Sep. 2015, Presentation Award at the 9th symposium on biorelevant chemistry, CSJ　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki

Apr. 2013, Chemical Society of Japan, CSJ Presentation Award 2013　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki

Nonequilibrium Self‐Assembly of Microtubules Through Stepwise Sequential Interactions of DNA
Jakia Jannat Keya, Mousumi Akter, Yuta Yamasaki, Yoshiyuki Kageyama, Kazuki Sada, Akinori Kuzuya, Akira Kakugo
Small, 23 Dec. 2024
Scientific journal

分子機械による巨視的な力学的仕事の実現
景山 義之
Colloid & Interface Communications, 48, 1, 34, 37, 公益社団法人 日本化学会 コロイドおよび界面化学部会, 10 Mar. 2023, [Domestic magazines]
Japanese, 生命体のような高度な自律機能を誇る分子システムを構築することは、超分子化学の一つの目標である。この分野では、従来、一個の分子機械の設計と合成に関心が向けられてきた。これに対して筆者は、分子機械を集積させることによって、巨視的な自律機能、例えば自律遊泳を実現する分子システムを構築したので報告する。

Complication and hysteresis of the self-sustaining motion of a molecular-machine assembly caused by the directionality of the applied light energy
Yoshiyuki Kageyama, Makiko Matsuura, Daisuke Yazaki
arXiv, 25 Jan. 2023, [Lead author, Corresponding author]
Living organisms show self-sustained motion, make behavioural decisions in response to their environment, and replicate themselves in a genetic manner. Recently, nanometre-sized molecular machines have been assembled to realise macroscopic systems that exhibit self-sustaining dynamics. However, it is unclear how such systems can acquire the ability to make decisions in response to their environment. We have previously reported that the behaviour of a light-driven self-oscillating crystal becomes complicated when the driving light is polarised. Here, we reveal by incorporating a theoretical analysis that the apparent complexity is due to the orientation of the crystal relative to the incident light. An additional reason for this complexity is that the components remember the polarity of the preceding light input. Our results provide a new concept, i.e., collaboration between a motor molecule to achieve self-sustaining motion and a responsive machine for storing information to realise self-governed dynamics in a multimolecular architecture., 27475905

Potential curves illustrating a dissipative self-assembly system and the meaning of away-from-equilibrium
Yoshiyuki Kageyama, Goro Maruta
arXiv, 14 Nov. 2022, [Lead author, Corresponding author], [International Magazine]
English, Dissipative self-assembly is a recently proposed concept in the field of
non-equilibrium systems. This concept catches the reader's attention owing to
its relationship with life phenomena. Recently, Credi's group has reported the
behavior of a directional supramolecular pump that works under continuous light
irradiation with the regime of dissipative self-assembly. Despite their
remarkable results, the thermodynamic aspects illustrated in their paper have
the potential to mislead readers about the chemistry of non-equilibrium
systems., 27475905

Site-Selective Spin-Probe with a Photocleavable Macrocyclic Linker for Measuring the Dynamics of Water Surrounding a Liposomal Assembly
Gyeorye Lee, Yoshiyuki Kageyama, Sadamu Takeda
Bulletin of the Chemical Society of Japan, 95, 6, 909, 921, The Chemical Society of Japan, 15 Jun. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, 27475905

Self‐Propulsion of a Light‐Powered Microscopic Crystalline Flapper in Water
Kazuma Obara, Yoshiyuki Kageyama, Sadamu Takeda
Small, 2105302, 2105302, Wiley, Feb. 2022, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, https://www.global.hokudai.ac.jp/blog/mobile-molecular-robots-swim-in-water/, 27475905

機械的な挙動で力学的仕事を継続的に行う有機分子デバイスの創出
景山 義之
日本応用物理学会 有機分子・バイオエレクトロニクス分科会誌, 32, 4, 194, 204, 24 Nov. 2021, [Invited], [Lead author, Last author, Corresponding author]
Japanese, Scientific journal, 27475905

偏光で振付けを変えて踊る分子ロボットを実現
景山 義之
Isotope News, 775, 31, 35, 日本アイソトープ協会, 01 Jun. 2021, [Invited], [Lead author, Last author, Corresponding author], [Domestic magazines]
Japanese

Robust Dynamics of Synthetic Molecular Systems as a Consequence of Broken Symmetry
Yoshiyuki Kageyama
Symmetry, 12, 10, 1688, 1688, {MDPI} {AG}, 14 Oct. 2020, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author], [International Magazine]
English, Scientific journal, The construction of molecular robotic-like objects that imitate living things is an important challenge for current chemists. Such molecular devices are expected to perform their duties robustly to carry out mechanical motion, process information, and make independent decisions. Dissipative self-organization plays an essential role in meeting these purposes. To produce a micro-robot that can perform the above tasks autonomously as a single entity, a function generator is required. Although many elegant review articles featuring chemical devices that mimic biological mechanical functions have been published recently, the dissipative structure, which is the minimum requirement, has not been sufficiently discussed. This article aims to show clearly that dissipative self-organization is a phenomenon involving autonomy, robustness, mechanical functions, and energy transformation. Moreover, the author details the recent experimental results of an autonomous light-driven molecular device that achieves all of these features. In addition, a chemical model of cell-amplification is also discussed to focus on the generation of hierarchical movement by dissipative self-organization. By reviewing this research, it may be perceived that mainstream approaches to synthetic chemistry have not always been appropriate. In summary, the author proposes that the integration of catalytic functions is a key issue for the creation of autonomous microarchitecture., 27475905

Light-driven flipping of azobenzene assemblies - sparse crystal structures and responsive behavior to polarized light.
Yoshiyuki Kageyama, Tomonori Ikegami, Shinnosuke Satonaga, Kazuma Obara, Hiroyasu Sato, Sadamu Takeda
Chemistry (Weinheim an der Bergstrasse, Germany), 19 Mar. 2020, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, For creation of autonomous microrobots which are able to move under conditions of a constant environment and a constant energy supply, a mechanism for maintenance of mechanical motion with a capacity for self-control is required. This requirement, known as self-organisation, represents the ability of a system to evade equilibrium through formation of a spatio-temporal pattern. Following our previous finding of a self-oscillatory flipping motion of an azobenzene-containing co-crystal, we present here regulation of the flipping motion by a light-receiving sensor molecule in relation to the alignment and role of azobenzene molecules in crystals. In the anisotropic structure, a specific azobenzene molecule acts as a reaction centre for the conversion of light to a mechanical function process, while the other molecules act as modulators for spatio-pattern regulation. The present results demonstrate that autonomously drivable molecular materials can exhibit information-responsive, self-sustainable motion by incorporating stimulus-responsive sensors., 27475905

Light‐Powered Self‐Sustainable Macroscopic Motion for the Active Locomotion of Materials
Yoshiyuki Kageyama
ChemPhotoChem, 3, 327, 336, Wiley, Jun. 2019, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal, オープンアクセス。

自律運動発現の要件についてまとめたMinireview。
雑誌の趣旨を踏まえ、光照射下での挙動についてまとめている。自己組織化を専門としない化学者に向け、基礎的な内容に焦点を絞って記載。

Dancing Crystals under Light
OBARA Kazuma, KAGEYAMA Yoshiyuki
Chemistry & Education, 67, 2, 74, 75, 日本化学会, Feb. 2019, [Invited], [Last author, Corresponding author]
Japanese

動け!高分子 自律駆動するアゾベンゼン分子集合体
景山義之
高分子, 67, 6, 328‐329, 329, Jun. 2018, [Invited], [Lead author, Last author, Corresponding author]
Japanese, Scientific journal

