The confirmation of the formation of clathrate-like hydrates of poly(tetrabutylammonium ethenesulfonate) and of poly(tetraisopentylammonium ethenesulfonate)

A thermal method using differential scanning calorimeter has been applied to aqueous solutions of a series of poly(tetraalkylammonium ethenesulfonates) (R₄NPES). It was found that only the salts withR=n-C₄H₉ andR=i-C₅H₁₁ could form stable hydrates having large hydration numbers. The melting point and hydration numbers of these two hydrates were 12.0°C and 30±1 for the (n-C₄H₉)₄NPES hydrate and 16.0°C and 53±2 for the (i-C₅H₁₁)₄NPES hydrate, respectively. It was concluded that these hydrates were clathrate-like essentially similar to such hydrates as (n-C₄H₉)₄NF·30H₂O and (i-C₅H₁₁)₄NF·40H₂O.     

Polycyclic N-heterocyclic compounds. XLI. Synthesis of 4-substituted 6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepines, 1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzazepines and their related compounds as a series of potential blood platelet aggregation inhibitors

As a series of polyheterocyclic compounds for exploitation as anti-platelet agents, tricyclic heterocyclic compounds, 4-substituted 6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepines 3–6, 9, 12–14 , and 16–26 , having nitrogen, oxygen, or sulfur containing functional groups at the 4-position, were prepared. In addition, tetra-cyclic heterocyclic compounds, 3-methyl-1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzaze-pinium chloride ( 7 ), 1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzazepines 10a-e , 2,3,6,7-tetrahydro-1H 5H-pyrimido[1′,2′:1,6]pyrimido[5,4-d][1]benzazepine ( 11 ), and 1,2,5,6-tetrahydro-4H-thiazolo-[3′,2′:1,6]pyrimido[5,4-d][1]benzazepinium chloride ( 15 ) via ring closure of 4-(hydroxyalkylamino)- 6, 9a-e , and 3c , and 4-(2-hydroxyethylthio)-6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepine ( 14 ) with phosphoryl chloride or thionyl chloride, respectively, were also prepared. Their inhibitory activities against collagen-induced aggregation of rabbit blood platelets in vitro were investigated. Among them, compound 5 having a morpholino group at the 4-position on the tricyclic nucleus, which enhanced the activity more than 14-fold as compared with aspirin, was found to have the most satisfactory in inhibitory activity.     

4-(Pyrrolidinyl)methoxybenzoic acid derivatives as a potent, orally active VLA-4 antagonist

A novel series of benzoic acid derivatives as VLA-4 antagonists were synthesized. Optimization, focusing on activity and lipophilicity needed for cell permeability, resulted in the identification of 15b and 15e with good activity (IC50 = 1.6 nM each) and moderate lipophilicity (Log D = 2.0, 1.8). Furthermore, 15e demonstrated efficacy in murine asthma model by an oral dose of 30 mg/kg.     

Coordination framework hosts consisting of 4-pyridyl-substituted carboxylic acid (PCA) dimers and 1D chains of Ni2+ and SCN-: a rational structural extension toward coordination framework hosts with large rectangular cavities

