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Development of Small-molecule Fluorescent Probes Based on the Reactivity of Metal Complexes

Research Project

Project/Area Number 16H04124
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Inorganic chemistry
Research InstitutionDoshisha University

Principal Investigator

Hitomi Yutaka  同志社大学, 理工学部, 教授 (20335186)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywords過酸化水素 / 細胞 / 蛍光プローブ / 鉄錯体 / 反応 / 酸化 / 金属錯体 / 発光 / 蛍光 / ユーロピウム / 置換基効果 / ペルオキシダーゼ / 分析科学 / 細胞・組織 / 錯体化学 / 細胞化学 / 生物無機化学 / 生体機能関連化学 / 酸化反応
Outline of Final Research Achievements

We have developed a fluorescent probe that can rapidly visualize hydrogen peroxide released from cells as a signal. Fluorescent probes comprise complexes, profluorophores, and linkers linking them. In this study, the complex structure, profluorophore, and linker were improved. Hydrogen peroxide could be detected even in HeLa cells which do not overexpress the EGF receptor, when the most sensitive hydrogen peroxide fluorescent probe was used. In addition, it was shown that the emission of nitrogen monoxide could be achieved in the hypoxia region of cell spheroids by using MnNO complex. The mechanism by which the complex cleaves DNA by reductive oxygen activation was also elucidated.

Academic Significance and Societal Importance of the Research Achievements

生体で酸化反応をつかさどる酵素の機能を人工的な小分子で再現することに成功している。本研究ではその機能を大幅に向上させることに成功した。これらの成果は、微量な過酸化水素を検収することが必要なあらゆる場所で役立つ。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (51 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (36 results) (of which Int'l Joint Research: 9 results,  Invited: 8 results)

  • [Int'l Joint Research] University of California, Santa Barbara/Department of Chemistry and Biochemistry(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of California, Santa Barbara/Department of Chemical Engineering(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Harvard University/School of Eng. and Applied Sciences(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Lawrence Berkeley National Laboratory(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Acceleration of Hydrolytic DNA Cleavage by Dicopper(II) Complexes with p-Cresol-Derived Dinucleating Ligands at Slightly Acidic pH and Mechanistic Insights2019

    • Author(s)
      Kodera Masahito、Kadoya Yuki、Aso Kenta、Fukui Katsuki、Nomura Akiko、Hitomi Yutaka、Kitagishi Hiroaki
    • Journal Title

      Bulletin of the Chemical Society of Japan

      Volume: 92 Issue: 4 Pages: 739-747

    • DOI

      10.1246/bcsj.20180353

    • NAID

      130007632580

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen Peroxide-Reducing Factor Released by PC12D Cells Increases Cell Tolerance against Oxidative Stress2018

    • Author(s)
      Asami Muraishi, Emi Haneta, Yoshiro Saito, Yutaka Hitomi, Mamoru Sano, Noriko Noguchi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 5 Pages: 777-785

    • DOI

      10.1248/bpb.b18-00016

    • NAID

      130006730719

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-05-01
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macrophage-Mediated Delivery of Light Activated Nitric Oxide Prodrugs with Spatial, Temporal and Concentration Control2018

    • Author(s)
      Michael A. Evans, Po-Ju Huang, Yuji Iwamoto, Kelly N. Ibsen, Emory M. Chan, Yutaka Hitomi, Peter C. Ford, Samir Mitragotri
    • Journal Title

      Chemical Science

      Volume: 9 Issue: 15 Pages: 3729-3741

    • DOI

      10.1039/c8sc00015h

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Green fabrication of nanoporous BiVO4 films on ITO substrates for photoelectrochemical water-oxidation2018

    • Author(s)
      Okunaka Sayuri、Hitomi Yutaka、Tokudome Hiromasa
    • Journal Title

      RSC Advances

      Volume: 8 Issue: 55 Pages: 31575-31580

    • DOI

      10.1039/c8ra05831h

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Artificial Bleomycin: Pentadentate Monocarboxylamide Ligand Having a Spermine Tail for DNA Binding2018

    • Author(s)
      Akiko Nomura, Masahito Kodera, Yutaka Hitomi
    • Journal Title

      Peptide Scicence 2017

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structurally Simple Cell-permeable Porphyrins: Efficient Cellular Uptake and Photo-toxicity of Porphyrins with Four Peripheral Primary-amine-terminated Oligo(ethylene oxide) Chains2017