Creation of bioinspired molecular assembly which shows continuous motion with self-organization　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
News Letter of the Division of Organic Crystals, CSJ, 40, 67, 70, Mar. 2017, [Lead author, Last author, Corresponding author], [Domestic magazines]
Japanese

時空間的非対称性が鍵になる次世代超分子デバイス 生物に近づく有機分子デバイス
景山義之
化学と工業, 69, 9, 736‐737, 737, Chemical Society of Japan, Sep. 2016, [Invited], [Lead author, Last author, Corresponding author], [Domestic magazines]
Japanese, Scientific journal

Dissipative and Autonomous Square-Wave Self-Oscillation of a Macroscopic Hybrid Self-Assembly under Continuous Light Irradiation
Tomonori Ikegami, Yoshiyuki Kageyama, Kazuma Obara, Sadamu Takeda
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 55, 29, 8239, 8243, WILEY-V C H VERLAG GMBH, Jul. 2016, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Building a bottom-up supramolecular system to perform continuously autonomous motions will pave the way for the next generation of biomimetic mechanical systems. In biological systems, hierarchical molecular synchronization underlies the generation of spatio-temporal patterns with dissipative structures. However, it remains difficult to build such self-organized working objects via artificial techniques. Herein, we show the first example of a square-wave limit-cycle self-oscillatory motion of a noncovalent assembly of oleic acid and an azobenzene derivative. The assembly steadily flips under continuous blue-light irradiation. Mechanical self-oscillation is established by successively alternating photoisomerization processes and multi-stable phase transitions. These results offer a fundamental strategy for creating a supramolecular motor that works progressively under the operation of molecule-based machines.

Mechanism of Macroscopic Motion of Oleate Helical Assemblies: Cooperative Deprotonation of Carboxyl Groups Triggered by Photoisomerization of Azobenzene Derivatives
Yoshiyuki Kageyama, Tomonori Ikegami, Yuta Kurokome, Sadamu Takeda
CHEMISTRY-A EUROPEAN JOURNAL, 22, 25, 8669, 8675, WILEY-V C H VERLAG GMBH, Jun. 2016, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, Macroscopic and spatially ordered motions of self-assemblies composed of oleic acid and a small amount of an azobenzene derivative, induced by azobenzene photoisomerization, was previously reported. However, the mechanism of the generation of submillimeter-scale motions by the nanosized structural transition of azobenzene was not clarified. Herein, an underlying mechanism of the motions is proposed in which deprotonation of carboxyl groups in co-operation with azobenzene photoisomerization causes a morphological transition of the self-assembly, which in turn results in macroscopic forceful dynamics. The photoinduced deprotonation was investigated by potentiometric pH titration and FTIR spectroscopy. The concept of hierarchical molecular interaction generating macroscale function is expected to promote the next stage of supramolecular chemistry.

分子機械が誘起する分子集合体の巨視的ダイナミクス
景山 義之
C & I commun : colloid & interface communication : newsletter from DCSC, 41, 3, 13, 15, 日本化学会コロイドおよび界面化学部会, 2016, [Invited], [Lead author, Last author, Corresponding author], [Domestic magazines]
Japanese

Formation of Monodisperse Hierarchical Lipid Particles Utilizing Microfluidic Droplets in a Nonequilibrium State
Masahiro Mizuno, Taro Toyota, Miki Konishi, Yoshiyuki Kageyama, Masumi Yamada, Minoru Seki
LANGMUIR, 31, 8, 2334, 2341, AMER CHEMICAL SOC, Mar. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal, A new microfluidic process was used to generate unique micrometer-sized hierarchical lipid particles having spherical lipid-core and multilamellar-shell structures. The process includes three steps: (1) formation of monodisperse droplets in a nonequilibrium state at a microchannel confluence, using a phospholipid-containing water-soluble organic solvent as the dispersed phase and water as the continuous phase; (2) dissolution of the organic solvent of the droplet into the continuous phase and concentration of the lipid molecules; and (3) reconstitution of multilamellar lipid membranes and simultaneous formation of a lipid core. We demonstrated control of the lipid particle size by the process conditions and characterized the obtained particles by transmission electron microscopy and microbeam small-angle X-ray scattering analysis. In addition, we prepared various types of core-shell and core-core-shell particles incorporating hydrophobic/hydrophilic compounds, showing the applicability of the presented process to the production of drug-encapsulating lipid particles.

Structure and growth behavior of centimeter-sized helical oleate assemblies formed with assistance of medium-length carboxylic acids
Yoshiyuki Kageyama, Tomonori Ikegami, Natsuko Hiramatsu, Sadamu Takeda, Tadashi Sugawara
SOFT MATTER, 11, 18, 3550, 3558, ROYAL SOC CHEMISTRY, 2015, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, The nonequilibrium organization of self-assemblies from small building-block molecules offers an attractive and essential means to develop advanced functional materials and to understand the intrinsic nature of life systems. Fatty acids are well-known amphiphiles that form self-assemblies of several shapes. Here, we found that the lengths of helical structures of oleic acid formed in a buffered aqueous solution are dramatically different by the presence or absence of certain amphiphilic carboxylic acids. For example, under the coexistence of a small amount of N-decanoyl-L-alanine, we observed the formation of over 1 centimeter-long helical assemblies of oleate with a regular pitch and radius, whereas mainly less than 100 mm-long helices formed without this additive. Such long helical assemblies are unique in terms of their highly dimensional helical structure and growth dynamics. Results from the real-time observation of self-assembly formation, site-selective small-angle X-ray scattering, high-performance liquid chromatography analysis, and pH titration experiments suggested that the coexisting carboxylates assist in elongation by supplying oleate molecules to a scaffold for oleate helical assembly.

Intrinsic Surface-Drying Properties of Bioadhesive Proteins
Yasar Akdogan, Wei Wei, Kuo-Ying Huang, Yoshiyuki Kageyama, Eric W. Danner, Dusty R. Miller, Nadine R. Martinez Rodriguez, J. Herbert Waite, Songi Han
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 53, 42, 11253, 11256, WILEY-V C H VERLAG GMBH, Oct. 2014, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Sessile marine mussels must dry underwater surfaces before adhering to them. Synthetic adhesives have yet to overcome this fundamental challenge. Previous studies of bioinspired adhesion have largely been performed under applied compressive forces, but such studies are poor predictors of the ability of an adhesive to spontaneously penetrate surface hydration layers. In a force-free approach to measuring molecular-level interaction through surface-water diffusivity, different mussel foot proteins were found to have different abilities to evict hydration layers from surfacesa necessary step for adsorption and adhesion. It was anticipated that DOPA would mediate dehydration owing to its efficacy in bioinspired wet adhesion. Instead, hydrophobic side chains were found to be a critical component for protein-surface intimacy. This direct measurement of interfacial water dynamics during force-free adsorptive interactions at solid surfaces offers guidance for the engineering of wet adhesives and coatings.

Intrinsic Surface-Drying Properties of Bioadhesive Proteins
Yasar Akdogan, Wei Wei, Kuo-Ying Huang, Yoshiyuki Kageyama, Eric W. Danner, Dusty R. Miller, Nadine R. Martinez Rodriguez, J. Herbert Waite, Songi Han
Angew. Chem., 126, 42, 11435, 11438, Wiley-Blackwell, Aug. 2014, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
Scientific journal

2SDP-04 Macroscopic Motion of Soft Non-covalent Molecular Assembly in Water Actuated by Chemically Synthesized Molecular Machine(Biomolecular machinery driven by surrounding water,Symposium,The 52th Annual Meeting of the Biophysical Society of Japan(BSJ2014))
Kageyama Yoshiyuki
Seibutsu Butsuri, 54, 1, S134, The Biophysical Society of Japan General Incorporated Association, 2014
English

Macroscopic motion of supramolecular assemblies actuated by photoisomerization of azobenzene derivatives
Yoshiyuki Kageyama, Naruho Tanigake, Yuta Kurokome, Sachiko Iwaki, Sadamu Takeda, Kentaro Suzuki, Tadashi Sugawara
CHEMICAL COMMUNICATIONS, 49, 82, 9386, 9388, ROYAL SOC CHEMISTRY, 2013, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, Submillimetre size self-assemblies composed of oleate and azobenzene derivatives show forceful motions such as screw-type coiling-recoiling motion by photoirradiation.

