Development of Rapid and Sensitive Fluorescent Probes for Hydrogen Peroxide Bio-imaging

• Project/Area Number: 24550197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemistry related to living body
• Research Institution: Doshisha University
• Principal Investigator: HITOMI Yutaka 同志社大学, 理工学部, 教授 (20335186)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: イメージング / 蛍光 / 過酸化水素 / 検出 / 細胞 / 錯体 / シグナル / 鉄錯体 / 蛍光プローブ

Outline of Final Research Achievements

A series of fluorescent probes for hydrogen peroxide have been developed that have a mononuclear nonheme iron complex as a reaction site toward hydrogen peroxide. They are all non-fluorescent, but once reacting with low concentrations of hydrogen peroxide inside cells, they release green- or red-emitting fluorescent dyes such as resorufin and fluorescein. We have succeeded in real-time imaging of hydrogen peroxide that was produced as a messenger inside A431 cells upon stimulation of epidermal growth factors.

Research Products

• [Journal Article] Facile preparation of stable aqueous titania sols for fabrication of highly active TiO2 photocatalyst films (2015)
  • Author(s): S. Okunaka, *H. Tokudome, Y. Hitomi, *R. Abe
  • Journal Title: J. Mater. Chem. A Volume: 3 Issue: 4 Pages: 1688-1695
  • DOI: 10.1039/c4ta04680c
  • Peer Reviewed
• [Journal Article] Synthesis, Stability and Reactivity of the First Mononuclear Nonheme Oxoiron(IV) Species with Monoamido Ligation: A Putative Reactive Species Generated from Iron-Bleomycin (2014)
  • Author(s): *Y. Hitomi, K. Arakawa, M. Kodera
  • Journal Title: Chem. Commun. Volume: 50 Issue: 56 Pages: 7485-7487
  • DOI: 10.1039/c4cc01409j
  • Peer Reviewed
• [Journal Article] Gold Nanoparticles Coated with Manganese-Porphyrin that Effectively Shorten the Longitudinal Relaxation Time of Water Molecules Depending on the Particle Size (2014)
  • Author(s): *Y. Hitomi, K. Aoki, R. Miyachi, J. Ohyama, M. Kodera, T. Tanaka, F. Sugihara
  • Journal Title: Chem. Lett. Volume: 43 Issue: 12 Pages: 1901-1903
  • DOI: 10.1246/cl.140812
  • NAID: 130004687290
  • Peer Reviewed
• [Journal Article] Development of Green-Emitting Iron Complex-Based Fluorescent Probes for Intracellular Hydrogen Peroxide Imaging (2014)
  • Author(s): Yutaka Hitomi, Toshiyuki Takeyasu, Masahito Kodera
  • Journal Title: Bulletin of the Chemical Society of Japan Volume: (印刷中) Issue: 7 Pages: 819-824
  • DOI: 10.1246/bcsj.20140055
  • NAID: 130004059123
  • Peer Reviewed
• [Journal Article] Water Proton Relaxivity, Superoxide Dismutase-like Activity, and Cytotoxicity of a Manganese(III) Porphyrin Having Four Poly(ethylene glycol) Tails (2014)
  • Author(s): *Y. Hitomi, T. Ekawa, M. Kodera
  • Journal Title: Chem. Lett. Volume: 43 Issue: 5 Pages: 732-734
  • DOI: 10.1246/cl.140029
  • NAID: 130004868139
  • Peer Reviewed
• [Journal Article] Electronic Tuning of Nitric Oxide Release from Manganese Nitrosyl Complexes by Visible Light Irradiation: Enhancement of Nitric Oxide Release Efficiency by Nitro-Substituted Quinoline Ligand (2014)
  • Author(s): *Y. Hitomi, Y. Iwamoto, M. Kodera
  • Journal Title: Dalton Trans. Volume: 43 Issue: 5 Pages: 2161-2167
  • DOI: 10.1039/c3dt51719e
  • Peer Reviewed
• [Journal Article] Roles of Carboxylate Donors in O-O Bond Scission of Peroxodiiron(III) to High-Spin Oxodiiron(IV) with a New Carboxylate-Containing Dinucleating Ligand (2014)
