京都大学化学研究所

令和元年度

国際共同利用・共同研究拠点 成果報告書
化学関連分野の深化・連携を基軸とする
先端・学際グローバル研究拠点

京都大学化学研究所

国際共同利用・共同研究拠点

化学関連分野の深化・連携を基軸とする
先端・学際グローバル研究拠点

令和元年度

成果報告書

令和元年度 共同利用・共同研究報告書 目次
１．共同研究成果報告
分野選択型共同研究
ビーム科学分野
Advanced functionality on materials induced by Intense THz pulse irradiation
2019-1※
Setsunan University Takeshi Nagashima
Ultra directional neutron beam generation by using laser driven x-ray and2019-2※
spin polarized deuterium target
Osaka University Yasunobu Arikawa
Research on the high-performance superconducting cavity and the cost2019-3※
reduction by noble inner-surface processes
KEK Takayuki Saeki
Study on magnification of the pulsed-neutron transmission image using the2019-4※
sextupole magnet, aimed at visualization of charge and discharge in theelectrode materials of Li-ion batteries
AIST Koichi Kino
鏡像体過剰率による金ナノワイヤーのらせん構造制御
2019-5
東京理科大学 河合 武司
Crystal structure analysis of GraE protein from root-nodule-forming bacterium2019-6
Kansai University Tadao Oikawa
マルチピコ秒の相対論的放射圧で駆動される臨界面の超高速運動の観測
2019-7
大阪大学 藤岡 慎介
プリパルス付与による高変換TNSA イオン加速2019-8
大阪大学
砂原 淳
レーザー吸収制御によるシリコンの微細加工に関する基礎研究
2019-9大阪産業大学 草場 光博
カーボンナノチューブを用いたISOL
用標的の開発2019-10
理化学研究所 大西 哲哉
Development of a fast and efficient neutron trigger device for electron-RI
2019-11
scattering experiments
RIKEN Akitomo Enokizono
化学反応の量子制御を目指したCEP安定化自由電子レーザのための省
2019-12電力型超伝導加速空洞の製作方法の高度化
量子科学技術研究開発機構 羽島 良一
グラファイト化薄膜テープ標的を用いたレーザー駆動イオン加速実験
2019-13
量子科学技術研究開発機構 近藤 康太郎
元素科学分野2019-14※ High pressure approach to the synthesis of novel ferroelectric
photovoltaic transition metal oxides
National Taiwan University Wei-tin Chen
2019-15※ Catalysis research of transition metal oxides
Ningbo Institute of Industrial Technology Haichuan Guo“Smallmolecule
activation
using
anionic crypto-FLPs”
2019-16※
University of Bonn Rainer Streubel
Developmentof
unsymmetrical
π-electron
systemsof heavier main group2019-17※elements and elucidation of their property
Tohoku University Takeaki Iwamoto※ 国際共同利用・共同研究

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2019-18※

Mechanistic studies of C–H bond functionalization reactions catalyzed by
3d transition metals
Nanyang Technological University Naohiko Yashikai
Development of iron-catalyzed strategies for diversity oriented synthesisof heterocycles and carbocycles

18

Visva-Bharati University Alakananda Hajra
Iron-catalyzed carbometalation of heterobicyclic alkenes: development ofasymmetric reactions and application to synthesis of polycyclic aromatichydrocarbons
Nanyang Technological University Shingo Ito
Open-cage fullerenes incorporating hydrogen as n-type composite
materials for polymer solar cell applications

19

National Chiao Tung University Shih-Ching Chuang
中赤外レーザー光源の開発とナノ物質科学への応用
東京大学 板谷 治郎
Study on the mechanism for the stability of an In-doped novel Fe-Pd phase
Meio Unibersity Yasutomi Tatetsu
ウルシオール金属錯体を構成要素とする新規機能性塗料の開発
京都市産業技術研究所
橘 洋一
Study on nickelate complexes constructed by a monoanionic tridentate
pincer-type ligand

21

Yokohama National University Yoshitaka Yamaguchi
アクリロニトリル系ポリマー末端ラジカルの反応機構研究とその合成応用
物質・材料研究機構 中村 泰之
高性能ペロブスカイト太陽電池作成を指向した高活性酸化スカベンジャーの開発
2019-27
名古屋市立大学 笹森 貴裕
ヘテロダイン干渉分光法を用いた鉛ペロブスカイト太陽電池の光電流の研究
2019-28
上越教育大学 小川 佳宏
バイオ情報学分野
2019-29※ Network analyses for data-driven exploration and hypothesis testing in
microbial ecology

25

CNRS UMR6004 Samuel Chaffron
Distribution of prasinoviruses and their association with natural hosts in
the global ocean

29

2019-30※

30

2019-31※CNRS UMR 7232 Nigel Grimsley
Integrating omics data and module-based network with deep learning todevelop cancer type predictive models
National Chiao Tung University Jinn-Moon Yang
Next-generation bioinformatics approaches for the accurate identificationof protease-specific substrate cleavage sites

31

2019-32※

Monash University Jiangning Song
Viral impacts on microbial ecosystems in the highly-enclosed inlet,
Uranouchi Bay, Kochi
Kochi University Kenzo Nagasaki
新規巨大ウイルスの単離とゲノム・トランスクリプトーム解析
東京理科大学 武村 政春
環境サンプルからの赤潮藻類の濃縮とその藻類に感染するウイルスの同定
京都大学 吉田 天士

32

2019-19※2019-20※

2019-21※2019-222019-232019-242019-25

20

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2019-26

2019-33

2019-34
2019-35※ 国際共同利用・共同研究

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2019-36

生物ネットワーク構造の局所構造変化の網羅的解析
36

岐阜大学 志賀 元紀
分子ネットワーク解析のための統計的機械学習法の開発と応用
帯広畜産大学 茅野 光範
Control and analysis of complex networks via minimum dominating sets
Toho University Jose C. Nacher

37

物質合成分野2019-39※ Application of s-tetrazines in guanidine functionalization of fullerenes
Rudjer Boskovic Institute Davor Margetic
2019-40※ Coupling of planar and curved π-systems for the development of novel
functional materials

39

2019-37
2019-38

2019-41※

2019-42
2019-43

2019-442019-45

2019-46

38

Max Planck Institute for Polymer Research Akimitsu Narita
Design, synthesis, and characterization of charge transport materials for
non-lead perovskite

40

Osaka University Akinori Saeki
新規π共役系ポリマーの開発と有機薄膜太陽電池への応用
広島大学
尾坂 格
Preparation of novel brunched block copolymer with well-controlledstereoregularity and evaluation of its molecular aggregation state

41

Osaka Institute of Technology Tomoyasu Hirai
キラルネマチック液晶のアンカリング挙動に関する研究
立命館大学 赤木 和夫
Molecular engineering of organic semiconductors toward the control of molecular
packing in thin films via a thermal precursor approach
Osaka University Mitsuharu suzuki
電子ドナー性アニオンと電子アクセプター性カチオンを連結したπ共役双性イオンの合成と物性
大阪大学 清水 章弘

43

42

44

45

46

現象解析分野2019-47※ The elemental and isotopic composition of particulate trace metals in thesubarctic Pacific Ocean: sources and internal cycling
Academia Sinica Tung-Yuan Ho
2019-48※

2019-49※

2019-50※

2019-51※
2019-52※
2019-53

98/95

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Application of δ
Mo and δ
W isotopes ratios for thereconstruction of late miocene oxygenation in the Arabian sea
Birbal Sahni Institute of Palaeosciences Gurumurthy Gundiga Puttojirao
Investigation on the decay process of hot carriers in heavily doped
semiconductor nanocrystals
University of Castilla-La Mancha Abderrazzak Douhal A.
Development of photocatalytic materials by quantitative charge carrier
dynamics and structural analysis
RMIT University Yasuhiro Tachibana
High frequency rheological and dielectric response of polymeric liquids
Yamagata University Sathish K. Sukumaran
Elongational rheology of telechelic-type ionomers
Changchun Institute of Applied Chemistry Quan Chen
都市大気エアロゾルの起源および発生メカニズム解明に関する研究
近畿大学
中口 譲

※ 国際共同利用・共同研究

－iii－

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2019-54

Study on transportation and separation of metal ions through a liquid
membrane using ionic liquid
Kyoto University of Education Hiroshi Mukai
Study on gelation behaviors of polymer oleogels
2019-55
Okayama University of Science Noboru Osaka
機能性配位子保護量子ドットの緩和過程の解明
2019-56
関西学院大学 玉井 尚登
新規部分フッ素化リン脂質分子群の膜物性・構造のキャラクタリゼーション
2019-57
群馬大学 園山 正史
スチレン系ブロック共重合体をベースとした非共有結合性エラストマーの2019-58
調製と力学特性名古屋大学 野呂 篤史
課題提案型共同研究
2019-59※ Regulatory network of gene expression for plant cell morphogenesis
Peking University Li-Jia Qu
2019-60※ Role of PX-PH-type phospholipase Ds in plant intracellular membrane traffic
University of Cambridge Yohei Ohashi
2019-61※ Site-selective protein acetylation by a small molecule
Fudan University Lu Zhou
2019-62※ Proteomic approach to discovering specific inhibitors for bile-acidinteracting enzymes
Peking University Xiaoguang Lei
2019-63※ Study of magnonic properties of ferrimagnets
KAIST Kab-Jin Kim
2019-64※ Development of highly efficient and stable blue organic light emitting diodes using
thermally activated delayed fluorescent materials as sensitizer

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60
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62
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Tsinghua University Dongdong Zhang
Highly efficient blue thermally activated delayed fluorescence emittersusing sterically hindered donor skeleton
Kyung Hee University Jang Hyuk Kwon
Structural analysis of organic amorphous thin films using solid effectdynamic nuclear polarization NMR
U.S. Department of Energy Takeshi Kobayashi
Memory of chirality using flow electrochemistry
Cardiff University Thomas Wirth
Creation of functional molecules based on hydrogen bond networks
University of Bristol Jonathan Clayden
Micro- and nano-structural characterization by advanced transmission
electron microscopy of novel functional materials for battery development

64

Chiang Mai University Torranin Chairuangsri
Structural and functional analysis of the surface components of bacterial
outer membrane vesicles

69

2019-70※

70

2019-71※

University of Naples Federico II Maria Michela Corsaro
Construction of low-temperature protein expression system by using coldadapted microorganisms
Southwest University Xianzhu Dai

71

Hiroshima University Kensuke Homma72

2019-65※

2019-66※

2019-67※
2019-68※
2019-69※

2019-72※

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Search for four-wave-mixing in the vacuum- Unveiling dark components in the Universe -※ 国際共同利用・共同研究－iv－2019-73※

2019-74※

2019-75※

2019-76※

2019-77※
2019-78※
2019-79※
2019-80※
2019-81※2019-82
2019-83
2019-84
2019-852019-86
2019-872019-882019-892019-90

2019-91

Development of biosensors by combining stimuli-responsive polymer
brushes with electrochemical analysis
South China University of Technology Ying Ma
Exploring new polyether nanocomposite electrolytes to enhance energy
storage of lithium ion batteriesMichigan State University Robert C. Ferrier, Jr.
Fluorinated polymer-brush-grafted nanoparticles: Precise synthesis andapplications to membrane technology
University of Montpellier Vincent Ladmiral

73

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Determine the three-dimensional structure of C labeled αsynuclein(61-95) in the Langmuir-Blodgett film and supported
phospholipids bilayers by p-MAIRS FT-IR
Middle Tennessee State University Chengshan Wang
Real-time imaging of single-molecule mRNA with different methylation states
Colorado State University Timothy J. Stasevich
Structural and functional analysis of curvature-inducing peptides
Karlsruhe Institute of Technology Anne S. Ulrich
Research of multi-qubit diamond quantum processors
Australian National University Marcus W. Doherty
Research on shallow NV center in diamond
Max-Planck Institute for Biophysical Chemistry Gopalakrishnan Balasubramanian
Effect of dipole alignment along chain backbone on dielectric relaxation of
type-A polymers at association/dissociation equilibrium
Sungkyunkwan University Youngdon Kwon
植物表皮細胞の分化における制御ネットワークの研究
広島大学 冨永 るみ
アシルドーパミンの新機能
東京薬科大学 伊藤 昭博
ビタミンＤの新機能の調節
東京農工大学 長澤 和夫
高スピン偏極電流源の開発のためのコバルトフェライト薄膜の磁気・電気的性質の評価名古屋工業大学 田中 雅章
Develop of the epitaxial thin film of Weyl semimetal Mn3Sn
Hokkaido University Taro Nagahama
Effect of microstructure on damping constant in polycrystalline Bi-YIG
thin films prepared by sol-gel method
Gifu University Keisuke Yamada
Giant isotope effects of deuterium atoms terminating on nanocrystalline
silicon and their use
Nagoya City University Takahiro Matsumoto
4-ピロリジン‐ピリジン型分子触媒による化学選択的アシル化反応の理論的解析
立教大学 山中 正浩
α-フッ素化アミノ酸を含む抗腫瘍性環状オクタデプシペプチドの合成と生物学的評価
岐阜薬科大学 永澤 秀子
Studies on total synthesis of gonytolides
Kanazawa University Tomoyuki Yoshimura※ 国際共同利用・共同研究

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2019-92

Analysis of the physiological functions of membrane vesicles produced byintestinal bacteria and fermented food-derived bacteria and their application

