Issei Otsuka

Oligosaccharide/Silicon-Containing Block Copolymers with 5 nm Features for Lithographic Applications

Block copolymers demonstrate potential for use in next-generation lithography due to their ability to self-assemble into well-ordered periodic arrays on the 3-100 nm length scale. The successful lithographic application of block copolymers relies on three critical conditions being met: high Flory-Huggins interaction parameters (χ), which enable formation of <10 nm features, etch selectivity between blocks for facile pattern transfer, and thin film self-assembly control. The present paper describes the synthesis and self-assembly of block copolymers composed of naturally derived oligosaccharides coupled to a silicon-containing polystyrene derivative synthesized by activators regenerated by electron transfer atom transfer radical polymerization. The block copolymers have a large χ and a low degree of polymerization (N) enabling formation of 5 nm feature diameters, incorporate silicon in one block for oxygen reactive ion etch contrast, and exhibit bulk and thin film self-assembly of hexagonally packed cylinders facilitated by a combination of spin coating and solvent annealing techniques. As observed by small angle X-ray scattering and atomic force microscopy, these materials exhibit some of the smallest block copolymer features in the bulk and in thin films reported to date.

Elaboration of chitosan-coated nanoparticles loaded with curcumin for mucoadhesive applications.

Polycaprolactone (PCL) nanoparticles decorated with a mucoadhesive polysaccharide chitosan (CS) containing curcumin were developed aiming the buccal delivery of this drug. These nanoparticles were prepared by the nanoprecipitation method using different molar masses and concentrations of chitosan and concentrations of triblock surfactant poloxamer (PEO-PPO-PEO), in order to optimize the preparation conditions. Chitosan-coated nanoparticles showed positive surface charge and a mean particle radius ranging between 114 and 125 nm, confirming the decoration of the nanoparticles with the mucoadhesive polymer, through hydrogen bonds between ether and amino groups from PEO and CS, respectively. Dynamic Light Scattering (DLS) studies at different scattering angles and concentrations have shown that the nanoparticles are monodisperse (polydispersity indices were lower than 0.3). The nanoparticle systems were also examined with Nanoparticle Tracking Analysis (NTA), and the results were in good agreement with those obtained by DLS. Colloidal systems showed mean drug content about 460 μg/mL and encapsulation efficiency higher than 99%. Finally, when coated with chitosan, these nanoparticles show a great ability to interact with mucin indicating also their suitability for mucoadhesive applications.

Size-specific, colorimetric detection of counteranions by using helical poly(phenylacetylene) conjugated to L-leucine groups through urea acceptors.

A colorimetric detection susceptible to the dimensions of guest counteranions has been demonstrated by using poly(phenylacetylene) with L-leucine and urea functionalities (poly-PA-Leu). Poly-PA-Leu was prepared from N-(4-ethynylphenylcarbamoyl)-L-leucine ethyl ester (PA-Leu) by using [Rh(+){eta(6)-C(6)H(5))B(-)(C(6)H(5))(3)}(2,5-norbornadiene)] as a catalyst. The biased helical conformation of poly-PA-Leu was demonstrated through Cotton effects in the circular dichroism (CD) spectra. The addition of ammonium salts, including tetra-n-butylammonium acetate, tetra-n-butylammonium chloride, and tetra-n-butylammonium bromide anions (CH(3)COO(-), Cl(-), and Br(-)), into the poly-PA-Leu solution intensified the CD responses of poly-PA-Leu, which is indicative of the chiral adjustability of anion recognition by using urea groups. In addition, the combination of poly-PA-Leu with the CH(3)COO(-), Cl(-), and Br(-) anions promoted large redshifts in the absorption spectra, thus providing dramatic color changes from pale yellow to red. Guest dependency in the CD and UV/Vis spectra was clearly correlated with the size of the counteranions. Fundamentally, the addition of tetra-n-butylammonium nitrate, tetra-n-butylammonium hydrogen sulfate, tetra-n-butylammonium perchlorate, tetra-n-butylammonium azide, tetra-n-butylammonium fluoride, and tetra-n-butylammonium iodide anions (NO(3) (-), HSO(4) (-), ClO(4) (-), N(3) (-), F(-), and I(-)) has no effect on either the CD or UV/Vis profiles of poly-PA-Leu. The guest specificity observed in the CD and UV/Vis spectra clearly demonstrated the guest-dimension selectivity of poly-PA-Leu in counteranion recognition.

Control of 10 nm scale cylinder orientation in self-organized sugar-based block copolymer thin films

The present paper describes the orientational control of 10 nm scale cylinders in sugar-based block copolymer thin films by simply varying the composition of the annealing co-solvent. The affinity of the block copolymer to the solvent vapor could be systematically adjusted in this way.

