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2018 Fiscal Year Research-status Report

Creation of Suparmolecular Catalyts by Design of Functionalized Molecular Blocks and Reaction Field

Research Project

Project/Area Number 17K08225
Research InstitutionTokyo University of Science

Principal Investigator

青木 伸  東京理科大学, 薬学部生命創薬科学科, 教授 (00222472)

Project Period (FY) 2017-04-01 – 2020-03-31
Keywords超分子 / 加水分解 / 亜鉛錯体 / 銅イオン / リン酸エステル
Outline of Annual Research Achievements

近年の超分子化学の発展により、様々な機能性集積体が生み出されてきた。しかし、有機化学反応、特にアミドやリン酸エステルの加水分解など基本的反応の触媒は未開拓である。その主な理由は、i)酵素のように、反応中心において一定の間隔で酸と塩基を配置する設計が困難である事、iI)反応の遷移状態の安定化が困難である事、iii)従来の触媒例では金属イオンの第一配位圏の再現だけにとどまっていて、酵素の活性中心周囲(外圏)のアミノ酸などを、三次元的かつ適切に配置できていない事、iv) 上記の条件を満たす構造を、共有結合だけで構築するのは困難である事、などである。本研究の目的は、これらの課題を克服するために、様々な官能基をもつ分子ブロックを短時間で多数合成し、溶液中で様々な分子やイオンと混合するだけで多様な三次元的活性中心を構築することである。同時に、反応場(単層系、液―液二相系など)を含めた触媒システムの設計を行っている。
これまでに、二本の長鎖アルキル基を導入した二核亜鉛錯体(Zn2L3)を合成し、Bar誘導体とCu2+との自己集積体を生成して、二層系溶媒中におけるリン酸モノエステル(MNP)の加水分解を検討した。しかしながら、この超分子は殆ど触媒回転活性を示さなかった。この原因は、この超分子の疎水性が強く、ほぼ有機相(CHCl3, ClCH2CH2Cl)に存在し、界面における存在比が低いためであると考えた。そこで、長鎖アルキル基の数を一つにすることによって、非対称化された超分子を合成し、二層系溶媒中でのNMP加水分解を行った。そしてMichaelis-Menten速度論に基づいて解析した。超分子が二層系溶媒中で、水中、有機溶媒中、界面のどこに局在しているのかを、UV/Vis吸収および発光スペクトル、DLSなどで検討し、超分子の疎水性/親水性のバランスが触媒回転に重要であることが示唆された。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

本年度に合成した二核亜鉛錯体とバルビタール誘導体、銅イオンの2:2:2自己集積体が、長鎖アルキル基の数を一つにすることによって、水層/有機層の二相系溶媒中でNMPを触媒的に加水分解する超分子を発見した。バルビタール誘導体に疎水性基やアミノ酸誘導体を導入することにも成功し、MNP加水分解をMichaelis-Menten速度論に基づいて解析した。超分子超分子の疎水性/親水性のバランスが触媒回転に重要であることが示唆された。このことは、酵素の触媒回転のメカニズムの理解にも重要であると考えている。

Strategy for Future Research Activity

上記「研究実績の概要」項で述べた、新しい2:2:2自己集積体の触媒活性をさらに向上する。バルビタールの側鎖に水酸基、カルボキシル基、アミノ基、グアニジウム基をもつアミノ酸を導入し、二核亜鉛錯体とバルビタール誘導体(+銅イオン)の組み合わせのバリエーションを飛躍的に増やすことによって、二核亜鉛錯体との様々な組み合わせによる自己集積体のMNPおよびエステルやアミドの加水分解活性を検討する。またエステル、アミドの加水分解反応やリン酸基転位反応への応用を検討する。

Causes of Carryover

購入を予定していた消耗品のうち、購入する必要がなくなったものがあるため。

  • Research Products

    (41 results)

All 2019 2018 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (31 results) (of which Invited: 7 results) Remarks (1 results)

  • [Journal Article] Simple and Convenient Method for the Isolation, Culture, and Re-collection of Cancer Cells from Blood by Using Glass-Bead Filters2019

