American Chemical Society Acta Medica Okayama 2470-1343 2025 High-Resolution HPLC for Separating Peptide-Oligonucleotide Conjugates EN Miyako Naganuma Division of Organic Chemistry, National Institute of Health Sciences Genichiro Tsuji Division of Organic Chemistry, National Institute of Health Sciences Misato Amiya YMC CO., LTD. Reira Hirai YMC CO., LTD. Yuki Higuchi YMC CO., LTD. Naoko Hata YMC CO., LTD. Saoko Nozawa YMC CO., LTD. Daishi Watanabe Division of Organic Chemistry, National Institute of Health Sciences Taeko Nakajima YMC CO., LTD. Yosuke Demizu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Science, Okayama University Peptide-oligonucleotide conjugates (POCs) are chimeric molecules that combine the specificity of oligonucleotides with the functionality of peptides, improving the delivery and therapeutic potential of nucleic acid-based drugs. However, the analysis of POCs, particularly those containing arginine-rich sequences, poses major challenges because of aggregation caused by electrostatic interactions. In this study, we developed an optimized high-performance liquid chromatography (HPLC) method for analyzing POCs. Using a conjugate of DNA and nona-arginine as a model compound, we systematically investigated the effects of various analytical parameters, including column type, column temperature, mobile-phase composition, and pH. A column packed with C18 resin with wide pores combined with butylammonium acetate as the ion-pairing reagent and an optimal column temperature of 80 degrees C provided superior peak resolution and sensitivity. The optimized conditions gave clear separation of POCs from unlinked oligonucleotides and enabled the detection of nucleic acid fragments lacking an alkyne moiety as a linkage part, which is critical for quality control. Our HPLC method is robust and reproducible and substantially reduces the complexity, time, and cost associated with the POC analysis. The method may improve the efficiency of quality control in the production of POCs, thereby supporting their development as promising therapeutic agents for clinical applications. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 9 50 2024 Conformational Flexibility of D1-Glu189: A Crucial Determinant in Substrate Water Selection, Positioning, and Stabilization within the Oxygen-Evolving Complex of Photosystem II 50041 50048 EN Hiroshi Isobe Research Institute for Interdisciplinary Science, Okayama University Takayoshi Suzuki Research Institute for Interdisciplinary Science, Okayama University Michihiro Suga Research Institute for Interdisciplinary Science, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Okayama University Kizashi Yamaguchi Center for Quantum Information and Quantum Biology, Osaka University Photosynthetic water oxidation is a vital process responsible for producing dioxygen and supplying the energy necessary to sustain life on Earth. This fundamental reaction is catalyzed by the oxygen-evolving complex (OEC) of photosystem II, which houses the Mn4CaO5 cluster as its catalytic core. In this study, we specifically focus on the D1-Glu189 amino acid residue, which serves as a direct ligand to the Mn4CaO5 cluster. Our primary goal is to explore, using density functional theory (DFT), how the conformational flexibility of the D1-Glu189 side chain influences crucial catalytic processes, particularly the selection, positioning, and stabilization of a substrate water molecule within the OEC. Our investigation is based on a hypothesis put forth by Li et al. (Nature, 2024, 626, 670), which suggests that during the transition from the S2 to S3 state, a specific water molecule temporarily coordinating with the Ca ion, referred to as O6*, may exist as a hydroxide ion (OH-). Our results demonstrate a key mechanism by which the detachment of the D1-Glu189 carboxylate group from its coordination with the Ca ion allows the creation of a specialized microenvironment within the OEC that enables the selective attraction of O6* in its deprotonated form (OH-) and stabilizes it at the catalytic metal (MnD) site. Our findings indicate that D1-Glu189 is not only a structural ligand for the Ca ion but may also play an active and dynamic role in the catalytic process, positioning O6* optimally for its subsequent participation in the oxidation sequence during the water-splitting cycle. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 9 19 2024 Superstructure of Fe5–xGeTe2 Determined by Te K-Edge Extended X-ray Absorption Fine Structure and Te Kƒ¿ X-ray Fluorescence Holography 21287 21297 EN Ritsuko Eguchi Research Institute for Interdisciplinary Science, Okayama University Halubai Sekhar Department of Physical Science and Technology, Nagoya Institute of Technology Koji Kimura Department of Physical Science and Technology, Nagoya Institute of Technology Hirokazu Masai Department of Materials and Chemistry, National Institute of Advanced Industrial Science and Technology (AIST) Naohisa Happo Graduate School of Information Sciences, Hiroshima City University Mitsuki Ikeda Research Institute for Interdisciplinary Science, Okayama University Yuki Yamamoto Research Institute for Interdisciplinary Science, Okayama University Masaki Utsumi Research Institute for Interdisciplinary Science, Okayama University Hidenori Goto Research Institute for Interdisciplinary Science, Okayama University Yasuhiro Takabayashi Department of Physical Science and Technology, Nagoya Institute of Technology Hiroo Tajiri Japan Synchrotron Radiation Research Institute (JASRI) Koichi Hayashi Department of Physical Science and Technology, Nagoya Institute of Technology Yoshihiro Kubozono Research Institute for Interdisciplinary Science, Okayama University The local structure of the two-dimensional van der Waals material, Fe5–xGeTe2, which exhibits unique structural/magnetic phase transitions, was investigated by Te K-edge extended X-ray absorption fine structure (EXAFS) and Te Kƒ¿ X-ray fluorescence holography (XFH) over a wide temperature range. The formation of a trimer of Te atoms at low temperatures has been fully explored using these methods. An increase in the Te–Fe distance at approximately 150 K was suggested by EXAFS and presumably indicates the formation of a Te trimer. Moreover, XFH displayed clear atomic images of Te atoms. Additionally, the distance between the Te atoms shortened, as confirmed from the atomic images reconstructed from XFH, indicating the formation of a trimer of Te atoms, i.e., a charge-ordered (3⎯⎯ã~3⎯⎯ã)𝑅30◦ superstructure. Furthermore, Te Kƒ¿ XFH provided unambiguous atomic images of Fe atoms occupying the Fe1 site; the images were not clearly observed in the Ge Kƒ¿ XFH that was previously reported because of the low occupancy of Fe and Ge atoms. In this study, EXAFS and XFH clearly showed the local structure around the Te atom; in particular, the formation of Te trimers caused by charge-ordered phase transitions was clearly confirmed. The charge-ordered phase transition is fully discussed based on the structural variation at low temperatures, as established from EXAFS and XFH. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2694-2453 3 5 2023 Highly Stretchable Stress-Strain Sensor from Elastomer Nanocomposites with Movable Cross-links and Ketjenblack 394 405 EN Ryohei Ikura Department of Macromolecular Science, Graduate School of Science and Forefront Research Center for Fundamental Sciences, Osaka University Kota Kajimoto Department of Macromolecular Science, Graduate School of Science, Osaka University Junsu Park Department of Macromolecular Science, Graduate School of Science and Forefront Research Center for Fundamental Sciences, Osaka University Shunsuke Murayama Graduate School of Organic Materials Engineering, Yamagata University Yusei Fujiwara Department of Mechanical Engineering, Osaka Institute of Technology Motofumi Osaki Department of Macromolecular Science, Graduate School of Science and Forefront Research Center for Fundamental Sciences, Osaka University Tomohiro Suzuki Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Hidenori Shirakawa Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Yujiro Kitamura Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Hiroaki Takahashi Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Yasumasa Ohashi Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Seiji Obata Research Core for Interdisciplinary Sciences, Okayama University Akira Harada SANKEN (The Institute of Scientific and Industrial Research), Osaka University Yuka Ikemoto Japan Synchrotron Radiation Research Institute Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Yasutomo Uetsuji Department of Mechanical Engineering, Osaka Institute of Technology Go Matsuba Graduate School of Organic Materials Engineering, Yamagata University Yoshinori Takashima Department of Macromolecular Science, Graduate School of Science and Forefront Research Center for Fundamental Sciences, Osaka University Practical applications like very thin stress-strain sensors require high strength, stretchability, and conductivity, simultaneously. One of the approaches is improving the toughness of the stress-strain sensing materials. Polymeric materials with movable cross-links in which the polymer chain penetrates the cavity of cyclodextrin (CD) demonstrate enhanced strength and stretchability, simultaneously. We designed two approaches that utilize elastomer nanocomposites with movable cross-links and carbon filler (ketjenblack, KB). One approach is mixing SC (a single movable cross-network material), a linear polymer (poly(ethyl acrylate), PEA), and KB to obtain their composite. The electrical resistance increases proportionally with tensile strain, leading to the application of this composite as a stress- strain sensor. The responses of this material are stable for over 100 loading and unloading cycles. The other approach is a composite made with KB and a movable cross-network elastomer for knitting dissimilar polymers (KP), where movable cross-links connect the CD-modified polystyrene (PSCD) and PEA. The obtained composite acts as a highly sensitive stress-strain sensor that exhibits an exponential increase in resistance with increasing tensile strain due to the polymer dethreading from the CD rings. The designed preparations of highly repeatable or highly responsive stress-strain sensors with good mechanical properties can help broaden their application in electrical devices. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 8 12 2023 Development of Pipetteless Paper-Based Analytical Devices with a Volume Gauge 11213 11219 EN Kaewta Danchana Department of Chemistry, Okayama University Hiroshi Iwasaki Department of Chemistry, Okayama University Yada Thayawutthikun Flow Innovation-Research for Science and Technology Laboratories (FIRST Labs), Mahidol University Phoonthawee Saetear Flow Innovation-Research for Science and Technology Laboratories (FIRST Labs), Mahidol University Takashi Kaneta Department of Chemistry, Okayama University In this work, we propose a new design for paper based analytical devices (PADs) that eliminate the need to use a micropipette for sample introduction. With this design, a PAD is equipped with a distance-based detection channel that is connected to a storage channel that indicates the volume of a sample introduced into the PAD. The analyte in the sample solution reacts with a colorimetric reagent deposited into the distance-based detection channel as the sample solution flows into the storage channel where the volume is measured. The ratio of the lengths of the detection channel and that of the storage channel (D/S ratio) are constant for a sample containing a certain concentration, which is independent of the introduced volume. Therefore, the PADs permit volume-independent quantification using a dropper instead of a micropipette because the length of the storage channel plays the role of a volume gauge to estimate the introduced sample volume. In this study, the D/S ratios obtained with a dropper were comparable to those obtained with a micropipette, which confirmed that precise volume control is unnecessary for this PAD system. The proposed PADs were applied to the determinations of iron and bovine serum albumin using bathophenanthroline and tetrabromophenol blue as colorimetric reagents, respectively. The calibration curves showed good linear relationships with coefficients of 0.989 for iron and 0.994 for bovine serum albumin, respectively. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 8 2023 Detection of Membrane Potential-Dependent Rhodopsin Fluorescence Using Low-Intensity Light Emitting Diode for Long-Term Imaging 4826 4834 EN Shiho Kawanishi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichi Kojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Shibukawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayuki Sakamoto Department of Optical Neural and Molecular Physiology, Graduate School of Biostudies Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Faculty of Medicine, Dentistry and Pharmaceutical Sciences Microbial rhodopsin is a family of photoreceptive membrane proteins that commonly consist of a seven-transmembrane domain and a derivative of vitamin-A, retinal, as a chromophore. In 2011, archaeorhodopsin-3 (AR3) was shown to exhibit voltage-dependent fluorescence changes in mammalian cells. Since then, AR3 and its variants have been used as genetically encoded voltage indicators, in which mostly intense laser stimulation (1-1000 W/cm(2)) is used for the detection of dim fluorescence of rhodopsin, leading to high spatiotemporal resolution. However, intense laser stimulation potentially causes serious cell damage, particularly during long-term imaging over minutes. In this study, we present the successful detection of voltage-sensitive fluorescence of AR3 and its high fluorescence mutant Archon1 in a variety of mammalian cell lines using low-intensity light emitting diode stimulation (0.15 W/cm2) with long exposure time (500 ms). The detection system enables real-time imaging of drug-induced slow changes in voltage within the cells for minutes harmlessly and without fluorescence bleaching. Therefore, we demonstrate a method to quantitatively understand the dynamics of slow changes in membrane voltage on long time scales. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 7 50 2022 Oligoarginine-Conjugated Peptide Foldamers Inhibiting Vitamin D Receptor-Mediated Transcription 46573 46582 EN Mami Takyo National Institute of Health Sciences Yumi Sato National Institute of Health Sciences Naoya Hirata National Institute of Health Sciences Keisuke Tsuchiya National Institute of Health Sciences Hiroaki Ishida Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University Takashi Kurohara National Institute of Health Sciences Yuta Yanase National Institute of Health Sciences Takahito Ito National Institute of Health Sciences Yasunari Kanda National Institute of Health Sciences Keiko Yamamoto Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University Takashi Misawa National Institute of Health Sciences Yosuke Demizu National Institute of Health Sciences The vitamin D receptor (VDR) is a nuclear receptor, which is involved in several physiological processes, including differentiation and bone homeostasis. The VDR is a promising target for the development of drugs against cancer and bone-related diseases. To date, several VDR antagonists, which bind to the ligand binding domain of the VDR and compete with the endogenous agonist 1 alpha,25(OH)D3, have been reported. However, these ligands contain a secosteroidal skeleton, which is chemically unstable and complicated to synthesize. A few VDR antagonists with a nonsecosteroidal skeleton have been reported. Alternative inhibitors against VDR transactivation that act via different mechanisms are desirable. Here, we developed peptide-based VDR inhibitors capable of disrupting the VDR-coactivator interaction. It was reported that helical SRC2-3 peptides strongly bound to the VDR and competed with the coactivator in vitro. Therefore, we designed and synthesized a series of SRC2-3 derivatives by the introduction of nonproteinogenic amino acids, such as beta-amino acids, and by side-chain stapling to stabilize helical structures and provide resistance against digestive enzymes. In addition, conjugation with a cell-penetrating peptide increased the cell membrane permeability and was a promising strategy for intracellular VDR inhibition. The nona-arginine-conjugated peptides 24 with side-chain stapling and 25 with cyclic beta-amino acids showed strong intracellular VDR inhibitory activity, resulting in suppression of the target gene expression and inhibition of the cell differentiation of HL-60 cells. Herein, the peptide design, structure-activity relationship (SAR) study, and biological evaluation of the peptides are described. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 2022 Characteristics of Vertical Ga2O3 Schottky Junctions with the Interfacial Hexagonal Boron Nitride Film 26021 26028 EN Venkata Krishna Rao Rama Graduate School of Natural Science and Technology, Okayama University Ajinkya K. Ranade Department of Physical Science and Engineering, Nagoya Institute of Technology Pradeep Desai Department of Physical Science and Engineering, Nagoya Institute of Technology Bhagyashri Todankar Department of Physical Science and Engineering, Nagoya Institute of Technology Golap Kalita Department of Physical Science and Engineering, Nagoya Institute of Technology Hiroo Suzuki Graduate School of Natural Science and Technology Masaki Tanemura Department of Physical Science and Engineering, Nagoya Institute of Technology Yasuhiko Hayashi We present the device properties of a nickel (Ni)- gallium oxide (Ga2O3) Schottky junction with an interfacial hexagonal boron nitride (hBN) layer. A vertical Schottky junction with the configuration Ni/hBN/Ga2O3/In was created using a chemical vapor-deposited hBN film on a Ga(2)O(3 )substrate. The current-voltage characteristics of the Schottky junction were investigated with and without the hBN interfacial layer. We observed that the turn-on voltage for the forward current of the Schottky junction was significantly enhanced with the hBN interfacial film. Furthermore, the Schottky junction was analyzed under the illumination of deep ultraviolet light (254 nm), obtaining a photoresponsivity of 95.11 mA/W under an applied bias voltage (-7.2 V). The hBN interfacial layer for the Ga2O3-based Schottky junction can serve as a barrier layer to control the turn-on voltage and optimize the device properties for deep-UV photosensor applications. Furthermore, the demonstrated vertical heterojunction with an hBN layer has the potential to be significant for temperature management at the junction interface to develop reliable Ga2O3-based Schottky junction devices. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1932-7447 126 22 2022 Role of Oxygen Vacancy in the Photocarrier Dynamics of WO3 Photocatalysts: The Case of Recombination Centers 9257 9263 EN Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Yohei Uemura Institute for Molecular Science Kiyotaka Asakura Institute for Catalysis, Hokkaido University Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Defects in powder photocatalysts determine the photocatalytic activity. The addition of defects sometimes enhances the activity, but sometimes decreases it. However, the factors determining the difference between these cases have not been fully elucidated yet. Herein, we investigated the effects of oxygen vacancies on photocarrier dynamics in WO3 powder using broadband transient absorption spectroscopy. It was found that the decay of deeply trapped electrons was accelerated when the number of oxygen vacancies was increased by H-2 reduction. This result suggests that oxygen vacancies in WO3 mainly act as recombination centers. This is in contrast to many other photocatalysts such as TiO2 and SrTiO3, where the carrier lifetime increases with increasing oxygen vacancy concentration. These differences can be attributed to the difference in the distance between oxygen vacancies. When defects are dispersed, trapped electrons need to travel over long distances by repeatedly hopping and tunneling between defects to combine with holes, resulting in decelerated recombination. In contrast, when the defects are connected or located close together, the trapped electrons can readily migrate among defects, leading to enhanced recombination. Control of the distance between defects is thus important for enhancing photocatalytic activity. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 7 15 2022 Eco-Benign Orange-Hued Pigment Derived from Aluminum-Enriched Biogenous Iron Oxide Sheaths 12795 12802 EN Katsunori Tamura Graduate School of Natural Science and Technology, Okayama University Yuri Oshima Graduate School of Natural Science and Technology, Okayama University Yuta Fuse Graduate School of Natural Science and Technology, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Tatsuki Kunoh Graduate School of Natural Science and Technology, Okayama University Makoto Nakanishi Graduate School of Natural Science and Technology, Okayama University Tatsuo Fujii Graduate School of Natural Science and Technology, Okayama University Tokuro Nanba Graduate School of Environmental and Life Science, Okayama University Jun Takada Graduate School of Natural Science and Technology, Okayama University Inorganic pigments have been widely used due to their low cost of production, strong hiding power, and chemical resistance; nevertheless, they have limited hue width and chromaticity. To eliminate these disadvantages, we herein propose the use of an ingenious biotemplate technique to produce Al-enriched biogenic iron oxide (BIOX) materials. Spectrophotometric color analysis showed that high levels of Al inclusion on heat-treated BIOX samples produced heightened yellowish hues and lightness. The Al-enriched BIOX sheaths exhibited a stable tubular structure and excellent thermal stability of color tones after heating at high temperatures and repetitive heat treatments. Ultrastructural analysis and mechanical destruction experiments revealed that the highly chromatic orange-hue of these pigments are ascribed probably to an ingenious cylindrical nanocomposite architecture composed of putative Fe-included low crystalline Al oxide regions and hematite particles embedded therein. The present work therefore demonstrates that the bioengineered material can serve as an epochal orange-hued inorganic pigment with low toxicity and marked thermostability that should meet large industrial demand. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2379-3694 7 4 2022 Dip-and-Read, Organic Solvent-Compatible, Paper-Based Analytical Devices Equipped with Chromatographic Separation for Indole Analysis in Shrimp 1194 1200 EN Sasikarn Seetasang Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takashi Kaneta Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University We developed an organic solvent-compatible paper-based analytical device (PAD) for the quantitative analysis of indole, which is an indicator of shrimp freshness. Although indole is insoluble in water, ethyl acetate is a suitable solvent to dissolve and extract indole from shrimp. The PADs are fabricated using a cutting method that allows the use of an organic solvent because no hydrophobic barrier is needed to form fluidic channels. Ehrlich's reagent consists of 4-(dimethylamino)benzaldehyde and p-dimethylaminobenzaldehyde and was deposited onto the reaction zone of the PAD followed by lamination to prevent evaporation of the ethyl acetate. Samples are introduced into the PAD via immersion in organic sample solutions. When the PAD is immersed into an indole solution of ethyl acetate in a closed bottle, the sample solution penetrates the channel of the PAD and successively flows into the detection zone to form a hydrophilic colored product. The PADs provide a linear relationship between the logarithm of the indole concentration and the color intensity within a range of 1.0-20 ppm with correlation coefficients of r2 > 0.99. The limits of detection and quantification are 0.36 and 0.71 ppm, respectively. Relative standard deviations for both the intraday (n = 2) and interday (n = 3) precision were less than 2.5%. In the indole analysis of shrimp, the PADs separated the interfering orange-colored astaxanthin in the extract from the colored product of indole via the paper chromatographic principle. We used the PADs to investigate the degradation of shrimp, and the results showed a rapid increase in the indole level after 7 days. High-performance liquid chromatography verified the accuracy of the PADs by showing good agreement with the obtained indole levels. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 7 6 2022 Evaluation of Effective Field-Effect Mobility in Thin-Film and Single-Crystal Transistors for Revisiting Various Phenacene-Type Molecules 5495 5501 EN Yanting Zhang Research Institute for Interdisciplinary Science, Okayama University Ritsuko Eguchi Research Institute for Interdisciplinary Science, Okayama University Shino Hamao Research Institute for Interdisciplinary Science, Okayama University Hideki Okamoto Department of Chemistry, Okayama University Hidenori Goto Research Institute for Interdisciplinary Science, Okayama University Yoshihiro Kubozono Research Institute for Interdisciplinary Science, Okayama University The magnitude of the field-effect mobility mu of organic thin-film and single-crystal field-effect transistors (FETs) has been over-estimated in certain recent studies. These reports set alarm bells ringing in the research field of organic electronics. Herein, we report a precise evaluation of the mu values using the effective field-effect mobility, mu(eff), a new indicator that is recently designed to prevent the FET performance of thin-film and single-crystal FETs based on various phenacene molecules from being overestimated. The transfer curves of a range of FETs based on phenacene are carefully categorized on the basis of a previous report. The exact evaluation of the value of mu(eff) depends on the exact classification of each transfer curve. The transfer curves of all our phenacene FETs could be successfully classified based on the method indicated in the aforementioned report, which made it possible to evaluate the exact value of mu(eff) for each FET. The FET performance based on the values of mu(eff) obtained in this study is discussed in detail. In particular, the mu(eff) values of single-crystal FETs are almost consistent with the mu values that were reported previously, but the mu(eff) values of thin-film FETs were much lower than those previously reported for mu, owing to a high absolute threshold voltage, vertical bar V-th vertical bar. The increase in the field-effect mobility as a function of the number of benzene rings, which was previously demonstrated based on the mu values of single-crystal FETs with phenacene molecules, is well reproduced from the mu(eff) values. The FET performance is discussed based on the newly evaluated mu(eff) values, and the future prospects of using phenacene molecules in FET devices are demonstrated. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 6 15 2021 Design of Clickable Ionic Liquid Monomers to Enhance Ionic Conductivity for Main-Chain 1,2,3-Triazolium-Based Poly(Ionic Liquid)s 10030 10038 EN Ruka Hirai Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tsutomu Ono Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University A series of clickable alpha-azide-omega-alkyne ionic liquid (IL) monomers with an ethylene oxide spacer were developed and applied to the synthesis of 1,2,3-triazolium-based poly(ionic liquid)s (TPILs) with high ionic conductivities via one-step thermal azide-alkyne cycloaddition click chemistry. Subsequently, the number of IL moieties in the resultant TPILs was further increased by N-alkylation of the 1,2,3-triazole-based backbones of the TPILs with a quarternizing reagent. This strategy affords the preparation of TPILs having either one or two 1,2,3-triazolium cations with bis(trifluoromethylsulfonyl)imide anions in a monomer unit. Synthesis of the TPILs was confirmed by H-1 and C-13 NMR spectroscopy and gel permeation chromatography. The effects of the length of the ethylene oxide spacer and the number of IL moieties in the IL monomer unit on the physicochemical properties of the TPILs were characterized by differential scanning calorimetry, thermogravimetric analysis, and impedance spectroscopy. The introduction of a longer ethylene oxide spacer or an increase in the number of IL moieties in the monomer unit resulted in TPILs with lower glass-transition temperatures and higher ionic conductivities. The highest ionic conductivity achieved in this study was 2.0 x 10(-5) S cm(-1) at 30 degrees C. These results suggest that the design of the IL monomer provides the resultant polymer with high chain flexibility and a high IL density, and so it is effective for preparing TPILs with high ionic conductivities. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 5 42 2020 Preparation and Characterization of Additional Metallic Element-Containing Tubular Iron Oxides of Bacterial Origin 27287 27294 EN Katsunori Tamura Graduate School of Natural Science and Technology, Okayama University Tatsuki Kunoh Graduate School of Natural Science and Technology, Okayama University Makoto Nakanishi Graduate School of Natural Science and Technology, Okayama University Yoshihiro Kusano Department of Applied Chemistry and Biotechnology, Okayama University of Science Jun Takada Graduate School of Natural Science and Technology, Okayama University Biogenic microtubular iron oxides (BIOXs) derived from Leptothrix spp. are known as promising multifunctional materials for industrial applications such as ceramic pigments and catalyst carriers. Here, we report unprecedented BIOX products with additive depositions of various metallic elements prepared by a newly devised "two-step" method using an artificial culture system of Leptothrix cholodnii strain OUMS1; the method comprises a biotic formation of immature organic sheaths and subsequent abiotic deposition of Fe and intended elements on the sheaths. Chemical composition ratios of the additional elements Al, Zr, and Ti in the respective BIOXs were arbitrarily controllable depending on initial concentrations of metallic salts added to reaction solutions. Raman spectroscopy exemplified an existence of Fe-O-Al linkage in the Al-containing BIOX matrices. Time-course analyses revealed the underlying physiological mechanism for the BIOX formation. These results indicate that our advanced method can contribute greatly to creations of innovative bioderived materials with improved functionalities. