Translational medicine of the glutamate AMPA receptor

Psychiatric and neurological disorders severely hamper patient’s quality of life. Despite their high unmet needs, the development of diagnostics and therapeutics has only made slow progress. This is due to limited evidence on the biological basis of these disorders in humans. Synapses are essential structural units of neurotransmission, and neuropsychiatric disorders are considered as “synapse diseases”. Thus, a translational approach with synaptic physiology is crucial to tackle these disorders. Among a variety of synapses, excitatory glutamatergic synapses play central roles in neuronal functions. The glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a principal component of glutamatergic neurotransmission; therefore, it is considered to be a promising translational target. Here, we review the limitations of current diagnostics and therapeutics of neuropsychiatric disorders and advocate the urgent need for the promotion of translational medicine based on the synaptic physiology of AMPAR. Furthermore, we introduce our recent translational approach to these disorders by targeting at AMPARs.     

Specific reactivity of 2,4,6-tri-tert-butylanilide anions and its application to benzylation reagent

The reaction of methyl iodide with an anilide anion prepared from 2,4,6-tri-tert-butylanilide and NaH in CH₃CN gave N-methyl anilide (N-alkylation product) as a major product, while in the reaction of benzyl bromide with the anilide anion in DMF, O-benzyl imidate (O-alkylation product) was obtained with almost complete selectivity. The treatment of O-benzyl imidate with alcohols and carboxylic acids in the presence of trifluoromethane sulfonic acid gave benzyl ethers and benzyl esters, respectively.     

Preparation, properties, and crystal structures of organometallic ionic liquids comprising 1-ferrocenyl-3-alkylimidazolium-based salts of bis(trifluoromethanesulfonyl)amide and hexafluorophosphate

Bis(trifluoromethanesulfonyl)amide (TFSA), hexafluorophosphate (PF(6)(-)), and iodide salts of 1-ferrocenyl-3-alkylimidazolium were prepared and their thermal and physical properties, including the dependence on alkyl chain length (methyl-hexadecyl), were investigated. The TFSA salts were highly viscous ionic liquids with melting points around room temperature. 1-Ferrocenyl-4-methyltriazolium salts were also prepared for comparison. The ferrocenylimidazolium and ferrocenyltriazolium cations showed redox waves for both the ferrocenyl moiety and the azolium moiety and exhibited corresponding charge-transfer bands at around 330 nm, which were analyzed using the Marcus-Hush model. Crystal structure determinations at low temperature revealed that the PF(6) and iodide salts form layerlike structures composed of ionic layers of the charged moieties. The TFSA salt exhibited short hydrogen-bond-like intermolecular contacts between the hydrogen atoms of the cation and oxygen atoms of the anion.     

Synthesis of β‐Methoxyacrylate Natural Products Based on Box‐PdII‐Catalyzed Intermolecular Methoxycarbonylation of Alkynoles

Bis(oxazoline)‐palladium(II) catalyzed carbonylation of homopropargyl alcohols afforded acyclic methoxyacrylate 2 and 6‐membered lactone 3a , 3b , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k in good combined yield. In the case of propargyl alcohols, 5‐membered lactones 3p , 3q , 16 were obtained in moderate yields. The one‐pot synthesis of kawa lactones 3a , 3r , 3s and formal synthesis of dihydroxycystothiazole A and dihydroxycystothiazole C are presented. To elucidate the stereochemistry of (+)‐annularin G and (?)‐annularin H, the first asymmetric syntheses of these natural products were achieved.     

Cross-relaxation and spectral broadening of gain for Nd/Cr:YAG ceramic lasers with white-light pump source under high-temperature operation

Spectral broadening of the fluorescence of a Nd/Cr:YAG ceramic at the 1064 nm lasing wavelength was observed, and the amplification properties at a high temperature were investigated by considering cross-relaxation. These ceramics are promising for use as a solid-laser material pumped with solar or lamp light. It has been found that whenever the temperature of a laser medium is high and a spectral shift occurs, a high small-signal gain remains owing to the broad spectral band and the cross-relaxation. This optical property is remarkably different from that of a Nd:YAG laser. For a conventional Nd:YAG laser, the bandwidth at 1064 nm is 0.45 nm, and a reduction in small-signal gain occurs at a temperature of 373 K because the spectral peak shift is 0.005 nm/K. However, for the Nd/Cr:YAG ceramic, the bandwidths are 1.2 and 1.9 nm in the case of 0.1% Cr ion doping and 3% Cr ion doping, respectively, owing to the existence of excited Cr ions and the shortening of the effective Nd ion coherence time. It is prospected that the laser medium can be used at a high temperature of 600 K.     

Biomimetic growth of gallic acid–ZnO hybrid assemblies and their applications

In this study, we probed the biomimetic formation of gallic acid (GA)–ZnO nanoparticle hybrids. It was found that the morphologies formed were dependent upon pH values, resulting in GA–ZnO hybrids of varying shapes such as micro or nanoplates or fibers. The formed supramolecular GA–ZnO hybrids were found to be luminescent as indicated by confocal microscopy and were utilized for the photocatalytic degradation of the organic dye methylene blue. We also explored the bactericidal effects of the hybrids on Staphylococcus aureus (S. aureus) as well as Escherichia Coli (E. Coli). Thus, we have developed a new class of shape-controlled nanohybrid assemblies via mild, green synthetic methods that may be utilized for photocatalytic degradation for environmental remediation as well as for antibacterial applications.     

Curdlan as a Polymeric Starting Material to Access C6-Modified Glucose Derivatives

We evaluated the potential of a linear β-1,3-glucan (curdlan) as a starting material to access C6-modified glucose derivatives and found that 6-bromo-6-deoxyglucose, 6-azide-6-deoxyglucose, and 6-acetamido-6-deoxyglucose could be readily prepared from curdlan through its C6-selective and quantitative modifications and subsequent acid-catalyzed hydrolysis.     

Syntheses and characterizations of 4-(3,17beta-dihydroxyestra-1,3,5(10)-trien-6alpha- and 6beta-yl)amino-7-nitro-2,1,3-benzoxadiazoles as fluorescent probes.

4-(3,17Beta-dihydroxyestra-1,3,5(10)-trien-6alpha- and 6beta-yl)amino-7-nitro-2,1,3-benzoxadiazoles have been synthesized and characterized as fluorescent probes for use in a receptor assay and/or a homogeneous immunoassay for estradiol. The fluorescence intensities are strongly dependent upon the solvent polarity used. The intensities in water were reduced to less than 1% of those in ethyl acetate, and a blue shift was also observed in polar solvents. The quenched fluorescence in aqueous solution was recovered by adding bovine serum albumin or an anti-estradiol antibody. Adding intact estradiol inhibited the fluorescence recovered by the antibody.     

Disk-type Nd/Cr:YAG ceramic lasers pumped by arc-metal-halide-lamp

We observed the lasing of highly sensitized Nd/Cr:YAG ceramic disks that use artificial solar radiation pumping. The disk material can be used for high power multi-stage amplifiers pumped by lamplight or sunlight because of its scalability and ability to handle high power densities. A maximum output power of 86 mW was experimentally obtained, and this value correlated well with the calculated results. A small signal gain of 1.9 was obtained, and the estimated stored energy was 0.6 J/cm³, which is three or four times higher than that from a Nd:YAG medium.