    • Author(s)
      B. Shashni, H. Matsuura, R. Saito, T. Hirata, S. Ariyasu, K. Nomura, H. Takemura, K. Akimoto, N.Aikawa, A. Yasumori and S. Aoki,
    • Journal Title

      ACS Biomater. Sci. Eng

      Volume: 5 Pages: 438-452

    • DOI

      10.1021/acsbiomaterials.8b01335

    • Peer Reviewed
  • [Journal Article] Stereoselective Aldol Reactions of Dihydroxyacetone Derivatives Catalyzed by Chiral Zn2+ Complexes2019

    • Author(s)
      M. Yasuda, Y. Saga, T. Tokunaga, S. Itoh, and S. Aoki
    • Journal Title

      Tetrahedron

      Volume: 75 Pages: 5603-5616

    • DOI

      org/10.1016/j.tet.2018.12.060

    • Peer Reviewed
  • [Journal Article] Highly Active Copper(I) Complexes of Aroylthiourea Ligands Against Cancer Cells; Synthetic and Biological Studies2019

    • Author(s)
      Kumaramangalam Jeyalakshmi, Jebiti Haribabu, Chandrasekar Balachandran, Eswaramoorthi Narmatha, Nattamai S. P. Bhuvanesh, Shin Aoki, and Ramasamy Karvembu
    • Journal Title

      New Journal of Chemistry

      Volume: none Pages: 3188-3198

    • DOI

      org/10.1039/C8NJ04246B

    • Peer Reviewed
  • [Journal Article] Size-based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer Assisted by a Cell-recognition PC Software2018

    • Author(s)
      Babita Shashni, Shinya Ariyasu, Reisa Takeda, Toshihiro Suzuki, Shota Shiina, Kazunori Akimoto, Takuto Maeda, Naoyuki Aikawa, Ryo Abe, Tomorhiro Osaki, Norihiko Itoh, and Shin Aoki
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Pages: 487-503

    • DOI

      org/10.1248/bpb.b17-00776

    • Peer Reviewed / Open Access
  • [Journal Article] Stereospecific Synthesis of Tris-Heteroleptic Tris-Cyclometalated Iridium(III) Complexes via Different Heteroleptic Halogen-Bridged Iridium Dimers and Their Photophysical Properties2018

    • Author(s)
      Yuichi Tamura, Yosuke Hisamatsu, Ayami Kazama, Kenji Yoza, Kyouhei Sato, Reiko Kuroda and Shin Aoki,
    • Journal Title

      Inorganic Chemistry

      Volume: 57 Pages: 4571-4589

    • DOI

      10.1021/acs.inorgchem.8b00323

    • Peer Reviewed
  • [Journal Article] Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides2018

    • Author(s)
      Hidehisa Someya, Taiki Itoh, Mebae Kato, and Shin Aoki
    • Journal Title

      Journal of Visualized Experiments (JoVE)

      Volume: none Pages: e57897

    • DOI

      10.3791/57897

    • Peer Reviewed
  • [Journal Article] Luminescent Iridium Complex-Peptide Hybrids (IPHs) for Therapeutics of Cancer: Design and Synthesis of IPHs for Detection of Cancer Cells and Induction of Their Necrosis-type Cell Death2018

    • Author(s)
      Abdullah-Al Masum, Yosuke Hisamatsu, Kenta Yokoi, and Shin Aoki
    • Journal Title

      Bioinorganic Chemistry and Applications

      Volume: 2018 Pages: ID 7578965

    • DOI

      org/10.1155/2018/7578965

    • Peer Reviewed / Open Access
  • [Journal Article] Design and Synthesis of a Luminescent Iridium Complex-Peptide (IPH) that Detects Cancer Cells and Induces Their Apoptosis2018

    • Author(s)
      Abdullah-Al Masum, Kenta Yokoi, Yosuke Hisamatsu, Kana Naito, Babita Shashni, and Shin Aoki,
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 26 Pages: 4804-4816

    • DOI

      org/10.1016/j.bmc.2018.08.016

    • Peer Reviewed
  • [Journal Article] Design and Synthesis of Boron Containing Monosaccharides by the Hydroboration of D-Glucal for Use in Boron Neutron Capture Therapy (BNCT)2018