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0743-7463 35 6 2019 Microfluidic Formation of Hydrogel Microcapsules with a Single Aqueous Core by 2358 2367 EN Takaichi Watanabe Division of Applied Chemistry, Graduate School of Natural Science, Okayama University Ibuki Motohiro Division of Applied Chemistry, Graduate School of Natural Science, Okayama University Tsutomu Ono Division of Applied Chemistry, Graduate School of Natural Science, Okayama University We report a simple process to fabricate monodisperse tetra-arm poly(ethylene glycol) (tetra-PEG) hydrogel microcapsules with an aqueous core and a semipermeable hydrogel shell through the formation of aqueous two-phase system (ATPS) droplets consisting of a dextran-rich core and a tetra-PEG macromonomer-rich shell, followed by a spontaneous cross-end coupling reaction of tetra-PEG macromonomers in the shell. Different from conventional techniques, this process enables for the continuous production of hydrogel microcapsules from water-in-oil emulsion droplets under mild conditions in the absence of radical initiators and external stimuli such as heating and ultraviolet light irradiation. We find that rapid cross-end coupling reaction of tetra-PEG macromonomers in ATPS droplets in the range of pH from 7.4 to 7.8 gives hydrogel microcapsules with a kinetically arrested core–shell structure. The diameter and core–shell ratio of the microcapsules can be easily controlled by adjusting flow rates and ATPS compositions. On the other hand, the slow cross-end coupling reaction of tetra-PEG macromonomers in ATPS droplets at pH 7.0 and lower induces structural change from core–shell to Janus during the reaction, which eventually forms hydrogel microparticles with a thermodynamically stable crescent structure. We believe that these hydrogel microparticles with controlled structures can be used in biomedical fields such as cell encapsulation, biosensors, and drug delivery carriers for sensitive biomolecules. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0743-7463 30 9 2014 Microfluidic Approach to the Formation of Internally Porous Polymer Particles by Solvent Extraction 2470 2479 EN Takaichi Watanabe Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Carlos G. Lopez Department of Chemical Engineering, Imperial College London Jack F. Douglas Materials Science and Engineering Division, National Institute of Standards and Technology Tsutomu Ono Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University João T. Cabral Department of Chemical Engineering, Imperial College London We report the controlled formation of internally porous polyelectrolyte particles with diameters ranging from tens to hundreds of micrometers through selective solvent extraction using microfluidics. Solvent-resistant microdevices, fabricated by frontal photopolymerization, encapsulate binary polymer (P)/solvent (S1) mixtures by a carrier solvent phase (C) to form plugs with well-defined radii and low polydispersity; the suspension is then brought into contact with a selective extraction solvent (S2) that is miscible with C and S1 but not P, leading to the extraction of S1 from the droplets. The ensuing phase inversion yields polymer capsules with a smooth surface but highly porous internal structure. Depending on the liquid extraction time scale, this stage can be carried out in situ, within the chip, or ex situ, in an external S2 bath. Bimodal polymer plugs are achieved using asymmetrically inverted T junctions. For this demonstration, we form sodium poly(styrenesulfonate) (P) particles using water (S1), hexadecane (C), and methyl ethyl ketone (S2). We measure droplet extraction rates as a function of drop size and polymer concentration and propose a simple scaling model to guide particle formation. We find that the extraction time required to form particles from liquid droplets does not depend on the initial polymer concentration but is rather proportional to the initial droplet size. The resulting particle size follows a linear relationship with the initial droplet size for all polymer concentrations, allowing for the precise control of particle size. The internal particle porous structure exhibits a polymer density gradient ranging from a dense surface skin toward an essentially hollow core. Average particle porosities between 10 and 50% are achieved by varying the initial droplet compositions up to 15 wt % polymer. Such particles have potential applications in functional, optical, and coating materials. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0743-7463 29 46 2013 Microfluidic Fabrication of Monodisperse Polylactide Microcapsules with Tunable Structures through Rapid Precipitation 14082 14088 EN Takaichi Watanabe Department of Chemistry and Biotechnology, Graduate School of Natural Science and Technolog Yukitaka Kimura Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Tsutomu Ono Department of Chemistry and Biotechnology, Graduate School of Natural Science and Technology We describe a versatile and facile route to the continuous production of monodisperse polylactide (PLA) microcapsules with controllable structures. With the combination of microfluidic emulsification, solvent diffusion, and internal phase separation, uniform PLA microcapsules with a perfluorooctyl bromide (PFOB) core were successfully obtained by simply diluting monodisperse ethyl acetate (EA)-in-water emulsion with pure water. Rapid extraction of EA from the droplets into the aqueous phase enabled the solidification of the polymer droplets in a nonequilibrium state during internal phase separation between a concentrated PLA/EA phase and a PFOB phase. Higher-molecular-weight PLA generated structural complexity of the microcapsules, yielding core–shell microcapsules with covered with small PFOB droplets. Removal of the PFOB via freeze drying gave hollow microcapsules with dimpled surfaces. The core–shell ratios and the diameter of these microcapsules could be finely tuned by just adjusting the concentration of PFOB and flow rates on emulsification, respectively. These biocompatible microcapsules with controllable size and structures are potentially applicable in biomedical fields such as drug delivery carriers of many functional molecules. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1948-7185 11 11 2020 Application of First-Principles-Based Artificial Neural Network Potentials to Multiscale-Shock Dynamics Simulations on Solid Materials 4536 4541 EN Masaaki Misawa Graduate School of Natural Science and Technology, Okayama University Shogo Fukushima Department of Physics, Kumamoto University Akihide Koura Department of Physics, Kumamoto University Kohei Shimamura Department of Physics, Kumamoto University Fuyuki Shimojo Department of Physics, Kumamoto University Subodh Tiwari Collaboratory for Advanced Computing and Simulations, University of Southern California Ken-ichi Nomura Collaboratory for Advanced Computing and Simulations, University of Southern California Rajiv K. Kalia Collaboratory for Advanced Computing and Simulations, University of Southern California Aiichiro Nakano Collaboratory for Advanced Computing and Simulations, University of Southern California Priya Vashishta Collaboratory for Advanced Computing and Simulations, University of Southern California The use of artificial neural network (ANN) potentials trained with first-principles calculations has emerged as a promising approach for molecular dynamics (MD) simulations encompassing large space and time scales while retaining first-principles accuracy. To date, however, the application of ANN-MD has been limited to near-equilibrium processes. Here we combine first-principles-trained ANN-MD with multiscale shock theory (MSST) to successfully describe far-from-equilibrium shock phenomena. Our ANN-MSST-MD approach describes shock-wave propagation in solids with first-principles accuracy but a 5000 times shorter computing time. Accordingly, ANN-MD-MSST was able to resolve fine, long-time elastic deformation at low shock speed, which was impossible with first-principles MD because of the high computational cost. This work thus lays a foundation of ANN-MD simulation to study a wide range of far-from-equilibrium processes. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 5 17 2020 Minimization of Amounts of Catalyst and Solvent in NHC-Catalyzed Benzoin Reactions of Solid Aldehydes: Mechanistic Consideration of Solid-to-Solid Conversion and Total Synthesis of Isodarparvinol B 10207 10216 EN Kenta Iwai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Masakazu Ono Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Yoshiko Nanjo Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Attempts were made to minimize the amounts of catalyst and solvent in the NHC-catalyzed benzoin reactions of solid aldehydes. In some case, solid-to-solid conversions proceeded in the solvent-free NHC-catalyzed benzoin reactions. Even if a mixture of the substrate, N-heterocyclic carbene (NHC) precursor, and inorganic base was initially a powdery solid, the reaction did proceed at reaction temperature lower than the melting points of each compound. The solid mixture partially melted or became a slurry or suspension in the meantime. We call this solid/liquid mixture a semisolid state. The reaction giving an optically active product was faster than that giving a racemic mixture of the same product. Melting-point depression was observed for a series of mixtures of the substrate and product in different substrate/product ratios. Solvent-free solid-to-solid conversions were accelerated by the formation of a semisolid state resulting from the melting-point depression of the solid substrate accompanied by the product formation. In the case of solid substrates with high melting points, melting-point depression was useless, and the addition of a small amount of solvent was needed. The first total synthesis of isodarparvinol B was achieved via the NHC-catalyzed intramolecular benzoin reaction using a small amount of solvent as an additive. