Search

The dispersibility of hexagonal boron nitride (hBN) particles in epoxy resin with different chemical structures, such as bisphenol and naphthalene, was investigated. The viscosities of hBN slurries...

Biomass-based copolymers with alternating ricinoleic acid and 4-hydroxycinnamic acid derivatives (p-coumaric acid, ferulic acid, and sinapinic acid) exhibit a repeating structure based on soft and hard segments, derived from ricinoleic and 4-hydroxycinnamic acids, respectively. To achieve this alternating sequence, copolymers were synthesised by the self-condensation of hetero-dimeric monomers derived by the pre-coupling of methyl ricinolate and 4-hydroxycinnamic acid. The glass transition temperature (Tg) was observed to increase as the number of methoxy groups on the main chain increased; the Tg values of poly(coumaric acid-alt-ricinoleic acid), poly(ferulic acid-alt-ricinoleic acid), and poly(sinapinic acid-alt-ricinoleic acid) are −15 °C, −4 °C, and 24 °C respectively, 58 °C, 69 °C, and 97 °C higher than that of poly(ricinoleic acid). The polymers were processed into highly flexible, visually transparent films. Among them, poly(sinapinic acid-alt-ricinoleic acid) bearing two methoxy groups on each cinnamoyl unit, is mechanically the strongest polymer, with an elastic modulus of 126.5 MPa and a tensile strength at break of 15.47 MPa.

To develop a highly thermally conductive composite film, two types of ceramic fillers with different shapes were bound with cellulose nanofiber (CNF) composite fibrils densely covered with nanodiamond (ND) particles. A hexagonal boron nitride (h-BN) filler with a plate-like structure was oriented in the in-plane direction of the CNF/ND nanosheets, increasing the in-plane thermal conductivity of the h-BN-based composite film by 38.7% from 4.45 to 6.17 W/m K compared with the raw CNF/ND composite film. Conversely, the Al2O3 particles inflected the CNF/ND nanosheets and lowered the orientation of the nanosheets. The in-plane thermal conductivity of the Al2O3-based composite film was lower than that of the CNF/ND film. To develop a highly thermally conductive CNF/ND/ceramic composite film, the ceramic filler should be oriented in the plane direction, and h-BN with a high thermal conductivity is a suitable filler.

The in-plane thermal conductivity of cellulose nanofiber (CNF) composite film densely covered with nanodiamond (ND) particles has been improved by using the wet-rotating disc milling (WRDM) process and optimizing the compositional ratio of ND and CNF. The aspect ratio of CNF fibrils was increased by 42% using the WRDM. Furthermore, the in-plane thermal conductivities of CNF and ND/CNF films composed of WRDM-assisted CNF fibrils were improved with the increase of the aspect ratio of CNF fibrils. In addition, the mass ratio of ND to CNF and the in-plane thermal conductivity of the ND/CNF composite film were enhanced by using the WRDM-assisted ND suspensions owing to the improvement of dispersibility of ND particles. Consequently, the in-plane thermal conductivity of the ND/CNF film increased by 82% from 2.67 to 4.85 W/m K with the increase of the aspect ratio of CNF fibrils, thus improving the dispersibility of ND particles and optimizing the compositional ratio of ND and CNF. The dense adsorption of ND particles on the surface of CNF fibrils with high aspect ratio led to the improvement of the in-plane thermal conductivity of the composite film.

Thermally conductive and electrically insulating composite materials are required for thermal management in advanced electronic industry. The present work aimed at creating a composite film of cellulose nanofiber (CNF) and nanodiamond (ND) with superior thermal conductivity. The thermal conductivity of the prepared nanocomposite film was ∼2.7 Wm−1 K−1, which corresponds to triple of usual CNF/ND composites with similar composition. The distinct thermal conductivity is attributed to a unique nanostructure we made out in the nanocomposite film. The nanostructure can be characterized by CNF fibrils which are densely covered with ND particles.

