Blood compatibility of poly(propylene glycol diester) and its water structure observed by differential scanning calorimetry and 2H-nuclear magnetic resonance spectroscopy.

Recently, we applied solution 2H-nuclear magnetic resonance spectroscopy (2H NMR) to analyze the water (deuterium oxide, D2O) structure in several biopolymers at ambient temperature. We established that polymers with good blood compatibility (i.e. poly(2-methoxyethyl acrylate) (PMEA)) have water observed at high magnetic fields (upfield) compared with bulk water. Polymers containing poly(propylene glycol) (PPG) or poly(propylene oxide) (PPO) exhibit good compatibility; however, the reason for this remains unclear. In addition, reports on the blood compatibility of PPO/PPG are limited. Therefore, PPG diester (PPGest) was prepared as a model polymer, and its blood compatibility and water structure were investigated. PPGest exhibited excellent blood compatibility. The water in PPGest was observed upfield by 2H NMR, and it was defined as non-freezing water via differential scanning calorimetry. Based on these observations, the relationship between the blood compatibility and water structure of PPGest is discussed by comparing with those of PMEA, and the reason for the good performance of PPG/PPO-based polymers is discussed.

Morphological Observation of the Pupal Body of Trypoxylus dichotomus Using 9.4T MR Imaging.

Metamorphosis in the pupae of the Trypoxylus dichotomus was continuously observed at 9.4T until their emergence. A large liquid-like mass occupied most of the volume in the trunk, while the surrounding tissue already existed at the beginning of the observation period. As the mass shrunk, tissues such as flight muscle formed, whereas the reservoir became prolonged to form the intestinal tract. This implies that the liquid-like mass worked as the raw material for creating adult tissues.

Photoluminescent Layered Crystal Consisting of Anderson-Type Polyoxometalate and Surfactant toward a Potential Inorganic-Organic Hybrid Laser.

The hybridization of inorganic and organic components is a promising strategy to build functional materials. Among several functions, luminescence is an important function which should be considered for practical usage. Inorganic-organic hybrid luminescent materials have been investigated as phosphors, sensors, and lasers. Organic luminescent centers such as dye molecules have often been hybridized with inorganic matrices. Polyoxometalate anions (POMs) are effective inorganic luminescent centers due to their luminescent properties and structural designability. However, most luminescent POM components are limited to lanthanide-based POMs. In this report, a photoluminescent inorganic-organic hybrid crystal based on a non-lanthanide POM was successfully synthesized as a single crystal. Anderson-type hexamolybdochromate ([CrMo6O18(OH)6]3-, CrMo6) anion exhibiting emission derived from Cr3+ was utilized with n-dodecylammonium ([C12H25NH3]+, C12NH3) surfactant cation to obtain a photoluminescent hybrid crystal. The grown single crystal of C12NH3-CrMo6 comprised a distinct layered structure consisting of inorganic CrMo6 layers and interdigitated C12NH3 layers. In the CrMo6 layers, the CrMo6 anions were associated with water molecules by hydrogen bonding to form a densely packed two-dimensional network. Steady-state and time-resolved photoluminescence spectroscopy revealed that the C12NH3-CrMo6 hybrid crystal exhibited characteristic emission from the CrMo6 anion. Preliminary lasing properties were also observed for C12NH3-CrMo6, which shows the possibility of using the C12NH3-CrMo6 hybrid crystal as an inorganic-organic hybrid laser.

Wall teichoic acid-dependent phagocytosis of intact cell walls of Lactiplantibacillus plantarum elicits IL-12 secretion from macrophages.

