KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2005.04

  -

  2006.03

  harvard University, Departmernt of Chemistry and Chemical Biology, Postdoctoral Fellow

• 2006.04

  -

  2010.03

  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Assistant Professor

• 2010.04

  -

  2010.12

  Institute of Microbial Chemistry, Laboratory of Synthetic Organic Chemnistry, Researcher

• 2010.04

  -

  2017.03

  Rikkyo University, Department of Science, Adjunct Lecturer

• 2011.01

  -

  2013.03

  Insttitute of Microbial Chemistry, Laboratory of Synthetic Organic Chemistry, Senior Researcher

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Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 1996.04

  -

  2000.03

  The University of Tokyo, Department of Pharmaceutical Sciences

  University, Graduated

• 2000.04

  -

  2002.03

  The University of Tokyo, Graduate School of Pharmaceutical Sciences

  Graduate School, Completed, Master's course

• 2002.04

  -

  2005.03

  The University of Tokyo, Graduate School of Pharmaceutical Sciences

  Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• The University of Tokyo, The University of Tokyo, Coursework, 2005.03

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• Pharmacist, 2000.09

• senior [first class] radiation protection supervisor, 2012.04

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Nanotechnology/Materials / Structural organic chemistry and physical organic chemistry

• Life Science / Bioorganic chemistry

Books 【 Display / hide 】

Books 【 Display / hide 】

• Interplay of diamides and rare earth metals: Specific molecular spaces and catalytic activity

  Kumagai N., Shibasaki M., Designed Molecular Space in Material Science and Catalysis, 2018.01

  　View Summary

  A catalytic system comprising functionalized small diamides and rare earth metals (REs) exerts intriguing catalytic properties that are dictated by dynamic construction of flexible molecular spaces. The dynamic interaction of diamides and REs is characterized by broad applicability to distinct reaction systems as well as notable switchable catalysis. Structural modification of the diamide allows for enhanced intermolecular interactions to afford a self-assembled solid-phase catalyst with a specific molecular space that engages in heterogeneous asymmetric catalysis with a continuous-flow platform.

• Chiral Bimetallic Lewis Acids

  Shibasaki M., Kumagai N., Topics in Organometallic Chemistry, 2018

  　View Summary

  Here, we review the utility of chiral bimetallic (multimetallic) Lewis acidic complexes in catalytic asymmetric transformations. Bimetallic complexes are endowed with dual catalytic functions that synergistically activate multiple substrates and functionalities. This cooperative activation mode is particularly effective for activating low reactivity substrates in a highly stereoselective manner without the aid of stoichiometric activating reagents. The privileged bimetallic catalysts presented here highlight the importance of catalyst design in the development of widely applicable catalytic systems.

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• TriQuinazoline and Related Quinoline/Quinazoline Cyclic Trimers: Unified Synthesis, Planar Discotic Architecture, and Proton Dynamics in an Atomic-Scale Cavity

  Sakurai T., Tsutsumi R., Kumagai N.

  Chemistry of Materials 38 ( 5 ) 2453 - 2463 2026.03

  ISSN  08974756

  　View Summary

  Heteroatom-doped graphitic materials, particularly those bearing nitrogen, have attracted considerable attention because of their unique physicochemical properties, which are unattainable in pristine carbon frameworks. To rigorously investigate the effects of doping and to enable fine-tuning of their functions at the atomic scale, bottom-up synthesis of well-defined molecular surrogates provides a powerful approach. Herein, we report the design, synthesis, and physicochemical characterization of a series of quinoline/quinazoline cyclic trimers, TriQuinoline (TQ, Q3), Q2Qz1, Q1Qz2, and TriQuinazoline (TQz, Qz3), featuring an atomic-sized central cavity surrounded by three pyridinic nitrogens that mirrors the local topology of nitrogen-doped graphene defects. A modular synthetic strategy enabled facile access to all of the quinazoline-containing congeners. Systematic X-ray analysis and computational studies revealed increasing molecular planarity with increasing quinazoline incorporation, arising from stepwise elimination of destabilizing CH···HC contacts and the emergence of favorable CH···N interactions. Spectroscopic and theoretical studies demonstrated that quinazoline substitution progressively decreases the proton affinity at the central cavity owing to the electron-withdrawing nature of the quinazoline units, which markedly accelerates proton exchange. Even with these electronic modifications, supramolecular association with polycyclic aromatics, such as coronene and [12]cycloparaphenylene ([12]CPP), substantially remained preserved upon quinazoline incorporation. These findings highlight the cooperative interplay of structural planarity and heteroatom substitution in dictating the properties of discotic heteroaromatics, offering a versatile platform for material design.

