Joint Symposium of Peking University & Waseda
University
on Practical Nano-Chemistry
51-Bldg., Conference Room 2,
School of Science and Engineering,
Waseda University
November 27, 2004
Organized by College of Chemistry, Peking University, China
and 21COE Program “ Practical Nano-Chemistry”
at Waseda University from MEXT, Japan
1
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 photos
10:55-11:25 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. Ishihara
13:00-13:30 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 Break
15:05-15:35 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"
Poster Session
2
16:00-17:30
1. 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
Sulfur-Containing Aromatic Ring”
Comprised
of
Fused
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”
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”
3
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 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.
4
Electrochemical Fabrication Processes for
Functional Micro/Nano Structures and Devices
Takayuki HOMMA
Department of Applied Chemistry, Waseda University
Okubo, 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).
5
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.
EuS-1
EuS-2
EuS-3
EuS-3d
EuS-3w
EuS-3m
15
-3
M / cm mol
-1
20
10
5
0
5
10
15
20
25
30
T/K
This work was supported by the National Science Fund for Distinguished Young Scholars
(20125104), NSFC no. 20221101 and 20490210.
6
Nano-chemistry Based on Layered Perovskites: "Chimie Douce" Approach
Yoshiyuki SUGAHARA
Department of Applied Chemistry, Waseda University
Ohkubo-3, Shinjuku-ku, Tokyo 169-8555 JAPAN
TEL/FAX: +81-3-5286-3204 E-mail: ys6546@waseda.jp
http://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, 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.
7
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
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.
8
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+
-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 PtIII
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
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 Pt III 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).
9
Controlled Synthesis of Silver Nanostructures with Novel Morphologies.
Limin QI
College of Chemistry, Peking University, Beijing 100871, China
E-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
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.
10
Chiro-Optical Study of Nano-Structured Materials
Toru ASAHI
1
2
Institute for Biomedical Engineering,
Laboratory 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
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 (
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).
11
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 60C in solution via a
retro-Dial-Alder addition, where the electron poor C=C bond (A (=)) is formed again. In this
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
12
Modulation of Molecular Assembling States for Drug Delivery
Shinji TAKEOKA
Department of Applied Chemistry, Waseda University
Okubo, 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
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).
13