Histone acetyltransferases (HATs) play a crucial role in post-translational modification. Among them, overexpression, mutation, or hyperfunction of EP300/CBP has been associated with various cancers. In this study, we identified the novel compound 2-chloro-5-[5-[(E)-[1-(3-chlorophenyl)-3-methyl-5-oxo-pyrazol-4-ylidene]methyl]-2-furyl]benzoic acid (1) as an EP300 HAT inhibitor via virtual screening. Further research has been focused on the design, synthesis, and in vitro biological evaluation of virtual hit derivatives. The studies revealed that 4-pyridone-3-carboxylic acid derivatives exhibited bioisosterism of benzoic acid. Replacement proved effective, providing compounds with similar EP300 HAT-inhibitory activity and improved cell growth-inhibitory activity compared to the benzoic acid analogs. Through these studies, we identified a potent and selective EP300/CBP HAT inhibitor.

The exfoliation of layered muscovite with non-swelling property has been performed by combining various processes, such as heating, intercalation, and wet-jet milling. The c axis of muscovite was expanded from 2004.0 to 2022.8 pm at 800 °C without the destruction of crystallinity of muscovite. The heating at 800 °C led to the weak attraction force between potassium ions and silicate layers by hydroxylation of muscovite. The muscovite heated at 800 °C progressed the intercalation of dodecylammonium chloride (DDAC) into the layers effectively. Furthermore, the DDAC molecules were inserted to the interlayer of muscovite effectively by suppressing the formation of micelle of DDAC. The sedimentation test of wet-jet milled muscovite slurry showed that the relative packing density of muscovite was decreasing with increasing the amount of the intercalated DDAC. As results, the aspect ratio of muscovite prepared with combining the heating, the intercalation and the wet-jet milling was increased by 253% as compared to the raw muscovite. The aspect ratio was calculated from laser particle size distribution and thickness size distribution which was estimated from field emission-scanning electron microscopic images. The expansion of the interlayer led to the effective exfoliation of muscovite with high aspect ratio.

We report molecularly imprinted polymers (MIPs) for selective adsorption of proteins using a poly(ethylene glycol) (PEG)-based cross-linker with ionic monomers. To clarify the utility of the concept for preparation of the imprinted polymers using a PEG-based cross-linker, we employed lysozyme or cytochrome c as a template molecule. A few sulfonic functional monomers including sodium allylsulfonate, 2-acrylamido-2-methylpropanesulfonic acid, and sodium p-styrenesulfonate were utilized. After optimization of the concentration of the cross-linker and the washing process with a NaCl solution, we confirmed the complete eluting of the template lysozyme. The optimized lysozyme MIP showed the selective adsorption ability for lysozyme against the other proteins in higher salted condition, in which nonspecific ionic interaction due to the functional monomers were suppressed. Also, the imprinting factor toward the nonimprinted polymer was reached to over 8.6. Similar approaches were carried out for cytochrome c MIPs...

Novel sponge-based monoliths containing ionic functional groups were developed for rapid separation and/or concentration of ionic solutes. The cationic and anionic spongy monoliths were prepared by chemical modifications of the pore surface on an original spongy monolith consisting of poly(ethylene-co-vinyl acetate). After hydrolysis of the spongy monolith, an anionic or a cationic moiety was introduced with succinyl chloride or acryloyl chloride/diethylamine, respectively. As a result of liquid chromatographic evaluations for the columns packed with these ionic spongy monoliths, both anionic and cationic monoliths showed ionic interactions with the opposing ionic solutes even if a higher flow rate (9.0 mL/min) was employed. Furthermore, we demonstrated the effective and rapid preconcentration of adenosine 5′-monophosphate in water using column-switching LC combined with the cationic spongy monolith as an online SPE adsorbent.

To achieve selective adsorption of gaseous compounds, we synthesized the molecularly imprinted polymers (MIPs). In this study, we utilized two different types of MIPs, the first one was examination of the effect by the porogen imprinting, and another was authentic molecular imprinting by template and a functional monomer. The results of BET evaluation of MIPs showed that the specific surface area were depended on octanol–water partition coefficient (log Pow) between cross-linker and porogenic solvents, also became larger as log Pow of porogen being closer to that of cross-linker. Furthermore, the adsorption performance per unit weight of MIPs was observed under single gas adsorption by using MIPs prepared with target compound as porogenic solvents. As results, each MIP which was prepared with chloroform or toluene showed selective adsorption for each vapor in point of the adsorbed amount. Thus, MIPs tended to have selective adsorption ability for the used porogen in preparation. Additionally, the Gas-MIPs prepared with a functional monomer and template molecule adsorbed target compound in selectively as increase the amount of functional monomer and template molecule. Consequently, the authentic molecular imprinting method could be worked for the effective adsorption of gaseous compounds as well as the general procedures in solution.