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 22 6 2020 Palladium-Catalyzed Decarbonylative Alkylation of Acyl Fluorides 2350 2353 EN Liyan Fu Graduate School of Natural Science and Technology, Okayama University Qiang Chen Graduate School of Natural Science and Technology, Okayama University Zhenhua Wang Graduate School of Natural Science and Technology, Okayama University Yasushi Nishihara Research Institute for Interdisciplinary Science, Okayama University Palladium-catalyzed decarbonylative alkylation reactions of acyl fluorides have been developed using alkylboranes having ƒÀ-hydrogens. A wide range of functional groups were well tolerated, even at the high temperature required for decarbonylation. This protocol provides a diverse C(sp2)–C(sp3) bond formation via a highly efficient decarbonylative process. The hemilabile bidentate ligand DPPE plays a crucial role for retardation of the undesired ƒÀ-hydride elimination. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00062960 59 17 2020 Development and Characterization of Novel Molecular Probes for Ca2+/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609 1701 1710 EN Satomi Ohtsuka Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Yui Ozeki Graduate School of Education, Okayama University Moeno Fujiwara Faculty of Education, Okayama Universit Tomoyuki Miyagawa Graduate School of Education, Okayama University KanayamaNaoki Kanayama Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Masaki Magari Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama Universityayama University Naoya Hatano Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Futoshi Suizu Institute for Genetic Medicine, Hokkaido University Teruhiko Ishikawa Graduate School of Education, Okayama University Hiroshi Tokumitsu Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) activates particular multifunctional kinases, including CaMKI, CaMKIV, and 5ŒAMP-activated protein kinase (AMPK), resulting in the regulation of various Ca2+-dependent cellular processes, including neuronal, metabolic, and pathophysiological pathways. We developed and characterized a novel pan-CaMKK inhibitor, TIM-063 (2-hydroxy-3-nitro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) derived from STO-609 (7H-benzimidazo[2,1-a]benz[de]isoquinoline-7-one-3-carboxylic acid), and an inactive analogue (TIM-062) as molecular probes for the analysis of CaMKK-mediated cellular responses. Unlike STO-609, TIM-063 had an inhibitory activity against CaMKK isoforms (CaMKKƒ¿ and CaMKKƒÀ) with a similar potency (Ki = 0.35 ƒÊM for CaMKKƒ¿, and Ki = 0.2 ƒÊM for CaMKKƒÀ) in vitro. Two TIM-063 analogues lacking a nitro group (TIM-062) or a hydroxy group (TIM-064) completely impaired CaMKK inhibitory activities, indicating that both substituents are necessary for the CaMKK inhibitory activity of TIM-063. Enzymatic analysis revealed that TIM-063 is an ATP-competitive inhibitor that directly targets the catalytic domain of CaMKK, similar to STO-609. TIM-063 suppressed the ionomycin-induced phosphorylation of exogenously expressed CaMKI, CaMKIV, and endogenous AMPKƒ¿ in HeLa cells with an IC50 of ∼0.3 ƒÊM, and it suppressed CaMKK isoform-mediated CaMKIV phosphorylation in transfected COS-7 cells. Thus, TIM-063, but not the inactive analogue (TIM-062), displayed cell permeability and the ability to inhibit CaMKK activity in cells. Taken together, these results indicate that TIM-063 could be a useful tool for the precise analysis of CaMKK-mediated signaling pathways and may be a promising lead compound for the development of therapeutic agents for the treatment of CaMKK-related diseases. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00027863 141 25 2019 Deoxygenative Insertion of Carbonyl Carbon into a C(sp3)–H Bond: Synthesis of Indolines and Indoles 9832 9836 EN Sobi Asako Graduate School of Natural Science and Technology, Okayama University Seina Ishihara Graduate School of Natural Science and Technology, Okayama University Keiya Hirata Graduate School of Natural Science and Technology, Okayama University Kazuhiko Takai Graduate School of Natural Science and Technology, Okayama University A simple deoxygenation reagent prepared in situ from commercially available Mo(CO)6 and ortho-quinone has been developed for the synthesis of indoline and indole derivatives. The Mo/quinone complex efficiently deoxygenates carbonyl compounds bearing a neighboring dialkylamino group and effects intramolecular cyclizations with the insertion of a deoxygenated carbonyl carbon into a C(sp3)–H bond, in which a carbonyl group acts as a carbene equivalent. The reaction also proceeds with a catalytic amount of Mo/quinone in the presence of disilane as an oxygen atom acceptor. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 21 17 2019 Rhenium-Catalyzed Cyclization via 1,2-Iodine and 1,5-Hydrogen Migration for the Synthesis of 2-Iodo-1H-indenes 6756 6760 EN Masahito Murai Graduate School of Natural Science and Technology, Okayama University Kazuhiko Takai Graduate School of Natural Science and Technology, Okayama University A rhenium complex catalyzed the formation of 2-iodo-1H-indene derivatives through iodine and hydrogen migration of 3-iodopropargyl ethers. The reaction proceeded via generation of 1-iodoalkenylrhenium carbene species by sequential 1,2-iodine and 1,5-hydrogen shifts with readily available precursors under neutral conditions. The reaction mechanism and the reactivity of the generated alkenylcarbene species were also investigated. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 21 9 2019 Rhenium-Catalyzed Regioselective ortho-Alkenylation and [3 + 2 + 1] Cycloaddition of Phenols with Internal Alkynes 3441 3445 EN Masahito Murai Graduate School of Natural Science and Technology, Okayama University Masaki Yamamoto Graduate School of Natural Science and Technology, Okayama University Kazuhiko Takai Graduate School of Natural Science and Technology, Okayama University An operationally simple and direct rhenium-catalyzed ortho-alkenylation (C-alkenylation) of unprotected phenols with alkynes was developed. The protocol provided ortho-alkenylphenols exclusively, and formation of para- or multiply alkenylated phenols and hydrophenoxylation (O-alkenylation) products were not observed. The [3 + 2 + 1] cycloaddition of phenols and two alkynes via ortho-alkenylation was also demonstrated, in which the alkynes functioned as both two- and one-carbon units. These reactions proceeded with readily available starting materials under neutral conditions without additional ligands. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 21 8 2019 Chromium-Mediated Stannylcyclopropanation of Alkenes with (Diiodomethyl)stannanes 2668 2672 EN Masahito Murai Graduate School of Natural Science and Technology, Okayama University Ryuji Taniguchi Graduate School of Natural Science and Technology, Okayama University Chisato Mizuta Graduate School of Natural Science and Technology, Okayama University Kazuhiko Takai Graduate School of Natural Science and Technology, Okayama University A stannyl-group-substituted gem-dichromiomethane species, generated in situ from CrCl2, TMEDA, and tributyl(diiodomethyl)stannane, worked as an efficient stannylcarbene equivalent to promote cyclopropanation of alkenes. The reaction provided synthetically useful stannylcyclopropanes directly from commercially available unactivated alkenes without using potentially flammable alkylzinc and diazo compounds. Structural characterization of stannyl- and germyl-group-substituted gem-dichromiomethane complexes and the effect of group 14 elements containing substituents for cyclopropanation are also described. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00027863 140 45 2018 Use of Cyclopropane as C1 Synthetic Unit by Directed Retro- Cyclopropanation with Ethylene Release 15425 15429 EN Asako Sobi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takaaki Kobashi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuhiko Takai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Cyclopropanation of alkenes is a well-established textbook reaction for the synthesis of cyclopropanes, where a ghigh-energyh carbene species is exploited to drive the reaction forward. However, little attention has been focused toward molecular transformations involving the reverse reaction, retro-cyclopropanation (RC). This is because of difficulties associated with both cleaving the two geminal C–C single bonds and exploiting the generated carbenes for further transformations in an efficient and selective manner. Here, we report that a molybdenum-based catalytic system overcomes the above challenges and effects the RC of cyclopropanes bearing a pyridyl group with the release of ethylene (alkene) and the subsequent intramolecular cyclization leading to pyrido[2,1-a]isoindoles. The reaction allows for the uncommon use of cyclopropanes as C1 synthetic units in contrast to most conventional reactions in which cyclopropanes are used as C3 synthetic units. We anticipate that this new strategy will pave the way for C1 cyclopropane chemistry. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2155-5435 8 6 2018 Amine-Promoted anti-Markovnikov Addition of 1,3-Dicarbonyl Compounds with Terminal Alkynes under Rhenium Catalysis 5454 5459 EN Masahito Murai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Erika Uemura Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuhiko Takai Division of Applied Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Amines have been identified to greatly accelerate the intermolecular anti-Markovnikov addition of carbon nucleophiles to unactivated terminal alkynes. Using a combination of [ReBr(CO)3(thf)]2 and iPr2NEt, construction of cyclic all-carbon quaternary centers was achieved with various 1,3-ketoesters, diketones, and diesters with lower catalyst loading under milder conditions. The type of addition could be easily controlled by choice of additive, highlighting the unique features of rhenium catalysis No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0006-2960 59 3 2019 The Unlimited Potential of Microbial Rhodopsins as Optical Tools 218 229 EN Keiichi Kojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Atsushi Shibukawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Microbial rhodopsins, a photoactive membrane protein family, serve as fundamental tools for optogenetics, an innovative technology for controlling biological activities with light. Microbial rhodopsins are widely distributed in nature and have a wide variety of biological functions. Regardless of the many different known types of microbial rhodopsins, only a few of them have been used in optogenetics to control neural activity to understand neural networks. The efforts of our group have been aimed at identifying and characterizing novel rhodopsins from nature and also at engineering novel variant rhodopsins by rational design. On the basis of the molecular and functional characteristics of those novel rhodopsins, we have proposed new rhodopsin-based optogenetics tools to control not only neural activities but also "non-neural" activities. In this Perspective, we introduce the achievements and summarize future challenges in creating optogenetics tools using rhodopsins. The implementation of optogenetics deep inside an in vivo brain is the well-known challenge for existing rhodopsins. As a perspective to address this challenge, we introduce innovative optical illumination techniques using wavefront shaping that can reinforce the low light sensitivity of the rhodopsins and realize deep-brain optogenetics. The applications of our optogenetics tools could be extended to manipulate non-neural biological activities such as gene expression, apoptosis, energy production, and muscle contraction. We also discuss the potentially unlimited biotechnological applications of microbial rhodopsins in the future such as in photovoltaic devices and in drug delivery systems. We believe that advances in the field will greatly expand the potential uses of microbial rhodopsins as optical tools. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0022-3263 85 2 2019 Formal Total Synthesis of Manzacidin B via Sequential Diastereodivergent Henry Reaction 798 805 EN Yuya Araki Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Natsumi Miyoshi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuki Morimoto Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takayuki Kudoh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Haruki Mizoguchi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Akira Sakakura Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University A formal total synthesis of manzacidin B is described. beta,beta-Disubstituted gamma-hydroxy-beta-aminoalcohol, the key structure of manzacidin B, is stereoselectively constructed via sequential Henry reactions. By taking advantage of noncovalent interactions, such as intramolecular hydrogen bonding and chelation, we could diastereodivergently control the stereoselectivity of the Henry reaction. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0022-3263 84 23 2019 Copper-Catalyzed Regioselective Aminothiolation of Aromatic and Aliphatic Alkenes with N-Fluorobenzenesulfonimide and Thiols through Three-Component Radical Coupling 15373 15379 EN Masayuki Iwasaki Research Institute for Interdisciplinary Science, Okayama University Kosei Nonaka Graduate School of Natural Science and Technology, Okayama University Song Zou Yuta Sawanaka Graduate School of Natural Science and Technology, Okayama University Takaaki Shinozaki Graduate School of Natural Science and Technology, Okayama University Tomoya Fujii Graduate School of Natural Science and Technology, Okayama University Kiyohiko Nakajima Graduate School of Natural Science and Technology, Okayama University Yasushi Nishihara Research Institute for Interdisciplinary Science, Okayama University Copper-catalyzed regioselective aminothiolation of terminal and internal alkenes with N-fluorobenzenesulfonimide and thiols has been developed. The three-component reaction is promoted by the addition of dimethyl sulfide. In addition to aromatic alkenes, aliphatic alkenes are subjected to the reaction, affording various aminothiolation adducts as single regioisomers. The radical process is proposed by preliminary mechanistic studies, involving radical trap and radical clock experiments. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1523-7060 21 7 2019 Thioureas as Highly Active Catalysts for Biomimetic Bromocyclization of Geranyl Derivatives 2073 2076 EN Miyuki Terazaki Graduate School of Natural Science and Technology, Okayama University Kei-ichi Shiomoto Graduate School of Natural Science and Technology, Okayama University Haruki Mizoguchi Graduate School of Natural Science and Technology, Okayama University Akira Sakakura Graduate School of Natural Science and Technology, Okayama University Thioureas bearing electron-deficient aryl groups show high catalytic activity in the biomimetic bromocyclization of geranyl derivatives. The reaction of geranyl derivatives with N-bromosuccinimide (NBS) proceeds rapidly in CH2Cl2 to give the corresponding bromocyclization products in high yields as a ca. 1:1 mixture of endo- and exo-isomers. The reactivity of geranyl derivatives highly depends on the terminal substituent: electron-donating substituents increase the reactivity, while electron-withdrawing substituents decrease the reactivity. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15306984 19 9 2019 Asymmetric Phosphorus Incorporation in Homoepitaxial P-Doped (111) Diamond Revealed by Photoelectron Holography 5915 5919 EN T. Yokoya Research Institute for Interdisciplinary Science (RIIS), Okayama University K. Terashima Research Institute for Interdisciplinary Science (RIIS), Okayama University A. Takeda Graduate School of Science and Technology, Okayama University T. Fukura Graduate School of Science and Technology, Okayama University H. Fujiwara Graduate School of Science and Technology, Okayama University T. Muro Japan Synchrotron Radiation Research Institute (JASRI)/SPring-8 T. Kinoshita Japan Synchrotron Radiation Research Institute (JASRI)/SPring-8 H. Kato Energy Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) S. Yamasaki Energy Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) T. Oguchi Institute of Scientific and Industrial Research, Osaka University T. Wakita Research Institute for Interdisciplinary Science (RIIS), Okayama University Y. Muraoka Research Institute for Interdisciplinary Science (RIIS), Okayama University T. Matsushita Japan Synchrotron Radiation Research Institute (JASRI)/SPring-8 Diamond has two crystallographically inequivalent sites in the unit cell. In doped diamond, dopant occupation in the two sites is expected to be equal. Nevertheless, preferential dopant occupation during growth under nonequilibrium conditions is of fundamental importance, for example, to enhance the properties of nitrogen-vacancy (N-V) centers; therefore, this is a promising candidate for a qubit. However, the lack of suitable experimental techniques has made it difficult to study the crystal- and chemical-site-resolved local structures of dopants. Here, we confirm the identity of two chemical sites with asymmetric dopant incorporation in the diamond structure, via the photoelectron holography (PEH) of heavily phosphorus (P)-doped diamond prepared by chemical vapor deposition. One is substitutionally incorporated P with preferential site occupations and the other can be attributed to a PV split vacancy complex with preferential orientation. The present study shows that PEH is a valuable technique to study the local structures around dopants with a resolution of crystallographically inequivalent but energetically equivalent sites/orientations. Such information provides strategies to improve the properties of dopant related-complexes in which alignment is crucial for sensing of magnetic field or quantum spin register using N-V centers in diamond. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00222623 62 19 2019 Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening 8809 8818 EN Shoya Yamada Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Kawasaki Michiko Fujihara Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Watanabe Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Takamura Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Maho Takioku Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromi Nishioka Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Takeuchi Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Makishima Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine Tomoharu Motoyama Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Sohei Ito Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Hiroaki Tokiwa Department of Chemistry and Research Center of Smart Molecules, Rikkyo University Shogo Nakano Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Hiroki Kakuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2H-chromene-3-carboxylic acid (10, CU-6PMN) as a new fluorescent RXR agonist and developed a screening system of rexinoids using 10. Compound 10 was designed based on the fact that umbelliferone emits strong fluorescence in a hydrophilic environment, but the fluorescence intensity decreases in hydrophobic environments such as the interior of proteins. The developed assay using 10 enabled screening of rexinoids to be performed easily within a few hours by monitoring changes of fluorescence intensity with widely available fluorescence microplate readers, without the need for processes such as filtration. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 20 22 2018 Synthesis and Properties of Dithieno-Fused 1,4-Azaborine Derivatives. 7336 7340 EN Koichi Mitsudo Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Keisuke Shigemori Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroki Mandai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Atsushi Wakamiya Institute for Chemical Research, Kyoto University Seiji Suga Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University The first synthesis of dithieno[3,2- b:2',3'- e][1,4]azaborinine (DTAB) derivatives has been achieved by Buchwald-Hartwig coupling and subsequent Friedel-Crafts-type C-H borylation. A facile method for further ƒÎ-extension of DTAB was also developed via stannylation and subsequent Kosugi-Migita-Stille cross-coupling reaction. The fundamental properties of DTAB derivatives were also investigated. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 19 11 2017 Synthesis of 3-Benzo[b]thienyl 3-Thienyl Ether via an Addition-Elimination Reaction and Its Transformation to an Oxygen-Fused Dithiophene Skeleton: Synthesis and Properties of Benzodithienofuran and Its ƒÎ-Extended Derivatives 2821 2824 EN Koichi Mitsudo Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Yuji Kurimoto Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroki Mandai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University The synthesis of 3-benzo[b]thienyl 3-thienyl ether and its dehydrogenative cyclization leading to benzodithienofuran (BDTF; [1]benzothieno[3,2-b]thieno[2,3-d]furan) are described for the first time. Further transformation of BDTF to more ƒÎ-extended BDTF derivatives and their fundamental physical properties are also studied. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 21 7 2019 Iodide-Mediated or Iodide-Catalyzed Demethylation and Friedel-Crafts C-H Borylative Cyclization Leading to Thiophene-Fused 1,2-Oxaborine Derivatives 2171 2175 EN Keisuke Shigemori Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Momoka Watanabe Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Julie Kong Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Koichi Mitsudo Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Atsushi Wakamiya Institute for Chemical Research, Kyoto University Hiroki Mandai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University The first synthesis of dithieno-1,2-oxaborine derivatives was achieved via iodide-mediated or iodide-catalyzed demethylation of 3-methoxy-2,2'-bithiophene and subsequent C-H borylation. A wide variety of thiophene-fused oxaborines could be synthesized by the procedure. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15306984 19 5 2019 Is F-1-ATPase a Rotary Motor with Nearly 100% Efficiency? Quantitative Analysis of Chemomechanical Coupling and Mechanical Slip 3370 3378 EN Tomonari Sumi Research Institute for Interdisciplinary Science, Department of Chemistry, Faculty of Science, Okayama University Stefan Klumpp Department Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces We present a chemomechanical network model of the rotary molecular motor F1-ATPase which quantitatively describes not only the rotary motor dynamics driven by ATP hydrolysis but also the ATP synthesis caused by forced reverse rotations. We observe a high reversibility of F1-ATPase, that is, the main cycle of ATP synthesis corresponds to the reversal of the main cycle in the hydrolysis-driven motor rotation. However, our quantitative analysis indicates that torque-induced mechanical slip without chemomechanical coupling occurs under high external torque and reduces the maximal efficiency of the free energy transduction to 40–80% below the optimal efficiency. Heat irreversibly dissipates not only through the viscous friction of the probe but also directly from the motor due to torque-induced mechanical slip. Such irreversible heat dissipation is a crucial limitation for achieving a 100% free-energy transduction efficiency with biological nanomachines because biomolecules are easily deformed by external torque. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00062960 58 26 2019 Photochemical Characterization of a New Heliorhodopsin from the Gram-Negative Eubacterium Bellilinea caldifistulae (BcHeR) and Comparison with Heliorhodopsin-48C12 2934 2943 EN Atsushi Shibukawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University Keiichi Kojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University Yu Nakajima Atmosphere and Ocean Research Institute , The University of Tokyo Yosuke Nishimura Atmosphere and Ocean Research Institute , The University of Tokyo Susumu Yoshizawa Atmosphere and Ocean Research Institute , The University of Tokyo Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University Many microorganisms express rhodopsins, pigmented membrane proteins capable of absorbing sunlight and harnessing that energy for important biological functions such as ATP synthesis and phototaxis. Microbial rhodopsins that have been discovered to date are categorized as type-1 rhodopsins. Interestingly, researchers have very recently unveiled a new microbial rhodopsin family named the heliorhodopsins, which are phylogenetically distant from type-1 rhodopsins. Among them, only heliorhodopsin-48C12 (HeR-48C12) from a Gram-positive eubacterium has been photochemically characterized [Pushkarev, A., et al. (2018) Nature 558, 595-599]. In this study, we photochemically characterize a purple-colored heliorhodopsin from Gram-negative eubacterium Bellilinea caldifistulae (BcHeR) as a second example and identify which properties are or are not conserved between BcHeR and HeR-48C12. A series of photochemical measurements revealed several conserved properties between them, including a visible absorption spectrum with a maximum at around 550 nm, the lack of ion-transport activity, and the existence of a second-order O-like intermediate during the photocycle that may activate an unidentified biological function. In contrast, as a property that is not conserved, although HeR-48C12 shows the light adaptation state of retinal, BcHeR showed the same retinal configuration under both dark- and light-adapted conditions. These comparisons of photochemical properties between BcHeR and HeR-48C12 are an important first step toward understanding the nature and functional role of heliorhodopsins. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 24701343 4 12 2019 Characterization of Pieces of Paper That Form Reagent Containers for Use as Portable Analytical Devices 15249 15254 EN Supatana Buking Flow Innovation-Research for Science and Technology Laboratories (FIRST Labs) and Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University Yusuke Suedomi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Duangjai Nacapricha Flow Innovation-Research for Science and Technology Laboratories (FIRST Labs) and Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University Takashi Kaneta Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Reagent-deposited pieces of paper were characterized by the use of a compact conductometer, a compact pH sensor, and a conventional spectrophotometer to assess their suitability for use as reagent containers. The pieces of paper were fabricated by wax printing to form a limited hydrophilic area to which a consistent volume of an aqueous reagent could be added. The pieces of paper without the reagent increased the conductivity of water gradually because of the release of sodium salts, whereas pH of NaOH decreased because of the acidity of the functional groups in the paper. Three reagents, sulfamic acid as an acid, Na2CO3 as a base, and BaCl2 as a metal salt, were deposited on the pieces of paper to evaluate their ability to release from the pieces of paper. Sulfamic acid and Na2CO3 were released in quantities of 58 and 73% into water after 420 s, whereas 100% of BaCl2 was released after 480 s. The conductometric titrations of NaOH, HCl, and Na2SO4, and the spectrophotometry of Fe2+ were examined using the pieces of paper that contained sulfamic acid, Na2CO3, BaCl2, and 1,10-phenanthroline. Titrations using the pieces of paper suggested that the reagents were quantitatively released into the titrant, which resulted in a linear relationship between the endpoints and the equivalent points. In 120 s of soaking time, 60-70% of the reagents were released. The spectrophotometric measurements of Fe2+ indicated that when an excess amount of the reagents was deposited onto the pieces of paper, they nonetheless sufficiently fulfilled the role of a reagent container. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0022-3263 83 18 2018 Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation of Sarcophytonolides 11028 11056 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Takahiro Kikuchi Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Kohei Iwamoto Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Eiji Nakao Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Naoki Harada Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Taichi Otsu Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Noriyuki Endo Himeji EcoTech Co., Ltd. Yuji Fukuda Himeji EcoTech Co., Ltd. Osamu Ohno Department of Chemistry and Life Science, School of Advanced Engineering , Kogakuin University Kiyotake Suenaga Department of Chemistry, Faculty of Science and Technology , Keio University Yue-Wei Guo Shanghai Institute of Materia Medica , Chinese Academy of Sciences Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Sarcophytonolides are cembranolide diterpenes isolated from the soft corals of genus Sarcophyton. Unified total synthesis of sarcophytonolides C, E, F, G, H, and J and isosarcophytonolide D was achieved. The synthetic routes feature NaHMDS- or SmI2-mediated fragment coupling, alkoxycarbonylallylation, macrolactonization, and transannular ring-closing metathesis. These total syntheses led to the absolute configurational confirmation of sarcophytonolide H, elucidation of sarcophytonolides C, E, F, and G, and revision of sarcophytonolide J and isosarcophytonolide D. We also evaluated the antifouling activity and toxicity of the synthetic sarcophytonolides H and J and their analogues as well as the cytotoxicity of the synthetic sarcophytonolides and the key synthetic intermediates. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00223263 80 6 2015 Stereodivergent synthesis and relative stereostructure of the C1-C13 fragment of symbiodinolide 3111 3123 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroko Wada Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Mao Ogino Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takahiro Kikuchi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Daisuke Uemura Department of Chemistry, Faculty of Science, Kanagawa University Four possible diastereomers of the C1-C13 fragment of symbiodinolide, which were proposed by the stereostructural analysis of the degraded product, were synthesized in a stereodivergent and stereoselective manner. The key transformations were aldol reaction of methyl acetoacetate with the aldehyde, diastereoselective reduction of the resulting ƒÀ-hydroxy ketone, and the stereoinversion at the C6 position. Comparison of the (1)H NMR data between the four synthetic products and the degraded product revealed the relative stereostructure of the C1-C13 fragment of symbiodinolide. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 18 9 2016 Total Synthesis of Sarcophytonolide H and Isosarcophytonolide D: Structural Revision of Isosarcophytonolide D and Structure-Antifouling Activity Relationship of Sarcophytonolide H 2110 2113 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takahiro Kikuchi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Noriyuki Endo Himeji EcoTech Co., Ltd. Yuji Fukuda Himeji EcoTech Co., Ltd. Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University The first total syntheses of sarcophytonolide H and the originally proposed and correct structures of isosarcophytonolide D have been achieved via transannular ring-closing metathesis (RCM). These total syntheses culminated in the stereostructural confirmation of sarcophytonolide H and the reassignment of isosarcophytonolide D, respectively. The antifouling activity of the synthetic sarcophytonolide H and its analogues was also evaluated. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1523-7060 18 17 2016 Synthesis and Properties of Sila[n]helicenes via Dehydrogenative Silylation of C-H Bonds under Rhodium Catalysis 4380 4383 EN Masahito Murai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Ryo Okada Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Atsushi Nishiyama Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuhiko Takai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Use of a rhodium catalyst with (R)-(S)-BPPFA ligand allows efficient synthesis of sila[n]helicenes via dehydrogenative silylation of C-H bonds. By selecting the proper ligands, the current method provides the ability to prepare unsymmetrical sila[n]helicene derivatives without any oxidants. The resulting sila[6]helicene is a rare example of a five-membered ring-fused [6]helicene, which was isolated as a single pure enantiomer without substituents on the terminal benzene rings. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1523-7060 18 7 2016 Palladium-Catalyzed Regio- and Stereoselective Carbothiolation of Terminal Alkynes with Azolyl Sulfides 1642 1645 EN Masayuki Iwasaki Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Nikola Topolovčan Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Hao Hu Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Yugo Nishimura Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Glwadys Gagnot Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Rungsaeng Na nakorn Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Ramida Yuvacharaskul Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Kiyohiko Nakajima Department of Chemistry, Aichi University of Education Yasushi Nishihara Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Palladium-catalyzed carbothiolation of terminal alkynes with azolyl sulfides affords various 2-(azolyl)alkenyl sulfides with perfect regio- and stereoselectivities. The present addition reaction proceeded through a direct cleavage of carbon-sulfur bonds in azolyl sulfides. The resulting adducts that are useful intermediates in organic synthesis are further transformed to multisubstituted olefins containing azolyl moieties. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1523-7060 18 9 2016 Lewis Acid and Fluoroalcohol Mediated Nucleophilic Addition to the C2 Position of Indoles 2020 2023 EN Naoki Morimoto Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Div Pharmaceut Sci Kumika Morioku Okayama Univ, Fac Engn, Dept Appl Chem & Biotechnol Hideyuki Suzuki Okayama Univ, Res Core Interdisciplinary Sci Yasuo Takeuchi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Div Pharmaceut Sci Yuta Nishina Okayama Univ, Res Core Interdisciplinary Sci Indole readily undergoes nucleophilic substitution at the C3 site, and many indole derivatives have been functionalized using this property. Indole also forms indolium, which allows electrophilic addition in acidic conditions, but current examples have been limited to intramolecular reactions. C2 site-selective nucleophilic addition to indole derivatives using fluoroalcohol and a Lewis acid was developed. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1523-7060 19 5 2017 Synthesis of Benzoisoselenazolone Derivatives by Nickel-Catalyzed Dehydrogenative Direct Selenation of C(sp2)-H Bonds with Elemental Selenium in Air 1092 1095 EN Masayuki Iwasaki Research Institute for Interdisciplinary Science, Okayama University Natsumi Miki Graduate School of Natural Science and Technology, Okayama University Yuta Tsuchiya Graduate School of Natural Science and Technology, Okayama University Kiyohiko Nakajima Department of Chemistry, Aichi University of Education Yasushi Nishihara Research Institute for Interdisciplinary Science, Okayama University Nickel-catalyzed direct selenation of benzamides bearing an 8-quinolyl auxiliary with elemental selenium provides benzoisoselenazolones in good yield via carbon-selenium and nitrogen-selenium bond formation under aerobic conditions. In addition to aryl C-H bonds, the method can also be applied to alkenyl C-H bonds, constructing an isoselenazolone skeleton. Simple mechanistic analysis shows that the reaction proceeds through a rate-determining C-H bond cleavage. The obtained benzoisoselenazolones are transformed into various organoselenium compounds and utilized as the catalyst for bromolactonization of alkenoic acids. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15205002 29 5 2017 Real-Time, in Situ Monitoring of the Oxidation of Graphite: Lessons Learned 2150 2156 EN Naoki Morimoto Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Division of Pharmaceutical Sciences, Okayama University Hideyuki Suzuki Research Core for Interdisciplinary Sciences, Okayama University Yasuo Takeuchi Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Division of Pharmaceutical Sciences, Okayama Universit Shogo Kawaguchi Japan Synchrotron Radiation Research Institute (JASRI), SPring-8 Masahiro Kunisu Toray Research Center, Inc., Surface Science Laboratories Christopher W. Bielawski Center for Multidimensional Carbon Materials (CMCM), Institute for Basic Science (IBS) Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Graphite oxide (GO) and its constituent layers (i.e., graphene oxide) display a broad range of functional groups and, as such, have attracted significant attention for use in numerous applications. GO is commonly prepared using the gHummers methodh or a variant thereof in which graphite is treated with KMnO4 and various additives in H2SO4. Despite its omnipresence, the underlying chemistry of such oxidation reactions is not well understood and typically affords results that are irreproducible and, in some cases, unsafe. To overcome these limitations, the oxidation of graphite under Hummers-type conditions was monitored over time using in situ X-ray diffraction and in situ X-ray absorption near edge structure analyses with synchrotron radiation. In conjunction with other atomic absorption spectroscopy, UV–vis spectroscopy and elemental analysis measurements, the underlying mechanism of the oxidation reaction was elucidated, and the reaction conditions were optimized. Ultimately, the methodology for reproducibly preparing GO on large scales using only graphite, H2SO4, and KMnO4 was developed and successfully adapted for use in continuous flow systems. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00027863 139 12 2017 Demonstration of a Light-Driven SO42- Transporter and Its Spectroscopic Characteristics. 4376 4389 EN Akiko Niho Faculty of Pharmaceutical Sciences, Okayama University Susumu Yoshizawa Atmosphere and Ocean Research Institute, The University of Tokyo Takashi Tsukamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Marie Kurihara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinya Tahara Molecular Spectroscopy Laboratory, RIKEN Yu Nakajima Atmosphere and Ocean Research Institute, The University of Tokyo Misao Mizuno Department of Chemistry, Graduate School of Science, Osaka University Hikaru Kuramochi Ultrafast Spectroscopy Research Team, RIKEN Center for Advanced Photonics Tahei Tahara Ultrafast Spectroscopy Research Team, RIKEN Center for Advanced Photonics Yasuhisa Mizutani Department of Chemistry, Graduate School of Science, Osaka University Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In organisms, ion transporters play essential roles in the generation and dissipation of ion gradients across cell membranes. Microbial rhodopsins selectively transport cognate ions using solar energy, in which the substrate ions identified to date have been confined to monovalent ions such as H+, Na+, and Cl-. Here we report a novel rhodopsin from the cyanobacterium Synechocystis sp. PCC 7509, which inwardly transports a polyatomic divalent sulfate ion, SO42-, with changes of its spectroscopic properties in both unphotolyzed and photolyzed states. Upon illumination, cells expressing the novel rhodopsin, named Synechocystis halorhodopsin (SyHR), showed alkalization of the medium only in the presence of Cl- or SO42-. That alkalization signal was enhanced by addition of a protonophore, indicating an inward transport of Cl- and SO42- with a subsequent secondary inward H+ movement across the membrane. The anion binding to SyHR was suggested by absorption spectral shifts from 542 to 536 nm for Cl- and from 542 to 556 nm for SO42-, and the affinities of Cl- and SO42- were estimated as 0.112 and 5.81 mM, respectively. We then performed time-resolved spectroscopic measurements ranging from femtosecond to millisecond time domains to elucidate the structure and structural changes of SyHR during the photoreaction. Based on the results, we propose a photocycle model for SyHR in the absence or presence of substrate ions with the timing of their uptake and release. Thus, we demonstrate SyHR as the first light-driven polyatomic divalent anion (SO42-) transporter and report its spectroscopic characteristics. No potential conflict of interest relevant to this article was reported.