Kotaro Fujii

Cocrystallization and amorphization induced by drug–excipient interaction improves the physical properties of acyclovir

Although acyclovir is one of the most important antiviral drugs used today, there are several problems with its physical properties. The aim of this study is to prepare cocrystals or amorphous complex of acyclovir using drug-excipient interactions to improve the physical properties of the drug, especially its dissolution rate and transdermal absorption. Screening for formation of cocrystals and the presence of amorphous acyclovir was conducted with various pharmaceutical excipinents, with the use of the solution-crystallization method and liquid-assisted cogrinding. The potential cocrystalline phase and the amorphized complex were characterized by PXRD, TG/DTA, IR, DSC and HPLC techniques. The screening indicated that acyclovir formed novel cocrystals with tartaric acid and was amorphized with citric acid. The acyclovir-tartaric acid cocrystal (ACV-TA cocrystal) structure was determined from synchrotron X-ray powder diffraction data. T(g) of the amorphous acyclovir-citric acid compound (ACV-CA amorphous) was determined by DSC. The initial dissolution rate of the ACV-TA cocrystals was considerably faster than that of anhydrous acyclovir. In vitro skin permeation of ACV-CA amorphous from polyethylene glycol (PEG) ointment was remarkably higher than that of the crystalline acyclovir. We successfully improved the physical properties of acyclovir by the cocrystallization and amorphization techniques, using pharmaceutical excipients.

Exploiting powder X-ray diffraction for direct structure determination in structural biology: The P2X4 receptor trafficking motif YEQGL

We report the crystal structure of the 5-residue peptide acetyl-YEQGL-amide, determined directly from powder X-ray diffraction data recorded on a conventional laboratory X-ray powder diffractometer. The YEQGL motif has a known biological role, as a trafficking motif in the C-terminus of mammalian P2X4 receptors. Comparison of the crystal structure of acetyl-YEQGL-amide determined here and that of a complex formed with the μ2 subunit of the clathrin adaptor protein complex AP2 reported previously, reveals differences in conformational properties, although there are nevertheless similarities concerning aspects of the hydrogen-bonding arrangement and the hydrophobic environment of the leucine sidechain. Our results demonstrate the potential for exploiting modern powder X-ray diffraction methodology to achieve complete structure determination of materials of biological interest that do not crystallize as single crystals of suitable size and quality for single-crystal X-ray diffraction.

Hexaradialenes by Successive Ring Openings of Tris(alkoxy-tricyclobutabenzenes): Synthesis and Characterization†

Hexaradialenes are alicyclic cross-conjugated hydrocarbons, in which all of the carbon atoms in the six-membered ring are sp hybridized and have as many exocyclic double bonds as possible. Interesting physical properties and reactivities are expected from their unique structures, which also have potential utility for constructing polycyclic molecules. The parent system (I), however, is unstable and polymerizes immediately on formation; only a few substituted hexaradialenes have been structurally characterized, including hexamethyl, dodecamethyl, and hexabromo derivatives II–IV. One possible synthetic route to such systems is from the valence isomer, tricyclobutabenzene V; this route is particularly interesting as it considers the question of the relative thermodynamic preference of the two isomers. Although the corresponding interconversion between monocyclobutabenzene and quinodimethane has been thoroughly studied, their tricyclobutabenzene analogues have remained unstudied, presumably owing to their poor availability. We previously developed a flexible synthetic route to tricyclobutabenzenes that contain various oxygenated motifs by repeated [2+2] cycloadditions of benzyne and ketene silyl acetal (KSA), which allowed the study of the thermal behavior of oxygenated triannelated systems, such as VI. Herein, we report that the thermal isomerization of VI indeed offers a highly stereoselective access to stereodefined hexaradialenes VII, given that the hydroxy groups on the fourmembered rings were protected by bulky substituents.

Search for bosonic superweakly interacting massive dark matter particles with the XMASS-I detector

Bosonic superweakly interacting massive particles (super-WIMPs) are a candidate for warm dark matter. With the absorption of such a boson by a xenon atom, these dark matter candidates would deposit an energy equivalent to their rest mass in the detector. This is the first direct detection experiment exploring the vector super-WIMPs in the mass range between 40 and 120 keV. With the use of 165.9 day of data, no significant excess above background was observed in the fiducial mass of 41 kg. The present limit for the vector super-WIMPs excludes the possibility that such particles constitute all of dark matter. The absence of a signal also provides the most stringent direct constraint on the coupling constant of pseudoscalar super-WIMPs to electrons. The unprecedented sensitivity was achieved exploiting the low background at a level 10(-4)  kg-1 keVee-1 day-1 in the detector.

Reversible solid state redox of an octacyanometallate-bridged coordination polymer by electrochemical ion insertion/extraction.

Coordination polymers have significant potential for new functionality paradigms due to the intrinsic tunability of both their electronic and structural properties. In particular, octacyanometallate-bridged coordination polymers have the extended structural and magnetic diversity to achieve novel functionalities. We demonstrate that [Mn(H2O)][Mn(HCOO)(2/3)(H2O)(2/3)](3/4)[Mo(CN)8]·H2O can exhibit electrochemical alkali-ion insertion/extraction with high durability. The high durability is explained by the small lattice change of less than 1% during the reaction, as evidenced by ex situ X-ray diffraction analysis. The ex situ X-ray absorption spectroscopy revealed reversible redox of the octacyanometallate. Furthermore, the solid state redox of the paramagnetic [Mo(V)(CN)8](3-)/diamagnetic[Mo(IV)(CN)8](4-) couple realizes magnetic switching.

Singlet Ground State and Spin Gap in S = 1/2 Kagomé Antiferromagnet Rb2Cu3SnF12

We investigated the crystal structure of Rb 2 Cu 3 SnF 12 and its magnetic properties using single crystals. This compound is composed of Kagome layers of corner-sharing CuF 6 octahedra with a 2 a ×2 a enlarged cell as compared with the proper Kagome layer. Rb 2 Cu 3 SnF 12 is magnetically described as an S = 1/2 modified Kagome antiferromagnet with four kinds of neighboring exchange interaction. From magnetic susceptibility and high-field magnetization measurements, it was found that the ground state is a disordered singlet with the spin gap, as predicted from a recent theory. Exact diagonalization for a 12-site Kagome cluster was performed to analyze the magnetic susceptibility, and individual exchange interactions were evaluated.We investigated the crystal structure of Rb 2 Cu 3 SnF 12 and its magnetic properties using single crystals. This compound is composed of Kagome layers of corner-sharing CuF 6 octahedra with a 2 a ×2 a enlarged cell as compared with the proper Kagome layer. Rb 2 Cu 3 SnF 12 is magnetically described as an S = 1/2 modified Kagome antiferromagnet with four kinds of neighboring exchange interaction. From magnetic susceptibility and high-field magnetization measurements, it was found that the ground state is a disordered singlet with the spin gap, as predicted from a recent theory. Exact diagonalization for a 12-site Kagome cluster was performed to analyze the magnetic susceptibility, and individual exchange interactions were evaluated.

Magnetic susceptibilities in a family of S = 1/2 kagome antiferromagnets

Hexagonal antiferromagnets Cs

Improved oxide-ion conductivity of NdBaInO4 by Sr doping

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Metastable polymorphic form of isopropylbenzophenone derivative directly obtained by the solid-state photoreaction investigated by ab initiopowder X-ray diffraction analysis

Cu

Performance of the micro-PIC gaseous area detector in small-angle X-ray scattering experiments

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