ドナーアクセプター連結型中分子による生物機能/光機能分子創出

• Project Area: Middle molecular strategy: Creation of higher bio-functional molecules by integrated synthesis.
• Project/Area Number: 18H04376
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Research Institution: Hokkaido University
• Principal Investigator: 鈴木 孝紀 北海道大学, 理学研究院, 教授 (70202132)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: バイオイメージング / 硫化水素 / 近赤外光 / エレクトロクロミズム / 光線力学療法 / 中分子 / 酸化還元 / 生物機能 / 電気化学的両性 / ヘテロ環 / 近赤外吸収 / 有機酸化還元系 / ドナーアクセプター / 光機能

Outline of Annual Research Achievements

電位の変化を入力としてその色調を可逆に変化させるエレクトロクロミック物質(EM)として、先にヘキサアリールブタジエン型電子供与体2と、その二電子酸化により生じる安定な二価陽イオン1の酸化還元対を開発している。バイオイメージングに有効なNIR領域で応答すること、及び1が水中でも分解せず非常に安定であることを利用し、今年度、1と2のEMに基づくH2Sのバイオプローブを構築した。H2Sは近年、生物界で第3のガス状伝達物質として認知され、また、肝ガンなど多くの疾患との関係が示唆されている。この有機EMを用いて、H2Sの非侵襲的かつリアルタイムイメージングシステムを構築できたのは、生体内の他の還元性物質に優先して、1がH2Sと高選択的かつ迅速に反応するためである。
イメージングには上記EMを蛍光性ポリマーと組み合わせて使用した。NIRに強い吸収を持つ二価陽イオン1 は、蛍光共鳴エネルギー移動によって、ポリマーのNIR蛍光を効率良く消光するのに対し、可視部にほとんど吸収のない中性ジエン2は消光しない。そのため、1がH2Sと反応して2になる反応を、NIR蛍光のON/OFFメカニズムとして利用することができた。ポリマーとEM色素の共存は、リポソームで両者を包含することで達成した。バイオプローブ中の1は マクロファージ細胞中で、内在性/外在性のH2Sと迅速に反応し、蛍光を発することが明らかになった。また、マウスを用いたin vivoの実験では、肝臓の内在性H2Sをバイオプローブの静脈注射によりイメージングできることも示された。ナノ粒子作成に際して葉酸タグを組み込んだ場合には、KB細胞へのバイオプローブの集積が起こるため、腫瘍部分の蛍光イメージングが可能であり、また、蛍光性半導体ポリマーの代わりに一重項酸素増感剤を組み込んだナノ粒子を用いることで、光線力学療法を通じた腫瘍体積の減少も確認された。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] 南京大学(中国)
• [Int'l Joint Research] リヨン大学(フランス)
• [Int'l Joint Research] Nanjing University(中国)
• [Journal Article] H2S-activatable near-infrared afterglow luminescent probes for sensitive molecular imaging in vivo (2020)
  • Author(s): Wu Luyan、Ishigaki Yusuke、Hu Yuxuan、Sugimoto Keisuke、Zeng Wenhui、Harimoto Takashi、Sun Yidan、He Jian、Suzuki Takanori、Jiang Xiqun、Chen Hong-Yuan、Ye Deju
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 446-446
  • DOI: 10.1038/s41467-020-14307-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hexaarylbutadiene: A Versatile Scaffold with Tunable Redox Properties towards Organic Near‐Infrared Electrochromic Material (2020)
  • Author(s): Ishigaki Yusuke、Harimoto Takashi、Sugimoto Keisuke、Wu Luyan、Zeng Wenhui、Ye Deju、Suzuki Takanori
  • Journal Title: Chemistry An Asian Journal Volume: 15 Issue: 7 Pages: 1147-1155
  • DOI: 10.1002/asia.201901816
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Switching of Redox Properties Triggered by a Thermal Equilibrium between Closed-Shell Folded and Open-Shell Twisted Species (2020)
  • Author(s): Ishigaki Yusuke、Hashimoto Takumi、Sugawara Kazuma、Suzuki Shuichi、Suzuki Takanori
  • Journal Title: Angewandte Chemie International Edition Volume: - Issue: 16 Pages: 6581-6584
  • DOI: 10.1002/anie.201916089
  • NAID: 120007018433
  • Peer Reviewed
• [Journal Article] 5-Arylidenetetronate as a Versatile Electrophore for Pi-Extended Electron Acceptors (2020)
  • Author(s): Yuki Hayashi, Yusuke Ishigaki, Jeremy Merad, Takanori Suzuki, Maurice Medebielle