Kindai University Atsushi Kurata 92
Studies on the physiological significance of two alanine dehydrogenases in
2019-93
Geobacillus kaustophilus
Osaka Institute of Technology Taketo Ohmori 93
異常高原子価イオンを含む機能性酸化物合成とその構造物性研究
2019-94
高エネルギー加速器研究機構 齊藤 高志 94
溶媒含浸樹脂を用いた白金族元素抽出における界面活性剤の利用
2019-95
大阪府立大学工業高等専門学校 倉橋 健介 95
ポリマーブラシ付与強磁性ナノプレートの精密合成による強磁性フォトニッ
2019-96
ク液晶の実現大阪大学 内田 幸明 96
Additive Manufacturing による多孔性高分子複合材料の3 次元構造制御
2019-97
共立女子大学 村瀬 浩貴 97
Ferromagnetic single-electron transistor
2019-98
Tokyo Insitute of Technology Yutaka Majima 98
パーフルオロアルキル鎖とアミノ酸頭部基を有する新規な界面活性剤型
2019-99
防錆剤の探索千葉大学 山田 哲弘 99
2019-100 NanoBRET 型CXCR4 結合解析によるペプチドリガンド評価系の構築
広島大学
野村 渉 100
2019-101 がん深部到達型修飾膜透過ペプチドの創出と大腸がん幹細胞効率的除去への展開
富山大学 大橋 若奈 101
2019-102 ダイヤモンド表面近傍のNV 中心作製
金沢大学 徳田 規夫 102
ダイヤモンド中のNV
中心量子ビットの電気的制御と電気的検出
2019-103
産業技術総合研究所 牧野 俊晴 103
2019-104 シクロパラフェニレンの励起ダイナミクスの環サイズ依存性大阪大学
藤塚 守 104
2019-105 半屈曲性高分子溶液の非線形レオロジー
大阪大学 井上 正志 105
2019-106 Analysis of Soret effect for DNA in molecular-scale temperature gradientJapan Women's University Ryoko Shimada 106
連携・融合促進型共同研究
2019-107※ Fabrication of nanotopographical polymer surfaces with bactericidal properties
Stony Brook University Maya K. Endoh 107
2019-108※ Synthesis of structurally controlled polymers having green fluorescence
protein chromophore and their photophysical properties in solution
National Taiwan University Jye-Shane Yang 109
2019-109※ Vinyl azides as new monomers of radical polymerization for the fabricationof green polymers having chemically- and biodegradable properties
Nanyang Technological University Shunsuke Chiba 111
2019-110※ The 15th International workshop for East Asian Young Rheologists
Osaka University Tadashi Inoue 113
2019-111 第８回日本—中国有機化学シンポジウム
静岡県立大学 濱島 義隆 115※ 国際共同利用・共同研究－vi－2019-112

第26回酸化物エレクトロニクスに関する国際会議

大阪大学
施設・機器利用型共同研究
2019-113※ Atomic level analysis and fabrication of highly stable perovskite films andlight emitting diodes

松野 丈夫 117

Tsinghua University Juan Qiao 119
2019-114※ High-pressure synthesis of potential multiferroic oxides
University of Edinburgh J. Paul Attfield 120
Synthesis
andcharacterizationof
novel
organoselenium
and -tellurium compouds
2019-115※
Rikkyo University Mao Minoura 121
2019-116 核融合プラズマ対向材中の水素・ヘリウム挙動に関する電子分光学的研究
島根大学 宮本 光貴 122
2019-117 プラズモニック結晶上でのプラズモン-エキシトン結合
九州大学
斉藤 光 123
2019-118 完璧なπ共役二次元シートを持つフラットシリセンの設計
東北大学 高橋 まさえ 124
2019-119 Synthesis and structures of acene molecules bearing chalcogenopyrylium units
Fukuoka University Noriyoshi Nagahora 125
2019-120 Synthesis and structural characterization of divalent species of heavier
group 14 elements
2019-121

2019-122

Kindai University Tsukasa Matsuo 126
Elucidation of the fluorous interactions in the crystal structures of fluorine-containing
conjugated molecules by the single-crystal X-ray structural analysis
Ibaraki University Tomohiro Agou 127
生体組織由来のカルボニル化合物を標的とする高感度質量分析イメージング解析
奈良県立医科大学
秦野 修 128※ 国際共同利用・共同研究－vii－

２．国際学会、シンポジウム・研究報告会
国際会議
・9th Pacific Symposium on Radical Chemistry
・19th Annual International Workshop on Bioinformatics and Systems Biology

129
130

シンポジウム・研究会
・2019 年 日本分光学会年次講演会
・The 1st Germany–Japan–China Joint Workshop on Extremely Large π-Systems
・第 12 回台湾－日本機能性有機分子構築に関する二国間シンポジウム

132
133
135

137

３．成果発表論文（令和 2 年 2 月までに刊行された論文で、平成 22－30 年度の成果報告書に掲載されていないもの）

紙数の都合により、*を付けた論文のみについて、別刷りを本報告書に記載する。

*Reversible Isomerizations between 1,4-Digermabenzenes and 1,4-Digerma-Dewar-benzenes:
Air-stable Activators for Small Molecules, J. Am. Chem. Soc., 141, 2263–2267 (2019).
*Probabilistic controllability approach to metabolic fluxes in normal and cancer tissues, Nat.
Commun., 10, 2725 (2019).
The Formation of a 1,4-Disilabenzene and its Isomerization into a Disilabenzvalene Derivative,
Dalton Trans., 48, 9053–9056 (2019).
A Mixed-Anion System Consisting of a Germyl Anion and Anions Delocalized on Conjugated
Carbon Ring Skeletons, Chem. Eur. J., 25, 6284–6289 (2019).
Synthesis and Properties of Perfluoroalkylated TIPS-pentacenes, Tetrahedron, 75, 130678(2019).
Dibromometallyl-iron Complexes Generated by the Recombination of an Alumanyl-ironComplex with EBr (E = Al, Ga), Heteroat. Chem., 29, e21465 (2018).
Syntheses and Structures of Novel λ3,λ3-Phosphanylalumanes Fully Bearing Carbon
Substituents and Their Substituent Effects, Inorganics, 7, 132–143 (2019).
H2O/Olefinic-π Interaction inside a Carbon Nanocage, J. Am. Chem. Soc., 141, 12928–12938(2019).
Probing the Regioselectivity by Encapsulated H2: Diels-Alder Reaction of a Cage-Opened C60
Derivative with Anthracene, Chem. Eur. J., 25, 2482–2485 (2019).
pMAIRS Analysis on Chain-End Functionalization of Densely Grafted, Concentrated Polymer
Brushes, Macromolecules, 52, 6673–6682 (2019).
The Effect of Viscosity on the Diffusion and Termination Reaction of Organic Radical Pairs,
Chem. Eur. J., 25, 9846–9850 (2019).
Multifunctionalization of Cells with a Self-Assembling Molecule to Enhance Cell Engraftment,
ACS Chem. Biol., 14, 775–783 (2019).
Nutrient-Based Chemical Library as a Source of Energy Metabolism Modulators, ACS Chem.
Biol., 14, 1860–1865 (2019).
Synthetic Chemical Probes That Dissect Vitamin D Activities, ACS Chem. Biol., 14, 2851–2858(2019).

－viii－

Raman Optical Activity on Solid Sample: Identification of Atropisomers of Perfluoroalkyl
Chains Having a Helical Conformation and No Chiral Center, J. Phys. Chem. A, 18, 3985–3991(2019).
Determination of pH Dependent Structures of Thymol Blue Revealed by Cooperative
Analytical Method of Quantum Chemistry and Multivariate Analysis of Electronic Absorption
Spectra, Bull. Chem. Soc. Jpn., 92, 1759–1766 (2019).
Dielectric Relaxation of Type-A Chains Undergoing Head-to-Tail Association/Dissociation:
Difference from Head-to-Head Case and Correlation with Viscoelastic Relaxation,
Macromolecules, 52, 8484–8502 (2019).
Increased energy of THz waves from a cluster plasma by optimizing laser pulse duration, AIP
Adv., 9, [015134-1]–[015134-4] (2019).
Detection of alpha particles from 7Li(p,α)4He and 19F(p,α)16O reactions induced bylaser-accelerated protons using CR-39 with potassium hydroxide–ethanol–water etchingsolution., Rev. Sci. Instrum., 90, 83307 (2019).
Ablation suppression of a titanium surface interacting with a two-color double-pulse
femtosecond laser beam, Appl. Surf. Sci., 478, 882–886 (2019).
Dynamic Behavior of Helium Bubbles at High Temperature in Si Studied by in-situ TEM,
STEM-EELS and TDS, J. Appl. Phys., 126, [131504-1]–[135104-11] (2019).
Bulk Dzyaloshinskii–Moriya Interaction in Amorphous Ferrimagnetic Alloys, Nat. Mater., 18,
685–690 (2019).
Recognition Behavior of a Porphyrin Heterodimer Self-Assembled throughAmidinium-Carboxylate Salt Bridge, Asian J. Org. Chem., 7, 2087–2093 (2018).

anIron-Catalysed Enantioselective Suzuki–Miyaura Coupling of Racemic Alkyl Bromides, Chem.
Commun., 55, 1128–1131 (2019).
Iron-Catalyzed Cross Coupling of Aryl Chlorides with Alkyl Grignard Reagents: Synthetic
Scope and FeII/FeIV Mechanism Supported by X-ray Absorption Spectroscopy and Density
Functional Theory Calculations, Bull. Chem. Soc. Jpn., 92, 381–390 (2019).
Iron-catalyzed Alkyl–Alkyl Negishi Coupling of Organoaluminum Reagents, Chem. Lett., 48,
238–241 (2019).
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Reversible Isomerizations between 1,4-Digermabenzenes and 1,4Digerma-Dewar-benzenes: Air-Stable Activators for Small Molecules
Tomohiro Sugahara,† Jing-Dong Guo,†,‡ Daisuke Hashizume,§ Takahiro Sasamori,*,∥and Norihiro Tokitoh†,‡†Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
Integrated Research Consortium on Chemical Sciences, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan§RIKEN Center for Emergent Matter Science (CEMS), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan∥
Graduate School of Natural Sciences, Nagoya City University, Yamanohata 1, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8501,
Japan‡

S Supporting Information*

Chart 1. Potential Small-Molecule Activators Containing
Low-Coordinated Ge Atoms Such As Digermynes, 1,2Digermabenzenes, and 1,4-Digermabenzenes

ABSTRACT: The ﬁrst examples of stable, crystalline, andair-sensitive 1,4-digermabenzenes were isolated. These
species photochemically isomerize into the corresponding
air-stable digerma-Dewar-benzenes. More importantly,
alkyl-substituted Dewar-type-1,4-digermabenzenes can beconsidered as reversible “air-stable activators” for small
molecules such as dihydrogen, carbon dioxide, andacetylene at room temperature. The regeneration ofthese activators can be accomplished via a thermal retroisomerization that aﬀords the corresponding 1,4-digermabenzenes.

Classic aromatic compounds, i.e., [4n + 2]π-electron cyclic
conjugated systems such as benzene are widely known as
intriguing chemical species with unusual electric, magnetic, andoptical properties that have been applied to pharmaceuticals,organic electronic materials, and ﬂuorescence probes.1 In
contrast to the wealth of physical functionality of benzene, its
chemical functionality is relatively limited due to considerable
aromatic stabilization energy.2 However, replacing a C−H
moiety of benzene with a main-group moiety (group 13/15
elements) signiﬁcantly aﬀects the physical and chemical
properties of such cyclic-π-conjugated systems.3 Therefore, we
are interested in the replacement of C−H or HCCH moieties
with moieties that contain heavier group-14 elements (E−R or
RE = ER; E = Si, Ge, Sn, or Pb; R = organic substituent) in order
to control the physical and chemical properties of the resulting
metalla- and 1,2-dimetallabenzenes.4−7 Although the isolation of
the heavier-element analogues of benzene is diﬃcult due to theirextremely high propensity toward self-oligomerization and/or
valence-isomerization,4 kinetic stabilization can eﬀectively
permit the isolation of stable metalla- and 1,2-dimetallabenzenes(Chart 1).4−7
Although hitherto isolated 1,2-dimetallabenzenes exhibit
considerable aromaticity,6−8 they also show extremely highreactivity toward air, moisture, and alkynes. Accordingly, notonly the physical but also the chemical properties of metalla- and1,2-dimetallabenzenes should be of great interest. While
investigating the reactivity of the isolable digermyne,
TbbGe≡GeTbb (1; Tbb = 2,6-[CH(SiMe3)2]-4-tBu-phenyl),7© 2019 American Chemical Society

we observed that the reaction of 1 with acetylene resulted in the
predominant formation of 1,2-digermabenzene 2 together withsmall amounts of 9,10-digermabarrelene 3 (Scheme 1).7b The
mechanism for the formation of 1,2-dimetallabenzenes has been
investigated on the basis of theoretical calculations,6c,7b whereby
1,2-digermacyclobutadiene 4 was identiﬁed as a likely key
intermediate for the ﬁnal products (2 and 3). The Ge−C
Scheme 1. Synthesis and Potential Formation ofDigermabenzenes

Received: January 5, 2019
Published: February 1, 2019
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Communication

insertion of acetylene in 4, initiated by a ≡CH···Ge interaction,
was calculated to aﬀord 2 via a pathway with a slightly smaller
barrier relative to that of a GeGe insertion of acetylene in 4
triggered by the CC(π)···Ge interaction that gives 1,4digermabenzene 5, followed by a facile further [4 + 2]cycloaddition with acetylene to furnish 3. This proposedmechanism was experimentally corroborated by the isolation of
1,2-digermacyclobutadiene 6 from the reaction of 1 withtolan.7b,9 The aforementioned results of the theoretical
calculations led us to speculate that the insertion of alkynes in
the GeGe bond of 4 could be an appropriate synthetic route tounprecedented 1,4-digermabenzenes.10 While 1,2-dimetallabenzenes can be obtained from the reaction of stable dimetallynes11
with alkynes,6,7 1,3- and 1,4-dimetallabenzenes have not yet been
isolated.12,13 The generation of a 1,4-silabenzene from thephotochemical isomerization of a 1,4-disila-Dewar-benzene has
been reported.14 The intriguing nature of the transiently
generated 1,4-disilabenzene was demonstrated by, e.g., trappingwith butadiene and benzene. However, further investigations on
its chemical/physical properties, its aromaticity, and its behavior
in the activation of small molecules have not been carried out,
most likely due to the instability of the photogenerated species.15
Herein, we report the synthesis of stable 1,4-digermabenzenes,
their photochemical isomerization reactions, and their behavior
in the context of main-group-element-based activation of small
molecules.
Stirring a mixture of tolan and 1,2-digermacyclobutadiene 6,
which was generated by the reaction of digermyne 1 with tolan,
for 3 days in C6D6 at 60 °C quantitatively aﬀorded thecorresponding tetraphenyl-1,4-digermabenzene 7 (20% isolated
yield)16 (Scheme 2). The alkyl-substituted 1,4-digermabenzene

The structural parameters of isolated 1,4-digermabenzenes 7−
9 were unambiguously determined by single-crystal X-ray
diﬀraction analysis (Figure 1).17 1,4-Digermabenzenes 7−9

Figure 1. Molecular structures of 1,4-digerma-benzenes (a) 7, (b) 8, and(c) 9 (ORTEP drawings with thermal ellipsoids set to 50% probability;hydrogen atoms are omitted for clarity) together with selected bondlengths (Å; black), Ge−C4 bent angles (red), and angle sums around Ge(green).