Compartment size dependence of performance of polymerase chain reaction inside giant vesicles
Koh-ichiroh Shohda, Mieko Tamura, Yoshiyuki Kageyama, Kentaro Suzuki, Akira Suyama, Tadashi Sugawara
SOFT MATTER, 7, 8, 3750, 3753, ROYAL SOC CHEMISTRY, 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal, The amplification of a 1229 bp template DNA that encoded the green fluorescent protein (GFP) was conducted in cell-sized giant vesicles (GVs, phi > 1 mu m) using a real-time polymerase chain reaction (PCR) technique. The proportion of PCR-proceeded GV reached up to 16% of all GVs. The dependence of PCR on GV size was elucidated by flow cytometry analysis.

Autocatalytic membrane-amplification on a pre-existing vesicular surface
Hiroshi Takahashi, Yoshiyuki Kageyama, Kensuke Kurihara, Katsuto Takakura, Shigeru Murata, Tadashi Sugawara
CHEMICAL COMMUNICATIONS, 46, 46, 8791, 8793, ROYAL SOC CHEMISTRY, 2010, [Peer-reviewed], [International Magazine]
English, Scientific journal, In water, phosphoric membrane molecule (V(-)) self-assembled to form an anionic giant vesicle, the surface of which served as a catalyst for the autocatalytic formation of V(-) from its membrane precursor (V(star)), and the amplified V(-) produced a new vesicle using the original vesicle as a scaffold.

Design and Synthesis of Photocleavable Biotinylated-Dopamine with Polyethyleneoxy Photocleavable Linkers
Shin Aoki, Kengo Hanaya, Yoshiyuki Kageyama, Masanori Kitamura
HETEROCYCLES, 82, 2, 1601, 1601, Japan Institute of Heterocyclic Chemistry, 2010, [Invited], [International Magazine]
English, Scientific journal, Previously, we reported the synthesis of a biotin dopamine conjugate (Btn-DA) with a photocleavable 8-quinolinyl benzenesulfonate (QB) linker for the isolation of an intact complex of DA and anti-DA antibody (IgG(1)) (DA-IgG(1) complex). In this work, we synthesized a photocleavable Btn-DA conjugate with a polyethyleneoxy linker to improve the complexation efficiency and the recovery yields of DA-IgG(1) complex. The results of QCM, ELISA, and Western blot analyses indicate that the introduction of polyethyleneoxy linkers improved the efficiency of DA-IgG(1) complexation.

Photochemical Cleavage Reactions of 8-Quinolinyl Sulfonates in Aqueous Solution
Yoshiyuki Kageyama, Ryosuke Ohshima, Kazusa Sakurama, Yoshihisa Fujiwara, Yoshifumi Tanimoto, Yasuyuki Yamada, Shin Aoki
CHEMICAL & PHARMACEUTICAL BULLETIN, 57, 11, 1257, 1266, PHARMACEUTICAL SOC JAPAN, Nov. 2009, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, Pholochemical cleavage reactions of 8-quinolinyl benzenesulfonate derivatives anti related sulfonates in aqueous solutions are reported. The 8-quinolinyl benzenesulfonates undergo photolysis upon photoirradiation at 300-330 nm to give the corresponding 8-quinolinols and benzenesulfonic acids with the product ion of only negligible amounts of by products. The effects of substituent groups of the 8-quinolinyl moiety and the benzene ring on the photolysis reactions were examined. Based on steady-state mechanistic studies using a triplet sensitizer, a triplet quencher, and electron donors, it was suggested that the photolysis proceeds mainly via the homolytic cleavage of S-O bonds in the excited triplet state.

Design and synthesis of a photocleavable biotin-linker for the photoisolation of ligand-receptor complexes based on the photolysis of 8-quinolinyl sulfonates in aqueous solution
Shin Aoki, Nanako Matsuo, Kengo Hanaya, Yasuyuki Yamada, Yoshiyuki Kageyama
BIOORGANIC & MEDICINAL CHEMISTRY, 17, 9, 3405, 3413, PERGAMON-ELSEVIER SCIENCE LTD, May 2009, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, The ability of avidin (Avn) to form strong complex with biotin (Btn) is frequently used in the detection and isolation of biomolecules in biochemical, analytical, and medicinal research. The fact that the binding is nealy irreversible, however, constitutes a drawback in term of the isolation and purification of intact biomolecules. We recently found that 8-quinolinyl esters of aromatic or aliphatic sulfonic acids undergo photolysis when irradiated at 300-330 nm in aqueous solution at neutral pH. In this work, a biotin-dopamine (BD) conjugate containing a photocleavable 8-quinolinyl benzenesulfonate (QB) linker, BDQB, was designed and synthesized for use in the efficient recovery of dopamine-protein (e.g., antibody) complexes from an Avn-Btn system. The complexation of BDQB with a primary anti-dopamine antibody (anti-dopamine IgG(1) from mouse) on an Avn-coated plate was confirmed by an enzyme-linked immunosorbent assay ( ELISA) utilizing a secondary antibody (anti-IgG(1) antibody) conjugated with horseradish peroxidase (HRP). Upon the photoirradiation (at 313 nm) of the BDQB-IgG(1) complex, the release of dopamine-IgG(1) complex was confirmed by ELISA. Characterization of the resulting photoreleased dopamine anti-dopamine IgG(1) complex was performed by SDS-PAGE and Western blot. (C) 2009 Elsevier Ltd. All rights reserved.

Photolysis of the Sulfonamide Bond of Metal Complexes of N -Dansyl-1,4,7,10-Tetraazacyclododecane in Aqueous Solution: A Mechanistic Study and Application to the Photorepair of cis,syn -Cyclobutane Thymine Photodimer
Shin Aoki, Yumiko Tomiyama, Yoshiyuki Kageyama, Yasuyuki Yamada, Motoo Shiro, Eiichi Kimura
Chem. Asian J., 4, 4, 561, 573, Wiley-Blackwell, 06 Apr. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal, Sulfonamide constitutes a ubiquitous functional group that is frequently used in organic chemistry, analytical chemistry, and medicinal chemistry. We report herein on the photolysis of a dansylamide moiety of 1-dansyl-1,4,7,10-tetraazzacyclododecane (N-dansylcyclen, L-2) in the presence of a zinc(II) ion in aqueous solution. By potentiometric pH titrations, the complexation constant for the 1:1 complex of L-2 and Zn2+, logK(s)(ZnL2), in aqueous solution at 25 degrees C with I=0.1 (NaNO3) was determined to be 6.5 +/- 0.1. The structure of the ZnL2 complex was confirmed by single-crystal X-ray diffraction analysis. During fluorescence titrations of L-2 With Zn2+ (irradiation at 308 or 350 nm) in aqueous solution at pH 7.4 (1.0 mM HEPES with I=0.1 (NaNO3)) and 25 degrees C, considerable enhancement in fluorescence emission of the Zn2+ complex of L-2 (ZnL2) was observed, while metal-free 12 exhibited only a negligible emission change upon UV irradiation. It was revealed that this emission enhancement arose from the photoinduced cleavage of a sulfonylamide moiety in ZnL2, yielding the Zn2+-cyclen complex and 5-dimethylaminonaphthalene-1-sulfinic acid, which has a greater quantum yield (0) for fluorescence emission than that of L-2 and ZnL2. For comparison, the photolysis of N-(1-naphthalenesulfonyl)cyclen (L-3) and its Zn2+ complex (ZnL3) under the same conditions (irradiation at 313 nm) gave the corresponding sulfonate (1-naphthylsulfonate). We also describe the results of a photoreversion reaction of cis,syn-cyclobutane thymine photodimer (T[c,s]T) utilizing the photolysis of ZnL2 and ZnL3.