    • Author(s)
      Natsumi Ohashi, Akiko Nomura, Masahito Kodera, Yutaka Hitomi
    • Journal Title

      Chemistry Letters

      Volume: 46 Issue: 12 Pages: 1754-1756

    • DOI

      10.1246/cl.170821

    • NAID

      130006243178

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific Enhancement of Catalytic Activity by a Dicopper Core: Selective Hydroxylation of Benzene to Phenol with Hydrogen Peroxide2017

    • Author(s)
      Tsuji Tomokazu、Zaoputra Antonius Andre、Hitomi Yutaka、Mieda Kaoru、Ogura Takashi、Shiota Yoshihito、Yoshizawa Kazunari、Sato Hiroyasu、Kodera Masahito
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 56 Issue: 27 Pages: 7779-7782

    • DOI

      10.1002/anie.201702291

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DNA Cleavage through Reductive Dioxygen Activation by Iron-Bleomycin Mimics with Carboxamido Ligation: Correlation between DNA Cleavage Efficacy and Redox Potential2017

    • Author(s)
      Nomura, A.; Iwamoto, Y.; Arakawa, K.; Kashida, A.; Kodera, M.; Hitomi, Y.
    • Journal Title

      Chem. Lett.

      Volume: 印刷中 Issue: 8 Pages: 1109-1111

    • DOI

      10.1246/cl.170354

    • NAID

      130005907008

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cellular Application of Cell-membrane Permeable Fluorescent Zinc Probe Having a Cationic Peptide Tail2017

    • Author(s)
      Nomura, A.; Kashida, A.; Kodera, M.; Hitomi, Y.
    • Journal Title

      Peptide Science 2016

      Pages: 173-174

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation and High Reactivity of the anti-Dioxo Form of High- Spin m-Oxodioxodiiron(IV) as the Active Species That Cleaves Strong C2016

    • Author(s)
      Masahito Kodera,* Shin Ishiga, Tomokazu Tsuji, Katsutoshi Sakurai, Yutaka Hitomi, Yoshihito Shiota, P. K. Sajith, Kazunari Yoshizawa, Kaoru Mieda, and Takashi Ogura
    • Journal Title

      Chemistry A European Journal

      Volume: 17 Issue: 17 Pages: 1-14

    • DOI

      10.1002/chem.201600048

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Preparation of Fine Particles of Sheelite-Monoclinic Phase BiVO4 via an Aqueous Chelating Method for Efficient Photocatalytic Oxygen Evolution under Visible-light Irradiation2016

    • Author(s)
      Okunaka, S.; Tokudome, H.; Hitomi, Y.; Abe, R.
    • Journal Title

      J. Mater. Chem. A

      Volume: 4 Issue: 10 Pages: 3926-3932

    • DOI

      10.1039/c5ta09789d

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Development of Mononuclear Manganese Complexes for Selective Alkane Oxidation2018

    • Author(s)
      竹林 大貴、増田 瑛介、小寺 政人、人見 穣
    • Organizer
      第28回金属の関与する生体関連反応シンポジウム (SRM2018)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Selective Alkane Oxidation Catalyzed by Mononuclear Nonheme Iron Complex2018

    • Author(s)
      Yutaka Hitomi
    • Organizer
      43rd International Conference on Coordination Chemistry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ブレオマイシン機能モデル系における鉄(III)ヒドロペルオキシド種の解析2018

    • Author(s)
      野村 章子・坂井 僚介・小寺 政人・人見 穣
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] アニオン性カルボキサミド配位金属錯体を触媒とする選択酸化反応2018

    • Author(s)
      山岡功二・森川直人・吉澤直志・竹林大貴・上田純平・和村聡士・小寺政人・人見穣
    • Organizer
      第122回触媒討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of Oxidation Catalysts Based on Bio-inspired Iron Complexes2018

    • Author(s)
      Yutaka Hitomi
    • Organizer
      The 25th International SPACC Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DEVELOPMENT OF USEFUL FUNCTIONAL MOLECULES BASED ON BIOINSPIRED COMPLEXES2018

    • Author(s)
      Yutaka Hitomi
    • Organizer
      9th Asian Biological Inorganic Chemistry Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of Selective Oxidation Catalyst Based on Stimuli-Responsive Mononuclear Nonheme Complex”2018

