Joint Symposium of Peking

University & Waseda University

on Practical Nano-Chemistry

51-Bldg., Conference Room 2,School of Science and Engineering,

Waseda UniversityNovember 27, 2004

Organized by College of Chemistry, Peking University, Chinaand 21COE Program “ Practical Nano-Chemistry”

at Waseda University from MEXT, Japan

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Scientific Program

9:30 Welcoming Remarks (Prof. K. Tatsuta)9:40 Opening Remarks (Prof. S. Gao)

Morning Session:Chairman: Prof. H. Nishide

9:45-10:15 Prof. Y-H. Shao"Electrochemistry at Liquid/liquid Interfaces and its Application in Detection of Molecules with Biological Interest "

10:15-10:40 Assoc. Prof. T. Homma"Electrochemical Fabrication Processes for Functional Micro/Nano Structures and Devices"

10:40-10:55 Coffee break and take photos10:55-11:25 Prof. S. Gao

"Mixed-magnet Behaviors of EuS Nanoparticles Synthesized by Thermal Decomposition of Molecular Precursors”

11:25-11:50 Prof. Y. Sugahara"Nano-Chemistry Based on Layered Perovskites: "Chimie Douce" Approach"

12:00-13:00 Lunch

Afternoon Session:Chairman: Prof. K. Ishihara13:00-13:30 Prof. Jian-Bin Huang

"Transformation of Organized Assemblies in Surfactant Solutions"13:30-13:55 Prof. K. Ishihara

"Novel Reactivity of Platinum(III) Dinuclear Complexes"13.55-14:25 Prof. Li-Min Qi

"Controlled Synthesis of Silver Nanostructures with Novel Morphologies"14:25-14:50 Prof. T. Asahi

"Chiro-Optical Study of Nano-Structured Materials"14:50-15:05 Coffee Break15:05-15:35 Prof. Z-C. Li

"Synthesis and Photochemical Behavior of Vinyl Monomers Having Chromophore Moieties and Their Polymers"

15:35-16:00 Assoc. Prof. S. Takeoka"Modulation of Molecular Assembling States for Drug Delivery"

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Poster Session16:00-17:301. K. Sumitomo and K. Matsumoto“Fluorescence Properties of Lanthanide Fluorescence Chelates”

2. Y. Yamauchi and H. Nakai“Analysis Technique of ab Initio Molecular Dynamics Simulation: Energy Transfer Spectrogram”

3. T. Iwasaki, Y. Kohinata, K. Katayose, and H. Nishide“Synthetically Helicity-Control in Conjugated Polymers Comprised of Fused Sulfur-Containing Aromatic Ring”

4. M. Yoshino, T. Masuda, J. Sasano, I. Matsuda, and T. Osaka“Proposal of Novel Fabrication Process for the Diffusion Barrier Layer-Application to Low-K Material-“

5. K. Tatsumura, T. Simura, and I. Ohdomari“Structural Analysis of Thermally Grown Si02 on c-Si by X-ray Diffraction and Molecular Dynamics Simulation”

6. E. Miyasaka, Y. Kato, and I. Hirasawa“Effect of Ultrasound Irradiation on the Crystal Size of Aspirin Produced in the Supersaturated Solution”

7. K. Urasaki, Y. Sekine, E. Kikuchi, and M. Matsukata“Hydrogen Production by Steam Reforming of Methane over Ni/Perovskite Catalysts”

8. S. Tahara and Y. Sugahara“Interlayer Surface Modification of the Protonated Ion-Exchangeable Layered Perovskite

HCa2Nb3O10・ｘH2O with n-Alcohol”

9. M. Tanaka, N. Nakamura, T. Asahi, T. Osaka, K. Kuroda, and M. Ogawa“Optical Study of Dye Intercalated in K4Nb6017 Single Crystal Using the Generalized High Accuracy Universal Polarimeter”

10. D. Mochizuki and K. Kuroda“Novel Silica Nanostructures Derived from Hydrolysis of Alkoxysilylated Layered Silicate”

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11. M. Sato and K. Kino“Substrate Specificity of D-Alanine-D-Alanine Ligase and Utilization of the Enzyme for D-Amino Acid Dipeptide Production”