Scheme 2. Synthesis of 1,4-Digermabenzenes 7−9

exhibit virtually planar [Ge2C4] rings, even though the Ge atoms
slightly protrude the C4 planes in a trans-pyramidalized fashion
including Ge−C4 angles of 4.0−9.0° (cf. Figure 1a). In addition,
both Ge atoms are partially pyramidalized in a transpyramidalized fashion, which is reﬂected in the bond angle
sums around the Ge atoms (ΣGe = 349−357°). 1,4Digermabenzenes 7 and 8 contain crystallographic centers of
symmetry at the center of the six-membered [Ge2C4] ring, which
would render a conclusion on the aromaticity based on thepresence of bond alternation in the ring skeleton ambiguous. In
the case of 9, which does not contain a crystallographic center ofsymmetry, the four Ge−C bond lengths [1.877(2), 1.878(2),1.882(2), 1.871(2) Å] in its [Ge2C4] ring are similar to eachother, suggesting a highly symmetric structure due to the cyclic
conjugation of π-electrons as in aromatic rings. In addition, theGe−C bond lengths fall in between typical values for Ge−C
single and double bonds18 and are comparable to those ofpreviously reported 1,2-digermabenzenes [1.883(2)−1.920(2)Å].7 The C−C bond lengths in the [Ge2C4] ring [1.410(3) and
1.391(3) Å] fall within the typical range of C−C bonds inbenzene rings. The structural features of 1,4-digermabenzenes 7
and 8 are very similar to those of 9, suggesting that their highly
symmetric structures should arise from the highly delocalized
cyclic conjugation of π-electrons and not from crystallographic
pseudodisorder. A combined consideration of the structuralparameters suggests that the 1,4-digermabenzenes contain six

8 was obtained directly from digermyne 1. Treatment of a C6D6
solution of digermyne 1 with an excess of 3-hexyne at room
temperature quantitatively aﬀorded 1,4-digermabenzene 8. All
attempts to isolate and/or observe the intermediate were
unsuccessful, most likely due to the facile formation of 8. Single
crystals of 7 and 8 (vide infra) exhibit a crystallographic center ofsymmetry. However, we could not draw meaningful conclusions
on whether the symmetry actually reﬂects the intrinsic electron
density or if it is due to pseudocrystallographic symmetry causedby the severe disorder in the crystals. In order to circumvent thisobstacle, unsymmetrically substituted 1,4-digermabenzene 9 wassynthesized in 16% isolated yield from the reaction of the isolated
1,2-digermacyclobutadiene 6 with an excess of 2-hexyne inhexane at room temperature.
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cyclic delocalized π-electrons on the [Ge2C4] rings, which isindicative of considerable aromaticity.
The structural features of 7−9, including the experimentallyobserved bent geometries, could be reproduced by theoreticalstructure optimizations at the TPSSTPSS-D3(BJ)/6-311G(2d,p) level of theory.19 The theoretically optimized structureof the parent 1,4-digermabenzene Ge2C4H6 (10) at the MP2/6311G(2d,p) or TPSSTPSS-D3(BJ)/6-311G(2d,p) level oftheory suggested completely planar geometries. Conversely, at
the CASSCF(6,6)/6-311G(2d,p) level of theory, bent structures
were obtained for 10 (Figure 2), suggesting that a partial open-

Scheme 3. Photoreactions of 1,4-Digermabenzenes 7−9

Dewar-benzenes, i.e., 11 is 6.9 kcal/mol more stable than 7,
and 12 is 2.2 kcal/mol less stable than 8.19 Since thethermodynamic energies of 9 and 13 are comparable, thethermal reaction of 13 would result in a partial conversion giving
9. It should be noted that 11−13 are inert toward air andmoisture for at least 2 weeks, even though 7−9 are highly air- andmoisture-sensitive.
The extremely high reactivity of 7−9 toward air/moisture
prompted us to examine their reactivity toward small inert
molecules such as acetylene, CO2, and H2 (Scheme 4).24,25

Figure 2. Frontier orbitals of parent 1,4-digerma-benzene 10 calculated
at the CASSCF(6,6)/6-311G(2d,p) level of theory.

Scheme 4. Reactions of 1,4-Digermabenzene 8 with Air,
Acetylene, CO2, and H2shell character of the 1,4-digermabenzenes should be crucial toexplain the bent structures. The corresponding diradicalcharacter values (y0 = 0.36) were calculated using the Yamaguchi
scheme.20 NICS(0) calculations21a for 7−9 furnished negative
NICS(0) values of −4.2, − 5.9, and −5.0, respectively, suggesting
lower levels of aromaticity relative to benzene (−8.3 at the samelevel of theory). Similarly, NICSzz(r) scan calculations21b
delivered NICSzz(1.4) = −13.5 (7), NICSzz(1.7) = −18.1 (8),and NICSzz(1.5) = −15.6 (9), indicating that the alkylsubstitution might expand the frontier π-orbitals in the 1,4digermabenzene ring relative to 10 (NICS(0) = −5.0;
NICS(1.4) = −17.3) based on the larger r values. The
NICS(0) and NICSzz(1.2) values for a planar geometry (D2h)of 10 were much more negative (−6.6 and −19.6, respectively)
than those for a bent structure; in other words, a bent geometry of
7−9 would partially reduce their aromaticity.
1,4-Digermabenzenes 7−9 are NMR active and give sharp
signals in their 1H and 13C NMR spectra, suggesting negligible
radical character in C6D6. The 13C NMR signals for the [Ge2C4]
rings of 7−9 were shifted to low ﬁeld [161.6−169.3 ppm], whichis indicative of a ring current eﬀect from the six π-electrons. The
UV−vis spectra of 7−9 in hexane showed characteristic strong
absorptions for their π−π* electron transitions (7, λmax(ε) = 442(10000) and 511 (8100); 8, 468 (16000); 9, 448 (2600)). Thus,
it seems feasible to conclude that 7−9 retain their cyclic systems
with six conjugated π-electrons in the crystalline state and in
solution. Notably, 7−9 are photoresponsive when n-hexane
solutions of 7−9 are exposed to LED light (410−490 nm).22 We
observed facile photochemical isomerizations, resulting in thequantitative formation of the corresponding 1,4-digerma-Dewarbenzenes 11−13 (Scheme 3).17,23 While the photochemical
isomerization of 7 into 11 was thermally irreversible, i.e., a retroconversion was not observed upon heating to 100 °C in toluene,
8 was regenerated quantitatively from heating 12 to 100 °C for 2
h in toluene. When a toluene solution of 13 was heated to 100 °C
for 24 h, 9 was regenerated in 55% yield (1H NMR yield). The
thermal conversion of 11−13 can be reasonably interpreted interms of the relative thermodynamic energies between thecorresponding 1,4-digermabenzenes and the 1,4-digerma-

Exposing 8 in C6D6 to air quantitatively aﬀorded oxidized 14.
When an n-hexane solution of 8 was exposed to acetylene (1atm), digermabarrelene 15 was quickly and quantitatively
formed via a [4 + 2]cycloaddition. Exposure of 8 in hexane toCO2 (1 atm) quantitatively furnished [4 + 2]cycloadduct 16.
Notably, the reaction of 8 with CO2 is reversible, i.e., heating a
C6D6 solution of 16 to 60 °C aﬀorded 8 via a retro-[4 +2]cycloaddition.26 Moreover, 8 activates H2 and cleaves the H−
H bond, even under moderate conditions, i.e., exposing an nhexane solution of 8 to H2 (1 atm, r.t., 30 min) aﬀorded the
reduced product 17. Upon considering the photochemical andchemical reactivity of 1,4-digermabenzene 8 in its entirety, wedeveloped the idea to activate H2 with an air-stable compound.
The reaction of air-stable 1,4-digerma-Dewar-benzene 12 withH2 (1 atm, 100 °C, toluene, 2 h) resulted in the quantitative
formation of hydrogen-adduct 17, which should most likely beinterpreted in terms of a thermal isomerization to giveintermediate 8, which can activate H2. Thus, 1,4-digermaDewar-benzene 12 can be considered as an air-stable main2265－139－

DOI: 10.1021/jacs.9b00129
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Chem. Soc. Jpn. 2016, 89, 1375−1384. (c) Sugahara, T.; Guo, J.-D.;
Sasamori, T.; Nagase, S.; Tokitoh, N. Regioselective Cyclotrimerizationof Terminal Alkynes Using a Digermyne. Angew. Chem., Int. Ed. 2018,57, 3499−3503.
(8) Baldridge, K. K.; Uzan, O.; Martin, J. M. L. The Silabenzenes:
Structure, Properties, and Aromaticity. Organometallics 2000, 19, 1477−
1487.
(9) Cui, C.; Olmstead, M. M.; Power, P. P. Reactivity of Ar‘GeGeAr‘(Ar‘ = C6H3-2,6-Dipp2, Dipp = C6H3-2,6-iPr2) toward Alkynes:

group-element-based activator for small molecules that can bethermally activated.
In summary, we have isolated the ﬁrst stable 1,4digermabenzenes (7−9), which exhibit central [Ge2C4] rings
with a cyclic conjugation of six π-electrons and indicate
considerable levels of aromaticity despite their nonplanar
structures. Compounds 7−9 are photoresponsive and easily
isomerize into 1,4-digerma-Dewar-benzenes 11−13 upon
exposure to visible light. In the case of alkyl-substituted 1,4digermabenzenes 12 and 13, their thermal retro-reaction
regenerates the 1,4-digermabenzenes. 1,4-Digermabenzene 8 isable to activate small molecules such as acetylene, CO2, and H2.
1,4-Digerma-Dewar-benzene 12 serves as a air-stable promoter
for H2 that can be thermally activated.

■

ASSOCIATED CONTENT

S Supporting Information*

The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.9b00129.
Experimental section and spectral data (PDF)
Theoretically optimized coordinates (XYZ)
Crystallographic data (CIF)■

AUTHOR INFORMATION

Corresponding Author*sasamori@nsc.nagoya-cu.ac.jp
ORCID

Tomohiro Sugahara: 0000-0002-7127-7571
Jing-Dong Guo: 0000-0002-3388-6181
Daisuke Hashizume: 0000-0001-7152-4408
Takahiro Sasamori: 0000-0001-5410-8488
Norihiro Tokitoh: 0000-0003-1083-7245
Notes

The authors declare no competing ﬁnancial interest.

■

ACKNOWLEDGMENTS
This work was supported by JSPS KAKENHI grants
JP15H03777 and JP15K13640 from MEXT (Japan), a Grantin-Aid for Research at Nagoya City University, the Collaborative
Research Program of the Institute for Chemical Research, Kyoto
University, and the DAIKO FOUNDATION, as well as JURC,IRCCS, and KURCA (Kyoto University). The authors are
grateful for the assistance of the Research Equipment Sharing
Center at Nagoya City University. T.S. gratefully acknowledges
support from a grant-in-aid for JSPS fellows (JP16J05501). The
authors would also like to thank Mr. Toshiaki Noda and Ms.
Hideko Natsume (Nagoya University) for the expert manufacturing of custom-tailored glassware.

■

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Reprinted from Nat. Commun., 10, 2725 (2019)with permission from Nature Publishing Group.

ARTICLEhttps://doi.org/10.1038/s41467-019-10616-z

OPEN

Probabilistic controllability approach to metabolic
ﬂuxes in normal and cancer tissues

1234567890():,;

Jean-Marc Schwartz

1, Hiroaki Otokuni2, Tatsuya Akutsu

3 & Jose C. Nacher

2

Recent research has shown that many types of cancers take control of speciﬁc metabolic
processes. We compiled metabolic networks corresponding to four healthy and cancer tissues, and analysed the healthy–cancer transition from the metabolic ﬂux change perspective.
We used a Probabilistic Minimum Dominating Set (PMDS) model, which identiﬁes a minimum set of nodes that act as driver nodes and control the entire network. The combination ofcontrol theory with ﬂux correlation analysis shows that ﬂux correlations substantially
increase in cancer states of breast, kidney and urothelial tissues, but not in lung. No change in
the network topology between healthy and cancer networks was observed, but PMDS analysis shows that cancer states require fewer controllers than their corresponding healthy
states. These results indicate that cancer metabolism is characterised by more streamlined
ﬂux distributions, which may be focused towards a reduced set of objectives and controlled
by fewer regulatory elements.