  • Journal Title: HETEROCYCLES Volume: in press Issue: 1 Pages: 165-165
  • DOI: 10.3987/com-20-s(k)2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Novel Condensed Heterocyclic Quinone with a Dibezofuranobisthiadiazole Skeleton. (2019)
  • Author(s): K. Sugawara, W. Nojo, Y. Ishigaki, J. Ohkanda, T. Suzuki
  • Journal Title: Heterocycles Volume: - Issue: 1 Pages: 99-99
  • DOI: 10.3987/com-19-s(f)7
  • Peer Reviewed
• [Journal Article] Electric-Field-Controllable Conductance Switching of an Overcrowded Ethylene Self-Assembled Monolayer (2019)
  • Author(s): Fujii Shintaro、Koike Masato、Nishino Tomoaki、Shoji Yoshiaki、Suzuki Takanori、Fukushima Takanori、Kiguchi Manabu
  • Journal Title: Journal of the American Chemical Society Volume: 141 Issue: 46 Pages: 18544-18550
  • DOI: 10.1021/jacs.9b09233
  • Peer Reviewed
• [Journal Article] Photo- and Thermal Interconversion of Multiconfigurational Strained Hydrocarbons Exhibiting Completely Switchable Oxidation to Stable Dicationic Dyes (2019)
  • Author(s): Ishigaki Yusuke、Hayashi Yuki、Suzuki Takanori
  • Journal Title: Journal of the American Chemical Society Volume: 141 Issue: 45 Pages: 18293-18300
  • DOI: 10.1021/jacs.9b09646
  • NAID: 120006893193
  • Peer Reviewed
• [Journal Article] Two-way Chromic Systems Based on Tetraarylanthraquinodimethanes: Electrochromism in Solution and Mechanofluorochromism in a Solid State. (2019)
  • Author(s): Y. Ishigaki, K. Sugawara, M. Yoshida, M. Kato, T. Suzuki
  • Journal Title: Bull. Chem. Soc. Jpn。 Volume: - Issue: 7 Pages: 1211-1217
  • DOI: 10.1246/bcsj.20190094
  • NAID: 130007679358
  • Peer Reviewed
• [Journal Article] Dual dynamic chirality generated in the assembly of three achiral rods through the three-fold twisting of a macrocycle (2019)
  • Author(s): Katoono Ryo、Sakamoto Kazuki、Suzuki Takanori
  • Journal Title: Chemical Communications Volume: - Issue: 38 Pages: 5503-5506
  • DOI: 10.1039/c9cc02226k
  • NAID: 120006843069
  • Peer Reviewed
• [Journal Article] Selective Formation of a Mixed‐valence State from Linearly‐bridged Oligo(aromatic diamines): Drastic Structural Change into a Folded Columnar Stack for Half‐filled Polycations** (2019)
  • Author(s): Nojo Wataru、Ishigaki Yusuke、Takeda Takashi、Akutagawa Tomoyuki、Suzuki Takanori
  • Journal Title: Chemistry A European Journal Volume: - Issue: 32 Pages: 7759-7765
  • DOI: 10.1002/chem.201901272
  • Peer Reviewed
• [Journal Article] Chiral diversification through the assembly of achiral phenylacetylene macrocycles with a two-fold bridge (2019)
  • Author(s): Katoono Ryo、Kusaka Keiichi、Saito Yuki、Sakamoto Kazuki、Suzuki Takanori
  • Journal Title: Chemical Science Volume: - Issue: 18 Pages: 4782-4791
  • DOI: 10.1039/c9sc00972h
  • NAID: 120006709315
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis of the cyclohexene segment of portimine (2019)