We have developed hybrid photocatalysts by introducing molecular recognition sites to the surface of titanium dioxide (TiO2) nanoparticles. The synthesized hybrid photocatalysts indicated the selective recognition ability for target molecules based on specific molecular recognition sites constructed by the interval immobilization technique, and also the photostability of the recognition sites was confirmed by long time UV irradiation in an aqueous solution. Furthermore, the hybrid photocatalysts showed selective degradation performance to saxitoxins which are one of the famous neurotoxins. All basic and application results suggested that the newly developed methods for preparation of nano sized hybrid-TiO2 can be worked for selective adsorption and photodegradation of targeting compounds.

Background: RET gene rearrangement has been detected in several cancers including 1-2% and 50% of non-small cell lung cancer (NSCLC) and papillary thyroid carcinoma, respectively, and it is known as a driver mutation. Several US Food and Drug Administration (FDA)-approved multi-tyrosine kinase inhibitors (MTKIs) have shown inhibitory effects on RET kinase activity and have been tested in several clinical studies. However, MTKIs do not appear potent enough to show clinical benefits. The FDA-approved MTKIs have been reported to exhibit dose-limiting toxicity (DLT) at doses below those suppressing RET kinase activity. Kinase insert domain receptor (KDR) inhibition especially leads to anti-angiogenesis-related DLT such as hypertension. Thus, the development of highly potent and selective second-generation RET inhibitors is desired. DS-5010 is an orally available small-molecule RET inhibitor that shows a specific and highly potent activity against RET and gatekeeper-mutated RET (RET-GKm) and slight KDR activity. In this study, we characterized the in vitro and in vivo activities of DS-5010. Results: In biochemical assays of 106 kinases, RET and platelet-derived growth factor receptor (PDGFR) alpha/beta were inhibited more than 80% by 193 nM DS-5010. The half-maximal inhibitory concentration (IC50) values of DS-5010 against RET, RET-GKm (V804L) were single digit nano-molar even under a condition of high concentration of ATP; besides it against KDR was more than 1000 nM. In a Ba/F3-RET subcutaneous tumor model, DS-5010 dosing at 10 mg/kg twice daily (bid) induced tumor regression. Moreover, DS-5010 exhibited a similar antitumor effect in a Ba/F3-RET-GKm (V804L) subcutaneous tumor model. In contrast, the FDA-approved MTKIs (cabozantinib, vandetanib, and alectinib) showed no significant antitumor effect on a Ba/F3-RET-GKm (V804L) subcutaneous tumor model. In an LC2/ad NSCLC xenograft model, which has the RET-CCDC6 fusion gene, DS-5010 dosing at 1 mg/kg thrice daily (tid) induced tumor regression. To predict acquired mutations against FDA-approved MTKIs, resistant clones were established by prolonged incubation of Ba/F3-RET cells with cabozantinib. A sequence analysis revealed that all the resistant clones possessed V804E mutation in the RET kinase domain and DS-5010 inhibited cell proliferation of Ba/F3-RET (V804E) mutation in the low nano-molar range. However, the FDA-approved MTKIs failed to show strong growth inhibitory effects (half-maximal growth inhibition [GI50]: 1584-5381 nM). Conclusion: These results indicate that DS-5010 has potent in vitro and in vivo activities against RET and RET-GKm, suggesting the potential usefulness of the compound for targeted therapy of cancers with RET gene rearrangements and mutations. Moreover, its potential effectiveness against acquired MTKI-resistant cells was also demonstrated. We are currently performing investigational new drug-enabling studies of DS-5010. Citation Format: Yasuyuki Kaneta, Takahiro Komatsu, Masashi Miyamoto, Megumi Goto, Hidenori Namiki, Yoshihiro Shibata, Hideaki Kageji, Hiroaki Inagaki, Kiyoshi Nakayama, Yuichi Tominaga, Takeshi Isoyama. Preclinical characterization and antitumor efficacy of DS-5010, a highly potent and selective RET inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B173.