  • Author(s): M. Kodera, T. Tsuji, T. Yasunaga, Y. Kawahara, T. Hirano, Y. Hitomi, T. Nomura, T. Ogura, Y. Kobayashi, Sajith P. K., Y. Shiota, and K. Yoshizawa
  • Journal Title: Chem. Sci. Volume: 5 Issue: 6 Pages: 2282-2292
  • DOI: 10.1039/c3sc51541a
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nucleophilic Ring-opening of meso-Substituted 5-Oxaporphyrin by Oxygen, Nitrogen, Sulfur, and Carbon Nucleophiles (2014)
  • Author(s): K. Kakeya, M. Aozasa, *T. Mizutani, Y. Hitomi, M. Kodera
  • Journal Title: J. Org. Chem. Volume: 79 Issue: 6 Pages: 2591-2600
  • DOI: 10.1021/jo5000412
  • Peer Reviewed
• [Journal Article] 細胞内の過酸化水素を可視化するプローブ分子の開発 (2014)
  • Author(s): 武安俊幸、人見 穣、小寺政人
  • Journal Title: 同志社大学理工学研究報告 Volume: 55 Pages: 1-9
  • NAID: 110009799484
• [Presentation] Selective Oxidation by Mononuclear Oxoiron Complexes with Monoamido Ligation (2014)
  • Author(s): Y. Hitomi
  • Organizer: 錯体化学会第64回討論会(2014)シンポジウム
  • Place of Presentation: 東京都文京区
  • Year and Date: 2014-09-18 – 2014-09-20
  • Invited
• [Presentation] Metal Complex-Based Fluorescent Probes for Imaging Hydrogen Peroxide (2014)
  • Author(s): Y. Hitomi
  • Organizer: 41st International Conference on Coordination Chemistry (ICCC)
  • Place of Presentation: Singapore
  • Year and Date: 2014-07-21 – 2014-07-25
  • Invited
• [Presentation] Alkane Hydroxylation by Oxoiron Species Supported by Pentadentate N5 Ligands with Monoamido Coordination (2014)
  • Author(s): Y. Hitomi
  • Organizer: International Conference on Hydrogen Atom Transfer (iCHAT 2014)
  • Place of Presentation: Italy
  • Year and Date: 2014-06-22 – 2014-06-26
  • Invited
• [Presentation] Development of Metal Complexes Working in Cells: Fluorescent Probes for Intracellular Hydrogen Peroxide (2013)
  • Author(s): 人見 穣
  • Organizer: 錯体化学会第63回討論会
  • Place of Presentation: 琉球大学千原キャンパス
  • Invited
• [Presentation] 細胞内の過酸化水素の可視化を目指した金属錯体型蛍光プローブの開発 (2013)
  • Author(s): 武安 俊幸・人見 穣・小寺 政人
  • Organizer: 第7回バイオ関連化学シンポジウム
  • Place of Presentation: 名古屋大学東山キャンパス
• [Presentation] 金属錯体型蛍光プローブを利用した生体内活性酸素種の検出 (2013)
  • Author(s): 武安 俊幸，人見 穣，小寺 政人
  • Organizer: 第66回日本酸化ストレス学会
  • Place of Presentation: ウインク愛知
• [Presentation] 金属錯体型H2O2蛍光プローブの開発(1) (2013)
  • Author(s): 武安俊幸・人見 穣・小寺政人
  • Organizer: 日本化学会第93春季年会
  • Place of Presentation: 立命館大学びわこ・くさつキャンパス
• [Presentation] 金属錯体型H2O2蛍光プローブの開発(2) (2013)
  • Author(s): 高野弘都・武安俊幸・人見 穣・小寺政人
  • Organizer: 日本化学会第93春季年会
  • Place of Presentation: 立命館大学びわこ・くさつキャンパス
• [Presentation] 金属錯体を利用した過酸化水素の蛍光検出 (2012)
  • Author(s): 武安 俊幸・人見 穣・小寺 政人
  • Organizer: 第6回バイオ関連化学シンポジウム
  • Place of Presentation: 北海道大学高等教育推進機構
• [Presentation] 水中でペルオキシダーゼ活性を示す単核鉄(III)錯体の開発 (2012)
  • Author(s): 平松 和明・荒川 健吾・人見 穣・小寺 政人
  • Organizer: 錯体化学会 第６２回討論会
  • Place of Presentation: 富山大学五福キャンパス
• [Presentation] 過酸化水素の高感度検出を目的とした金属錯体蛍光プローブの開発 (2012)
  • Author(s): 武安俊幸・人見 穣・小寺政人
  • Organizer: 第45回酸化反応討論会
  • Place of Presentation: 名古屋市立大学病院
• [Patent(Industrial Property Rights)] 複素環化合物，金属錯体および蛍光プローブ (2013)
  • Inventor(s): 人見 穣、武安 俊幸
  • Industrial Property Rights Holder: 学校法人同志社大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-07-29
  • Overseas
• [Patent(Industrial Property Rights)] 複素環化合物，金属錯体および蛍光プローブ (2012)
  • Inventor(s): 人見 穣、武安 俊幸
  • Industrial Property Rights Holder: 人見 穣、武安 俊幸
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-08-27