1 Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK. 2 Department of Information Science, Faculty of Science, Toho
University, Funabashi 274-8510, Japan. 3 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji 611-0011, Japan. Correspondence andrequests for materials should be addressed to J.-M.S. (email: jean-marc.schwartz@manchester.ac.uk) or to J.C.N. (email: nacher@is.sci.toho-u.ac.jp)

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Metabolic pathways are essential chemical processes thatcatalyse complex reactions indispensable for development and life. Recent research has shown that many
types of cancers take control of speciﬁc metabolic processes1. In
particular, cancer pathogenesis has recently been closely associated to serine, glycine and one-carbon metabolism2. Preclinicalanalyses have shown that by adopting a speciﬁc diet that limits
the amount of serine and glycine, tumour growth was severely
inhibited.
Understanding how metabolic networks are controlled is achallenging question though. Metabolic control analysis was
originally developed to evaluate how metabolic ﬂuxes depend on
kinetic parameters of enzymatic reactions or metabolite concentrations. The level of control is quantiﬁed by calculating
control or elasticity coefﬁcients3,4. However, these approaches are
not easily applicable to large systems since they rely on a kinetic
model of the metabolic pathways. More recently, an approach
was developed that uses ﬂux couplings between metabolic reactions5. Flux couplings identify constrained relations between
ﬂuxes of different reactions, which arise from the network
topology and mass conservation6. Five types of couplings wereidentiﬁed, namely directional, partial, full, anti and inhibitive
couplings. The networks were analysed using a minimum dominating set (MDS) approach to identify potential driver nodes
reactions5. The MDS approach was proposed by Nacher andAkutsu7 and has been used to analyse many biological systems
and identify proteins associated to cancer8–12. However, the ﬂux
coupling approach uses a discrete deﬁnition of coupling between
reactions and does not take into account the full range of possible
ﬂux distributions that the metabolic system is able to support. For
example, two reactions are deﬁned as anti-coupled if when one ofthem is inactive then the other carries a non-zero ﬂux (in a nonzero steady state), but this deﬁnition does not take into accountthe relation between both ﬂuxes in situations where both reactions are active.
Here, we argue that in order to investigate the distributed
control of metabolic ﬂux in large-scale metabolic networks, adifferent approach is needed. Coupling should be measured by acontinuous value characterising the relations between reaction
ﬂuxes over all feasible steady states, instead of a set of binary
values that represent particular subsets of steady states. In order
to distinguish this continuous measure from previously used
deﬁnitions of coupling, we hereon use the term correlation. Sucha measure already exists: as demonstrated by Poolman et al.13, it
can be obtained from the angles between the vectors forming an
orthonormal basis of the null-space (or kernel) of the stoichiometric matrix deﬁning the metabolic network. The cosine of thisangle precisely represents Pearson’s correlation coefﬁcient
between the ﬂuxes carried by a pair of reactions over all possible
steady states of the system, and was therefore named reaction
correlation coefﬁcient. Hence, the reaction correlation coefﬁcientϕij of a pair of reactions i and j is a continuous value comprised
between –1 and 1, where ϕij = 0 indicates that the ﬂuxes of bothreactions are completely independent, ϕij = 1 indicates that they
are perfectly correlated and ϕij = −1 indicates that they are perfectly anti-correlated.
In this work, we compiled metabolic networks corresponding
to four healthy and cancer tissues, namely breast, lung, kidney
and urothelial cancer. This data allows us to analyse thetransition from healthy to cancer states from the metabolic ﬂux
perspective (Fig. 1). We ﬁrst assembled a metabolic ﬂux correlation network obtained from biochemical metabolic pathways inhealthy and cancer tissues. Indeed, the above-mentioned ﬂux
correlation coefﬁcient can be interpreted as a failure probability,
which suggests that a probabilistic model can be suitable toaddress ﬂux control. For example, a positive correlation interaction with value 1 could be understood as an interaction with
failure probability of zero. Similarly, an absence of correlation
with value zero would suggest a failure probability of 1. These
concepts pave the way to the applicability of a probabilistic
control theory for complex metabolic networks. Here, we used a
Probabilistic Minimum Dominating Set (PMDS) model that canidentify a minimum set of nodes that act as driver nodes andcontrol the entire network in a context of probabilistic

Metabolic network
Stoichiometric matrix (S)
–1
1
1
0
0
0

B
R1
A

R2
C

R3

D

R4
E

R5

0
–1
1
0
0
0

0 –1
0
0
–1
0
1
0
0
1
0
0

Orthonormal kernel (K)

0
0
0
0
–1
1

K·KT = I

ij

Kj

F

Probabilistic minimum dominating set (PMDS)
R1

0.8

Flux correlations

R2

R1

–0.2

R2
0.0

0.8

–0.2

0.4
R5

PMDS
Θ = 0.5

Ki

S·KT = 0

0.9

0.6

R5

R3

–0.1

R3

1.0

0.0

R4

R4

Fig. 1 Method for the application of probabilistic control theory to metabolic ﬂux analysis. The stoichiometric matrix of the metabolic network is
constructed and used to compute the orthonormal kernel matrix. The reaction correlation coefﬁcient ϕij is the cosine of the angle between the reaction
rows in the kernel and represents the strength of control between both reactions. The failure probability ρij is deﬁned as 1−|ϕij|, which is used to determine
the probabilistic minimum dominating set. We require that each node (reaction) is covered by multiple nodes in PMDS so that the probability that at least
one edge (incoming ﬂux) is active is greater than the threshold Θ
2

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102

102

Breast healthy
Breast cancer

101
Frequency

Frequency

101
100
10–1
10–2
10–3
0.0

Lung healthy
Lung cancer

100
10–1
10–2

0.2

0.4

0.6

0.8

10–3
0.0

1.0

0.2

Correlation
102

0.8

1.0

Urothelial healthy
Urothelial cancer

101
Frequency

Frequency

0.6

102

Kidney healthy
Renal cancer

101
100
10–1

100
10–1
10–2

10–2
10–3
0.0

0.4

Correlation

0.2

0.4

0.6

0.8

1.0

10–3
0.0

0.2

Correlation

0.4

0.6

0.8

1.0

Correlation

Fig. 2 Probability distribution of reaction correlations. Probability distribution of reaction correlations in healthy (blue) and cancer (purple) states of fourhuman tissues

interaction failures14. In this network representation, the nodes
are interpreted as metabolic reactions and the weighted edges
correspond to the probabilistic ﬂux exchanged among reactions.
The application of PMDS in the context of metabolic ﬂuxes
makes it possible to connect controllability theory with ﬂux
correlations.
Results
Cancer metabolic reaction ﬂuxes show higher correlations.
Frequency distributions of all correlations in models of healthy
and cancer cells corresponding to four different tissues werecomputed and the results are shown in Fig. 2. In general, weobserved that the correlations are stronger in the cancer statethan the healthy state for breast, kidney and urothelial tissues.
However, for lung cancer the results show an opposite tendencywith a weaker correlation distribution for the cancer state.
Statistical analysis of genome-scale metabolic ﬂux networks.
The clustering degree in all networks shows, however, a similar
local structure (Table 1). This indicates that the differences
observed in cancer states are not due to changes in the network
structure, but to changes in the relations between ﬂuxes.
We also determined the degree distributions in all these
networks and found that they are similar and adhere to theclassical scale-free distribution observed in most biologicalnetworks, including metabolic networks (Fig. 3). It is interestingthat in spite of large metabolic ﬂux changes, the global statistical
pattern of the network remains conserved.
However, the speciﬁcity of lung cancer appears in the fractionof nodes connected to the giant connected component (Table 2
and Fig. 4). Breast, urothelial and renal cancers show larger giant
components than the corresponding healthy states. In contrast,
healthy lung tissue shows a larger giant component than the

Table 1 Topological properties of the complete metabolic
networks
Network
Breast healthy
Breast cancer
Lung healthy
Lung cancer
Kidney healthy
Renal cancer
Urothelial healthy
Urothelial cancer

Clustering coefﬁcient
0.780
0.766
0.772
0.771
0.770
0.764
0.780
0.769

Connected components
4
7
5
8
6
5
6
8

cancer state. This may imply a higher correlation between ﬂuxes
in the cancer state for 3 out of 4 cancer types.
Cancer states require fewer controllers except in lung cancer.
Based on the PMDS model described in the Methods section, we
computed the number of reactions necessary to achieve fullcontrol of each network in a probabilistic context of ﬂux correlations. We calculated the PMDS for each network using different
values of Θ (threshold probability). The results (Fig. 5) show thatthe fraction of driver nodes is smaller in all cancer tissues compared to their corresponding healthy states, suggesting that it may
be theoretically easier to control these cancer states. This change
is consistent with an increase in ﬂux correlations observed inthree out of four cancer states. In lung the PMDS fraction is still
smaller in the cancer state, even though the healthy state showshigher ﬂux correlations than the cancer state. The size of thelargest component is higher in the healthy state for lung, which
may explain the observed higher correlations.
To account for possible inaccuracies in the original models, we
veriﬁed that these results are stable with respect to small

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Breast healthy
100

100

10–1

Lung healthy

Urothelial healthy
100

10–1

10–1

10–1

10–2

10–2

10–2

10–2

10–3

10–3

10–3

10–3

10–4

1

10

100

10–4
1000 1

10

Breast cancer

100

100

10–4
1000
1

10

k

k

Pcum (k)Kidney healthy
100

10–4
1000
1

100

Renal cancer

100

10–1

10–1

10–1

10–2

10–2

10–2

10–2

10–3

10–3

10–3

10–3

1

10

100

10–4
1000
1

10

k

100

10–4
1000
1

k

b

10

100
k

0.5

100

1000

k

10–1

10–4

10

k

Lung cancer

100

100

10–4
1000
1

Urothelial cancer

10

100

1000

k

1.0

Breast healthy

Lung healthy

Kidney healthy

Urothelial healthy

Breast cancer

Lung cancer

Renal cancer

Urothelial cancer

Fig. 3 Topology of healthy and cancer networks. a Cumulative degree distributions of healthy and cancer high ﬂux correlation networks. b Visual
representation of high ﬂux correlation networks; the edge colour represents the ﬂux correlation ranging from 0.5 (red) to 1.0 (green)

Table 2 Properties of high ﬂux correlation networks inhealthy and cancer states of human tissues
Network

Total
network size

Size of giant
component

Breast healthy
Breast cancer
Lung healthy
Lung cancer
Kidney healthy
Renal cancer
Urothelial healthy
Urothelial cancer

3729
3741
3510
3350
3986
3444
3890
3618

611
1103
1091
598
711
677
660
1078

4

Fraction of
giant
component
0.164
0.295
0.311
0.179
0.178
0.197
0.170
0.298

alterations in the topologies of the four healthy andcancer networks. For each tissue type and for each value of Θ,
we constructed 10 randomised networks by rewiring 1%, 5%
and 10% of the edges, respectively. In order to conserve thetopological properties of the networks during randomisation,
we applied an edge rewiring algorithm that preserves thedegree distribution (see Methods). Even with a moderate
perturbation of 10%, the average PMDS fraction only marginally
increased and the PMDS fraction in the healthy state always
remained larger than in the corresponding cancer state(Supplementary Figs 1, 2 and 3).
Distribution of controllers in metabolic pathways. In order tocompare the controller and non-controller nodes from a perspective of biological signiﬁcance, we analysed the distribution of

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Giant component fraction

0.35
0.3
0.25
0.2
0.15
0.1
0.05
0
Breasthealthy

BreastcancerLung
healthyLungcancerKidneyhealthy

Renal Urothelial Urothelial
cancer healthy cancer

Fig. 4 Fraction of giant component in healthy and cancer tissues. In these networks, nodes represent reactions and two reactions are connected if theabsolute ﬂux correlation between them is higher than 0.5, as described in Methods. The giant component is the largest connected component in each
network; the fraction was calculated by dividing the number of nodes in the giant component through the total number of nodes in each network

0.6

0.6

PMDS fraction

a
0.5

b

0.5
Breast healthy

0.4

0.4

Lung healthy

0.3

0.3

Lung cancer

Breast cancer
0.2

0

0.2

0.6

0.4

0.8

1

0.2

0

0.2

0.4

θ
0.6

PMDS fraction

0.8

1

0.6

0.8

1

0.6

c

d
0.5

0.5

0.4

0.4

Kidney healthy

Urothelial healthy

0.3

0.3
Renal cancer
0.2

0.6
θ

0

0.2

Urothelial cancer

0.4

0.6

0.8

1

0.2

θ

0

0.2

0.4
θ

Fig. 5 Fraction of PMDS in healthy and cancer tissues. a–d The PMDS fraction in four healthy (blue) and cancer (red) tissues is displayed for different
values of the threshold Θ

PMDS and non-PMDS nodes among metabolic pathways fromthe KEGG database. Since we are using metabolic models, acomparison to metabolic pathways is more appropriate than for
example the Gene Ontology, which contains other types of biological functions not included in the data. We found that some
central metabolic pathways are enriched in PMDS nodes across
cancer and non-cancer networks: these pathways include glycolysis (p-values from 0.009 to 0.06; all p-values derived from twotailed Fisher exact tests) and pyruvate metabolism (p-values from0.003 to 0.06, except renal cancer p = 0.12). The citrate cycle issigniﬁcantly enriched in PMDS nodes in breast and renal
tissues (p-values from 0.01 to 0.05) but not in urothelial and lung;inositol phosphate metabolism was enriched in healthy breast(p = 0.03). Conversely, aminoacyl-tRNA biosynthesis was signiﬁcantly depleted in PMDS nodes in all cancer and non-cancer
networks (p-values from 3e−5 to 0.05), as well as N-glycan biosynthesis (p-values from 3e−5 to 0.03). Overall, the fact that ahigher proportion of controller nodes are found in central

metabolic pathways is consistent with expectations, since thesepathways distribute ﬂuxes towards other parts of the metabolic
network, and this property is maintained between healthy andcancer cells. Additionally, these results conﬁrm that each cancer
type has distinctive characteristics in terms of pathways enrichedin PMDS nodes, with lung cancer being more distinct than thethree other types.
Folate cycle subnetwork. There is growing evidence of relations
between metabolic perturbations and cancer. In particular,
serine and glycine pathways were found to be associated with
oncogenesis2. These amino acids feed into the folate cycle,
whose outputs feed into the synthesis of nucleotides andphospholipids. To illustrate how control analysis can shed lighton changes occurring in metabolic pathways, we show theresults obtained on a subnetwork centred on the folate cycle(Fig. 6).