12. T. Terahara, S. Harayama and S. Tsuneda“Development of Methods to Isolate Useful Genes from Uncultured Microorganisms”

13. Y. Okamura and S. Takeoka“Hemostatic Effects of Fibrinogen-γ Chain Dodecapeptide-Nanoparticles in vitro and in vivo”

Electrochemistry at Liquid/liquid Interfaces and its Application in Detection of Molecules with Biological Interest

Yunahua SHAO

Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

In this presentation, we will provide a brief introduction about electrochemistry at liquid/liquid (L/L) interface and report our recent work related to biomolecules detection based on charge transfer reactions at L/L interfaces. We will focus on the following three systems: (1) Charge transfer kinetics; (2) Detection of ionizable drugs; (3) Detection of dopamin.

The kinetics of ET and IT has been evaluated by nanopipets and scanning electrochemical microscopy. The Marcus inverted region has been observed for electron transfer and facilitated ion transfer reactions.

The electrochemical behavior of ionizable drugs (Amitriptyline, Diphenhydramine and Trihexyphenedyl ) at the water/1,2-dichloroethane interface with different phase volume ratios (r = VO/VW) are investigated by a droplet electrode setup. The system is composed of an aqueous (or an organic) droplet supported at an Ag/AgCl (or at an Ag/AgTPBCl)disk electrode and covered it with an organic (or an aqueous) solution. In this manner, a conventional three-electrode potentiostat can be used to study ionizable drugs transfer process at a liquid /liquid interface. Physicochemical parameters such as the formal transfer potential, the Gibbs energy of transfer and the standard partition coefficients of the ionized forms of these drugs can be evaluated from cyclic voltammograms obtianed. The obtained results have been summarized in ionic partition diagrams, which are useful tool to predict and interpret the transfer mechanisms of ionizable drugs at the liquid/liquid interfaces and biological membranes.

Ion transfer (IT), facilitated ion transfer (FIT) of protonated dopamine and electron transfer (ET) between dopamine and ferrocene are investigated at the water/1,2-dichloroethane (W/DCE) interface. The IT and FIT reactions of protonated dopamine can be observed simultaneously within the same potential window. The experimental results demonstrate that dibenzo-18-crown-6 (DB18C6), dibenzo-24-crown-8 (DB24C8), benzo-15-crown-5 (B15C5) work well with the protonated dopamine. The amperometric detection of dopamine based on either the IT or the FIT of protonated dopamine can get rid of the interference of ascorbic acid, and the lowest concentration can be determined is about 0.05 μM by differential pulse voltammetry. For the ET reaction, its kinetics can be evaluated by

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scanning electrochemical microscopy (SECM), and the results show that the relationship between rate constants and driving force at the unmodified W/DCE interface obeys the Butler-Volmer equation in a rather wide potential region. When the W/DCE interface is modified by the egg lecithin, the ET rate constants decrease with the increasing concentration of egg lecithin, which indicates that the egg lecithin hinders the ET reaction. When the driving force is increased to a certain degree, the linear relationship between ET rate constants and the driving force is distorted. These results will be helpful to understand both the pharmacodynamics and the neural signal transmission mechanism of dopamine at biological membranes, and also provide a novel way to detect dopamine.

Electrochemical Fabrication Processes for Functional Micro/Nano Structures and Devices

Takayuki HOMMA

Department of Applied Chemistry, Waseda UniversityOkubo, Shinjuku, Tokyo 169-8555, Japan

Electrochemical processes such as electrolytic and electroless deposition, as well as etching, have been utilized in various field of micro and nano scale fabrication such as MEMSs and micro-TASs featuring their capability to form precise micro/nano structures. In order to fabricate the devices and systems with higher performance and smaller size, demands for developing further presice processes are continuously increasing. In this paper, results of our resent researches for developing novel electrochemical micro/nano fabricatig processes are described.

We attempted to develop the area-selective formation process of the array of micropores at the Si surface for the potential use of various microscale systems such as interconnects for 3D packaging and fluid channels for micro TAS, using electrochemical anodization process of Si wafer surface [1]. Furthermore, by using this process in combination with the surface oxidation process, array of the nanovolume glass tubes was fabricated.