    • Author(s)
      Yutaka Hitomi
    • Organizer
      International Congress on Pure & Applied Chemistry 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 二核銅錯体が触媒する H2O2によるベンゼンの直接酸化に及ぼ す配位子の電子効果:活性制御と反応機構解明2018

    • Author(s)
      髙橋宏仁、辻 朋和、人見 穣、小寺政人
    • Organizer
      日本化学会 第98春季年会 (2018)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酸素発生触媒を目的とする二核コバルト錯体の開発2018

    • Author(s)
      岩永 修、オプトラ アントニウス アンドレ、辻 朋和、人見 穣、小寺政人
    • Organizer
      日本化学会 第98春季年会 (2019)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 環状アミン修飾アミド型二核化配位子の合成とその二核銅錯体 による DNA 切断と抗がん活性2018

    • Author(s)
      前川雄哉・角谷優樹・人見 穣・小寺政人
    • Organizer
      日本化学会 第98春季年会 (2020)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mechanism of High Activity in Hydrolytic DNA Cleavage by Dicopper Complex at low pH region2018

    • Author(s)
      KADOYA, Yuki; HITOMI, Yutaka; KODERA, Masahito
    • Organizer
      日本化学会 第98春季年会 (2020)
    • Related Report
      2017 Annual Research Report
  • [Presentation] DNA二重鎖を切断する人工ブレオマイシンの合成2018

    • Author(s)
      野村章子、坂井僚介、岩本勇次、小寺政人、人見穣
    • Organizer
      日本薬学会 第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Anti-oxidative Activity of Mononuclear Nonheme Iron Complex: Effect of Albumin Binding2017

    • Author(s)
      Iwamoto, Y.; Kato, S.; Kodera, M.; Onoda, A.; Hayashi, T.; Hitomi, Y.
    • Organizer
      第27回金属の関与する生体関連反応シンポジウム(SRM2017)
    • Place of Presentation
      千葉県野田市
    • Year and Date
      2017-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 環状オリゴオキシエチレン基を有するシッフ塩基金属錯体によるカチオン認識2017

    • Author(s)
      吉澤 直志,山村 諒,小寺 政人,人見 穣
    • Organizer
      第15回ホスト-ゲスト・超分子化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 鉄オキソ種により選択的に不活性C?H結合を酸化する触媒の設計:酵素の戦略をもとに今どこまで設計できるのか?2017

    • Author(s)
      人見 穣
    • Organizer
      錯体化学若手の会夏の学校2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Photoluminescence Properties of Zinc Sulfide Nanoparticles Classified by Size Selective Precipitation2017

    • Author(s)
      Yasushige MORI, Kyoko YAMAMOTO,Yutaka HITOMI, Doris SEGETS, Wolfgang PEUKERT, Katsumi TSUCHIYA
    • Organizer
      10th World Congress of Chemical Engineering
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒドロペルオキシド鉄(III)錯体の生成とその反応性に関する研究2017

    • Author(s)
      坂井 僚介,野村 章子,小寺 政人,人見 穣
    • Organizer
      2017年度先端錯体工学研究会(SPACC)年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] がん細胞内のDNAを特異的に切断する膜透過性二核銅錯体の開発2017

    • Author(s)
      角谷 優樹,福井 克樹,人見 穣,小寺 政人
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] DNAに特異的に結合する蛍光プローブを持つ二核金属錯体の開発2017

    • Author(s)
      齋藤 樹,人見 穣,小寺 政人
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 二核銅錯体が触媒するベンゼンの直接酸化による高速・高選択的フェノール合成2017

    • Author(s)
      小寺 政人,辻 朋和,ZAOPUTRA, Antonius Andre,人見 穣,小倉 尚志,塩田 淑人,吉澤 一成
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 鉄ブレオマイシン機能モデル錯体を用いた酸素の還元的活性化による酸化的DNA切断2017

    • Author(s)
      野村 章子,奥田 夏未,岩本 勇次,加藤 俊介,小寺 政人,小野田 晃,林 高史,人見 穣
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] カルボキサミド配位単核非ヘム鉄錯体を用いた選択酸化触媒の開発2017