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NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-10616-zaGlycineSerine
SHMT

GLDC

MeTHF

THF

TS

DHFR

Folic
acid

MS

MTHFR
mTHF

Healthy

Cancer

b

c
GLDC

SHMT

GLDC

SHMT

DHFR

DHFR

Breast

TS
TS
MS

MTHFR
MS

d

e
GLDC

SHMT

DHFR

GLDC

SHMT

DHFR

Kidney
TS

TS

MS

MS

f

g
GLDC

GLDC

SHMT

SHMT

DHFR

DHFR

Lung
TS

TS

MS

MTHFR

h

i
GLDC

SHMT

DHFR

GLDC

SHMT

DHFR

Urothelial
TS

TS

MS

0.5

MS

1.0

Fig. 6 Flux correlation changes in the folate cycle. a Simpliﬁed representation of the folate cycle. In this representation, nodes represent metabolites andedges represent metabolic reactions. b–i Reaction correlation coefﬁcients in the metabolic system depicted in A for four types of healthy and cancer
tissues. In these representations, nodes represent metabolic reactions and the edge colour represents the ﬂux correlation value between the reactions
connected by the edge; the colour bar represents the correlations value from red (0.5) to green (1.0). Abbreviations: THF, tetrahydrofolate; MeTHF, 5–10methylene-tetrahydrofolate; mTHF, 5-methyl-tetrahydrofolate; DHFR, dihydrofolate reductase; GLDC, glycine decarboxylase; MS, methionine synthase;
MTHFR, methylene-tetrahydrofolate reductase; SHMT, serine hydroxymethyl transferase; TS, thymidylate synthase

In the healthy states, we observe that SHMT and TS arestrongly coupled (Fig. 6b, d, f, h) indicating that the production of
THF is strongly coupled to its methylation into MeTHF. In
addition, there is a strong positive correlation between TS andDHFR, which means that THF production from folic acid is also
coupled to the THF cycle. In the cancer states though, these
correlations become weaker (Fig. 6c, e, g, i) and several newconnections appear. In breast and lung cancer, MTHFR becomesstrongly coupled to SHMT and MS, suggesting that the folate
cycle uses mTHF as an intermediate rather than directtransformation of MeTHF to THF. Overall, the cancer states
induce more ﬂux interactions between reactions of the THF
6system. This increases the complexity of the relations and at thesame time opens more possibilities to control the ﬂuxes in thesystem.
Discussion
Links between metabolism and cancer have been known for along time, as sustained aerobic glycolysis is well known to occur
in cancer cells15. How these changes are connected to cell proliferation and accumulation is not well understood though. It wasalso widely observed that obesity increases cancer risk, whichraises questions about the existence of causal links between

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increased metabolic activity and tumour progression. Conversely,
large animals with low metabolic rate are generally found to havelower incidence of cancer than smaller animals with fastermetabolic rate, which strengthens the view that metabolic activity
could be a factor favouring cancer, at least as important as
mutations16. Several oncogenes are known to stimulate metabolic
pathways, in particular glucose and glutamine metabolism17.
Alternative carbon sources such as acetate were found to be better
utilised by tumour cells than normal tissue18. Metabolic ﬂux
distributions in tumour cells were observed to correlate withincreased lactate production19 and to maintain levels of NADPH,
allowing cells to better resist to oxidative stress20,21.
Our results show that, in the four tissue types for which
comparative models of healthy and cancer metabolic networks
are available, namely breast, lung, kidney and urothelial, controllability in cancer metabolism is easier than that in healthy
metabolism. A generic interpretation of this result can be foundby combining knowledge from Fig. 3. The network visualizationshows signiﬁcant ﬂux correlation changes. However, the cumulative degree distribution shows that, in spite that many reactions
change ﬂux correlations, the global statistical degree pattern ofthe network does not change and still follows a power-law for the
degree of nodes. This is important technically because in general
the PMDS can be computed faster in networks that have a powerlaw distribution, i.e. scale-free networks. However, the new ﬂux
distribution in cancer state seems to be more highly correlated(lower failure probabilities) as shown in Fig. 2, which makes
cancer states easier to control from a PMDS view point since key
ﬂux routes have lower probability of failure. Indeed, these results
are based on comparative analyses of metabolic reconstructions ofcancer and healthy tissues and remain dependent on the qualityof the models used. Nevertheless, we veriﬁed that these results arepreserved under moderate alterations of the networks, and as thequality of metabolic models increases and new models become
available for other tissue types, these properties can be further
tested in the future. It is worth mentioning that other types ofanalyses not related to controllability may be able to identify
differences between cancer and healthy metabolism. For example
null-space analysis can characterise properties of genome-scale
metabolic networks based on stoichiometry alone13 and othertypes of constraints such as thermodynamics may be taken into
consideration.
Nevertheless, speciﬁc differences in metabolic ﬂux correlations
were observed in lung cancer. These differences were also
reﬂected in the number of reactions assembled in the main
connected component of the network. Heterogeneity in metabolic
pathway activity has been reported before, not only between
different types of cancers22 but also between different types oflung tumours23,24. In spite of the heterogeneous metabolic ﬂux
response observed in cancers and in particular a large ﬂuctuationof active correlations (i.e. number of links) among reactions inlung cancer, the number of necessary reactions to be controlled incancer does not largely change. More importantly, the metabolic
ﬂux space in cancer remains easier to control than that inhealthy state.
The number of active correlations in lung cancer is twice aslarge as that number in breast cancer. Counterintuitively, the
PMDS size of both lung and breast cancer is lower than that in
the corresponding healthy state. This indicates that the size of thereaction control backbone of both lung and breast cancer is very
similar. The increase in correlations observed in lung cancer,
consistent with the already reported variability on cancer metabolism, might only perform peripheral metabolic functions
without critical control roles. Glutamine metabolism is altered inmany types of cancer cells, but the consumption of glutamine
by lung cancer cells is higher than in other cancer types25.

The glutamine metabolic pathway is tightly interconnected withthe mTOR signalling pathway, which promotes cell survival andis activated by glutamine efﬂux; this particular feature is being
investigated for potential therapeutic applications26. The tyrosine
kinase epidermal growth factor receptor (EGFR) is frequently
mutated in non-small cell lung cancer and has strong interrelations to several metabolic pathways. It was shown that EGFR
signalling promotes not only glucose consumption and lactate
production, but also de novo pyrimidine synthesis, therefore it
plays a major regulatory role on global metabolism27. Different
KRAS mutations are also found in lung cancer, which do not havethe same cellular activity. It was shown that they affect different
metabolic pathways, with distinguishing effects in particular in
the glutaminolysis and glutathione pathways28. These examples
show that, in addition to strong metabolic effects shared withother types cancers such as aerobic glycolysis, lung cancers canalso be characterised by original relations with metabolic pathways. The full extent of these relations is still poorly understood
but is an active area of research towards new therapies25.
Methods
Computation of reaction correlation coefﬁcients. The computation starts byconstructing the stoichiometric matrix of the network, S, whose elements are thestoichiometric coefﬁcients of each metabolite in each reaction. The kernel matrix K
is deﬁned by vectors constituting a basis of the null-space of S, such that S KT = 0.
In most cases, K is not unique. However, if the vectors of K form an
orthonormal basis, which means K KT = I, then the angles θij between the row
vectors of K are invariant. The reaction correlation coefﬁcient ϕij is deﬁned as the
cosine of ϑij:
ki kTjffiffiffiffiffiffiffiffiffiffiffiffiffiffi ¼ cosðϑij Þ
ϕij ¼ rffiffiffiffiffiffiffiffiffiffiffiffiffi T
ki ki kj kTj

ð1Þ

where ki and kj are the row vectors of K corresponding to reactions i and jrespectively. As demonstrated in Poolman et al.13, ϕij represents the Pearson
correlation coefﬁcient between the ﬂuxes carried by reactions i and j over all
possible steady states of the system. The mathematical demonstration is based on
introducing a random matrix R that contains all possible steady states, s being thenumber of steady states which can be arbitrarily large. Then the Pearson
correlation r of this distribution is deﬁned, and when s tends towards inﬁnite it isshown that r tends towards a product of k vectors, which represents the cosine of
the angle.
We calculated K using the null function in Matlab and veriﬁed that it meets theorthonormality condition for each metabolic network. After obtaining ϕij for eachpair of reactions, the probability of failure between reactions i and j was deﬁned as
ρij = 1 − abs(ϕij).
Probabilistic control model. Natural and engineered complex networks arecomposed of thousands of nodes and tens of thousands of links. These links
representing regulatory interactions or transmission lines suffer from probabilistic
failures. The ﬂux correlation coefﬁcient allows us to deﬁne the probability of failure
between reactions i and j (ρij) and integrate it into a probabilistic control model.
We want each node (reaction) to be covered by multiple nodes in MDS so theprobability that at least one edge (incoming ﬂux) is active is at least Θ. This
problem can be formulated as a probabilistic minimum dominated (PMDS) as
follows. Let S be a dominating set, then we require S to satisfy:!
Yð2Þρij  Θ; 8j 2 V1
i2S

which can be rewritten as:

X
i2S

 
ln ρij  lnð1  ΘÞ

ð3Þwhere ρij indicates the probability of failure between reactions (i, j).
The standard MDS problem is formalized by the following integer linear
programmingP(ILP) problem:
xi
Minimisesubject to:

i2V

xi þ

X

ðj;iÞ2E

ð4Þ

xi 2 f0; 1g; 8i 2 V;

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where an MDS is obtained by the set fxjxi ¼ 1g; V indicates the set of reaction
nodes in the network and E denotes the set of undirected edges between reaction
nodes. Then, inserting the probabilistic condition shown in Eqs 2 into 3 leads to the
PMDS formalized
P as the following ILP:xi ;Minimise

6.
7.

i2V

subject to: xj  1; 8j 2 V such that degð jÞ ¼ 0;
X lnð1  ΘÞxj þlnðρij Þxi  lnð1  ΘÞ; 8j 2 V such that degð jÞ>0;ði;jÞ2E

ð5Þ

xi 2 f0; 1g; 8v 2 V
where deg(j) denotes the degree of reaction node j. In the above expression, theﬁrst term  lnð1  ΘÞxj is added because if node j is included in the PMDS, theinequality needs to be hold. In the implementation of the ILP-based method, asmall number (10−6) is added to ρij to avoid inﬁnity occurrence at ρij ¼ 0. The ILP
problem was solved using the IBM ILOG CPLEX Optimiser package version 12.0.

8.
9.
10.
11.
12.
13.

Construction of cancer networks. Genome-scale models representing humanmetabolic pathways in healthy and cancer states were compiled from Basler et al.5
and Gatto et al.29 Supplementary data. Then, ﬂux correlation networks wereconstructed by computing the reaction correlation coefﬁcients. To create healthy
and cancer networks a threshold of 0.5 was used, which means that absolutecorrelations smaller than 0.5 were deleted, or conversely that failure probabilities
higher than 0.5 were deleted; in the resulting networks, nodes represent reactions
and two reactions are connected if their correlation is higher than 0.5. This meansthat we are considering the high ﬂux correlation networks in our analysis.
Construction of randomised networks. For each tissue type and for each value ofΘ, we constructed 10 randomised networks by rewiring 1%, 5% and 10% of theedges, respectively. We used the rewire function from the R igraph package,
together with the keeping_degseq function that preserves the original network’s
degree distribution, in order to conserve the topological properties of the networks.
Pathway enrichment analysis. We analysed the distribution of PMDS and nonPMDS nodes across all metabolic pathways of the KEGG database in order todetermine whether some pathways are signiﬁcantly enriched or depleted in controller nodes. Enzyme Commission numbers associated to reactions were extracted
from the raw metabolic models, then were mapped to PMDS and non-PMDS node
lists in the same conditions as described above. These node lists were searchedagainst KEGG pathways using the KEGG Mapper tool30 in order to obtain thenumber of PMDS and non-PMDS nodes in each pathway, then two-tailed Fisher
exact tests were conducted using R in order to determine signiﬁcant enrichment ordepletion.
Reporting summary. Further information on research design is available in
the Nature Research Reporting Summary linked to this article.

14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.

Data availability
The models used in this study are available from https://doi.org/10.1101/gr.202648.115,
Supplemental Material section. Data that support the tables and ﬁgures of this study areavailable from the corresponding authors upon request.

27.
28.

Code availability
29.

Custom code used in this study is available from the corresponding authors uponrequest.

30.

Received: 8 June 2018 Accepted: 17 May 2019

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J.C.N. thanks the Royal Society for an International Exchange grant (IE160248). J.C.N.
was partially supported by JSPS KAKENHI Grant Number 18K11535. T.A. was partially
supported by JSPS KAKENHI Grant Number 18H04113. This research was also supported in part by Research Collaboration Projects of the Institute for Chemical Research,
Kyoto University.

Author contributions
J.M.S. and J.C.N. designed the study, performed the analysis and wrote the manuscript. J.M.S., H.O. and J.C.N. analysed the data. T.A. contributed to the theoretical
discussion and data analysis interpretation. All authors read and approved the ﬁnal
manuscript.

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Additional information
Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467019-10616-z.
Competing interests: The authors declare no competing interests.
Reprints and permission information is available online at http://npg.nature.com/
reprintsandpermissions/
Peer review information: Nature Communications thanks Jürgen Zanghellini andthe other anonymous reviewer(s) for their contribution to the peer review of this work.
Peer reviewer reports are available.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional afﬁliations.

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京都大学化学研究所
化学関連分野の深化・連携を基軸とする先端・学際グローバル研究拠点
令和元年度国際共同利用・共同研究公募要領
京都大学化学研究所は、「化学に関する特殊事項の学理及び応用の研究を掌る」ために、化学を中心とする分野で基礎研究に重点を置いた先端研究に邁進してまいりました。平成２２〜３０年度の期間には、文部科学大臣から国立大学共同利用・共同研究拠点としての認定を受け、化学研究所の活性を基盤とする「化学関連分野の深化・連携を基軸とする先端・学際研究拠点」として国内外の化学関連分野の研究者との共同利用・共同研究を推し進めてまいりました。この拠点活動におけるグローバル共同利用・共同研究が評価され、平成３０年化学研究所は文部科学省から国際共同利用・共同研究拠点に認定されました。これを受けて、令和元年度からの国際共同利用・共同研究拠点活動においては、多様でグローバルな化学分野の共同研究を一層強力に推進すべく、さらなる事業展開を図っております。
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この公募に当たりましては、分野選択型（計画研究型）、課題提案型、連携・融合促進型および施設・機器利用型の四つに分けて研究課題を募集いたします。これらの課題の実施に際しては当研究所の専任教員または客員教員との共同研究を基調といたしますが、いずれの課題でも後述の共通設備・機器・資料等のご利用が可能です。なお、各課題とも、海外研究者を研究代表者あるいは研究協力者とする国際共同研究（この場合、英語フォームで申請下さい）と、国内研究者を研究代表者とする国内共同研究を実施致します。これらの点も勘案いただき、本公募要領の詳細について十分ご確認の上、期日（平成３１年１月３１日）までにご申請下さいますようお願いいたします。
京都大学化学研究所長
辻井敬亘
共同研究ステーション長 寺西利治

1．研究期間１年間（平成３１年４月１日から令和２年３月３１日まで）。
2．研究課題分類
下記のような分類（型）ごとに研究課題を募集いたします。いずれの課題についても、分類ないし分野の担当者もしくは当研究所で対応する共同研究者にご一報の上、ご申請下さい。また、研究経費に関しては、
p.3 の表をご覧下さい。
2-1．分野選択型（計画研究型）研究課題
分野選択型（計画研究型）研究課題は、あらかじめ設定された分野に関して化学研究所内の研究者と共同で遂行する課題です。令和元年度は下記の５分野について課題を公募いたします。５分野を合わせて、萌芽的な課題と発展的な課題をそれぞれ２０件程度、採択の予定です。
ビーム科学分野（担当者：阪部 周二; sakabe@laser.kuicr.kyoto-u.ac.jp）
基本テーマ：先進量子ビームの開発と新奇診断分析手法の創出
趣旨：レーザー、X 線、電子線、イオンビームなどの量子ビームの高度化とその先端的診断分析法への応用を進めます。また、これらの量子ビームを複合的に用いて、極微細領域での超高速化学・物理現象の解明を目指します。
元素科学分野（担当者：中村 正治; masaharu@scl.kyoto-u.ac.jp）
基本テーマ：元素科学に基づく物質創製・機能創出
趣旨：元素の新たな特性を引き出し、この特性をもとに優れた機能を有する新物質を創製します。元素と社会との関わりを俯瞰した元素戦略研究も推進します。物質の機能は、構成元素の特性を相乗的に反映して発現します。この発現機構を明らかとし、望みの機能を意のままに創出することを目指します。