Enhancement of Plant and Bacterial Lectin Binding Affinities by Three-Dimensional Organized Cluster Glycosides Constructed on Helical Poly(phenylacetylene) Backbones

A series of poly(phenylacetylene)s bearing diverse saccharide pendants—N‐acetyl‐D‐glucosamine, D‐lactose, and N‐acetyl‐D‐neuraminic acid—were synthesized by rhodium‐mediated polymerizations of the corresponding acetyl‐protected glycosylated phenylacetylenes followed by deprotection. The circular dichroism spectra of these glycosylated poly(phenylacetylene)s each displayed split‐type Cotton effects in the long absorption region of the conjugated polymer backbone (260–500 nm), thus indicating predominantly one‐handed helical conformations in their backbones. The binding affinities of these glycosylated poly(phenylacetylene)s, and those of previously reported phenylacetylenes bearing D‐galactose, towards plant and bacterial lectins were investigated by hemagglutination inhibition assay and isothermal titration calorimetry (ITC). The stoichiometries of binding vary strongly, depending on the lectin binding sites and the accessibilities of the carbohydrate residues in the helices. The measured affinities also vary, with the maximum value observed for the interaction between poly‐PA‐α‐Gal and lectin I from Pseudomonas aeruginosa, with a Kd value of 4 μM per monosaccharide representing a 200‐fold increase relative to the corresponding monomer.

Self-assembly of maltoheptaose-block-polystyrene into micellar nanoparticles and encapsulation of gold nanoparticles.

The present paper discusses the controlled self-assembly of sugar-containing block copolymer, maltoheptaose-block-polystyrene (MH(1.2k)-b-PS(4.5k)), into micellar nanoparticles of ca. 30 nm radius in aqueous media and their possibility of gold encapsulation. Micellar association of MH(1.2k)-b-PS(4.5k) into nanoparticles was demonstrated by mixing a large amount of water (MH-selective solvent) with a solution of MH(1.2k)-b-PS(4.5k) in a mixture of tetrahydrofuran (THF) (PS-selective solvent) and water with a certain weight fraction [4:1 (w/w) THF/water], where MH(1.2k)-b-PS(4.5k) exists as well-swollen single chains, followed by evaporation of THF. The mean hydrodynamic radii (Rh) of the nanoparticles were determined by dynamic light scattering (DLS) to be ca. 30 and 80 nm depending upon the method of preparation. The resulting nanoparticles were clearly visualized by transmission electron microscopy (TEM), atomic force microscopy (AFM), and field emission gun-scanning electron microscopy (FEG-SEM) imaging and complemented by nanoparticle tracking analysis (NTA) using a NanoSight instrument. The preliminary study of the self-assembly of MH(1.2k)-b-PS(4.5k) in the presence of gold nanoparticles functionalized with PS chains grafted on their surface indicated potential possibilities of encapsulation of gold nanoparticles into the block copolymer nanoparticles in aqueous media.

Xyloglucan-block-Poly(ϵ-Caprolactone) Copolymer Nanoparticles Coated with Chitosan as Biocompatible Mucoadhesive Drug Delivery System

The development of novel xyloglucan-block-poly(ϵ-caprolactone) (XGO-b-PCL) nanoparticles coated with the mucoadhesive polysaccharide chitosan is described. XGO-b-PCL nanoparticles show monodisperse size distribution (Rh  = 50 nm). Curcumin is successfully encapsulated within the PCL core within drug to polymer ratio of 1:5 (w/w). The coating of nanoparticles with chitosan results in an increased particle size and positive surface charge due to the polycation nature of the chitosan. Mucoadhesive properties of chitosan-coated nanoparticles are demonstrated by its exceptional ability to interact with mucin through electrostatic forces. Finally, in vitro studies show that curcumin-loaded nanoparticles exhibit higher cytotoxic effects against B16F10 melanoma cells than L929 fibroblast cells.