It was also found that, by immersing Si wafer into aqueous solution containing trace amount of metal ion species, preferential deposition of metal nanoparticles took place at nanoscopic defect sites on the wafer surface. Scanning surface potential microscopy (SPoM) analysis revealed that the defect sites possessed relatively negative potential with respect to the non-defected area. By controlling such a local potential of the surface sites, a maskless fabrication process of patterned nanostructures such as nano dot arrays of Au, Ag, Cu, and Co, onto Si surfaces, has been developed [2].

[1] T. Homma, H. Sato, K. Mori, T. Osaka, S. Shoji, J. Phys. Chem. B, submitted.[2] T. Homma, N. Kubo, T. Osaka, Electrochim. Acta, 48, 3115 (2003).

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Mixed-magnet Behaviors of EuS Nanoparticles Synthesized by Thermal Decomposition of Molecular Precursors

Fei ZHAO1, Hao-Ling SUN1, Song GAO1,*, Gang SU2

1 State Key Laboratory of Rare Earth Materials Chemistry and Applications & PKU-HKU Joint Laboratory on Rare Earth Materials and Bioinorganic Chemistry, College of Chemistry

and Molecular Engineering, Peking University, Beijing 100871, P. R. China. E-mail: gaosong@pku.edu.cn

2 College of Physical Sciences, Graduate School of the Chinese Academy of Sciences, P. O. Box 3908, Beijing 100039, P. R. China.

In this work, we developed an direct and facile method to synthesize Europium(II) sulfide nanoparticels with average particle size of 5.5 nm and small size distribution by thermal decomposition of molecular precursors at quite low temperature 200 C. A gradually change from bulk ferromagnet to spin glass and cluster glass and finally to superparamagnet was observed when the particle size is reduced close to the critical size of single domain. Moreover, a quasi-ferrimagnetic behavior was observed in the smallest EuS sample upon oxidation of the surface. These results are interesting and helpful in systematically understanding the relationship between the magnetic properties and the size of nanoscale ferromagnetic materials.

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This work was supported by the National Science Fund for Distinguished Young Scholars (20125104), NSFC no. 20221101 and 20490210.

Nano-chemistry Based on Layered Perovskites: "Chimie Douce" Approach

Yoshiyuki SUGAHARA

Department of Applied Chemistry, Waseda UniversityOhkubo-3, Shinjuku-ku, Tokyo 169-8555 JAPAN

TEL/FAX: +81-3-5286-3204 E-mail: ys6546@waseda.jphttp://www.appchem.waseda.ac.jp/fm-eng/SUGAHA-E.HTM

Ion-exchangeable layered perovskites, M[Am-1BmO3m+1] (the “Dion-Jacobson phases”) and M2[Am-1BmO3m+1] (the “Ruddlesden-Popper phases”), consist of two-dimensional perovskite-like slabs characterized by a sliced ABO3 perovskite structure (m expressing the thickness of the perovskite slabs) and exchangeable interlayer cations.[1] When the layered perovskites are treated with mineral acids, corresponding protonated forms (H[Am-1BmO3m+1] and H2[Am-

1BmO3m+1]) can be easily obtained. We have developed novel routes to the protonated forms of ion-exchangeable layered perovskites and layered tungstic acid via acid treatment of Aurivillius Phases, Bi2Am-1BmO3m+3, which possess similar perovskite-like slabs in their structures. The selective leaching of bismuth oxide sheets and simultaneous introduction of protons in their interlayer space result in the formation of new protonated compounds. Acid treatment of Bi2NaAB3O12 (A = Sr, Ca, B=Nb; A = Ca, B = Ta) led to the formation of triple-layered H1.8NaA0.8Bi0.2Nb3O10. In a similar fashion, double-layered H1.8Sr0.2Bi0.8Nb2O7 was formed upon acid treatment of Bi2SrNb2O9. When an A-site deficient Aurivillius Phase,

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Bi2W2O9, was acid-treated, double-layered tungstic acid, H2W2O7.xH2O, was obtained. The

resulting protonated compounds exhibit interesting properties, including photocatalytic activity and intercalation behavior.