Selected lactic acid bacteria can stimulate macrophages and dendritic cells to secrete IL-12, which plays a key role in activating innate and cellular immunity. In this study, we investigated the roles of cell wall teichoic acids (WTAs) displayed on whole intact cell walls (ICWs) of Lactiplantibacillus plantarum in activation of mouse macrophages. ICWs were prepared from whole bacterial cells of several lactobacilli without physical disruption, and thus retaining the overall shapes of the bacteria. WTA-displaying ICWs of several L. plantarum strains, but not WTA-lacking ICWs of strains of other lactobacilli, elicited IL-12 secretion from mouse bone marrow-derived macrophages (BMMs) and mouse macrophage-like J774.1 cells. The ability of the ICWs of L. plantarum to induce IL-12 secretion was abolished by selective chemical elimination of WTAs from ICWs, but was preserved by selective removal of cell wall glycopolymers other than WTAs. BMMs prepared from TLR2- or TLR4-deficient mouse could secret IL-12 upon stimulation with ICWs of L. plantarum and a MyD88 dimerization inhibitor did not affect ICW-mediated IL-12 secretion. WTA-displaying ICWs, but not WTA-lacking ICWs, were ingested in the cells within 30 min. Treatment with inhibitors of actin polymerization abolished IL-12 secretion in response to ICW stimulation and diminished ingestion of ICWs. When overall shapes of ICWs of L. plantarum were physically disrupted, the disrupted ICWs (DCWs) failed to induce IL-12 secretion. However, DCWs and soluble WTAs inhibited ICW-mediated IL-12 secretion from macrophages. Taken together, these results show that WTA-displaying ICWs of L. plantarum can elicit IL-12 production from macrophages via actin-dependent phagocytosis but TLR2 signaling axis independent pathway. WTAs displayed on ICWs are key molecules in the elicitation of IL-12 secretion, and the sizes and shapes of the ICWs have an impact on actin remodeling and subsequent IL-12 production.

S-Denitrosylase-Like Activity of Cyclic Diselenides Conjugated with Xaa-His Dipeptide: Role of Proline Spacer as a Key Activity Booster.

This study developed dipeptide-conjugated 1,2-diselenan-4-amine (1), i. e., 1-Xaa-His, as a new class of S-denitrosylase mimic. The synthesized compounds, especially 1-Pro-His, remarkably promoted S-denitrosylation of nitrosothiols (RSNO) via a catalytic cycle involving the reversible redox reaction between the diselenide and its corresponding diselenol ([SeH,SeH]) form with coexisting reductant thiols (R'SH), during which the [SeH,SeH] form as a key reactive species reduces RSNO to the corresponding thiol (RSH). Structural analyses of 1-Pro-His suggested that the peptide backbone of [SeH,SeH] is rigidly bent to form a γ-turn, possibly including an NH⋅⋅⋅Se hydrogen bond between the imidazole ring of His and selenol group, thus stabilizing the [SeH,SeH] form thermodynamically, and dramatically enhancing the catalytic activity. Furthermore, the synthetic compounds were found to prohibit S-nitrosylation-induced protein misfolding in the presence of RSNO, eventually implying their potential as a drug seed for misfolding diseases caused by the dysregulation of the S-denitrosylation system.

Comparative study on water structures of poly(tetrahydrofurfuryl acrylate) and poly(2-hydroxyethyl methacrylate) by nuclear magnetic resonance spectroscopy.

It is well known that poly(2-methoxyethyl acrylate) (PMEA) has good blood compatibility and its performance is attributed to its water structure. Recently, we applied solution nuclear magnetic resonance spectroscopy (solution-NMR) for analyzing the water structure in PMEA at ambient temperature and concluded that this method is useful because of the clear observation of the resonance peaks at low and high magnetic field (downfield and upfield, respectively) areas indicating the existence of more than two types of water. The present study was performed to compare the water structure of poly(tetrahydrofurfuryl acrylate) (PTHFA) and poly(2-hydroxyethyl methacrylate) (PHEMA) using solution 2H-NMR and deuterium oxide as water at the temperature range 15-45 °C. It was found that PTHFA has a different water structure from that of PHEMA. Water in PTHFA clearly showed two resonance peaks at downfield and upfield areas, with different spin-lattice relaxation times, T12H (high and low values, respectively). These observations are similar to those of PMEA. In contrast, PHEMA showed only one broad resonance peak (at downfield) with a low T12H value. Based on these observations, this study discusses the effect of water structures on the blood compatibility of these polymers.

Composition of the white precipitate formed on the surface of damaged triacetyl cellulose-based motion picture films.