  • Access to Document (DOI)

• Insights into coordination and (semi-)rigidity in the molecular design of bicyclic heterocycle frameworks

  Kobayashi T., Sakurai T., Kumagai N.

  Chemistry Letters 55 ( 2 )  2026.02

  ISSN  03667022

  　View Summary

  Macrocyclic compounds, exhibiting unique properties arising from their large-ring frameworks, have captivated the attention of organic chemists over the last few decades. These molecules serve specific functions across disciplines, including synthetic chemistry, materials science, and biology. Representative molecules in this category, including crown ethers, calix[n]arenes, and porphyrinoids composed of ether/phenol/pyrrole subunits, exhibit unparalleled structural and functional diversity. In contrast, macrocycles exploiting quinoline/quinazoline as key building blocks to construct specific macrocyclic architectures have received limited attention and are much less explored. In this Highlight Review, we summarize our recent advances in oligo-quinoline/quinazoline macrocycles. Emphasis is focused on synthetic strategies, structural features, and emerging applications in organometallic, supramolecular, and photophysical chemistry. We anticipate that these collective results will guide new molecular designs within the broader family of heterocycle-based macrocycles.

  • Access to Document (DOI)

• Revisiting C4N4 Fluorophore: Theoretical Elucidation of the Origin of Fluorescent Properties of 2,5-Diaminopyrimidines and Strategic Applications to Pd Detection

  Kohei M., Kondo I., Kawamura G., Harabuchi Y., Maeda S., Kumagai N.

  Chemistry A European Journal  2026

  ISSN  09476539

  　View Summary

  Compact organic fluorophores are attractive scaffolds for probe design, yet their emission is often compromised by efficient nonradiative decay. Here, we introduce 2,5-diaminopyrimidine-based C4N4 as an intrinsically emissive, exceptionally small platform, which remains bright without extended π-conjugation. Systematic substitution at 4,6-positions with alkyl, alkenyl, and alkynyl groups reveals robust emission for alkyl and alkynyl derivatives, and a striking bimodality for alkenyls. TDDFT combined with ES/SC-AFIR mapped the S<inf>1</inf>→S<inf>0</inf> internal-conversion landscape, providing a rationale for substituent-dependent relaxation behavior. Manipulation at the 5-position allowed for independent trigger-responsive emission behavior. This orthogonal design, where the 4,6-substituted C4N4 core serves as the fluorophore and the 5-position operates as ON/OFF gate, enabled the development of turn-on probes for Pd²⁺.

  • Access to Document (DOI)

• DiazaChrysenes (DC): Nitrogen-Containing π-Extended Molecules for Photocatalytic C–H Amination

  Xu W., Iwai A., Nagasaka I., Watanabe S., Tsutsumi R., Kumagai N.

  Organic Letters (American Chemical Society)  27 ( 39 ) 10937 - 10942 2025.10

  Research paper (scientific journal), Joint Work, Last author, Corresponding author, Accepted,  ISSN  15237060

  　View Summary

  We report a new class of nitrogen-containing π-extended heterocycles, DiazaChrysenes (DCs), and their dimeric analogues (dDCs) as metal-free photocatalysts for C–H amination. DCs featuring a quinolino[1,2-c]quinazolin-5-ium core were synthesized via electrophilic amide activation and arylation. The resulting compounds displayed tunable photophysical and redox properties, with CF<inf>3</inf>-substituted DCs enabling the C–H amination of arenes with azoles under visible light and aerobic conditions, achieving yields up to 85%. The reaction tolerated a range of arene and azole substrates without requiring metal salts or additives. In contrast, dDCs exhibited diminished activity, likely due to their extended π-curvature. Computational studies, including NCI, ACID, and NICS analyses, revealed locally aromatic but electronically isolated π-systems and deshielded central 8-membered cores. This work highlights the utility of DC scaffolds as synthetically accessible and redox-tunable organic photocatalysts.

  • Access to Document (DOI)

• Enlarged-TriQuinoline (Enl-TQ): Disparity in Chemical Behaviors by Geometric Scaling of the Trimeric Quinoline Ring System

  Yamashita M., Tsutsumi R., Kobayashi T., Kumagai N.