[1] Schaak, R. E.; Mallouk, T. E. Chem. Mater. 2002, 14, 1455.

Transformation of Organized Assemblies in Surfactant Solutions

Jian-Bin HUANG

College of Chemistry, Peking University, Beijing 100871, China

Email：JBHuang@.pku.edu.cn

By the variation of molecular structure and physi-chemical conditions, the formation and transformation of amphiphilic molecular organized assemblies such as: micelle, vesicle, were systematically studied in cationic-anionic surfactant systems.

Transition of surfactant aggregates by adding non-polar organic compounds was investigated in the mixed systems of cationic-anionic surfactants. The two-phase systems were transformed into single-phase isotropic solutions with the addition of a certain amount of octane. The results of dynamic light scattering demonstrate the decrease of vesicles and the increase of spherical micelles upon octane addition. Such transformation of the surfactant aggregates was also corroborated by the results of time-resolved fluorescence quenching (TRFQ) and viscometry.

Vesicles and surfactant aggregates were also studied in the mixed systems bolaform amphiphiles and opposite charged conventional surfactant. Superior high temperature stability

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of vesicles was found in some mixed systems of bola/oppositely charged conventional surfactants. DSC, VT-IR and Fluorescence probe results all revealed that vesicles in C20Na2/DEAB mixed systems can keep stable even at 80℃.

Further adjustment on amphiphilic molecular organized assemblies by temperature were also performed and interestingly temperature-induced rodlike micelle—vesicle transformation was found in the mixed cationic-anionic surfactant systems. Cylindrical micelle to vesicle transition upon the increase of temperature was demonstrated in the system of SDS/DEAB (2:1, Ctotal=10mM). Notable transition occurred during 30-50oC and such transition was remarkably influenced by anionic/cationic surfactant mixing molar ratio and total surfactant concentration.

References:[1] M. Mao, J. B. Huang et al. J.Phys.Chem. B 2002, 106, 219.[2] H. Q. Yin, J. B. Huang et al. Angew. Chem. Int. Ed. 2003, 42, 2188.[3] Y. Yan, J. B. Huang et al. J. Phys. Chem. B 2003, 107, 1479.

Novel Reactivity of Platinum(III) Dinuclear Complexes

Koji ISHIHARA

Department of Chemistry, School of Science and Engineering, Waseda University, Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

E-mail: ishi3719@waseda.jp

A substantial number of head-to-head (HH) amidato-bridged PtIII dinuclear complexes [(L)Pt(NH3)2(μ-amidato)2Pt(NH3)2(L)]n+ (amidato =α-pyridonato, etc., L = Cl, Br, etc.) having a metal-metal bonding have been reported. Prof. K. Matsumoto’s group of Waseda university with whom we are collaborating have shown that the HH amidato-bridged Pt III

dinuclear complexes (PtIII dimers) act as catalysts for the oxidation of olefins; several alkyl PtIII dimers as reaction products have been synthesized and structurally characterized by X-ray crystallographic analysis.1 We have carried out kinetic study on the axial ligand substitution of the HH amidato-bridged PtIII dimers with halides and olefins, and proposed the detailed reaction mechanisms2-6

The reaction of the HH diaqua PtIII dimer, [(H2O)Pt(N4)-Pt(N2O2)(H2O)]4+, with olefin (L) to form the alkyl PtIII dimer proceeds as a consecutive basically three-step reaction under the pseudo first-order conditions (CL >> CHH). The olefin π-coordinates preferentially to the Pt(N2O2) atom in the first step, followed by the second π-coordination of another olefin molecule to the Pt(N4) atom in the second step. The first step consists of two paths, the reaction of diaqua dimer complex and the reaction of the aquahydroxo dimer complex. The second step also consists of two paths, the normal path of the direct substitution of H2O and

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the unusual path of the coordinated OH substitution path. In the third step, the nucleophilic attack of a water molecule to the coordinated olefin causes the π-σ bond conversion on the Pt(N2O2) to form the σ-complex, and the second π-bonding olefin molecule on the Pt(N4) is released. When the β-hydroxy σ-complex is unstable, the fourth step in which the alkyl group on the Pt(N2O2) is liberated as the ketonyl compound, and the PtIII dimer reduced to the PtII

dimer is observed. We are trying to prepare the functional nano-PtIII multi-nuclear complexes having more effective catalytic activity.