To achieve a better understanding of the "vinegar syndrome" phenomenon, which has caused serious damage to triacetyl cellulose-based motion picture films, the white powder obtained from damaged film surfaces was analysed in this study. The powder was found to be soluble in acetone, diethyl ether, dimethylformamide, and chloroform, but insoluble in water. From the results of 1H, 13C and 31P nuclear magnetic resonance spectroscopy, mass spectrometry, and X-ray fluorescence measurements, it was concluded that the white precipitate had a molecular weight of 326 amu and was composed of triphenyl phosphate (C18H15O4P).

Structural analyses of a hemolytic compound found in an extract of Hypsizygus marmoreus fruiting bodies at a low pH.

The current study determined the structure of a hemolytic compound found in an extract from the fruiting bodies of the edible mushroom Hypsizygus marmoreus when its pH was lowered. The hemolytic compound was purified using the modified Bligh and Dyer method followed by chromatography using reversed phase and silica gel columns. Structural analyses of the purified hemolytic compound were performed using NMR and ESI-MS. The deduced structure indicated a trans,trans-5,8-docosadienoic acid calcium salt. Although numerous proteinous hemolysins from various mushrooms have been described, the current study is the first to report on a low-molecular-weight hemolytic compound derived from an H. marmoreus extract.

pH-Dependent exhibition of hemolytic activity by an extract of Hypsizygus marmoreus fruiting bodies.

The current study found that an extract from the fruiting bodies of the edible mushroom Hypsizygus marmoreus exhibited hemolytic activity against sheep red blood cells when its pH was lowered. Although hemolytic activity was not detected when an extract had a neutral pH, an extract with a low pH exhibited potent hemolytic activity. The maximal hemolytic activity was exhibited by an extract with a pH of 5.5. A heat-treated extract did not exhibit hemolytic activity before its pH was lowered, and that activity was inhibited in the presence of PMSF and EDTA. The turbidity of the extract increased during lowering of its pH, and the precipitate fraction exhibited hemolytic activity. Fractionation by a modified Bligh and Dyer method and TLC analyses suggested that a hemolytic compound in the extract might be a type of lipid. These results suggest that a hemolytic lipid-like compound in an extract of H. marmoreus fruiting bodies may be released by a non-active precursor substance(s) through metalloenzyme(s) while the extract has a low pH.

Stability of Glyme Solvate Ionic Liquid as an Electrolyte for Rechargeable Li-O2 Batteries.

A solvate ionic liquid (SIL) was compared with a conventional organic solvent for the electrolyte of the Li-O2 battery. An equimolar mixture of triglyme (G3) and lithium bis(trifluoromethanesulfonyl)amide (Li[TFSA]), and a G3/Li[TFSA] mixture containing excess glyme were chosen as the SIL and the conventional electrolyte, respectively. Charge behavior and accompanying gas evolution of the two electrolytes was investigated by electrochemical mass spectrometry (ECMS). From the linear sweep voltammetry performed on an as-prepared cell, we demonstrate that the SIL has a higher oxidative stability than the conventional electrolyte and, furthermore, offers the advantage of lower volatility, which would benefit an open-type lithium-O2 cell design. Moreover, CO2 evolution during galvanostatic charge was less in the SIL, which implies less side reaction. However, O2 evolution during charge did not reach the theoretical value in either of the two electrolytes. Several mass spectral fragments were generated during the charge process, which provided evidence for side reactions of glyme-based electrolytes. We further relate the difference in observed discharge product morphology for these electrolytes to the solubility of the superoxide intermediate, determined by rotating ring disk electrode (RRDE) measurements.

Complete NMR assignment of a bisecting hybrid-type oligosaccharide transferred by Mucor hiemalis endo-ß-N-acetylglucosaminidase.

This study describes the complete nuclear magnetic resonance (NMR) spectral assignment of a bisecting hybrid-type oligosaccharide 1, transferred by Mucor hiemalis endo-ß-N-acetylglucosaminidase (Endo-M). Through (1)H- and (13)C-NMR, DQF-COSY, HSQC, HMBC, TOCSY, and NOESY experiments, we determine the structure of the glycoside linkage formed by the Endo-M transglycosylation, i.e., the connection between GlcNAc and GlcNAc in oligosaccharide 1.