Population study of sizes and components of self-reproducing giant multilamellar vesicles
Taro Toyota, Katsuto Takakura, Yoshiyuki Kageyama, Kensuke Kurihara, Naoto Maru, Kiyoshi Ohnuma, Kunihiko Kaneko, Tadashi Sugawara
LANGMUIR, 24, 7, 3037, 3044, AMER CHEMICAL SOC, Apr. 2008, [Peer-reviewed], [International Magazine]
English, Scientific journal, Population analysis of a system of self-reproducing giant multilamellar vesicles (GMVs) was carried out by means of flow cytometry. The multidimensional distribution of forward light scattering (FS), side light scattering (SS), and fluorescence (FL) intensities originating from each GMV provided information about changes in a population composed of 10(4) vesicles. FS-FL dot plots indicated that, after the addition of the membrane precursor, the size distribution of the newly generated vesicles was nearly the same as that of the original, but the catalyst content was reduced. This result can be interpreted as evidence for the occurrence of the self-reproduction of GMVs. Moreover, the new GMVs recovered the amount of catalyst to the initial value, keeping their size distribution constant, when a solution of the catalyst was added to the new GMVs. These results are the first experimental evidence for a novel phenomenon on GMV size distribution during their self-reproducing cycle.

1P-225 PCR in Phospholipid Giant vesicles(The 46th Annual Meeting of the Biophysical Society of Japan)
Tamura Mieko, Kageyama Yoshiyuki, Shohda Koh-ichiroh, Suzuki Kentaro, Sugawara Tadashi
Seibutsu Butsuri, 48, S56, The Biophysical Society of Japan General Incorporated Association, 2008
English

Design and synthesis of porphyrin-based telomerase inhibitors having Zn(II)-cyclen complex
Hanae Ueyama, Yoshiyuki Kageyama, Masanori Kitamura, Eiiehi Kimura, Tomoko Okada, Shin Aoki
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 128, 27, 27, PHARMACEUTICAL SOC JAPAN, 2008, [Peer-reviewed], [Domestic magazines]
English

Study on structural changes in supramolecular assemblies composed of amphiphilic nicotinamide and its dihydronicotinamide derivative by flow cytometry
Yoshiyuki Kageyama, Taro Toyota, Shigeru Murata, Tadashi Sugawara
SOFT MATTER, 3, 6, 699, 702, ROYAL SOC CHEMISTRY, 2007, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, Flow cytometric analysis revealed that the redistribution of components of a hybrid vesicular system composed of amphiphilic nicotinamide and its reduced form occurred associated with the emergence of nonlamellar aggregates that emitted an enhanced blue emission together with a green emission due to exciplex formation.

2P471 A liposome containing an autonomous DNA computing system inside(50. Non-equilibrium and complex system,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)
Shohda Koh-ichiroh, Kiga Daisuke, Takinoue Masahiro, Kageyama Yoshiyuki, Sugawara Tadashi, Suyama Akira
Seibutsu Butsuri, 46, 2, S413, The Biophysical Society of Japan General Incorporated Association, 2006
English

Oxidative formation of thiolesters in a model system of the pyruvate dehydrogenase complex
Y Kageyama, S Murata
JOURNAL OF ORGANIC CHEMISTRY, 70, 8, 3140, 3147, AMER CHEMICAL SOC, Apr. 2005, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, In the presence of a catalytic amount of 3-butyl-4-methylthiazolium bromide, the reaction of benzaldehydes with azobenzene in dichloromethane containing octanethiol and Et3N gave the corresponding S-octyl thiobenzoates in good yields. The thiolesters were produced by trapping of the 2-benzoylthiazolium salts with the thiol, which were generated through the azobenzene oxidation of the active aldehydes. This is the first example for the thiolester formation mimicking the function of the pyruvate dehydrogenase complex. An electron-withdrawing substituent at the 4-position of benzaldehyde enhanced the reaction rate. The effect of benzaldehyde substituents on the reaction rate was examined quantitatively on the basis of kinetic measurements, leading to a nonlinear correlation of log(k(obs)) with Hammett's substituent constants (a), The origin of the nonlinear Hammett plot was interpreted in terms of a shift in the rate-determining step of the multistep reaction with change of the electronic nature of substituent. Further support for this assumption was given by the observation that the reaction constant (p) of the Hammett plot for the azobenzene substituent effect on the oxidation rate of 4-bromobenzaldehyde was much smaller than that of 4-cyanobenzaldehyde.

紅茶葉からのカフェインの昇華(小・中・高のページ)
井上 正之, 清家 直樹, 中尾 守男, 中川 貴嗣, 景山 義之
化学と教育, 43, 10, 668, 668, 社団法人日本化学会, 20 Oct. 1995
Japanese

分子機械による巨視的な力学的仕事の実現
景山 義之, Colloid & Interface Communications, 48, 1, 34, 37, 10 Mar. 2023
生命体のような高度な自律機能を誇る分子システムを構築することは、超分子化学の一つの目標である。この分野では、従来、一個の分子機械の設計と合成に関心が向けられてきた。これに対して筆者は、分子機械を集積させることによって、巨視的な自律機能、例えば自律遊泳を実現する分子システムを構築したので報告する。, 公益社団法人 日本化学会 コロイドおよび界面化学部会, Japanese

Self-propulsion of a light-powered microscopic crystalline flapper in water
Kazuma Obara, Yoshiyuki Kageyama, Sadamu Takeda, Small, e2105302, 31 Aug. 2021, [Lead author, Corresponding author], [International Magazine]
A key goal in developing molecular microrobots that mimic real-world animal
dynamic behavior is to understand better the self-continuous progressive motion
resulting from collective molecular transformation. This study reports, for the
first time, the experimental realization of directional swimming of a
microcrystal that exhibits self-continuous reciprocating motion in a
two-dimensional water tank. Although the reciprocal flip motion of the crystals
was like that of a fish wagging its tail fin, many of the crystals swam in the
opposite direction to which a fish would swim. Here we explore the
directionality generation mechanism and physical features of the swimming
behavior by constructing a mathematical model for the crystalline flapper. The
results show that a tiny crystal with a less-deformable part in its flip fin
exhibits a pull-type stroke swimming, while a crystal with a fin that uniformly
deforms exhibits push-type kicking motion., English, 27475905

Micro-scale thin crystals swimming with a fish-like fin at low Reynolds number
小原一馬, 景山義之, 武田定, 日本化学会春季年会講演予稿集(CD-ROM), 100th, 2020

Motion and structural analysis of an azobenzene derivative crystal showing wave-type self-oscillation
矢崎大介, 池上智則, 景山義之, 武田定, 日本化学会春季年会講演予稿集(CD-ROM), 100th, 2020

可視光照射下において巨視的振動をする両親媒性アゾベンゼン誘導体結晶の構造と運動の解析
里永慎之介, 池上智則, 佐藤寛泰, 景山義之, 武田定, 日本化学会春季年会講演予稿集(CD-ROM), 99th, ROMBUNNO.3PB‐048, 01 Mar. 2019
Japanese