To achieve selective recognition of water-soluble ionic compounds, we developed an effective preparation method that can construct specific recognition sites on a cross-linked polymer surface using ionic complexes of functional monomers and template molecules. The specific ionic complexes used for selective recognition were attached on the surface of cross-linked polymer pores via a reaction between ionic complexes and unreacted vinyl groups on the polymer. In this paper, we show that ionic complexes can attach to the polymer surface by determining the number of unreacted vinyl groups on the cross-linked base polymer. The prepared polymers had greater effective adsorption ability than normally prepared molecularly imprinted polymer because there were no dead sites in the cross-linked network. Furthermore, according to chromatographic evaluations involving frontal analyses, the prepared polymer has selective recognition ability based on the interval recognition of ionic compounds. The adsorption isotherm also suggests selectivity for the template molecule on the prepared polymer. Finally, the paralytic shellfish poison saxitoxin was selectively extracted using the prepared polymer.

Affinity and kinetic analyses for the evaluation of lectin-reactive α -fetoprotein (AFP) were performed using a biosensor based on surface plasmon resonance (SPR). Human AFP, purified from HCC (hepatocellular carcinoma) patients, was immobilized on the surface of a sensor chip. The interaction of this bound AFP with three lectins, Lens culinaris agglutinin [LCA], concanavalin A [Con-A] and erythroagglutinating phytohemagglutinin [E-PHA]) were monitored in real-time with the change in the SPR response. These three lectins produced an increase in the SPR response, indicating that all three bound specifically to the immobilized AFP. The association ( k ass ) and the dissociation ( k diss ) rate constants clearly differed among the three lectin-AFP interactions. These affinity and kinetic analyses of the sugar binding specificities of lectins, employing a biosensor based on SPR, are expected to serve as a new technique with the potential for simple rapid evaluation of lectin-reactive AFP.

We report an effective and a quantitative analysis method for one of pharmaceuticals, sulpiride, in river water by online solid phase extraction (SPE) connected with liquid chromatography–mass spectrometry (LC–MS) using a molecularly imprinted polymer as a preconcentration medium. The polymer prepared with a pseudo template molecule showed the selective retention ability based on the interval recognition of functional groups in sulpiride. Also, the imprinted polymer provided an effective concentration of a trace level of sulpiride in offline SPE with dual washing processes using water and acetonitrile, although another imprinted polymer prepared by an authentic method using sulpiride and methacrylic acid as a template and a functional monomer, respectively, showed the selective adsorption only in organic solvents. Furthermore, we employed the imprinted polymer as the preconcentration column of online SPE-LC–MS and the results supposed that the proposed system allowed the quantitative analysis of sulpiride with high sensitivity and recovery (10 ng/L at 96%). Additionally, the determination of sulpiride in real river water without an additional spiking was effectively achieved by the system.

This short communication describes a newly developed open-tubular capillary which was coated with C60-fullerene by a covalent bonding via a photo/thermal active agent. We utilized perfluorophenyl azide (PFPA) as an active agent, which can be used for the "photo click" coupling of the carbon materials. The inner wall of a fused silica capillary was treated with silane conjugated PFPA, and then C60-fullerene was chemically modified by a photoreaction or a thermal reaction. Through evaluations of the capillaries by liquid chromatography, the separation characteristics of three polycyclic aromatic hydrocarbons (PAHs) were confirmed in both capillaries. With comparison of the retention behavior to a commonly used C18 column, the prepared capillaries showed the specific separation ability based on the π-π stacking by C60-fullerene. The capillary prepared by the thermal reaction provided the base line separation of phenanthrene, triphenylene, and benz[a]pyrene within 3min at 18.8cm capillary length.

Hybrid materials using a macroporous sponge and spherical microporous adsorbents have been developed for an effective rapid pretreatment of water samples. Various adsorbents, including methacrylate series, divinylbenzene (DVB), and graphite particles, were utilized for hybridization with a macroporous sponge consisting of polyethylene and polyvinyl acetate, EVA resin. Both the EVA resin and each of the particles were thermally blended at 150°C with water-soluble pore templates, pentaerythritol and poly (oxyethylene, oxypropylene) triol. After molding as a columnar shape, the hybrid materials were observed by a scanning electron microscope both before and after washing with water/methanol sonication. Only methacrylate series could be effectively fixed onto the pore surface of sponge, whereas DVB and graphite particles were incorporated to the EVA matrix. We assume that the chemical interactions between EVA and adsorbents are very important for effective hybridization to fix the adsorbents onto the pore surface. Furthermore, we demonstrated the hybridization of ion-exchange resin and sponge for a high throughput purification of ionic compounds. The ion-exchangeable polymers prepared by methacrylic acid, 4-vinylpiridine, and p-styrene sulfonic acid with ethyleneglycol dimethacrylate could be fixed at a given ratio of "20, wt%", and its effective adsorption based on the ion-exchange ability was observed under rapid elution (3 mL min(-1)).