Synthesis, structure, and evaluation of a ß-cyclodextrin-artificial carbohydrate conjugate for use as a doxorubicin-carrying molecule.

This paper describes the synthesis of a ß-cyclodextrin (ß-CyD) derivative conjugated with a C,C-glucopyranoside containing a benzene unit. Its doxorubicin-inclusion ability and structure are also discussed. SPR analysis revealed that the ß-CyD conjugate had a high inclusion association value of 3.8×10(6)M(-1) for immobilized doxorubicin. NMR structural analysis suggested that its high doxorubicin-inclusion ability was due to the formation of the inclusion complex as a result of the π-π stacking interaction between the benzene ring of the conjugate and the A ring of doxorubicin.

Sugar-sensitive supramolecular structures based on phenylboronic Acid-modified cyclodextrins.

Supramolecular structures were developed from phenylboronic acid-modified cyclodextrins (PBA-CyDs). The intermolecular interaction between the PBA moiety and the CyD cavity was proved using two dimensional (2D)-NMR and powder X-ray diffraction techniques. PBA-α-CyD formed a head-to-tail supramolecular polymer, whereas PBA-ß-CyD formed a head-to-head dimer. The supramolecular structures were disintegrated in the presence of sugars owing to the resulting boronate sugar interactions.

Improvement of some physicochemical properties of arundic acid, (R)-(-)-2-propyloctanonic acid, by complexation with hydrophilic cyclodextrins.

Arundic acid, (R)-(-)-2-propyloctanonic acid, is a novel neurological agent for intractable neurodegenerative diseases. However, arundic acid, an oily drug, has low aqueous solubility and severe bitter/irritating tastes. Consequently, these physicochemical properties of arundic acid need to be improved to develop its pharmaceutical preparations. In the present study, we evaluated whether parent cyclodextrins (CyDs) and 2-hydroxypropylated CyDs (HP-CyDs) can interact with arundic acid, and have powderization, solubilization and taste-masking properties. Of various CyDs, HP-ß-CyD had the most potent solubilizing effect for arundic acid. UV and (1)H NMR spectroscopic studies demonstrated that arundic acid formed inclusion complexes with CyDs at a molar ratio of 1:1 in solution. The complexation with CyDs changed an oily form of arundic acid to a solid form. The gustatory sensation studies indicate that of various CyDs, HP-ß-CyD and γ-CyD showed the most significant taste-masking effects in solution and powders, respectively. HP-ß-CyD significantly reduced the response of the electric potential caused by the adsorption of arundic acid to the taste sensor. These results suggest that hydrophilic CyDs have potential as multifunctional excipients for preparing solutions and powders containing arundic acid.

Syntheses and doxorubicin-inclusion abilities of beta-cyclodextrin derivatives with a hydroquinone alpha-glycoside residue attached at the primary side.

This paper describes syntheses and doxorubicin-inclusion abilities of beta-cyclodextrin (CyD) derivatives with a hydroquinone alpha-glycoside residue attached at the primary side. The hydroquinone glycoside having an alpha-D-glucosidic or 2-acetamido-2-deoxy-alpha-D-glucosidic linkage became a useful component for providing an alpha-D-glucose- or 2-acetamido-2-deoxy-alpha-D-glucose-beta-CyD conjugate. The surface plasmon resonance analyses of these beta-CyD derivatives for the anticancer agent, doxorubicin, indicated that they had excellent inclusion associations on the order of 10(5 m)-1 for the immobilized doxorubicin.

Synthesis of a novel D-glucose-conjugated 15-crown-5 ether with a spiro ketal structure.

This paper describes a synthetic approach to a novel D-glucose-conjugated 15-crown-5 ether having a spiroketal structure starting from a 1-C-vinylated glucose derivative. The approach consists of the glycosylation of the vinylated glucose derivative to give an ethyleneoxy spacer derivative using bismuth(III) triflate, the conversion of the 1-C-vinyl group of the glucoside produced into a carboxylic acid group, and the intramolecular condensation between the carboxyl group and the terminal hydroxyl group in the ethyleneoxy spacer. A D-glucose-conjugated 15-crown-5 ether having a unique spiroketal structure was thus successfully synthesized.