Acknowledgments. Financial support from the 21COE “Practical Nano-Chemistry” from MEXT, Japan is gratefully acknowledged.

[1] Kazuko Matsumoto, et al., J. Am. Chem. Soc., 120, 2900-2907 (1998). [2] Nami Saeki, et al., J. Am. Chem. Soc., 125, 3605-3616 (2003). [3] Moritatsu Arime, et al., Inorg. Chem., 43, 309-316 (2004). [4] Nami Saeki, et al., Eur. J. Inorg. Chem., 2081-2088 (2001). [5] Nami Saeki, et al., Bull. Chem. Soc. Jpn., 74, 861-868 (2001). [6] Kazuhiro Shimazaki, et al., Eur. J. Inorg. Chem., 1785-1793 (2003).

Controlled Synthesis of Silver Nanostructures with Novel Morphologies.

Limin QI

College of Chemistry, Peking University, Beijing 100871, ChinaE-mail: liminqi@chem.pku.edu.cn

Controlled synthesis of silver nanostructures with novel morphologies, such as nanowire thin films, nanoplates, hollow spheres, and rhombdodecahedral cages, has been realized in aqueous solution in the presence of organic additives or specific templates. It has been revealed that polyanionic additives can exhibit significant influence on the morphology of the silver crystals. For example, silver nanowire thin films, which consist of interwoven bundles of single-crystalline silver nanowires about 30-40 nm in diameter, were successfully synthesized on glass wall by mild chemical reduction in aqueous solutions of poly(methacrylic acid) at room temperature. A polymer-mediated heterogeneous nucleation and growth process was proposed for the formation of the unique metal nanowire thin films. Silver crystals with unusual morphologies including solid or multi-holed single-crystalline plates, flower-like aggregates consisting of plate-like petals were synthesized by using a sulfated polysaccharide, dextran sulfate, as crystal growth modifier. On the other hand, hollow silver structures consisting of primary nanoparticles can be synthesized by using either soft or hard templates. In this regard, submicrometer-sized hollow silver spheres were readily synthesized by in solution by using polymer-surfactant complex micelles as soft templates. Furthermore, hierarchical, rhombdodecahedral silver cages were successfully synthesized by the reduction of micrometer-sized silver phosphate crystals with a perfect rhombdodecahedral shape through a microscale Kirkendall effect. The controlled self-assembly of silver particles

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around the precursor crystal surfaces led to the formation of morphology-reserved, single- or double-walled silver cages. This process may provide a general route to the synthesis of metal superstructures with a variety of morphologies and complex hierarchy.

References:[1] D. Zhang, L. Qi, J. Yang, J. Ma, H. Cheng, L. Huang, Chem. Mater. 2004, 16, 872-876.[2] J. Yang, L. Qi, D. Zhang, J. Ma, H. Cheng, Cryst. Growth Des. 2004, 4, 1371-1375.[3] D. Zhang, L. Qi, J. Ma, H. Cheng, Adv. Mater. 2002, 14, 1499-1502.[4] J. Yang, L. Qi, C. Lu, J. Ma, H. Cheng, Angew. Chem. Int. Ed., accepted.

Chiro-Optical Study of Nano-Structured Materials

Toru ASAHI

1Institute for Biomedical Engineering,2Laboratory of Nano-Chiral Science, Major in Nano-Science and Nano- Engineering,