    • Author(s)
      Taiki Itoh, Kei Tamura, Hiroki Ueda, Tomohiro Tanaka, Kyouhei Satoh, Reiko Kuroda, and Shin Aoki
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 26 Pages: 5922-5933

    • DOI

      org/10.1016/j.bmc.2018.10.041

    • Peer Reviewed
  • [Presentation] Development of New Boron Compounds for Biomedical Sciences by Means of Traditional rRactions of Sugar Derivatives2019

    • Author(s)
      Shin Aoki, Taiki Itoh, Hidehisa Someya, Hiroki Ueda, Kosuke Mizuno
    • Organizer
      2019 International Biomedical Interface Symposium (2019IBMI)
    • Invited
  • [Presentation] Design and Synthesis of Cyclometalated Iridium(III) Complexes Based on Post-Complexation Functionalization for Photochemistry and Chemical Biology2019

    • Author(s)
      Shin Aoki
    • Organizer
      Invited Seminar at National Tsing Hua University
    • Invited
  • [Presentation] ell Death Induction of Cancer Cells by Cyclometalated Iridium(III) Complex-Peptide Hybrids and Mechanism2019

    • Author(s)
      青木 伸、横井 健汰、内藤 佳奈、Chandrasekar Balachandran
    • Organizer
      日本化学会第99春季年会
  • [Presentation] Mechanistic Study of Cell Death of Cancer Cells Induced by Cyclometalated Iridium(III)-Peptide Hybrids (IPHs)2019

    • Author(s)
      Chandrasekar Balachandran, Kenta Yokoi, Kana Naito, Shin Aoki
    • Organizer
      日本薬学会第139年会
  • [Presentation] アミノ酸で修飾したバルビタール誘導体・二核亜鉛錯体・銅イオンの自己集積型超分子の設計、合成とphosphatase活性2019

    • Author(s)
      宮澤 有哉、Akib Bin Rahman、今福 浩輝、嵯峨 裕、青木 伸
    • Organizer
      日本薬学会第139年会
  • [Presentation] 新規二核亜鉛錯体、イミド誘導体、銅から成る自己集積的多核銅錯体の構築と反応活性2018

    • Author(s)
      嵯峨 裕、宮澤 有哉、青木 伸
    • Organizer
      第16回ホストゲスト・超分子化学シンポジウム
  • [Presentation] Catalytic Hydrolysis of Phosphate Monoester by Supramolecular Phosphatase Formed from Monoalkylated Dizinc(II) Complex, Diimide Units & Copper(II) in Two-Phase Solvent System2018

    • Author(s)
      Akib Bin Rahman, Hiroki Imafuku, Yuya Miyazawa, Yutaka Saga, Shin Aoki
    • Organizer
      第16回ホストゲスト・超分子化学シンポジウム
  • [Presentation] がん細胞死誘導活性を有するシクロメタレート型Ir(III)錯体;ペプチドハイブリッドの設計とメカニズム解析2018

    • Author(s)
      内藤 佳奈、久松 洋介、横井 健汰、吉原利忠、飛田成史、青木 伸
    • Organizer
      日本ケミカルバイオロジー学会第12回年会
  • [Presentation] シクロメタレート型イリジウム(III)錯体-塩基性ペプチドハイブリッドのがん細胞死誘導活性に対するペプチドの影響2018

    • Author(s)
      青木 伸、横井 健汰、内藤 佳奈、Abdullah-Al Masum、久松 洋介
    • Organizer
      第28回金属の関与する生体関連反応シンポジウム
  • [Presentation] Selective Synthesis of Tris-cyclometalated Tris-Heteroleptic Iridium(III) Complexes Based on Zn2+-Promoted Degradation Reaction of Ir Complexes and Their Photophysical Properties2018

    • Author(s)
      Shin Aoki, Yuichi Tamura, Ayami Kazama, Kennichi Yoza, Kyohei Sato, Reiko Kuroda, Yosuke Hisamatsu
    • Organizer
      錯体化学会第68回討論会
  • [Presentation] Asymmetric Aldol Reactions of Acetone and Benzaldehydes Catalyzed by Chiral Zn2+ Complexes: Computational Study of Relationship between Structures and Reactivity of the Complexes2018