We report antibacterial activities of the epoxy-resin-based monolithic media (epoxy monoliths) having macroporous co-continuous structure as well as hydrophobic and/or hydrophilic surface. Utilizing epoxy monoliths containing ammonium groups, the antibacterial experiments were examined using Escherichia coli. As the results, the monolithic media prepared with an epoxy monomer having nitrogen atoms clearly showed antibacterial activities, while those prepared using the monomer without nitrogen atom showed less antibacterial activities. Additionally, the quaternization of the epoxy polymers were expressed significant antibacterial activities. Further studies elucidated that the observed antibacterial activities involved the steep effect based on pH changing of solution and hydrophobic interactions by the quaternary ammonium.

We developed a novel polymer type sulfoxide-modified solid phase enabling to achieve selective separation of polychlorinated biphenyls (PCBs) from insulation oil. In this study, firstly we prepared base-polymer based on the concept of the molecular imprinting to capture PCBs in selectively, then, the sulfoxide groups were modified on the pore surface of base-polymers by changing preparation methods. As results of liquid chromatographic analyses for the polymers as columns, the base-polymer prepared by xylene as a porogenic solvent showed selective retention ability for chlorinated aromatic compounds by the porogen imprinting effect. Additionally, the polymer-type sulfoxide solid phases showed highly retention ability for PCBs by increasing amount of introduced sulfoxide groups. Consequently, the results of separation of PCBs comparing to insulation oil suggested that the prepared solid phase can be used for the selective separation of PCBs at the same level as a commercially available media utilized for the regulated method.

Uniformity recognition sites for water-soluble ionic compounds were constructed onto the pores of porous polymer particles. This concept is based on a modified interval immobilization technique, which was used for the selective recognition of paralytic shellfish poison, saxitoxins (STXs). The results of batch adsorption and solid-phase extraction for one of the STX analogues, a prepared polymer that had special sites for the recognition of STXs, showed that the analogue could selectively recognize and concentrate STXs. Selective recognition was facilitated by interval-immobilized functional groups.

The interaction between lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is of importance in a number of cellular events, including antigen-specific T cell activation and emigration of leukocytes into sites of inflammation. We describe here the first use of a recombinant soluble form of human LFA-1 (sLFA-1) for the measurement of the binding between LFA-1 and ICAM-1. sLFA-1 has been successfully expressed and purified. The expressed sLFA-1 was shown to be functionally active by their binding to ICAM-1. Binding of sLFA-1 to ICAM-1 was observed by receptor binding assay. Both monomeric (soluble ICAM-1 or the first two domains of ICAM-1) and dimeric ICAM-1 (IgG chimera of each ICAM-1 fragment) showed inhibitory activity on assay with IC50 values of 400 nM and 40 nM, respectively. These results suggest that the soluble constructs would be useful tools for molecular analysis of ICAM-1/LFA-1 interaction as well as in screening for ICAM-1/LFA-1 antagonists.

Spontaneous cleanup processes based on capillary action for natural water containing humic acids were carried out using an epoxy-based polymer monolith. We were able to control the microstructures of monoliths by changing the polymerization conditions, including the curing agent/monomer/porogenic solvent ratio and the polymerization temperature. Furthermore, we confirmed that updrawing of water based on capillary action was highly dependent on the microstructures of the monolith, i.e., whether they are structures of particle aggregates, non-porous structures, or three-dimensional monolithic structures. The epoxy-based monoliths have a unique ability to adsorb hydrophobic and anionic compounds because the monoliths are prepared using epoxy monomers and curing agents with amines, and therefore, the monoliths can be used for the selective adsorption of polyphenols such as humic acids. In fact, we used a siphonic system to completely remove the humic acids in water samples and for the spontaneous cleanup of real pond water via spontaneous updrawing of water by “J”-shaped monoliths.