Design of Chemical Environment available for Life Science based on Hydrated Ionic Liquids and Polymerized Ionic Liquids

• Project/Area Number: 17H01225
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Polymer/Textile materials
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Ohno Hiroyuki 東京農工大学, 工学(系)研究科(研究院), 学長 (00176968)
• Co-Investigator(Kenkyū-buntansha): 藤田 恭子 東京薬科大学, 薬学部, 講師 (90447508)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥43,940,000 (Direct Cost: ¥33,800,000、Indirect Cost: ¥10,140,000); Fiscal Year 2019: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000); Fiscal Year 2018: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000); Fiscal Year 2017: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
• Keywords: イオン液体 / 水和状態 / 生体内環境 / タンパク質 / 相転移 / 高分子 / 生体環境 / 相変化

Outline of Final Research Achievements

Reconstruction of aggregated proteins has been succeeded in ionic liquids containing a small amount of water. Ionic liquids which show lower critical solution temperature (LCST)-type phase transition after mixing with water were then examined to apply the separation process of biomolecules. Cytochrome c was found to distribute both water and ionic liquid phase depending on solely the oxidation state which was controlled by the given potential. LCST type gels were then prepared by polymerizing the LCST type ionic liquid monomers. Protein adsorption and desorption were found to be controlled in the gels with slight temperature change. This is a great advantage of the use of such functional ionic liquids in the life science.

Academic Significance and Societal Importance of the Research Achievements

これまで我々は多くのイオン液体を合成し、それらの物理的性質を整理し、エネルギーデバイスをはじめとした様々な分野に応用してきた。その過程で、生体分子との親和性の高い水和イオン液体を見出した。生体分子は水又は緩衝水溶液中でしか存在できないと思われていたが、高塩濃度液体である水和イオン液体中でも一部のタンパク質は失活せず、さらには再構成まで行えることがわかった。水和イオン液体のタンパク質科学への応用の可能性を大きく拡げることができた。また、LCST型の相転移を示すイオン液体を用いることで、タンパク質を分離抽出する新技術を提案でき、生命科学分野への多大な貢献が期待できた。