  • Author(s): T. Saito, K. Fujiwara, Y. Kondo, U. Akiba, T. Suzuki
  • Journal Title: Tetrahedron Letters Volume: 60 Issue: 4 Pages: 386-389
  • DOI: 10.1016/j.tetlet.2018.12.063
  • Peer Reviewed
• [Journal Article] Total synthesis of kehokorins A and B (2019)
  • Author(s): K. Fujiwara, R. Motousu, D. Sato, Y. Kondo, U. Akiba, T. Suzuki, T. Tokiwano
  • Journal Title: Tetrahedron Letters Volume: 60 Issue: 18 Pages: 1299-1301
  • DOI: 10.1016/j.tetlet.2019.04.011
  • Peer Reviewed
• [Journal Article] Molecular Wires with Controllable π-Delocalization Incorporating Redox-Triggered π-Conjugated Switching Units (2018)
  • Author(s): Nojo Wataru、Tamaoki Hitomi、Ishigaki Yusuke、Katoono Ryo、Fujiwara Kenshu、Fukushima Takanori、Suzuki Takanori
  • Journal Title: ChemPlusChem Volume: ー Issue: 6 Pages: 634-642
  • DOI: 10.1002/cplu.201800341
  • Peer Reviewed
• [Journal Article] Direct synthesis of aryl-annulated [c]carbazoles by gold(I)-catalysed cascade reaction of azide-diynes and arenes (2018)
  • Author(s): Yuiki Kawada, Shunsuke Ohmura, Misaki Kobayashi, Wataru Nojo, Masaki Kondo, Yuka Matsuda, Junpei Matsuoka, Shinsuke Inuki, Shinya Oishi, Chao Wang, Tatsuo Saito, Masanobu Uchiyama, Takanori Suzuki, Hiroaki Ohno
  • Journal Title: Chem. Sci. Volume: 9 Issue: 44 Pages: 8416-8416
  • DOI: 10.1039/c8sc03525c
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Engineering of Electrochromic Materials as Activatable Probes for Molecular Imaging and Photodynamic Therapy (2018)
  • Author(s): Wu Luyan、Sun Yidan、Sugimoto Keisuke、Luo Zhiliang、Ishigaki Yusuke、Pu Kanyi、Suzuki Takanori、Chen Hong-Yuan、Ye Deju
  • Journal Title: Journal of the American Chemical Society Volume: 140 Issue: 47 Pages: 16340-16352
  • DOI: 10.1021/jacs.8b10176
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Expandability of a long C-O bond by a scissor effect in acenaphthofuran (2018)
  • Author(s): Uchimura Yasuto、Shimajiri Takuya、Ishigaki Yusuke、Katoono Ryo、Suzuki Takanori
  • Journal Title: Chemical Communications Volume: 54 Issue: 73 Pages: 10300-10303
  • DOI: 10.1039/c8cc05998e
  • Peer Reviewed
• [Journal Article] Transmission of Point Chirality to Axial Chirality for Strong Circular Dichroism in Triarylmethylium-o,o-dimers (2018)
  • Author(s): Suzuki Takanori、Ishigaki Yusuke、Iwai Tomohiro、Hayashi Yuki、Nagaki Aiichiro、Katoono Ryo、Fujiwara Kenshu、Yoshida Jun-ichi
  • Journal Title: Synlett Volume: 29 Issue: 16 Pages: 2147-2154
  • DOI: 10.1055/s-0037-1610190
  • Peer Reviewed
• [Journal Article] An improved synthesis of the C42-C52 segment of ciguatoxin 3C (2018)
  • Author(s): Saito Takafumi、Fujiwara Kenshu、Sano Yusuke、Sato Takuto、Kondo Yoshihiko、Akiba Uichi、Ishigaki Yusuke、Katoono Ryo、Suzuki Takanori
  • Journal Title: Tetrahedron Letters Volume: 59 Issue: 14 Pages: 1372-1376
  • DOI: 10.1016/j.tetlet.2018.02.052
  • Peer Reviewed
