, and identified using a Mascot database search. Protein sequence analyses revealed that glutathione S-transferase (GST) was one of the candidate target proteins for MC-LR. This protein was confirmed as a target protein for MC-LR based on the results of for the inhibition of an enzymatic reaction by Dhb-MC-LR. Moreover, L-3-hydroxyacyl coenzyme A dehydrogenase (HDHA) was shown to be one of the proteins that specifically interacts with MC-LR. Our results demonstrated that our analytical systems based on an original affinity resin and nano-LC/MS/MS were effective for target protein research.     

INTERACTION OF RHODOPSIN, G-PROTEIN AND KINASE IN OCTOPUS PHOTORECEPTORS

Light induced phosphorylation of octopus rhodopsin was greatly enhanced by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), suggesting that the kinases are involved in regulating interaction between rhodopsin and G-protein. We determined phosphorylated peptides of octopus rhodopsin in the presence or absence of GTP gamma S. Possible phosphorylation sites for octopus rhodopsin enhanced by GTP gamma S were Thr329, Thr330 and/or Thr336, which suggest that the G-protein associates with cytoplasmic loops including C-terminal peptide in the seventh helix of octopus rhodopsin.     

Optimization of capillary array electrophoresis single-strand conformation polymorphism analysis for routine molecular diagnostics

Mutation screening is widely used for molecular diagnostics of inherited disorders. Furthermore, it is anticipated that the present and future identification of genetic risk factors for complex disorders will increase the need for high-throughput mutation screening technologies. Capillary array electrophoresis (CAE) SSCP analysis is a low-cost, automated method with a high throughput and high reproducibility. Thus, the method fulfills many of the demands to be met for application in routine molecular diagnostics. However, the need for performing the electrophoresis at three temperatures between 18 degrees C and 35 degrees C for achievement of high sensitivity is a disadvantage of the method. Using a panel of 185 mutant samples, we have analyzed the effect of sample purification, sample medium and separation matrix on the sensitivity of CAE-SSCP analysis to optimize the method for molecular diagnostic use. We observed different effects from sample purification and sample medium at different electrophoresis temperatures, probably reflecting the complex interplay between sequence composition, electrophoresis conditions and sensitivity in SSCP analysis. The effect on assay sensitivity from three different polymers was tested using a single electrophoresis temperature of 27 degrees C. The data suggest that a sensitivity of 98-99% can be obtained using a 10% long chain poly-N,N-dimethylacrylamide polymer.     

Determination of Hexachlorocyclohexane by Gas Chromatography Combined with Femtosecond Laser Ionization Mass Spectrometry

Structural isomers and enantiomers of hexachlorocyclohexane (HCH) were separated using a chiral column by gas chromatography and quantitatively determined by multiphoton ionization mass spectrometry using an ultraviolet femtosecond laser (200 and 267 nm) as the ionization source. The order of elution of the enantiomers (i.e., (+)-α-HCH and (-)-α-HCH) was predicted from stabilization energies calculated for the complexes using permethylated γ-cyclodextrin as the stationary phase of the column, and the results were compared with the experimental data. The molecular ions observed for HCH were weak, even though they can be ionized through a process of resonance enhanced two-photon ionization at 200 nm. This unfavorable result can be attributed to the dissociation of the molecular ion, as predicted from quantum chemical calculations.

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