Research Products

• [Int'l Joint Research] University of Aveiro(ポルトガル)
• [Journal Article] Hydration states of cholinium phosphate-type ionic liquids as the function of water contents (2019)
  • Author(s): Y. Nikawa, S. Tsuzuki, H. Ohno, and K. Fujita
  • Journal Title: Aust. J. Chem. Volume: 72 Issue: 5 Pages: 392-399
  • DOI: 10.1071/ch18381
  • Peer Reviewed
• [Journal Article] Effects of Charge Balance and Hydrophobicity of the Surface of Cytochrome c on the Distribution Behaviour in an Ionic Liquid/Buffer Biphasic System (2019)
  • Author(s): K. Ikeda, K. Fujita, H. Ohno, and N. Nakamura
  • Journal Title: Org. Biomol. Chem. Volume: 17 Issue: 31 Pages: 7337-7341
  • DOI: 10.1039/c9ob00900k
  • Peer Reviewed
• [Journal Article] Novel bis(fluorosulfonyl)imide-based and ether-functionalized ionic liquids for lithium batteries with improved cycling properties (2019)
  • Author(s): A. Tsurumaki, H. Ohno, S. Panero, and M. A. Navarra
  • Journal Title: Electrochimica Acta Volume: 293 Pages: 160-165
  • DOI: 10.1016/j.electacta.2018.09.205
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Hydrated ionic liquids enable both solubilisation and refolding of aggregated concanavaline A (2019)
  • Author(s): K. Fujita, R. Nakano, R. Nakaba, N. Nakamura, and H. Ohno
  • Journal Title: Chemical Communications Volume: 55 Issue: 25 Pages: 3578-3581
  • DOI: 10.1039/c8cc10102g
  • Peer Reviewed / Open Access
• [Journal Article] Dissolution of oligo(tetrafluoroethylene) and preparation of poly(tetrafluoroethylene)-based composites by using fluorinated ionic liquids (2018)
  • Author(s): A. Tsurumaki and H. Ohno
  • Journal Title: Chemical Communications Volume: 54 Issue: 4 Pages: 409-412
  • DOI: 10.1039/c7cc08449h
  • Peer Reviewed
• [Journal Article] Hydrated Ionic Liquids: Potential Solvent for Biomolecules (2018)
  • Author(s): 藤田恭子
  • Journal Title: MEMBRANE Volume: 43 Issue: 3 Pages: 101
  • DOI: 10.5360/membrane.43.101
  • NAID: 130007378567
  • ISSN: 0385-1036, 1884-6440
  • Peer Reviewed
• [Journal Article] An integrated process for enzymatic catalysis allowing product recovery and enzyme reuse by applying thermoreversible aqueous biphasic systems (2018)
  • Author(s): A. M. Ferreira, H. Passos, A. Okafuji, A. P. M. Tavares, H. Ohno, M. G. Freire, and J. A. P. Coutinho
  • Journal Title: Green Chemistry Volume: 165 Issue: 6 Pages: 1218-1223
  • DOI: 10.1039/c7gc03880a
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Design and properties of functional zwitterions derived from ionic liquids (2018)
  • Author(s): Hiroyuki Ohno, Masahiro Yoshizawa-Fujita, Yuki Kohno
  • Journal Title: Physical Chemistry Chemical Physics Volume: 20 Issue: 16 Pages: 10978-10991
  • DOI: 10.1039/c7cp08592c
  • Peer Reviewed / Open Access
• [Journal Article] Distribution of cytochrome c in LCST-type ionic liquid/water mixtures controlled by applied potential and temperature (2018)
  • Author(s): K. Ikeda, N. Nakamura, H. Ohno, R. Ikari, and K. Fujita
  • Journal Title: J. Electrochemical Society Volume: 165 Issue: 7 Pages: G96-G100
  • DOI: 10.1149/2.1071807jes
  • Peer Reviewed
• [Journal Article] 458.Designing the thermal behaviour of aqueous biphasic systems composed of ammonium-based zwitterions (2018)
  • Author(s): A. M. Ferreira, H. Passos, A. Okafuji, M. G. Freire, J. A. P. Coutinho, and H. Ohno
  • Journal Title: Green Chemistry Volume: 19 Issue: 17 Pages: 4012-4016
  • DOI: 10.1039/c7gc02262j
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Design of thermoresponsive poly(ionic liquid) gels containing proline units to catalyse aldol reaction in water (2018)
  • Author(s): Akiyoshi Okafuji, Yuki Kohno, Nobuhumi Nakamura, Hiroyuki Ohno
  • Journal Title: Polymer Volume: 134 Pages: 20-23
  • DOI: 10.1016/j.polymer.2017.11.047
  • Peer Reviewed
• [Presentation] 生体分子と親和性を示す水和イオン液体 (2020)
  • Author(s): 藤田恭子
  • Organizer: 鶴田フォーラム
  • Invited
• [Presentation] 水和イオン液体によるリコンピナントセルラーゼ凝集体の溶解・リフォールディング (2020)
  • Author(s): 柳澤 峻、市田公美、中村暢文、大野弘幸、藤田恭子
  • Organizer: 日本化学会第100春季年会
• [Presentation] Renaturation of inactivated concanavalin A (ConA) by treatment with hydrated ionic liquid (2020)
  • Author(s): R. Fujii, K. Ichida, K. Fujita
  • Organizer: 日本化学会第100春季年会
• [Presentation] Functionalization of ionic liquids (2019)
  • Author(s): H. Ohno
  • Organizer: GSFMT Summer School
  • Int'l Joint Research / Invited
• [Presentation] Thermoresponsive ionic liquid/water mixtures for separation and purification technologies (2019)
  • Author(s): H. Ohno
  • Organizer: 4th International Conference on Ionic Liquids in Separation and Purification Technology (ILSEPT)
  • Int'l Joint Research / Invited
• [Presentation] Controlling Factors of Distribution Behaviour of Cytochrome c in Ionic Liquid/ Buffer Biphasic System (2019)