Graduate School of Science & Engineering, Waseda University

120-6, 513 Wasedatsurumaki-cyo, Shinjuku-ku, Tokyo 162-0041, Japan

Studies of optical properties such as circular dichroism (CD) and circular birefringence (CB) of condensed matters had been limitedly performed on isotropic media or anisotropic media along the direction of optical axes because the coexisting linear birefringence (LB) and linear dichroism (LD) overwhelm CD and CB and it is very difficult to separate them. For measuring CB of the anisotropic media, high accuracy universal polarimeter (HAUP) was developed in 1983. This original HAUP has been known to be special polarimeter, which enables us to measure LB and CB of anisotropic media simultaneously, and has been applied to optical studies of amino acids, proteins, ferroelectrics, and so on. However, it is impossible to measure CD and LD using the original HAUP. Based on the original HAUP, we have developed the measuring theory of LB, CB, LD and CD [1] and recently constructed the novel optical apparatus called the generalized HAUP. The generalized HAUP was equipped with Xe and deuterium lamps as light sources and a monochrometer, and thereby it have become possible to measure temperature (280 ~ 370 K) and wavelength (230 ~ 850 nm) dependencies of LB, CB, LD and CD automatically. Namely, the measuring method of chiro-optical properties of the anisotropic media has been established.

In this presentation, we introduce the measuring theory of the generalized HAUP and

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also chiro-optical studies of nano-structured materials using the generalized HAUP. Particularly, we show the results for K4Nb6O17 single crystals in which dye molecules such an azobenzene derivative or Rh6G were intercalated.

We found that the K4Nb6O17 crystal with the azobenzene derivative exhibited peaks of CD and LD at a wavelength (of 370 nm, which are considered to originate from the torsion of the molecular structure of the azobenzene derivative and the preferred orientation of them in the crystal at room temperature. Furthermore, LB showed a minimum at λ = 380 nm and a maximum at λ= 350 nm. The Kramers-Kronig relationship between LD and LB holds, and in the case of CD and CB the similar relationship between them was observed.

This work has been performed as a collaboration study of the 21COE program “Center for Practical Nano-Chemistry”. We thank Professors K. Kuroda, M. Ogawa, and T Osaka for their collaboration and also Dr. M. Tanaka and Mr. N. Nakamura for their supports for HAUP experiments.

[1] T. Asahi & J. Kobayashi, ‘Polarimeter for anisotropic optically active materials’, Introduction to Complex Mediums for Optics and Electromagnetics, Edited by W. Weiglehofer & A. Lakhtakia, SPIE Press 645-676 (2003).

Synthesis and Photochemical Behavior of Vinyl Monomers Having Chromophore Moieties and Their Polymers

Zi-Chen LI, Fu-Sheng DU, Fu-Mian LI

Department of Polymer Science and Engineering, College of Chemistry and Molecular Engineering,

Peking University, Beijing 100871, China

A series of vinyl monomers and their saturated model compounds containing different chromophores were synthesized. These monomers display strong intramolecular fluorescence quenching, as a result, their fluorescence quantum yields and lifetimes are generally lower than those of their model compounds and the corresponding polymers. It has been concluded that the C=C bonds in these monomers played a key role in the intramolecular quenching. On the basis of the intramolecular quenching, a new fluorescence approach has been developed to monitor the process of polymerization of these monomers and the curing of bismaleimides. As an extension of our previous work, we synthesized a kind of trismaleimide (TMPA) bearing electron-donating chromophore and its corresponding model compound, TSPA. For comparison, two other compounds, Michael adduct (TMPA-P ) of TMPA and piperidine, Diels-Alder adduct (TMPA-F) of TMPA and furan, were also prepared. For TMPA, an intramolecular multiple charge transfer (CT) pathway leads to its fluorescence quenching. Therefore, it is assumed that the fluorescence is switched off because the CT pathway is open. For the Michael adduct TMPA-P, the electron poor C=C bond (A (=)) was consumed, thus, the fluorescence was switched on because the CT pathway was close. However, the fluorescence switch is irreversible. Interestingly, we found that the Diels-Alder adduct TMPA-F also displayed a strong fluorescence, while TMPA-F can give out furan at 60C in solution via a retro-Dial-Alder addition, where the electron poor C=C bond (A (=)) is formed again. In this

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case, the intramolecular charge transfer (CT) pathway is open again to cause the intramolecular fluorescence quenching. Due to a reversible Diels-Alder addition leading to a reversible intramolecular CT pathway (open and close), the fluorescence can thus be reversibly switched on and off.