Design, synthesis and evaluation of D-galactose-beta-cyclodextrin conjugates as drug-carrying molecules.

Several kinds of D-galactose-beta-cyclodextrin conjugates having a phenyl group in the spacers between the D-galactose and beta-cyclodextrin were designed and synthesized as drug-carrying molecules. Their evaluation as drug-carrying molecules was done by measuring the molecular interactions with the anticancer agent, doxorubicin, and with the d-galactose-binding peanut lectin using an SPR optical biosensor. The SPR analyses showed that these conjugates had remarkably high inclusion associations of 10(5) approximately 10(7)M(-1) levels for the immobilized doxorubicin. Their association constants for immobilized peanut lectin were at the level of 10(4) approximately 10(5)M(-1), as we expected. These conjugates will be useful drug-carrying models which can site-specifically carry doxorubicin to the cells containing D-galactose-binding lectin.

Beta-cyclodextrin conjugates with glucose moieties designed as drug carriers: their syntheses, evaluations using concanavalin A and doxorubicin, and structural analyses by NMR spectroscopy.

Three kinds of beta-cyclodextrin derivatives conjugated with glucose moieties, which were expected as models for a drug carrier targeting the drug delivery systems, were designed and synthesized from beta-cyclodextrin and the natural product, 4-hydroxyphenyl-beta-D-glucopyranoside called arbutin. Arbutin was used because it had a phenyl group with a hydroxyl function which could be used to link the glucose moiety to beta-cyclodextrin. The evaluations of these conjugates as the drug-carrying molecules were done by investigating the molecular interactions with the carbohydrate-binding Concanavalin A (Con A) lectin and the anticancer agent, doxorubicin (DXR), using an SPR optical biosensor. The association constants of the conjugates with immobilized Con A were 2.0 x 10(3) approximately 8.8 x 10(3) M(-1). The result showed that the Con A bound to the glucose moieties from arbutin in the conjugates with prospective association constants. The inclusion associations of the conjugates with immobilized DXR reached 2.2 x 10(5) approximately 1.4 x 10(8) M(-1). The extremely high inclusion associations for DXR suggested their potential abilities as drug-carrying molecules for carrying DXR. The NMR analyses indicated that the phenyl group of the conjugates greatly served to increase the inclusion associations for DXR. In their DXR inclusion complexes, the formation of the stacking complexes by the pi;-pi interactions between the phenyl groups and the included DXR also enhanced their inclusion abilities for DXR.

Synthesis of mono-glucose-branched cyclodextrins with a high inclusion ability for doxorubicin and their efficient glycosylation using Mucor hiemalis endo-beta-N-acetylglucosaminidase.

The mono-glucose-branched cyclodextrins having an appropriate spacer between the beta-cyclodextrin and a glucose moiety were synthesized from beta-cyclodextrin and arbutin. They had the significantly high association constants for doxorubicin, the anticancer agent, in the range of 10(5)-10(6)M(-1), and worked as highly reactive glycosyl acceptors for the transglycosylation reaction by endo-beta-N-acetylglucosaminidase of Mucor hiemalis to produce sialo-complex type oligosaccharide-branched cyclodextrins in the high yields of 65-67%.

Transglycosylation reaction of Mucor hiemalis endo-beta-N-acetylglucosaminidase using sugar derivatives modified at C-1 or C-2 as oligosaccharide acceptors.

We investigated the transglycosylation reaction of the recombinant endo-beta-N-acetylglucosaminidase from Mucor hiemalis (Endo-M) expressed in Candida boidinii using such sugar derivatives as N-acylated d-glucosamines, C-glucosyl derivatives, and a 2-O-glycosylated disaccharide as acceptors. We found that a variety of sugar derivatives modified at C-1 or C-2 could be used as acceptors for transglycosylation by Endo-M to create novel oligosaccharides.