-1－151－

バイオ情報学分野（担当者：緒方 博之; ogata@kuicr.kyoto-u.ac.jp）
基本テーマ：バイオ情報を含む複合情報の融合解析
趣旨：ゲノムやメタゲノムに代表される最新バイオ情報に立脚して、バイオ情報がいかに生体内や自然環境における化学現象と関わっているかを明らかにし、生命システムについての化学的理解の深化を図ります。さらに、その成果を応用して、ゲノム創薬やパーソナライズド医療などへの展開も目指します。
物質合成分野（担当者：村田 靖次郎; yasujiro@scl.kyoto-u.ac.jp）
基本テーマ：複合機能材料の戦略的創製
趣旨：異種材料のハイブリッド化・複合化ならびにナノサイズ化に重点を置き、新規な機能をもつ新世代材料の創製を目指すとともに、生体の認識、応答、反応などの諸機能を担う例えば生体膜等も複合機能材料と捉え、機能物質と生命現象の化学的相関の解明も目指します。
現象解析分野（担当者：寺西 利治; teranisi@scl.kyoto-u.ac.jp）
基本テーマ：複合測定に基づく物質解析
趣旨：化学を基盤とする多種の分光学的手法・解析的手法を複合的に駆使して、天然および人工物質の構造・性質を分子レベルから巨視的レベルまで階層的に理解・記述することを目指し、一方、その結果を還元することによって新たな物質科学の枠組みを構築する取組みも目指します。
2-2．課題提案型研究課題（担当者：梶 弘典; kaji@scl.kyoto-u.ac.jp）
課題提案型研究課題は、前項１で設定した一つの分野に留まらない分野、あるいはそれ以外の分野について、化学関連分野の研究者から自由にご提案いただく課題です。萌芽的な課題と発展的な課題を、それぞれ２０件程度、採択の予定です。新分野の開拓につながるような課題を特に歓迎いたします。なお、緊急性・重要性が極めて高いと判断した課題については、前記の応募期日にかかわらず、直ちに採択することもあります。
2-3．連携・融合促進型研究課題（担当者：渡辺 宏; hiroshi@scl.kyoto-u.ac.jp）
連携・融合促進型研究課題は、化学関連分野における国内外の研究連携の強化を主目的とする共同研究課
題 で す 。 国 外 も 念 頭 に 置 く 場 合 は 、 化 学 研 究 所 の 部 局 間 国 際 学 術 交 流 締 結 先 (http://www.kuicr.
kyoto-u.ac.jp/sites/international_exchange/agreement/ 参照)との共同研究を開始する場を求めていただくことも可能です。また、この目的に沿った研究集会の開催も本課題として応募いただけます。５件程度を採択する予定です。
2-4．施設・機器利用型研究課題（担当者：倉田 博基; kurata@eels.kuicr.kyoto-u.ac.jp）
施 設 ・ 機 器 利 用 型 研 究 課 題 は 、 http://www.kuicr.kyoto-u.ac.jp/sites/research_activities/joint_
research/kaken_kyodo_instr/(拠点ホームページ)に記載の共通設備・機器・資料等の利用を主とする共同研究課題です。１５件程度を採択する予定です。

-2－152－

令和元年度国際共同利用・共同研究経費概算値

経費上限／件*（千円）

国際共同研究国内共同研究分野選択型萌芽的研究

1,000

800

分野選択型発展的研究

2,000

1,500

課題提案型萌芽的研究

1,000

800

課題提案型発展的研究

2,000

1,500

連携・融合促進型研究

1,000

800

施設・機器利用型研究

1,000

800

*表中の金額は目安です。予算の状況に応じた減額もありえますことをご了解下さい。
経費内での備品費、消耗品費、旅費の配分は、申請者と化学研究所の共同研究者が協議して決定下さい。特に、旅費については、地域性を勘案してご決定下さい。

3．共同研究応募方法
3-1．申請資格
国公私立大学、国公私立研究機関、独立行政法人等の専任研究者、または、これに準ずる者。
3-2．申請書記入要領
申請に当たっては、該当する募集分類・分野の担当者もしくは当研究所で対応する共同研究者と、事前に研究課題、研究内容、研究経費に関して、必ずご協議下さい。対応する共同研究者は、当研究所の専任教員
または令和元年度客員教員からお選び下さい。なお、教員のリストは下記の化学研究所ホームページをご参照下さい。
教員リスト http://www.kuicr.kyoto-u.ac.jp/sites/research_activities/chemist/
また、対応する共同研究者をお決めになれない場合は、各分類・分野の担当者に、まず、ご相談ください。
上記の表の経費上限は目安です。特に、経費内での備品費、消耗品費、旅費の配分については、当研究所で対応する共同研究者と十分にご協議の上で申請下さい。特に、旅費については、地域性を勘案してご申請下さい。
課題申請は、本要領に添付の分野選択型共同利用・共同研究申請書（様式１）、課題提案型共同利用・共同
研究申請書（様式２）、連携・融合促進型共同利用・共同研究申請書（様式３）、施設・機器利用型共同利用・共同研究申請書（様式４）に必要事項を記入し、下記の要領で、化学研究所共同研究推進室にご提出下さい。
なお、各課題とも、海外研究者を研究代表者あるいは研究協力者とする国際共同研究も実施可能です。この場合、英語フォーム（Forms 1~4）の左肩の欄にチェックを入れて、ご申請下さい。
<記入上の注意事項>
1. ※を付した事項は当研究所で記入します。
2. 当研究所で対応する共同研究者は必ずご記入下さい。
3. 申請者（研究代表者）と共同研究者の役割分担を明記して下さい。事前に共同研究者の承諾を得ていただくことが必要です。
3-3．提出期限および提出先応募に当たっては、前記の申請書にご記入の上、平成３１年１月３１（木）までに、下記宛に電子メール
添付書類（Word 書類）としてお送り下さい。
書類提出先および問い合わせ先
京都大学化学研究所共同研究推進室 国際共同利用・共同研究係
E-mail: icr-hub@scl.kyoto-u.ac.jp，電話: (0774)38-3121-3－153－

4．課題選考と採択通知
応募課題の採否は、当研究所の共同研究委員会で審査し、運営評議会の承認を経て決定されます。審査に際しては、共同研究の申請内容だけでなく、予算枠や、共通設備・機器・資料の使用時間等も考慮いたします。採否の結果（内定）については、平成３１年３月に当研究所の所長から研究代表者に通知いたします。
5．研究の実施および研究成果報告
5-1．研究経費等
研究代表者と当研究所で対応する共同研究者には、予算の範囲内で、研究経費（備品費および消耗品費）と旅費が支給されます。また、研究協力者（学生も含めることが可能です*）にも予算の範囲内で旅費が支給されます。共同研究の実施に当たっては、まず対応する共同研究者にご連絡下さい。なお、当研究所には、共同研究者のための宿泊施設はありません。
＊研究協力者について、学生の場合は原則として大学院生といたします。なお、傷害保険等に加入していることが必要です。
5-2．研究成果報告採択された研究課題については、研究成果報告書を次に記す作成要領に従って記載・提出していただきます。その報告書は、まとめて当研究所の国際共同利用・共同研究報告書集として公開させていただく予定です。また、その内容を研究成果報告会でご報告いただくことがあります。なお、報告会についての詳細は、採択課題の研究代表者に後日お知らせいたします。
5-3．研究成果報告書の作成要領
分野選択型研究、課題提案型研究、施設・機器利用型研究については１頁、連携・融合促進型研究については２頁の報告書を（様式５）を用いて作成下さい。Ａ４版の用紙には１頁あたり１，２００字程度が記載できます。図表などカラーを用いても構いませんが、報告書集刊行の際はモノクロ印刷になることもありますので、その点をお含み置き下さい。
１頁の１行目の中央に研究課題名、３行目に右詰めで研究代表者の氏名と所属、５行目から本文を記載して下さい。なお、当研究所で対応した共同研究者は報告書の共著者とはせず、必要に応じて本文中に明記して下さい。また、国際共同研究の場合、報告書は必ず英文でご作成ください。
5-4．報告書の内容
形式は自由ですが、例えば、実験的研究では、目的、実験方法、実験結果、考察、成果報告（論文、学会発表等）をお書き下さい。なお、連携・融合促進型研究で研究集会を開催した場合には、研究集会のプログ
ラム、参加者名簿（所属機関・部局・職名を明記）、および、作成された場合は要旨集またはプロシーディン
グスを添付して下さい。
5-5．報告書の提出
提出締切日は、令和２年２月末日とします。電子ファイル（PDF ファイル）を、下記へ電子メール添付書類としてお送り下さい。なお、添付ファイル名は「課題番号＋代表者名（姓）」として下さい（例：2019-1
田中.doc、2019-1 田中.pdf）。
報告書提出先京都大学化学研究所共同研究推進室 国際共同利用・共同研究係
E-mail: icr-hub@scl.kyoto-u.ac.jp，電話: (0774)38-3121
5-6．研究成果の公開
学術論文などによる研究成果の公開に際しては、京都大学化学研究所の国際共同利用・共同研究として行われたことを明記して下さい。英文での謝辞例を次に示します。
謝辞例: This work was supported by the International Collaborative Research Program of Institute for
Chemical Research, Kyoto University (grant # XXXX).
日本語での謝辞は、この英文表記に準ずるものとして下さい。

-4－154－

－155－

岩下 芳久

岩下 芳久

Accelerator division VI, KEK

Research Institute for Measurement and Analytical
Instrumentation, Advanced Industrial Science andTechnology (AIST)

東京理科大学･工学部

関西大学･化学生命工学部

大阪大学･レーザー科学研究所

2019-3 Takayuki Saeki

2019-4 Koichi Kino

2019-5 河合 武司

2019-6 老川 典夫

2019-7 藤岡 慎介

橋田 昌樹

島川 祐一

島川 祐一

大阪産業大学･工学部･電子情報通信工学科

理化学研究所･仁科加速器科学研究センター

理化学研究所･仁科加速器科学研究センター

量子科学技術研究開発機構

量子科学技術研究開発機構 関西光科学研究所

Center for Condensed Matter Sciences, National
Taiwan University

Ningbo Institute of Industrial Technology (CNITECH)of the Chinese Academy of Sciences

Institute for Inorganic Chemistry, University of Bonn

2019-9 草場 光博

2019-10 大西 哲哉

2019-11 榎園 昭智

2019-12 羽島 良一

2019-13 近藤 康太郎

2019-14 Wei-Tin Chen

2019-15 Haichuan Guo

2019-16 Rainer Streubel

時任 宜博

岩下 芳久

若杉 昌徳

若杉 昌徳

橋田 昌樹

大阪大学･レーザー科学研究所

2019-8 砂原 淳

井上 俊介

井上 俊介

藤井 知実

倉田 博基

井上 俊介

Institute of Laser Engineering, Osaka University

橋田 昌樹

化研内
研究協力者

2019-2 Yasunobu Arikawa

研究代表者所属

Faculty of Science and Engineering, Setsunan
University

研究代表者

2019-1 Takeshi Nagashima

課題番号

型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

化学研究所共同利用・共同研究拠点令和元年度採択課題（応募179件、採択 122件）

リチウムイオン二次電池の電極材内の充放電反応可視化を目的とした、六極磁石によるパルス中性子透過イメージ拡大の研究

Research on the high-performance superconducting cavity and the cost reduction by noble inner-surface processes

超電導空洞の内面処理による高性能化とコスト削減の研究

Ultra directional neutron beam generation by using laser driven x-ray and spin polarized deuterium target

レーザー駆動X線とスピン偏極重水素標的による超高指向性中性子ビームの発生

Advanced functionality on materials induced by Intense THz pulse irradiation

高輝度テラヘルツ波パルスによる材料表面への新規機能性付与

課題名（和文・英文）

2 発展的 国際

2 萌芽的 国際

2 発展的 国際

1 萌芽的

1 発展的

1 発展的

1 萌芽的

1 発展的

1 発展的

1 萌芽的

1 発展的

1 発展的

“Small molecule activation using anionic crypto-FLPs”「新規なアニオン性FLP を用いた小分子活性化」

Catalysis research of transition metal oxides

遷移金属酸化物における触媒性能研究

High pressure approach to the synthesis of novel ferroelectric photovoltaic transition metal oxides

Laser driven ion acceleration experiment using carbonized thin tape target

グラファイト化薄膜テープ標的を用いたレーザー駆動イオン加速実験

Optimization of fabrication process of a superconducting electron accelerating cavity operated by small electricity power for a
CEP-stabilized free-electron laser

化学反応の量子制御を目指したCEP安定化自由電子レーザのための省電力型超伝導加速空洞の製作方法の高度化

Development of a fast and efficient neutron trigger device for electron-RI scattering experiments

RI超前方電子散乱実験のための高速・高感度中性子トリガー検出器の開発

Development of new target material using CNT

カーボンナノチューブを用いたISOL 用標的の開発

Fundamental study on micro-fabrication of Si with controlling laser absorption

レーザー吸収制御によるシリコンの微細加工に関する基礎研究

Enhanced production of fast ions by TNSA with pre-pulse Laser

プリパルス付与による高変換TNSA イオン加速

Probing ultrafast motion of critical surface pushed by multi-pico-second relativistic radiation pressure

マルチピコ秒の相対論的放射圧で駆動される臨界面の超高速運動の観測

Crystal structure analysis of GraE protein from root-nodule-forming bacterium

根粒菌由来GraE タンパク質の結晶構造解析

Controlling chiral structure of Au nanowires by enantiomeric excess

鏡像体過剰率による金ナノワイヤーのらせん構造制御

and discharge in the electrode materials of Li-ion batteries

1 発展的 国際 Study on magnification of the pulsed-neutron transmission image using the sextupole magnet, aimed at visualization of charge