    • Author(s)
      Shotaro Sonoike, Shin Aoki, Chiharu Kikuchi, Miho Hatanaka, Yuichi Kitagawa, Yasuchika Hasegawa
    • Organizer
      錯体化学会第68回討論会
  • [Presentation] シクロメタレート型イリジウム錯体(Ⅲ)と発光団ハイブリッド錯体の設計・合成と発光特性2018

    • Author(s)
      風間 彩水、湯浅 順平、青木 伸
    • Organizer
      錯体化学会第68回討論会
  • [Presentation] Design & Synthesis of Cyclometalated Iridium Complexes for Biomedical and Material Sciences2018

    • Author(s)
      Shin Aoki, Yosuke Hisamatsu, Yuichi Tamura, Kenta Yokoi, Kana Naito, Abdullah-Al Masum
    • Organizer
      43rd International Conference on Coordination Chemistry (ICCC2018)
    • Invited
  • [Presentation] Design & Synthesis of Boron-Containing Sugar Derivatives for Boron Neutron Capture Therapy2018

    • Author(s)
      Taiki Itoh, Hiroki Ueda, Kei Tamura, Kosuke Mizuno, Yasuhiro Sawamoto, Tomohiro Tanaka, Shin Aoki
    • Organizer
      43rd International Conference on Coordination Chemistry (ICCC2018)
  • [Presentation] Design and Synthesis of Supramolecular Phosphatases Mimicking an Active Center of Alkaline Phosphatase2018

    • Author(s)
      Yuya Miyazawa, Akib Bin Rahman, Hiroki Imafuku, Shin Aoki
    • Organizer
      43rd International Conference on Coordination Chemistry (ICCC2018)
  • [Presentation] Design & Synthesis of Cyclometalated Iridium Complexes Controlling Apoptosis and Necroptosis2018

    • Author(s)
      Kenta Yokoi, Kana Naito, Abdullah-Al Masum, Shin Aoki
    • Organizer
      43rd International Conference on Coordination Chemistry (ICCC2018)
  • [Presentation] Recent Development of Zinc Chemistry; Zinc Supramolecular Chemistry and Zn-promoted Reactions-2018

    • Author(s)
      Shin Aoki
    • Organizer
      6th International Postgraduate Conference on Pharmaceutical Sciences 2018 (iPoPS2018)
    • Invited
  • [Presentation] O-Glycosylation Utilizing Boronic Ester for Synthesis of Disaccharide Nucleosides and Oligosaccharides2018

    • Author(s)
      Hidetoshi Someya, Taiki Itoh, Mebae Katoh, Ryota Naoi, Shin Aoki
    • Organizer
      6th International Postgraduate Conference on Pharmaceutical Sciences 2018 (iPoPS2018)
  • [Presentation] Catalytic Hydrolysis of Phosphate Monoester by Supramolecular Phosphatase Fomred by Complexation of Monoalkylated Dizinc(II) Complex, Dimide Units & Copper(II)2018

    • Author(s)
      Akib Bin Rahman, Hiroki Imafuku, Yuya Miyazawa, Yutaka Saga, Shin Aoki
    • Organizer
      6th International Postgraduate Conference on Pharmaceutical Sciences 2018 (iPoPS2018)
  • [Presentation] Design and Synthesis of Chemical Linkers to Modify Magnetic Beads for Capture and Isolation of Target Cells2018

    • Author(s)
      Makito Kayano, Makito Kayano, Hiroto Kuchiishi, Kazue Matsumoto, Babita Shashni, Reisa Takeda, Yuto Mukai, Ryo Abe, Hideki Sakai, Tomohiro Tanaka, Satoshi Katayose, Nobuko Onoda, Shin Aoki
    • Organizer
      6th International Postgraduate Conference on Pharmaceutical Sciences 2018 (iPoPS2018)
  • [Presentation] Design, Synthesis and Biological Evaluation of Boron Carriers based on Glucosamine Scaffolds for Boron Neutron Capture Therapy2018

    • Author(s)
      Hiroki Ueda, Hiroki Ueda, Taiki Itoh, Kosuke Mizuno, Tomohiro Tanaka, Shin Aoki
    • Organizer
      6th International Postgraduate Conference on Pharmaceutical Sciences 2018 (iPoPS2018)
  • [Presentation] Design and Synthesis of Molecular Shuttles Driven by Phosphate-Zn(Ⅱ) Coordination2018