For the expansion of a rectangular cavity (RC) defined by two isonicotinic acid (isoH) dimers as bridging ligands and two SCN bridges, we conducted a structural extension based on the elongation of the bridging ligands by the replacement of isoH with longer 4-pyridyl-substituted carboxylic acid (PCA). For this purpose, the following three PCAs have been employed: trans-3-(4-pyridyl)propenoic acid (acrylH), 4-(4-pyridyl)benzoic acid (pybenH), and trans-3-(4-(4-pyridyl)phenyl)propenoic acid (pppeH). Self-assembly of Ni2+, SCN-, and each of four PCAs involving isoH, acrylH, pybenH, and pppeH in the presence of an aromatic guest gave four inclusion compounds formulated as [Ni(SCN)2(isoH)2].1/2(benz[a]anthracene) (1), [Ni(SCN)2(acrylH)2].1/2(benz[a]anthracene) (2), [Ni(SCN)2(pybenH)2].(pyrene) (3), and [Ni(SCN)2(pppeH)2](3/)(2).(benz[a]anthracene) (4). X-ray crystal structural determination of 1-4 revealed that the proposed structural extension was successful. Their crystal structures are layered structures of two-dimensional (2D) grid-type coordination frameworks (2D host layers) framed with bridging ligands of the corresponding PCA dimers and 1D chains consisting of Ni2+ ions and mu(1,3)-SCN- ions. The lengths of the PCA dimers are 12.269(5) A (isoH dimer), 16.890(4) A (acrylH dimer), 20.89(2) A (pybenH dimer), 25.387(3) A (pppeH dimer A), and 25.527(4) A (pppeH dimer B). Each 2D host layer has RCs defined by the two corresponding PCA dimers and the two SCN bridges. The dimensions of RCs are expanded in proportion to the increase in the lengths of the PCA dimers: 29.52 x 5.60-7.20 A2 (4) > 24.95 x 5.46-7.38 A2 (3) > 20.88 x 5.49-7.25 A2 (2) > 16.41 x 5.53-7.43 A2 (1). These expansions reflect the number of aromatic guests that can be included in RCs. RC of 1 include only one molecule of benz[a]anthracene, whereas RCs of 3 or 4 includes two molecules of pyrene or benz[a]anthracene, respectively. Comparison of the lengths between the PCA dimers and 4,4'-bipyridine-type ligands demonstrated that a design strategy-the preparation of a bridging ligand through self-assembly of two PCAs-is both efficient and particularly suitable for the preparation of very long bridging ligands.     

Functional Fluorescence Labeling of Carbohydrates and Its Use for Preparation of Neoglycoconjugates

Abstract

New bifunctional reagents, 2-amino-6-carboxyethylpyridine and 2-amino-6-cyanoethylpyridine, were designed and synthesized in order to provide a novel procedure for preparation of neoglycoconjugates from fluorescence-labeled and purified sugar chains. Labeling of model sugar chains with these reagents was effected by reductive amination using BH₃.Me₂NH to give corresponding 6-carboxyethylpyridylaminated (CEPA-) and 6-cyanoethylpyridylaminated (CNEPA-) derivatives, which were readily purified by reversed phase HPLC. The reagent parts of the labeled products possess the functional groups which then serve as linkers for coupling with matrices such as proteins and polymers. A CEPA-derivative of glucose was directly coupled with the ε-amino group of a Lys derivative to give a neoglycoprotein model. CNEPA-sugars were hydrogenated to give 6-aminopropylpyridylaminated (APPA-) derivatives, which can then be readily used for the preparation of various types of neoglycoconjugates by use of appropriate spacers as exemplified by the coupling of APPA-maltotriose with bovine serum albumin (BSA), biotin, and acrylic acid. The reaction of APPA-maltotriose with succinimidyl 3-(3-nitro-2-pyridyldithio)propionate gave the corresponding amide to be used for a disulfide formation with BSA. Condensation with biotin was effected by use of N-hydroxysuccinimidobiotin. The conjugation of APPA-maltotriose with acrylic acid was carried out by use of 4-acryloyloxyphenyldimethylsulfonium methylsulfate to give the corresponding acrylamide, which can be used for the preparation of sugar-acrylamide copolymers.     

Circumventing air bubbles in microfluidic systems and quantitative continuous-flow PCR applications

Polymerase chain reaction (PCR) is an essential part of research based on genomics or cell analysis. The development of a microfluidic device that would be suitable for high-temperature-based reactions therefore becomes an important contribution towards the integration of micro-total analysis systems (μTAS). However, problems associated with the generation of air bubbles in the microchannels before the introduction of the assay liquid, which we call the “initial start-up” in this study, made the flow irregular and unstable. In this report, we have tried to address these problems by adapting a novel liquid-flow method for high-temperature-based reactions. A PDMS-based microfluidic device was fabricated by soft-lithography techniques and placed on a cartridge heater. The generation of the air bubbles was prevented by introducing the fluorinated oil, an inert and highly viscous liquid, as the cap just before the introduction of the sample solutions into the microchannels. The technique was applied for continuous-flow PCR, which could perform PCR on-chip in a microfluidic system. For the evaluation of practical accuracy, plasmid DNA that serves as a reference molecule for the quantification of genetically modified (GM) maize was used as the template DNA for continuous-flow PCR. After PCR, the products were collected in a vial and analyzed by gel electrophoresis to confirm the accuracy of the results. Additionally, quantitative continuous-flow PCR was performed using TaqMan technology on our PCR device. A laser detection system was also used for the quantitative PCR method. We observed a linear relationship between the threshold cycle (Ct) and the initial DNA concentration. These results showed that it would be possible to quantify the initial copies of the template DNA on our microfluidic device. Accurate quantitative DNA analysis in microfluidic systems is required for the integration of PCR with μTAS, thus we anticipate that our device would have promising potential for applications in a wide range of research.     