ミクロサイズの薄膜結晶の定常青色光照射で誘起される素早い振動運動による水中での遊泳運動
小原一馬, 景山義之, 武田定, 日本化学会春季年会講演予稿集(CD-ROM), 99th, ROMBUNNO.2I7‐50, 01 Mar. 2019
Japanese

極性高分子錯体の極性分子吸脱着による誘電応答と熱物性
溝上諒平, 景山義之, 丸田悟朗, 武田定, 分子科学討論会講演プログラム&要旨(Web), 13th, 2019

Synthesis of a probe for analysis hydration environment in the vicinity of phospholipid vesicle by using dynamic nuclear polarization NMR
LEE Gyeorye, 景山義之, 武田定, 電子スピンサイエンス学会年会講演要旨集, 58th, 2019

Design and synthesis of radical probe with photolabile group for DNP‐NMR analysis of dynamic water nearly molecular assembly
LEE Gyeorye, 景山義之, 武田定, 電子スピンサイエンス学会年会講演要旨集, 57th, 70‐71, 01 Nov. 2018
Japanese

自泳するアゾベンゼン含有ソフトマター
景山義之, 池上智則, 小原一馬, 里永慎之介, 武田定, 高分子学会予稿集(CD-ROM), 67, 2, ROMBUNNO.1S05, 29 Aug. 2018
Japanese

〔Major achievements〕MDB技術予測レポート　　　　　　　　　　　　　　　
景山義之, 自律的に物質を輸送する分子ロボットへの挑戦と課題
日本能率協会MDB, 13 Oct. 2023, [Contributor]

〔Major achievements〕Photosynergetic Responses in Molecules and Molecular Aggregates
KAGEYAMA Yoshiyuki, (Chapter 26) Interplay of photoisomerization and phase transition events provide a working supramolecular motor
Springer, Sep. 2020, English, 27475860, [Contributor]

自然科学実験2019　　　　　　　　　　　　　　　
景山 義之, C4 ものさしで測る分子の大きさと表面圧
学術図書出版社, Mar. 2019, 9784780606904, 11頁, Textbook, 授業用教科書, [Contributor]

〔Major achievements〕Molecular Technology: Energy Innovation
KAGEYAMA Yoshiyuki, TAKENAKA Yoshiko, HIGASHIGUCHI Kenji, (Chapter 8) Material Transfer and Spontaneous Motion in Mesoscopic Scale with Molecular Technology
Wiley, Jul. 2018, 9783527341634, 187-208, English, 11342187, [Contributor]

自然科学実験2018　　　　　　　　　　　　　　　
景山 義之, C4 ものさしで測る分子の大きさと表面圧
学術図書出版社, Mar. 2018, 11頁, Japanese, Textbook, 授業用教科書, [Contributor]

Submillimeter‐scale molecular‐based robots with self‐sustaining behavior
Yoshiyuki Kageyama
Workshop on Dissipative Processes in Molecular Systems, 20 Jun. 2024, English, Invited oral presentation
17 Jun. 2024 - 21 Jun. 2024, 42082235, [Invited]

〔Major achievements〕Synthesized micro-materials for self-sustainable works: Morphologies of active-molecule assemblies alter the apparent reaction kinetics　　　　　　　　　　　　　　　
Yoshiyuki Kageyama
The 61st Annual Meeting of the Biophysics Society of Japan, 15 Nov. 2023, English, Invited oral presentation
14 Nov. 2023 - 16 Nov. 2023, 名古屋市, [Invited], [International presentation]

Chemistry of Molecular Assemblies Demonstrating Self-Organized Behavior at the Cellular Scale
Yoshiyuki Kageyama
The 17th Symposium on Biorelevant Chemistry, 10 Sep. 2023, Japanese, Public symposium
08 Sep. 2023 - 10 Sep. 2023, 42082235, [Invited]

〔Major achievements〕Far-from-equilibrium behavior of ten-micrometer-scale artificial chemical assemblies ― Autocatalytic vesicular self-reproduction and light-powered crystalline self-oscillation
Yoshiyuki Kageyama
Systems Chemistry Virtual Symposium 2023, 10 Jul. 2023, English, Invited oral presentation
10 Jul. 2023 - 11 Jul. 2023, France, 27475905, [Invited], [International presentation]

〔Major achievements〕Light-driven self-oscillatory crystal — Concerted mechanical function generated in a reaction system with varying kinetic rate constants
Yoshiyuki Kageyama
日本化学会第103春季年会 中長期テーマシンポジウム 「次世代分子システム化学のフロンティア―協奏的機能発現のメカニズム」, 23 Mar. 2023, Japanese, Invited oral presentation
22 Mar. 2023 - 25 Mar. 2023, Macroscopic functions of multimolecular systems of molecular machines under non-equilibrium conditions attract increasing attention, with the aim of constructing life-like autonomous objects and realizing autonomous molecular robots. Such research will take advantage only when the composition of the system continuously changes and consequently continues to perform mechanical work, even when the energy supply is constant without any information. Such a system is known as far-away-from-equilibrium, which is the antonym of steady state. The composition of a multi-molecular object under a steady condition is generally determined by the reaction kinetic coefficients in the object. It means that concerted mechanisms to oscillate or fluctuate the kinetic coefficients are required for far-from- equilibrium dynamics. In our light-driven self-oscillatory crystal, reversible photoisomerization-induced phase-transition of the crystal acts as a bifurcation for switching the kinetic coefficients of the photoisomerization. The oscillation in the component and the repetitive morphological change causes the oscillation in the free energy of the object to realize mechanical work. The physical background of the light-powered behavior will be discussed., 27475905, [Invited], [Domestic Conference]

発動分子の階層化による自己秩序機能の創出
景山義之
「発動分子科学」成果報告会～分子の発動が拓く次世代の化学～ 日本化学会第103春季年会併催シンポジウム, 22 Mar. 2023, Japanese, Public discourse
27475905

〔Major achievements〕自律性を有した合成分子ロボットと実機能化のための課題
景山義之
新化学技術推進協会 電子情報技術部会 マイクロナノシステムと材料・加工分科会勉強会, 13 Dec. 2022, 公益社団法人 新化学技術推進協会（JACI）・電子情報技術部会・マイクロナノシステムと材料・加工分科会, Public discourse
13 Dec. 2022 - 13 Dec. 2022, オンライン, 27475905, [Invited], [Domestic Conference]

光で駆動する自励振動結晶 ― その仕組みと特徴
景山義之
第32回 非線形反応と協同現象研究会, 03 Dec. 2022, 非線形反応と協同現象研究会
03 Dec. 2022 - 03 Dec. 2022, お茶の水大学, 27475905, [Invited]

ナノ構造からの自律機能性材料の実現
景山義之
第26回VBLシンポジウム, 24 Nov. 2022, 名古屋大学ベンチャー・ビジネス・ラボラトリー, Public discourse
24 Nov. 2022 - 25 Nov. 2022, 名古屋大学, 27475905, [Invited], [Domestic Conference]

化学反応で自律系を創るということと、そこから生まれる新視点　　　　　　　　　　　　　　　
景山義之
氷雪セミナー（日本分析学会・北海道支部）, 11 Jan. 2022, Invited oral presentation
[Invited]

Self-organization of repetitive transformations in tiny azobenzenes to realize autonomous mechanical function on a macroscopic scale
Yoshiyuki Kageyama, Tomonori Ikegami, Sadamu Takeda
PACIFICHEM2021, 20 Dec. 2021, English, Invited oral presentation
15 Dec. 2021 - 20 Dec. 2021, 27475905, [Invited], [International presentation]