  • Author(s): K. Fujita, K. Ikeda, K. Ichida, H. Ohno, N. Nakamura
  • Organizer: 4th International Conference on Ionic Liquids in Separation and Purification Technology (ILSEPT)
  • Int'l Joint Research
• [Presentation] イオン液体の発見・発展・未来 (2019)
  • Author(s): 大野弘幸
  • Organizer: 第9回CSJ化学フェスタ
  • Invited
• [Presentation] Hydrated Ionic Liquids for Solubilisation and Refolding of Aggregated Proteins (2019)
  • Author(s): K. Fujita
  • Organizer: 2019-Sustainable Industrial Processing Summit and Exhibition
  • Int'l Joint Research / Invited
• [Presentation] イオン液体/緩衝液二相系におけるリフォールディング後 concanavalin A の分配挙動 (2019)
  • Author(s): 中野 呂香、 大野 弘幸、中村 暢文、市田 公美、藤田 恭子
  • Organizer: 第10回イオン液体討論会
• [Presentation] Solubilization and refolding of thermally aggregated concanavalin A in hydrated ionic liquids (2019)
  • Author(s): R. Nakano, H. Ohno, N. Nakamura, K. Ichida and K. Fujita
  • Organizer: 第29回日本MRS年次大会
• [Presentation] Hydrated Ionic Liquid for the Re-naturation of Aggregated Proteins (2019)
  • Author(s): K. Fujita
  • Organizer: 13th Annual International Electromaterials Science Symposium
  • Int'l Joint Research / Invited
• [Presentation] Hydrated Ionic Liquids: Potential Use in Bioscience (2018)
  • Author(s): K. Fujita
  • Organizer: 2018 Sophia Symposium on Ionic Liquids
  • Int'l Joint Research / Invited
• [Presentation] Design of functional ionic liquids and their derivatives for electrochemical devices (2018)
  • Author(s): H. Ohno
  • Organizer: 6th International Conference on Ionic Liquids for Electrochemical Devices (ILED-6)
  • Int'l Joint Research / Invited
• [Presentation] Distribution of cytochrome c in LCST-type ionic liquid/ water mixtures controlled by applied potential and temperature (2018)
  • Author(s): K. Fujita, K. Ikeda, R. Ikari, N. Nakamura and H. Ohno
  • Organizer: 6th International Conference on Ionic Liquids for Electrochemical Devices (ILED-6)
  • Int'l Joint Research
• [Presentation] Mixture of DNA and ionic liquids as ion conductive films (2018)
  • Author(s): N. Nishimura and H. Ohno
  • Organizer: 6th International Conference on Ionic Liquids for Electrochemical Devices (ILED-6)
  • Int'l Joint Research
• [Presentation] Design and properties of thermo-responsive polymers derived from ionic liquids having moderate hydrophobicity (2018)
  • Author(s): H. Ohno
  • Organizer: 27th conference on molten salts and ionic liquids-EuCheMSIL201
  • Int'l Joint Research
• [Presentation] 温度応答性を示すイオン液体由来ハイドロゲルのタンパク質吸脱着能の評価 (2018)
  • Author(s): 濱健一朗、大野弘幸、中村暢文
  • Organizer: 第9回イオン液体討論会
• [Presentation] What can be done with keywords of “polymer” and “ionic liquid”? (2018)
  • Author(s): H. Ohno
  • Organizer: 6th Asian-Pacific Cenference on Ionic Liquids and Green Processes (APCIL-6)
  • Int'l Joint Research / Invited
• [Presentation] Effect of anion on solubility and refolding behavior of aggregated concanavalin A in hydrated ionic liquids (2018)
  • Author(s): R. Nakano, H. Ohno, N. Nakamura, and K. Fujita
  • Organizer: 6th Asian-Pacific Cenference on Ionic Liquids and Green Processes (APCIL-6)
  • Int'l Joint Research
• [Presentation] 熱凝集したコンカナバリンAを溶解、リフォールディングする水和イオン液体の探索 (2018)
  • Author(s): 中野呂香、半 リサ、大野弘幸、中村暢文、藤田恭子
  • Organizer: 日本化学会第98春季年会
• [Presentation] Electron Transfer Reaction of Proteins in Hydrated Ionic Liquids (2017)
  • Author(s): Kyoko FUJITA
  • Organizer: 21st International Conference on Solid State Ionics
  • Int'l Joint Research / Invited
• [Presentation] タンパク質吸着に向けた温度応答性イオン液体由来ゲルの設計 (2017)
  • Author(s): 濱健一郎、岡藤亮佳、大野弘幸、中村暢文
  • Organizer: 第66回高分子討論会
• [Presentation] Redox Reaction of Proteins in Hydrated Cholinium Dihydrogen Phosphate (2017)
  • Author(s): Kyoko FUJITA
  • Organizer: 232nd ECS Meeting
  • Int'l Joint Research / Invited
• [Presentation] 配位子を導入した温度応答性イオン液体由来高分子電解質ゲルの金属イオン吸着能 (2017)
  • Author(s): 大隈崇裕、岡藤亮佳、大野弘幸、中村暢文
  • Organizer: 第8回イオン液体討論会
• [Presentation] リン酸二水素アニオンを有するイオン液体由来ゲルのリン酸緩衝液中でのタンパク質吸着能評価 (2017)
  • Author(s): 濱健一郎、岡藤亮佳、大野弘幸、中村暢文
  • Organizer: 第8回イオン液体討論会
• [Presentation] 凝集タンパク質を溶解できる水和イオン液体の探索：構成イオンと含水量の効果 (2017)
  • Author(s): 中野呂香、半リサ、藤田恭子、大野弘幸、中村暢文
  • Organizer: 第8回イオン液体討論会
• [Book] Advances in Biochemical Engineering/Biotechnology (Synthesis of ionic liquids originated from natural products) (2018)
  • Author(s): H. Ohno
  • Publisher: Springer
• [Book] Advances in Biochemical Engineering/Biotechnology (Ionic Liquids as Stabilization and Refolding Additives and Solvents for Proteins) (2018)
  • Author(s): K. Fujita
  • Publisher: Springer
• [Patent(Industrial Property Rights)] 凝集タンパク質の再生剤およびこれを用いた凝集タンパク質の再生方法 (2017)
  • Inventor(s): 藤田 恭子、大野 弘幸
  • Industrial Property Rights Holder: 東京薬科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-225090
  • Filing Date: 2017