マルチレドックスサイト型オリゴマー中分子による生物機能分子創出

• Project Area: Middle molecular strategy: Creation of higher bio-functional molecules by integrated synthesis.
• Project/Area Number: 16H01125
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• 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): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 中分子 / 酸化還元 / オリゴマー / 集積合成

Outline of Annual Research Achievements

有機酸化還元系は、生体電子伝達系への関与やDNAインターカレーション能などの特性により、医農薬分野で活躍する生物機能分子として高いポテンシャルを持つ。π電子系化合物を利用した分子創薬に於いては、新規な低分子酸化還元系分子骨格の開発ばかりでなく、その骨格の中分子化による酸化還元機能/生理活性の調節が有効なアプローチであると考えた。このようなマルチレドックスサイトをもつオリゴマーは、電子授受以外の外部刺激によっても分子構造の変調が可能なため、モノマーには無い特異な制御性を持つ。本研究では、カスケード環化やフロー合成を利用して効率よく合成される低分子酸化還元骨格を、共有結合で複数連結したマルチレドックス型中分子において、リンカーや連結数に応じた摂動の様子をパラメータ化して理解する。またその基礎的知見を基づき、分子創薬に望ましいパラメータを持つよう特性をチューニングし、生物機能分子開発につなげることを目的として研究を展開している。
新規低分子モノマーとして、平面ディスク形状を持つπ縮環型パラフェニレンジアミンであるbenz[a]indolo[2,3-c]carbazole(BIC)を用い、メタキシリレン型スペーサーで6つまで連結された一連の電子供与体を合成した。BIC骨格の酸化状態は積層構造形成による安定化を受け、BICユニット個数の半分が陽イオン種となった状態を取りやすいことが明らかとなった。 またピラジン縮環キノン類の生理活性は分子構造の特徴についての、領域内共同研究成果を論文発表することができた。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] BIO-HPC, UCAM(スペイン)
• [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] 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] 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] 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] 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
• [Journal Article] 9,10-Dihydrophenanthrene with Two Spiro(dibenzocycloheptatriene) Units: A Highly Strained Caged Hydrocarbon Exhibiting Reversible Electrochromic Behavior (2017)
  • Author(s): Ishigaki Yusuke、Hayashi Yuki、Sugawara Kazuma、Shimajiri Takuya、Nojo Wataru、Katoono Ryo、Suzuki Takanori
  • Journal Title: Molecules Volume: 22 Issue: 11 Pages: 1900-1900
  • DOI: 10.3390/molecules22111900
  • NAID: 120006383818
  • Peer Reviewed / Open Access
• [Journal Article] Stereoselecive Encapsulation for a Triarylmethylium o,o-Dimer by Natural gamma-Cyclodextrin: Origin of Chiral Recogntion For the Acially Chiral Dicationic Guest (2017)
  • Author(s): T. Suzuki, J. P. Cerón-Carrasco, H. Tamaoki, Y. Ishigaki, R. Katoono, T. Fukushima, H. Pérez-Sánchez,
  • Journal Title: Heterocycles Volume: - Issue: 6 Pages: 1123-1123
  • DOI: 10.3987/com-17-13674
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Organic Molecular Layer with High Electrochemical Bistability: Synthesis, Structure, and Properties of a Dynamic Redox System with Lipoate Units for Binding to Au(111), (2017)
  • Author(s): E. Ohta, H. Uehara, Y. Han, K. Wada, H. Noguchi, R. Katoono, Y. Ishigaki, H. Ikeda, K. Uosaki, T. Suzuki
  • Journal Title: ChemPlusChem Volume: - Issue: 7 Pages: 1043-1047
  • DOI: 10.1002/cplu.201600649
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] xidative Desulfurization of Electron-Donating 5,5,7,7-Tetraaryl-5,7-dihydrodibenzo[c,e]thiepins and the Related Heterocycles: Generation of Dicationic Dyes upon Two-Electron Oxidation (2017)
  • Author(s): T. Suzuki, T. Kuroda, H. Tamaoki, S. Higasa, T. Nehira, R. Katoono, Y. Ishigaki, K. Fujiwara, T. Fukushima, H. Yamada
  • Journal Title: Heterocycles Volume: 95(2), Issue: 2 Pages: 816-829
  • DOI: 10.3987/com-16-s(s)50
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bis(diarylethenyl)thiophenes, -bithiophenes, and -terthiophenes: A New Series of Electrochromic Systems that Exhibit a Fluorescence Response (2016)
  • Author(s): Y. Ishigaki, H. Kawai, R. Katoono, K. Fujiwara, H. Higuchi, H. Kikuchi, T. Suzuki
  • Journal Title: Can. J. Chem. Volume: 95(3) Issue: 3 Pages: 243-252
  • DOI: 10.1139/cjc-2016-0222
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Redox-induced conformational changes in 1,3-propylene- and m-xylylenebis[5-(10-butyl-5,10-dihydrobenzo[a]indolo[2,3-c]carbazole)]: Twin-BIC donors that form sandwich-like dimeric cations exhibiting NIR absorption (2016)
  • Author(s): T. Suzuki, W. Nojo, Y. Sakano, R. Katoono, Y. Ishigaki, H. Ohno, K. Fujiwara,
  • Journal Title: Chem. Lett. Volume: 45 Issue: 7 Pages: 2582-2586
  • DOI: 10.1246/cl.160278
  • NAID: 130005253001
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dynamic helical cyclophanes with two quadruply-bridged planes arranged in an “obverse and/or reverse” relation (2016)
  • Author(s): R. Katoono, S. Kawai, T. Suzuki
  • Journal Title: Chem. Sci Volume: 7 Issue: 5 Pages: 3240-3247
  • DOI: 10.1039/c5sc04673d
  • NAID: 120006220021
  • Peer Reviewed / Open Access
• [Journal Article] Assembly of an Axially Chiral Dynamic Redox System with a Perfluorobiphenyl Skeleton into Dumbbell- or Tripod-type Electron Donors (2016)
  • Author(s): H. Tamaoki, R. Katoono, K. Fujiwara, T. Suzuki
  • Journal Title: Angew. Chem. Int. Ed. Volume: 55(7) Issue: 7 Pages: 2582-2586
  • DOI: 10.1002/anie.201510935
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Planar chiral desymmetrization of a two-layered cyclophane and control of dynamic helicity through the arrangement of two nonstereogenic centers (2016)
  • Author(s): Ryo Katoono* and Takanori Suzuki
  • Journal Title: Chemical Communications Volume: 52 Issue: 5 Pages: 1029-1031
  • DOI: 10.1039/c5cc09069e
  • NAID: 120005866833
  • Peer Reviewed / Open Access
• [Presentation] 有機酸化還元系設計の愉しみ： 世界一の構造から単一分子メモリまで (2018)
  • Author(s): 鈴木孝紀
  • Organizer: 日本化学会第９８春季年会特別企画招待講演
• [Presentation] Dynamic redox system that can form an organic molecular layer : Toward the realization of molecular-based data storage devices (2017)
  • Author(s): Takanori Suzuki
  • Organizer: 17th International Symposium on Novel Aromatic Compounds (ISNA-17)
• [Presentation] Toward the realization of molecular-based data storage Devices: An apporach from the organic chemistry based on dynamic redox systems (2017)
  • Author(s): Takanori Suzuki
  • Organizer: 17th International Symposium on Novel Aromatic Compounds (ISNA-17)
• [Presentation] 単一分子メモリユニットとしての動的酸化還元系：発想とプロトタイプ構築 (2017)
  • Author(s): 鈴木孝紀
  • Organizer: 第41回有機電子移動化学討論会