Toshiyuki Kida

Layer‐by‐Layer Assembly Through Weak Interactions and Their Biomedical Applications

The surface design and control of substrates with nanometer- or micrometer-sized polymer films are of considerable interest for both fundamental and applied studies in the biomedical field because of the required surface properties. The layer-by-layer (LbL) technique was discovered in 1991 by Decher and co-workers for the fabrication of polymer multilayers constructed mainly through electrostatic interaction. The scope and applicability of this LbL assembly has been extended by introducing molecularly regular conformations of polymers or proteins by employing, for the first time, weak interactions such as van der Waals interactions and biological recognition. Since these weak interactions are the sum of the attractive or repulsive forces between parts of the same molecule, they allow macromolecules to be easily arranged into the most stable conformation in a LbL film. By applying this characteristic feature, the template polymerization of stereoregular polymers, stereoregular control of surface biological properties, drastic morphological control of biodegradable nano materials, and the development of three-dimensional cellular multilayers as a tissue model were successfully achieved. It is expected that LbL assembly using weak interactions will promote further interest into fundamental and applied studies on the design of surface chemistry in the biomedical field.

Surface-active properties of novel cationic surfactants with two alkyl chains and two ammonio groups

A series ofbis-quaternary ammonium salts was easily prepared by the reaction of a long-chaintert-alkylamine with epichlorohydrin, and their surface-active properties were measured. The prepared amphipathic compounds had good water solubility and showed characteristic surface-active properties, particularly, extremely excellent foaming ability and foam stability for some specific compounds, such as the compound with a dodecyl and a tetradecyl group as the lipophilic chains. Their critical micelle concentration, which decreased with increased alkyl chainlength, is two orders of magnitude lower compared with the conventionalmono-quaternary ammonium salts. In comparison with surface-active properties ofbis-quaternary ammonium salts, prepared from various organic dichlorides, there are little differences based on the kind of connecting group in the surface-active properties except for foaming.

Locally Controlled Release of Basic Fibroblast Growth Factor from Multilayered Capsules

Biodegradable multilayered capsules encapsulating basic fibroblast growth factor (bFGF) were developed as a cytokine release carrier for drug delivery systems. The multilayered hollow capsules were fabricated via the layer-by-layer (LbL) assembly of chitosan (CT) and dextran sulfate (Dex). The bFGF was encapsulated into the CT/Dex multilayered capsules by controlling the membrane permeability, and the local and sustained release of bFGF from the capsules was examined. At pH < 8.0, the capsule membrane tightened, and FITC-dextran ( Mw = 4000) could not enter the capsules. However, FITC-dextran ( M w = 250000) easily entered the capsules at pH > 8.0, which can be attributed to the electrostatic repulsion of Dex caused by the deprotonation of the amine group in CT. After treatment with acetic acid buffer (pH 5.6), FITC-dextran or bFGF was successfully encapsulated into the capsules. The amount of encapsulated bFGF was approximately 34 microg/1 mg of capsule. Initially, about 30% of the encapsulated bFGF was released in serum-free medium within a few hours, however, the release was sustained over 70 h. When the bFGF encapsulating capsules were added to cell culture medium (serum-free), the mouse L929 fibroblast cells proliferated well for 2 weeks as compared to cultures, where bFGF was added to the medium or where bFGF and empty hollow capsules were added separately. The proliferation is due to the local and sustained release of bFGF from the adsorbent capsule to the cell surface.

Diphenylphosphinooxazoline ligands with a chiral binaphthyl backbone for Pd-catalyzed allylic alkylation

Novel diphenylphosphinooxazoline ligands with a chiral binaphthyl backbone were prepared. It was interestingly found that the two diastereomeric ligands afforded two enantiomeric products, respectively, with excellent catalytic activities and enantioselectivities for the palladium-catalyzed allylic alkylation, regardless of the identical (S)-oxazoline ring existing in both ligands. This is the first example using an (S)-oxazoline ligand to afford an (R)-product for this reaction.

