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2022 Fiscal Year Annual Research Report

Electron and NMR nano-crystallography for pharmaceutical formulation

Research Project

Project/Area Number 20K05483
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

西山 裕介  国立研究開発法人理化学研究所, 科技ハブ産連本部, ユニットリーダー (20373342)

Project Period (FY) 2020-04-01 – 2023-03-31
Keywords3D ED / microED / 固体NMR / NMR crystallography / 微結晶 / 結晶多形 / API / 製剤
Outline of Annual Research Achievements

本研究課題は、製剤中の低分子医薬品(API: active pharmaceutical ingredient)の結晶構造を一切の前提条件なしに解くことを目的とする。全体の結晶構造は3D電子回折法(3D ED, microED)により行う。一方で3D ED法には、水素原子の位置の精密測定や炭素・窒素・酸素原子の明瞭なアサインを行うにあたって問題があった。申請者らの先行研究により固体NMRがこれらの問題を解くうえで非常に有用であることが2019年に示されていた。本課題においては、初年度(2020年度)に製剤そのままで分離することなくAPIの固体NMR測定を行う技術を確立した。さらに次年度(2021年度)には、水素位置の精密測定を目指し1H-14Nの距離測定技術の開発、また3D EDで得られた構造を1H-14N距離を用いて精密化する技術を確立した。これにより、当初目的としていた技術開発の基盤部分は達成することができた。最終年度(2022年度)には、技術のさらなる高度化を目指し長距離の1H-14N相関測定法の確立を行った。さらにキニーネの結晶構造解析など実用的な応用を積極的に進めた。今後の手法の進展を目指し、本課題で開発した測定手法をアモルファス試料の構造解析に用いた。実用材料の解析を目指し、IISER KolkataのProf. Rahul Banerjeeと強力な共同研究を推進し、共有結合によるナノチューブ、ナノシートの構造解析やその反応機構の解明に貢献した。

  • Research Products

    (17 results)

All 2023 2022 Other

All Int'l Joint Research (5 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Int'l Joint Research] TIFR/IISER Kolkata/IIT Ropar(インド)

    • Country Name
      INDIA
    • Counterpart Institution
      TIFR/IISER Kolkata/IIT Ropar
    • # of Other Institutions
      2
  • [Int'l Joint Research] AMES lab/University of Michigan/Merck(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      AMES lab/University of Michigan/Merck
  • [Int'l Joint Research] University of Lille(フランス)

    • Country Name
      FRANCE
    • Counterpart Institution
      University of Lille
  • [Int'l Joint Research] South China University of Technology(中国)

    • Country Name
      CHINA
    • Counterpart Institution
      South China University of Technology
  • [Int'l Joint Research] University of Warwick(英国)

    • Country Name
      UNITED KINGDOM
    • Counterpart Institution
      University of Warwick
  • [Journal Article] Structural and Morphological Transformations of Covalent Organic Nanotubes2023

    • Author(s)
      Koner Kalipada、Karak Suvendu、Ogaeri Yutaro、Nishiyama Yusuke、Banerjee Rahul
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 62 Pages: -

    • DOI

      10.1002/anie.202300652

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ultrafast Magic Angle Spinning Solid-State NMR Spectroscopy: Advances in Methodology and Applications2022

    • Author(s)
      Nishiyama Yusuke、Hou Guangjin、Agarwal Vipin、Su Yongchao、Ramamoorthy Ayyalusamy
    • Journal Title

      Chemical Reviews

      Volume: 123 Pages: 918~988

    • DOI

      10.1021/acs.chemrev.2c00197

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] NMR Crystallographic Approach to Study the Variation of the Dynamics of Quinine and Its Quasienantiomer Quinidine2022

    • Author(s)
      Lodhi Lekhan、Yadav Jai Prakash、Yamazaki Toshio、Duong Nghia Tuan、Poojary Srinivasa L.、Dey Krishna Kishor、Nishiyama Yusuke、Ghosh Manasi
    • Journal Title

      The Journal of Physical Chemistry C

      Volume: 126 Pages: 17291~17305

    • DOI

      10.1021/acs.jpcc.2c04470

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Making Polyisoprene Self‐Healable through Microstructure Regulation by Rare‐Earth Catalysts2022

    • Author(s)
      Wang Haobing、Yang Yang、Nishiura Masayoshi、Hong You‐lee、Nishiyama Yusuke、Higaki Yuji、Hou Zhaomin
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 61 Pages: -

    • DOI

      10.1002/anie.202210023

    • Peer Reviewed
  • [Journal Article] Combining heteronuclear correlation NMR with spin-diffusion to detect relayed Cl?H?H and N?H?H proximities in molecular solids2022

    • Author(s)
      Raval Parth、Tr?bosc Julien、Pawlak Tomasz、Nishiyama Yusuke、Brown Steven P.、Manjunatha Reddy G.N.
    • Journal Title

      Solid State Nuclear Magnetic Resonance

      Volume: 120 Pages: 101808~101808

    • DOI

      10.1016/j.ssnmr.2022.101808

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Practical guides for 1H detected solid-state NMR under fast MAS for small molecules2022

    • Author(s)
      Nishiyama Yusuke、Duong Nghia Tuan
    • Journal Title

      Journal of Magnetic Resonance Open

      Volume: 10-11 Pages: 100062~100062

    • DOI

      10.1016/j.jmro.2022.100062

    • Peer Reviewed
  • [Journal Article] 3次元電子回折とNMR結晶学2022

    • Author(s)
      西山 裕介
    • Journal Title

      応用物理

      Volume: 91 Pages: 82~85

    • DOI

      10.11470/oubutsu.91.2_82

    • Peer Reviewed
  • [Presentation] Internuclear distance measurements between 1H and 14N in rigid solids2023

    • Author(s)
      Yusuke Nishiyama
    • Organizer
      3rd India-Japan NMR meeting
    • Int'l Joint Research / Invited
  • [Presentation] 14N NMRにおける磁場依存性: 高磁場の方が有利か?2022

    • Author(s)
      魚返祐太朗,西山裕介
    • Organizer
      NMR討論会
  • [Presentation] Correlation and distance measurements between 1H and 14N using 14N overtone NMR spectroscopy2022

    • Author(s)
      Yusuke Nishiyama
    • Organizer
      NMR討論会
  • [Presentation] Correlation and distance measurements between 1H and 14N using 14N overtone NMR spectroscopy2022

    • Author(s)
      Nghia Tuan Duong, Zhehong Gan, Yusuke Nishiyama
    • Organizer
      Alpine Conference on Magnetic Resonance in Solids
    • Int'l Joint Research
  • [Presentation] Correlation and distance measurements between 1H and 14N using 14N overtone NMR spectroscopy2022

    • Author(s)
      Yusuke Nishiyama
    • Organizer
      Rocky Mountain Conference on Chemistry
    • Int'l Joint Research

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Published: 2023-12-25  

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