Shape change and work behavior of bistable self-oscillatory photochromic material in aqueous condition towards microrobot
第21回名古屋国際数学コンファレンス, 28 Sep. 2021, English, Invited oral presentation
26 Sep. 2021 - 29 Sep. 2021, 27475912, [Invited]

Mechanically “working” softcrystal under steady light irradiation　　　　　　　　　　　　　　　
Yoshiyuki Kageyama
錯体化学討論会シンポジウム, 16 Sep. 2021, English, Invited oral presentation
[Invited]

やわらかい結晶のしなやかな光駆動自律運動
景山義之
第80回分析化学討論会, 日本分析化学会, Japanese, Invited oral presentation
23 May 2020 - 24 May 2020, 北海道教育大学札幌校（ＣＯＶＩＤのため開催中止）, Japan, 27475905, [Invited], [Domestic Conference]

両親媒性アゾベンゼン誘導体の集合体がみせる自己秩序型メカニカル運動　　　　　　　　　　　　　　　
景山 義之, 池上 智則, 小原 一馬, 里永 慎之介, 佐藤 寛泰, 武田 定
第68回高分子討論会, 26 Sep. 2019, Japanese, Invited oral presentation
[Invited], [Domestic Conference]

生命システムを有機化学で模倣する：分子集合体の自己複製と自律運動　　　　　　　　　　　　　　　
景山 義之
高分子研究会（鳥取）, 02 Jul. 2019, Japanese, Public discourse
[Invited], [Domestic Conference]

化学で創る分子モーターと実働のための自己組織化　　　　　　　　　　　　　　　
景山 義之
分子モーター研究会, 28 Jun. 2019, Japanese, Invited oral presentation
[Invited], [Domestic Conference]

Continuous Mechanical Motion of Layered Self -Assembly of Azobenzene Derivatives under Photo Stationary State　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
Asian International Symposium - Photochemistry -, 18 Mar. 2019, English, Invited oral presentation
[Invited], [International presentation]

Light-driven limit-cycle self-oscillation and autonomous swimming of azobenzene-assembly under photostationary state
KAGEYAMA Yoshiyuki
Active Matter Workshop 2019, 12 Jan. 2019, English, Invited oral presentation
Nakano, Tokyo, [Invited], [Domestic Conference]

Self-sustained dynamics of molecular assembly towards construction of autonomous molecular systems　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
Hokkaido-Strasbourg Symposium Biotic and Abiotic Molecular Machines and Motors, 14 Nov. 2018, English, Invited oral presentation
[Invited], [International presentation]

Creations of molecular assemblies which show continuous morphological changes　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
Muroran Seminar of CSJ-Hokkaido, 09 Oct. 2018, Japanese, Public discourse
[Invited], [Domestic Conference]

Light-powered self-sustained mechanical motion of azobenzene crystal as the resultant of a couple of photoreaction and phase transition
KAGEYAMA Yoshiyuki
The 79th Okazaki Conference: Synthetic, Biological, and Hybrid Molecular Engines, 31 Aug. 2018, 分子科学研究所, English, Invited oral presentation
岡崎市, [Invited], [International presentation]

〔Major achievements〕Self-oscillatory motion of molecular assembly with self-organization in non-equilibrium steady-state
KAGEYAMA Yoshiyuki
International Symposium on Biofunctional Chemistry, 15 Dec. 2017, 日本化学会生体機能関連化学部会, English, Invited oral presentation
宇治市, [Invited], [International presentation]

Self-organization of molecular machine for autonomous macroscopic motion under non-equilibrium steady state
KAGEYAMA Yoshiyuki
First MIRAI Seminar, 18 Oct. 2017, English, Invited oral presentation
[Invited], [International presentation]

集団として動き続ける分子システムの創出 ― 生命の散逸性の模倣とそ こから生まれる機能
景山 義之
ChemBioハイブリッドセミナー, 30 Sep. 2017, 東京大学大学院工学系研究科化学生命専攻, Japanese, Invited oral presentation
[Invited], [Domestic Conference]

自己秩序的に動き続ける分子集合体の創出 — 散逸性とその機能　　　　　　　　　　　　　　　
景山 義之
北海道高分子若手研究会, 09 Sep. 2017, Japanese, Invited oral presentation
[Invited], [Domestic Conference]

Design and creation of autonomous dynamics in self-assemblies　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
The 3rd International Conference on Organic & Inorganic Chemistry, 18 Jul. 2017, English, Keynote oral presentation
[Invited], [International presentation]

定常状態でリミットサイクル振動を実現したアゾベンゼン含有分子集合体の光誘起メカニカル運動　　　　　　　　　　　　　　　
景山 義之
ソフトロボット：メカニカル材料 シンポジウム, 27 May 2017, Japanese, Invited oral presentation
[Invited], [Domestic Conference]

Auto-Oscillatory Flipping Motion of Azobenzene Containing Organic Co-crystal under Continuous Light Irradiation　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
Asian International Symposium (Organic Crystals), 17 Mar. 2017, English, Invited oral presentation
[Invited], [International presentation]

Organized Motion of Macroscopic Molecular Assembly Comprised of Azobenzene Derivatives under Light Irradiation　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
HOKUDAI-NCTU International Joint Symposium on Nano, Opto and Bio Sciences, 04 Oct. 2016, English, Invited oral presentation
[Invited], [International presentation]

Macroscopically Working Artificial Molecular Motor: Steady and Autonomous Conversion of Light Energy to Mechanical Motion with Dissipative Self-Organization　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
International Symposium on Pure and Applied Chemistry, 17 Aug. 2016, English, Invited oral presentation
[Invited], [International presentation]

Macroscopically Working Light-Powered Molecular Motor: Dissipative Self-Organization Resultant Oscillation　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
The 12th HU-NU-MINS/MANA joint symposium, 29 Jul. 2016, English, Invited oral presentation
[Invited], [International presentation]

ヘテロ集積分子集合体の方向性をもった遊泳
Yoshiyuki Kageyama
日本化学会春季年会講演予稿集, 10 Mar. 2016, Japanese, Invited oral presentation
[Invited], [Domestic Conference]

Dissipative and Autonomous Motion of a Self-Assembly　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
The 4th International Postgraduate Conference on Pharmaceutical Sciences 2016, 28 Feb. 2016, English, Invited oral presentation
[Invited], [International presentation]

Cooperative Deprotonation Induced Macroscopic Morphological Transformation of Multi-Component Molecular Assembly Actuated by Azobenzene- Photoisomerization　　　　　　　　　　　　　　　
KAGEYAMA Yoshiyuki
International Conference on Small Science, 06 Nov. 2015, English, Invited oral presentation
[Invited], [International presentation]

2SDP-04 Macroscopic Motion of Soft Non-covalent Molecular Assembly in Water Actuated by Chemically Synthesized Molecular Machine(Biomolecular machinery driven by surrounding water,Symposium,The 52th Annual Meeting of the Biophysical Society of Japan(BSJ20
Kageyama Yoshiyuki
Biophysics, 20 Aug. 2014, English, Invited oral presentation
[Invited]

踊るケミカルAIの計算間違いを量る
科学研究費助成事業 学術変革領域研究(A)
01 Apr. 2023 - 31 Mar. 2025
景山 義之
日本学術振興会, 学術変革領域研究(A), 北海道大学, 23H04392