    • Author(s)
      Yoshiyuki Sekine, Yutaka Saga, Shin Aoki
    • Organizer
      6th International Postgraduate Conference on Pharmaceutical Sciences 2018 (iPoPS2018)
  • [Presentation] Design and Synthesis of Cyclometalated Iridium(III)-Peptide Hybrids Inducing Different Types of Cell Death of Cancer Cells2018

    • Author(s)
      Kenta Yokoi, Kana Naito, Masum, Abdullah-Al, Shin Aoki
    • Organizer
      6th International Postgraduate Conference on Pharmaceutical Sciences 2018 (iPoPS2018)
  • [Presentation] アミノ酸で修飾したバルビタール誘導体・二核亜鉛錯体・銅イオンの自己集積型超分子の設計、合成とphosphatase活性2018

    • Author(s)
      宮澤 有哉、Akib Bin Rahman、今福 浩輝、嵯峨 裕、青木 伸
    • Organizer
      第62回日本薬学会関東支部大会
  • [Presentation] Supramolecular Complexes of a Monoalkylated Bis(Zinc(II)-Cyclen) Complex, Diimide Units & Copper(II) as Catalysts for Hydrolysis of Phosphate Monoester2018

    • Author(s)
      Akib Bin Rahman, Hiroki Imaffuku, Yuya Miyazawa, Shin Aoki
    • Organizer
      第62回日本薬学会関東支部大会
  • [Presentation] Development of Boron-containing Monosaccharide Derivatives for Boron Neutron Capture Therapy.2018

    • Author(s)
      Taiki Itoh, Hiroki Ueda, Kei Tamura, Kosuke Mizuno, Balachandran Chandrasekar, Shin Aoki
    • Organizer
      The 18th International Congress on Neutron Capture Therapy (ICNCT-18)
  • [Presentation] Development of Supramolecular Complexes by Combinatorial Assembly of Functionalized Zinc(II) Complexes, Building Blocks and Metals.2018

    • Author(s)
      Shin Aoki, Akib Bin Rahman, Hiroki Imafuku, Yuya Miyazawa, Yuka Kobayashi, Yutaka Saga
    • Organizer
      International Congress on Pure & Applied Chemistry Langkawi (ICPAC Langkawi 2018)
    • Invited
  • [Presentation] ボロン酸エステルをヌクレオシド水酸基の一時的保護として利用した位置選択的O-グリコシル化反応による二糖ヌクレオシドの合成2018

    • Author(s)
      染谷英寿、伊藤太基、加藤萌、青木伸
    • Organizer
      第44回反応と合成の進歩シンポジウム
  • [Presentation] 47.糖骨格をもつBNCTホウ素キャリアーの設計、合成とがん細胞への移行性2018

    • Author(s)
      青木伸、伊藤太基、上田大貴、水野皓輔、鈴木実、櫻井良憲
    • Organizer
      東京理科大学・日本医科大学第5回合同シンポジウム
  • [Presentation] Photophysical and Biological Activity of Cyclometalated Iridium(III) Complex-Peptide Conjugates Synthesized by Post-Complexation Functionalization2018

    • Author(s)
      Shin Aoki, Kenta Yokoi, Kana Naito, Abdullah-Al Masum, Ayami Kazama, Yuki Imai, Junpei Yuasa
    • Organizer
      9th Asian Biological Inoganic Chemistry Conference (AsBIC9)
    • Invited
  • [Presentation] Development of New Methods for Cancer Theranostics in Interdisciplinary Collaboration of Tokyo University of Science2018

    • Author(s)
      Shin Aoki, Babita Shashni, Kazunori Akimoto, Masanori Hayase, Hiroshi Takemura, Atsuo Yasumori, Naoyki Aikawa, Masato Kubo, and Masahiro Motosuke
    • Organizer
      International Symposium of Tokyo University of Science, Translational Research (TR) Center -Frontiers in Developmental Strategy for Cancer Therapeutics-
    • Invited
  • [Remarks] 青木研究室ホームページ

    • URL

      https://www.rs.noda.tus.ac.jp/aokilab/

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Published: 2019-12-27  

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