1 発展的 国際

1 萌芽的 国際

1 発展的 国際

選択 実施
国際
分野 状況

－156－

中村 正治

中村 正治

Department of Chemistry, Visva-Bharati University

School of Physical and Mathematical Sciences,
Nanyang Technological University

Department of Applied Chemistry, National Chiao Tung
村田 靖次郎 分野選択型
University

東京大学･物性研究所

名桜大学･リベラルアーツ機構

京都市産業技術研究所 高分子系チーム

2019-18 Naohiko Yoshikai

2019-19 Alakananda Hajra

2019-20 Shingo Ito

2019-21 Shih-Ching Chuang

2019-22 板谷 治郎

2019-23 立津 慶幸

2019-24 橘 洋一

遠藤 寿

阿久津 達也 分野選択型

名古屋市立大学･大学院システム自然科学研究科

上越教育大学･学校教育研究科

CNRS UMR6004

Sorbonne University

Department of Biological Science andTechnology/Institute of Bioinformatics & Systems
Biology, National Chiao Tung University

Biomedicine Discovery Institute, Monash University

高知大学･農林海洋科学部

2019-27 笹森 貴裕

2019-28 小川 佳宏

2019-29 Samuel Chaffron

2019-30 Nigel Grimsley2019-31 Jinn-Moon Yang

2019-32 Jiangning Song

2019-33 長崎 慶三

分野選択型

分野選択型

遠藤 寿

分野選択型

阿久津 達也 分野選択型

分野選択型

Blanc-Mathie分野選択型

金光 義彦

若宮 淳志

分野選択型

物質・材料研究機構･統合型材料開発･情報基盤部門

2019-26 中村 泰之

山子 茂

横浜国立大学･大学院工学研究院

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

2019-25 山口 佳隆

中村 正治

中村 正治

寺西 利治

金光 義彦

分野選択型

Division of Chemistry and Biological Chemistry, Schoolof Physical and Mathematical Sciences, Nanyang
中村 正治
Technological University
分野選択型

分野選択型

時任 宜博

Department of Chemistry, Tohoku University

2019-17 Takeaki Iwamoto

ヘテロビシクロアルケンの鉄触媒カルボメタル化：不斉反応の開発と多環芳香族炭化水素合成への応用

Development of iron-catalyzed strategies for diversity oriented synthesis of heterocycles and carbocycles

Mechanistic studies of C–H bond functionalization reactions catalyzed by 3d transition metals

3d 金属触媒によるC–H 結合変換反応の反応機構研究

Development of unsymmetrical π-electron systems of heavier main group elements and elucidation of their property

非対称型高周期典型元素π電子系の開拓と物性解明

3 萌芽的

3 発展的 国際

3 発展的 国際

3 萌芽的 国際

3 萌芽的 国際

2 萌芽的

2 発展的

2 発展的

2 発展的

2 萌芽的

2 萌芽的

2 萌芽的

2 萌芽的 国際

Viral impacts on microbial ecosystems in the highly-enclosed inlet, Uranouchi Bay, Kochi

赤潮頻発性閉鎖海域の微生物生態系にウイルスが及ぼす影響の解明

Next-generation bioinformatics approaches for the accurate identification of protease-specific substrate cleavage sites

タンパク質分解酵素による切断部位の高精度予測のための次世代バイオインフォマティスクス技術

Integrating omics data and module-based network with deep learning to develop cancer type predictive models

深層学習を用いたオミクスデータとモジュールに基づくネットワークデータの統合解析による腫瘍細胞分類

Distribution of prasinoviruses and their association with natural hosts in the global ocean

全球海洋におけるプラシノウイルスの分布および宿主予測に関する研究

Network analyses for data-driven exploration and hypothesis testing in microbial ecology

微生物生態学におけるデータ駆動型探索と仮説検証のためのネットワーク解析の利用

Photocurrent of Pb perovskite solar cells by heterodyne interference spectroscopy

ヘテロダイン干渉分光法を用いた鉛ペロブスカイト太陽電池の光電流の研究

Creation of effective oxidation scavenger for efficient perovskite-based solar cells

高性能ペロブスカイト太陽電池作成を指向した高活性酸化スカベンジャーの開発

Mechanistic and synthetic studies of poly((meth)acrylonitrile) chain end radicals

アクリロニトリル系ポリマー末端ラジカルの反応機構研究とその合成応用

Study on nickelate complexes constructed by a monoanionic tridentate pincer-type ligand

モノアニオン性3座ピンサー型配位子を有するニッケラート錯体の研究

Development of the novel functional paint using metallic urushiol complexes

ウルシオール金属錯体を構成要素とする新規機能性塗料の開発

Study on the mechanism for the stability of an In-doped novel Fe-Pd phase

微量In 元素添加型新奇Fe-Pd 相の安定機構に関する研究

Development of mid-infrared laser and applications to nano-material sciences

中赤外レーザー光源の開発とナノ物質科学への応用

Open-cage fullerenes incorporating hydrogen as n-type composite materials for polymer solar cell applications

高分子太陽電池応用のためのn 型複合材料としての水素を組み込んだ開放かご型フラーレン

polycyclic aromatic hydrocarbons

2 萌芽的 国際 Iron-catalyzed carbometalation of heterobicyclic alkenes: development of asymmetric reactions and application to synthesis of

2 萌芽的 国際

2 発展的 国際

2 発展的 国際

－157－

村田 靖次郎 分野選択型

分野選択型

馬見塚 拓

阿久津 達也 分野選択型

分野選択型

馬見塚 拓

廣瀨 崇至

若宮 淳志

廣瀨 崇至

岐阜大学･工学部･電気電子･情報工学学科

帯広畜産大学･グローバルアグロメディシン研究セン
ター

東邦大学･理学部･情報科学科

Division of organic chemistry and biochemistry,
Laboratory for physical organic chemistry

Max Planck Institute for Polymer Research

Department of Applied Chemistry, Graduate School ofEngineering, Osaka University

広島大学･大学院工学研究科

大阪工業大学･応用化学科

立命館大学･総合科学技術研究機構

大阪大学･工学研究科

大阪大学･大学院基礎工学研究科

Research Center for Environmental Changes, Academia
宗林 由樹
Sinica2019-37 茅野 光範

2019-38 ホセ ナチェル

2019-39 Davor Margetic

2019-40 Akimitsu Narita

2019-41 Akinori Saeki

2019-42 尾坂 格

2019-43 平井 智康

2019-44 赤木 和夫

2019-45 鈴木 充朗

2019-46 清水 章弘

2019-47 Tung-Yuan Ho

分野選択型

分野選択型

分野選択型

宗林 由樹

坂本 雅典

寺西 利治

渡辺 宏

Geochemistry Research lab, Birbal Sahni Institute of
2019-48 Gurumurthy Gundiga Puttojirao
Palaeosciences

Physical Chemistry, University of Castilla-La Mancha(UCLM, Spain)

School of Engineering, RMIT University

Graduate School of Organic Materials Science,
Yamagata University

2019-49 Abderrazzak Douhal A

2019-50 Yasuhiro Tachibana

2019-51 Sathish K. Sukumaran

分野選択型

分野選択型

分野選択型

分野選択型

村田 靖次郎 分野選択型

辻井 敬亘

竹中 幹人

脇岡 正幸

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

2019-36 志賀 元紀

緒方 博之

京都大学･大学院農学研究科･応用生物科学専攻

分野選択型

2019-35 吉田 天士

緒方 博之

東京理科大学･理学部

2019-34 武村 政春

5 発展的 国際

5 発展的 国際

5 萌芽的 国際

5 萌芽的 国際

5 発展的 国際

4 発展的

4 発展的

4 萌芽的

4 萌芽的

4 発展的

4 発展的 国際

4 発展的 国際

4 萌芽的 国際

3 萌芽的

3 発展的

3 萌芽的

3 萌芽的

3 萌芽的

Mo and δ

186/184

186/184

Mo および δ

W 同位体比の応用
W isotopes ratios for the reconstruction of late miocene oxygenation in the Arabian sea

98/95

High frequency rheological and dielectric response of polymeric liquids

高分子液体の高周波レオロジーおよび誘電応答

Development of photocatalytic materials by quantitative charge carrier dynamics and structural analysis

キャリアダイナミクスと構造の定量的解析による光触媒材料の開発

Investigation on the decay process of hot carriers in heavily doped semiconductor nanocrystals

ヘビードープ半導体ナノ粒子における熱キャリアの緩和過程の調査

Application of δ

98/95

後期中新世アラビア海の環境推定へのδ

The elemental and isotopic composition of particulate trace metals in the subarctic Pacific Ocean: sources and internal cycling

亜寒帯太平洋における粒子態微量金属の元素・同位体組成：起源と内部循環

Synthesis and properties of π-conjugated zwitterions composed of an electron-donating anion and an electron-accepting cation

電子ドナー性アニオンと電子アクセプター性カチオンを連結したπ共役双性イオンの合成と物性

Molecular engineering of organic semiconductors toward the control of molecular packing in thin films via a thermal precursor
approach

薄膜構造制御を志向した有機半導体の分子エンジニアリング：熱前駆体法によるアプローチ

Study of anchoring behavior of chiral nematic liquid crystal

キラルネマチック液晶のアンカリング挙動に関する研究

Preparation of novel brunched block copolymer with well-controlled stereoregularity and evaluation of its molecular aggregationstate

分岐型立体規則性ブロック共重合体の合成とその分子鎖凝集構造解析

Development of novel π-conjugated polymers and their application to organic photovoltaics

新規π共役系ポリマーの開発と有機薄膜太陽電池への応用

Design, synthesis, and characterization of charge transport materials for non-lead perovskite

非鉛ペロブスカイトに特化した電荷輸送材料の設計・合成・評価

Coupling of planar and curved π-systems for the development of novel functional materials

平面π系と湾曲π系の組み合わせによる新規機能性材料の創出

Application of s-tetrazines in guanidine functionalization of fullereness-テトラジンを利用したフラーレンのグアジニン官能基化

Control and analysis of complex networks via minimum dominating sets

最小支配集合による複雑ネットワークの制御と解析

Statistical machine learning methods for molecular network analysis

分子ネットワーク解析のための統計的機械学習法の開発と応用

Exhaustive analysis of local structural changes of biological networks

生物ネットワーク構造の局所構造変化の網羅的解析

Concentration of bloom forming algae from environmental samples and identification of the viruses infecting the alga

環境サンプルからの赤潮藻類の濃縮とその藻類に感染するウイルスの同定

Isolation of new giant viruses and their genomic and transcriptomic characterization

新規巨大ウイルスの単離とゲノム・トランスクリプトーム解析

－158－
課題提案型

課題提案型

課題提案型

青山 卓史

青山 卓史

上杉 志成

梶 弘典

岡山理科大学･大学院理学研究科

関西学院大学･理工学部

群馬大学･大学院理工学府

名古屋大学･大学院工学研究科

School of Life Sciences, Peking University

MRC Laboratory of Molecular Biology, University ofCambridge

School of Pharmacy, Fudan University

College of Chemistry and Molecular Engineering, Peking
上杉 志成
University

梶 弘典

京都教育大学･教育学部理学科

Department of Physics, Korea Advanced Institute of
Science and Technology

Department of Chemistry, Tsinghua University

Department of Information Display, Kyung Hee
University

Ames National Laboratory, U.S. Department of Energy

School of Chemistry, Cardiff University

School of Chemistry, University of Bristol

2019-55 大坂 昇

2019-56 玉井 尚登

2019-57 園山 正史

2019-58 野呂 篤史

2019-59 Li-Jia Qu

2019-60 Yohei Ohashi

2019-61 Lu Zhou

2019-62 Xiaoguang Lei

2019-63 Kab-Jin Kim

2019-64 Dongdong Zhang

2019-65 Jang Hyuk Kwon

2019-66 小林 武史

2019-67 Thomas Wirth

2019-68 Jonathan Clayden

川端 猛夫

川端 猛夫

梶 弘典

小野 輝男

渡辺 宏

長谷川 健

坂本 雅典

竹中 幹人

宗林 由樹

課題提案型

課題提案型

課題提案型

課題提案型

課題提案型

課題提案型

課題提案型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

分野選択型

2019-54 向井 浩

宗林 由樹

近畿大学･理工学部

分野選択型

2019-53 中口 譲

松宮 由実

Changchun Institute of Applied Chemistry, Chinese
Academy of Sciences (CAS)2019-52 Quan Chen

Study of magnonic properties of ferrimagnets

フェリ磁性体でのマグノン特性研究

Proteomic approach to discovering specific inhibitors for bile-acid interacting enzymes

プロテオーム解析による胆汁酸結合酵素の阻害剤探索

Site-selective protein acetylation by a small molecule

小分子化合物による選択的タンパク質アセチル化

Role of PX-PH-type phospholipase Ds in plant intracellular membrane traffic

植物細胞内の膜交通におけるPX-PHタイプホスホリパーゼDの役割

Regulatory network of gene expression for plant cell morphogenesis

植物細胞形態形成における遺伝子発現制御ネットワーク

Preparation and mechanical properties of noncovalent bonded elastomers based on styrenic block copolymers

スチレン系ブロック共重合体をベースとした非共有結合性エラストマーの調製と力学特性

Characterization of physical properties and structure of partially fluorinated phospholipid membrane

新規部分フッ素化リン脂質分子群の膜物性・構造のキャラクタリゼーション

Investigation on the carrier relaxation processes of quantum dots protected with functional organic molecules

機能性配位子保護量子ドットの緩和過程の解明

Study on gelation behaviors of polymer oleogels

高分子オレオゲルのゲル化機構の解明

Study on transportation and separation of metal ions through a liquid membrane using ionic liquid

イオン液体を液膜とした金属イオンの液膜輸送と分離に関する研究

Study on the origin and generation mechanism of urban atmospheric aerosol

都市大気エアロゾルの起源および発生メカニズム解明に関する研究

Elongational rheology of telechelic-type ionomers

テレケリック型イオノマーの伸長レオロジー

発展的 国際

発展的 国際

発展的 国際

発展的 国際Creation of functional molecules based on hydrogen bond networks

水素結合ネットワークに基づく機能性分子の創製

Memory of chirality using flow electrochemistry

フローケミストリーを用いる不斉記憶型反応

Structural analysis of organic amorphous thin films using solid effect dynamic nuclear polarization NMR

固体効果による動的核分極NMRを用いた有機デバイス非晶膜の局所構造解析

Highly efficient blue thermally activated delayed fluorescence emitters using sterically hindered donor skeleton

materials as sensitizer

発展的 国際 Development of highly efficient and stable blue organic light emitting diodes using thermally activated delayed fluorescent

発展的 国際

萌芽的 国際

発展的 国際

萌芽的 国際

発展的 国際

5 萌芽的

5 発展的

5 萌芽的

5 萌芽的

5 萌芽的

5 発展的

5 萌芽的 国際－159－

課題提案型

阪部 周二

大野 工司

大野 工司

College of Resources and Environment, Southwest
University

Physics, Hiroshima University

Department of Chemistry and Chemical Engineering,South China University of Technology

Chemical Engineering and Materials Science, Michigan
State University

University of Montpellier

Middle Tennessee State University

2019-71 Xianzhu Dai

2019-72 Kensuke Homma

2019-73 Ying Ma

2019-74 Robert C. Ferrier, Jr.