Maltopentaose-Conjugated CTA for RAFT Polymerization Generating Nanostructured Bioresource-Block Copolymer

We now describe the synthesis of a new family of oligosaccharide-conjugated functional molecules, which act as chain transfer agents (CTAs) for the reversible addition-fragmentation chain transfer (RAFT) polymerization. The synthesis was started from the catalyst-free direct N-glycosyl reaction of 5-azidopentylamine onto maltopentaose (Mal5) in dry methanol at room temperature and subsequent N-protected reaction with acetic anhydride, producing a stable oligosaccharide-building block, such as Mal5 with an azidopentyl group (Mal5-N3). The azido group was hydrogenated using platinum dioxide (PtO2) as a catalyst to give Mal5 with aminopentyl group (Mal5-NH2), which was then reacted with CTA molecules bearing activated ester moieties. These reactions produced Mal5-modified macro-CTAs (Mal5-CTAs, 1), which were used for the RAFT polymerizations of styrene (St) and methyl methacrylate (MMA) in DMF. The polymerizations were performed using the [M]0/[1]0 values ranging from 50 to 600, affording the Mal5-hybrid amphiphilic block copolymers (BCPs), such as Mal5-polystyrene (2) and Mal5-poly(methyl methacrylate) (3), with a quantitative end-functionality and the controlled molecular weights between 4310 and 20 300 g mol(-1). The small-angle X-ray scattering (SAXS) measurements were accomplished for 2 and 3 to ensure their abilities to form phase separated structures in their bulk states with the increasing temperatures from 30 to 190 °C. The featured results were observed for 2 (ϕMal5 = 0.14) and 3 (ϕMal5 = 0.16) at temperatures above 100 °C, where ϕMal5 denotes the volume fraction of the Mal5 unit in the BCP sample. For both BCP samples, the primary scattering peaks q* were clearly observed together with the higher-ordered scattering peaks √2q* and √3q*. Thus, these Mal5-hybrid amphiphilic BCP samples have a body centered cubic (BCC) phase morphology. The domain spacing (d) values of the BCC morphology for 2 (ϕMal5 = 0.14) and 3 (ϕMal5 = 0.16) were 10.4 and 9.55 nm, respectively, which were determined using Braggs relation (d = 2π/q*). The present RAFT agents were shown to eventually provide the phase separated structural polymeric materials in which 5.4 nm bioresource-spherical domains were periodically arrayed at the interval of about 10 nm.

Self-Assembly of Oligosaccharide-b-PMMA Block Copolymer Systems: Glyco-Nanoparticles and Their Degradation under UV Exposure.

This paper discusses the self-assembly of oligosaccharide-containing block copolymer and the use of ultraviolet (UV) to obtain nanoporous glyco-nanoparticles by photodegradation of the synthetic polymer block. Those glyco-nanoparticles consisting of oligosaccharide-based shell and a photodegradable core domain were obtained from the self-assembly of maltoheptaose-block-poly(methyl methacrylate) (MH-b-PMMA48) using the nanoprecipitation protocol. MH-b-PMMA48 self-assembled into well-defined spherical micelles (major compound) with a hydrodynamic radius (Rh) of ca. 10 nm and also into large compound micellar aggregates (minor compound) with an Rh of ca. 65 nm. The oligosaccharide shells of these glyco-nanoparticles were cross-linked through the Michael-type addition of divinyl sulfone under dilute conditions to minimize the intermicellar cross-linking. The core domain photodegradation of the cross-linked glyco-nanoparticles was induced under exposure to 254 nm UV radiation, resulting in porous glyco-nanoparticles with an Rh of ca. 44 nm. The morphology of the cross-linked shell and the core photodegradation of these glyco-nanoparticles were characterized using static light scattering, dynamic light scattering, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, field-emission gun-scanning electron microscopy, and transmission electron microscopy. The innovative aspect of this approach concerns the fact that after removing the PMMA domains the porous nanoparticles are mostly composed of biocompatible and nontoxic oligosaccharides.

Self-assembly of maltoheptaose-b-PMMA block copolymer systems: 10 nm Resolution in thin film and bulk states

This paper describes the self-assembly of oligosaccharide-based hybrid block copolymers (BCPs) consisting of maltoheptaose (MH) and poly(methyl methacrylate) (PMMA) into 10nm scale lamellar and cylindrical phases depending on the volume fractions of MH (ϕMH) and the annealing process. Time resolved SAXS study of the BCP bulk samples during thermal annealing indicated that the BCPs phase separate into 10nm scale periodical structures. The solvent vapor annealing induced self-organizations of the BCP into different phases depending on ϕMH and the weight fraction of THF/H2O. BCPs with relatively higher ØMH, MH-b-PMMA3k (ϕMH=0.27) and MH-b-PMMA5k (ϕMH=0.16) self-organized into lamellar phases while the BCP sample with relatively lower ϕMH, MH-b-PMMA9k (ϕMH=0.10), self-organized into cylindrical phase by using THF/H2O=1/4 (w/w). On the other hand, the solvent vapor annealing with larger fraction of THF, i.e. THF/H2O=2/3 (w/w), induced cylindrical phases for MH-b-PMMA3k and MH-b-PMMA5k.