Emergence of autonomous functions through hierarchical integration of molecular engines
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
29 Jun. 2018 - 31 Mar. 2023
角五 彰, 景山 義之
生体分子モーターは優れた運動効率、高い比出力を備えた生体由来の発動分子（生体発動分子）である。この発動分子を動力源としたアクチュエーターの開発が各国で盛んに行われている。しかし、依然として実用化への道のりは遠いのが現状である。その理由として発動分子の決定論的な動作が保障されていない、耐久性や熱安定性が低い、ダイナミクスを制御・操作する技術が確立されていないなどの要因がある。本研究では生体分子モーターに人工修飾を加えたハイブリッド型生体発動分子を創出・集積し、集団で機能するエネルギー変換素子の創成を目指す。併せて人工の発動分子の集団エネルギー変換系の構築に取り組み、時空間的階層性を有した分子運動系の基礎学理構築を目指している。本年度（平成 30 年度）には、二次元界面上での生体発動分子（キネシン）の運動発現に取り組み、生体発動分子をエラストマーやリン脂質などから構成されるソフトな二次元界面上に固定化する技術を確立させた。さらに領域内連携によりATPをエネルギー源とした生体発動分子（微小管）の機械的な運動を二次元界面上で発現させ、ロバストな運動のイメージング解析を確立させた。また実験環境下での生体発動分子、特にキネシンの効率的な駆動を実現するために、班員が有する特許（熱安定化変異体のスクリーニング法をもとに熱耐性キネシンの開発に着手した。
同時に人工発動分子の集団エネルギー変換系の学理構築に向け、①既に構築している人工発動分子集合体の自律運動について数理科学者・物理学者との連携研究の開始、および②新たに構築する化学基質駆動型の人工発動分子システムの創出に向けた試料の合成と、その二次元界面への固定化に着手した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Hokkaido University, 18H05423

光異性化分子の「動き」がつくる分子集合体の「動き」を数理モデルから解き明かす
科学研究費助成事業 新学術領域研究(研究領域提案型)
01 Apr. 2020 - 31 Mar. 2022
景山 義之
日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, 20H04622

Investigation into Interplay of Reversible Photoisomerization and Structural Phase Transition in the Self-Oscillatory Flipping of Molecular Assemblies
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
01 Apr. 2017 - 31 Mar. 2019
景山 義之
物質自体の性質により光照射下で自発的に屈曲運動を繰り返す「アゾベンゼン誘導体含有薄膜状結晶」について、物理化学的あるいは化学物理的考察を推進することが、当該研究である。結晶であるにもかかわらず屈曲することに加え、光定常状態でその屈曲を繰り返す点で、研究大雨小の物質は他に類を見ない物質といえる。
前年度に、アゾベンゼン誘導体(1)を成分とする結晶の暗所での構造解析に成功した。原子密度が疎な層と原子密度が密な層とが交互に積層した結晶構造から、原子密度が疎な相での光異性化が結晶の構造相転移を誘起すること、および原子密度が密な相が結晶の集積状態を保っていること、が推測された。
今年度は、光照射下で形成するもう一つの結晶相の構造解析や過渡的変化の計測を目標に、独ポツダム大学との国際共同研究で、欧州放射光施設でのX線回折実験を試みた。しかし、一時的に形成する結晶を対象にしたX線回折実験は難しく、目標は達成できなかった。計測できなかった要因の一つは、光照射下で形成した屈曲した結晶が、単結晶ではなく、小さな結晶ドメインの集合体であるためではないかと考えている。
この仮説は、構造の異なるアゾベンゼン誘導体(2)が形成する大きめの結晶の光照射下での運動を観察することで、信憑性を帯びてきた。大きめの結晶は、屈曲運動ではなく、波状運動をみせる。これは、結晶が単結晶である場合には説明しにくい、「伝搬」が働く現象である。
すなわち、分子レベルでの可逆な光異性化が微視的な結晶の可逆な相転移を引き起こすこと、微視的結晶の可逆な相転移がマクロな結晶の可逆な構造変化を引き起こすこと、の二段階の自己組織化ダイナミクスが、この「光照射下で自律的に機械振動をみせる結晶」の中で起きていると推察された。これは、多くの化学者が漠然と興味を抱く「自己組織化」現象の基礎的かつ本質的理解を促す成果であり、継続的な研究展開が望まれる。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Hokkaido University, 17H05247

Creation of Autonomous Macroscopic Motion using Asymmetric Transition of Organometallic Catalyst with Consumption of Chiral Chemical Fuels
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
01 Apr. 2017 - 31 Mar. 2019
景山 義之
分子機械の構造変化を、熱力学の規律が働くマクロスコピックな継続運動へと変換するためには、空間的な対称性の破れが必要である。これに、時間的な対称性の破れ・反応の継続性が加わり、相や場で組織化することにより、マクロなレベルで自律的に動き続ける散逸分子システムを創出可能である。
このコンセプトの確立を目的に、本研究課題では、化学反応で連続駆動する有機金属触媒を、自己配向性を有する液晶分子を用いて集積し、供給したエネルギーを消費しながら自律的に駆動する分子システムを創出する。この研究を通じて、上記仮説の証明と、ミクロとマクロをつなぐ物理的な関係を追究し、自律駆動デバイス・能動的デバイス創出にかかわる基礎学理を構築していく。
平成２９年度は、当初計画に従い、芳香族配位子を有したパラジウム触媒とシアノビフェニル系液晶分子を混合した液晶性触媒反応場を調製し、その反応場を利用した鈴木宮浦カップリング反応を行った。まずは、不斉炭素を持たない基質を用い、反応場の触媒活性を評価した。一般的な溶液系での反応と比較し、触媒反応効率の低下が起きたものの、目的のカップリング反応を進めることはできた。反応効率低下の理由は、反応が起こる表面が少ないこと、液晶分子自体の反応による目的反応の阻害、あるいは、触媒分子の構造変化自由度が液晶分子によって阻害された、などの原因が考えらえるが、三つ目の仮説の場合、触媒分子の構造変化が液晶分子の運動状態に影響を与えていることになる。このほか、基質の反応率に対して目的物の生成量が十分ではないなど、計画申請当初想定していた「研究上の困難点」が現れてきている。
これに伴い、困難が生じた場合の対処法として計画していた、自己集積膜(SAM)などの組織化膜を用いた実験系の準備にも取り掛かり始めた。なお、困難点の発生も含め、研究はほぼ計画通りに進行している。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Hokkaido University, 17H05346

Comparing the rheology of water surrounding soft matter surfaces using dynamic nuclear polarization NMR measurement.
Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
01 Apr. 2016 - 31 Mar. 2019
KAGEYAMA Yoshiyuki, TAKEDA Sadamu, KONDO Ryota, LEE Gyeorye
Polymers and molecular assemblies exhibited in water (e.g. peptides and bio-membranes), stabilize their structures with the interaction between water and are worked cooperatively with water molecules. The aim of this research project is in developing the method to reveal the dynamic behavior of water surrounding such soft assemblies.
In this project, we developed our home-made measurement system for in-situ dynamic nuclear polarization nuclear magnetic resonance, with synthesizing a newly functional probe, which change its structure by light-irradiation. Next step, we will develop the understanding about movement of water molecule around soft materials via discussion about the obtained results with physicists.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 16K17849

ヘテロ集積分子集合体の方向性をもった遊泳
PRESTO
Oct. 2013 - Mar. 2017
KAGEYAMA Yoshiyuki
「光異性化による分子集合体の散逸自己組織化」を世界で初めて実現した。
JST, Principal investigator, Competitive research funding