2019-75 Vincent Ladmiral

2019-76 Chengshan Wang

課題提案型

課題提案型

課題提案型

Research School of Physics and Engineering, Australian
水落 憲和
National University

Max-Planck Institute for Biophysical Chemistry,
水落 憲和
Göttingen, Germany, Max-Plank Independent Research

School of Chemical Engineering, Sungkyunkwan
University (Korea)

広島大学･生物圏科学研究科

東京薬科大学･生命科学部

東京農工大学･工学部･生命工学科

名古屋工業大学･物理工学科

2019-78 Anne S. Ulrich

2019-79 Marcus W. Doherty

2019-80 Gopalakrishnan Balasubramanian

2019-81 Youngdon Kwon

2019-82 冨永 るみ

2019-83 伊藤 昭博

2019-84 長澤 和夫

2019-85 田中 雅章

小野 輝男

上杉 志成

上杉 志成

青山 卓史

課題提案型

課題提案型

課題提案型

課題提案型

課題提案型

二木 史朗

Institute of Organic Chemistry (IOC) and Institute of
Biological Interfaces (IBG-2), Karlsruhe Institute ofTechnology (KIT)

松宮 由実

課題提案型

Dept. of Biochemistry and Molecular Biology, Colorado
今西 未来
State University

課題提案型

課題提案型

2019-77 Tim Stasevich

長谷川 健

大野 工司

課題提案型

課題提案型

課題提案型

課題提案型

Department of Chemical Sciences, University of Naples
栗原 達夫
Federico II

2019-70 Maria Michela Corsaro

栗原 達夫

課題提案型

倉田 博基

Industrial Chemistry, Chiang Mai University

2019-69 Torranin Chairuangsri

萌芽的

発展的

発展的

萌芽的

萌芽的 国際

発展的 国際

発展的 国際

発展的 国際

発展的 国際

萌芽的 国際

発展的 国際

発展的 国際

発展的 国際

発展的 国際

萌芽的 国際

発展的 国際Investigation of magnetic and electric properties of cobalt ferrite films for development of high spin-polarized current source

高スピン偏極電流源の開発のためのコバルトフェライト薄膜の磁気・電気的性質の評価

Modulation of new cellular functions of vitamin D

ビタミンＤの新機能の調節

New cellular functions of acyldopamine

アシルドーパミンの新機能

Study on the regulatory network of plant epidermal cell differentiation

植物表皮細胞の分化における制御ネットワークの研究

Effect of dipole alignment along chain backbone on dielectric relaxation of type-A polymers at association/dissociation equilibrium

末端会合/解離平衡下におけるA型高分子鎖の誘電緩和に対する双極子配置の効果

Research on shallow NV center in diamond

表面近傍のNV 中心の研究

Research of multi-qubit diamond quantum processors

ダイヤモンド多量子ビット量子プロセッサーの研究

Structural and functional analysis of curvature-inducing peptides

曲率誘導ペプチドの構造活性相関

Real-time imaging of single-molecule mRNA with different methylation states

13
Determine the three-dimensional structure of C labeled α-synuclein(61-95) in the Langmuir-Blodgett film and supported
phospholipids bilayers by p-MAIRS FT-IR

Fluorinated polymer-brush-grafted nanoparticles: Precise synthesis and applications to membrane technology

フッ素系ポリマーブラシ付与ナノ粒子の精密合成と膜技術への応用

Exploring new polyether nanocomposite electrolytes to enhance energy storage of lithium ion batteries

リチウムイオン電池の性能向上に向けたポリエーテル系ナノコンポジット電解質の開発

Development of biosensors by combining stimuli-responsive polymer brushes with electrochemical analysis

刺激応答性ポリマーブラシと電気化学解析を駆使したバイオセンサーの開発

Search for four-wave-mixing in the vacuum - Unveiling dark components in the Universe -宇宙暗黒成分解明へ向けた真空内四光波混合の探索

Construction of low-temperature protein expression system by using cold-adapted microorganisms

低温適応微生物を用いたタンパク質低温発現システムの構築

Structural and functional analysis of the surface components of bacterial outer membrane vesicles

細菌外膜小胞表層成分の構造機能解析

battery development

萌芽的 国際 Micro- and nano-structural characterization by advanced transmission electron microscopy of novel functional materials for－160－

共立女子大学･家政学部被服学科

東京工業大学･フロンティア材料研究所

千葉大学･教育学部

東京医科歯科大学･生体材料工学研究所

富山大学･大学院医学薬学研究部

金沢大学･ナノマテリアル研究所

2019-98 真島 豊

2019-99 山田 哲弘

2019-100 野村 渉

2019-101 大橋 若奈

2019-102 徳田 規夫

大阪工業大学･工学部 生命工学科

2019-93 大森 勇門

2019-97 村瀬 浩貴

近畿大学･農学部 応用生命化学科

2019-92 倉田 淳志

大阪大学･大学院基礎工学研究科

金沢大学･医薬保健学域薬学系 機能性分子合成学

2019-91 吉村 智之

2019-96 内田 幸明

岐阜薬科大学･薬学部

2019-90 永澤 秀子

大阪府立大学工業高等専門学校

立教大学･理学部化学科

2019-89 山中 正浩

2019-95 倉橋 健介

名古屋市立大学･芸術工学研究科

2019-88 松本 貴裕

高エネルギー加速器研究機構･物質構造科学研究所

岐阜大学･工学部･化学・生命工学科

2019-87 山田 啓介

2019-94 齊藤 高志

北海道大学･工学研究院

2019-86 長浜 太郎

水落 憲和

二木 史朗

二木 史朗

長谷川 健

寺西 利治

辻井 敬亘

大野 工司

宗林 由樹

島川 祐一

栗原 達夫

栗原 達夫

川端 猛夫

川端 猛夫

川端 猛夫

金光 義彦

小野 輝男

小野 輝男

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発展的

発展的

発展的

萌芽的

発展的

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発展的

萌芽的

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ワイル半金属Mn3Sn エピタキシャル薄膜の開発

Manufacture of shallow NV centers in diamond

ダイヤモンド表面近傍のNV 中心作製

Establishment of cell penetrating peptide (CPP)-based delivery system into resident cancer stem cells in deep cancer tissue

がん深部到達型修飾膜透過ペプチドの創出と大腸がん幹細胞効率的除去への展開

Development of NanoBRET-based screening system for peptidic CXCR4 ligands

NanoBRET 型CXCR4 結合解析によるペプチドリガンド評価系の構築

Investigation of new anti-lust surfactant containing a perfluoro-alkyl chain and an amino acid head group

パーフルオロアルキル鎖とアミノ酸頭部基を有する新規な界面活性剤型防錆剤の探索

Ferromagnetic single-electron transistor

強磁性単電子トランジスタ

Manipulation of three dimensional structure of porous polymer composites controlled by additive manufacturing

Additive Manufacturing による多孔性高分子複合材料の3 次元構造制御

Fine synthesis of polymer brash on ferromagnetic nano-platelet for ferromagnetic photonic LC

ポリマーブラシ付与強磁性ナノプレートの精密合成による強磁性フォトニック液晶の実現

Application of surfactant for extraction of platinum group elements using solvent impregnated resin

溶媒含浸樹脂を用いた白金族元素抽出における界面活性剤の利用

Synthesis and study of oxides with unusually high-valent cation

異常高原子価イオンを含む機能性酸化物合成とその構造物性研究

Studies on the physiological significance of two alanine dehydrogenases in Geobacillus kaustophilus

Geobacillus kaustophilusにおける2種類のアラニン脱水素酵素の生理的意義の解析

Analysis of the physiological functions of membrane vesicles produced by intestinal bacteria and fermented food-derived bacteria
and their application

腸内細菌および発酵食品由来細菌が生産する膜小胞の生理機能解析と応用

Studies on total synthesis of gonytolides

Gonytolide 類の全合成研究

Synthesis and biological evaluation of antitumor cyclic octadepsipeptide containing α-fluorinated amino acid

α-フッ素化アミノ酸を含む抗腫瘍性環状オクタデプシペプチドの合成と生物学的評価

Theoretical study on chemoselective acylation catalyzed by 4-pyrrolidinopyridine derivatives

4-ピロリジン‐ピリジン型分子触媒による化学選択的アシル化反応の理論的解析

Giant isotope effects of deuterium atoms terminating on nanocrystalline silicon and their use

ナノ結晶シリコン表面に終端した重水素元素が有する巨大同位体効果の分光学的解明とその応用

Effect of microstructure on damping constant in polycrystalline Bi-YIG thin films prepared by sol-gel method

ゾル・ゲル法により作製した多結晶Bi-YIG薄膜の微細構造と損失定数の相関解明

Develop of the epitaxial thin film of Weyl semimetal Mn3Sn

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連携・融合促進型

連携・融合促進型

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渡辺 宏

竹中 幹人

山子 茂

大阪大学･大学院理学研究科

日本女子大学･理学部･数物科学科

Department of Material Science and Chemical
Engineering, Stony Brook University

Department of Chemistry, National Taiwan University

School of Physical and Mathematical Sciences, Divisionof Chemistry and Biological Chemistry, Nanyang
山子 茂Technological University

Department of Macromolecular Science, Osaka
University

2019-106 島田 良子

2019-107 Maya K. Endoh2019-108 Jye-Shane Yang

2019-109 Shunsuke Chiba

2019-110 Tadashi Inoue

梶 弘典

島川 祐一

時任 宜博

大阪大学･大学院理学研究科

Department of Chemistry, Tsinghua University

Centre for Science at Extreme Conditions and Schoolof Chemistry, University of Edinburgh

College of Science, Department of Chemistry, Rikkyo
University

島根大学･総合理工学部

九州大学･大学院総合理工学研究院

東北大学･大学院農学研究科

福岡大学･理学部化学科

2019-112 松野 丈夫

2019-113 Juan Qiao

2019-114 J. Paul Attfield

2019-115 Mao Minoura

2019-116 宮本 光貴

2019-117 斉藤 光

2019-118 高橋 まさえ

2019-119 長洞 記嘉

時任 宜博

時任 宣博

倉田 博基

倉田 博基

菅 大介

静岡県立大学･薬学部

2019-111 濱島 義隆

川端 猛夫

松宮 由実

松宮 由実

施設・機器利用型

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2019-105 井上 正志

山子 茂

大阪大学･産業科学研究所

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2019-104 藤塚 守

水落 憲和

産業技術総合研究所
先進パワーエレクトロニクス研究センター

2019-103 牧野 俊晴

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Fabrication of nanotopographical polymer surfaces with bactericidal properties

殺菌性を有する高分子ナノ表面設計

国際

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Synthesis and structures of acene molecules bearing chalcogenopyrylium units

カルコゲノピリリウム部位を含むアセン型分子の合成と構造解析

Design of flat silicene with perfect pai-conjugate 2D sheet

完璧なπ共役二次元シートを持つフラットシリセンの設計

Plasmon-exciton coupling on a plasmonic crystal

プラズモニック結晶上でのプラズモン-エキシトン結合

Nano-electron spectroscopic study on hydrogen and helium behavior in plasma facing materials for nuclear fusion devices

核融合プラズマ対向材中の水素・ヘリウム挙動に関する電子分光学的研究

Synthesis and characterization of novel organoselenium and -tellurium compouds

新規有機セレンおよびテルル化合物の合成と性質解明

High-pressure synthesis of potential multiferroic oxides

Atomic level analysis and fabrication of highly stable perovskite films and light emitting diodes

26th International workshop on oxide electronics

第26回酸化物エレクトロニクスに関する国際会議

The 8th Japanese-Sino Symposium on Organic Chemistry for Young Scientists

第８回日本—中国有機化学シンポジウム

The 15th International workshop for East Asian Young Rheologists

東アジア圏の若手レオロジストのための第15回ワークショップ

biodegradable properties

国際 Vinyl azides as new monomers of radical polymerization for the fabrication of green polymers having chemically- andin solution

国際 Synthesis of structurally controlled polymers having green fluorescence protein chromophore and their photophysical properties

国際

Analysis of Soret effect for DNA in molecular-scale temperature gradient

分子スケールの温度勾配下におけるDNAの Soret 効果の解析

Nonlinear rheology of semiflexible polymer solutions

半屈曲性高分子溶液の非線形レオロジー

Ring-size-dependent excitation dynamics of cycloparaphenylenes

シクロパラフェニレンの励起ダイナミクスの環サイズ依存性

Electrical control and detection of qubit of NV center

ダイヤモンド中のNV 中心量子ビットの電気的制御と電気的検出

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近畿大学･理工学部

茨城大学･工学部･物質科学工学科

奈良県立医科大学･医学部

2019-120 松尾 司

2019-121 吾郷 友宏

2019-122 秦野 修

施設・機器利用型

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時任 宣博
水畑 吉行

磯﨑 勝弘

施設・機器利用型

時任 宜博

High sensitive imaging mass spectrometry targeting the carbonyl compounds derived from biological tissues

生体組織由来のカルボニル化合物を標的とする高感度質量分析イメージング解析

Elucidation of the fluorous interactions in the crystal structures of fluorine-containing conjugated molecules by the single-crystal
X-ray structural analysis

単結晶X 線構造解析を用いた、含フッ素共役分子の結晶構造におけるフルオラス相互作用の解明

Synthesis and structural characterization of divalent species of heavier group 14 elements

高周期14族元素二価化学種の合成と分子構造の解明