Thiiranation of 2′‐adamantylidene‐9‐benzonorbornenylidene using 4,4′‐oligothiodimorpholine and brønsted acid

On leaving 4,4′‐dithiodimorpholine 6 powder undisturbed at room temperature over 10 years, it led to the formation of 4,4′‐tetrathiodimorpholine 7 . Reactions of 2′‐adamantylidene‐9‐benzonorbornenyidene 1 with 6, 7 , and 4,4′‐thiodimorpholine 8 and a Brønsted acid in CH₂Cl₂ at room temperature proceeded to afford the corresponding thiiranes, 2 and 3 . The order of reactivity of 4,4′‐oligothiodimorpholines combined with a Brønsted acid is 7 > 6 > 8 . The thiirane 3 was transformed to 1 and 2 under the reaction conditions. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:12–18, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20505     

Antibacterial metal implant with a TiO2‐conferred photocatalytic bactericidal effect against Staphylococcus aureus

Photocatalysis with anatase Titanium dioxide (TiO₂) under ultraviolet A (UVA) has a well recognized bactericidal effect. There have been a few reports, however, on the effects of photocatalysis on bio‐implant‐related infections. The purpose of present study was to evaluate the photocatalytic bactericidal effects of anatase TiO₂ on Staphylococcus aureus (S. aureus) associated with surgical site infections. TiO₂ films were synthesized on commercially pure titanium substrates and SUS316 stainless steel using a plasma source ion implantation method followed by annealing. The chemical composition of the surface layers was determined using GXRD and XPS. The disks were seeded with cultured S. aureus and exposed to UVA illumination from black light. The bactericidal effect of the TiO₂ films was evaluated by counting the survived colonies statistically. A structural gradient anatase type TiO₂ layer formed on all substrates. The viability of the bacteria on the photocatalytic TiO₂ film coated on titanium was suppressed to 7.0% at 30 minutes and 5.5% at 45 minutes, whereas that on a similarly coated stainless steel was suppressed to 45.8% at 30 minute and 28.6% at 45 minutes (ANOVA: p < 0.05). Complete bacterial inactivation was achieved after 90 minutes on titanium and after 60 minutes on stainless steel. The photocatalytic bactericidal effect of TiO₂ is useful for sterilizing the contaminated surfaces of bioimplants. Copyright © 2008 John Wiley & Sons, Ltd.     

Aerobic photo-decarboxylation of α-hydroxy carboxylic acid derivatives under visible light irradiation in the presence of catalytic iodine

A catalytic amount of iodine enables us to carry out aerobic photo-decarboxylation of α-hydroxy carboxylic acid derivatives to the corresponding carboxylic acids or ketones selectively in high yields under irradiation of vis. This new oxidation is interesting in keeping with the notion of Green Chemistry due to the non-use of heavy metals and halogenated solvents, waste reduction, and the use of molecular oxygen.     

The formation of clathrate-like hydrates of tetrabutylammonium halogenated carboxylates

The solid-liquid phase diagrams of binary mixtures of tetrabutylammonium halogenated carboxylates with water were examined in order to confirm the formation of clathrate-like hydrates. It was found that, among thirteen carboxylates examined, four carboxylates having CH₂FCOO^–, CHF₂COO^–, CF₃COO^–, and CH₂ClCOO^–, formed a hydrate with hydration numbers around 30 and seven carboxylates having CHCl₂COO^–, CCl₃COO^–, CH₂BrCOO^–, CHBr₂COO^–, CBr₃COO^–, CH₃CHClCOO^–, and CH₃CHBrCOO^– formed a hydrate with hydration numbers around 23. The latter hydrate has not been reported earlier. The melting points of these newly found hydrates were fairly high: they lie between 10 and 16°C. The effect of Cl and Br atoms attached to the carbon atom of the-position of a carboxylate anion both on the type of hydrate formed and on its stability was greatly different from that of a CH₃ group attached to the same position of the carboxylate anion.Dedicated to Dr D. W. Davidson in honor of his great contributions to the sciences of inclusion phenomena.