Dynamic property at molecular scale in large molecular assembly
Grants-in-Aid for Scientific Research
01 Apr. 2014 - 31 Mar. 2016
TAKEDA SADAMU, KAGEYAMA YOSHIYUKI
In our laboratory, we have found reversible macroscopic motion of supramolecular aggregate was induced by photo-isomerization of doped azo-benzene derivative as a minor component. This phenomenon is similar to biological system, in which motion of molecules is hierarchically and cooperatively developed to induce macroscopic movement. In this research project, we made an attempt to develop “Scanning NMR Microscope” for investigating change at molecular level in supramolecular aggregate at spatial resolution of 100 micrometer by use of micro-coil NMR method. As a complementary approach of this “Scanning NMR Microscope”, enhancement of NMR signal was investigated by use of dynamic nuclear polarization.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 26620001

Spin Transition and Crystal Defects in Coordination Compounds: a Solid-State High-Resolution NMR Study
Grants-in-Aid for Scientific Research
01 Apr. 2012 - 31 Mar. 2015
GORO Maruta, KAGEYAMA Yoshiyuki
Changes in temperature of a solid material containing metal ions may cause electron jump between (1) atomic orbitals in the metal ion or (2) the metal ion and carbon atoms or (3) metal ions arranged in the crystal, which in turn causes a drastic change in the magnetic property of the solid.
This research has showed that the electron jump can be detected using the accompanying alterations in molecular shape and in ionic size with a commercially available apparatus called NMR spectrometer.
With this method, we have succeeded in measuring the frequency of an electron jump, which is difficult to measure by other experimental methods.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24550003

Measurement of rheology of water surrounding molecular assembly toward revealing the water-cooperated chemical phenomena in life
Grants-in-Aid for Scientific Research
2013 - 2014
KAGEYAMA YOSHIYUKI, TAKEDA Sadamu
As the main component of living cells is water, life phenomena are presented in water. Water surrounds cellular membranes, peptides, and other biomolecules. The surrounding water has different characteristics than general water, and the characteristics are related to the brilliant functions of biomolecules. Therefore, a development of a characteristic water analysis is required to reveal the biological phenomena.
Selective analysis of specific water in bulk water is difficult. One potent method is the Overhauser dynamic nuclear polarization nuclear magnetic resonance (DNP-NMR). For our project, we equipped an instrument to measure the water molecules using DNP-NMR. We also used organic synthetic techniques to prepare artificial molecular assemblies, and measured the water surrounding the assemblies. In perspective, it is required to improve the accuracy of quantitative discussions for rheology of water by merging the theoretical approach with further measurements.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 25620002

Control of Proton-Cooperated Macroscopic Flexible Dynamics ofHelical Myelin Tube
Grants-in-Aid for Scientific Research
2011 - 2012
KAGEYAMA Yoshiyuki
The aim of the project is to control the motion of sub-millimeter size myelin self-assembly (myelin tube) composed of oleic acid and functional organic molecules. Amphiphilic azobenzene containing myelin tubes showed straighten and coiling motion by photoirradiation with ultraviolet light and visible light, respectively. In the photoinduced macroscopic dynamics, it became clear that both of structural change of azobenzene molecule by photoisomerization and acid dissociation behavior of oleic acids byazobenzene-isomerization take an important role.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 23750142

オレイン酸を主成分とする螺旋状超分子の形成挙動に対する添加分子の役割の解明　　　　　　　　　　　　　　　
笹川科学研究助成(学術)
Apr. 2010 - Mar. 2011
景山 義之
日本科学協会, Principal investigator, Competitive research funding

細胞内イオンを利用する分子集積に基づく新しい抗がんシステムの開発
科学研究費助成事業
2007 - 2009
青木 伸, 北村 正典, 景山 義之
アポトーシスは、固体の生命を維持するために、遺伝子によって制御された細胞死であり、不要になった細胞や有害な細胞を除去する現象である。アポトーシスの誘起機構の一つとして、ミトコンドリアから遊離したカスパーゼ-9がカスパーゼ-3を活性化する経路がある。しかし、がん細胞は、カスパーゼ-9と複合体を生成するタンパクであるXIAPが、カスパーゼ-9と複合体を生成して不活性化する防御機構をもっている。
そこで本研究では、XIAPを認識するペプチドと金属イオンキレート部をもつ化合物(L-ペプチド)を設計、合成する。がん細胞内でbpy-ペプチドが金属イオンによって自己集積してM(L-ペプチド)を生成し、M(L-ペプチド)-XIAP複合体の生成によってカスパーゼ-9を遊離してアポトーシス誘導を行う。
平成21年度は、平成20年度に合成した2,2'-bipyridyl(bpy)基を有するジペプチド体とモノペプチド体の合成に加えて、リンカーとしてbis(picolyl)amino(BPA)基とN,N'-bis(picolyl)ethylenediamine(BISPICEN)基を有する化合物の合成に成功した。これらのXIAP結合能を蛍光偏光法によって測定したところ、いずれの化合物もnMオーダーのIC_<50>値を有することが明らかになった。亜鉛イオンの効果を検討したところ、BPAリンカーを有する化合物において、亜鉛イオンの効果が認められた。亜鉛イオン存在下、非存在下での差は決して大きくはないが(Zn^<2+>非存在下で44nM、Zn^<2+>存在下で27nM)、さらに強いZn^<2+>キレーターを加えると、IC_<50>値がZn^<2+>非存在下の値に近づいたことなどから、Zn^<2+>との錯体生成がXIAPへの結合を増大させたことが示唆された。また、弱いながらもがん細胞に対するアポトーシス誘導も観測された。現在、これらの成果を発表するべく、論文投稿の準備中である。
日本学術振興会, 挑戦的萌芽研究, 東京理科大学, 19659026

Development of Photolabile Biotin Linkers by Using New Caged Compounds
Grants-in-Aid for Scientific Research
2006 - 2009
AOKI Shin, YAMADA Yasuyuki, KITAMURA Masanori
(+)-ビオチン(Btn)は、アビジン(Avn)と非常に安定な複合体を生成する。その解離定数Kdは約1fMであり、通常の抗原-抗体複合体の100万倍も強く、実質上不可逆である。本研究は、申請者らが発見したCaged化合物(8-quinolinyl sulfonates, QS)の光分解反応を利用することにより、光分解性Btn標識試薬の開発を目的とした。中性pH、常温という温和な条件下、光照射によってリガンド-レセプター複合体をintactな状態で回収し、特異的レセプターの同定、構造解析を行うための全く新しいBtn-Avnシステムを提供する。
脳内神経伝達分子であるドーパミンを、光分解性QSリンカーを介してビオチンに結合した化合物(Biotin-Dopamine-HQ)の合成を行った。Biotin-Dopamine-HQと抗ドーパミン抗体(IgG)、および二次抗体(抗IgG抗体)を用いてELISAを行い、Avn、Biotin-Dopamine-HQ、IgG、抗IgG抗体の四者の複合体が生成することを確認した。さらにAvn、Biotin-Dopamine-HQ、IgGの三元複合体に光を照射し、リンカーが分解できることを確認し、分解後のDopamine-IgGの、Western blottingによる検出に成功した。以上の結果は、すでに論文発表された(Bioorg. Med. Chem. 2009, 17, 3405-3413)。
また、上記の化合物もよりも長いリンカーを有するビオチン標識リンカーの合成にも成功した。同様にELISA、Western blottingを行ったところ、リンカーの延長は抗体との複合体形成、光分解にDopamine-抗体複合体の回収率に大きな変化はなかった。本結果についても、論文投稿の準備中である。さらに、本技術の基盤となるQS基質の光分解反応の反応機構についても詳細に検討し、論文投稿済みである。
このように、本研究ではQS基質の新規光分解反応の発見、反応機構の解明を行い、それを光分解性Btn標識リンカーにまで応用した。現在、光分解性リポソームなどにも展開可能であり、今後が期待される。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Tokyo University of Science, 18390009