    • Author(s)
      人見 穣
    • Organizer
      第120回触媒討論会,2017年9月
    • Related Report
      2017 Annual Research Report
  • [Presentation] Electronic effect on rapid and efficient hydroxylation of benzenes and alkanes with H2O2 catalyzed by dicopper complexes2017

    • Author(s)
      Tomokazu TSUJI, Yutaka HITOMI, Kaoru MIEDA, Takashi OGURA, Yoshihito SHIOT, Kazunari YOSHIZAW, Hiroyasu SATO, Masahito KODERA
    • Organizer
      第67回錯体化学会討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mechanistic Studies for Selective Benzene Hydroxylation with Hydrogen Peroxide Catalyzed by Nickel Complexes2017

    • Author(s)
      Antonius Andre ZAOPUTRA, Tomokazu Tsuji, Yutaka Hitomi, Kaoru Mied, Takashi Ogur, Masahito Kodera
    • Organizer
      第67回錯体化学会討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] N2S型大環状配位子のヘテロ二核金属錯体が触媒する電気化学的CO2還元2017

    • Author(s)
      北川 竜也,吉田 剛,人見 穣,小寺 政人
    • Organizer
      第67回錯体化学会討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] H2O2/二核銅錯体によるベンゼンの選択的水酸化に及ぼすキノリン側鎖の効果2017

    • Author(s)
      八塚 駿,辻 朋和,人見 穣,小寺 政人
    • Organizer
      第67回錯体化学会討論会,2017年10月
    • Related Report
      2017 Annual Research Report
  • [Presentation] Aerobic Oxidation Catalyzed by Mononuclear Non-heme Iron Complexes2017

    • Author(s)
      竹林 大貴,坂井 僚介,森川 直人,平松 南実,小寺 政人,笹野 裕介,岩渕 好治,人見 穣
    • Organizer
      第67回錯体化学会討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 銅錯体が触媒するH2O2によるアルカン酸化:二核銅の効果2017

    • Author(s)
      岸本 竜弥,辻 朋和,人見 穣,小寺 政人
    • Organizer
      第50回酸化反応討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 二核銅(II)錯体が触媒するベンゼンの直接酸化による選択的フェノール生成:水分子の効果に基づく高活性触媒の開発2017

    • Author(s)
      辻 朋和,人見 穣,塩田 淑人,吉澤 一成,小寺 政人
    • Organizer
      第50回酸化反応討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酸素発生触媒を目的とする二核コバルト錯体の開発2017

    • Author(s)
      岩永 修,Antonius Andre ZAOPUTRA,辻 朋和,人見 穣,小寺 政人
    • Organizer
      第50回酸化反応討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 二核銅錯体が触媒するH2O2によるベンゼンの直接酸化による選択的フェノール生成:6-hpa配位子の電子効果による酸化触媒活性制御2017

    • Author(s)
      髙橋 宏仁,辻 朋和,人見 穣,小寺 政人
    • Organizer
      第50回酸化反応討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of artificial bleomycin analogue: Pentadentate carboxamide ligand having spermine moiety for DNA binding2017

    • Author(s)
      Akiko Nomura, Ryosuke Sakai, Yuji Iwamoto,Masahito Kodera,Yutaka Hitomi
    • Organizer
      The 54th Japanese Peptide Symposium
    • Related Report
      2017 Annual Research Report
  • [Presentation] Site-Selective C-H Bond Oxidation Catalyzed by Mononuclear Nonheme Iron Complexes: Additive Effects of Carboxylic Acids2017

    • Author(s)
      Yutaka Hitomi
    • Organizer
      2017 DGIST Global Innovation Festival
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Generation of Hydrogen Peroxide by Functional Model Complexes for Superoxide Dismutase2017

    • Author(s)
      Yutaka Hitomi
    • Organizer
      EWHA Bioinorganic Chemistry Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Biologically Useful Functional Models of Metalloenzymes2016

    • Author(s)
      Hitomi, Y.
    • Organizer
      8th Asian Biological Inorganic Chemistry Conference
    • Place of Presentation
      Auckland, New Zealand
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Bioinspired Mononuclear Nonheme Iron Complexes for Detection of Hydrogen Peroxide inside Living Cells2016

    • Author(s)
      Hitomi, Y.
    • Organizer
      42nd International Conference on Coordination Chemistry
    • Place of Presentation
      Brest, France
    • Year and Date
      2016-07-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2021-01-27  

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