[1] Du, F. S.; Cai, H.; Li, Z. C.; Li, F. M. J. Polym. Sci., Part A: Polym. Chem, 1998, 36, 1111-1116.; Du, F. S.; Li, Z. C. Li, F. M. J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 179-187.; Du, F. S.; Li, Z. C.; Hong, W.; Gao, Q. Y. Li., F. M. J. Polym. Sci., Part A: Polym. Chem. 2000, 38, 679-688.[2] Zhang, X.; Du, F. S.; Li, Z. C.; Li, F. M. Macromol. Rapid Commun. 2001, 22, 983-987.; Zhang, X.; Y. H. Jin, H. X. Diao, Du, F. S.; Li, Z. C.; Li, F. M. Macromolecules 2003, 36, 3115-3127.[3] Zhang, X.; Li, Z.C.; Li, K. B.; Du, F. S.; Li, F. M., J. Am. Chem. Soc.; 2004, 126, 12200-12201

Modulation of Molecular Assembling States for Drug Delivery

Shinji TAKEOKA

Department of Applied Chemistry, Waseda UniversityOkubo, Shinjuku, Tokyo 169-8555, Japan

e-mail:takeoka@waseda.jp

We have been developing the technology of stabilized and functionalized nanoparticles such as liposomes for 20 years. When phospholipids and cholesterol are dispersed into an aqueous solution, they spontaneously assemble to form vesicles (or liposomes) with bimolecular (bilayer) membrane. There are many parameters such as size, size distribution, lamellarity (the number of bilayer membrane), membrane fluidity, surface charge, surface modification, membrane permeability, which characterize liposomes. They can be adjusted as need dictates to allow for changing encapsulation of functional molecules, release triggered by external stimuli, conjugation of functional sites on the surface, rolling or adhesion properties of liposomes, and control of blood circulation time. On the other hand, we have to consider their physical and chemical stability during storage or blood circulation. Surface modification with polyoxyethylene (POE) chains is one of the effective ways to impart such stabilization[1, 2].

In this presentation, I will introduce one typical example of nanoparticle application: a liposome encapsulating concentrated hemoglobin (Hb-vesicle) for a red-blood-cell substitute. In this case, though Hb is a kind of drug and the liposome is a carrier, the dose amount of the Hb-vesicles is tremendously high because more than 50 % of total blood is replaced with the Hb-vesicle dispersion.[3] We succeeded in encapsulating Hb with a high encapsulating efficiency and in providing liposomes with high blood compatibility by using

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the highly purified lipids and the optimized lipid composition.[4] The microcirculation, pharmacokinetics and histopathological change were studied in relation to the characteristics of the particles, especially surface modulation as well as their oxygen affinity and in vivo oxygen distribution.[5, 6] Since our liposomes have been proved to be very safe from various safety tests using rodents and primates, they can be applied as carriers for the other drugs with small changes in lipid structures and surface modification. I will also introduce and discuss how the drug carriers are designed by the modulation of molecular assembling phenomena of amphiphilic molecules.

[1] Sou, K., Endo, T., Takeoka, S., Tsuchida, E., Bioconjugate Chem., 11, 372-379 (2000).[2] Takeoka, S., Mori, K., Ohkawa, H., Sou, K., Tsuchida, E., J. Am. Chem. Soc., 122, 7927-7935 (2000).[3] Sakai, H., Hara, H., Yuasa, M., Tsai, AG., Takeoka, S., Tsuchida, E., Intaglietta, M., Am. J. Physiol.-Heart Circul. Physiol., 279, H908-H915 (2000).[4] Sou, K., Naito, Y., Endo, T., Takeoka, S., Tsuchida, E., Biotechnol. Prog., 19, 1547-1552 (2003).[5] Sakai, H., Horinouchi, H., Masada, Y., Takeoka, S., Kobayashi, K., Tsuchida, E., Biomaterials, 25, 4317-4325 (2004).[6] Sakai, H., Masada, Y., Horinouchi, H., Yamamoto, M., Ikeda, E., Takeoka, S., Kobayashi, K., Tsuchida, E., Crit. Care Med., 32, 539-545 (2004).

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