  Chemistry an Asian Journal (Wiley)  20 ( 17 )  2025.09

  Research paper (scientific journal), Last author, Corresponding author,  ISSN  18614728

  　View Summary

  TriQuinoline (TQ), a quasi-planar cyclic quinoline trimer concatenated at the 2,8-positions in a head-to-tail arrangement, strongly captures a proton at the 12-membered inner cycle and exhibits unusual physicochemical properties, including unexpected water solubility and the ability to engage in complexation with other π-conjugated molecules. In this study, we designed and synthesized its expanded analog, coined Enlarged-TriQuinoline (Enl-TQ), in which three alkyne units are embedded between three quinoline units to acquire an expanded planar 18-membered ring system. DFT calculations and X-ray crystallographic analysis revealed its planar architecture with three inwardly facing pyridinic nitrogen atoms. Despite its structural similarity to TQ, Enl-TQ displayed distinct host capability and photophysical characteristics.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Porphyrin 2.0 : chemistry of warped-porphyrin

  Kumagai, Naoya

  科学研究費補助金研究成果報告書 2023

• Strategic molecular design aiming at streamlined chemical transformations

  Kumagai, Naoya

  科学研究費補助金研究成果報告書 2022

• Medicinal chemistry based on exotic water-soluble aromatic molecule TriQuinoline

  Kumagai, Naoya

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2022

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Author Correction: TriQuinoline (Nature Communications, (2019), 10, 1, (3820), 10.1038/s41467-019-11818-1)

  Adachi S., Shibasaki M., Kumagai N.

  Nature Communications (Nature Communications)  11 ( 1 )  2020.12

  　View Summary

  An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • Access to Document (DOI)

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• Revisiting C4N4: 蛍光発光メカニズムの計算化学的解明と重金属検出プローブへの応用

  公平実希、川村剛、原渕祐、前田理、熊谷直哉

  [Domestic presentation]  日本化学会第105春季年会, 

  2025.03

  , 

  Oral presentation (general)

• キナゾリンを構成要素とする酸素架橋型大環状オリゴマー群の合成と物理化学的特性

  竹内伶旺、 小林透威、熊谷直哉

  [Domestic presentation]  日本化学会第105春季年会, 

  2025.03

  , 

  Poster presentation

• 大環状3量体分子[HyD-Py]3の合成とカゴ型化合物への応用

  鶴岡航太朗、野崎雅人、工藤駿、熊谷直哉

  [Domestic presentation]  日本化学会第105春季年会, 

  2025.03

  , 

  Oral presentation (general)

• カルボン酸を基質とした触媒的還元的アミノ化反応の開発

  中村健人、堤亮祐、熊谷直哉

  [Domestic presentation]  日本薬学会第145年会, 

  2025.03

  , 

  Oral presentation (general)

• キノリンベースドカーボンナノリングの創製

  山下舞、小林透威、熊谷直哉

  [Domestic presentation]  日本薬学会第145年会, 

  2025.03

  , 

  Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• 軽元素分子触媒戦略によるアミド生産技術の刷新

  2024.12

  -

  2027.03

  科学技術振興機構（JST）, 研究成果最適展開支援プログラム（A-STEP）産学共同 ステージⅠ（育成フェーズ）, Joint research, Principal investigator

• Expeditious Sophistication of Seed Molecular Entities Aided by Theory and Machine Learning

  2023.04

  -

  2026.03

  学術変革領域研究(B), Principal investigator

• Diversification of Molecular Functions via Unique Molecular Design

  2023.04

  -

  2026.03

  基盤研究(B), Principal investigator

• Porphyrin 2.0: Chemistry of Warped-Porphyrin

  2022.06

  -

  2024.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, 挑戦的研究（萌芽）, Principal investigator

• Strategic Molecular Design Aiming at Streamlined Chemical Transformations

  2020.04

  -

  2023.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

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Awards 【 Display / hide 】

Awards 【 Display / hide 】

• Mukaiyama Award

  2023

  Type of Award： International academic award (Japan or overseas)

• Merck Banyu Lectureship Award（MBLA）

  2018

  Type of Award： International academic award (Japan or overseas)

• 三井化学触媒科学奨励賞

  2014

  Type of Award： International academic award (Japan or overseas)

• Thieme Chemistry Journal Award

  2013

  Type of Award： International academic award (Japan or overseas)

• 文部科学大臣表彰若手科学者賞

  2013

  Type of Award： International academic award (Japan or overseas)

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• STUDY OF MAJOR FIELD (MOLECULAR DESIGN)

  2026

• BACHELOR'S THESIS

  2026

• DRUG SYNTHESIS LABORATORY COURSE

  2026

• ADVANCED MEDICINAL AND ORGANIC CHEMISTRY

  2026

• MEDICINAL CHEMISTRY 2

  2026

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