Multifunctional conjugation of proteins on/into bio-nanoparticles prepared by amphiphilic poly(γ-glutamic acid)

The present study focuses on nanoparticles composed of amphiphilic poly(γ-glutamic acid) (γ-PGA) as potential protein carriers. Amphiphilic graft co-polymers composed of γ-PGA as the hydrophilic backbone and L-phenylalanine ethylester (L-PAE) as the hydrophobic segment were synthesized by grafting L-PAE to γ-PGA using water-soluble carbodiimide (WSC). Due to their amphiphilic properties, the γ-PGA-graft-L-PAE co-polymer formed monodispersed nanoparticles in water. The particle size of the nanoparticles composed of γ-PGA-graft-L-PAE (γ-PGA nanoparticles) was about 200 nm and showed a highly negative zeta potential. To evaluate their potential applications as multifunctional protein carrier, we prepared protein-entrapped γ-PGA nanoparticles by encapsulation, covalent immobilization or physical adsorption methods. For this purpose, 11 different proteins with various molecular weights and isoelectric points (pI values) were used as model proteins. The encapsulation of the protein into the nanoparticles was observed for all tested proteins. The amount of protein covalently immobilized or adsorbed onto the nanoparticles showed different tends based on the molecular weight and pI of each protein. Positively charged proteins could be adsorbed onto the negatively charged nanoparticles by electrostatic interaction. Moreover, it was found that enzyme-encapsulated nanoparticles showed higher enzymatic activity than surface-immobilized nanoparticles. These results indicated that the enzymatic activity of the enzyme-entrapped nanoparticles was significantly affected by the conjugation method, and that encapsulation was the optimal method for the conjugation of proteins and nanoparticles. It is expected that the γ-PGA nanoparticle will have great potential as multifunctional carriers in pharmaceutical and biomedical applications, such as drug and vaccine delivery systems.

Chiral Recognition and Kinetic Resolution of Aromatic Amines via Supramolecular Chiral Nanocapsules in Nonpolar Solvents

Herein we report the first example of chiral recognition and kinetic resolution of aromatic amine guests using supramolecular nanocapsules assembled from cyclodextrin derivatives in nonpolar media. With these nanocapsules, an extremely high chiral recognition of 1-(1-naphthyl)ethylamine (1) in cyclohexane was achieved, with a binding selectivity of up to 41 for (S)-1 over (R)-1. In addition, kinetic resolution of 1 through enantioselective N-acylation was accomplished with an enantiomeric excess of up to 91%.

Novel chiral P,N-ferrocene ligands in palladium-catalyzed asymmetric allylic alkylations

Abstract Novel chiral P,N-ferrocene ligands, 1-diphenylphosphino-1′-oxazolinylferrocenes, were prepared from ferrocene via 1,1′-bis(tributylstannyl)ferrocene and 1-diphenylphosphino-1′-methoxycarbonylferrocene as intermediates, and with this new kind of ligand up to 91% ee with 99% chemical yield was afforded for the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethylmalonate anion. The complexation behavior of this kind of ligand with dichlorobis(acetonitrile)palladium and bis(μ-chloro)(1,3-diphenyl-η 3 -allyl)dipalladium was investigated.

Nanotube Formation through the Continuous One-Dimensional Fusion of Hollow Nanocapsules Composed of Layer-by-Layer Poly(lactic acid) Stereocomplex Films

Hollow nanocapsules composed of a poly(lactic acid)s (PLAs) stereocomplex can be fabricated by a combination of the layer-by-layer assembly technique and the silica template method. These hollow capsules one-dimensionally fuse together to generate novel PLA nanotubes. The formation of nanotubes was affected by the molecular weights of PLAs constituting the hollow capsules.

Separation of fructose from a mixture of sugars using supported liquid membranes

The main purpose of this study was to investigate the feasibility of using supported liquid membranes to extract fructose from a mixture of sugars contained in a fermentation broth. The membrane consisted of a microporous polypropylene support impregnated with a solution of a phenylboronic acid derivative in 2-nitrophenyl octyl ether. Transport through a flat sheet membrane was studied as a function of carrier and feed concentration. A hollow fiber system was also examined, and the effects of the carrier and feed concentrations, as well as the flow rate through the fiber lumen, on the glucose and fructose fluxes and fructose selectivity were studied. The hollow fiber system is more stable than the flat sheet supported liquid membrane, and produces higher fructose selectivities using a lower carrier concentration. The hollow fiber supported liquid membrane is able to remove fructose from a fermentation broth, although the membrane flux and long term stability need further improvement.

Novel C2-symmetric diphosphine ligand with only the planar chirality of ferrocene

Abstract The first C 2 -symmetric diphosphine ligand possessing only the planar chirality of ferrocene was prepared from 1,1′-bis(diphenylphosphino)-2,2′-bis(oxazolinyl)ferrocene by the transformation of the oxazoline moieties in the molecule and with this new chiral ferrocene diphosphine ligand, up to 92% ee was obtained for the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with 2,4-pentanedione.