• [Journal Article] Double bond formation based on nitroaldol reaction and radical elimination: A prototype segment connection method for the total synthesis of nigricanoside A dimethyl ester (2018)
  • Author(s): Tsunoda Takayuki、Fujiwara Kenshu、Okamoto Satoshi、Kondo Yoshihiko、Akiba Uichi、Ishigaki Yusuke、Katoono Ryo、Suzuki Takanori
  • Journal Title: Tetrahedron Letters Volume: 59 Issue: 19 Pages: 1846-1850
  • DOI: 10.1016/j.tetlet.2018.03.091
  • Peer Reviewed
• [Journal Article] Narrower HOMO-LUMO gap attained by conformational switching through peripheral polyarylation in 1,4,5,8-tetraaza-9,10-anthraquinodimethanes (2018)
  • Author(s): Suzuki Takanori、Ishigaki Yusuke、Sugawara Kazuma、Umezawa Yu、Katoono Ryo、Shimoyama Atsushi、Manabe Yoshiyuki、Fukase Koichi、Fukushima Takanori
  • Journal Title: Tetrahedron Volume: 74 Issue: 18 Pages: 2239-2244
  • DOI: 10.1016/j.tet.2018.03.041
  • Peer Reviewed
• [Journal Article] Enhanced circular dichroism at elevated temperatures through complexation-induced transformation of a three-layer cyclophane with dualistic dynamic helicity (2018)
  • Author(s): Katoono Ryo、Obara Yudai、Fujiwara Kenshu、Suzuki Takanori
  • Journal Title: Chemical Science Volume: 9 Issue: 8 Pages: 2222-2229
  • DOI: 10.1039/c7sc05242a
  • NAID: 120006473606
  • Peer Reviewed / Open Access
• [Journal Article] Supramolecular chiroptical switching of helical-sense preferences through the two-way intramolecular transmission of a single chiral source (2018)
  • Author(s): Katoono Ryo、Kusaka Keiichi、Tanaka Yuki、Fujiwara Kenshu、Suzuki Takanori
  • Journal Title: Organic & Biomolecular Chemistry Volume: 16 Issue: 7 Pages: 1167-1171
  • DOI: 10.1039/c7ob03057f
  • NAID: 120006558997
  • Peer Reviewed
• [Journal Article] Longest C-C Single Bond among Neutral Hydrocarbons with a Bond Length beyond 1.8A (2018)
  • Author(s): Ishigaki Yusuke、Shimajiri Takuya、Takeda Takashi、Katoono Ryo、Suzuki Takanori
  • Journal Title: Chem Volume: 2018 Issue: 4 Pages: 795-806
  • DOI: 10.1016/j.chempr.2018.01.011
  • Peer Reviewed
• [Journal Article] Dynamic or undynamic chirality generated by helical arrangement of a shape-persistent ring and rod doubly bridged in a molecule (2018)
  • Author(s): Katoono Ryo、Obara Yudai、Kusaka Keiichi、Suzuki Takanori
  • Journal Title: Chemical Communications Volume: 54 Issue: 7 Pages: 735-738
  • DOI: 10.1039/c7cc09485j
  • NAID: 120006549167
  • Peer Reviewed
• [Presentation] Organic Electrochromic Systems as Bioprobes of H2S for Imaging and Photodynamic Therapy (2019)
  • Author(s): Takanori Suzuki
  • Organizer: Strasbourg-Hokkaido Symposium
  • Int'l Joint Research / Invited
• [Presentation] Studies on Dynamic Redox Systems: Construction of Record-breaking Strained Compounds and Development of Unimolecular Memory (2019)
  • Author(s): 鈴木孝紀
  • Organizer: 第９９回日本化学会春季年会(受賞講演）
  • Invited
• [Presentation] 超結合:共有結合の限界を超えた化学 (2019)
  • Author(s): 鈴木孝紀
  • Organizer: 第９９回日本化学会春季年会(特別企画）
  • Invited